JHSCI 2012 v2 I2 September

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES
UNIVERZITET U SARAJEVU FAKULTET ZDRAVSTVENIH STUDIJA
Journal of Health Sciences

Editorial Board
Editor in chief
Advisory Board
Dijana Avdi (BiH)
Kasim Bajrovi
Mirza Dili
Associate editor
Faris Gavrankapetanovi
Demal Pecar (BiH)
Ismet Gavrankapetanovi
Mirsada Huki
Secretary
Sebija Izetbegovi
Aida Rudi (BiH)
Lidija Lincender
Slobodan Loga
Members
Farid Ljuca
Jasmina Berbi-Fazlagi (BiH)
Senka Mesihovi-Dinarevi
Fatima Jusupovi (BiH)
Muzafer Muji
Mirsad Mufti (BiH)
Ljerka Ostoji
Budimka Novakovi (SRB)

Naris Pojski (BiH)
Electronic Publishing
Borut Poljak (SI)
Refet Gojak
Isabelle Rishard (F)
Muris Pecar
Sandra Vegar-Zubovi (BiH)

Zarema Obradovi (BiH)
Technical editor
Faruk pilja
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www.jhsci.ba
Volume 2, Number 2, September 2012
Table of contents:
EDITORIAL: The autumn brings the fruits
DIJANA AVDIC. . . . . . . . . . . . . . . . . . . . . . . . . 99
RESEARCH ARTICLES
Etiological factors as predictor of rehabilitation in
patients after carebrovascular insult
EDINA TANOVI, DAMIR CELIK . . . . . . . . . . 100-103
Risk factors for long term complications among patients
of endocrine clinic in Hospital Penang, Malaysia
SYED WASIF GILLANI, SYED AZHAR SYED
SULAIMAN, SHAMENI SUNDRAM, SITI
MAISHARAH SHEIKH GHADZI, SABARIAH
NOOR HAROON, NUR HAFZAN MD
HANAFIAH . . . . . . . . . . . . . . . . . . . . . . . . . . . 104-117
Dietary calcium intake and osteoporosis in
postmenopausal women living in Sarajevo area
AMILA KAPETANOVI, DIJANA AVDI . . . . . 118-121
Analysis of lipid status, body mass index and waist-hip
ratio in post-menopausal women
LEJLA MEALI, EDHEM HASKOVI . . . . . . 122-126
Does wound infiltration of tramadol reduce
postoperative pain in laparoscopic or open
herniorrhaphy?
REMZIYE SIVACI, EROL EROGLU,
LUTFI YAVUZ, FUSUN EROGLU,
YAAR SIVACI . . . . . . . . . . . . . . . . . . . . . . . . 127-131
Smoking and BMI as a risk factor of cardiovascular
disease at a doctors in Tuzla canton
MERISA IMAMOVI-KULUGLI,
FATIMA JUSUPOVI . . . . . . . . . . . . . . . . . . . 132-137
The possible role of tumor antigen CA 15-3, CEA and
ferritin in malignant and benign disease
NAFIJA SERDAREVI,
SAMIRA MEHANOVI . . . . . . . . . . . . . . . . . . 138-143
CASE REPORTS
Minimally invasive treatment of iatrogenic complete left
ureter obstruction after hysterectomy
YIGIT AKIN, ISIL BASARA,
ALISEYDI BOZKURT . . . . . . . . . . . . . . . . . . . 144-147
Lebers hereditary optic neuropathy - case report
MIRJANA A. JANICIJEVIC-PETROVIC,
TATJANA SARENAC VULOVIC, NENAD PETROVIC,
SUNCICA SRECKOVIC, SVETLANA PAUNOVIC,
KATARINA JANICIJEVIC, DEJAN VULOVIC,
DRAGAN VUJIC . . . . . . . . . . . . . . . . . . . . . . . 148-152
Endocarditis lenta-patient survived septic shock: a
case report
AMRA MACI-DANKOVI, NINA BURINA,
MEHMED KULI, SNJEANA MEHANI . . . . 153-158
INSTRUCTIONS TO AUTHORS
Instructions and guidelines to authors for the
preparation and submission of manuscripts
in the Journal of Health Sciences . . . . . . . . . . 159-162
www.jhsci.ba
Editorial
The autumn brings the fruits

