HealthMed Vol03-No1

Volume 3 / Number 1 / 2009
HealthMED
Journal of Society for development of teaching and business processes in new net environment in B&H
EDITORIAL BOARD Editor-in-chief Editorial assistant Secretaries Technical editor Lectors Members Mensura Kudumovic Jasmin Musanovic Dzenana Jusupovic Azra Kudumovic Eldin Huremovic Mirnes Avdic Adisa Spahic Farah Mustafa (Islamabad) Maizirwan Mel (Kuala Lumpur) Bakir Mehic (Sarajevo) Farid Ljuca (Tuzla) Emina Nakac-Icindic (Sarajevo) Ago Omerbasic (Sarajevo) Slavica Ibrulj (Sarajevo) Fatima Jusupovic (Sarajevo) Aida Hasanovic (Sarajevo) Dijana Avdic (Sarajevo) Selma Alicelebic (Sarajevo)
Sadraj / Table of Contents

Profile of Venous Thromboembolism at the Patients with Non-Small Cell Lung Carcinoma Profil venskog tromboembolizma kod pacijenata sa nemikrocelularnim karcinomom plua ................. 3-7
Bakir Mehi, Hasan uti, Amina Mehi ***
In a way to treat addiction; is therapeutic outcomes effective? Naini tretmana ovisnosti; koliko je terapija efikasna? .................................................... 8-16
Wasif S., Azhar S., Tahir MK., Amir HK., Hadi A., Forouzan Bayat Nejad ***
Use of mathematical modeling in predicting the impact of a disease: An example of measles dynamic model Matematsko modeliranje u predvidjanju kretanja bolesti: dinamicki model morbila ....................... 17-23
Semra avaljuga, Mladen avaljuga, Mira avaljuga ***
Address of the Sarajevo, Bolnicka BB Editorial Board phone/fax 00387 33 640 407 healthMed_bih@yahoo.com http://www.healthmed_bih.org Published by DRUNPP, Sarajevo Volume 3 Number 1, 2009 ISSN 1840-2291 Indexing on:
Health Promotion in Silicon Valley: A Study of 11 Corporations Promocija zdravlja u Silikonskoj dolini: Studija provedena u 11 korporacija ............................... 24-27
Yann A. Meunier ***
The most frequent reasons for visits to patients in Emergency Medical Care Center Sarajevo Najei razlozi za kune posjete u ZHMP Sarajevo ................................................. 28-32
Enes Slatina ***
EBSCO Publishing (EP) USA http://www.epnet.com
Science Citation Index Expanded http://www.isiwebofknowledge.com
The most frequent congenital cardiovascular anomalies Najee kongenitalne anomalije kardiovaskularnog sistema ............................................................. 33-37
Selma Alielebi
Volume 3 / Number 1 / 2009
HealthMED
Sadraj / Table of Contents
Flock level risk factors for ovine brucellosis in several cantons of Bosnia and Herzegovina Riziko faktori na nivou stada za pojavu ovije bruceloze u nekoliko Kantona Bosne i Hercegovine ......................................... 38-44
Sabina Seric Haracic, Mo Salman, Nihad Fejzic, Brian J. McCluskey, Thomas J. Keefe ***
***
Intrathoracic metastases of a breast cancer treated in Clinic for pulmonary diseases and tb Podhrastovi- Sarajevo in the four-year period from 2004.2007. Intratorakalne metastaze karcinoma dojke tretirane na klinici za plune bolesti i tuberkulozu Podhrastovi u etvorogodisnjem periodu od 2004. do 2007. godine ........................................................................... 66-70
Vesna uki ***
***
Hypertension as leading cardiovascular illness among minners Hipertenzija kao vodea kardiovaskularna bolest rudara ............................................................... 45-50
Muvedeta Leme, Belma Pojski
Dependence of lower extremies amputations to caracteristics of Diabetes Mellitus Ovisnost amputacija donjih ekstremiteta u odnosu na osobine dijabetes melitusa .......................... 51-54
Dijana Avdi, Demal Pecar, Mensura Kudumovi, Mirela Avdi ***
Treatment of elderly patients with rectal prolapse with modified anal cerclage method Tretmana starijih pacijenata sa prolabiranim rektumom metodom modificirane analne serklae .... 71-79
Nedad ehovi, Amela Sofic, Adnan Zeo ***
Alpha-lipoic acid and quercetin protect against methotrexate induced-hepatotoxicity in rats ............................................................... 80-89
Hebatallah A. Darwish, Amina Mahdy
De Quervains tenosynovitis occurence in patients with u Repetitive Stress Injurys treated at the basic rehabilitation PRAXIS center Efikasnost tretmana teniskog lakta (Epicondylitis humeri radialis)u ambulanti CBR -PRAXIS .... 55-60
Demal Pecar, Dijana Avdi ***
PREVIEW PAPERS
New classification of epidermolysis bullosa group of blistering disorders ........................ 90-93

Naima Mutevelic Arslanagic, Rusmir Arslanagic, Selma Arslanagic ***
Influence of early physiotherapy to recovery after Paresis N. Facialis Uticaj rane fizikalne terapije na oporavak nakon pareze n. Facialisa ................................................ 61-65
Edina Tanovi
Instructions for the autors ................................. 94-95
HealthMED - Volume 3 / Number 1 / 2009
Profile of Venous Thromboembolism at the Patients with Non-Small Cell Lung Carcinoma
ProfiL VeNSkog TromboemboLizma kod PaCijeNaTa Sa NemikroCeLuLarNim karCiNomom PLua
Bakir Mehic1, Hasan Zutic1, Amina Mehic2
1 2
Clinical Centre University of Sarajevo, Clinic of Lung Diseases and TB, Bosnia and Herzegovina University of Sarajevo, Faculty of Medicine, Bosnia and Herzegovina
Summary Although lung cancer incidence has increased during the last decades and non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung tumors, few reports exist on the incidence of (venous thromboembolism) VTE in NSCLC. The purpose of this paper is to try to make definition of predictive parameters for onset of VTE at the patients with NSCLC. Clinical records of all NSCLC patients with VTE, treated at Clinic of Lung Diseases and TB, Clinical Centre University of Sarajevo, from 2006 - 2008 were retrospectively reviewed. In total there were 1563 patients with NSCLC. Results of the research: Among 1563 hospitalized patients with NSCLC during three years period, 92 (5.88%) were diagnosed with VTE and 0.58% with pulmonary embolism (PE). Mean age of our patients with VTE was 62.8 8.6 years (range 36 86), and male sex was 3.6 time more frequent than female. After calculating the correlation coefficient, it is evident that there is strong correlation between performace status (PS) and the time of onset of VTE, and low correlation between the location and the time of the onset VTE, as well as low correlation between PS and the location of the VTE. Conclusion: As predictive parameters for onset of VTE at the patients with NSCLC we could in-
clude adenocarcinoma as the most frequent histology type of NSCLC at the cases of VTE (65.2%). Advanced cancer stage (84.8%) could be the significant predictor of appearance of VTE. The biggest percent of patients with VTE (44.56%) had this vascular event before the start of chemotherapy and during the first line treatment with chemotherapy. The most frequent location of VTE was on the veins of legs. Diseases of the heart were the most frequent comorbidity, in 39.13% of cases. Key words: venous thromboembolism, nonsmall cell lung cancer, predictive parameters, retrospectively reviewed. Saetak Mada je incidencija raka plua u toku posljednje decenije u porastu, a na nemikrocelularni rak plua (NSCLC) otpada odprilike 80% svih tumora plua, posatoji samo nekoliko radova kada je u pitanju incidencija venoznog tromboembolizna (VTE) u sluajevima NSCLC. Svrha ovog rada je da pokua da definie prediktivne parametre za nastanak VTE kod pacijenata sa NSCLC. Rad je retrospektivni pregled klinikih podataka svih pacijenata sa NSCLC i VTE tretiranih na Klinici za plune bolesti i TB, Klinikog Centra Univerziteta u Sarajevu od 2006 2008 godine. Ukupno je bilo 1563 pacijenta sa NSCLC. 3
Rezultati istraivanja: u trogodinjem periodu, kod 92 (5.88%) pacijenata sa NSCLC dijagnosticiran je VTE, a 0.58% njih je imalo emboliju plua (PE). Prosjena dob pacijenata sa VTE bila je 62.8 8.6 godina (raspon 36 86), mukarci su 3.6 puta bili zastupljeniji u odnosu na ene. Nakon izraunavanja koeficijenta korelacije, nali smo da postoji jaka korelacija samo izmeu performan statusa (PS) i vremena nastanka VTE, te slaba korelacija izmeu vremena nastanka VTE i njene lokacije, kao i slaba korelacija izmeu PS i lokacije VTE. Zakljuak: kao prediktivne parametre za nastanak VTE kod pacijenata sa NSCLC mogli bi smo smatrati adenokarcinom kao najei histoloki tip NSCLC jer je u 65.2% sluajeva VTE bio prisuutan. Odmakli statdij NSCLC (84.8%) mogao bi biti znaajan prediktor pojave VTE. Najvei procenat pacijenata sa VTE (44.56%) imao je razvoj ove bolesti prije poetka kemoterapije, te za vrijeme prve linije tretmana kemoterapijom. Najea lokacija VTE bila je na venama nogu. Najei nalaz komorbiditetnih bolesti otpadao je na bolesti srca, 39.13% sluajeva. Kljune rijei: venski tromboembolizam, nemikrocelularni rak plua, prediktivni parametri, retrospektivni pregled Introduction Thromboembolism is a well recognized complication of malignant disease with a spectrum of clinical manifestations varying from venous thromboembolism (VTE) and Trousseaus syndrome to disseminated intravascular coagulation. [1] The link between activation of the blood coagulation system and malignancy dates back to 1865. [2] Thereafter venous thrombosis has been reported to be a common complication in patients with malignancy,[3,4] but although lung cancer is the second most common cancer in western countries and the leading cause of cancer death in men and women[5] strikingly few papers on the phenomenon of VTE in lung cancer patients are found and data on mortality due to VTE are limited. Utilizing a Medicare database, Levitan et al. [6] found that the incidence of VTE is high among cancer patients, and lung cancer belonged to the group of malignancies with the highest inciden4
ce rates. More recently, the overall risk of venous thrombosis was found to be increased seven-fold in patients with a malignancy vs. persons without malignancy.[7] Although lung cancer incidence has increased during the last decades and non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung tumors, few reports exist on the incidence of VTE in NSCLC. The purpose of this paper is to try to make definition of predictive parameters for onset of VTE at the patients with NSCLC. The goals of this paper are to give answers to the next questions: what pathological type of NSCLC and what stage of NSCLC is most frequently followed by VTE, what performance status (PS) is most frequently affected by VTE? What time during of treatment the onset of VTE is most frequent? Whats the common venous location and what is the role of comorbidity and level of platelets during the onset VTE? Patients and Methods Clinical records of all NSCLC patients with VTE, treated at Clinic of Lung Diseases and TB, Clinical Centre University of Sarajevo, from 2006 - 2008 were retrospectively reviewed. In total there were 1563 patients with NSCLC. To be eligible for this study, patients were to have histologicaly confirmed diagnosis of NSCLC with evidence of way of treating methods till the onset of VTE. Histological types of tumors were classified according to the 1999 World Health Organization classification. The diagnosis of VTE has been made set based on clinical signs, spiral computed tomography scan and ventilation-perfusion gamma scans for pulmonary embolism (PE), or Doppler ultrasonography for confirmation of thromboses in peripheral veins. Statistical analysis was performed using the SPSS software system (SPSS for Windows version 11.0, Chicago, IL). After analysis of distribution of frequency for nonparametric data and mean values for parametric data, we performed a correlation test to analyze rate of linkage between the observed variables, and for showing the curve of regression we used a model of simple regression.
Results Our retrospective review identified 92 NSCLC patients with confirmed VTE (Table 1). The most frequent histological type was adenocarcinoma (65.2%), and 74% of patients had a good performance status (PS) at the moment of onset of VTE. Table 1. Patients characteristics
Patients, no. (%) Sex, no (%) Male Female Age, yr. Mean SD Range Pathology, no. (%) Adenocarcinoma Squamous Large cell Clinical stage, no. (%) I II IIIA IIIB IV Performance status, no. (%) 0 1 2 3 4 27 (29.35) 25 (25.17) 16 (17.39) 20 (21.74) 4 (4.35) 1 (1.1) 4 (4.3) 9 (9.8) 26 (28.3) 52 (56.5) 60 (65.2) 25 (27.2) 7 (7.6) 62.8 8.6 36 86 72 (78.2) 20 (21.8) 92 (100)
Table 2. Characteristics of VTE

Time of the onset, no. (%) Before treatment During the first line of treatment During the time free from disease During the second line of treatment During the third line of treatment During the palliation During the best supportive care Location of onset, no. (%) Brain veins Carotid veins Pulmonary arteries Veins of upper arm Veins of forearm Intestinal veins Renal veins Iliac veins Iliac-femoral veins Femoral veins Femoral and shin veins Shin veins Medical comorbidities, no. (%) No comorbidities COPD Liver metastasis Heart failure Arterial hypertension Arrhythmias Diabetes mellitus After stroke Peripheral vascular diseases Platelets, no. Mean SD Range 466.73 140.47 210 812 12 (13.04) 11 (11.96) 11 (11.96) 10 (10.87) 13 (14.13) 13 (14.13) 14 (15.22) 1 (1.09) 7 (7.61) 7 (7.61) 8 (8.70) 9 (9.78) 9 (9.78) 7 (7.61) 3 (3.26) 3 (3.26) 9 (9.78) 8 (8.70) 10 (10.87) 7 (7.61) 12 (13.04) 19 (20.65) 22 (23.91) 9 (9.75) 5 (5.43) 8 (8.70) 8 (8.70) 21 (22.83)
The majority of patients (78.2%) were males, and 56.5% of patients had stage IV disease. Characteristics of VTE (the time and location of onset, number of platelets) and chronic medical comorbidities are shown in table 2. There were 50 cases of VTE (54.34%) with the onset before the second line of treatment of NSCLC. More than 20% of VTE happened before the beginning of causal treatment of NSCLC. 40.22% VTE were located in veins of legs too. The most frequent comorbidity in our population of patients with NSCLC and VTE was the heart diseases (36 patients vs. 39.13%).
Table 3. Correlation coefficient for variables of VTE in population patients with NSCLC
Variables VTE Time of the onset PS Location of the onset Time of the onset PS Location of the onset Correlation coefficient 0.873890309 -0.27692448 0.263892037 One-sided significance 3.06793E-30 0.0003766367 0.005514431
After calculating the correlation coefficient (Table 3), it is evident that there is strong correlation between PS and the time of onset of VTE, and low correlation between the location and the time of the onset VTE, as well as low correlation between PS and the location of the onset of VTE. This is better shown by the model of simple regression curve (Fig 1). PS is followed by the time of the onset of VTE.
Fig 3. Model of simple regression curve for variables: PS and location VTE of onset VTE Discussion VTE contributes to morbidity and mortality in cancer patients and is a frequent complication of anticancer therapy. In the current study, the frequency, risk factors, and trends associated with VTE were examined among hospitalized cancer patients. Among 1563 hospitalized patients with NSCLC during three years period, 92 (5.88%) were diagnosed with VTE and 0.58% with PE. In study Khorana AA et al [8] on 1,015,598 cancer patients 4.1% were diagnosed with VTE. Mean age of our patients with VTE was 62.8 8.6 years (range 36 86), and male sex was 3.6 time more frequent than female. In the same study Khorana AA et al, age 65 years, female sex and black ethnicity were risk factors associated with VTE. Adenocarcinoma was the most frequent histology type of NSCLC followed with VTE (65.2%). This is the same result like Bloom at al [12]: Patients with adenocarcinoma of the lung had a three-fold higher risk (incidence: 66.7 per 1000 years) than patients with squamous cell carcinoma of the lung incidence: 21.2 per 1000 years). Advanced cancer stage patients (84.8%) could be the significant predictor of developing VTE. Even that, in our cancer patients with VTE,
Fig 1. Model of simple regression curve for variables PS and the time of the onset VTE The simple regression curves for the location of the onset of VTE to time of the onset of VTE and the PS to the location of the onset of VTE are shown on Fig 2 and Fig. 3.
Fig 2. Model of simple regression curve for variables: location of the onset of VTE and time of the onset of VTE 6
vascular events were the most frequent in PS 0 and 1 (54.5%). There were very similar opinions in studies of Chew HK et al [9] and Tesselaar ME et al [10]. In studies Tesselaar ME at al [10], Numico G et al [11], and Bloom et al [12] authors finding chemotherapy as a risk factor for VTE, and Khorana AA et al [8] said that patients receiving chemotherapy were disproportionately at risk. In our study the biggest percent of patients with VTE (44.56%) had this vascular event before the start of chemotherapy and during the first line of chemotherapeutical treatment. Also, we found that most frequent location of VTE were on the leg veins. In this population of patients we found heart comorbidity as the most frequent, in 39.13% of cases, besides that the 12 cases (13.4%) stay without registered comorbidity. Also, we found a higher average number of platelets 466.73140.47 range 210 812, but there was no correlation between the higher average number of platelets and other observing variables, besides results of Korana et al.[13] who found an elevated prechemotherapy platelet count was associated with a three-fold increased rate of VTE. Conclusions As predictive parameters for onset of VTE at the patients with NSCLC we could include adenocarcinoma as the most frequent histology type of NSCLC followed with VTE (65.2%). Advanced cancer stage patients (84.8%) could be the significant predictor of developing VTE. The biggest percent of patients with VTE (44.56%) had this vascular event before the start of chemotherapy and during the first line treatment with chemotherapy. The most frequent location of VTE was on the leg veins. Diseases of the heart were the most frequent comorbidity, in 39.13% of cases. There was no correlation between registered a higher average number of platelets (466.73140.47) and the other observing variables. Literature
1. Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation 2003; 107(23 Suppl 1):I17-I21.
2. Trousseau A. Phlegmasia alba dolens. In: Clinique medicale de lHotel-dieu de Paris. Paris: JB Balliere et Fils; 1865. pp. 654-715. 3. Mao C, Domenico DR, Kim K, et al. Observations on the developmental patterns and the consequences of pancreatic exocrine adenocarcinoma. Findings of 154 autopsies. Arch Surg 1995; 130:125-134. 4. Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002; 87:575-579. 5. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55:10-30. 6. Levitan N, Dowlati A, Remick SC, et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 1999; 78:285-291. 7. Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293:715-722. 8. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007; 110(10):2339-46. 9. Chew HK, Davies AM, Wun T, Harvey D, Zhou H, White RH. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost. 2008; 6(4):601-8. 10. Tesselaar ME, Osanto S. Risk of venous thromboembolism in lung cancer. Curr Opin Pulm Med. 2007; 13(5):362-7. 11. Numico G, Garrone O, Dongiovanni V, Silvestris N, Colantonio I, Di Costanzo G, Granetto C, Occelli M, Fea E, Heouaine A, Gasco M, Merlano M. Prospective evaluation of major vascular events in patients with non-small cell lung carcinoma treated with cisplatin and gemcitabine. Cancer 2005; 103(5):994-9. 12. Blom JW, Osanto S, Rosendaal FR. The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost 2004; 2:1760-1765. 13. Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104:2822-2829.
Corresponding author: Bakir Mehic Clinical Centre University of Sarajevo, Clinic of Lung Diseases and TB, Bardakije 90, 71000 Sarajevo, Bosnia and Herzegovina e-mail: mehicb@yahoo.com
in a way to treat addiction; is therapeutic outcomes effective?

NaiNi TreTmaNa oViSNoSTi; koLiko je TeraPija efikaSNa?
Wasif S.1, Azhar S.2, Tahir MK.1, Amir HK.4, Hadi A.3, Forouzan Bayat Nejad5 Lecturer in Island college of technology (ICT), Balik Pulau, Pulau Pinang, Malaysia Dean of School of Pharmaceutical Sciences, USM, Pulau Pinang, Malaysia. 3 Lecturer in University technology Malaysia (UITM), Shahalam, Selangor, Malaysia 4 PhD fellow in clinical Pharmacy, University Sains Malaysia (USM), Malaysia. 5 MD student, Tehran University of Medical Scienses (TUMS), Iran
1 2
Summary Background: Despite the use of methadone for the treatment and management of Addiction, still there are controversial theories in dose setting. Aim of the study describes the clinical outcomes of the Methadone maintenance treatment program in the Penang state of Malaysia. Reason to select Penang is the highest prevalence of drug addiction in this region of Malaysia known as drug hub. A way to ensure the sustainability in the harm reduction plan. Methodology: A descriptive data collection form was used to collect the prospective and retrospective information from the medical profile of out-patients of methadone clinics in Pinang. The data was collected from all of three methadone clinics of Pinang state governed by Ministry of Health, Malaysia. Universal sampling technique was employed for data collection. Following are the some concern criteria employed in the study. - Patients active on methadone therapy - Registered during Jan 2007 May 2008. - Evaluation of National Protocol (methadone maintenance guideline) The reason for above mention time frame was selected because Ministry of Health Malaysia officially started methadone treatment in the middle end of 2006. Results and discussion: The mean age of males admitted in methadone clinic was 41.0 years while it is slightly lowers in female 39.5 years. 8
Majority 97.4% respondents on three methadone clinics were male, only 2.6% females. Ethnic distribution showed no significant difference between Chinese and Malays (39.8% ; 44.4%). While upon religion 45.1% were Muslims and 39.5% were Buddhists. Majority of them were single (57.9%), remaining married (32.3%) and few were divorced (9.8%). Baseline information on withdrawal and intoxication showed 57.3% respondents of methadone experiencing withdrawal symptoms, 15.1% experiencing intoxication signs only 27.6% with no evidence. The most frequent withdrawal symptoms found were yawning, lacrimation, mydriasis, perspiration and anxiety. The findings showed that only 30.6% active respondents were on therapeutic comfort dose (TCD) while remaining 69.4% were on ineffective therapeutic setting and pertaining a risk of relapse. Therapy response shows that 71.2% subjects were on maintenance dose, 21.9% on stabilization stage while 7.0% were subsequent to withdrawal stage. Tabulated data showed the methadone dosing and description of management found in methadone clinic of Pinang. The resulted revealed that 72.5% respondents were experiencing the dose plan inconsistent to the National guidelines of Malaysia. Recommendations: The above study revealed the need to review the National guidelines on evidence based management. Also there is a strong need for the training of practitioners for achieving and designing the therapeutic comfort dose plan.
The results showed that to crop the drug abuse problem in the present situation more strategic informations will be needed as to better control on the drug addiction and achieve 20-20 Vision of Malaysia to make the country as a drug-free zone and a step ahead to harm reduction. Key words: Methadone Maintenance Treatment (MMT), Drug addiction, Addiction, Narcotics addiction, drug dependency, addiction and dependency. Introduction In context to make Malaysia a drug free society, 2015 vision was created (Sattler, 2004), so to ensure the time being harm reduction in term of treatment and educational settings a lot of researches were done on such topic (Mazlan, 2007; Muhaamda Mazlan, 2006; Reid, 2007; Viknasingam, B et al., 2007 and Viknasingam, B ., Navaratnam, V, 2006 etc..). Such studies were mainly emphasized on the risk assessment of sexually transmitted infections as well as blood-borne infection among drug addicts. In the time span of 2001 to 2006 various studies were done by Naveratnaam to identified the respective medical health related problems in the treatment of addiction. Methadone maintenance program was officially started in mid - end of 2006, so far the outcomes were not properly identified on such large scale application The Aims of this study was to evaluate the setting settings and methadone dose titration regarding to the medical outcomes of the methadone maintenance program (MMT). As a common concept that Quality of Health among the methadone receiving respondents was a important factor pertaining to relapse or drop-out. Methodology All of three registered methadone clinics of Penang state, Malaysia were selected to identify the methadone dosing & therapy management for drug addiction. A year retrospective (Jan 2007 to Dec 2007) with six month prospective (Jan 2008 to may 2008) study was designed to collect the necessary information from the methadone cli-
nics. All the respondents registered to methadone during this mentioned period was included in the study while exception was made on those being defaulted or drop-out from the methadone program. Approvals were made from Ministry of health Malaysia, Local authorities of the concern hospital and ethical committee. Universal sampling technique was used in this study. A self designed data collection form was used to collect the information from the medical profiles of MMT patients. A descriptive statistical report was generated after the complete analysis of data collected from the methadone centers. All the analysis was made through the statistical software (SPSS) version 13.0. Results A total of 283 respondents from three different methadone maintenance clinics of Penang state participated in the study. Total of 215 (76.0%) were accepted for the study because of active on MMT program, while remaining of 68 (24.0%) were excluded after being defaulted from MMT program. Complete descriptive data is available in table 1 & table 2. Forty-seven about (70.1%) relapse cases were detected in Pinang hospital. There was only 1 (1.9%) patient who had successfully followed to MMT program and was free from drugs. Figure 1 contains the %-age relapse from last 1 year (Jan 2007- May 2008) among three methadone clinics of Pinang state. Table 3 contains the information regarding the therapy module of MMT program, 116 (54.0%) taking methadone from 7 -12 months only 26 (12.1%) >12 months of treatment. The findings showed high rate of relapse and it was significant with Chinese as mentioned in table 4. Baseline data on withdrawal sign & symptoms indicated that 57.3% of patients who undergone the treatment experienced some adverse sign & symptoms during the treatment with methadone (figure 2). Majority of respondents 65 (30.2%) had evidence of withdrawal and intoxication sig & symptoms on 3rd day during the first week of treatment plan (table 4). while table 5 contains the information regarding the withdrawal sign & symptoms commonly observed during the MMT program. 9
Table 1. Methadone maintenance treatment (MMT) program

Gender Methadone clinics of Penang state a. Centre Pulau Pinang General Hospital (P.P)a Bukit Mertajam Hospital (BM)b Butterworth Health Clinic (B.W)b Total b. MMT treatment active Pulau Pinang General Hospital Bukit Mertajam Hospital Butterworth Health Clinic Total
a
b
Male N (%) 145(96.0) 83 (98.6) 48 (100.0) 276 (97.5) 99 (95.2) 68 (97.1) 41 (100.0) 208 (96.7)
Female N (%) 6 (3.9) 1 (1.4) 7 (2.5) 6 (4.8) 1 (2.9) 7 (3.3)
Total
151 84 48 283 105 69 41 215
patient consensus from march 2007 to May 2008. patient consensus from Jan 2007 to May 2008.
Table 2. Frequency of related outcomes of the MMT program

Characteristics Defaulted cases a. Prison b. Untraceable c. Rehabilitation centre Successful treatment cases Deaths: a. Abnormal liver function b. Aspirated Pneumonia c. Overdose of methadone Total N = 68 (24.2) N (%) P.P 9 (15.7) 39 (76.5) 47 (70.1) BM 9 (13.4) 2 (2.9) 1(1.9) 1(1.9) 13 (19.4) B.W 3 (4.5) 2 (2.9) 1 (1.9) 1 (1.9) 7 (10.4)
Table 3. Duration of treatment among the out-patients of MMT program Duration of Treatment 6 moths 7 12 months > 12 moths Total 10 MMT clinics N % P.P 24 (11.1) 71 (33.0) 9 (11.2) 104 (48.4) B.M 28 (13.0) 33 (15.3) 9 (4.2) 70 (32.6) B.W 21 (9.8) 12 (5.6) 8 (3.7) 41 (19.1) Total 73 (33.9) 116 (54.0) 26 (12.1) 215
Table 6 describes the complete information regarding the dose setting and titration on each level of treatment (initial, maintenance, withdrawal). The comparison was made with the per mg dose of methadone on each stage to that of the National Protocol Guidelines of Ministry of Health Malaysia. The results were identified that 72.5% of out-patients taking DOT therapy in addiction treatment methadone centers were in the inconsistent dosing practice with the National Guideline of Ministry of Health Malaysia.
Table 4. Evidence of withdrawal and intoxication sign and symptoms during first week of MMT treatment among out-patients
Characteristics Evidence of withdrawal signs and symptoms 2nd day 3 day
rd
N (%)
54 (25.1) 65 (30.2) 7 (3.3) 89 (41.4)
4th day No evidence Evidence of intoxication sign and symptoms 2nd day 3rd day 4 day
th
1 (0.5) 1 (0.5) 3 (1.4) 6 (2.8) 1 (0.5) 11 (5.1) 192 (89.3)
5th day 6th day 7 day

th
Figure 1. Percentage relapses during (Jan 2007 may 2008) MMT program
No evidence
Table 5. Listed withdrawal sign & symptoms found among out-patients

Sign & symptoms Observed among (N = 126) Yawning Rhinorrhoea Piloerection Perspiration Lacrimation Mydriasis Vomiting Muscle twitches Abdominal cramps Anxiety N (%) 112 (88.9) 54 (42.8) 47 (37.3) 82 (65.1) 121 (96.0) 107 (84.9) 27 (21.4) 41 (32.5) 79 (62.7) 98 (77.8)
Figure 2. Baseline data for the withdrawal and intoxication sign & symptoms
11
Table 6. Dose schedule for MMT program in outpatients

Characteristic Maintenance dose: Std dose (3060 mg per day) Practice dose : 40 mg 45 mg 50 mg 55 mg 60 mg 65 mg 70 mg 75 mg 80 mg 85 mg 90 mg 95 Withdrawal dose: 10 mg / week 5 mg / week 10 mg / month Retention to 40 mg Retention on > 40 mg 1 (4.2) 3 (1.4) 5 (2.3) 13 (7.0) 20 (9.3) 17 (12.6) 11 (5.1) 4 (1.9) 19 (18.1) 22 (11.2) 6 (7.4) 32 (19.5) 10 (66.7) 3 (20.0) 2 (13.3) 14 (93.3) 1 (6.7) Consistent 13 (86.7) 111 (72.5) Inconsistent N (%) Dose level 42 (27.5) Consistent
Chart 1 represent the diagrammatic presentation of the basic issues of therapeutic comfort dose (TCD), while chart 2 showed that 149 (69.4%) have ineffective TCD plan and pertaining to risk of relapse on MMT program.
Chart 1. Clinical feature adherence to therapeutic dose setting in MMT program
Chart 2. Evaluation of MMT outcomes related to therapeutic comfort dose (TCD)