The September issue of Journal of Health Sciences brings you several interesting original studies
from different parts of the world, as well as few important case reports which may inspire a new research on larger group of subjects. Authors from Bosnia and Herzegovina, Tanovic and Celik, have
been researching the predictive value of etiological factors in cerebrovascular insult and found that
hemorrhagic CVI costs are higher than the ischemic CVI. This study could initiate further research
and put emphasis to hemorrhagic CVI as that could make important savings in healthcare funds.
Gillani et al. from Malaysia were researching the risk factors for long term complications in diabetes
mellitus patients. As the incidence of this disease is in a continual increase data from new studies are
of high importance in a global effort to slow down the rate of new cases occurring every year worldwide. The authors found that the risk factors for long term complications are pervasive among the
diabetes mellitus patients and that they are not related to socio-demographic factors. Two studies,
by Kapetanovic et al. and Mesalic et al. were investigating the post-menopausal women. The Journal
of Health Sciences brings more hot topic papers this autumn, covering the cardiovascular diseases,
tumor biomarkers, hereditary optical neuropathy, iatrogenic surgical injury and its management
and a case of survived septic shock due to the endocarditis.
We are proud to announce that a Journal of Health Sciences is now indexed in EBSCO Academic
Search Complete database which will improve the visibility of the scientific achievements of our authors. The Journal is in evaluation procedure for several more scientific databases and the Editorial
board is convinced that the results of the evaluation will be positive.
We thank all the contributors until know with whom we established successful cooperation for mutual benefit and call the authors to submit their high quality research over the Journals web page
www.jhsci.ba.
The editorial board is dedicated to establish through JHSci a solid base for improvement of research
and publishing environment in Bosnia and Herzegovina and give its contribution globally.
Dijana Avdic, MD, PhD

Editor-in-chief
JOURNAL OF HEALTH SCIENCES 2012; 2 (2)
99
www.jhsci.ba
Etiological factors as predictor of rehabilitation

in patients after carebrovascular insult
Edina Tanovi*, Damir Celik
Clinic for Physical medicine and rehabilitation, Clinical Center University of Sarajevo, Bolnicka 25, 71000 Sarajevo, Bosnia and
Herzegovina
Abstract
Introduction: Cerebrovascular insult (CVI) is acute or sub-acute occurrence of symptoms which signal death
of cerebral cells caused by localized disruption of arterial circulation in the brain. The goal of this study is to
investigate whether ischemic or hemorrhagic CVI can be used as predictor of rehabilitation.
Methods: A retrospective study was conducted in the period from January 2009 to the December 2009 and
as a source of data we used medical records. The study included 89 patients who had CVI and who were
hospitalized at the Clinic for Physical medicine and rehabilitation, Clinical Center University of Sarajevo
(KCUS). We analyzed socio-demographic variables such as gender and age and clinical variables: the diagnosis, the length of stay in hospital (LOH), and Barthel index (BI) at admission and discharge from hospital.
Results: Out of 89 patients, 78/89 (87.6%) were patients with ischemic CVI (group A), and 11/89 (12.4%)
with hemorrhagic CVI (group B). There was not a significant association between the gender and type of CVI
[(2(1)= .041, P> .05]. There was a statistically significant difference in median of length of hospitalization
(LOH) between two groups (U=186.5; z=-3,025; P= .002). There was not a statistically significant difference
in median of BI at admission (U=317.0; z=-1,399; P= .162) and discharge (U=319.0; z=-1.374; P= .169)
between two groups.
Conclusion: Patients with hemorrhagic CVI have a longer stay in hospital and consequently more expensive
cost of treatment.
2012 All rights reserved
Keywords: cerebrovascular insult (CVI), etiology, rehabilitation, length of stay in hospital (LOH)
Introduction
Cerebrovascular insult (CVI) is acute or subacute occurrence of symptoms caused by localized occlusion in arterial circulation in the brain
(1). Acute form of this disease is marked as stroke,
apoplexy or brain attack. It is the third cause of illness and mortality as well as leading cause of disability in the world (1, 2). Etiological classification
explains the causes that led to this condition, and
the most common causes are vascular lesions in
the brain that can generally be divided to hemorrhagic lesions and ischemic CVI which can be
consequence of embolism and thrombosis (1, 3).
Sequelae of CVI are: clinical paralysis affect* Corresponding author: Edina Tanovic,
Clinic for Physical medicine and rehabilitation,
Clinical Center Universitiy of Sarajevo,
Bosnia & Herzegovina,
E-mail: tanovicedina@hotmail.com
Submitted: 7 July 2012 / Accepted: 24 August 2012
100
ing one side of the body, hemiparesis if it has