Methadone clinic
Table 4. Percentage of relapse among races in MMT Program

Race enroll Malay Chinese Indian Other Total 52 (34.5) 70 (46.3) 28 (18.5) 1 (0.7) P.P N (%) active 40 (26.5) 43 (28.5) 21 (13.9) 0 (0.0) 47 (31.1) 0.001 sig enroll 37 (44.0) 31 (36.9) 16 (19.1) B.M N (%) active 35 (41.6) 31 (36.9) 4 (4.8) 14 (16.7) 0.000 sig enroll 29 (60.4) 10 (20.8) 9 (18.8) B.W N (%) active 26 (54.2) 8 (16.7) 7 (14.6) 7 (14.5) 0.024 sig
Sig: chi-square 12
Discussion The treatment of opioid addiction was a controversial issue since late 70s. A lot of clinical studies were carried out in this span of time to analyze the therapeutic effectiveness of the methadone treatment and majority of them have modest results (Einat Pele, 2005; Kreek M.J, 1992; Leavitt S.B et al., 2000; Ward, J., 1995; Sarz Maxwell, 1999; Jeff ward, 1999; Lubmir Okruhlica, 2002; Icro Maremmani, 2007; Yasukazu Ogai et al., 2007; Jason Luty, 2003). The effectiveness of Methadone maintenance treatment in this study was observed by: 1. Checking the rate of relapse among the MMT patients 2. Medical complication found during the treatment 3. Life quality (medical complication before the treatment and medical complication found during the treatment). Chronic disease and subsequent supportive pharmacotherapy and therapeutic comfort dose setting correlation with urine analysis and psychotherapy session during the treatment. Findings of this study showed high controversial practices in the implementation of MMT program that were found inconsistent to the National guidelines of methadone maintenance treatment protocol of Ministry of Health Malaysia (2006).
Relapse and Defaulted percentage A total of 283 drug addicts were registered in the three registered methadone clinics of Penang state during Jan 2007 to May 2008. The mean S.D age was 41.0 (9.32), majority of them were males (97.5%) and they also formed the majority (53.4%) of admission were found in Hospital Pulau Pinang. The total of 54.6% relapsed cases were identified from all three registered methadone clinics among them 70.1% relapse cases were found in Hospital Pulau Pinang, 19.4% in Butterworth methadone clinic and 10.4% in Bukit Meratajam Hospital. Majority of relapses were identified in the first six month of MMT program, few relapse cases were found after the completion of 1 year
treatment. Majority of relapse cases were reported in Chinese least in Indian. Currently only 12.1% patients were successfully completed the 1 year of treatment, while majority of them only followed the treatment program for a period of 7 12 months of treatment. Few studies identified that craving for drugs, emotional pressure and boredom were the main reasons found among relapsed cases (Research report No. 31, 1997; Yasukazu Ogai et al., 2007). As American National consensus Development panel (1998) reported 50% common drop-out from the MMT studies. Yasukazu Ogai and his collegues worked in Japan for the development and validation of relapse prevention technique through risk scale assessment for drug abusers in Japan, while his basis emphasize were focused on craving, quality of life experience by drug addicts and time frame spent in the treatment program. Modest findings and outcomes were associated with his study but the limitation was applied for Opioid users as the validation was done on cocaine users alone. Such model may help the Ministry of Health Malaysia to control the relapse cases of drug addiction. As certain reliability was found in the study to establish such a model as a preventive measure to reduce relapse cases. Baseline data evidence that 57.3% patients were experienced withdrawal sign & symptoms, while 15.1% suffered with intoxication symptoms and only 27.6% MMT patients showed no evidence of any sign & symptoms during the treatment of methadone. Majority of withdrawal symptoms were yawning and anxiety. The reason behind these findings represent the low dose setting of methadone which would revealed the withdrawal symptoms and cravings that will also associated with the risk of relapse. The current study showed that 89.8% of drug addicts were pre-suffered with different types of medical complications before starting the methadone treatment, while after the completion of 3 months therapy 95.9% of drug addicts among them still carrying the medical complication only 4.1% drug addicts improved, predominantly in Malays. Majority of patients were experiencing General complications (like; fatigue, trouble sleep, loss of appetite, teeth problem and eye/vision problem), 13
musculo-skeletal problem (joint pain and stiffness), neurological disorder (headache, numbness, dizziness, forgetting things), gastro-intestinal problems (constipation, stomach pain, diarrhea) and cardio-respiratory disorders (persistent cough, wheezing, chest pain). These findings could be the possible cause of psycho-disturbance which may lead to depression. It could be the predictive factor for relapse; similar findings were reported by Icro Maremmani (2007) in his study in Italy. Therapeutic comfort dose (TCD) The therapeutic comfort dose (TCD) is termed as the effective dose plan that will suppress the withdrawal sign & symptoms while will not show any sign of intoxication. The objective withdrawal sign & symptoms can be suppressed by increasing the potency dose of methadone while subjective intoxicated symptoms can be overcome by decreasing the potency dose. So TCD is the middle dose setting between objective and subjective sign & symptoms. The findings of the study reported only 30.6% of all the patients were on TCD setting while remaining 69.4% seemed to be on ineffective dose setting. Urine analysis for the drug of abuse is one of the reasonable marker to determine the therapeutic effectiveness of the dose. Several studies suggested that with an increase in the average dose of methadone could possibly lower down the number of drop-out cases and also a lower proportion of urine tested positive for opioid (Maxwell S, Schinderman, 1999; Strain E. C., Stitzer M. L., Liebson I. A., Bigelow G. E, 1998; Strain E.C et al., 1999; Ceplehorn J.RM., Bell J., 1991). Findings of our study showed that 93.5% of total 215 patients induce positive urine analysis for opioid. Majority reports were positive from 8 to 16 month of therapy. Surprisingly 98.8% were on maintenance dose setting of 30 80 mg / day. Similar findings were explained in several studies (Einat Peles et al., 2005; Maxwell, Shinderman, 1999; levit S. B., et al., 2000; Ward. J., 1995; Lubomir. Okruhlica. et al., 2002 and Jason Lutty., 2003). They reported the direct proportion of methadone dose and urine positive results. Their findings were preliminary based on Serum 14
methadone level (SML), majority of them reported that to achieve an effective therapeutic dose it is necessary to adopt a methadone serum level of 600ng/ml or higher for the completely suppression of opioid withdrawal symptoms. Overall all the above researchers suggested that effective therapeutic treatment was achieved with 100mg dose of methadone and above. Cepelhorn & Bell (1991) did a research on drug respondents in Italy, the results of this study concluded that patients who were on methadone dose less than 60 mg have five times more risk of dropping out as those receiving doses of 80 100mg. Similarly a double-blind trials done by Strain et al. (1999) revealed that 53% positive urine results were found after 30 weeks in patients receiving methadone dose 80 100 mg as compared to 62% of those on 40 50 mg of methadone dose setting. In view the results of this study and the standard MOH (Ministry Of Health, Malaysia) guidelines of MMT and other dose optimizing studies conducted all over the World, following were the important issues found in the protocol; No therapeutic monitoring of methadone as SML value. Maintenance dose range was between 30 80 mg. Highly Urine positive results were found even after the 14 months of treatment. Increase relapse rate was found during the first six months of treatment. Increased evidences of withdrawal and intoxicated sign & symptoms. Low percentage of improve quality of life in term of medical conditions in the treatment with methadone. In those who follow the therapy. Conclusion & Recommendations Overall management of drug addiction in three methadone clinics are quiet satisfactory, as considerable number of drop-outs are observed in past one and half year. While dose setting and few other practices are found inconsistent to protocol, although inconsistent practices in the dose setting found satisfactory adherence of patients to MMT program over one year. There are still sizeable gaps in everyday practices of methadone maintenance treatment in Hospital Pulau Penang and Butterwor-
th clinic; like patient follow-up, and counseling particularly emphasizing on addiction education. The study found no improvement in the quality of life among drug addicts as far as medical complications are concerned. Almost every respondent receiving methadone has developed chronic infection. Surprisingly no supportive therapy is added in combination to methadone. Study strongly underlines to highlight this issue because greater risk of relapse is found in such risky group. This can adversely impact on transmission of infection to the other parts of community. There is a strong need to update national guidelines for the management of Drug addiction and to reassure the national addiction control strategy & policy. The aims of this strategy should have to include- reducing the incidence of clinically apparent and ensure the treatment for addicts never been treated before, also reducing the social stigma associated with drug abuse as it is a elemental factor for relapse. Few targets have to set in this policy as; providing clear information to the general public especially the village site, to enable people to make informed decisions about diagnosis, treatment and prevention of transmission of infection, providing a range of easily accessible screening and management options (including general practices), setting secondary poly setting for screening and management, and establish practices for future research thereby improving the evidence base information for providing good practices in management of addiction. Educational programs for practitioners are strongly recommended as to increase the therapeutic outcome of the MMT program by adopting evidence-based treatment in IVDUs. Future researches are required to evaluate practitioners belief, attitudes and practices. Approaches should be optimize HIV/AIDS counseling and promote behaviors that will prevent future drug practices. In order to improve the quality of care and optimize the management of addiction, there is a need to increase the knowledge of nursing staff, development and evaluation of strategies to ensure that the majority of general practitioners have the skills, knowledge and confidence to treat drug addicts and counsel them to adopt a responsive behavior. Alternatively pharmacists expertise in counseling and assessing the effec-
tiveness of pharmacotherapy can be practiced in the methadone clinics to optimize the quality of management of addiction. It is strongly suggested to initiate methadone maintenance program during the rehabilitation period of drug addicts, as they will get a social support as well as better control on drugs during the treatment (urine positive). Literature
1. Sattler, G. (2004), Harm reduction among injecting drug users: Malaysia. Mission report. Manila, Philippines: Regional Office for the western Pacific, World Health Organization. 2. Viknasingam, B and Navartnam, V, 2006. The use of Rapid Assessment methodology to compliment existing national assessment/surveillance system: A study among injecting Drug users in Kepala Batas, Penang, Malaysia, International journal to Drug policy, doi:10.1016/j.drugpro.2006.11.004 3. Vicknasingam, B et al., 2007, Malaysias evolving response to heroin dependence, injecting drug use and HIV/AIDS initial experience with buprenorphine maintenance treatment. Abstract submitted to NIDA international conference, Quebec city, Canada, june 15- 18, 2007. 4. Mazlan, M et al., 2007, Injecting buprenorphine in malaysia: demographic and drug use characteristics of Buprenorphine injectors: Abstract submitted to NIDA international conference, Quebec City, Canada, June 15-18, 2007. 5. Mahmud Mazlan et al., 2006, New Challenges and opportunities in managing substance abusers in Malaysia. Drug and Alcohol review, 25, 473-478. 6. Einat peles, Shaul Schreiber, Miriam Adelson., (2006). Factors predicting retension in treatment: 10-year experience of a methadone maintenance treatment (MMT) clinic in Israel. Drug and Alcohol dependence, 2006, volume 82, issue 3, pp: 211217. 7. Kreek M.J., (1992), Rationale for maintenance pharmacotherapy of opiate dependence, In: OBrein, C.P., Jaffe, J.H. eds. Addictive states. Research publications: Association for research in Nervous and mental disease. Ravan Press, New York: 210.
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8. Levitt S.B et al., (2000), When Enough is not Enough: New perspectives on optima methadone maintenance dose, Mt Sinai J Med. 67(5-6): 404411. 9. Ward, J., (1995), Factor influencing the effectiveness of methadone maintenance treatment: An evaluation of change and innovation in the methadone program in New South Wales, Australia 19851995, PhD thesis. National Drug and Alcohol Research Centre. 10. Jeff ward, Wayne Hall, Richard. P. Mattick., (1999). Role of maintenance treatment in opioid dependence, The Lancet, vol. 353. issue: 9148. pp. 221-226. 11. Lubomir Okruhlica et al., (2002). Does therapeutic threshold of methadone concentration in plasma exist?, Heroin Addiction & Rehabilitation Clinical Problems, 4(1): 29-36. 12. Icro Maremmani, Pier Paolo Pani, Matteo Pacini, Giulio Perugi., 2007. Substance use and quality of Life over 12 months among buprenorphine maintenance-treatment and methadone maintenance-treatment heroin-addicted patients., Journal of Substance Abuse Treatment 33. 91-98. 13. Yasukazu Ogai et al., (2007), Development and validation of the stimulant relapse risk scale for drug abusers in Japan, Drug and Alcohol Dependence, 88: 174-181. 14. Jason Luty., (2003), What works in drug addiction?. Advance in Psychiatric treatment, vol.9, 280-288. 15. Research Report No.31, (1997). A Follow-up study on Drug addicts after treatment and Rehabilitation, Centre of Drug research, University Sains Malaysia (USM). 16. American National consensus Development panel, 1998., Advisory council on the misuse of the drugs, Drug misuse and the environment. London: Home office. 17. Strain EC, et al.,1999. Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA; 281:10001005 18. Saraz Maxwell, Marz Shinderman., (1999). Optimizing Response to methadone maintenance treatment: Higher Dose Methadone, Journal of Psychoactive Drugs: Vol-31(2)
19. Strain E.C., Stitzer M.L., Liebson I.A., Bigelow G.E., (1998), Useful predictors of outcome in methadone-treated patients: Results from a controlled clinical trial with three doses of methadone, Journal of Maintenance in the addiction, 1(3): 15-28. 20. Ceplehorn J.R.M., Bell J. (1991), Methadone dosage and retention of patients in maintenance treatment, Med J Aust, 154(1): 195-199. Corresponding author: Forouzan Bayat Nejad H/p: + 98-9355491159 No. 45, 2nd Floor, Gisha 33th St., Tehran, Iran E-mail: forouzan@ioksp.com, forouzan.bayat@gmail.com
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use of mathematical modeling in predicting the impact of a disease: an example of measles dynamic model
maTemaTSko modeLiraNje u PredVidjaNju kreTaNja boLeSTi: diNamiCki modeL morbiLa
Semra Cavaljuga, Mladen Cavaljuga, Mira Cavaljuga Institute of Epidemiology and Biostatistics, Faculty of Medicine, University of Sarajevo Bosnia and Herzegovina
Summary Protecting children from vaccine-preventable diseases, such as measles, is among primary goals of public health professionals worldwide. Since vaccination turned out to be the most effective strategy against major childhood diseases, developing a mathematical model that would predict an optimal vaccine coverage level needed to control the spread of these diseases becomes a challenge for various experts Worldwide as well designed mathematical model could be extremely helpful for the daily routine practice. Elaborating a mathematical models for monitoring of measles with its vaccination coverage and predicting the impact of this disease in a population is the basic objective of this paper. The model was elaborated with the population of B&H as at the census of 1971 -- just before the obligatory vaccination was introduced -- used as a theoretical population. The epidemiological classification of the population was performed for all of the age groups. In this paper we assume that all vaccinated individuals develop antibody following vaccination. Known variables of susceptible, sick and immune population to create a mathematical model of the dynamics of measles showing spread within a population to design this model were used. A dynamic model expressed by a global model with its sub-model based on the dynamics of measles infection was created. The model, which fully incorporates elements of measles dynamics relevant for the spread
of the disease is quantitative and dynamic. It facilitates long-term projections of the spread of the disease and identifies the possibilities for an efficient protection. The model shows percentage of the immune persons at any given immunisation level and morbidity and lethality that can be expected at that level of immunisation. Key words: mathematical models, measles, disease dynamics, vaccination, Bosnia and Herzegovina Saetak Meu najvanijim ciljevima svih zaposlenih u sektoru javnog zdravstva je i prevencija djece od zaraznih bolesti kao to su morbili. Poto se pokazalo da je vakcinacija najefikasnija strategija u prevenciji djeijih zaraznih bolesti pravljenje matematskog modela koji predvia optimalan procenat obuhvata vakcinacijom potreban da bi se kontrolisalo irenje ovih bolesti u nekoj populaciji je, ne samo postao izazov za eksperte u ovoj oblasti irom svijeta, nego bi takav model bio i vrlo koristan u svakodnevnoj praksi. Osnovni cilj ovoga rada je dizajniranje matematskog modela monitoringa morbila sa procentom obuhvata vakcinacijom u predvianju kretanja ove bolesti u populaciji. Ovaj model je napravljen na populaciji Bosne i Hercegovine prema popisu stanovnitva iz 1971. godine, odnosno neposredno prije uvoenja obavezne vakcine protiv ove bolesti u 17
program imunizacija, koja je uzeta kao teoretska populacija. Epidemioloka klasifikacija populacije je napravljena za sve dobne grupe. U ovom radu je pretpostavljeno da su svi vakcinisani razvili antitijela nakon dobivene vaccine, odnosno da je svaka vakcinacija i imunizacija. Pri dizajniranju matematskog modela dinamike morbila koji pokazuje irenje bolesti u populaciji koritene su poznate varijable: osjetljivih, bolesnih i imunih. Dinamiki model baziran na dinamici infekcije morbilima je predstavljen kao globalni model sa svojim sub-modelom. Ovaj model, koji u potpunosti ukljuuje sve elemente dinamike morbila vanih za irenje bolesti, je kvantitativan i dinamiki. On ukljuuje dugoronu projekciju irenja bolesti i identificira mogunosti za efikasnu prevenciju. Model pokazuje procenat imunih osoba za bilo koji nivo obuhvata vakcinacijom, kao i koji se morbiditet i letalitet mogu oekivati za taj procenat obuhvata. Kljune rijei: matematiki modeli, morbili, dinamika bolesti, vakcinacija, Bosna i Hercegovina Introduction Diseases that motivated the development of modern epidemiological theory are arguably those of childhood infections, most notably measles. This arose predominantly from their large public health importance in the late 19th and early 20th century (5). In middle 19th century Englands sophisticated system of vital statistics was initiated by William Farr, and data series relating to several childhood infections became available that were both reliable enough and long enough to generate hypotheses about the mechanisms underlying epidemic spread. It was only at this time that the microbe theory of infection - the notion that certain infections are caused by living organisms multiplying within the host and capable of being transmitted between hosts replacing the miasmatic theory of infection - became firmly established, due to the work of Pasteur and others. Many facts are widely known about Measles: it is an acute, highly communicable viral disease -- highly contagious through person-to-person transmission with > 90% secondary attack rates among susceptible persons -- caused by the Me18
asles virus, a member of the genus Morbillivirus of the family Paramyxoviridae. It is the first and worst eruptive fever occurring during childhood. It produces also a characteristic red blotchy rash which appears on the third day to seventh day. The disease is more serious in infants and adults then in children. Complications may result from viral replication or bacterial superinfection and include mild form as Otitis media, but can lead to serious and even fatal including pneumonia, croup, diarrhea and encephalitis. Many infected children subsequently suffer blindness, deafness or impaired vision. Measles confer lifelong immunity from further attacks. The case fatality rates in the developing countries are estimated to be between 3-5%, but commonly 10-30% in some localities (1). Prior to widespread immunization, measles with its contagionity index over 95% was common in childhood (2). The first measles vaccine was introduced by Edmonston 1963 (2). Worldwide today, measles vaccination has been very effective, preventing an estimated 80 million cases and 4.5 million deaths annually (3). Although global incidence has been significantly reduced through vaccination, measles remains an important public health problem. Since vaccination coverage is not uniformly high worldwide, measles stands as the leading vaccine-preventable killer of children worldwide; it is estimated to have caused 614,000 global deaths annually in 2002, with more than half of measles deaths occur in Sub-Saharan Africa (4). The World Health Assembly in 1989 and the World Summit for Children in 1990 set goals for measles morbidity and mortality reduction of 90% and 95%, respectively, compared with prevaccine levels (3). Therefore, vaccination against measles with one dose is one of the components of WHOs EPI (World Health Organisations Expanded Programme on Immunization) implemented from the 1970s in most countries. The fundamental characteristic of vaccination is that it reduces the incidence of disease in those immunized, the susceptible. Also, vaccination protects indirectly non-vaccinated susceptibles against infection by producing herd immunity. Since the introduction of the vaccination incidence of measles has been decreasing worldwide.
Mathematical modeling of measles The most striking aspect of measles epidemics (particularly observed prior to vaccination era), i.e. their regular cyclic behavior, was noticed first by Arthur Ransome around 1880 (5). Cyclic occurrence was observed in Bosnia and Herzegovina as well. Speculation about the underlying cause centered on the availability of a sufficient number of susceptible individuals of the right age in close enough proximity to each other; hence precursory ideas of critical community sizes for sustaining endemic measles were present. A factor that commonly occurs in many mathematical models of a disease - particularly measles - is the age structure of the population. The age of a population and seasonality linked to school season were recognized as important as early as 1896. William Hamer published a discrete time epidemic model for the transmission of measles in 1906. The work of W.H. Hamer was continued some decade after with H.E. Soper and this model today is known as Hamer-Soper model. Their observation can be reformulated as stating that the incidence of new cases in a time interval is proportional to the product SI of the (spatial) density S of susceptibles and the (spatial) density I of infectives in the population. This assumption of mass action - in analogy to its origin in chemical reaction kinetics is fundamental to the modern theory of deterministic epidemic modeling. The popularity of mass action is explained by its mathematical convenience and the fact that at low population densities it is a reasonable approximation of a much more complex contact process (10, 11). Following Hamer and Soper, many measles mathematical models have being created. Measles in Bosnia and Herzegovina Prior to introducing mandatory vaccination in 1970 for all children of 12 months, average morbidity rate for the period 1952-1970 was 252.0 0/0000. In the period following 1970, from 1970 to 1976, measured average morbidity rate was 138.5 0/0000. Maintaining rather high incidence rate even after introduction of the immunization program was the leading reason that in Bosnia and Herzegovina
single-dose revaccination with Measles vaccine was introduced 1976 for all children age 7 (2). Morbidity rate following this period was significantly lower than recorded previously 57.5 0/0000 in average from 1977 until 1992 (8, 9). Graph 1 shows measles morbidity rate per 100.000 populations in Bosnia and Herzegovina 1952-1992. Data on any communicable disease after 1992 due to the 1992-1995 war, followed by the health system restructuring in the transition and posttransition period are not taken into this paper as they are considered unreliable. Despite very good vaccine with high coverage level, measles persist. Oscillation in a fight against measles remain present regardless all efforts. In this paper we tried to give a method of prediction of magnitude of a future epidemic based on a population age structure and vaccination level. The basic objective of this paper is a discussion of an adequate theoretical model for monitoring of measles and predicting the impact of measles in population. Sources & Methods From the data collected from standard, official sources, such as Statistical yearbooks for population (age and sex structure) [(7)]; and other relevant epidemiological and official sources such is e.g. the PhD thesis of R. Muli, MD, MSc, from 1990 (8) who refer to the major relevant official sources: Annual analyses on outcome of immunization (8); Central contagious diseases register of the Public Health Institute (8); Records on immunization status of the affected population groups (8); etc., a general mathematical model was formulated, and definitions found for several major variables: - Key variables - Assumptions on relations among the key variables, - Course of events the epidemiological process (changes occurring in the key variables), - Dynamics of the disease. The presented model is quantitative, but it clearly reflects the transition of the population from one epidemiological category into another. 19
The population is classified according to the following criteria: - Demographic, based on the age groups: - Newborns (0-1 years) - Preschool children (1-7 years) - Remaining population (7 and more years) - Epidemiological, based on the health status: - Population at risk - Affected population - Immune population The classifications were combined, and the epidemiological, health status categories were determined in each age group. The global model and its sub-model are presented graphically as blockdiagram showing clear flow from one demographic as well as epidemiological category to another in Charts 1 and 2. Charts 3 and 4 show empirical model for the given population with calculated situation in year t based on theoretical population of Bosnia and Herzegovina, according to the census in 1971 as presented in Tables 1 and 2. Results and discussion Simulation models for the year t and for a theoretical population and input are shown in charts 3 and 4. The age structure of the theoretical population (Table 1) is the same as the structure of population of Bosnia and Herzegovina as at 1971 census which overlaps with the very first year of measles vaccination, while the theoretical morbidity (Table 2) was based on the official records of B&H Public Health Institute for the period before the immunization became mandatory (1961 - 70) and after the introduction of revaccination. Although model is hypothetical and theoretical it is empirical too as the basis for prediction is a real population of BiH virgin of any Measles immunization strains as it is prior to introducing Measles immunization program in the 1970/1971 season. Quantitative, mathematical models of measles can be: 1) Empirical, created for the purpose of investigating and elimination of an epidemic for a specific country for a given time20
or: 2) Theoretical, based on the time series analysis for creation of a quantitative frame for an epidemic and - when possible for the basic strategy for its elimination. Examples of this group are: Box-Jenkins model, which uses existing data on a disease and hence belongs to autoregressive models; model using moving averages in addition to autoregression method is known as STARMA model or Space-Time-AutoregressiveMoving-Average (14); MacDonald uses stochastic model with exact population data and several assumptions (15); mathematical model for dynamics of directly transmitted viral and bacterial infections, or Anderson & May model, which was used to estimate that about 96% of a population should be vaccinated against measles in order to eradicate the disease, assuming that each vaccination is immunization. One of their conclusions from analysis of measles data for England and Wales since 1968 is that the risk of new measles outbreaks is present if herd immunity falls below 94% (16). Unlike the mentioned models, model presented in this paper represents an attempt of creation of a simple tool, flexible enough to take into account epidemic process with all its phases and to serve as an empirical model if needed. The empirical model should be based on the available data and formulated goals of measles eliminations strategy and should provide precise indicators and results. This model combines approaches developed by the models which monitor epidemic process and time flow of a disease and models allowing monitoring of a disease among different age groups and it provides an option for quantitative analysis of both aspects. The model incorporates and defines all phases of an epidemiological process and also serves as
frame such as: Hamer-Soper (10,11); chain binomial Reed-Frost model (12); discrete time model known as S-I-R or Suspect -Infectious-Removed (13), which can be considered as continuation of the Reed-Frost model as it uses the same base of stochastic contagious index;
an empirical foundation for predicting concrete indicators and results. The flexibility of the model allows: Simple introduction of additional age groups (e.g. school children 7-14 years and/or 14-18, students, adults, etc.), Simple introduction of additional epidemiological categories along a logical chain of newborns, maternal immune, persons at risk, latent, infectious or a combination of categories, Simple monitoring of seasonal variations, even in specifically set time-intervals of particular interest (e.g. school year starts 1 September, ends on 1 July. In between those two dates there are high degree of likelihood that school children will come into contact with infected persons, and that period can be incorporated in this model) With the presented model, based on dynamic quantitative analysis, changes of indicators in any period of time, most significantly during the epidemics, can be easily taken into account. If fixedindicators time-series analysis is used, however, the variations will on a long run be smoothed. The other quantitative approach to measles epidemic modeling could be statistical. However, there are two reasons why in our case a statistical model would not be acceptable:
1) Statistical approach does not view the problem from the same angle; 2) Statistical model would not predict vaccination coverage drop in Bosnia and Herzegovina to 57% during 1992-1995 (17). Conclusions This model facilitates long-term projections of measles morbidity and lethality for any given level of immunization. Based on the actual immunization level, it is possible to predict immunity, morbidity and lethality figures for any given period of time, as well as the outcome of any future immunization campaign. The model presented in this paper cannot be understood as a simple application of quantitative methods in medicine. It should be seen as an instrument in understanding of a problem, and not an answer to it. It allows the measles problem to be reviewed from many angles: clinical, epidemiological and population-based, as well as operational - simultaneous, dynamic, statistical, etc. It also provides for creation of instruments for solving the problem.
Table 1. Age Structure of Population of Bosnia and Herzegovina 1971

Population Less than 1 year 1 7 years More than 7 years Total 2,210 13,350 84,440 100,000 % 2.21 13.35 84.44 100.00
Table 2. Measles Morbidity in Bosnia and Herzegovina

Mb 0/0000 1961 1970 Less than 1 year 1 7 years More than 7 years 601 1,959 59 Mb 0/0000 1981 - 1992 160 301 132
21
Chart 1. Global model block diagram Chart 3. Global simulation model block diagram (situation in year t)
Chart 2. Measles dynamics sub-model with vaccination
Chart 4. Simulation sub-model (vaccination success 95 %)
22
Graph 1. Measles morbidity rate per 100.000 populations in Bosnia and Herzegovina 19521992
7. SZZZ. Statistiki godinjaci o narodnom zdravlju i zdravstvenoj zatiti u SFR Jugoslaviji. Savezni zavod za zdravstvenu zatitu, 1961.-1990. 8. Muli R. Epidemioloke karakteristike morbila na podruju SR Bosne i Hercegovine u period prije i poslije uvoenja obavezne vakcinancije. Doktorska disertacija. Medicinski fakultet Univerziteta u Sarajevu, Sarajevo 1990. 9. ZZZBiH. Epidemioloki bilten. Zavod za zdravstvenu zatitu Bosne i Hercegovine, 1992. God. II; Br. 10, 10. Hamer WH. Epidemic diseases in England the evidence of variability and persistency of types. Lancet, 1906. 2: (733-739),
Source: Muli PhD Thesis 1990 (8); Epidemiological Bulletin 1992 IPH BiH (9)
11. Soper HE. Interpretation of periodicity in disease prevalence. Journal of the Royal Statistical Society A, 1929.92: (34-73), 12. Greenwood M. On the statistical measure of infectiousness. Journal of Hygiene. 1931. 31: (336351), 13. Enderle JD. A Discrete-Time Communicable Disease Model with a Stochastic Rate for Nonhomogeneus Population. ISA, 1991. Paper#91-010, 14. Cliff AD. Statistical modeling of measles and influence outbreaks. Statistical Methods in Medical Research. 1993; 2: (43-73), 15. Thacker SB and Millar DJ. Mathematical modeling and Attempts to Eliminate Measles: A Tribute to Late Professor George Macdonald. American Journal of Epidemiology, 1991. 133; 6: (517525), 16. Anderson RM, May RM. Directly transmitted infectious diseases: control by vaccination. Science, 1982. 215: (1053-1060), 17. avaljuga S. Evaluacija programa obaveznih imunizacija u ratnom periodu u BiH. Specijalistiki rad. Medicinski fakultet Univerziteta u Sarajevu. 1995. Corresponding author: Semra Cavaljuga Institute of Epidemiology and Biostatistics Faculty of Medicine, University of Sarajevo Cekalua 90, 71 000 Sarajevo Bosnia and Herzegovina email: smcavalj@bih.net.ba
Literature
1. Heyman DL. (Ed.) Control of Communicable diseases Manual. 18th Edition. APHA, Washinghton DC. 2004; (347-354), 2. Gaon JA, Borjanovi S, Vukovi B, et al. Specijalna epidemiologija akutnih zaraznih bolesti. Svjetlost, Sarajevo 1982. (25-33) , 3. World Health Organization, Department of vaccines and biological. Measles Technical Working Group: strategies for measles control and elimination. Report of a meeting, Geneva, 11-12 May 2000. Geneva, Switzerland: World Health Organization, 2001., 4. Moussa Tessa O. Mathematical model for control of measles by vaccination. Mali Symposium of Applied Sciences - MSAS Aug 2006. http://www. maliwatch.org, 18 Dec 2008, 5. Roberts MG, Heesterbeek JAP. MATHEMATICAL MODELS IN EPIDEMIOLOGY, in Mathematical Models, [Eds. Filar JA, Krawczyk JB.] in Encyclopedia of Life Support Systems (EOLSS), Developed under the Auspices of the UNESCO, Eolss Publishers, Oxford ,UK, 2003. http://www.eolss.net, 20 Dec 2008, 6. avaljuga S. Predvianje kretanja morbila u populaciji (Dinamiki model). Magistarski rad. Medicinski fakultet Univerziteta u Sarajevu, Sarajevo 1997.
23
Health Promotion in Silicon Valley: a Study of 11 Corporations

PromoCija zdraVLja u SiLikoNSkoj doLiNi: STudija ProVedeNa u 11 korPoraCija
Yann A. Meunier Stanford Health Promotion Network
Summary A study was conducted with 11 organizations from Silicon Valley by the Stanford Health Promotion Network in December 2008 to assess the extent and quality of their corporate health promotion programs. It showed that in the sample No organization had a totally integrated science-based approach to health promotion, Organizations have a wide array of common issues in this area. The main topics of interest are how to measure return on investment and benchmark against the industry and demographics and there is a role to play for entities such as the Stanford Health Promotion Network to galvanize, enable and serve as a resource center for health promotion. Key Words: Health Promotion, Study, Silicon Valley, Stanford Health Promotion Network Introduction A study was conducted in December 2008 by the Stanford Health Promotion Network on health promotion programs in Silicon Valley. Its main purposes were: - To identify the top 4 health promotion issues that employers have relating to health plans and vice versa. - To have a profile of the extent and quality of corporate health promotion programs in these corporations.
Methodology 11 companies from Silicon Valley were studied in December 2008, including 5 cutting-edge global leaders. Their size varied from 120 to 20,000 people. Their spokespersons held the following positions: General Manager, Director (2), Regional Vice-President, Senior Manager (Benefits), Senior Benefits Analyst, Senior Account Manager, Corporate Health and Safety Manager, Employee Health Services Manager, Fitness Operations Manager, Principal. Two methods were used, as follows: a) An intensive and dynamic brain storming session with corporation representatives, which aimed at identifying the top 8 health promotion issues that they faced b) Gathering answers to the following 12 questions: 1. How would you rate support from your management to corporate health promotion programs? 2. Does your corporation have full-time health promotion employee(s)? 3. Does your corporation outsource its health promotion programs? 4. Is your corporation working with health plans regarding health promotion programs? 5. Does your corporation use a health risk assessment? 6. Did your corporation have an initial operating budget for health promotion programs?
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7. How would you rate your corporation health promotion programs efficiency? 8. Does you corporation measure return on investment in its health promotion programs? 9. Does your corporation have fitness programs? 10. Does your corporation have health promotion success stories? 11.What are the best aspects of your corporate health promotion programs? 12. What are your wishes for improving your corporate health promotion programs? Results The top 8 health promotion issues were as follows: - Performance guarantees for health outcomes / engagement - Benchmarking against industry and demographics - Communication to health plan members so that they know what is available to them - Providing incentive for healthy behavior - Senior management support - Internal committee - Budget incentives - Goals / objectives The answers to the above questionnaire were as follows: 1. Support from management to corporate health promotion programs: 4.1/5 (average) 2. Full-time health promotion employee(s): No: 2 / Yes: 6 3. Outsourcing of health promotion programs: No: 2 / Yes: 6 4. Working with health plans: No: 3 / Yes: 5 5. Health risk assessment: No: 3 / Yes: 7 6. Operating initial budget for health promotion programs: No: 3 / Yes: 8 7. Health promotion programs efficiency rating: 3.2/5 (average) 8. Return on investment assessment: No: 6 / Yes: 2 9. Fitness programs: No: 3 / Yes: 7
10. Health promotion success stories: No: 3 / Yes: 7 11. Best aspects of health promotion programs: Some programs from carriers are fee of charge, fitness group challenges, incorporation of employee and community programs, input of employees, cutting-edge fitness classes and programs, innovative web-based offerings to maximize employee reach and engagement, diversity and flexibility, qualified service provider, employee steering and implementation, variety, comprehensiveness, leadership buy-in, communication, integrated approach, executive commitment 12. Wishes for improving health promotion programs: On-site classes, weight management meetings, full complement of programs, HRA with labs available to all employees, more numerous and more accessible educational sessions Discussion Although drawn from a limited number of companies the survey data identified some common tendencies, as follows: * It is remarkable that regarding health promotion programs employers and health plans face many identical challenges among themselves. Before the study a plausible assumption was that small and medium size organizations had mostly different issues than large multinational corporations. Our results show that it is not the case. This finding has tremendous implications on the design and implementation of corporate health promotion programs1,2,3,4,5,6. * Most companies stated that they support corporate health promotion programs a lot (average: 4.1/5). However, the vast majority (6/8) outsources them, which shows that their commitment is not to the point of integrating them into their DNA. The discrepancy between perception and reality confirms that health promotion is not anchored in the workplace concept of corporate leaders. It also outlines the need for sensitization of corporate leadership to health promotion issues. This can be 25
done best by third parties with no vested interest such as the Stanford Health Promotion Network7. * No company has a comprehensive health promotion program i.e., including science-based health risk assessment, motivation rating, behavior change program, efficiency evaluation, return on investment determination, etc. Moreover, the notion that a science-based foundation is necessary in order to guarantee quality, consistency and results is not widespread. This calls for and educational approach to health promotion in the workplace8,9,10. * 37.5% of companies are not working with health plans. This fact is particularly interesting concerning small and medium enterprises. Indeed, health plans have some free corporate health promotion programs. In forums like the ones organized by the Stanford Health Promotion Network employers can learn from one another and from health plans, consultants and specialists. The interaction between these professionals hopefully will lead to a harmonization of best practices which will result in decreased health costs. * Most companies have health promotion success stories. This affirmation carries hope for the future of health promotion programs. The showcasing of such successes among co-workers can go a long way in advocating healthy behavior change. * The best aspects of corporate health promotion programs are multiple. It is important that these features be shared with others so that everybody can learn best practices and save time and money in the creation and implementation of corporate health promotion programs. * The best wishes for health promotion programs are varied. Therefore, there is much to be done and lots of room for improvement for corporate health promotion programs11,12,13. * The health promotion programs efficiency rating was relatively low (average: 3.2/5). The reasons for the poor performance in the efficiency of these programs must be determined on a case by case basis and ideally they should be shared with others to avoid repeating the same mistakes14,15,16. * Return on investment is a big issue to the vast majority of corporations (6 dont or cant measure it). This crucial topic must be addressed thoroughly at various levels in order to get the buy-in from upper management for corporate health promotion 26
programs and incite managers to champion health promotion initiatives17,18,19,20,21. The fact that some corporations sent their benefit executives reveals that they consider health promotion as a benefit to employees and not as a profit generating investment in their human capital. * Finally, for health promotion purposes, collaboration and team building are essential22,23,24,25,26,27,28. Conclusion The extent and quality of corporate health promotion programs in Silicon Valley varies greatly. However, corporations have several common issues. These can be better uncovered and addressed in catalytic think tanks such as the Stanford Health Promotion Network. The ability of these entities to produce positive outcomes can result in an overall improvement of healthcare not only in Silicon Valley but also at the state and national levels. Although this survey sheds some valuable new light on many issues, further work is needed on a wider scale to establish more reliable data in the same field.
Literature
1. Design of Workplace Health Promotion Programs, Michael P. ODonnell. 1995. Published by the American Journal of Health Promotion. 2. Hunnicutt, D., Deming, A., and Baun, B., Health Promotion Sourcebook for Small Business. Wellness Councils of America, 1998. 3. Wellness Councils of America (WELCOA): www. welcoa.org 4. National Business Coalition on Health (NBCH): www.nbch.org 5. Health Enhancement Research (HERO): www.the-hero.org Organization
16. Allen, Judd, Culture Change Planner, available online at www.healthyculture.com 17. Chapman, Larry S. Program Evaluation: A Key to Wellness Program Survival, 1996. 18. McKenzie J. and Smeltzer J. Planning, Implementing, and Evaluating Health Promotion Programs: A Primer, 2nd Edition Allyn and Bacon, 1997. 19. Schaloc, R. Outcome-Based Evaluation. Plenum Press, 1995. 20. Integrated Benefits, Inc. (IBI): www.ibionline.com 21. Healthcare Effectiveness Data and Information Set (HEDIS) in National Committee for Quality Assurance (NCQA): www.ncqa.org 22. Kanter, Rosabeth M., Successful Partnerships Manage the Relationship, not just the Deal. Collaborative Advantage, Harvard Business Review, July/August 1994. 23. Meyer, C., How the Right Measures Help Teams Excel, Harvard Business Review, May/June 1994. 24. Rapaport, R., To Build a Winning Team: An Interview with Head Coach Bill Walsh, Harvard Business Review, January/February 1993. 25. Wetlaufer, S., The Team That Wasnt, Harvard Business Review, November/December 1994. 26. Social Marketing by Philip Kotler and Eduardo Roberto. 27. Center for Disease Control and Prevention (CDC): www.cdc.gov 28. Consumer Assessment of Healthcare (CAHPS): www.cmc.hhs.gov/caps
6. 7 Steps to Health Promotion, Daphne Woolf and Veronica Marsden. Group Healthcare Management. February 1996. 7. Chapman, Larry S., Securing Support From Top Management. The Art of Health Promotion, Vol. 1: No. 2, May/June 1997, pp. 1-7. 8. Chapman, L., What Newer Forms of Health Management Technology Can Be Used in Programming? The Art of Health Promotion, September/October 1997, Vol. 1, No 4. 9. Chapman, L.S., Planning Wellness Getting Off to a Good Start. Seattle, WA; Summex Corporation, 1996. 10. McGinnis, J.M., Worksite Health Promotion Activities Summary Report, U.S. Department of Health and Human Services. Office of Disease Prevention and Health Promotion, 1992. 11. U.S. Preventive Services Task Force (USPSTF) in Agency for Healthcare Research and Quality (AHRQ): www.ahrq.gov 12. Pacific Business Group on Health (PBGH): www. pbgh.org 13. Estes Park Institute: www.estespark.org 14. Health Promotion: Sourcebook for Small Businesses published by the Wellness Councils of America and Canada. 15. Green, L.W., and Kreuter, M.W., Health Promotion Planning, An Educational and Environmental Approach, (2nd ed.). Mountain View, CA; Mayfield Publishing Company, 1991.
Corresponding author: Yann A. Meunier * Program Manager Stanford Health Promotion Network 1070 Arastradero Road, Rm 3C03G Palo Alto, CA 94304-1334 Tel: (650) 721 2802 Fax: (650) 723 6450 E-mail: ymeunier@stanford.edu http://shpn.stanford.edu
27
The most frequent reasons for visits to patients in emergency medical Care Center Sarajevo
Najei razLozi za kuNe PoSjeTe u zaVodu za HiTNu mediCiNSku Pomo SarajeVo
Enes Slatina Institute of Emergency Medical Care (IEMC) Sarajevo, Bosnia and Herzegovina
Summary The Institute of Emergency Medical Care Sarajevo is the institution which deals, in organized way, with rendering the emergency medical care at the level of Canton of Sarajevo. Rendering the medical care is carried out through the Central Outpatient Department of Emergency Medical Care and there exists the General Outpatient Department with four receiving boxes. There exists also the Pediatric Department as well as Surgical Department with additional diagnostic services. Aiming at faster and easier accessibility of emergency medical care, rendering help is carried out through the (*Emergency Medical Care) branches at the level of the municipality of Ilida during 24 hours, while the other branches work only during the evening/night hours and it is in function in: Hadii, Saraj polje (Novi Grad), Vogoa, Ilija and Trnovo. It is very specific for the work of Emergency Medical Care to work fast in the field which is carried out upon citizens phone call to Dispatch Centre on phone numbers: 124 and 611 111. While serving the purpose of justifiability and urgency, the ambulance goes to perform visits to homes, and along with it, depending on urgency level, we possess also differently equipped teams and ambulance vehicles for rendering emergency medical care. In this work, there are analyzed two weeks of emergency medical care teams going to the field. By random selection, these are first two weeks of the month of December, 2004, and, we wished to establish level of urgency of visits 28
to homes, justifiability of visits depending on the level of urgency, most frequent reasons for interventions, as well as patients gender and age, also, which are usual problems of emergency medical care in the field. Key words: emergency medical care, Dispatch Centre, visits to homes. Saetak Zavod za hitnu medicinsku pomo Sarajevo je ustanova koja se organizovano bavi pruanjem hitne medicinske pomoi na nivou Kantona Sarajevo. Pruanje pomoi se obavlja preko centralne ambulante hitne pomoi gdje postoji opta ambulanta sa etiri prijemna boksa. Postoji i pedijatrijska ambulanta kao i hiruka ambulanta uz pratee dijagnostike slube. Radi bre i lake dostupnosti hitne pomoi, pruanje pomoi se obavlja i preko punktova na nivou opina Ilida 24 sata dok ostalu punktovi rade samo u veernjim asovima i to Hadii, Saraj polje (Novi Grad), Vogoa, Ilija i Trnovo. Ono to ini specifinost rada Hitne pomoi je brzi rad na terenu koji se obavlja na poziv graana u dispeerski centar na tel: 124 i 611 111. Svrsishodno opravdanosti i hitnosti, odlazi se u kune posjete, s tim da ovisno o stepenu hitnosti posjedujemo i razliito opremljene ekipe i sanitetska vozila za pruanje hitne medicinske pomoi. U ovom radu su analizirane dvije sedmice rada ekipa hitne pomoi koje odlaze na teren. Sluajnim odabirom to su prve dvije sedmice mjeseca
decembra 2004., sa eljom da utvrdimo stepen hitnosti kunih posjeta, opravdanost posjeta ovisno o stepenu hitnosti, najei razlozi za intervencije, kao i spol i uzrast pacijenata; takoe, koji su to uobiajeni problemi hitne pomoi na terenu. Kljune rijei: hitna pomo, dispeerski centar, kune posjete. 1. Introduction The IEMC Sarajevo is the institution which offers help, in organized way, to all the citizens in the Canton of Sarajevo 24 hours or 365 days per year. Offering help is carried out in the outpatient departments of the Institute as well as by means of emergency medical care teams offering help in the field. In the Institute, the help is offered by staff members who are trained and qualified for all the possible situations either in the outpatient department or in the field. In this work, there is analyzed the field work of emergency medical teams. The experienced dispatchers receive the phone calls for visits to homes on phone numbers 124 or 611 111. The staff members receiving the phone calls in the Dispatch Centre, which usually represents the key part of the service, have several years of work experience, and, their duty is to be kind and to calm down the person asking for help, while giving them useful instructions. After having received the phone call, the dispatcher carries out triage of call depending on the level of urgency, while directing the calls, by communication system, to the field teams. By good communication system, there is enabled sending promptly the information on urgent case as well as organized management of service and field teams. When receiving the phone call, the dispatcher poses certain questions. 1. What did happen type of injury or illness and number of injured persons? 2. Where did that occur? 3. When did it happen? 4. When it is about the first degree of urgency, s/he asks if the person is conscious and if the person breathes? 5. What is the name of person (if possible to find out) and address? 6. Who does call and from which phone number (in case of need of subsequent contact)?
Depending on urgency degree, in the IEMC, there exist three degrees of urgency for work of field teams: The first degree is the degree for which it is a must to intervene, if possible, within first five minutes; usually it is about sudden heart disease or sudden failure of previously sick heart, CVI, traffic accidents, fights, falls, consciousness crises, delivery, profuse bleeding and all other situations when the life is directly endangered. The second degree of urgency represent usually the patients with chronic diseases in the phase of exacerbation when the life is not directly endangered and which can wait for the arrival of an ambulance for up to 30 minutes. The examples are: hypertension, chronic obstructive bronchitis (COB), febrile conditions, hypotention etc. The third degree of urgency represents usually giving the regular therapy in the field (for instance, imovable patients or patients who are movable with a lot of difficulty) or solving by therapy against pain for persons with verified cancer, lumbar sciatica when it is possibe to wait up to 1 hour. 2. Goal of work The goal of work is to establish the most frequent reasons for visits to homes of IEMC Sarajevo. 3. Material and methods This retrospective research comprises the emergency medical interventions in the field during first two weeks in the month of December, 2004. In the analysis, there were used the working protocols from the Dispatch Centre. There was analyzed the total of 688 patients. 4. Statistical analysis In the statistical analysis, there were used computer programs Microsoft Word and Excel. 29
Table 1.
Age Gender Total M 2 O 9 F 4 M 3 10 19 F 5 M 11 20 29 F 5 M 3 30 39 F 6 M 5 40 49 F 10 M 7 50 59 F 19 M 32 60 69 F 41 70 M 37 + Unknown F M F
84 188 215
5. Results Table 1. From the table, it is visible that the ambulance in the field intervened the most in cases of patients who are 70 years of age and over 70.
Graph 1. It shows he ratio of patients by gender and it is visible that the women seek help more in the field
Graph 4. The most frequent CVS diseases in field are myocardiopathies
Graph 2. The most frequent CNS disease in the field is the CVI ac.
Graph 5. The most frequently the injuries in the field are caused by falls
Graph 3. The most frequent respiratory disease in the field is COB Graph 6. The most frequent intoxications are caused by ethyl-alcohol 30
Graph 7. The most frequent diseases requiring visit to home are CVS diseases
Graph 8. The most of cases in the field are of II degree of urgency
Graph 9. The largest number of patients stay at home or is sent home after offered emergency medical care 6. Discussion From graphic and tabular analysis of information, it is visible that out of 688 patients, the largest
number of interventions in the field were carried out due to the persons who suffer cardiovascular diseases, then respiratory ones, then CVS diseases etc. (graph 7.). The cardiovascular diseases are the first reasons of mortality in the world as well as in our country. The table 1 shows the ratio of patients by age and it is visible that the largest number of interventions (visits to homes) is for the patients who are 70 years old and older than that. The number of interventions grows as the persons are older. The graph 1 shows the relation of patients by gender and it is visible that the women (58%) ask for help more often. The graph 2 shows the most frequent cardiovascular diseases when the ambulance intervened and it is visible that the most frequently the patients suffer myocardiopthy. The graph 3 shows the CVS diseases and the cases of acute stroke are the most frequent ones. The graph 4 shows the most frequent respiratory diseases and it is visible that it is COB. The graph 5 shows the most frequent injuries in the field and it is visible that these are the falls due to winter period, icy pavements from which the ice and snow were not removed. The teams intervened when 5 traffic accidents occured and there were 7 injured persons. The graph 6 shows the most frequent reasons of intoxication in the field and it is the intoxication with ethyl-alcohol, while there was a significant number of drug overdose. The graph 8 shows the percentage-related relation of urgency of interventions at home and it is visible thate there are the most of interventions of second degree of urgency, then of the first one. The graph 9 shows where the patients are sent after the intervention of emergency medical care. It is visible there that the majority of patients are sent home or they stay at home and the reason for that is the fact that the majority of patients are of II and III degree of urgency. The basic issue which influenced the results and made difficult the work of Emergency Medical Care is a huge number of phone calls made by citizens. Unlike the Emergency Medical Care in Zagreb, the Sarajevo Emergency Medical Care have five times more interventions. The reason for that is a large number of uninsured patients who ask for help in the Emergency Medical Care. There is certain number of unjustified phone calls which cannot be sanctioned. Also, the reason is the fact that scheduling appointment in the outpa31
tient departments of Health Centres, which takes a lot of time, influences the increased number of patients, especially of second degree of urgency. Poor cooperation between the Emergency Medical Care teams and family medicine in the field also influences the increased number of interventions which are not of the first degree of urgency. 7. Conclusions 1. The most frequent diseases that occupy the work of team in the field are the cardiovascular diseases. 2. From the results, it is visible that a large number of visits to homes and the majority of visits are of second degree of urgency. 3. There is indispensible better cooperation of Emergency Medical Care teams and family medicine in order to decrease the number of interventions of II and III degree of urgency and to direct one part of these patients to the Health Centres. 4. To educate the population by means of media regarding the place where and why the need to ask for help. 5. Due to enormous stress and frequent carrying of patients, it is necessary to change more often the teams working on special vehicles (cardio-vehicles) where mainly the help of I degree of urgency is offered. 6. Considering that the ambulances and equipment are in function during 24 hours, it is necessary to change them regularly and to renew due to safety of teams and better efficiency.
Literature
1. Mulaomerovi A., Elco H.Dykstra.: (Reform and Modernization of Emergency Medical Care System in FBiH) Reforma i modernizacija sistema hitne medicinske pomoi u FBIH, Medicinski arhiv, 2000; 54(4): 197-200. 2. Softi S,.: (Unique Dispatch Centre System of Communications) Jedinstven dispeerski centar sistem veza, Medicinski arhiv, 2000; 54(4): 227-230. 3. Smajki A., Niki D., Jelaa P.: (Bases of Research in Public Health) Osnove istraivanja u javnom zdrastvu, Sarajevo,1996. 4. Vlasta Jasprica-Hrlec i sar.: (Emergency Medical Care in Out-of Hospital Conditions) Hitna medicinska pomo u izvanbolnikim uvjetima Zagreb: Jaspra, 2003. 5. Vnuk, V.: (Emergency Medicine Pre-hospital Procedure) Urgentna medicina- prehospitalni postupak, I izdanje,Alfa Zagreb,1990. 6. Zlatko Puvai: (Statistics in Medicine) Statistika u medicini, Sarajevo, 1997. Corresponding author: Enes Slatina Institute of Emergency Medical Care (IEMC) Sarajevo, Bosnia and Herzegovina e-mail:
32
The most frequent congenital cardiovascular anomalies