smaller intensity and hemiplegia if it has increased intensity (4). Rehabilitation is inseparable part of treatment after CVI and patients
should start it as soon as they are medically in
stabilized. Rehabilitation itself is a complex process which has an aim to maximize functional
independence of every individual patient. Together with medication therapy which is immediately introduced, active approach to rehabilitation is of utmost importance in such patients (5,6).
The first part of rehabilitation, which takes place in
the Stroke Units of the Neurological Clinic, is considered early-stage rehabilitation. For this period, it
is important to emphasize that there is a difference
in rehabilitation in regard with etiological cause
of CVI. In case that patient's general condition is
stable active approach to rehabilitation is recommended 72 hours after ischemic CVI occurred. If
cause of the insult is hemorrhagia, caution is recJOURNAL OF HEALTH SCIENCES 2012; 2 (2)
EDINA TANOVI, DAMIR CELIK: ETIOLOGICAL FACTORS AS PREDICTOR OF REHABILITATION IN PATIENTS AFTER CAREBROVASCULAR INSULT
ommended in first two or three weeks after CVI.

Such patients require additional follow-up and
well dosed therapy in the rehabilitation process.
After the treatment and upon completion of this rehabilitation part it is recommended to continue rehabilitation in specialized facility, which is considered late-stage rehabilitation. The goal of this study
is to investigate whether ischemic or hemorrhagic
CVI can be used as predictor of rehabilitation.
The KolmogorovSmirnov statistic test with a

Lilliefors significance level was used for testing
normality. Results are expressed as median and
interquartile range (IQR) in case of continuous
non-normal distributed variables. In case of categorical variables, counts and percentages were
reported. Statistical analysis was performed with
Mann-Whitney U-test, Wilcoxon Signed Rank
test and Chi-Square test. A P-value < .05 was
considered as significant. Statistical analysis was
performed by using the Statistical Package for the
Social Sciences (SPSS Release 19.0; SPSS Inc., Chicago, Illinois, United States of America) software.
Methods
A retrospective study was conducted in the period
from January 2009 to the December 2009 and as a
source of data we used medical records. The study
included 89 patients who had CVI and who were
Results
hospitalized at the Clinic for Physical medicine Out of 89 patients, 78/89 (87.6%) were paand rehabilitation, Clinical Center University of
tient with ischemic CVI (group A), and 11/89
Sarajevo (KCUS). We analyzed socio-demograph- (12.4%) with hemorrhagic CVI (group B). In
ic variables and clinical variables: the diagnosis, group A, the frequency of males was 40/78
the length of stay in hospital (LOH), and Barthel (51.3%), in group B was 6/11 (54.5%). There
index (BI). The Barthel scale or Barthel ADL index was not a significant association between the
is an ordinal scale used to measure performance in gender and type of CVI [(2(1)= .041, P> .05].
activities of daily living (ADL). Each performance The median age was 66 years (IQR=59 to 73
item is rated on this scale with a given number years) in group A, and 69 years (IQR=64 to
of points assigned to each level or ranking (7). It 74 years) in group B. There was not a statistiuses ten variables describing ADL and mobility. A cally significant difference in median age behigher number is associated with a greater likeli- tween two groups (U=367.0; z=- .774; P=
hood of being able to live at home with a degree of .439). The highest number of patients in both
independence following discharge from hospital. groups was between 60-80 years of age (Fig. 1).
The measuring was performed at admission and In group A, the median of LOH was 32 days
discharge from the KCUS. The inclusion crite- (IQR=23.8 to 40.3 days), in group B was 46 days
ria were: patients aged over 18, patients who had (IQR=39.0 to 69.0 days). There was a statistiCVI followed by neurological deficit, patients who cally significant difference in median of LOH becompleted acute treatment with medications at tween two groups (U=186.5; z=-3,025; P= .002)
Neurological Clinic, patients who started rehabili- (Fig. 2). In group A, the median of BI at admistation at the Clinic for Physical
medicine and rehabilitation not
more than one month after cerebrovascular insult. The exclusion criteria (following the use of
therapeutical possibilities) were:
rapid regression of neurological
symptoms, gastrointestinal or
urinary bleeding within last 21
days, myocardial infarct within
last three months, evidence of
active bleeding, acute trauma or
fracture and patients who died
or transferred to another clinic.
FIGURE 1. Distribution of patients age in both groups
101
TABLE 1. Descriptive statistics of patients with CVI who were hospitalized at the Clinic for Physical medicine and rehabilitation,
Clinical Center University of Sarajevo, 2009, (n=89)
Variables
Age (years)
LOH (days)
BI *
BI **
CVI
Min.
Max.
0
1
0
1
0
1
0
1
78
11
78
11
78
11
78
11
38
29
7
19
0
0
2
4
82
78
74
84
20
12
20
17
25-th
59.0
64.0
23.8
39.0
2.0
2.0
8.0
8.0
Percentiles
50-th
66.0
69.0
32.0
46.0
8.0
5.0
14.0
11.0
75-th
73.0
74.0
40.3
69.0
15.0
9.0
18.0
14.0
P-value
.439
.002
.162
.169
0 ischemic; 1 hemorraggic; BI* Brathel index at admission; BI** Barthel index at discharge;
FIGURE 2. Box plot of LOH (days) in both groups
FIGURE 3. Box plot of Barthel index at admission and discharge in both groups (BI* Brathel index at admission; BI**
Barthel index at discharge)
102
sion was 8.0 (IQR=2 to 15), in group B was 5.0