Najee koNgeNiTaLNe aNomaLije kardioVaSkuLarNog SiSTema
Selma Alicelebic Institute of Histology and Embryology, University of Sarajevo, School of Medicine, Bosnia and Herzegovina
Summary The cardiovascular system is the first system that beginns to function in the embryo and blood already begins to circulate by the end of the third week of embryonal development. The critical period of heart development is from day 20 to day 50 after fertilization. Numerous critical events occur during cardiac and great vessels development and because of that the cardiovascular system anomalies are realtively common. In Bosnia and Herzegovina there is no existent unique evidence of congenital anomalies and registries. The aim of this study was to obtain the frequency of different types of cardiovascular anomalies, as the most frequent ones, among cases hospitalized in a Pediatric Clinic, University of Sarajevo Clinics Center, Bosnia and Herzegovina, during the period from January 2002 to December 2006. Retrospective study was carried out on the basis of clinical records. Standard methods of descriptive statistics were performed for the data analysis. Eleven different types of cardiovascular system anomalies were found among 539 patients that were hospitalized during the investigated period. In our country should be given more attention to the birth defects prevention programms. EUROCAT is a network of population-based registries for the epidemiologic surveillance of congenital anomalies that is active in Europe over last 25 years, covering 1,2 million births per year. The establishment of the Bosnia and Herzegovina registry and the Referral Centre of the Ministry of Health for the surveillance of Birth Defects
would improve the quality control and enhance the planning of the health care programmes for pregnancy and early childhood. Key words: congenital anomalies, cardiovascular system, frequency Saetak Kardiovaskularni sistem je prvi sistem koji u embriju pone funkcionirati i ve krajem tree sedmice embrionalnog razvoja pone cirkulacija krvi. Kritini period za razvoj srca je od 20. do 50. dana nakon oplodnje. Za vrijeme razvoja srca i velikih krvnih ila brojni su kritini momenti zbog ega su anomalije kardiovaskularnog sistema relativno este. U Bosni i Hercegovini ne postoji jedinstvena evidencija i registar kongenitalnih anomalija. Cilj ovoga istraivanja bio je ustanoviti uestalost razliitih tipova kongenitalnih anomalija kardiovaskularnog sistema, kao jednih od najeih anomalija, meu pacijentima hospitaliziranim na Pedijatrijskoj Klinici Klinikog Centra Univerziteta u Sarajevu, Bosna i Hercegovina, u periodu od januara 2002. do decembra 2006. godine. Podaci za ovo retrospektivno istraivanje dobiveni su iz klinikih prijemnih protokola i historija bolesti. Za analizu podataka primijenjene su uobiajene statistike metode. U istraivanom periodu ustanovljeno je jedanaest razliitih tipova anomalija kardiovaskularnog sistema kod 539 pacijenata koji su zbog istih hospitalizirani. U naoj se zemlji mora posvetiti vie panje za programe prevencije uroenih poremeaja. EUROCAT je evropska mrea registara za epidemioloko 33
praenje kongenitalnih anomalija, koja je aktivna preko 25 godina i godinje pokriva 1,2 miliona novoroenih. Uspostavljanje takvoga registra u Bosni i Hercegovini kao i referalnih centara za praenje uroenih poremeaja pri Ministarstvima zdravstva osiguralo bi kvalitetan nadzor i napredak u planiranju programa zdravstvene zatite u trudnoi i ranom djetinjstvu. Kljune rijei: kardiovaskularni sistem, razvoj, kongenitalne anomalije, uestalost Introduction Congenital anomalies are defined as structural defects, chromosomal abnormalities, inborn errors of metabolism, and hereditary disease diagnosed before, at, or after birth (1). Congenital anomalies represent a significant problem because of their frequency, unclear origin and the consequences for the society. The data of congenital anomalies in the different parts of the world are different due to differences in ecological, socio-economic, geographic and other conditions of living. The surveillance of congenital anomalies serves two main purposes: to facilitate the identification of teratogenic (malformation causing) exposures and to assess the impact of primary prevention and prenatal screening policy and practice at a population level. European Economic Communitys Committee on Medicinal and Public Health Research established in 1979 to improve the methodology of population studies throughout the Community. Congenital anomalies chosen as first topic for concerted action. The European Economic Communitys Committee on Medicinal and Public Health Research started already in 1979. a multicentric epidemiological study of congenital anomalies through the project called EUROCAT (acronym derived from its original name European Concerted Action on Congenital Anomalies and Twins) (2). Congenital anomalies are registered in almost every country all over the world on special designed questionnaires which management and outcome, however, vary considerably between the different countries. Due to the significance of congenital malformation in perinatal morbidity and mortality and its various types and diverse incidences in several countries, it is important for each population, even on regional basis, to 34
know the distribution and incidence of congenital malformations (3). In Bosnia and Herzegovina there is no existent unique evidence of congenital anomalies and registries (4). According to the literature data, birth defects involving the brain are the largest group all over the world at 10 per 1000 live births, compared to heart at 8 per 1000, kidneys at 4 per 1000, and limbs at 1 per 1000. All other defects have a combined incidence of 6 per 1000 live births (5). Hovewer, birth defects of the heart are the most common birth defect leading to death in infancy, accounting for 28% of infant deaths due to birth defects, while chromosomal abnormalities and respiratory abnormalities each account for 15%, and brain defects about 12% (6). The aim of this study was to obtain the frequency of different types of the cardiovascular system anomalies, as the most frequent ones, among the cases hospitalized at the Paediatric Clinic of the University of Sarajevo Clinics Centre, Bosnia and Herzegovina, during the period from January 2002 to December 2006. Patients and methods Retrospective study was carried out on the basis of the clinical records of the Paediatric Clinic of the University of Sarajevo Clinics Centre, Bosnia and Herzegovina. Standard methods of descriptive statistics were performed for the data analysis. Results During the period from 1st January 2002 to 31st December 2006, a total of 539 patients with cardiovascular system anomalies were hospitalized and out of that number 288 (53,4%) were male patients, while 251 (46,6%) were female (Table 1.). TABLE 1. Total number and gender of treated cardiovascular sytem anomalies
GENDER MALE FEMALE TOTAL N 288 251 539 % 53,4% 46,6% 100%
Eleven different types of cardiovascular system anomalies were found in this study. The most frequent were ventricular and atrial septal defects, patent ductus arteriosus and complex congenital cardiovascular anomalies of the heart and great vessels. (Figure 1.).
FIGURE 3. Sex distribution of cardiovascular system birth defects cases About 10% patients with cardiovascular anomalies have some of the chromosome abnormalities in this investigation (FIGURE 4.). FIGURE 1. Frequency of particular types of cardiovascular system birth defects Congenital heart defects were more frequent than great vessels anomalies and the combined anomalies of heart and great vessels were the least frequent (FIGURE 2.).
FIGURE 4. Frequency of chromosome abnormalities in cardiovascular system birth defects Trisomy 21 (Down syndrome) were the most frequent (94%) chromosome abnormality associated with cardiovascular anomalies but Turner syndrome and Edwards syndrome were considerably less (FIGURE 5.). FIGURE 2. Frequency of different kinds of cardiovascular system anomalies Figure 3. shows a total apsolute number of each cardiovascular anomaly found in the investigated period according to the sex.
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FIGURE 5. Frequency of particular types of chromosome abnormalities in cardiovascular system birth defects FIGURE 6. shows that heart septal defects were the most frequent anomalies associated with Down syndrome and the other were considerably less.
were more frequent (56,3%) than the great vessels anomalies (34,1%) and the complex heart and great vessels anomalies were the least frequent (9,6%) what corresponds with the data from the literature (7,8,9). From the total number of 539 patients with congenital cardiovascular anomalies, 56 patients or 10,4% had some of the chromosome abnormalities and that: 53 patients or 94,6% had Down syndrome, 2 patients or 3,6% had Turner syndrome and one patient or 1,8% had Edwards syndrome. The most frequent cardiovascular anomaly associated with Down syndrome was atrioventricular septal defect (24 patients or 45,3%), followed with ventricular septal defect (14 patients or 26,4%), atrial septal defect (6 patients or 11,3%), tetralogy Fallot (4 patients or 7,5%) and combined cardiovascular anomalies (3 patients or 5,7%) what corresponds with the data from the literature (10). Conclusion According to this study, congenital cardiovascular system anomalies, were higher in males (53,4%). Congenital heart defects were more frequent (56,3%) than great vessels anomalies (34,1%). Ventricular septal defect was the most frequent anomaly found both in males (22,2%) and in females (20,7%). Cardiovascular system anomalies were associated with chromosomal abnormalities in 10,4% cases, the most frequent with Down syndrome (94,6%). The most frequent cardiovascular anomaly (45,3%) associated with Down syndrome was atrioventricular septal defect, followed with ventricular septal defect (26,4%) and atrial septal defect (11,3%).
FIGURE 6. Frequency of particular types of cardiovascular system birth defects in Down syndrome
Discussion In the period from 1st January 2002 to 31st December 2006 a total number of 539 patients with congenital cardiovascular system anomalies were hospitalized at the Paediatric Clinic of the University of Sarajevo Clinics Centre. Out of that number 288 were males (53,4%) and 251 were females (46,6%); sex ratio-1,2:1. These findings correspond with literature ones (7). In this study eleven different types of cardiovascular system anomalies were found and their frequency in both sexes varried from 21,52% (ventricular septal defect) to 0,55% (pentalogy Fallot). Anomalies of the heart 36
Literature
1. Dastgiri S., Stone D.H., Le-Ha C., Gilmour W.H. Prevalence and secular trend of congenital anomalies in Glasgow. UK Archives of Disease in Childhood 2002;86:257-263 2. Eurocat European Surveillance of Congenital Anomalies. www.eurocat.ulster.ac.uk 3. Biri A., Onan A., Korucuolu U., Taner Z., Tra B., Himmetolu O. Distribution and Incidence of Congenital Malformations in a Universitiy Hospital. Perinatoloji Dergisi 2005; 13(2): 86-90 4. Dinarevi S. et al. Kongenitalne anomalije u KCUS Sarajevo. Materia socio medica 2005; 17 (1-2):3941 5. Connor JM, Ferguson-Smith MA. Essential Medical Genetics, 2nd ed. Oxford, Blackwell Scientific Publications, 1987. 6. Congenital abnormality. http://en.wikipedia.org/ wiki/Congenital abnormality (last accessed July 9, 2008) 7. Mesihovi-Dinarevi S. i sar. Pedijatrija za studente medicine, Sarajevo: SaVart 2005;99-199. 8. Mardei i sar. Pedijatrija, Zagreb: kolska knjiga 2003; 685-763. 9. Mesihovi-Dinarevi S. Djeija kardiologija (od fetusa do adolescenta), Sarajevo: Medicinski fakultet 2000; 99-199. 10. Novosel V. Citogenetika analiza kariotipa djece sa uroenim sranim manama, Sinopsis, UDK 575.11:613.12
Corresponding author: Selma Alicelebic Institute of Histology and Embryology, University of Sarajevo, School of Medicine, Cekalua 90, 71000 Sarajevo, Bosnia and Herzegovina e-mail: alicelebicselma@hotmail.com
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flock level risk factors for ovine brucellosis in several cantons of bosnia and Herzegovina
riziko fakTori Na NiVou STada za PojaVu oVije bruCeLoze u NekoLiko kaNToNa boSNei HerCegoViNe
Sabina Seric Haracic1*, Mo Salman2, Nihad Fejzic1, Brian J. McCluskey3, Thomas J. Keefe4
1 2
Animal Health Economic Centre, Faculty of Veterinary Medicine, Sarajevo, Bosnia and Herzegovina Animal Health Population Institute, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, United States of America Department of Environmental Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, United States of America Centers for Epidemiology and Animal Health, Fort Collins, United States of America
Summary Brucellosis has been recognized during the past five decades as an important infectious disease in ruminants in Bosnia and Herzegovina. Disease reports in recent years indicate an increase in the number of reported outbreaks in ruminants, especially sheep. The objective of this study was to investigate risk factors associated with the brucellosis status of sheep flocks in several cantons of Bosnia and Herzegovina. A cross sectional study was conducted on 138 sheep flocks during the period of July-September 2005. The brucellosis status of the flocks was established through serological testing of serum samples using Rose Bengal and complement fixation tests applied in series. Data on risk factors were obtained through a study questionnaire. Risk factor analysis was performed using logistic regression analysis. The brucellosis risk factors identified are those usually associated with traditional management of small ruminant flocks in this region. Key words: Brucellosis, small ruminants, risk factors
Introduction Brucella melitensis, the primary causative agent for caprine and ovine brucellosis, is highly pathogenic to humans capable of causing one of the most significant zoonosis- inflicted disease syndromes known (Corbel, 1997). Brucellosis has been recognized during the past five decades as an important infectious disease of ruminants in Bosnia and Herzegovina (B&H). A government program currently in effect to control the disease is based on a test and slaughter policy. Disease detection comes through serological testing of routinely collected serum samples and samples obtained from reported clinical cases. Rose Bengal (RB) and complement fixation (CF) tests are applied in series for serological testing. Vaccination against brucellosis is prohibited. When the existing brucellosis detection system and control measures were instituted, reports on disease occurrence documented sporadic outbreaks occurring predominantly in small ruminants after importation of new animals into the flock (Kolar, 1989). In recent years however, disease reports indicate a persistent increase in the number of reported outbreaks in ruminants, especi-
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ally sheep, along with a significant increase in the number of human cases. According to the State veterinary office of B&H animal health reports, the number of outbreaks reported in small ruminants in 2001 was increased more than ten-fold in 2006. Approximately the same level of increase was reported in human cases during the same period. These factors have had a profound influence on public health and animal production, and they have caused disruption in relations between farmers, consumers and the B&H veterinary service. Several authors suggest that, in the cased of endemic brucellosis it is important to assess many epidemiological characteristics of the disease, since these factors may be useful in defining alternative tools for more efficient and practical control (Mikolon et al., 1998; Robinson, 2003; Lithg-Pereira et al., 2004). The most important risk factors for small ruminant brucellosis, such as transhumance and the introduction of new animals into a flock, are universally recognized and well documented (MacPherson, 1995; Reviriego et al., 2000; Kabagambe et al., 2001). However, with a specific animal husbandry method, production type, climate or habitat, a risk factor may have a unique role that may be differently important. The objective of this study was to identify and investigate risk factors associated with the brucellosis status of the sheep flock in several cantons of Bosnia and Herzegovina. Materials and methods Study design Bosnia and Herzegovina has two administrative units or entities, the Federation of Bosnia and Herzegovina (FB&H) and the Republic of Srpska (RS). FB&H is further divided into ten cantons (Map 1). A cross-sectional study was conducted of 138 sheep flocks from five cantons within the entity of FB&H. We used the formula for the estimation of proportion in an infinite population for the calculation of the sample size. The expected proportion of brucellosis infected flocks was 10%, and the
Flock size Sample size <50 animals 15
allowed error rate for required sample size was 5%. (Fleiss, 1981). The participating cantons and their contribution to the overall sample were as follows: - Hercegovina-Neretva Canton (HNC) with 16 flocks, - Srednja- Bosna Canton (SBC) with 34 flocks, - Zenica-Doboj Canton (ZDC) with 32 flocks, - Una-Sana Canton (USC) with 35 flocks and - Tuzla Canton (TC) with 21 flocks.
Map 1: Administrative division of Bosnia and Herzegovina where yellow areas represent the study sampling area; five cantons in north (canton III or Tuzla Canton), northwest (canton I or Una Sana Canton), center (cantons IV and VI or Zenica Doboj and Srednja Bosna Cantons, respectively) and south (canton VII or HercegovinaNeretva Canton ) of Bosnia and Herzegovina Data used in this study were collected during the period July-September 2005. Data collection was conducted as a collaborative project between the Animal health economics centre (Veterinary faculty Sarajevo), Veterinary institute Biha and cantonal veterinary inspectors. Flocks included in this study came from the work areas of 23 veterinary practices, each participating in proportion to their work area size. Flocks tested were selected by participating local veterinarians who chose an
50-100 animals 17 >100 animals 19
Table 1. Sample size for each individual flock at estimated within flock prevalence of 15%
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equal share of small (up to 50 animals), medium (from 50 to 100 animals) and large (more than 100 animals) flocks from their work areas. Participation by the farmers and local veterinarians in the study was on a voluntary basis. The brucellosis status of the flocks was established through serological testing of serum samples. A flock was considered infected when one or more individual samples from the flock tested brucellosis positive. In order to calculate the number of individual animals to be sampled from each flock we assumed brucellosis prevalence within a flock to be 15%. The number of serum samples taken from each flock was based on the flock size (Robinson, 2003) (Table 1). A questionnaire was developed to obtain data on risk factors related to animal husbandry, introduction of new animals, and the occurrence of abortion as a primary symptom of disease. Data were collected on flock size, the occurrence of multiple ruminant species farming, housing of animals, seasonal animal movement practices, sources of rams, and housing and group sizes for ewes during lambing. We collected further data on new animal origin, gender, the existence of health certificates for new introductions, and the length of time new introductions were quarantined prior to their introduction to the flock. Data were also collected on abortion rates. Questionnaires were reviewed by collaborating veterinary officials prior to their use in this study. For the study, the questionnaires were administered through personal interviews with flock owners during sampling visits. In order to ensure the consistency in the information collected through the questionnaires, only one person was involved in questionnaire administration. Serological testing Blood samples were collected from adult animals (more than 1 year old) through venipuncture, using a single use vakutaner system. Once collected, samples were transported to the laboratory, where they were stored at 4C for a maximum of 2 days. Serological testing of the serum samples was accomplished using Rose Bengal and complement fixation tests applied in series. After testing with the RB test, the extracted serum was separa40
ted from the blood clot in the tubes and stored at -20C. Frozen serum samples were thawed overnight in the refrigerator prior to further testing. Tests were carried out according to the OIE Manual of standards for diagnostic tests and vaccines (Garin-Bastuji and Blasco, 2004). The RB test was performed by mixing 25l of the serum and an equal volume of antigen on a white, shallow welled, enamel plate. The mixture was rocked gently for 4 minutes at room temperature and then observed. Any sign of agglutination was considered positive. The CF test was performed using the warm procedure described by Alton et al. (1975) on standard 96-well micro-titre plates. The serum was considered positive if it showed at least 50% haemolysis at a given dilution (i.e. 20 ICFTU). Data management and statistical analysis The results from serological testing and the administered questionnaires were organized into a data base created specifically for this project (Microsoft Access 2000). MINITAB 14, student version (Thomson learning 2005), was used for logistic regression analysis. The investigated risk factors were initially assessed using univariable logistic regression analysis (Hosmer and Lemeshow, 2000). Prior to analysis, all continuous variables were categorized into quartiles in order to facilitate interpretation of the odds ratio. The chi- square (the likelihood ratio) or Fishers exact test (where observed cell frequencies were <5) were used to test for statistical significance of association between brucellosis flock status (1-one or more seropositive animal, 0- no seropositive animals) and categorical risk factors. In order to be considered eligible for multivariable logistic regression model, individual risk factor variables had to be significantly associated at the 20% significance level (i.e., p-values <0.2) in the univariable logistic regression analysis. Prior to multivariable analysis, selected individual variables were tested for co-linearity using correlation analysis. In cases where two variables had correlation coefficients larger than 0.3, only the variable that had more biological relevance (larger odds ratio) was retained for further analysis. The same criterion was used in selecting between risk factor
variables that resulted from the same data but were defined using different criteria for categorization. The multivariable logistic regression model was built using a stepwise approach described by Hosmer and Lemeshow (2000). A preliminary model contained all of the independent variables selected in the previous step of risk factor analysis. A backward elimination procedure was used to determine the best model. All of the variables found to be associated at the 5% significance level (i.e. p-values <0.05) were retained in the multivariable logistic regression model. Hierarchical models (at first with primary effects only and then later with two-way interactions terms) were also fitted.
Results The median flock size for the 138 flocks included in this study was 86 (mean flock size 125 animals). The flock size was found to be quite variable, ranging from 9 to 526 animals. In regards to farm management, 25.4% (35/138) of the flocks included in this study were managed as farm flocks, while the rest (103/138) were managed as either fenced - range or range flocks. It is important to note that 71.4% (25/35) of the farm flocks in this study were composed of less than 50 animals. None of the owners of these flocks practiced seasonal movement of animals. Fenced- range
Table 2. Questionnaire results for risk factor variables significantly associated with flock status at the 20% significance level by univariable analysis (the likelihood ratio chi square probability or Fishers exact test (<5 observed cell frequencies))
Variable Flock origin Number of flocks % of brucellosis positive flocks OR P
SBC 34 23.5 3.6 0.031 a 104 8.7 Other cantons >39 (Q1) 103 13.6 1.7 0.187b Flock size >86 (median) 68 17.6 2.8 0.057 >186 (Q3) 34 23.5 3.3 0.031 Yes 17 23.5 2.6 0.097b Cohabitation with goats Noa 121 10.7 Fenced range 50 20.0 2.9 0.043 Farm management Farm 35 5.7 0.4 0.101b c Other/Combined 53 9.4 Yes 31 29.0 5.1 0.003 Transhumance a 107 7.5 No Yes 13 46.2 8.9 0.001 Transhumance to cantons a where brucellosis is prevalent 125 8.8 No more than 1:20 45 17.8 2.9 0.070 Ratio rams to ewesd a 73 6.8 1:20 or less Fences 24 37.5 7.9 <0.001 d Housing during lambing Stables 103 5.8 0.1 <0.001 10 20 Other/Combinedc Yes 56 19.6 2.9 0.044 Abortiond a 77 7.8 No Yes 25 36.0 7.0 <0.001 Abortion > 3 per flock (Q3)d a 108 7.4 No Yes 8 62.5 14.7 <0.001 Previous history of brucellosisd a No 118 10.2 Legend: a- Reference category, b- Based on the Fishers exact test, c p>0.2 in the univariable analysis, not offered to the MLR model, d- Sample decreased due to the lack of data for some of the sample units
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flock management in B&H implies that animals are on pasture during the day and gathered inside fenced areas at night and during lambing. The fences are usually mobile, allowing farmers to move their flocks in search of better pasture. The investigated sheep farms were, for the most part, oriented towards meat production. Only in the canton Srednja- Bosna, is sheep farming primarily oriented towards dairy production. The destination for farm products is predominantly the local market. In this study, we determined that 22.5% (31/138) of farmers move their animals during the year in order to provide better pasture. These flocks are often pastured in minimally accessible mountainous areas, and consequently most animal health problems are handled by a shepherd. It is not uncommon for these flocks to be the product of a merger between several flocks, thus promoting intermingling of flocks. Of the 138 flocks, we identified 17 flocks with one or more infected animals yielding a proportion of brucellosis infected flocks in our sample of 12.3%. Risk factors found to be associated with brucellosis occurrence in the flock at a level of statistical significance of 20% based on univariable logistic regression analyses results are shown in the Table 2. These factors included: flock origin, flock size, cohabitation of sheep and goats, maintenance of animals as fenced range flocks, seasonal movement of flocks, ratios between rams and ewes of more than 1:20, the housing ewes within fences during lambing, and histories of abortion or increased abortion frequencies within the flock. Six of these variables were not considered for the multivariate logistic regression (MLR) analysis due to their high co-linearity with one or more
of the other variables with higher biological plausibility (larger odds ratio). The final MLR model (Table 3) retained the following risk factors: seasonal movement of flocks into cantons with a high level of brucellosis occurrence, housing of ewes in fences during lambing and the occurrence of more than 3 abortions during the previous lambing season (greater than the third quartile in the number of abortions in a flock used as continuous variable). The sample size for the multivariate model was decreased from 138 to 132 flocks due to lack of the specific data for 6 of the sample units (including one brucellosis positive flock). First-order interactions of these risk factors were evaluated via MLR analysis, but none were found to be statistically significant. Discussion This study represents the first epidemiological study with the aim to evaluate risk factors at the flock level for sheep brucellosis in Bosnia and Herzegovina. According to our results, the highest proportions of brucellosis positive flocks were found in cantons where: - producers were predominantly oriented towards dairy production (SBC), - larger flocks were predominant (SBC, USC, ZDC) and - seasonal movement of flocks was widely practiced among sheep farmers (SBC, ZDC). Generally, differences in susceptibility for brucellosis in individual animals are dependent almost exclusively on the invasion site, stage of gestation at the time of exposure and the infective dose
Table 3. Parameters of the final multiple regression model, that includes only those variables with p values for the odds ratios less than 0.05. Odds ratios and correspondent 95% confidence intervals are also provided for eligible variables.
Variable Constant Transhumance to cantons where brucellosis is prevalent Housing during lambing in fences Abortion >3 per flock (Q3) Logistic regression parameters b -3.2 1.9 2.2 2.31 SE (b) 0.59 0.84 0.71 0.7 p <0.001 0.023 0.002 0.001 OR 6.6 8.6 10.1 95%CI (OR) 1.3-34.2 2.2-34.3 2.540.1
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(Crowford et al., 1990). However, according to Alton (1985), milking sheep also appear to be more susceptible to brucellosis than animals used for other products. Even though we found an association between the brucellosis status of a flock and a farmers orientation towards dairy production, this association was not statistically significant. Based on the univariable logistic regression analysis results and findings of other authors (Lithg-Pereira et al., 2001), flock size appeared to be an important risk factor for brucellosis occurrence in the flock. Simple animal numbers are clearly not the only contributor to increased disease risk, as shown by further analysis. Larger flocks are also predominantly maintained as fenced range flocks, and fenced range flocks are, in addition, more likely to be composed of nomadic flocks. These three variables were highly correlated. Therefore, only the destination and conditional nomadic practices of the flock owner were provided as risk factor variables in the MLR model in this study. Nomadic and semi- nomadic husbandry systems are well established risk factors for brucellosis occurrence in sheep (MacPherson, 1995; Omer et al., 2000; Reviriego et al., 2000; Al-Talafhah et al., 2003). Logically, not the practice itself, but the opportunity for contact with other potentially infected animals through seasonal movement of flocks creates the risk for establishment of brucellosis in a nomadic flock. Accordingly, seasonal movement of sheep in previously established brucellosis- prevalent areas amplifies the risk of potential contact with infected flocks. This was also confirmed by the results of multivariate logistic regression analysis. Independent and multivariable assessment of the fencing of ewes during lambing shows that this practice increases the risk of brucellosis infection within a flock. The close contact that occurs between animals within fences, and the fact that aborted fetuses and placentas contain the highest concentrations of the agent, clearly support our findings (Garin-Bastuji and Blasco, 2004). Animals managed as farm flocks have close contact during lambing and, therefore have equal opportunity for the spread of brucellosis within the flock. However farm flocks are generally housed in stables and usually consist of smaller numbers of animals. These flocks are pastured on private pastures
around households, and therefore are at a lower risk of contacting a diseased animal. The practice of bringing new animals of undetermined origin and health status into a flock might represent a window for introducing brucellosis (Mikolon et al., 1998; Lithg-Pereira et al., 2004). Also, the rearing goats along with sheep was shown to have an influence on brucellosis occurrence (Mikolon et al., 1998). These risk factors, although found to have an association, were not determined to be statistically significant in our study. Even though, increased odds for brucellosis infection in flocks where ratio of rams to ewes was more than 1:20, were found to be almost statistically significant in univariable analysis, they had to be excluded from MLR model since this variable had failed to meet established criteria on variable relevance. For the same reason variable on previous history of brucellosis was excluded from MLR model, although it was highly significant in univariable analysis. Abortion occurrence is identified as a cause of suspicion for brucellosis by current control requirements in this country and in the OIE terrestrial manual (Garin-Bastuji and Blasco, 2004). The odds ratio quantifying the risk of brucellosis infection in flocks with previous history of abortion was shown to be statistically significant at the 5% significance level through univariable analysis. However, this variable demonstrated a significantly increased association with brucellosis status of a flock when transformed so that not only abortion occurrence but abortion frequency were taken into account. Conclusion Mediterranean countries, such as B&H, provide the specific conditions, including extensive farming, communal pastures and uncontrolled animal movement that form the historical context for the persistence and spread of brucellosis infection among small ruminants. Many of the identified brucellosis risk factors are associated with the traditional way of managing small ruminant flocks in this area. Planning of a targeted detection strategy should account for the established risk factors associated with brucellosis occurrence and spread. The risk 43
based approach to the disease surveillance would increase the overall sensitivity of the disease detection and allow more effective allocation of limited resources for disease containment. However, in order to reach comprehensive and scientifically based disease detection program, further investigation of disease epidemiology are needed. Primarily, future studies need to reliably establish small ruminant brucellosis prevalence and incidence in the country and investigate specific relationship between brucellosis in humans in animals. This would improve the market competitiveness of domestic sheep production by increasing consumer trust, and most importantly, help ih prevention of human cases. Literature
1. Al-Talafhah, A.H., Lafi, S.Q., Al-Tarazi, Y. (2003): Epidemiology of ovine brucellosis in Awassi sheep in Northern Jordan. Preventive Veterinary Medicine, 60, 297-306. 2. Alton, G.G., Jones, L.M., Pietz, D.E. (1975): Laboratory techniques in brucellosis. In: WHO monograph series No. 55, World Health Organization, Geneva, 163 pp. 3. Alton, G.G. (1985): The epidemiology of Brucella melitensis in sheep and goats. In: Verger, J.M., Plommet, M. (ed.): Brucella melitensis, a CEC seminar. Martinus Nijoff, Dordrecht-Boston-Lancaster, 187-196. 4. Corbel, M.J. (1997): Brucellosis: an overview. Emerging Infectious Diseases, 3, 213-221. 5. Crawford, R.P., Huber, J.D., Adams, B.S. (1990): Epidemiology and surveillance, 132-148. In: Nielsen, K., Duncan, J.R. (ed.): Animal brucellosis. CRC Press, Boca Raton, Florida, USA, 301 pp. 6. Fleiss, J.L. (1981): Determining sample size needed to detect a difference between two proportions. Statistical methods for rates and proportions. 2nd ed. John Wiley & Sons, Inc., New York, USA, 309 pp. 7. Garin-Bastuji, B., Blasco, J.M. (2004): Caprine and ovine brucellosis (excluding B. ovis). In: Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. OIE, Chapter 2.4.2. 8. Hosmer, D.W., Lemeshow, S. (2000): Applied logistic regression. 2nd ed. John Wiley & Sons, Inc., New York, USA.
9. Kabagambe, E.K., Elzer, P.H., Geaghan, J.P., Opuda-Asibo, J., Scholl, D.T., Miller, J.E. (2001): Risk factors for Brucella seropositivity in goat herds in eastern and western Uganda. Preventive Veterinary Medicine, 52, 91-108. 10. Kolar, J. (1989): Brucellosis in Eastern European countries. In: Young, E.J., Corbel, M..J. (ed.) Brucellosis; clinical and laboratory aspects. CRC Press, Inc., Boca Raton, Florida, SAD, 164-172. 11. Lithg-Pereira, P.L., Mainar-Jaime, R.C., lvarezSnchez, M.A., Rojo-Vzquez, F.A. (2001): Evaluation of official eradication-campaigns data for investigating small-ruminant brucellosis in the province of Leon, Spain. Preventive Veterinary Medicine, 51, 215-225. 12. Lithg-Pereira, P.L., Rojo-Vazquez, F.A., MainarJaime, R.C. (2004): Case-control study of risk factors for high within-flock small-ruminant brucellosis prevalence in a brucellosis low-prevalence area. Epidemiology and Infection, 132, 201-210. 13. MacPherson, C.N.L. (1995): The effect of transhumance on the epidemiology of animal diseases. Preventive Veterinary Medicine, 25, 213-214. 14. Mikolon, A.B., Gardner, I.A., Anda, J.H., Hietala, S.K. (1998): Risk factors for brucellosis seropositivity of goat herds in the Mexicali Valley of Baja California, Mexico. Preventive Veterinary Medicine, 37, 185-195. 15. Omer, M.K., Assefaw, T., Skjerve, E., Tekleghiorghis, T., Woldehiwet, Z. (2000): Prevalence of antibodies to Brucella spp. in cattle, sheep, goats, horses and camels in the State of Eritrea; influence of husbandry systems. Epidemiology and Infection, 125, 447-453. 16. Reviriego, F.J., Moreno, M.A., Dominguez, L. (2000): Risk factors for brucellosis seroprevalence of sheep and goat flocks in Spain. Preventive Veterinary Medicine, 44, 167-173. 17. Robinson, A. (2003): Guidelines for coordinated human and animal brucellosis surveillance. FAO, Rome, 46. Corresponding author: Sabina Seric Haracic, Animal health economics centre, Veterinary faculty, Zmaja od Bosne 90, 71 000 Sarajevo, Bosnia and Herzegovina, Tel./fax: +387 33 66 35 51, e-mail: sabina_seric@hotmail.com
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Hypertension as leading cardiovascular illness among minners

HiPerTeNzija kao Vodea kardioVaSkuLarNa boLeST rudara
Muvedeta Lemes, Belma Pojskic PZU INTERMED Kakanj, County hospital of Zenica internal department
Summary The aim: investigation of hypertension in miners, depending on working conditions inside and outside of mine- pit, number of years of working and influence of smoking as a risk factor. Methods: 828 miners or 40,66%, out of total number of employes, was covereed by this research. The control group consisted of 310 miners out of mine-pit or 15,2% out of total number o employees. Blood preasure was measured at the beggining and ending of working process throughout the month, following the work in shifts. Results: after complete examining and statisical processing of recieved datas, a conclussion can be made that statistical significant case of hypertension among miners is evident, and it it caused by influence of working area and influence of smoking as additional risk factor. Conclusion: The workers who worked in three shifts have had the hypertension evident more than those who worked outside the mine-pit, as well as increased smoking risk-factor in category up to 20 years in working process,and in both gorups, in category over 20 years in working process, the smoking as risk-factor is more evident. Apart from the legal regulations concerning working enviroment conditions and allowed negative factors in working enviroment, it is necessary to have better supervision of working conditions and better cooperation of service that controls protection in working with team of doctors, as well as activities on introducing of smoking risk-factors, esspecially to those elderly employees. Key words: hypertension, miners in mine-pits, working enviroment, cardiovascular dissease ( CVD)
Saetak Cilj: ispitati pojavu hipertenzije kod rudara ovisno o uslovima rada u jami i van jame, duini radnog staa i uticaja puenja kao faktora rizika. Metode: Ispitivanjem je obuhvaeno 828 rudara ili 40,66% od ukupnog broja zaposlenih. Kontrolnu grupu sainjavalo je 310 rudara van jame ili 15,2% od ukupnog broja zaposlenih. Krvni pritisak je mjeren na poetku i na kraju radnog procesa u toku mjesec dana pratei smjenski rad. Rezultati: Nakon kompletnog ispitivanja i statistike obrade dobijenih podataka moe se konstatovati da je dokazana statiki signjifikantna pojava hipertenzije kod jamskih radnika to je uzrokovano uslovima radne sredine i uticajem puenja kao dodatnog riziko faktora. Zakljuak: Radnici u jami radei u tri smjene imali su pojavu hipertenzije znatno vie nego radnici van jame, kao i poveani riziko faktor puenja u kategoriji do 20 godina staa, a u obje grupe radnika u kategoriji preko 20 godina staa znatno je izraeno puenje kao riziko faktor. Pored zakonske regulative vezane za uslove radne sredine i dozvoljene tetnosti vezane za tetne faktore radne sredine potreban je vei nadzor nad uslovim rada i bolja saradnja slube zatite na radu sa ljekarskim timovima, kao i aktivnosti na upoznavanju radnika o znaajnom riziko faktoru puenju posebno u kod starijih radnika. Kljune rijei: hipertenzija, jamski radnici, radna sredina, kardiovaskularna bolest (KVB).
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Introduction CVD ( cardiovascular disseases) are primary cause of lethal outcome in the world. In USA, leathal outcome of these disseases is 6 times larger than those of breast cancer. It is also the case in Europe, and we assume also in our country even though we do not have precise datas. There is no general register of cardiovascular disseases. In European congress of cardiologists in Stockholm, in 2005, the datas were given concerning neglecting of risk factors, esspecially to speciffic working area conditions. ( disseases related to Marija Zavalis paper ). One of conclusions was that the process of curring shouldnt be concentrated only on prevention of illness but also on working place and enviroment . according to WHO datas from 2004 cardio-vascular illnesses are the main reason of mortality in men and women, 44% in men and 55% in women. Regardless the fact that of male population and speciffic working enviroment which mostly has multiple risk factors, minners population is surelly the one with larger degree of cardiovascullar illnesses frequency. The outlook of mine pits, weather conditions, humidity, dusting, bad gasses, noise, vibrations, hevy work, narrow working place...all these represent risk factors that lead to cardiovascular illneses. Th aim of work is to explore the appearance of hypertension in minners regarding the working conditions in mine pits and outside of it, smoking as additional risk factor as well as the lenght of working period. The methods and the tested workers Testing was conducted on 828 workers , out of which 518 were those who work in mine pits , and 310 who work outside of mine pits. Hypertension is a state of increased systolic or diastoic blood preasure.according to directives published in 2007 as a result of cooperation of European cardiological society and European society for hypertension (ESH/ECH), there are reccomendations based on evidences for diagnosys determination, and for educative value among patients with hypertension. 46
According to most of the directives given, the bottom line for determination of diagnosis of hypertension is the level of blood preasure of 140/90mmHg.The preasure less than this is considered normal but Europeans directives make the difference between optimal, normal and increased blood preasure, and the higher one is considered as first degree hypertension according to mentioned directives with the level o blood preasure, systolic, from 140 to 159 mmHg and diastolic from 90 to 99 mmHg. As Second degree hypertension is considered systolic blood preasure from 160 to 179 mmHg, and diastolic from 100 to 109 mm, and third degree hypertenion is with blood preasure larger from 180 and diastolic larger from 110 mmHg. Testings were conducted according to age, lenght of work and smoking habitts. All workers preasure was measured before entering the mine pit and after working day in three shifts, as well as workers who work outside of mine pit. The testing lasted for a month. All results were processed in statistical methods and presented in tables. Even though the working enviroment of miners is speciffic, with many proffessional risks and damges, still, it is unknown how and in what way, certain proffessional damages are related to hypertension. Results In this paper, 828 of workers were tested, out of which 518 of them were those who work in minnig pits or 40,66% and 310 or 15,2% of those who work outside of minning pits. Table 1. The number of employees and the number of workers inside and outside of minnig pits
Workers ( Miners ) on coal digging Mine pit workers Suracedigging (outside of mine-pit) Other workers Total number of employees 828 518 310 1411 2.239 36,9% 23,1% 13,8% 63,1%
Table 2. Examined workers according to years of work

Examined workers Workers in mine pits Workers outside mining pits Total The years of work 0-20 yrs. 360 180 540 More than 20 yrs 158 130 288 Total 518 310 828
In table 2. the total amount of examined workers inside and outside of mine pits is presented and relation to years of work, up to 20 yrs and over 20 yrs of total number of working years . Table 3. Number of those who suffer from hypertension according to working place
Examined workers Workers in mine pit Workers outside mine pits Total Total 518 310 828 238 56 294 HTA 45,9% 18,1% 35,5%
Picture 2. graphic presentation of percentage of those who suffer from hypertension, working outside of mine pits. Regarding the years in work, up to 20 years, 118 of workers have been diagnosed with hypertension up to 20 years in work and 120 of them with over 20 years in work which is totaly 238 or 81% out of number of examined workers. In a group of workers outside of a minning pit, up to 20 years in work , 22 workers are with diagnosys of hypertension and over 20 years in work - 34 workers, what is 56 worers in total or 19 %.
In table 3. 828 of workers were tested, out of which 518 of them were those who work in minnig pits or 40,66% and 310 or 15,2% of those who work outside of minning pits.
Picture 1. Graphic presentation of percentage of those who suffer from hypertension, working in mine pits. Table 4. The number of those who suffer from hypertension according to years in work.
Workers with hypertension Workers in minning pit Workers outside minning pits Total Years in work Up to 20 yrs. 118 22 140 Over 20yrs. 120 34 154 238 56 294 Total 81% 19% 100%
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Picture 3. Graphic presentation of those with hypertension who work in a minnig pit.
Picture 4. Graphic presentation of percentage of those who suffer from hypertension, working outside of mine pits Using the 2 test, the hypothesis on significant difference in total number of those with hypertension is tested, regarding the working conditions. Three hypothesis were tested: 1. There is statistical signifficant difference in dignosing of hypertension regarding the working conditions (inside or outside the minnig pit). The final value of 2 = 65,84, what is significantly above the limited value 3,841, and with probability of p less than 0,05, the mentioned hypothesis can be approved, i.e. miners working in minning pits, are more exposed to hypertension, and they make 81 % of total number of workers with hypertension.
2. There is statisticaly significant difference in diagnosing of hypertension according to age and years of work ( up to 20 and over 20 years of work) between the groups defined according to working conditions. The final values for the first and the second case are 2 = 33,95 and 2 = 19,06, what is signifficantly above the limit value of 3,841, and with probability of p less than 0,05, the hypothesis can be aproved. i.e. in first group ( up to 20 years of work ) and in second group ( over 20 years of work), those who are working inside the minning pits and they are the members of the first group 84,3% and 77,9% for second group of workers with hypertension in some other groups. 3. There is signifficant difference in diagnosing of hypertension dependable on age, regading the working conditions. there is sttisticaly signifficant difference in number of smokers. The value 2 = 82,4 (for workers in minning pits) and 2 = 9,90 ( for workers outside the minning pit ), which is significantly above the limited value of 3,841, and with probability of p less than 0,05,the hypothesis can be approved, i.e, in first ( inside minning pits ) and in second group ( outside the minning pits ), the workers above 20 years of work are under the larger risk of diagnosing of hypertension and, at the same time, it is possible to apply that the value x2 is signifficantly less, i.e. the difference is signifficantly larger among workers who work inside the minning pits as well as the risk of diagnosing of hypertension throughout the years of work in minning pit.
Table 5. Total number of smokers and nonsmokers according to working years.