(IQR=2 to 9). There was not a statistically significant difference in median of BI at admission between two groups (U=317.0; z=-1,399; P= .162).
In group A, the median of BI at discharge was
14.0 (IQR=8 to 18), in group B was 11.0 (IQR=8
to 14). There was not a statistically significant
difference in median of BI at discharge between two groups (U=319.0; z=-1,374; P= .169).
In group A, there was a highly statistically significant difference in median of BI between
admission and discharge (Z=-7.105; P< .001).
In group B, there was a statistically significant difference in median of BI between admission and discharge (Z=-2.956; P< .01)..
Discussion
In our study, the frequency of males was 51.3%
in group A, and 54.5% in group B. These results are consistent with others similar studies
(2, 8). There was not a significant association
between the gender and type of CVI (P> .05).
In group A, the highest number of patients (55/78
or 71%) was between 60-79 years of age, followed by, 21/78 (27%) between 40-59 years, 1/78
(1%) between 20-39, and 1/78 (1%) 80 years.
In group B, the highest number of patients (9/11
or 82%) was between 60-79 years of age, followed by, 1/11 (9%) between 40-59 years, and
1/11 (9%) between 20-39 (Fig. 1). There was not
a statistically significant difference in median age
between two groups (P= .439). Our earlier research shows similar results which corresponding with the data from others studies (2,8,9).
In our study, the most patients (78/89 or 87.6%)

had ischemic CVI, and 11/89 (12.4%) were patients
with hemorrhagic CVI. These results are in agreement with results from medical literature (1,2,8).
In group A, the median of LOH was 32 days, in
group B was 46 days and there was a statistically
significant difference in median of LOH between
two groups (P= .002). Later start of active rehabilitation treatment for patients with hemorrhagic
CVI causing longer rehabilitation process (8,9,10).
In order to ensure faster and more economical recovery for the patients it is necessary to shorten
duration of rehabilitation, which corresponds to
the most recent data in the literature. This process
is in patients best interest, in their families interest and it also reduces treatment costs. Rehabilitation after stroke continues in home program after
completion of first phase of treatment (2,11,12).

There was not a statistically significant difference in median of BI at admission and discharge
between two groups, but there was a highly statistically significant difference in median of BI
between admission and discharge in group A
(P< .001), and group B (P< .01). These results
are consistent with others studies (8,11,12,13).
Conclusion
Patients with hemorrhagic CVI have a longer stay
in hospital and consequently more expensive cost
of treatment.
Competing interests
Authors declare no conflict of interest.
References
(1) Kantardi D. Klinika neurologija. Sarajevo: Svjetlost, 2001: 263-73.
(2) Tanovi E. Evaluacija vrijednosti
funkcionalne elektrine stimulacije
u rehabilitaciji hoda kod pacijenata
sa motornom lezijom nakon cerebrovaskularnog inzulta. Magistarski rad. Sarajevo 2002.
(3) Poeck K. Neurologija. Zagreb:
kolska knjiga, 1994: 151-84.
(4) Majki M. Klinika kineziterapija,
Zagreb: Inmedia, 1997: 3-83.
(5) Ferrucci L, Bandinelli S, Guralnik
JM, Lamponi M, Bertini C, Falchini
M, et al. R Recovery of functional
status after stroke. A postrehabilitation follow-up study. Stroke 1993:
24: 200-5.
(6) Randall LB. Physical medicine and
rehabilitation. Philadelphia: W.B.
Saunders company: 1996: 1053-79.