Years of work Workers in minning pits Workers outside of minning pits Total Up to 20 years Examined 360 180 540 Smokers 252 101 353 (%) (70) (56) (65) Over 20 years Examined 158 130 288 Smokers 138 118 256 (%) (87) (90) (89)
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In table 5, relation with smoking according to number of examined workers, is presented Using the 2 test, the hypothesis on signifficant difference in number of smokers related to working conditions is also presented . Three hypothesis were tested: 1. There is statisticaly signifficant difference in number of smokers related to working conditions (inside and outside of minning pits). The final value 2 = 2,15, what is less than limited value 3,841, and, with probability of p less than 0,05, the hypothesis cant be approved or established, i.e. there is no statisticaly signifficant difference in number of smokers related to working conditions. 2. There is sttisticaly signifficant difference in number of smokers according to age (up to 20 and over 20 years of work) between groups deffined according working conditions. The final value for the first case 2 = 10,23, and for the first group (up to 20 years of work) it means approval of hypothesis on existence of signifficant difference between those who work inside and outside of minning pits and the number of smokers who work inside minning pits is bigger. The final value for the second case 2 = 0,85. and for the second group (over 20 years of work), it means that the hypothesis on existence of signifficant difference between those who work inside and outside of minning pits can not be approved. 3. There is sttisticaly signifficant difference in number of smokers according to age group regardles on working conditions. The final values 2 = 17,75 (for workers in minning pits) and 2 = 43,72 ( for the workers outside the minning pits), what is signifficantly above limited value of 3,841, and, with probability of p less than 0,05, the hypothesis can be approved or established, i.e. in first group (minners in minning pits) and in second group (minners ouotside minning pits), the number of smokers with more than 20 years in working process regardless working conditions what increases the risk factors for hypertension for both groups, regardless the age.
Discussion and conclusions Minners working place has certain specifficities, characteristic proffessional damadges and health risks. The basic proffessional damadges in mines are: innapropriate metereological factotrs, dusting, noise, vibrations, hard work, working in shifts, narrow working space, innapropriate position, etc. This group is directly related to process of coal digging, which means working at the front of the group where these risk factors are highest. Increased physical effort, sensation activity, noise, vibrations, innapropriate position, all these factors lead to certain preasure of organism that leads to psychical preasure. Surface coal digging as working enviroment has pfoffessional damadges but in a lot less level than under the surface. as most important factor, this area has natural ventilation and possibillity of decreasing of dusting by moisturing of this area, what is more comfortable than in a pitt. (9,7). Constantly present feeling of tension has a direct influence on cardiovascular sytem and hypertension risks (5). All these damadges individualy or in a group have influence on cardiovascular system and lead to hypertension of certain level. Along with genetic predisposition, risk factors and other mentioned proffessional damadges, unless its detected in a right time and curred, lead to progressive hypertension that can also produce different cardiovascular incidents. After testing, it is obvious that hypertension is a leading dissease among minners. Based on research and sttistical processing, it is proved that there is signifficant difference in diagnosisng of hypertension regarding the age and no matter on working conditions. The research showed that those who work inside the minning pits are more exposed to hypertension regardless the years in work (in group up to 20 and over 20 years of work). Out of 518 workers, who work in minning pits, 238 is with diagnosed hypertension or 45,9 %, and in comparing to years of working, the difference is not evident, which means that risk factors in working area are extremly influential on diagnosing of hypertension in minners. In order to prevent these disseases in minners, an effort is made to decrease their exposure to bad influencess, primarly coal dust (3). 49
National institute for proffessional safety and health of workers in USA (NIOSH-national Institute for Occupational Safety and Health ) in septembre 1995. has proclaimed proposition that exposure limit (REL.recommended exposure limit) does not breach over 1mg/m3 of air during average working time of 10 hours per day with 40 hour working week. (5). Presented material shows tha factors of working enviroment, primarly coal dust, tension, narrow working space without ventilation, leads to certain tension of organism and hypertension. (1). Smoking is additional risk factor in working enviroment of minners. Irritation of vegetative ganglion leads to increase of cardio frequency , beating and minute volume and increase of artery preasure (10). It is evident that great number of minners additionaly increasses hypertension cases, esspecially in group over 20 years in work. Research show the signifficant difference between the groups working inside and outside the minning pits, i.e. the minners inside minning pits are smokers in most cases and get hypertension diagnose more often. The results of this paper show that these damaging factors seem mostly cumulative and the most number of tested cases have been exposed to respirative coal dust and smoking. In order to aplly these research results, it is necesary to present it to subjects incharge, with recomondation of preventive-promotional work as the way to influence the quality of living of minners as well as guarancy o microclimatic working conditions what would provide respirative dust to allowed level. This research should be used as reason for further similar ang bigger researches in future. There are no conditions of working enviroment without certain health risks on workers health. Proper evaluation of danger in work must include the work itself, working enviroment and total phisical and psychical markings of workers. When all these markings are known, including proffessional and nonproffessional risk factors, we can provide adequate evaluation of health condition in order to protect employees health. 50
It is mandatory to educate family doctors related to illnesses that can dissapear or get worse in time becouse of innapropriate working conditions and establish good cordination between medical services in order to prevent premature disseases, consequential sick-leaves and premature invalidity. Further on, it is mandatory to perform medical sistematic examinations in order to detect illness in proper time and to prevent progression of it, complications and to prevent invalidity This research should be used as influential for other bigger researches in order to include team aproach to overviewing and resolving of mentuioned problems. Literature
1. Hearth Disease and Stroke Statisties 2004 Update. Dallas, Texas: American Hearth association; 2003. 2. Deborach D. Risk factors for atherosclerosis among coal miners.2003;12:23-45. 3. Newman B. Ankle-arm index as a predictor of cardiovasular disease and mortality in the cardiovascular health study. 2002; 3:538-545. 4. Nordsrom K.Work related sress and early atherosclerosis miners. Epydemiology 2001;2:180-185. 5. Schnell L. The workplace and cardiovascular disease. OCCUP Med. 2000,1:12-23. 6. Gryn Y. Prevalence of silicosis at death in under round coal miners- Am. J Med. 2002;16:605-615. 7. Jensen H. Occupational miners diseases. Western Federation of miners. 2002; 1-54. 8. Institut za ocjenjivanjeradne sposobnosti. Radno angaovanje invalida rada i prijedlog mjera prevencije imnvalidnosti u rudnicima uglja u BiH. Sarajevo.1989g; 22-54. 9. Wang L. Clinical important FEV declines among coal miners. Ocup env Med J.1999,65:837-844. 10. Puvai Z. Statistika u medicini. Sarajevo.1999. Corresponding author: Muvedeta Lemes PZU INTERMED Kakanj, Adress: ZPO br: 52, 72240 KAKANJ Telephone /fax: + 387 ( 032 ) 55 46 84 E-mail: mlemes@bih.net.ba
dependence of lower extremies amputations to caracteristics of diabetes mellitus

oViSNoST amPuTaCija doNjiH ekSTremiTeTa u odNoSu Na oSobiNe dijabeTeS meLiTuSa
Dijana Avdic1, Dzemal Pecar, Mensura Kudumovic, Mirela Avdic Orthopedic Clinic, University Clinical Center Sarajevo, Bosnia and Herzegovina
Summary Introduction: There are two types of Diabetes mellitus (DM) and each have different ocurrence of lower extremitates amputation.The most common reason for amputation is existance of diabetic foot. Aim: Is to presentate occurrence of lower extremitates amputation in relation to DM type, when during the existance of DM is done the most of all amputations, type of antidiabetic therapy in the amputatet patients, number of dead outcomes among amputated patients by reason of additional complications. Patients and methods: Retrospective study is done at Clinic for orthopedy and traumathology and at Institut for vascular diseases KCUS. Study includes 87 patients of which 60 are evaluated which endured lower extremitates amputation due to DM existance during 2 years period. Results: Among amputated diabetic patients 91,7% were with DM type 2 and 8,3% with DM type 1.30% patients with DM for 5-10 years ,15 % less then 5 years , 13 % patients 16-20 years,13% 21-25 years,and 5% over 25 years. 88,3% patients were treated with Insulin therapy .11,7% were on oral antidiabetic therapy.Five patients died soon after amputation. Conclusion: There is difference in DM type between. Amputations are more often at patients with duration of DM from 5 to 10 years and at patiens on insulin therapy. Key words: Diabetes type,diabetic foot
Saetak Uvod: postoje dva osnovna tipa dijabetes melitusa kod kojih je uestalost amputacija donjih ekstremiteta razliita. Najei razlog za amputaciju kod dijabetiara jeste postojanje dijabetinog stopala. Cilj rada: prikazati uestalost amputacija donjih ekstremiteta prema tipu dijabetes melitusa, u kojem periodu trajanja dijabetes melitusa je uraeno najvie amputacija, tip antidijabetine terapije kod amputiranih pacijenata, broj (procenat) pacijenata kod kojih je nakon uraene amputacije nastupio smrtni ishod kao posljedica dodatnih komplikacija. Pacijenti i metode rada: istraivanje je provedeno na Klinici za ortopediju i traumatologiju i Institutu za vaskularne bolesti KCUS u vidu retrospektivne studije. U obzir je uzeto 87 pacijenata, a analizirano je njih 60 kod kojih je uraena amputacija donjeg ekstremiteta kao posljedica dijabetes melitusa u dvogodinjem periodu. Rezultati: meu amputiranim dijabetiarima 91,7 % pacijenata je imalo dijabetes melitus tip 2, a 8,3 % dijabetes melitus tip 1 (X=0,343, p>0,05). Najvie pacijenata, 30 %, imalo je trajanje dijabetesa 5 10 godina, 15 % pacijenata do 5 godina, 13 % pacijenata 16 20 godina, 13 % 21 25 godina i 5 % pacijenata trajanje dijabetes preko 25 godina (X=4,682, p>0,05). Na inzulinskoj terapiji bilo je 88,3 % pacijenata, dok je 11,7 % pacijenata bilo na terapiji oralnim antidijabeticima 51
(X=3,672, p>0,05). Kod 5 (8,3 %) pacijenata je nastupio exitus letalis nakon uraene amputacije. Zakljuak: utvreno je da je kod amputiranih pacijenata postojala znaajna razlika prema tipu dijabetes melitusa. Amputacije su bile najee kod pacijenata koji su imali trajanje bolesti 5 10 godina te kod pacijenata koji su bili na inzulinskoj terapiji. Kljune rijei: tip dijabetesa, dijabetino stopalo 1. Introduction Diabetes mellitus is basiclly deficitary disease which is result of apsolute or relative insufficiency of insulin.There are two basic types of diabetes mellitus: type 1 autoimmune disorder where immune system attack beta pancreatic cells which produce hormon insulin and type 2 - where pancreatic cells insulin production is not sufficient and other cells receptors do not t recognize insulin (1,2). Critical diabetic ishemic disease is the most complicated problem in vascular medicine Critical ishemia of extremity is definted as ishemia which endanger parts of extremity or whole exstremity. It is caracterised by persistent pain in pasive actions, ulcers, feet gangrena and pedal arteries sistolic pressure < then 50 mm Hg.(3) One of the most basic reasons for lower extremities amputation in diabetic patients is diabetic foot.Clinical signes are: ulcers, tipical foot deformations, occurrence of hronic oedema, ishemic changies leading to necrosis and gangrena.(4) Lower extremities amputation in diabetic patients can be resut of infection, neuropathia and microvascular disease. Analyse results show that 3,7% of amputated diabetic patients are with less then 45 years of age; 31,9% patients are in group with 45-65 years of age and 64,4% are older than 65.(5,6) Medical rehabitation is one possibiliy how to moderate phisical,psychical and social consequences of amputations. Rehabillitation aim is to prosthetic, to substitute amputated part of extremity with prosthesis and to train amputated person how to use prosthesis.(7)
2. AIMS - to presentate occurrence of lower extremities amputation according to DM type; - DM duration related to lower extremity amputations perfornance; - type of antidiabetic therapy in the amputatet patients; - number(and %) of dead outcomes among amputated patients by reason of additional complications. 3. Patients and methods Retrospective study is done at the Clinic for orthopedy and traumathology and at Institut for vascular diseases CCUS. Study includes 87 patients , 60 are evaluated which endured lower done by x2 test ( level of significancy ) and by Pearson correlation Coficient extremitates amputation, 41 (68%) male and 19(32%) female, due to DM complications during 1 year period. Data assasment is.
4. Results
Chart 1. Patients division by DM type X= 0,343 p>0,05 As it is visible at chart above there is significant difference in lower extremity amputation occurrance in relation to DM type. 91,7 % patients were with DM type 2 but only 8,3% DM type 1.
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5. Discussion According to DM type ,55 patients were with DM 2 and 5 patients were with DM 1, ratio 92%: 8%. Tseng and Van Gilis and associates also found in their study that majority of amputated patients were with DM2(8,9). Duration of DM is evaluated and we had 15 % of patients with DM less than 5 years; 30% 5-10 years; 13 % 16-20 years; 13% 21-25 years and 5% of patients with DM over 25 years. So in our study the majority of patients were diabetic from 5 to 10 years. Tseng and Van Gilis and associates got the same result in their study. Antidiabetic therapy in the evaluated patients was various. 88% of patients were treated with insulin; 12% with oral therapy. Our findings are similar to other studies which we used for comparisons .(8,9) 6. Conclusions - According to DM type there is significant statistic difference beween amputated patients with DM type 1 and DM type 2; - Duration of DM is not statisticly significant in the period from 5 to 25 years . We found that patients with DM duration over 25 years had less amputation occurrance then patients with shorter duration of DM; - Five patients died soon after lower extremity amputation by reason of additional complications.
Chart 2. DM duration ( years) X=4,682 p>0,05 Chart showes that majority of patients, 30 %, had DM duration 5 10 years and that minority of patient only 5% had DM duration over 25 years.
Chart 3. Patient division by antidiabetic treatment X=3,672 p>0,05 There is evident difference among amputated patients regarding therapy. 88,3 % of patients were treated with insulin, 12% with oral therapy .
Chart 4. Patients with exitus letalis after lower extremity amputation by reason of additional complications From 60 (69 %) amputated diabetic patients 5 (8,3 %) patients ended up with exitus letalis after lower extremity amputation by reason of additional complications
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7. Literature
1. Helji B. i saradnici. Diabetes mellitus kliniki aspekti, Medicinska knjiga, Sarajevo, 2002. (121 149 str.) 2. Guyton A. Human physiology and mechanisms of disease, Published by N.B. Saunders, Philadelphia, Pennsylvania, 1991. (78 80 str.) 3. Levin M., ONeal L., Bowker H. The Diabetic foot, Mosby year book, St. Louis, 1993. (57 59 str.) 4. Klein L., Lopes Virela F. New concept about the pathogenesis of atherosclerosis and thrombosis in diabetes mellitus, Journal Article, St. Louis, 1993. (33 35 str.) 5. Nedvidek B. Osnovi fizikalne medicine i medicinske rehabilitacije, Medicinska knjiga, Novi Sad, 1986. (70 80 str.) 6. Dahl Jorgensen K. Diabetic microangiopathy, Acta Paediatr Suppl, 1998, 31 (4) : 25 7. Pickup C., Williams G. Text book of Diabetes, Black well Scientific Publications: London, Edinburg, Boston, Melbourne, Paris, Berlin, Vienna, 1991. (45 48 str.) 8. Avdic, D., Buljugic, E. Osteophorosis, how prevent and how treat it. HealthMed, Dec2008, 2(4):305306, 9. Avdic, D., Jusupovic, F., Kudumovic, M. Anthropometric values for boys aged 14 - 15 years who actively train basketball in comparing to boys of same age who do not train any sports HealthMed, Dec2008, 2(4): 253-264.
Corresponding author:
Dijana Avdic Orthopedic Clinic, University Clinical Center Sarajevo, Bosnia and Herzegovina e-mail: dijana2007@gmail.com
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de Quervains tenosynovitis occurence in patients with u repetitive Stress injurys treated at the basic rehabilitation PraXiS center
efikaSNoST TreTmaNa TeNiSkog LakTa (ePiCoNdyLiTiS Humeri radiaLiS) u ambuLaNTi Cbr -PraXiS
Dzemal Pecar*1, Dijana Avdic2
1 2
High Medical School, University of Sarajevo, Bosnia and Herzeegovina Orthopedic Clinic, University of Sarajevo Clinical Center, Bosnia and Herzegovina
Summary Introduction: Among patients treated at clinic PRAXIS during past 15 years, there were 2422 patients treated for Repetitive stress injuries on upper and lower extremities. 18 diagnoses were included, among which there were 50 patients diagnosed with De Quervains tenosynovitis. Only patients with De Quervains tenosynovitis who had vertebral symptoms were excluded from the study. Repetitive Stress Injuries represent epidemiological emerging serious and important diseases. Incidence of Repetitive Stress Injuries increased from 14% to 56% in the period from 1978 to 1900 and has been associated with total increase in professional injuries. Method: 50 patients with De Quervains tenosynovitis were treated using local injection of depocorticosteroid with regular dosage. The treatment effects were evaluated on first and control examination. Disease severity was assessed from 1 to 5 using same general scheme with functional ability test. Results: Our results show that 96% of patients were treated sucsessfuly and the same effect was acomplished in 2 patients with recurent symtomes upon repeated injection. For complete recovery 3 patients received physical therapy during the pe-
riod of 3 weeks. Cost benefit and Cost efficiency analysis revealed that the above mentioned approach in the treatment of these patients is efficient and 96% of patients regained work ability after one examination and concurrent intervention. Practically the total expenses include: medication price, specialist examination and application without the loss of work engagement in active working population. Expressed in value points it amounts 50 points (1 point represents relative value determined by Federal Health Insurance Institute norms). Conclusion: Local instillation of corticosteroids leads to almost 100 % treatment efficiency and functional work ability in patients. Key words: De Quervains tenosynovitis, local application, depo-corticosteroid Saetak Teniski lakat (Epicondylitis humeri radialis) je najei razlog zbog koga pacijenti, sa bolom u lakatnom zglobu, idu ljekaru. Egzaktni uzrok nastajanja bola u laktu je jo uvijek nije razjanjen u potpunosti, ali je u uzronoj vezi sa vezivnim hvatitem miia podlaktice,sa kostima podlaktice u podruju lakta. 55
U ovom radu izvrena je analiza ukupnog uzorka pacijenata iz zdravstvene ustanove Praxis koji su se u toku petnaest godina javljali radi lijeenja bolnog lakta (Epicondylitis humeri radialis). Od ukupno 228 pacijenata bilo je 126 mukaraca, 101 ena i jedno dijete do 14 godina starosti. Poetnim pregledom utvrenoje je da zbirni prosjek poetnog zdravstvenog stanja pacijenata valorizovan sa ocjenom 2,87, a nakon zavrenog lijeenja, sa ocjenom 4,48. Od ukupnog broja od 223 pacijenta lijeenih kombinovanom metodom manipulacije i lokalne instilacije kortikosteroida, kod osam pacijenata je primjenjena i fizikalna terapija. Prema tome nije bilo potrebe da se primjeni operativni tretman ni kod jednog pacijenta. Tretman pacijenata je ukljuivao 1. primjenu manipulacijkih metoda radi uspostavljanja pokretljivosti blokiranog radio-humeralnog i gornjeg radio-ulnarnog zgloba, 2. lokalnu instilaciju depo kortikosteroida radi lijeenja upale (enthesitis-a), a time i eliminacije bola i uspostavljanja fiziolokih uslova funkcionisanja zgloba i lokalnih sturktura. Za razliku od konzervativne metode kojom se u poetnoj fazi primjenjuje imobilizacija, radi sprijeavanja iritacije i razvoja upalnog procesa, uz istovremeno analgetsku antireumatsku medikamentnu terapiju, poetna primjena manipulacije, sa uspostavljenjem pokretljivost zgloba, a ne imobilizacije, naknadnom instilacija steroidnih preparata, postie se, u pravilu, funkcionalna restitucija i veoma brzo uspostavljanje pune radne sposobnosti. Kljune rijei: Epicondylitis humeri radialis, manipulacija, medikamentnozna terapija. Introduction Repetitive strain injury (RSI), known also as a Cumulative Trauma Disorder (CTD) is a syndrome caused by profesional hand repetitive task, acompanied by nonspecific hand pain or disorder of upper extremities overuse is most common current disease manifestation caused by professional injury due to arms overuse or pathological alterations. 56
In typest a typing cramp often occurs. The main cause is typewriting machine, computer or musical instrument overuse which causes cumulative tissue damage, secondary inflammation and severe pain. Disorders such as repetitive strain injury are associated with both physical and psychosocial stressors(1,2,3,4). Statistical data from US Bureau of Labor Statistics for the year of 1980 show that the prevalence of RSI is 18% in total professional injuries, and the prevalence has increased during the period of eighteen years up to 66% in the year of 1998. It is estimated that for every reported RSI case there are 10 more which are unreported. In USA authorized institutions estimates that RSI expenses for the industry amounts up to 20 milliard US dollars on yearly bases measured in reimbursement and the additional 54 milliards US dollars in loss of working hours. For the RSI diagnosis, typical complaints are: - pain in the arm which irradiates in several directions, - pain worsens during the work, - weakness and reduction in endurance, - marked arm and shoulders muscles rigidness, - symptoms spread diffusely in nonanatomical manner, do not follow nerve distribution Patients believe that the pain is associated with the injury -. tissue damage. The cause for the belief is strong alarming pain which predicts danger (4). Physical examination for objective abnormalities determination starts with tender, gentle movements, without firm grip. Diagnostic, electrophysiological and radiological test are normal. Pain intensity and loss of function is associated with work stress (5). There are three simple mechanisms which can influence pain enhancement and pain related disability (6). Psychological distress (depression or anxietytension) causes pain enhancement (decrease or increase in pain threshold susceptibility for painful savors) Psychologist consider it catastrophic pain and believe it to be worse than standard pain sensation (7). Patient sense it to be something serious and that it will not lessen with standard examination and professional services (8). Psychologist calls this amplified anxiety or health anxiety.
There is evidence that the behavior affects health perception. Active illness can amplify sense of a person not being healthy. On contrary, health is in a great manner dependant on persons behavior and thinking. The term RSI is a term used for patients without specific related term with corresponding pathophysiology associated with the pain. It can also be used as an umbrella term incorporated in other discrete diagnoses that were related (usually without the reason) with the pain in the active arm such as: - Carpal tunnel syndrome, - Cubital tunnel syndrome (Ulnar nerve entrapment), - Thoracic Outlet Syndrome, - DeQuervains syndrome, - Stenosing tenosynovitis (Trigger finger/ tumb) - Intersection syndrome, - Golfers elbow (medial epicondylosis), - Tennis elbow (lateral epicondylosis), or - Focal dystonia. RSI is also used as an alternative or umbrella term for other nonspecific diseases and as a general term which defines partially unaddressed pathology. De Quervains tenosynovitis is a term for tendon and sheet inflammation of the abductor pollicis longus and extensor pollicis brevis muscles. Repeated ulnar deviation hand movements lead to inflammatory reaction which causes tendon and tendon sheet thickening additionally narrowing the canal with consequent irritation. This overstress syndrome occurs in athletes, musicians, tailors, physical workers and laundress in whom the activity of the thumb finger is frequent. Clinical pain dominates in the area of radial styloid process accompanied with crepitations which are amplified during the palpation. The most characteristic is a Finkelstein test which is performed so that the thumb is placed in the closed fist and the hand is ulnar deviated. If sharp pain occurs, the test is positive. The treatment is conservative in the beginning and includes rest, wrist immobilization and nonsteriodal antiinflammatory drugs. If there is no relieve of the symptoms, local application of corticosteroids with anesthetics is
indicated. In the later stages of the disease if the stenosis and thickening of the tendon sheets is present, the remaining treatment option is surgical with decompression and tendon sheet clean up. Physical rehabilitation begins two days later. Tenosynovitis styloidei radii or De Quervains tenosynovitis is always accompanied with local swelling, pain in the wrist which irradiates in the forearm and distally towards the thumb. Tendonitis is inflammation of the tendon or its bone connecting fibroses tissue composed of collagen bundle and blood vessels. Tenosynovitis is tendon sheet inflammation which can be caused by repetitive tension or microtraumatisation, calcium ions deposition, high blood cholesterol levels, rheumatoid arthritis or gout. De Quervains disease, an inflammatory disorder that can be caused by cumulative injury, is one of the most commonly diagnosed problems seen by hand surgeons, and is a major cause of lost workdays. Movement is accompanied by crepitations with decreased amplitude of wrist and thumb maximal movements. De Quervains tenosynovitis symptoms can be different only with involvement of a tendon. These symptoms are due to the inflammatory reaction of the wrist affecting the surrounding nerves, tendons, tendon sheets and fascia. Diagnosis of De Quervains tenosynovitis is based on local swelling, painful sensations and decreased hand function. Symptomatological relief can be achieved with the rest or immobilization (wrist splints), topical heat or cold application (usually helps the patient) and nonsteroidal antiinflammatory medications (NSAIDs). Corticosteroid application between sheet and tendon helps the most. Surgical intervention is rarely used. Surgical intervention of de Quervains tenosynovitis can be complicated by neuroma formation or radial nerve damage. Analyzing the demographical data from the Army medical databases in the period from 1998 to 2006 it was possible to find the data on de Quervain tenosinovitis prevalence. The prevalence was 11 332 cases in total population. Females were affected significantly more frequent (2,8 on 1000) compared with the males (0,6 on 1000). Risk factor besides the gender is age. In patients older then 40 years of age prevalence of the disease is 2 on 1000 compared with the patients below the age 57
of 20 (0,6 on 1000). Prevalence in African Americans is 1,3 on 1000, and in Caucasians 0,8 on 1000. Risk factors for the diseases in this study were gender, age and race (9). Radial nerve superficial branch is vulnerable to trauma and iatrogenic injuries. There is a close relationship between radial artery and this radial nerve branch, which can explain the pain during the tendon sheet incision in surgical interventions (10). In a prospective study which included two group of patients with Trriger finger and de Quervain syndrome, patients were given steroid medications and anesthetics. Pain decreased in both groups during first seven days, and in one third of patients pain reoccurred (11). The data indicates the efficiency of Triamcinolone injection in patients with de Quervain syndrome. Mixture of 1 ml Triamcinolone and 1 ml Lidocaine 1%, is usually given in two week intervals. This medication is instilled in a point above the induration as well as in the projection of extensor digiti brevis and abductor pollicis longus muscle tendon. Effectiveness is achieved in 89% of cases (12). The Author of Omega plastics accentuates the delicate surgery treatment procedure in relation with the preservation of periosteal contact of osteofibrosis tunnel on radius styloid process (13). Successful surgical treatment is influenced by anatomical variations of abductor pollicis longus and extensor pollicis brevis muscle tendons, which needs to be accounted (14). Material and methods The study included 2 422 patients diagnosed with repetitive strain injury (RSI) in the PRAXIS clinic for rehabilitation during the past 15 years. Retrospective analysis evaluated the occurrence of the RSI disease and treatment effects of locally instilled depo-corticosteroid medications in patients with de Quervains tenosynovitis. In patients with RSI syndrome the treatment effect was evaluated in 50 patients diagnosed with tenosynovitis styloidei radi or De Quervains tenosynovitis. Clinical condition was assessed before and after the treatment in accordance with the following common table: 58
Grade 0 : Grade 1 : Grade 2 : Grade 3 : Grade 4 : Grade 5 : Grade 6 : Grade 7 :
Immobile patient Hardly mobile with help from another Hardly mobile with the help of apparatus Independently mobile with the help of apparatus Good functional status with minimal consequences Preserved functional status Further medical treatment needed Treatment interrupted and continued at another clinic
Synthetic depo Betamethasone medication (1 mL ampoule) was used for the therapy of this syndrome in the dosage 2 + 5 mg, which has strong antinflammatory and secondary analgesic effects. The medication is injected locally between tendon and tendon sheet (intravaginally). Part of the medication is also instilled outside the tendon sheet between extensor pollicis brevis and abductor pollicis longus muscle tendon for the possible occurrence of nonspecific tendon inflammation (and its sheets) and styloid process. Upon the medication application according to the observed data, pain relieve can be expected in 6 to 12 hours, and full recovery after 24 hours. Usually there is function recovery and pain reduction at the same time. Therefore it is possible to assess treatment effects with clinical examination on the first control check-up. Results and discussion Prevalence of RSI was relatively high 11,51% or 2 422 patients out of which there were 50 (2%) patients diagnosed with tenosynovitis styloidei radii or de Quervains tenosynovitis (Table 1). Table 1. Baseline characteristics of patients treated in the past 15 years at the CBR PRAXIS
RSI 2.422 1.069 1.346 4 3 Total 21.042 11.091 9.738 78 135
Males Females Children -7 years Children 7-14 years
clinical symptoms grade (2,8) was lower than the general grade in RSI group.
Figure 1. RSI gender differences
Figure 3. Estimate primary functional ability patients with tenosynovitis styloidei radii before and after treatment In 96% patients, after the examination and locally medication application, already after 12 hours patients were feeling healthy and regained functional ability. Only two patients (4%) required repeated injection, and after 7 day were completely recovered. Cost benefit analysis revealed that above mentioned approach was far more efficient, considering the fact that 96% of patients regained functional ability after one application. Practically the total expenses include: medication price, specialist examination and application without the loss of work engagement in active working population. Expressed in value points it amounts 50 points (1 point represents relative value determined by Federal Health Insurance Institute norms), that is 24 times lesser than the using standard protocol. Standard protocol for this disease would consist of following procedures: after initial examination of general health practitioner and orthopedic specialist, patients would be given splint for 7 to 10 days, with analgesics and work absence.
Figure 2. Total number treated at the CBR PRAXIS clinic Our study revealed that 56% of patients were females (Table 1 and Picture 1). It is specific for De Quervains tenosynovitis to affect more females, over two thirds of patients with the disease are females (68%) and only 38% males. Analising gender prevalence, greater prevalence of females was observed also in other diseses which fall under RSI category and affect tendonsynovial tissue. It seems that the underlying pathophysiology in RSI diseases and greater occurences of active working females could be attributed to longer repetitive movments of upper extremities including the hand. Our results show that in patients with tenosynovitis styloidei radii or De Quervains tenosynovitis primary functional ability assesment, as well as
Table 2. Estimate primary functional ability patients with tenosynovitis styloidei radii before and after treatment
Grade Number patients: before traetment Number patients: after treated 0 nula 0 0 1 jedan 0 0 2 dva 17 0 3 tri 26 0 4 etiri 7 21 5 pet 0 26
59
Therefore, first two examinations - 30 points, two control examination - 20 points, splint application - 45 points and analgesic 10 points totally 105 points. Furthermore, for 10 days of work disability 1/3 of general LD=250 points, physical treatment 14 days =350 points, reimbursement for 14 day of absence= half of general LD=400 points. It sums up to 1210 points for three weeks treatment and rehabilitation. This procedure does not include contribution on work in working hours since this variable does not have adequately estimated value in our settings (In USA this loss would be 2 times more compared to personal income). Conclusions RSI represents growing problem for the mankind. During the past 20 years RSI constitutes great percentage in the diseases which leads to temporary work disability (Absentees). Among the RSI diseases, tenosinovitis styloidei radii occurs more frequently in females (68:32). Treatment of this disease with standard protocol is inefficient and more costly (24 times more). Local instillation of corticosteroids leads to almost 100 % treatment efficiency and functional work ability in patients. Literature
1. Pinsky, Mark A., The Carpal Tunnel Syndrome Book, Pinsky,Mark A.,The Carpal Tunnel Syndrome Statistics U.S. Bureau of Labor Statistics Book Warner Books, 1993, p. 44. 2. Szabo R.M., King K.J.Repetitive stress injury: diagnosis or self-fulfilling prophecy? J Bone Joint Surg Am. 2000 Sep;82(9):1314-22. Review. 3. Ring D., Guss D., Malhotra L., Jupiter J.B. Idiopathic arm pain. J Bone Joint Surg Am. 2004 Jul;86A(7):1387-91.. 4. Quintner J.L.The Australian RSI debate: stereotyping and medicine. Disabil Rehabil. 1995 Jul;17(5):256-62 5. Ring D., Kadzielsky J., Malhotra L., Lee S.P., Jupiter J.B. Psychological factors associated with idiopathic arm pain. JBJS 2005 10; 87: 374-380.
6. Nahit ES, Pritchard CM, Cherry NM, Silman AJ, Macfarlane GJ. The influence of work related psychosocial factors and psychological distress on regional musculoskeletal pain: a study of newly employed workers. J Rheumatol (2001)28 (6): 137884. 7. Vranceanu AM, Safren S, Zhao M, Cowan J, Ring D. Disability and psychologic distress in patients with nonspecific and specific arm pain. Clin Orthop Relat Res. 2008 Nov;466(11):2820-6. Epub 2008 Jul 18. 8. Vranceanu A.M., Safren S., Zhao M., Cowan J., Ring D. Disability and psychologic distress in patients with nonspecific and specific arm pain. Clin Orthop Relat Res. 2008 Nov;466(11):2820-6. Epub 2008 Jul 18. 9. Wolf JM, Sturdivant RX, Owens BD. Incidence of de Quervains tenosynovitis in a young, active population. J Hand Surg [Am]. 2009 Jan;34(1):112-5. Epub 2008 Dec 10. 10. Robson AJ, See MS, Ellis H. 2NApplied anatomy of the superficial branch of the radial nerve. Clin Anat. 2008 Jan;21(1):38-45. 11. Goldfarb CA, Gelberman RH, McKeon K, Chia B, Boyer MI. Extra-articular steroid injection: early patient response and the incidence of flare reaction. J Hand Surg [Am]. 2007 Dec;32(10):1513-20. 12. Sawaizumi T, Nanno M, Ito H -De Quervains disease: efficacy of intra-sheath triamcinolone injection. Int Orthop. 2007 Apr;31(2):265-8. 13. Bakhach J, Sentucq-Rigal J, Mouton P, Boileau R, Panconi B, Guimberteau JC. [The Omega Omega pulley plasty: a new technique for the surgical management of the De Quervains disease] Ann Chir Plast Esthet. 2006 Feb;51(1):67-73. 14. Bakhach J, Sentucq-Rigal J, Mouton P, Boileau R, Panconi B, Guimberteau JC. [The Omega Omega pulley plasty: a new technique for the surgical management of the De Quervains disease] Ann Chir Plast Esthet. 2006 Feb;51(1):67-73.
Corresponding author: Dzemal Pecar High Medical School, University of Sarajevo, Bolnika 25, 71000 Sarajevo, Bosnia and Herzeegovina e-mail:
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influence of early physiotherapy to recovery after Paresis N. facialis

uTiCaj raNe fizikaLNe TeraPije Na oPoraVak NakoN Pareze N. faCiaLiSa
Edina Tanovic Clinical Centar of the University of Sarajevo, Institute for Physiotherapy and Rehabilitation Bosnia and Herzegovina
Summary Nervus facialis is the seventh cerebral nerve which stimulates mimic muscles and it is also sensory nerve for frontal two thirds of the tongue. Lesion of nervus facialis can be caused by: trauma, inflamatory process on middle ear, with tumors, head or ear surgery. Paresis can be central and peripherial. Aim of this paper is presentation of results after rehabilitation of damage to nervus facialis and comparison of level of remaining damages between patients who undertook physiotherapy and patients who did not. In the study were treated two groups of patients, each consisting of 30 patients with paresis n. facialis. The first group which was subject of this research was treated by general standards with medicaments and physiotherapy. Physiotherapy was conducted through electro-stimulation and kinetic therapy during one month period. Second group was control group. Patients were treated by general standards and with medications only during one month period. Statistic data covers sex, age, coverage of n. facialis and treatment outcome. In the estimate of clinical features we used House-Brackman scale. Statistical data showed that there is no statistically important difference in sex distribution, most of patients were aged 10-50, majority of patients had all three branches of n. facialis covered (70% in test group and 76,6% in control group). 13,3 % patients in test group were completely cured after one month of physiotherapy, while the same result was shown in control group in only 3,33%
of patients. After one month of therapy recovery was noticed in 86, 6% of patients in the test group and 83, 3% in control group. There were no patients who have not recovered in the test group while in control group the percentage was 13, 3%. After the research we can draw the conclusion that the patients who received physiotherapy alongside with standard measures and medications showed better results of rehabilitation than the patients who did not receive physiotherapy. Multidisciplinary approach to treatment of damage to n. facialis that includes physiotherapist from the beginning shows the best rehabilitation results. Key words: paresis, physiotherapy, rehabilitation Saetak Nervus facialis je sedmi modani ivac, koji inervira miminu muskulaturu i senzorni ivac za prednje dvije treine jezika. Lezija nervus facialisa moe nastati: traumatskim djelovanjem, upalnim procesom na srednjem uhu, kod tumora, operativnog zahvata podruja glave ili samo uha. Pareze mogu biti centralne i periferne. Cilj rada je prikazati rezultate rehabilitacije oteenja nervus facialisa i komparirati stepen preostalog oteenja kod pacijenata koji su proveli i koji nisu proveli fizikalni tretman. U studiji su obraene dvije grupe od po 30 pacijenata sa paresom nervus facialisa. Prva grupa od 30 pacijenata, ispitivana grupa, je lijeena primjenom optih mjera, medikamentoznom terapijom kao i fizikalnom terapijom. Fizikalna terapija je 61
ordinirana u vidu elektrostimulacije i kineziterapije u trajanju od mjesec dana. Druga grupa, kontrolna je lijeena optim mjerama i medikamentoznom terapijom takoer mjesec dana. Statistiki su obraeni spol, dob, zahvaenost n. facialisa i ishod lijeenja. U procjeni teine klinike slike koristili smo se House-Brackmanovom skalom. Na osnovu statistike obrade i dobijenih rezultata uoili smo da nema statistiki znaajne razlike u spolnoj zastupljenosti, veina pacijenata je u dobi izmeu 10 i 50 godine Najvie pacijenata je imalo zahvaene sve tri grane n. Facialsia ( 70% u ispitivanoj i 76,6% u kontrolnoj grupi). Nakon lijeenjae u ispitivanoj grupi kod 13,3 % pacijenata dolo do potpunog izlijeenja u roku od mjesec dana koliko smo ordinirali fizikalni tretman dok je kod kontrolne grupe takav rezultat bio samo kod 3,33%. Nakon mjesec dana terapije pokazalo se da su oporavljeni, kod ispitivane grupe 86,6% , a kod kontrolne grupe 83,3 % pacijenta. U ispitivanoj grupi nije bilo neizljeenih pacijenata dok je u kontrolnoj grupi bilo 13,3 % pacijenata Nakon istraivanja moemo zakljuiti da su pacijenti kod kojih je uz opte mjere i medikametoznu terapiju ordinirana rana fizikalna terapija pokazali bolje rezultate rehabilitacije nego pacijenti kod kojih fizikalna terapija nije primjenjena. Multidiciplinarni pristup u lijeenju oteenja n. facialisa u koji je od samog poetka ukljuen fizijatar daje najbolje rezultate rehabilitacije. Kljune rijei: pareza, fizikalna terapija, rehabilitacija
Introduction Nervus facialis is the seventh cranial nerve that stimulates mimic muscles and frontal two thirds of the tongue. Lesion to n. facialis can be caused by: trauma, inflammatory process on middle ear, with tumors, after head or ear surgery. Paresis can be central and peripheral. (1, 2, 3). Prevalence of disease and injury of nervus facialis in the rehabilitation processes is not rare, so it is necessary to conduct physiotherapy and kinetic therapy for three months in most cases, depending on the level of changes and causes sometimes even longer. (4, 5, 6). 62
Level of damage is the most important factor in the evaluation of level of reinnervation. With the use of this method, changes that indicate previous paresis or paralysis can be found even after 10 years, which confirms the fact that reinnervation is never complete, although we clinically determine full function of facial muscles (7,8,9,10). Approach to rehabilitation has to be based on team work, which is in majority of cases based on cooperation between neurologist, maxillofacial surgeon, otorhinolaryngologist, traumatologist with physical therapist and physician (11, 12). Therapy duration is in most cases three weeks, break after that and then repetition as long as there are signs of functional training. Muscle fatigue must not be caused because dysfunctional muscle does not have the ability to accommodate and its stress causes reinnervation to slow down. Cooperation between patient, physician, physical therapist and members of consulting team is necessary for directing the course of therapy and rehabilitation process. Establishment of functional activity of facial muscles is not only functional aim but also aesthetical effect in the facial mimic. (13). Diagnosis is set up after physical examination (inspection, palpation, sensibility and reflex test), electromyoneurography (EMNG), electro status and manual muscle test. (15, 16). Therapy methods for rehabilitation of damage to nervus facialis consist of: general measures, conservative therapy (medications and physiotherapy) and surgery. In general measures we advise the patient to stay away from cold and wind, to wear dark protective glasses in order to prevent eye irritation, to shower the face with warm water several times a day or try to churn, which releases the tension and enhances blood flow and functionality of mimic muscles, and to use the muscles as often as possible. (17, 18, 19). Medication is performed through large doses of corticosteroids, pain killers, spasmolitics, anti-depressives, and almost half of the patients were treated with injection blockades. Physiotherapy aims to achieve muscle functionality through causing hyperemia, provoking the innervation, improvement of tonus and trofic, regaining of sensibility. For the purpose we use infrared radiation-solux lamp, galvanization through Bergonis half-mask, electro stimula-
tion, biofeedback, acupuncture, manual massage and kinetic therapy. Aims of the study Aims of this paper are: presentation of importance of physiotherapy in rehabilitation of patients after damage to nervus facialis and comparison of level of remaining damage in patients who did and who did not undertake physiotherapy. Material and methods Research sample consisted of two groups each consisting of 30 patients with paresis of nervus facialis. First group, the test group, was treated by Table 1. Overview of patients according to sex
Male Female Total N % N % N % Test 13 43,3 17 56,6 30 100,0
general measures, medications and physiotherapy. Physical therapy was ordinated as electric stimuli and kinesiotherapy and it lasted for one month. Second group, the control group, was treated by general treatment and medications also for one month. The research has been conducted as a retrospective study. Patients were selected randomly. Both groups were analyzed according to sex, age, type of disease and severity of clinical features. In the estimate of clinical features we used House-Brackman scale (19). In the scale cured patients had first and second level of damage, third and fourth level patients who recovered and fifth and sixth level of damage to n. facialis patients who were not cured. All the data is presented in the tables using the method of descriptive statistics: number of cases and percentage.
Results
Control 15 50 15 50 30 100,0 41-50 6 (20) 8 (26,6) 14 (46,6) Groups 51-60 5 (16,6) 4 (13,3) 9 (30) Control 23 76,6 6 20 1 3,33 30 100,0 Total 28 93,3 32 106,6 60 200,0 60 and more 2 (6,66) 1 (3,33) 3 (10) Total 44 146,6 11 43,3 3 10 60 200,0 Total 5 16,6 51 170 4 13,3 60 200,0
Groups ( 30+30)
Table 2. Overview of patients according to age

Test group Control group Total To 20 2 (6,66) 1 (3,33) 3 (10) 21-30 8 (26,6) 10 (33,3) 18 (60)
Table 3. Overview of coverage of n. facialis in both groups

All three branches symmetrically Primary upper branch (eye) Primary lower branch (mouth) Total N % N % N % N % Test 21 70 7 23,3 2 6,66 30 100,0 Group
31-40 7 (23,3) 6 (20) 13 (43,3)
Table 4. Overview of treatment results

Cured Recovered Not cured Total N % N % N % N %
Test 4 13,3 26 86,6 0 0 30 100,0
Control 1 3,33 25 83,3 4 13,3 30 100,0
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Discusion Nervus facialis, seventh cranial nerve belongs to the group of motoric nerves. In its composition it has secretorial strains for salivary glands, lacrimal and nasal glands and gustoreceptorial strains for sense of taste (16). Facial mimicry can express the mood, emotions, intentions and thoughts. Function of nervus facialis and mimic muscles is obvious in expression of joy, grief, pain, hate, love, hope concern, happiness, horror, admiration, fear etc. (20). Functions like speech, eating, drinking, sucking, swallowing, whispering, laughing, crying, whistling can not be imagined without nervus facialis. Functions where nervus facialis and mimic muscles participate are numerous. Patients with conditions in the facial area are disabled in everyday life, nutrition, speech and social contacts. (20). It is difficult to conclude whether damage to nervus facialis is more common in male or female population because results from various studies are controversial. Same number of studies gives advantage to men and women. (20). In our research groups were equal in terms of gender. Data in the literature shows that damage to nervus facialis is most common between the age of 10 and 50 (although it can appear at any time in life) and that every year we have 20 cases on 100 000 people (7). Our results are consistent with this data. In our research the largest number of patients had damage to all three branches of n.facialis (70% in test group and 76, 6% in control group) and the smallest number had damage to the lower branch of n. facialis. This is in favour of complexity of treatment of such patients. The condition starts suddenly and it culminates to its maximum within 48 hours. Gradual development of the condition with maximal development in the first week is rare. In majority of cases of damage to n. facialis certain level of spontaneous recovery can be expected. (3). Overview of treatment results shows that in test group 13, 3 % of patients completely cured within a month of exposure to physiotherapy while in control group only one patient or 3, 33% of patients showed such improvement. 64
After a month of therapy the largest number of patients were recovered, 86, 6% in test group and 83, 3% in control group. In the test group there were no patients who were not cured, while in control group there were 13,3% of such cases after a month of therapy. In easier cases, recovery with paresis only starts in the end of second week and in case of paralysis signs of recovery apper in the end of third and beginning of the fourth week from the start of condition. Complete recovery, if it happens, takes place 3-6 months from the beginning of the condition and crucial factor that determines the level of recovery is the level of paralysis or paresis. (3,5) Conclusion Based on the presented results and discussion in this research we can draw a conclusion that the patients who received physiotherapy alongside with general measures and medications showed better rehabilitation results than the patients who did not have physiotherapy. Multidisciplinary approach in the treatment of damage to n. facialis with physician involved from the beginning delivers the best rehabilitation results.
Literature
1. Chusid G. Joseph. Korektivna neuroanatomija i funkcionalna neurologija. Beograd: Savremena administracija, 1979: 210. 2. Grubor D. Ispitivanje vrijednosti klinike procjene Bell-ove paralize. Magistarski rad. Sarajevo l988: 41-5. 3. Jaji I. Specijalna fizikalna medicina. Zagreb: kolska knjiga l99l. 4. Jui A. Klinika elektromioneurografija i neuromuskularne bolesti. Zagreb: Jugoslovenska medicinska naklada. 1980. 5. Jani-Stefanovi J., Stefanovi D. Jednostrane paralize mimine muskulature sa akutnim poetkom. Zbornik radova. Trei kongres fizijatara Srbije i Crne Gore, Igalo, 2002. 6. Jovi N. Paraliza lica. VMA Beograd 2004: 84-85. 7. Lazi M. Zastupljenost rizikofaktora kod nastanka Belove paralize. Zbornik radova. Trei kongres fizijatara Srbije i Crne Gore, Igalo, 2002. 8. Milorad R. Jevti. Fizikalna medicina i rehabilitacija. Univerzitet u Kragujevcu. 1999. 9. Majki M. Klinika kineziterapija. Zagreb: Inmedia, l997: 77-83. 10. Mihajlovi V. Osnove fizikalne medicine. Titograd: Univerzitetska knjiga, 1983. 11. Mladenovi Z. Maksilofacialna hirurgija. Sarajevo 1984. 12. Zekovi P. Fizikalna terapija sa rehabilitacijom. Beograd: Zavod za udbenike i nastavna sredstva, 1996: 172-176. 13. Poeck K. Neurologija. Zagreb: kolska knjiga, 1994: 151-84. 14. Pavievi-Stojanovi M. Naa iskustva u lijeenju bolesnika sa perifernom paralizom facijalnog nerva. Zbornik radova Jugoslovenski kongres ljekara fizikalne medicine i rehabilitacije sa meunarodnim ueem, Zlatibor, 1997. 15. Radoji B. Bolesti nervnog sistema. BeogradZagreb: Medicinska knjiga, 1989: l83-85. 16. Semi N. Kaluerovi D. Kineziterapija i fizikalnom lijeenju periferne oduzetosti ivca lica. Beograd: Drago, 1994.
17. Stankovi I. Selektivni pristup u rehabilitaciji periferne paralize facijalnog nerva, Zbornik radova. Trei kongres fizijatara Srbije i Crne Gore, Igalo, 2002. 18. Sobotta J. Atlas anatomije ovjeka. Sv. 1: glava, vrat, gornji ud. Zagreb: Naklada, Slap, 2003. 19. Vokomanovi A. Testovi i skale za procjenu snage muskulature lica. Zbornik radova IV fizijatrijski dani Srbije i Crne Gore, Igalo, 2005: 76-8. 20. ercer A.Otorinolaringologija. Zagreb: Jugoslovenski Leksikografski zavod, 1965-1966. 65-73.
Corresponding author: Edina Tanovic Clinical Center of the University of Sarajevo Institute for Physiotherapy and Rehabilitation Center for paraplegics Bolnika 25, 71 000 Sarajevo, Bosnia and Herzegovina; e-mail: tanovicharis@hotmail.com
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intrathoracic metastases of a breast cancer treated in Clinic for pulmonary diseases and tb Podhrastovi- Sarajevo in the four-year period from 2004.2007.
iNTraTorakaLNe meTaSTaze karCiNoma dojke TreTiraNe Na kLiNiCi za PLuNe boLeSTi i TuberkuLozu PodHraSToVi u eTVorogodiSNjem Periodu od 2004. do 2007. godiNe
Vesna Cukic Clinic for pulmonary diseases and TB Podhrastovi, Clinical Centre of University Sarajevo, Bosnia and Herzegovina
Summary Objective: The aim of this study was to describe the patients with intrathoracic metastases of a breast cancer treated in Clinic Podhrastovi in the four-year period from 2004. to 2007. Material and methods: Retrospective study was carried out on the basis of clinical records of the patients with intrathoracic metastases of a breast cancer treated in four-year period in Clinic Podhrastovi. For each case it was determined the time from the first diagnosis of breast cancer to the first diagnosis of its metastases, the previous treatment (operation, chemotherapy, radiotherapy...) and association of the breast cancer with primary lung and the other organs cancer. The final diagnosis of each investigated case was established by lung and pleural biopsy. Results: It was totally 19 patients: four in 2004., five in 2005., five in 2006., five in 2007. That is 1,05 % of the total number of cancer patients treated in this period in Clinic Podhrastovi. They were aged from 37 to 74 year. In four of them it was the first diagnosis of breast cancer although they already had metastases. Fourteen 66
patients were treated previously by operation, chemotherapy, radiotherapy and one patient was treated by alternative methods. About five years after the first diagnosis of the breast cancer its metastases were diagnosed. In four cases there were lung metastases and one of them had skin metastases, one liver, and one brain metastases too. In six patients there were pleural metastases and one of them had also pericard metastases and one had bone metastases too. Five patients had both lung and pleural metastases, and among them one had liver, one had bone, and one both: bone and liver metastases.Three patients had primary lung carcinoma, and one had primary lung and laryngeal carcinoma beside the previously diagnosed breast carcinoma. Conclusion: Although there are very successful methods of early detection and treatment of breast cancer, there is a certain number of cases in which the diagnosis was late and therapy has no desirable results. Key words: breast, cancer, lung, pleura, metastases
Saetak Cilj: Prikazati pacijentkinje sa intratorakalnim metastazama karcinoma dojke koje su tretirane na Klinici Podhrastovi u etvorogodinjem periodu od 2004. do 2007. godine. Materijal i metode: Ovo je retrospektivna analiza pacijentkinja sa intratorakalnim metastazama karcinoma dojke koje su tretirane u etvorogodisnjem periodu . Odreeno je vrijeme od prve dijagnoze karcinoma dojke do razvoja metastaza, prethodni tretman: operacija, kemoterapija, radioterapija; postojala je udruenost karcinoma dojke sa primarnim karcinomom plua i karcinomima drugih organa. Konana dijagnoza je postavljena biopsijom plua i pleure. Rezultati: Ukupno je bilo 19 pacijentkinja: etiri u 2004., pet u 2005., pet u 2006. i pet u 2007. godini to predstavlja ukupno 1,05 % od ukupng broja pacijenata sa karcinomom koji su tretirani u ovom periodu na Klinici Podhrastovi. Pacijentkinje su bile stare od 37 do 74 godine. Kod etiri od njih to je bila prva dijagnoza karcinoma dojke , iako je on ve dao metastaze. etrnaest od njih je prethodno tretirano : operacija, citoterapija, radioterapija ili kombinacijom ovih metoda, a jedna je tretirana alternativnim metodama lijeenja.Metastaze su dijagnosticirane u prosjeku pet godina nakon prve dijagnoze karcinoma dojke . Kod njih etiri postojale su metastaze u pluima : jedna od njih je imala i metastaze na koi, jedna i u jetri, a jedna i u mozgu. Kod est pacijentkinja postojale su pleuralne metastaze: jedna od njih je imala i metastaze u perikardu, a jedna i metastaze u kostima. Pet pacijenktinja je imalo zajedno i plune i pleuralne metastaze, a meu njima jedna je imala i metastaze u jetri, jedna u kostima, a jedna oboje: i kotane i jetrene metastaze. Tri pacijentinje su imale primarni karcinom plua,a jedna primarni karcinom plua i primarni karcinom laringsa pored ranije dijagnosticiranog karcinoma dojk . Zakljuak: Iako postoje vrlo uspjene metode rane detekcije i tretmana karcinoma dojke, postoji izvjestan broj sluajeva gdje je dijagnoza kasno postavljena, a terapija nije dala eljene rezultate. Kljune rijei: dojka, karcinom, plua, pleura, mestastaze
Introduction Breast cancer is the cancer that starts in the cells of the breast (1). Worldwide, breast cancer is the second most common type of cancer after lung cancer (2) and the fifth most common cause of cancer death (3). There are many prognostic factors associated with breast cancer: staging, tumour size and location, grade, whether the disease has metastased, recurrence of the disease, and age of the patient. Stage is the most important as it takes into consideration size, local involvment, lymph node status and presence of metastatic disease. Breast cancer can metastasise (spread) via lymphatics to nearby lymph nodes, usually those under arm. Breast cancer can also spread to other parts of the body via blood vessels or the lymphatic system. So it can spread to the lungs, pleura, liver, brain and bones (most commonly) (1). The higher the stage at diagnosis, the worse is the prognosis (2). Intrathoracic metastases present most common as solitary or multiple nodes in one or both lungs, uniltaral or bilateral pleural effusion, lymphangiitis carcinomatosis ( which denotes involment of the pulmonary lymphatic network result of the extension of tumour from lung capillaries to the lymphatics) in both lungs; all of these with or without involment of mediastinal lymph nodes. The aim of this study was to describe the patients with intrathoracic metastases of a breast cancer treated in Clinic Podhrastovi in four-year period from 2004. to 2007. Material and methods This is retrospective analysis of the patients with intrathoracic metastases of a breast cancer treated in four-year period ( from 2004. to 2007.) in Clinic for Pulmonary Diseses and TB Podhrastovi Sarajevo. It was determined the time from the first diagnosis of breast cancer to the development of metastases, previous treatment: operation, chemotherapy, radiotherapy; there was association of breast carcinoma with primary lung cancer and cancersof other organs. Final diagnosis was established by lung and pleural biopsy.
67
Results They are shown on tables below. Table 1. Patients treated in 2004
Name Age (years) Time from first diagnosis of breast cancer without previous diagnosis five years ago six years ago eight years ago Previous treatment of breast cancer Type of metastases Lung Pleura Other right axill. lymph. vertebra th liver and right axill and. supraclav lymph. Other primary cancer
H.N.
65
no treatment right radical. mastectomia , chemoth. right radical. mastectomia left radical. mastectomia, radio th, chemoth..
right
left right
K.M.
50
L. J.
56
right,
right
P. J.
37
both
right
Table 2. Patients treated in 2005

Name Age (years) Time from first diagnosis of breast cancer without previous diagnosis five years ago without previous diagnosis seven years ago Previous treatment of breast cancer Type of metastases Lung right Pleura Other face and right arm skin, liver and right orbita. Other primary cancer
B.E.
59
no treatment left radical. mastectomia, chemoth., radio th no treatment left radical. mastecomia , radio th. right radical. mastectomia
K.M.
50
both
R.A.
66
both
S.F.
78
right
right
liver, vertebra th Ca planocell left lung
B.M.
67
two years ago
68
Table 3. Patients treated in 2006