(7) O'Sullivan, Susan B; Schmitz,
Thomas J. Physical Rehabilitation,
Fifth Edition. Philadelphia, PA: F.A.
Davis Company, 2007:385.
(8) Jorgensen HS, Nakamaya H, Raashou HO, Olsen TS. Recovery walking Function in Stroke Patioents:
The Copenhagen Stroke Study.
Archives of Physical Medicine and
Rehabilitation. Philadelphia: W.B.
Saunders company, 1995; (Vol. 76,
No. 1): 27-32.
(9) Keith RA, Wilson DB, Gutirrez P.
Acute and Subacute Rehabilitation
for stroke: A comparsion. Archives
of Physical Medicine and rehabilitation Philadelphia: W.B. Saunders
company, 1995; (Vol. 76, No. 6)
495-500.
(10) Volpe BT, Krebs HI, Hogan N, Edelstein L, Diels C, Aisen M. A novel
approach to stroke rehabilitation.
The American Academy of Neurology 2000; 1938-43.
(11) Tanovi E, Tanovi H. Functional
electric stimulation on walking
rehabilitation on patients with
hemiplegia after stroke. NEUROL
CROAT: 2007; 56(Suppl.1): 188-94.
(12) Tanovi E. ET- test a new valorization results of the rehabilitation.Folia Medica 2008;43 (suppl 2): 84-8.
(13) Tanovi E, Tanovi H. A new valorization by ET-test in the rehabilitation after cerebro vascular insult.
Edicioni Minerva Medica: 2010;
269-271.
103
www.jhsci.ba
Risk factors for long term complications

among patients of endocrine clinic
in Hospital Penang, Malaysia
Syed Wasif Gillani1*, Syed Azhar Syed Sulaiman1, Shameni Sundram2, Siti Maisharah
Sheikh Ghadzi3, Sabariah Noor Haroon3, Nur Hafzan Md Hanafiah3
School of Pharmaceutical Sciences, University Sains Malaysia, Pulau Pinang, Malaysia. 2 Hospital Pulau Pinang, 10990,
Residential street, Penang, Malaysia. 3 School of Pharmaceutical Sciences, University Sains Malaysia, Kubang Kerian, Kelantan.
Abstract
Introduction: The prevalence of diabetes is on the increase and an estimated 239 million people worldwide
are expected to have the condition by the year 2020 (1). Diabetes mellitus (DM) represents a serious health
care challenge. The aim of the study was to evaluate the patient clinical characteristics and risk factors for
long term complications in the endocrine clinic of Hospital Penang, Malaysia.
Methods: Descriptive Prospective cross-sectional study design was chosen. To achieve a power of 0.7 with
alpha set at 0.05, 186 subjects were required for the study but researcher increase the sample to 297 in case
of drop out. Self-developed data collection form was used to collect the patient information.
Results: 297 (100%) patients were enrolled from OPD diabetic clinic of Hospital Palau Pinang. Among the
sample 150 (50.5%) were males and rest 147 (49.5%) females. Malay males mean weight at the time of diagnosis significantly higher (p<0.001,) as compared to other ethnics, same results found among Malay females
(p<0.001). Findings suggested increased number of risk factors among the study population. Finding also
showed that hypertension found among all the classes of diagnosis. Significant variable are diagnosis class
and medication consideration.
Conclusion of the study suggested that majority of patients are at high risk of long-term complications and
comorbidies. It has been found that increased rate of risk factors have been found among the study population and non-significant to sociodemographic differences.
Keywords: diabetes mellitus, risk factors, long term complications, endocrine clinic, clinical health.
Introduction
The prevalence of diabetes is on the increase and
an estimated 239 million people worldwide are
expected to have the condition by the year 2020
(1). Diabetes mellitus (DM) represents a serious
health care challenge. It is a heterogeneous disorder characterized by varying degrees of insulin resistance and insulin deficiency, which leads to disturbances in glucose homeostasis. It is commonly
associates with prolonged ill health and premature
death (2). The mortality rate in patients with DM
* Corresponding author: Syed Wasif Gillani
School of Pharmaceutical Sciences, Universiti Sains
Malaysia, 11800, Gelugor, Pulau Pinang, Malaysia
Phone: +60174203027; Fax: +604-6570017
e-mail: wasifgillani@gmail.com
Submitted: 13 May 2012 / Accepted: 23 July 2012
104
may be up to eleven times higher than in persons without the disease (3, 4). DM is the leading
cause of blindness, renal failure and foot and leg
amputations in adults in developed countries (1).
The World Health Organization (WHO) classification system of DM recognized two major
forms of diabetes (5); Type 1 diabetes mellitus
(DM), formerly known as insulin dependent diabetes mellitus (IDDM; patient is dependent on
exogenous insulin for survival) and Type 2 DM,
formerly known as non-insulin dependent diabetes mellitus (NIDDM; patient is not necessary
dependent on exogenous insulin for survival).
Teamwork and collaboration are essential components of successful DM management, both to
prevent complications and maintain the patients
health-related quality of life (HRQOL) over a
SYED WASIF GILLANI ET AL.: RISK FACTORS FOR LONG TERM COMPLICATIONS AMONG
PATIENTS OF ENDOCRINE CLINIC IN HOSPITAL PENANG, MALAYSIA
lifetime of coping with the disease (1). Type 1

DM is characterized by insulin deficiency resulting from immune-mediated pancreatic beta-cell
destruction. The most serious acute consequence
of this is ketoacidosis. Pancreatic beta-cell destruction eventually results in absolute insulin
deficiency (1). Type 1 DM accounts for approximately ten percent of all DM cases. Type 2 DM
is generally characterized by peripheral insulin
resistance with relative insulin deficiency to predominant insulin secretory defeat with insulin
resistance (1). Type 2 DM accounts for approximately ninety percent of all DM cases. The major risk factors in the development of type 2 DM
are (3); Family history, Obesity, Race/ethnicity,
Increasing age (especially greater than forty five
years), Previous identified impaired fasting glucose or impaired glucose tolerance, Hypertension,
Hyperlipidemia and History of gestational DM.
There is evidence that good glycaemic control
can slow or prevent the development of diabetes
complications (6-10). The Diabetes Control and
Complication Trial (DCCT) demonstrated the association between the degree of glycaemic control
and the development of microvascular complications in type 1 DM patients (11-12). The DCCT
determined that there was an approximately
50% reductions in microvascular complications
in the intensive treatment group and a non-significant tendency to fewer major cardiovascular
events. Intensive control was accompanied by
a significantly between the groups. The DCCT
investigators did advice caution in extending
the findings to patients with type 2 DM without
careful regard for age and coexisting diseases.
The United Kingdom Prospective Diabetes Study
(UKPDS) was the largest scale long-term intervention study in newly diagnosed type 2 DM patients
and involved over 5000 patients. The UKPDS used
an intensive blood glucose control policy, which
achieved a medium HbA1c of 7% compared with
7.9% in those randomized to conventional treatment over a median 10 years follow-up (9). The
UKPDS confirmed the benefit of intense glycaemic control on microvascular disease in type 2
DM patients (4, 8-10, 13-20). The aim of the study
to evaluate the patient clinical characteristics and
risk factors for long term complications in the
endocrine clinic of Hospital Penang, Malaysia.
Methods
Study design
This study aimed to describe the risk factors and
association among sociodemographics, hence
Descriptive Prospective cross-sectional study design was chosen. Managing diabetes is a lifelong
process and requires total commitment from individuals with diabetes. Hence the framework of
this study was based on the principle of eight risk
factors (RF). RF1-Diabetes, RF2- Hypertension,
RF3- Hyperlipidemia, RF4- Smoking, RF5-Male >
45years, RF6=Female > 55years, RF7- Hypoglycemia, RF8- No exercise (3x/week > 20min). RF1Diabetes, since all the patients are from endocrine
clinic so the rational effect of this variable is 100%.
Setting
As 70% of people with diabetes in Malaysia receive treatment in the government healthcare
system, (21) data was collected from government healthcare settings. The general hospital
is the main government hospital in the Penang
state and is situated within the city area offering tertiary care. Subjects were not recruited
from private clinics and hospitals due to problems with accessibility and differences in socioeconomic status which could bias the outcomes.
Sample Size
The required sample size was calculated with
power analysis using the procedure provided by
the Polit and Hungler (22). The power was set at
0.80 with alpha being set at 0.05. Since the value
of the effect size (Gamma), was unavailable from
previous similar studies and the pilot study sample size was small (19 subjects), the investigator
chose to use the conversion based on the effect
size convention table in Polit and Hungler (22).
Polit and Hungler (22) advise to use medium effect size ranging from 0.2-0.3 for nursing studies.
This provided a range of sample size from 88-197
subjects. For logistical reasons the study had to
be a manageable size within the period of study,
so the investigator chose the sample size using
the medium effect size of Gamma y = 0.25. To
achieve a power of 0.7 with alpha set at 0.05, 186
subjects were required for the study but researcher increase the sample to 297 in case of drop out.
105
Inclusion criteria. Subjects who met the following criteria were recruited: non-pregnant adults
with either Type1 or Type 2 diabetes regardless
of gender and ethnicity, 18 years and above (legal
age for consent), diagnosed with diabetes with
year of more, speaking and understanding either
English, Bahasa Malaysia, Mandarin, Chinese
dialects (Cantonese, Hokkien, Teow-chew) because these were the languages used during the
interview, having poor diabetes control during the
last one year. Even though glycated haemoglobin
(HbA1c) is the gold standard for glycaemic assessment, it was not consistently measured for all
diabetic patients in the healthcare system where
the study was done. Therefore for the purpose of
this study, poor diabetes control was defined as
the mean of minimum of three fasting blood glucose (FBG) readings of more than 7 mmol/L in
the last year. Prior studies have shown that FBG of
more than 7 mmol/L is associated with increased
micro-and macro-vascular complications (23-26).
Exclusion criteria. The following subjects were excluded: Were adults 18 years of age and more with
either Type 1 of Type 2 diabetes unable to answer
the questionnaires independently, such as having
unstable medical condition, mental illness, and senility or hearing impairment. This was to avoid assistance from family members to cares that could
introduce bias in the data collection; had poor vision and unable to assess visually the portion sizes
of their carbohydrate food intake during dietary
assessment; were women who were pregnant or
had gestational diabetes due to different criteria on
standard of control; had record of random blood
glucose only because the definition of poor control was based on fasting blood glucose readings.
Research Tool
Self-developed data collection form was used to
collect the patient information.
Ethical issues
The Research Ethics Committee of hospital and the Malaysian Medical Research
and Ethics Committee approved the study.
Written consents which included information to
access the subjects medical records were taken
from all participants before the interviews. For
those who were illiterate and not able to give
106
their signature, thumbprints were used instead.