Name Age (years) 59 Time from first diagnosis of breast cancer five years ago five years ago Previous treatment of breast cancer alternative medicine right radical. mastectomia, chemoth.,radio th left radical. mastectomia , chemoth., radio th left radical. mastectomia, chemoth.. left partial. mastectomia , radio th right Ca microcell left lung. Ca laryngis- ten years ago Type of metastases Lung both Pleura Other brain left breast two years ago (chemoth.) Ca planocell bronh. principal. right Other primary cancer
B.F.
.M.
46
right
pericard
J.A.
65
one year ago
P.M.
59
16 years ago
S.A.
53
19 years ago
Table No4 patients treated in 2007

Name Age (years) Time from first diagnosis of breast cancer four years ago Previous treatment of breast cancer left radical. mastecomia, chemoth., radio th right radical. mastectomia , chemoth. , radio th left radical. mastectomia both Type of metastases Lung Pleura Other Other primary cancer
D. M
55
both
both
liver
D.A.
50
two years ago
Ca squamocel right lung
O.A.
60
one year ago without previous diagnosis, both breasts five years ago
S.S.
74
no treatment
right
mediastin. lymphnod.
S.A.
54
right radical. mastecomia
left
69
It was totally 19 patients : four in 2004., five in 2005., five in 2006., five in 2007 year . that is 1,05 % of the total number of patients with cancer treated in this period in Clinic Podhrastovi. They were aged from 37 to 74 year. In four of them it was the first diagnosis of breast cancer although it has already had metastases . Fourteen patients were treated previously: operation, citotherapy,radiotherapy, and one was treated by alternative methods. Metastases were diagnosed on average five years after the first diagnosis of breast cancer..In four of them there were lung metastases : one had and skin metastases, one had and liver, and one had and brain metastases. In six of them there were pleural metastases: one had and pericard metastases, and one had and bone metastases. Five of them had both lung and pleural metastases,and among them one had liver,one had bone, and one both: bone and liver metastases. Three patients had primary lung carcinoma, and one had primary lung and laryngeal carcinoma beside the previously diagnosed breast carcinoma. All patients were treated wiht citotherapy or radiotherapy or both (combinated cito and radiotherapy) with multidisciplinary approach (oncologist, radiotherapeutic ,pulmologist). Discussion Breast cancer is the second most common type of cancer after lung cancer [10,4% of all cancer incidence ,including both sexes (2)] and the fifth most common cause of cancer death (3). Worldwide, breast cancer is by far the most common cancer amongst women, especially 35 to 64 years old (1) with an incidence rate more than twice of colorectal cancer and cervical cancer and about three times of lung cancer (3). However, breast cancer mortality all over the world is just 25% greater than that of lung cancer in women (2) . In 2005.,breast cancer caused 502 000 deaths in the world (7% of cancer deaths , almost 1% of all deaths) (3). The number of cases in the world has significantly increased since the 1970.s - a phenomenon partly blamed on modern lyfestyles in the Western world with tendency for greater incidence in the next years (4). The incidence of breast cancer varies greatly in the world, being lower in 70
less developed countries and greatest in the more developed countries (4). However, the mortalty from breast cancer has been getting smaller in last decades owing to advance of radiologycal diagnostic methods, programmes of early detection and new methods of adjuvant systemic therapy (1, 5). Conclusion In spite of all advances in diagnostics, screening methods of early detection and new methods of therapy, breast cancer is still the most common cause of death of women in developed countries. There is a certain number of cases in which the diagnosis was late and therapy has no desirable results. Some of them have intrathoracic metastases which require treatment in Clinic for pumonary diseases. Literature
1. American Cancer Society, www.cancer.org, ( September 26, 2007): What Is Breast Cancer ? . Retrieved on 2008-02-03. 2. World Health Organization International agency for Research on Cancer, www.who.int/, ( June 2003). World Cancer Report . Retrieved on 200802-03 3. World Health Organization, www.who.int/, ( February 2006). Fact sheet No 297: Cancer. Retrieved on 2007-04-26 4. Parkin D.M., Pissani P., Ferlay J. Global Cancer Statistics. CA Cancer J. Clin. 1999; 352:930-942 5. Cancer Facts and Figures 1999,Atlanta Ga: American Cancer Society 1999. Corresponding author: Vesna Cukic Clinic for pulmonary diseases and TB Podhrastovi Clinical Centre of University Sarajevo, Bosnia and Herzegovina e-mail:
Treatment of elderly patients with rectal prolapse with modified anal cerclage method
TreTmaNa STarijiH PaCijeNaTa Sa ProLabiraNim rekTumom meTodom modifiCiraNe aNaLNe SerkLae
Nedzad Sehovic, Amela Sofic, Adnan Zeco Clinic of General and Abdominal Surgery, Clinical Center University of Sarajevo, Bosnia and Herzegovina
Summary Method of anal cerclage with prolene ribbon nowadays is mostly use in case of very old patients with rectal prolapse. Procedure is performed in manner that prolene net is placed orally, above anal sphincter, trough three to four incisions on skin of perianal region. Due to extreme pain surgery is done with general or spinal anesthesia depending on patients general health condition. Method is relatively rarely used due to pain it produce. But there is a group of patients for which this surgery provides wanted results. In order to reduce pain and make post surgical recovery easier, we made modification to this method using specially designed instrument in order to reduce tissue trauma and make placement of the net in adequate position easier. Key words: Rectal prolapse, anal cerclage. Saetak Metoda analne serklae prolenskom trakom danas se primjenjuje najee kod izrazito starijih pacijenata sa rektalnim prolapsom.Operacija se sastoji u tome da se prolenska mreica ubacuje oralno, iznad analnog sfinktera, kroz tri do etiri incizije perianalno na koi. Radi izrazite bolnosti operacija se vri u opoj ili spinalnoj anesteziji u
zavisnosti od opeg stanja pacijenta.Metoda se relativno rijetko primjenjuje radi svoje bolnosti. Ipak postoji grupa pacijenata kod koje ova operacija daje eljene efekte.U cilju smanjenja bolnosti i lakeg postoperativnog toka uradili smo modifiraciju ove metode koristei naroito konstrisan instrument sa ciljem to manje traumatizacije tkiva i lakeg plasiranja mreice na adekvatno mjesto. Kljune rijei: Rectalni prolaps,anal cerclage. Introduction There is a group of patients with rectal prolapse which poor general health status does not allow the adequate surgical treatment, so often used are procedures which does not produce adequate results but only relieve condition. Most often these are elderly patients with developed and long lasting rectal prolapse, incontinence, which without doubt influence both on their functioning and social life which eventually leads to mental disorders. Severe illness as this with poor general health state of the patient is very difficult to treat surgically. (1) That is why we use easier surgical procedures with satisfactory results. Standard method of anal cerclage is done with four incisions after which subcutis is tunneled, and then under control pean is introduced. Homeostasis is usually done with compression or diather71
mia. Tunnels are made under raphe orally to puborectal muscle and around the sphincter in ishiorectal space. After that rolled prolene net, previously measured is taken. With the instrument, it is placed trough the cannel under the skin and continues with other instruments until we reach initial incision. Ends are suturated with prolene 2-0 thread. Before surgery to each patient is administered enema several hours before procedure. Patient is in laying position, at the gynecology table, with legs raised in leg holders. After the cleaning of the surgical field injected is local anesthetic around the anal opening with intraluminal application of anesthetic in form of gel (if the surgery is performed under the local anesthesia). Each patient underwent rectal and rectoscopic examination, with the measurement and determining orientation of the anal opening as well as the size of the prolapsed part. Modification is in fact that the prolene ribbon is placed perianally trough one incision on the skin, and most often ventrally due to easier dissection of the rectovaginal space. Everything is done with the specially designed net carrier, and it is placed at the same level as in case of standard method. Goal Today all available methods for treatment of these patients are mainly based on general anesthesia and more extensive surgeries which this group of patients is not able to withstand without high mortality risk. Our wish was to introduce a method which this group of patients can stand, as surgically as well as n term of anesthesia, and at the same time to retain efficacy of the method itself on a high level, or close to the major surgeries under the general anesthesia.(2) Toward that goal we modified standard method of anal cerclage. Patients and methods Group of patients participating in this research was randomly selected. For the purpose of this research we used two groups of 30 patients older than 70 years. All patients were before surgery 72
examined and answered the questionnaire. In case of all patients before the surgery rectal prolapse is proven. Duration of illness was not taken in consideration. All the patients from the first group were operated by the team which has routine, with the method commonly used. All patients had same conditions before the surgery, starting with preparation, emptying of the colon, or enema, antibiotic prophylaxis, medications, anesthesia, cleaning of the surgery field and treatment after the surgery. Post surgical treatment involves therapy for pain, wound treatment, and diet in order to achieve softer stool. In case of patients with this disease we did not set any perquisites besides clinical finding which confirms prolapse. (3) Coming to surgeon because of the problems caused by this disease, after the examination they accepted the suggested surgery and voluntarily participated in research. All time they were divided into two groups. Majority of patients were women, with multiple child births, older than 70 years and partially with deteriorated health. One part of the patients had very poor health and bringing these patients under the general anesthesia was not recommended. Many patients had respiratory diseases which for sure contributed to prolapse development. (4) Due to long lasting prolapse, and also because patients earned to control it, changes on the rectum mucosa are inevitable. When we take in consideration that this area was for long time period exposed to different medical and non medical solutions, poorer nutrition due to compression and bacterial activity, anatomic changes and pre surgical preparations were very different compared to normal. Presentation of the net carrier and other necessary equipment Net carrier is instrument with the handle and one part with spiral shape. It is made of flexible material, so it can adjust to the size of the anal opening, but still rigid enough not to bend when passing trough ishiorectal tissue. On one end is a handle in shape which enables rotation with use of force. At the same time, it is easy to sterilize the handle and it fits well into the hand so the slipping
is reduced. Distal part is little bit narrower than the profile of the complete carrier with the opening of 1mm and with blunt peak in order to avoid damage of the surrounding tissue. Carrier is mad of stainless material, simple for cleaning after the surgery, with average profile of 1.52 mm. Beside the carrier we are using different types of catheters, usually silicone ones, single use, with different thickness from 14 to 24 Ch, depending on thickness of the used net. Due to financial reasons, we are usually use nelaton catheters, nose catheters and gastric probes. They can be easily found in all hospitals, so they do not require special acquisition procedures.
Figure 1. Features of prolene net and suturated matherial From antibiotic crmes we used standard ones that are available. Usually those are the crmes which are targeted on Gram + and Gram , and if possible on fungus, such as Bacimycin (Bacitracin) or Fucydin (acid. fusidici). In mixture with 2% of Xylocaine and this crme we have beside prophylaxis also analgesic effect if the patient is under anesthesia which last shorter than the gel. In this research we used nets VYPRO (II) ETHICON, which are in everyday use in case of hernioplastic surgeries due to its features. These nets are made of approximately equal parts of absorptive and non absorptive multifilament fibers tangled together in form of macro pores in net structure. Absorptive part of fibers is polyglactine, or copolymer, it is made of 90% of glycolide and 10%
lactide, which are also used in making Vicryl threads. Polymer of the none absorbs polypropylene fibers (6) is identical to fibers from which prolene threads are made. Fibers of absorption polyglactine are used for easier manipulation with the net because of their flexibility and for the easier fixation. Full resorption of these fibers last from 56 to 70 days. Large pores of the non absorptive polypropylene net structure retains its position permanently and in that manner act as a support for the tissue depending of the goal that we want to achieve with placing the net. These fibers act as isotropic in all directions, or to say that their biochemical features are very similar to abdominal wall tissue, so they act similar as the wall during mechanic and also pharmaco-kinetic induction. They dont cause almost any tissue reaction, and at the same time the tissue grows well into the net. Feeling of fling as well as rigidity that occurs with previous nets is avoided in case of this type thanks to the reabsoptive part, and the tolerance on direct pressure is still equivalent and measures around 20 thanks to non absorptive part. Most often tissue reaction on the net are seromas, which occurs after certain time. Although, cases of net removal due to infection are very rare because of it non irritating structure. Fixing of the net to the surface is usually done with Prolene 2-0 suture. Non absorptive thread is mostly used in order to avoid migration or movement of the net during time. Preparation of patients and post surgical recovery Preparation of patients for surgery is done in two parts first is cleaning and the second one is antibiotic prophylaxis. Preparation of patients for the surgery as well as for rectoscopy is done with enema and peranal laxatives. From enemas mostly used is mild soap solutions in warm water or oil based enema with castor oil, and among peranal laxatives used are Dulcolax, Medilax or Glycerol. Enemas are usually administered one to two hours before procedure. 73
All patients involved in study received antibiotic prophylaxis because insertion of the foreign object, especially into anal area, has high risk of post surgery infection. Prophylaxis was in form of Bactrim 2tbl and Flagyl 3tbl orally two hours before surgery. After surgery, patients were hospitalized for several days due to pains, caused by aggressive of the surgical procedure, and because of fear from next stool. Everyday showering of the wounds and washing in mild soap water, with application of local analgesics, helps to faster recovery. Patient is discharged from the hospital after defecation and when the post surgical pain can be covered with orally administered analgesics. Type of anesthesia During these surgeries, in both groups different types of anesthesia were used. From local anesthesia in form of 1% Xylocain with Adrenalin combined with intravenous sedation (Midazolam), and if needed epidural and general anesthesia, depending on general health state of the patient and anesthesiologist opinion.
Figure 2. and 3. Applying local anesthesia After cleaning of the surgical field injected is the local anesthetic Xylocaine 1% with Adrenalin around anal opening. Anesthesia is injected in two levels first under the skin and then in depth of 5 CM pararectally. Besides classic pudenal application of local anesthetic, always 15 minutes 74
is injected gel with 2% of Xylocaine into the rectum. Usually anesthesia of the surgical field in this manner was satisfactory. Also, when needed other forms of anesthesia were used. Initial incision of 1-2 cm is made usually from left or right side of the ventral raphe of m. levator anii also called central point of perineum. Subcutaneous tissue is dissected with scissors, and ligament is moved in order to ensure passage for net carrier. After tunneling under the raphe in rectovaginal space, we continue dorsally-pararectally tunneling on both sides. In this way minimal trauma is made to this very sensitive perianal area. After that we take net carrier, which adjust to the size of anal opening or size of the rectum. Net carrier is inserted into the wound and with control of finger in rectum, with which we can feel every movement, we avoid every movement, and avoid possible rupture of the rectum when making rotation movement more laterally from the rectum until the end of the carrier does not reach the rectovaginal raphe. When the carrier makes rotation movement around rectum circumference, which means almost 360 degrees, silicone or Nelaton (cheaper) catheter is inserted with diameter of about 14 CH with previously removed top and greased with Fucydin, Bacimycin or Xylocaine crme for easier application. Depending on subcutaneous tissue after the catheter of CH placed on carrier is catheter of 18 CH and then 22 CH. When the thickest catheter appears its proximal part is taken with two Kokher clamps and distal part is cut. Rolled net is attached with one suture for the opening at the top of the carrier which is made for this purpose. With movement of the carrier trough the catheter, which at the same time pulls the net, if needed with antibiotic crme, we are taking the net to the incision. Proximal end of the net s taken with the instruments and released from the carrier, and pulling of the catheter from the wound we are placing the net into the wanted position. Only remains to suturate ends of the net usually leaving anal opening transversally in size of two fingers. Next is rinsing of the wound with physiology solution, povidon solution and closing the wound in standard manner
Table 1. Photography and schematic review of the modified method of anal cerclage with application of net carrier
Figure 4. Rectal prolapse before surgery
Figure 5. Rectal prolapse - incision
Figure 6. Rectal prolapse - tunneling
75
Figure 7. Rectal prolapse instrument placement
Figure 8. Rectal prolapse instrument exit troug same incision
Figure 9. Rectal prolapse fixing of net
Figure 10. Rectal prolapse net extraction
76
Figure 11. Rectal prolapse connecting net ends
Figure 12. Rectal prolapse after net suture
Figure 13. Rectal prolapse after surgery
Results and discussion Because modification is in technical procedure of easier placement of the net, and the principle of the surgery is the same, we thought that the medical results of the surgeries should be identical.
That is why we sis not analyzed possible medical benefits which obviously existed especially during the period after the surgery.
77
Table 2. Duration of hospitalization of patients surgically treated with modified method (n1 = 30) and patients treated with standard method (n2 = 30). The difference is not statistically significant (one-way Mann-Whitney U-test: W = 862, p = 0.178). Analysis of results which show that the difference in duration of hospital treatment for the patients treated with these methods does not have a statistical significance. From the table no. 1 can be seen that much more patients treated with the modified method leaved on home treatment first day after the surgery (6) and that neither one patient stay in hospital 4 days after the surgery, unlike standard method, in case of which 2 patients stayed four days after the surgery. It is also shown that the total duration of hospital stay in case of patients treated with modified method is shorter for 12 days compared to the standard method. Based on this we can conclude that the modified method have shorter hospitalization, or less difficult recovery after the surgery. 2. Economic benefit Summarizing all analyzed results, we see that relatively large economic benefit lays on the side of modified method compared to the standard one. From the results analyzed in the table we can see that:
Figure 14. and 15. Preoperative and postoperatice case On the figures we can see the rectal prolapse, before surgery and state after the surgery (just after the end of the surgery, where still visible is one incision at 11 oclock, which is used to place the net). Our wish was to present the medical benefit. It is consisted of: 1. Duration of post surgical hospitalization One part of the patients, treated with modified method, after the surgery felt so good that there was no reason for further observation and treatment. They were discharged earlier on home based treatment with agreed control periods. At the same time, all patients were well informed before and after the surgery how to recognize complications symptoms, for example, wound infection and how to react.
78
Table 3. Benefit of modificated metod we used in comparing with standard metod we used before Number of in hospital days for all the patients treated with the modified method was by 19.6% lower compared to other group, or it was 7 hospital days shorter, which calculated today is 336 . On this economic benefit we can add the cost of treatment for patients which have repeated hospitalization, where the difference is 3 in hospital days in favor of modified method. Also, costs of the repeated surgery in case of standard method and orally administered antibiotics were for 7 hospital days longer than in case of modified method. In case of analgesics administered intravenously advantage was in 5 hospital days, but in case of orally applied therapy 3 days in favor of standard method. Explanation could be in probably longer intravenously administered analgesics in case of standard method, so that the need for oral analgesia was lower. Conclusions From the previous analyses we can conclude that with the modified method of anal cerclage is more easy to place prolene net with much less tissue trauma, which by itself leads to much shorter and easier recovery, lower percent of complications and by that economic benefit. After the analyses, because of tolerability of surgery and easy post surgical recovery, we came to conclusion that we can treat almost all patients as day-surgery patients. This means that all pati-
ents after shorter observation, same day, and leave home or at the institutions from which they came. For these patients and relatives this is very important that the patients does not change environment and by that lifestyle. That is why we think, that in case of patients with rectal prolapse at old age, high morbidity, which in majority of cases require care from others, this modification of surgical procedure can be recommended as better method that the standard anal cerclage. Regarding relapse of this illness after the surgery, results are identical with the standard method so we didnt consider analysis of that as necessary. Literature
1. Sainio AP Halme LE Husa AI. Anal encirclement with polypropylene mesh for rectal prolapse and incontinence.Dis Colon Rectum 1991 Oct; 34:905-8. 2. Pikarsky AJ Joo JS Wexner SD et al. Recurrent rectal prolapse: what is the next good option? Dis Colon Rectum 2000 Sep; 43:1273-6. 3. Herrera-Ramrez J, Andrade-Ibez A, GonzlezVelsquez F, Morales-Guzmn MI, Martnez-Mier G. Rectal prolapse. Surgical experience with helicoidal suture and anoplasty: short hospital stay. Cir Cir ; 75(6) :453-7. 4. Villanueva Senz E, Martnez Hernndez-Magro P, Alvarez-Tostado Fernndez JF. Helicoidal suture: alternative treatment for complete rectal prolapse in high-risk patients. Int J Colorectal Dis Jan 2003; 18(1) :45-9. 5. Mansilla JE, Bannura GC, Contreras JP, Barrera AE, Melo CL, Soto DC. Lomas-Cooperman technique for rectal prolapse in the elderly patient.Tech Coloproctol Jul 2006; 10(2) :106-10. 6. Nat Clin Pract Gastroenterol Hepatol.Surgical management of rectal prolapse.2007Oct;4(10):552-61.
Corresponding author: Nedzad Sehovic Clinic of General and Abdominal Surgery, Clinical Center University of Sarajevo, Bosnia and Herzegovina. e-mail: sehovicn@hotmail.com
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alpha-lipoic acid and quercetin protect against methotrexate induced-hepatotoxicity in rats