The medical records were sourced for two pieces
of information. First, the subjects glycaemic status was attained namely fasting blood glucose
levels to assist the investigator in identifying the
potential subjects (inclusion criteria). Second,
the subjects current medication(s) were attained
since research question three sorts to identify any
relationship between medication concordance
and poor glycaemic control. No other data was
extracted from the medical records. Viewing and
extracting information from the subjects medical
records was done solely by the investigator either
at the medical in-patient wards or the medical
outpatient clinics during official working hours.
Data Collection Procedure
Identification of Subjects. This was done initially by identifying all diabetic subjects. In the
out-patient department of the hospital, the investigator worked closely with the nursing staff
to identify patients with blood glucose tests
done prior to doctors consultation. They were
familiar with their patients with poor glycaemic control or the nurse in-charge identified
them via the patients blood glucose results.
Places of Data Collection. Data collection was
done in out-patient departments at the doctors
consultation rooms.
Statistical Analysis
The analysis was done in both descriptive and inferential statistics to make information in presentable
form. Data is presented in both graphical and tabular forms. The Statistical package for Social Sciences (SPSS) version 19 was used for this analysis. The
level of significance was set at 0.05 for all analysis.
Results
A total of 297 (100%) patients were enrolled
from OPD diabetic clinic of Hospital Palau
Pinang. Among the sample 150 (50.5%) were
TABLE 1. Frequency among gender of study population
Gender
Male
Female
Total
F (%)
150 (50.5)
147 (49.5)
297 (100.0)
Age mean (S.D.)