Hebatallah A. Darwish1, Amina Mahdy2
1 2
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Egypt Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Egypt
Summary Background: Methotrexate (MTX), a folic acid antagonist, is widely used as cytotoxic chemotherapeutic agent for malignancies as well as in the treatment of various inflammatory diseases .The efficacy of this agent is often limited by severe side effects and toxic conditions. Regarding the mechanism of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. Aims & Objectives: The present study was undertaken to determine whether -lipoic acid or quercetin, potent free radical scavengers, could ameliorate MTX-induced oxidative liver injury and modulate immune response. The study also aimed to investigate the possible role of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-) in the pathogenesis of MTX-induced hepatoxicity. Study design/Methods: Rats were randomly divided into four experimental groups beside a normal control group consisting each of 8 animals. Following a single injection of MTX (20 mg/kg; i.p), experimental groups were allowed to receive either -lipoic acid (50 mg/kg/day; orally), quercetin (10 mg/kg/day; i.p in dimethylsulphoxide (DMSO)) or the vehicle DMSO alone. Treatment was carried out for 5 consecutive days. On the sixth day, blood serum was separated and used for the determination of TNF- level as well as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities to assess the hepatic function. Liver tissue samples were collected for the estimation of tissue malondialdehyde (MDA), 80
reduced glutathione (GSH) and nitric oxide (NO) levels, myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activities as well as for histological examination. Results obtained were statistically analysed by one way analysis of variance (ANOVA) followed by TukeyKramer multiple comparison test. Significance was considered at p<0.05. Findings: MTX caused a significant reduction in hepatic GSH level, SOD and CAT activities while MDA and MPO activities were significantly increased. Hepatic NO as well as serum TNF- levels were markedly elevated following MTX treatment. Only ALT rather than AST activity was significantly increased. These changes were significantly reversed by either -lipoic acid or quercetin treatment. Similarly, histological analysis revealed that both treatments were effective in attenuating tissue damage. However, the effect of -lipoic acid was more pronounced. Conclusion: The study indicates that oxidative stress, NO as well as TNF- may play an important role in the pathogenesis of MTX-induced hepatoxicity. -Lipoic acid and quercetin have protective aspects in this process through their antioxidant and anti-inflammatory effects. These data imply that antioxidant therapy may be of therapeutic potential in alleviating hepatotoxicity in patients receiving MTX treatment. Key words: methotrexate, Lipoic acid, quercetin, nitric oxide, TNF- , oxidative stress.
Introduction Anti-tumor drugs are being increasingly used as adjuvant therapy for recurrent inflammatory disease. It was suggested that reactive oxygen species (ROS) and hydrogen peroxides (H2O2) are associated with adverse effects of anti-tumor agents (Sugiyama et al., 1989; Zhang et al., 1992). Methotrexate (MTX), an antimetabolite drug widely used in cancer therapy or in various recurrent inflammatory diseases, is known to have toxic effects due to oxidative reactions that take place during its metabolism in the liver (Chladek et al., 1997). Long-term MTX therapy has been associated with liver toxicity, including steatosis, cholestasis, fibrosis, and cirrhosis (Tobias & Auerbach, 1973; Vonen & Morland, 1984; Hytiroglou et al., 2004). The exact mechanism of MTX-induced hepatotoxicity is as yet unclear. However, some mechanisms that could explain the toxicity have been suggested. MTX conversion to its major metabolite, 7-hydroxymethotrexate, takes place in the liver, where it is oxidized by a soluble enzymatic system (Chladek et al., 1997). Inside cells, MTX is stored in polyglutamated form (Galivan et al., 1983). Long-term drug administration can cause accumulation of intracellular polyglutamates decreasing folate levels which has been suggested as a mechanism for MTX hepatotoxicity (Kamen et al., 1981; Kremer et al., 1986). Additionally, it was demonstrated that the cytosolic NAD(P)-dependent dehydrogenases and NADP malic enzyme are inhibited by MTX, suggesting that the drug could decrease the availability of NADPH in cells (Vogel et al., 1963; Caetano et al., 1997). NADPH is essential for glutathione reductase enzyme activity that sustains the levels of reduced glutathione (GSH), which is an important cytosolic antioxidant substance. Thus the reduction in the levels of GSH due to MTX leads to a weakening of the effectiveness of the antioxidant defense system protecting the cell against ROS (Babiak et al., 1998). Numerous experimental and clinical studies proved efficiency of treatment with -lipoic acid (or thioctic acid) in diseases in which antioxidant balance is disrupted (diabetes, neurodegenerative diseases, acquired immune deficiency syndrome, tumors, etc.). Efficiency of lipoate has been attributed to unique antioxidant properties of lipoate/
dihydrolipoate system manifested as ROS scavenging ability as well as enhancement of the tissue concentrations of other antioxidants, including one of the most powerful, glutathione (thus lipoate is called an antioxidant of antioxidants) (Bilska & Wlodek, 2005). Flavonoids are phenolic phytochemicals that are important constituents of the nonenergetic part of the human diet and are thought to promote optimal health, at least in part via their antioxidant effects in protecting cellular components against ROS (Hertog & Hollman, 1996). Quercetin is one of the most widely distributed flavonoids, present in fruits, vegetables, and many other dietary sources (Pawlikowska-Pawlega et al.,2003) .This compound was reported to scavenge superoxide in ischemia-reperfusion injury (Huk et al., 1998), to protect against oxidative stress induced by UV light (Erden Inal & Kahraman, 2000), spontaneous hypertension (Duarte et al., 2001) or biliary obstruction-induced liver damage (Peres et al., 2000), and to inhibit angiogenesis (Igura et al., 2001), carcinogenesis (Yang et al., 2000) and portal hypertensive gastropathy (Moreira et al., 2004). The present study was undertaken to determine whether -lipoic acid or quercetin as potent antioxidant compounds, could ameliorate MTX-induced oxidative liver damage and modulate immune response. The study also aimed to investigate the possible role of NO and/or TNF- in the pathogenesis of MTX-induced hepatoxicity. Materials & Methods 1. Chemicals: Methotrexate was purchased from Ebewe Pharma, Austria. Alpha-lipoic acid and quercetin were provided from Sigma-Aldrich chemicals Co., St. Louis, USA. All other chemicals were of analytical grade. 2. Animals: Male wistar rats weighing 140 160 g were obtained from the animal house of faculty of medicine, Cairo University, Egypt. They were kept at a constant temperature (22 10C) with 12 hour light and dark cycles, fed a standard rat chow and allowed to accommodate for one week before performing the study. 3. Experimental design: Rats were randomly divided into five experimental groups, each of 8 81
rats. The first group (Control group) was injected with saline. The second group (MTX group) was injected with a single dose of methotrexate in saline (20 mg/kg; intraperitoneally) (Cetinkaya et al., 2006). The third group (MTX + lipoic acid) received MTX as mentioned in the second group along with lipoic acid in saline containing 2 mol/l NaOH and adjusted to pH 7.4 (50 mg / kg; orally) (Kishi et al., 1999; Abdel-Zaher et al., 2008). The fourth group (MTX + Quercetin) received MTX along with quercetin in dimethylsulphoxide (DMSO) (10 mg/kg; intraperitoneally) (Coldiron et al., 2002). The last group (MTX+DMSO) received MTX together with the vehicle DMSO alone. Treatment was carried out for 5 consecutive days. 4. Estimation of blood parameters: Blood samples were collected from the retro-orbital plexus, serum was separated for the determination of tumor necrosis factoralpha (TNF) level by enzyme linked immunosorbent assay (ELISA) (using kit provided by Assaypro, USA). Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were estimated to assess the hepatic function (using kits provided by ProDia international, Germany). 5. Determination of oxidative biomarkers: Rats were sacrificed, the abdominal cavity of each animal was rapidly dissected, the liver was removed, washed with ice-cold saline, weighed and blotted dry. The liver was then homogenized in ice cold saline (20% w/v) using potter-Elvejhem glass homogenizer and the homogenate was divided into five portions. The first portion of the homogenate was mixed with ice cold 2.3% KCl solution and centrifuged at 600 xg for 15 minutes at 40C. The supernatant was used for malondialdehyde (MDA) determination which has been identified as the product of lipid peroxidation that reacts with thiobarbituric acid to give a pink color. The absorbance was recorded at 535 nm and 520 nm using tetramethoxypropane as a standard (Uchiyama & Mihara, 1978). The difference between the two determinations was calculated as TBA value and expressed as nmol/mg protein. Another portion of the homogenate was treated with 7.5% sulfosalicylic acid and centrifuged at 600 xg at 40C for 10 minutes. The protein free supernatant was used for the estimation of reduced glutathione (GSH) content based on the reaction 82
of GSH with 5,5-dithiobis-2-nitrobenzoic acid forming a product that has a maximal absorbance at 412 nm. The results were expressed as mol/g wet tissue (Beutler et al., 1963). The third portion of the homogenate was mixed with ice cold 50 mM tris buffer containing 0.1 mM EDTA (pH 7.6) and centrifuged at 105.000 xg at 40C for 40 minutes using Dupont survall ultracentrifuge, USA. The resulting cytosolic fraction was used for the estimation of both superoxide dismutase (SOD) and catalase (CAT) activities. SOD was measured by following the rate of autoxidation of pyrogallol at 420 nm. The change in absorbance was recorded and expressed in U/mg protein (Marklund & Marklund, 1974). CAT activity was assayed by following the decomposition of its substrate, H2O2 at 240 nm. The change in absorbance was recorded and expressed in U/mg protein (Aebi, 1974). 6. Determination of nitric oxide (NO) level and myeloperoxidase (MPO) activity: A portion of the homogenate was mixed with icecold 50 mM phosphate buffer containing 0.5% hexadecyltrimethyl ammonium bromide (pH 6). After three freeze and thaw cycles with sonication between cycles, the samples were centrifuged at 41,400 xg for 10 minutes and the supernatant was used for the determination of MPO activity. This was measured spectrophotometrically using O-dianisidine dihydrochloride as a substrate for MPO-mediated oxidation by H2O2. The change in absorbance at 460 nm was recorded and expressed in U/mg protein (Krawisz et al., 1984). The last portion of the homogenate was centrifuged at 17.000 xg at 40C for 15 minutes and the supernatant was used for the determination of NO level measured as total nitrites with the spectrophotometric Greiss reaction. Results were expressed as mol/g tissue (Miranda et al., 2001). The protein content in liver fractions was measured by the method of Lowry et al. (1951). 7. Histopathological examination: Liver specimens were fixed with 10% formaldehyde and processed routinely for embedding in paraffin. Sections of 5 m were stained with hematoxylin and eosin (H&E) and examined under the light microscope. 8. Statistical analysis: Results were expressed as mean standard error of the mean (SEM). Differences among means were tested for statisti-
cal significance by oneway analysis of variance (ANOVA). When differences were significant, Tukey-Kramers test was used for multiple comparisons between groups. Statistical significance was considered when p < 0.05. Results 1. Biochemical results: Testing of the hepatic function following a single injection of MTX (20 mg/kg, i.p) in normal rats revealed a significant rise in ALT which was restored by either -lipoic acid or quercetin treatment (table 1). AST was significantly unchanged among all the treatment groups. A considerable elevation of lipid peroxides (MDA) in hepatic tissue was demonstrated following MTX injection. This elevation was ameliorated and completely abolished by treatment with quercetin and -lipoic acid respectively (table 2). Further evidence for MTX-induced toxicity in the liver tissue was the profound reduction of
the antioxidant defense mechanisms as shown by a significant decrease in GSH content, SOD and CAT activities. Alpha-lipoic acid has demonstrated a powerful antioxidant effect as evidenced by restoring to normal the levels of GSH as well as SOD and CAT activities (table 2). Meanwhile, quercetin treatment normalized SOD activity, ameliorated GSH content and did not affect CAT activity in hepatic tissue (table 2). Following MTX injection, MPO activity showed about three-fold increase. This rise was completely normalized while significantly ameliorated by -lipoic acid and quercetin respectively (table 2). A two-fold increase in nitric oxide level in hepatic tissue of MTX-treated rats was observed in the present study. This marked rise was normalized by both antioxidant therapies (figure 1). Similarly, MTX injection in normal rats evoked a sixfold elevation in serum TNF- level. Treatment with either -lipoic acid or quercetin resulted in a beneficial restoration of normal level of this mediator in treated rats (figure 2).
Table 1. Effect of -lipoic acid and quercetin on MTX-induced alterations liver enzyme activities
Groups Control Parameters ALT (IU/L) AST (IU/L) 71.6 3.3 179.9 4.25 108.8 11.02 a 195 7.52 MTX MTX + Lipoic acid 70.2 3.46 b 175.9 4.92 MTX + Quercetin 74.5 7.49 b 180 5.26 MTX + DMSO 92.2 3 a 184.2 12.2
Values are expressed as mean SEM of 6-8 animals. a) significant difference from control group at p<0.05, b) significant difference from MTX group at p <0.05 Table 2. Effect of -lipoic acid and quercetin on MTX-induced alterations in oxidant/antioxidant status
Groups Parameters MDA (nmol/mg protein) GSH (mol/g wet tissue) SOD (U/mg protein) CAT (U/mg protein) MPO (U/mg protein) Control 2.53 0.32 3.03 0.06 15.5 0.55 13.7 1.09 2.53 0.17 MTX 5.6 0.41 a 1.53 0.75 a 11.05 0.84 a 9.54 0.81 a 7.19 0.81 a MTX + Lipoic acid 4.07 0.24 ab 2.61 0.18 b 15.2 0.48 b 13.3 1.14 b 2.61 0.25 b MTX + Quercetin 2.69 0.29 b 2.24 0.06 ab 15.5 0.5 b 10.8 0.24 4.85 0.43 ab MTX + DMSO 4.84 0.3 a 1.89 0.08 a 12 1.05 a 9.6 0.52 a 6.11 0.43 a
83
Values are expressed as mean SEM of 6-8 animals a) significant difference from control group at p<0.05, b) significant difference from MTX group at p<0.05 2. Histopathological results: As shown in figure (3), the liver of normal control rats revealed no histopathological alteration. Normal histological structure of the central vein and surrounding hepatocytes were recorded (A). By contrast, liver sections from rats receiving MTX showed proliferation of Kupffer cells around the central vein, in association with focal inflammatory cells infiltration in between the degenerated and necrosed hepatocytes (C). The portal area showed massive number of inflammatory cells infiltration with dilatation in both portal vein and bile ducts of MTX-treated rats (B). Concurrent administration of lipoic acid (D) and quercetin (E) improved the alterations in liver morphology as evidenced by moderate infiltration and vascularization. However, the hepatocytes showed fatty change in diffuse manner allover the hepatic parenchyma following quercetin (E) and in few manner following its vehicle DMSO (F). 84
Fig. 3. Photomicrographs of liver sections from (A) normal control rats (H&E, 64 x), (B & C) MTX-treated rats (H&E, 64 x and 160 x respectively), (D) MTX + Lipoic acid, (E) MTX + Quercetin and (F) MTX + DMSO (H&E, 160 x). Discussion Several mechanisms may lead to oxidative stress in cancer patients. This may involve a nonspecific chronic activation of the immune system accompanied by an excessive production of proinflammatory cytokines leading in turn to increased ROS production (Mantovani et al., 1997). The use of antineoplastic drugs may additionally result in an excess production of ROS and may therefore lead to oxidative stress (Weijl et al., 1997). Thus, we can hypothesize that the body redox systems, which include antioxidant enzymes and low molecular weight antioxidants, may be down regulated in cancer patients as a function of the administration of antineoplastic drugs just as it may be a result of the disease progression itself. GSH plays an important role in the detoxification of xenobiotics and various chemicals. A reduction in the cellular GSH levels in response to MTX medication have been reported to be related to inhibition of glutathione reductase activity, resulting in a failure to restore cellular GSH (Babiak et al., 1998). Moreover, Phillips et al. (2003) observed that monocyte GSH levels decreased markedly after MTX administration. In an experimental study, MTX was ascertained to decrease GSH levels in hepatocyte cultures (Walker et al., 2000). In the present study, the significant reduction in GSH levels, promoted by MTX, lead to a reduction of effectiveness of the antioxidant enzyme defense system, sensitizing the cells to ROS (Babiak et al., 1998).
Decreased GSH levels were restored or significantly ameliorated by -lipoic acid and quercetin respectively. Despite a rapidly growing interest in -lipoic acid and its therapeutic potential as a proglutathione agent (Busse et al., 1992), information regarding the effect of its supplementation on the level of GSH in tissues is limited. Exogenously supplied -lipoic acid is readily taken up by a variety of cells and tissues in which it is rapidly reduced by NADH- or NADPH-dependent enzymes to dihydro-lipoic acid (DHLA). DHLA was reported to improve cysteine availability within the cell, resulting in accelerated GSH synthesis (Sen, 1997). In view of this mechanism of action of -lipoic acid, it may be expected that the effect of -lipoic acid on tissue GSH would be most marked in organs that have a high activity of GSH-synthesizing enzymes as liver and erythrocytes in blood (Srivastava, 1971; Deneke & Fanburg, 1989). Moreover, DHLA is a strong reductant known to regenerate major physiological antioxidants of lipid and aqueous phases, such as vitamin E, and ascorbate (Packer et al., 1995). Therefore, the antioxidant power of DHLA contributes to the efficiency of -lipoic acid in reservation of all the antioxidant defense mechanisms observed in the present study. Similarly, quercetin, a member of the flavonoid family, has been shown to delay oxidant injury and cell death by scavenging ROS and free radicals, protecting against lipid peroxidation and thereby terminating the chain-radical reaction, and chelating metal ions (Silva et al., 2002). In particular, quercetin has been demonstrated to scavenge O2., singlet oxygen (1O2) and .OH radicals, to prevent lipid peroxidation, to inhibit cyclooxygenase and lipooxygenase enzymes, and to chelate transition metal ions (Gordon & Roedig-Penman, 1998). Lipid peroxidation, mediated by oxygen free radicals, is believed to be an important cause of destruction and damage to cell membranes (Jahovic et al., 2004) and this has been suggested to be a contributing factor to the MTX-mediated histopathological changes observed in hepatic tissue. Owing to their antioxidant activities, -lipoic acid and quercetin reduced the MTX-induced oxidative injury, and showed a cellular protective effect in this regards. In addition to direct damaging effects on tissues, free radicals seem to trigger the accumulation 85
of leukocytes in the tissues involved, and thus aggravate tissue injury indirectly through enhancement of the release of cytokines from activated neutrophils (Vaziri, 2004). It has been shown that activated neutrophils secrete enzymes such as MPO and liberate oxygen radicals (Sullivan et al., 2000). In turn, MPO plays a fundamental role in oxidant production by neutrophils. In our observation, elevated cytokine TNF- in the blood, and MPO levels in the liver, indicate that neutrophil accumulation contributes, at least in part, to MTXinduced oxidative organ injury. The results also revealed that both lipoic acid and quercetin have preventive effects through the inhibition of neutrophil infiltration and cytokine release. This was evidenced by restoration of TNF- level observed with both treatments along with either normalization or reduction of the elevated MPO activity following -lipoic acid or quercetin respectively. Moreover, the significant increase in hepatic NO level following MTX was shown to be normalized by both antioxidant used in the study. These beneficial effects of either lipoic acid or quercetin could be explained on the basis that; in the absence of an appropriate compensatory response from the endogenous antioxidant network, the system becomes overwhelmed (redox imbalance), leading to the activation of stress-sensitive signaling pathways, such as nuclear factor kappa (NF-kB), and others. Under normal physiologic conditions, NF-kB forms a complex with its inhibitors and is maintained in the cytosol in an inactive state. NF-kB can be freed from its inhibitors through the direct action of protein kinases, the IKKs that form a complex consisting of the catalytic subunits IKK and IKK (Zandi et al., 1997). Freed from its inhibitor, NF-kB enters the nucleus and transactivates NF-kBresponsive genes (Staal et al., 1990; Romics et al., 2004). It has been reported that -lipoic acid and quercetin block NF-kB activation through inhibition of both IKK and IKK in a dose-dependent manner (Peet & Li, 1999). Moreover, lipoic acid and quercetin are also effective chelators of iron and copper (Ou et al., 1995; Lodge et al., 1998). It has been suggested that the metal chelating rather than antioxidant properties, is responsible for such inhibitory effect on NF-kB activation (Bowie et al., 1997). 86
One major consequence of the activation of stress-sensitive signaling pathways (NF-kB) is the generation of gene products such as Nitric oxide. NO, a nontoxic mediator (vasodilator and neurotransmitter) under physiological conditions, has been shown to contribute to cell and tissue injury when it is formed at high rates and for prolonged periods by inducible NO synthase (iNOS). In cultured cells, induction of apoptotic and necrotic cell death and impairment of several metabolic functions such as mitochondrial energy production and DNA synthesis by NO have been described (Kroncke et al., 1998; Wink & Mitchell, 1998; Rauen et al., 2007). In addition to toxicity of NO itself, injury has been ascribed to oxidation products of NO such as NO2 or N2O3 (Grisham et al., 1999). Nitric oxide may react with superoxide radical to yield the highly reactive oxidant species peroxynitrite, leading to more aggressive oxidative and nitrosative stress (Lorens & Nava, 2003). Moreover, NO or its oxidation products appeared to inhibit both cellular-H2O2 degrading systems; catalase and the glutathione/ glutathione peroxidase system. Catalase appeared to be inhibited rapidly by NO itself, hence, NO can bind to the heme moiety of native catalase, resulting in heme nitrosylation (formation of a complex between the heme iron and NO). This heme nitrosylation prevents the interaction of H2O2 with the iron center and thus H2O2 degradation (Rauen et al., 2007). The observed normalization of TNF- level by -lipoic acid and quercetin could be correlated to suppression of the release of NF-kB. This correlation was previously demonstrated by Zhang and Freil (2001) in human aortic endothelial cells. Suppressed NF-kB in turn down regulated the expression of iNOS (Dias et al., 2005) providing a basis for the reduction achieved by these antioxidants in the encountered elevation of NO level caused by MTX administration. In conclusion, the findings of the current study indicate that -lipoic acid and quercetin effectively reduced oxidative and nitrosative stess caused by MTX. These data indicate that -lipoic acid and quercetin may be of therapeutic use in preventing hepatotoxicity in patients receiving chemotherapeutic agents. Hence, compensation of side effects, such as hepatotoxicity, affecting the continuation of the use of chemotherapeutic agents
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Corresponding author: Hebatallah A. Darwish Department of Biochemistry, Faculty of Pharmacy, Cairo University Egypt Phone: +2 011 2550300 e-mail: hebatallah_darwish@yahoo.com
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New classification of epidermolysis bullosa group of blistering disorders

Naima Mutevelic Arslanagic1, Rusmir Arslanagic2, Selma Arslanagic3
1 2 3
Department of Dermatology, Sarajevo, Bosnia and Herzegovina ORL Department, Sarajevo, Bosnia and Herzegovina Department of Plastic surgery, Sarajevo, Bosnia and Herzegovina
Summary This group of blistering disorders comprise the rare but serious group of mechanobullous disorders. They usually present at birth or in infancy, but cause problems thereafter throughout life. Categorizations of the types of epidermolysis bullosa group of blistering disorders were controversial and often confusing because more than 20 types of these disease have been described. This group of diseases are genetically determined and range from relatively mild problems to life threatening conditions. In this papaer we will shou new classification of epidermolysis bullosa group of blistering disorders. Key words: epidermolysis bullosa, epidermolysis bullosa simplex, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa The present classification Toward the end of last millenium, electron microscopy revealed abnormal keratin filaments ,diordered dermal anchoring fibril and defective hemidesmosomes, and discavered some of the major genes included those that encode keratins 5 and 14, collagen VII and laminin 5, and also genes responsible for the rare subtypes of epidermolysis bullosa blistering disorders (1). The main varieties of epidermolysis bullosa EB gropu of blistering disorders are: - Epidermolysis bullosa simplex - mainly autosomal dominant inherited - Epidermolysis bullosa junctionalis autosomal recessive inherited - Epidermolysis bullosa dystrophica both autosomal dominant, and autosomal recessive varieties. 90
Histopathology determines the level of cleavage, which is further defined by electron microscopy and immunohistochemical maping. A molecular technique including Western blot, Northen blot, restriction fragment length polymorphism analysis and DNA sequences may then identify the mutated gene (2). Epidermis, epidermodermal junction and the level places of cleavage are shematicaly shown on Shema 1
Shema 1. Classification of the epidermolysis bullosa group disorders, type inheritency and main clinical caractheristics are shown on Table 1. Adopted Fine JD, Bauer EA, Briggman RA et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcomittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol 1991 24 1 119 135 1. In each of these groups there are several distinct types of epidermolysis bullosa based on clinical, genetic, lighht microscopy, electron microscopy and biochemical molecular evaluation(3). These caractheristics are shown on Table 2.
TABLE 1. Type and subtype of the epidermolysis bullosa group of disorders

Type of disease EB simplex EB junctionalis EB dystrophica Number of verieties 11 7 Inheritance Mainly autosomal dominant All autosomal recessive Both, autosomal dominat and recessive Site of blister Basal cells Lamina lucida Below basement membrane, sublamina densa Specific defect Keratin 5 and 14 Hemidesmosomes Anchoring fibrils Type 7 collagen Clinical features After friction blisters on hands and feet Blistering of skin and mucosal membrane Blistering of skin and mucosal membrane, scaring and loss of nails
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TABLE 2 TYPE OF EPIDERMOLYSIS BULLOSA AND ASSOCIATED CHARACTERISTICS

Type of EB EB simplex Dowling Meara EB simplex Weber Cockayne EB with ectodermal dysplasis EB with muscular dystrophy EB junctionalis non Herlitz EB junctionalis with pyloric atresia EB junctionalis Herlitz, rarely non Herlitz EB dystrophica Feature on light microscopy Epidermis Epidermis Epidermis Epidermis Basement memebrane zone Basement membrane zone Basement membrane zone Dermis Feature on electron microscopy Keratin filaments Keratin filaments Desmosome, attachment plaque Hemidesmosome lamina lucida, attachment plaque Hemidesmosome lamina lucida, subbasal dense plate,anchoring filaments Hemidesmosome lamina lucida, subbasal dense plate, anchoring filaments Lamina densa Anchoring fibrils Protein or antigen Keratin 5 Keratin 14 Plakophilin Plectin Collagen XVII Gene KRT 5 KRT 14 PKP 1 PLEC 1 BPAG 2 ITGB6 ITBG 4 LAMA 3 LAMB 3 LAMC 2 COL7A1
Alpha6beta4integrin
Laminin 5 Collagen VII
Adopted Fine JD, Bauer EA, Briggman RA et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcomittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol 1991 24 1 119 135 1 Epidermolysis bullosa simplex Cytolisis causes blisters in the epidermis and causes blisters in the basal or spinous layers of the
epidermis, and keratinocytes often have abnormal density and organization of keratin filaments. Thus, there is true cell lysis . The pathological damage is based on split through the cytoplasm of the basal cells. The molecular defects lies in most cases on keratin gene mutations, genes which coding for keratin 5 and 14. Keratin 5 and 14 are found preferentially in the basal layer. Different subgroups have considerable phenotypic variations. There are 11 distinc forms of epidermolysis bullosa simplex. Seven of which are autosomal dominant inherited and four autosomal recessive inherited (1). 91
Table 3. Clinical phenotype and mollecular defect correlations in epidermolysis bullosa simplex
EBS Weber Cockaine EBS Kobner EBS Dowling Meara EBS with muscular dystophy EBS with pathy hyperpigemnation EBS, autosomal recessive without muscular dystrophy EBS superficialis Proteins Keratin 5 and 14 Keratin 5 and 14 Keratin 5 and 14 Plectin Keratin 5 Keratin 14 Unnown Clinical features Palms and soles Generalised Herpetiformic erythema and vesicles. Mucous membranes unaffected Generalised Keratinisation of palms and soles Keratinisation and vesicles of palm and soles Erythema and vesicles
Elewen variants of epidermolysis bullosa simplex are currently recognized and some of them are shown on Table 3. Adopted Fine JD, Bauer EA, Briggman RA et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa. A consensus report by the Subcomittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol 1991 24 1 119 135 1. Epidermolysis bullosa junctionalis All seven currently recognized variants of this type are inherited by autosomal recessive transmission and the basic abnormality appears to lie in the hemidesmosomes. Defective genes normally coding for bullous pemphigoid antigen and laminin have recently been identified in the generalized , atrophic, benign variant of this epidermolysis bullosa subtype. This results in the development of a split at the level of the lamina lucida (4). Some of clinical phenotype and mollecular defect correlations in epidermolysis bullosa junctionalis are shown on Table 4. Table 4. Clinical phenotype and mollecular defect correlations in epidermolysis bullosa junctionalis
EBJ Herlitz EBJ nonHerlitz EBJ with pyloric athresia EBJ inversa EBJ started later Protein Laminin 5 Kolagen VII Integrin alfa 6beta 4 Laminin 5 Unnown
of inherited epidermolysis bullosa. A consensus report by the Subcomittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol 1991 24 1 119 135 1. Dystrophic epidermolysis bullosa The abnormality cosists of defective anchoring fibrils connecting the basal lamina to the dermis and a subepidermal blister results. In the dominant varietie in later infancy or early childhood bullae form on friction sites and heal with scarring Figure 1 and 2. In the recessive types, there is also a defect of anchoring fibrils (5). Large bullae are present at birth, and they heal with scarring which is associated with the formation of webs between fingers Figure 3 a useless fist mucous membranes, hair, Figure 3, nails, Figure 3, and teeth may all be abnormal, Figure 1, and there are reports of the development of squamous carcinoma on the scar sites (6,7). Some of clinical phenotype and mollecular defect correlations in dystrophic epidermolysis bullosa are present on Table 5. Table 5. Clinical phenotype and mollecular defect correlations in epidermolysis bullosa dystrophica
EBD autosomal dominant inherited EBD autosomal recessive inherited Hallopeau Simens EBD autosomal recessive inherited non Hallopeau Simnes EBD autosomal dominant inherited, praetibialis EBD newborn transient EBD pruritic, autosomal dominant inherited Protein Kolagen VII Kolagen VII Kolagen VII Kolagen VII Kolagen VII Kolagen VII
Adopted Fine JD, Bauer EA, Briggman RA et al. Revised clinical and laboratory criteria for subtypes 92
Literature
1. Fine JD,Bauer Ea,Briggman RA et al. Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa.A consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis bullosa Registry .J Am Acad Dermatol 1991; 24 (1) :119-1352 2. Pfeneder EG. Nakano A, Pulkkinen L,Christiano AM, UittoJ.Prenatal diagnosis for epidermolysis bullosa: a studz of 144 consecutive pregnancies at risk. Prenat Diagn. 2003;23(6):447-456 3. Uitto J, Richard G. Progress in epidermolysis bullosa: from eponyms to molecular genetic classification. Clin dermatol 2005;23(1):33-40 4. Puvabanditsin S, Garrow E, Kim DU, Tirakitsoorn P, Luan J. Junctional epidermolysis bullosa associated with congenital localized absence of skin, and pyloric atresia in two newborn siblings. J Am Acad Dermatol 2001;44(2 Suppl):330-335 5. Horn HM, Tidman MJ. The clinical spectrum of dystrophic epidermolysis bullosa. Br J Dermatol 2002;146(2):267-274 6. Mallipeddi R.Epidermolysis bullosa and cancer. Clin Exp Dermatol . 2002;27(8):616-623 7. Ayman T, Yerebacan O, Ciftcioglu MA, Alpsoy. A 13-year-old girl with recessive dystrophic epidermolysis bullosa presenting with squamous cell carcinoma. Pediatr Dermatol.2002;19(5):436-4
Figure 1. Bullae form on fricion sites and heal with scaring. The teeth are not normal
Figure 2. Generalised blistering, milia and scar formation
Corresponding author:
Naima Arslanagic, Department of Dermatology, Sarajevo Bosnia and Herzegovina e-mail: prof.naima_arslanagic@yahoo.com
Figure 3. Large bullae heal with scaring which is associated with the formation of webs betwen fingers and scars alopecia
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Svaki upueni asopis dobija svoj broj i autor(i) se obavjetavaju o prijemu rada i njegovom broju. Taj broj koristit e se u svakoj korespondenciji. Rukopis treba otipkati na standardnoj veliini papira (format A4), ostavljajui s lijeve strane marginu od najmanje 3 cm. Sav materijal, ukljuujui tabele i reference, mora biti otipkan dvostrukim proredom, tako da na jednoj strani nema vie od 2.000 alfanumerikih karaktera (30 linija). Rad treba slati u triplikatu, s tim da original jedan prilog materijala moe biti i fotokopija. Nain prezentacije rada ovisi o prirodi materijala, a (uobiajeno) treba da se sastoji od naslovne stranice, saetka, teksta, referenci, tabela, legendi za slike i slika. Svoj rad otipkajte u MS Wordu i dostavite na disketi ili kompakt disku Redakcijskom odboru, ime e te olakati redakciju vaeg rada. NASLOVNA STRANA Svaki rukopis mora imati naslovnu stranicu s naslovom rada ne vie od 10 rijei: imena autora; naziv ustanove ili ustanova kojima autori pripadaju; skraeni naslov rada s najvie 45 slovnih mjesta i praznina; fusnotu u kojoj se izraavaju zahvale i/ili finansijska potpora i pomo u realizaciji rada, te ime i adresa prvog autora ili osobe koja e s Redakcijskim odborom odravati i korespondenciju. SAETAK Saetak treba da sadri sve bitne injenice rada-svrhu rada, koritene metode, bitne rezultate (sa specifinim podacima, ako je to mogue) i osnovne zakljuke. Saeci trebaju da imaju prikaz istaknutih podataka, ideja i zakljuaka iz teksta. U saetku se ne citiraju reference. Ispod teksta treba dodati najvie etiri kljune rijei. SAETAK NA BOSANSKOM JEZIKU Prilog radu je i proireni struktuirani saetak (cilj), metode, rezultati, rasprava, zakljuak) na bosanskom jeziku od 500 do 600 rijei, uz naslov rada, inicijale imena i prezimena auora te naziv ustanova na engleskom jeziku. Ispod saetka navode se kljune rijei koje su bitne za brzu identifikaciju i klasifikaciju sadraja rada. CENTRALNI DIO RUKOPISA Izvorni radovi sadre ove dijelove: uvod, cilj rada, metode rada, rezultati, rasprava i zakljuci. Uvod je kratak i jasan prikaz problema, cilj sadri kratak opis svrhe istraivanja. Metode se prikazuju tako da itaoci omogue ponavljanje opisanog istraivanja. Poznate metode se ne navode nego se navode izvorni literaturni podaci.
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Rezultate treba prikazati jasno i logiki, a njihovu znaajnost dokazati odgovarajuim statistikim metodama. U raspravi se tumae dobiveni rezultati i usporeuju s postojeim spoznajama na tom podruju. Zakljuci moraju odgovoriti postavljenom cilju rada. REFERENCE Reference treba navoditi u onom obimu koliko su stvarno koritene. Preporuuje se navoenje novije literature. Samo publicirani radovi (ili radovi koji su prihvaeni za objavljivanje) mogu se smatrati referencama. Neobjavljena zapaanja i lina saopenja treba navoditi u tekstu u zagradama. Reference se oznaavaju onim redom kako s pojavljuju u tekstu. One koje se citiraju u tabelama ili uz slike takoer se numeriraju u skladu s redoslijedom citiranja. Ako se navodi rad sa est ili manje autora, sva imena autora treba citirati; ako je u citirani lanak ukljueno sedam ili vie autora, navode se samo prva tri imena autora s dodatkom et al. Kada je autor nepoznat, treba na poetku citiranog lanka oznaiti Anon. Naslovi asopisa skrauju se prema Index Medicusu, a ako se u njemu ne navode, naslov asopisa treba pisati u cjelini. Fusnotekomentare, objanjenja, itd. Ne treba koristiti u radu. STATISTIKA ANALIZA Testove koji se koriste u statistikim anaizama treba prikazivati i u tekstu i na tabelama ili slikama koje sadre statistika poreenja. TABELE I SLIKE Tabele treba numerirati prema redoslijedu i tako ih prikazati da se mogu razumjeti i bez itanja teksta. Svaki stubac mora imati svoje zaglavlje, a mjerne jedinice (SI) moraju biti jasno oznaene, najbolje u fusnotama ispod tabela, arapskim brojevima ili simbolima. Slike takoer, treba numerisati po redoslijedu kojim se javljaju u tekstu. Crtee treba priloiti na bijelom papiru ili paus papiru, a crno-bijele fotografije na sjajnom papiru. Legende uz crtee i slike treba napisati na posebnom papiru formata A4. Sve ilustracije (slike, crtei, dijagrami) moraju biti originalne i na poleini sadravati broj ilustracije, prezime prvog autora, skraeni naslov rada i vrh slike. Poeljno je da u tekstu autor oznai mjesto za tabelu ili sliku. Slike je potrebno dostavljati u TIFF formatu rezolucije 300 DPI. KORITENJE KRATICA Upotrebu kratica treba svesti na minimum. Konvencionalne SI jedinice mogu se koristiti i bez njihovih definicija.
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Kardioloka ordinacija vl. prof.dr. Amila Arslanagi
Sarajevo, emalua 6, * asfeel@gmail.com * amila.arslanagic@gmail.com mob.: +061/136344 * tel.: +033 220000

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Volume 3 / Number 1 / 2009

Sadraj / Table of Contents

EBSCO Publishing (EP) USA http://www.epnet.com

Science Citation Index Expanded http://www.isiwebofknowledge.com

Volume 3 / Number 1 / 2009

Sadraj / Table of Contents

New classification of epidermolysis bullosa group of blistering disorders ........................ 90-93

Instructions for the autors ................................. 94-95

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

Table 2. Characteristics of VTE

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

in a way to treat addiction; is therapeutic outcomes effective?

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

Table 1. Methadone maintenance treatment (MMT) program

Female N (%) 6 (3.9) 1 (1.4) 7 (2.5) 6 (4.8) 1 (2.9) 7 (3.3)

151 84 48 283 105 69 41 215

Table 2. Frequency of related outcomes of the MMT program

HealthMED - Volume 3 / Number 1 / 2009

54 (25.1) 65 (30.2) 7 (3.3) 89 (41.4)

1 (0.5) 1 (0.5) 3 (1.4) 6 (2.8) 1 (0.5) 11 (5.1) 192 (89.3)

5th day 6th day 7 day

Table 5. Listed withdrawal sign & symptoms found among out-patients

HealthMED - Volume 3 / Number 1 / 2009

Table 6. Dose schedule for MMT program in outpatients

Chart 1. Clinical feature adherence to therapeutic dose setting in MMT program

Chart 2. Evaluation of MMT outcomes related to therapeutic comfort dose (TCD)

Table 4. Percentage of relapse among races in MMT Program

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

Table 1. Age Structure of Population of Bosnia and Herzegovina 1971

Table 2. Measles Morbidity in Bosnia and Herzegovina

HealthMED - Volume 3 / Number 1 / 2009

Chart 2. Measles dynamics sub-model with vaccination

Chart 4. Simulation sub-model (vaccination success 95 %)

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

Health Promotion in Silicon Valley: a Study of 11 Corporations

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

Graph 4. The most frequent CVS diseases in field are myocardiopathies

HealthMED - Volume 3 / Number 1 / 2009

Graph 8. The most of cases in the field are of II degree of urgency

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009

The most frequent congenital cardiovascular anomalies

HealthMED - Volume 3 / Number 1 / 2009

HealthMED - Volume 3 / Number 1 / 2009