58.23 (10.771)
59.04 (10.414)
58.64 (10.581)
TABLE 2. Mean age gender distribution among ethnic

Gender
Male
Female
Total
Ethnic
Malay
Chinese
Indian
Total
Malay
Chinese
Indian
Total
Malay
Chinese
Indian
Total
Mean
53.20
62.10
55.03
58.23
54.03
63.43
58.30
59.04
53.61
62.75
56.53
58.64
N (%)
Std. Deviation
40 (26.7)
12.831
77 (51.3)
8.612
33 (22)
9.600
150 (50.5)
10.771
36 (24.49)
8.013
81 (55.10)
11.090
30 (20.41)
9.063
147 (49.5)
10.414
76 (25.59)
10.627
158 (53.20)
9.959
63 (21.21)
9.422
297 (100.0)
10.581
TABLE 3. Mean weight in kg at diagnosis gender distribution

among ethnic
Gender
Male
Female
Total
Ethnic
Malay
Chinese
Indian
Total
Malay
Chinese
Indian
Total
Malay
Chinese
Indian
Total
Mean
79.17
66.64
69.19
70.34
69.38
60.53
59.95
62.37
74.74
63.31
64.96
66.29
N (%)
Std. Deviation
40 (26.67)
18.936
77 (51.33)
13.003
33 (22)
11.314
150 (50.5)
15.185
36 (24.49)
14.896
81 (55.10)
12.766
30 (20.41)
11.069
147 (49.5)
13.382
76 (25.59)
17.761
158 (53.20)
13.184
63 (21.21)
12.019
297 (100.0)
14.815
TABLE 4. Characteristic determination of RF2 hypertension

during study duration
RF2-hypertension
Characteristic
Gender
Male
Female
Ethnic
Malay
Chinese
Indian
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and
other complication
Medication
consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
Yes
N (%)
No
N (%)
Total N
(%)
pvalue
88 (58.7)
93 (63.2)
62 (41.3) 150 (100.0) 0.417

54 (36.8) 147 (100.0)
44 (57.9)
102 (65.4)
36 (55.4)
32 (42.1) 76 (100.0)
54 (34.6) 156 (100.0) 0.296*
29 (44.6) 65 (100.0)
3 (100.0)
3 (100.0)
8 (9.0)
81 (91.0) 89 (100.0) 0.000*
101 (100.0) 101 (100.0)
69 (66.3)
35 (33.7) 104 (100.0)
3 (50.0)
1 6 (66.7)
4 (22.2)
156 (63.4)
2 (66.7)
3 (50.0)
8 (33.3)
14 (77.8)
90 (36.6)
1 (33.3)
6 (100.0)
24 (100.0) 0.013*
18 (100.0)
246 (100.0)
3 (100.0)
Chi-square (*Pearson)
males and rest 147 (49.5%) females. Mean age

distribution among gender is presented in Table 1.
Ethnic distribution among males showed predominance of Chinese with 77 (51.3%) followed by
Malays 40 (26.7%) and rest 33 (22%) were Indians.
While among females almost same pattern was
found. The mean S.D age differences were found
FIGURE 1. Clinical risk factors founds among enrolled patients. (RF1 = Diabetes, RF2 = Hypertension, RF3 = Hyperlipidemia,
RF4 = Smoking, RF5 = Male >45years, RF6=Female>55years, RF7 = Hypoglycemia, RF8 = No exercise (3x/week>20min)).
107
TABLE 5. Characteristic determination of RF3 - hyperlipidemia in study population

Characteristic
RF3-hyperlipidemia
Yes N (%) No N (%)
Total N
(%)
pvalue
TABLE 6. Characteristic determination of RF4-Smoking in

study population
Characteristic
RF4-Smoking
Yes N (%) No N (%)
Total
N (%)
pvalue
Gender
Male
Female
43 (28.7)
52 (35.4)
107 (71.3) 150 (100.0) 0.0215

95 (64.6) 147 (100.0)
Gender
Male
Female
28 (18.7)
4 (2.7)
122 (81.3) 150 (100.0) 0.000

143 (97.3) 147 (100.0)
Ethnic
Malay
Chinese
Indian
20 (26.3)
55 (35.2)
20 (30.8)
56 (73.7) 76 (100.0)
101 (64.8) 156 (100.0) 0.258
45 (69 .2) 65 (100.0)
Ethnic
Malay
Chinese
Indian
6 (8.0)
13 (8.3)
12 (18.5)
70 (92.0) 76 (100.0)
143 (91.7) 156 (100.0) 0.441*
53 (81.5) 65 (100.0)
1 (33.3)
2 (2.2)
4 (4.0)
2 (66.7)
87 (97.8)
97 (96.0)
3 (100.0)
89 (100.0) 0.000*
101 (100.0)
1 (33.3)
8 (9.0)
8 (7.9)
2 (66.7)
81 (91.0)
93 (92.1)
3 (100.0)
89 (100.0) 0.096*
101 (100.0)
88 (84.6)
16 (15.4)
104 (100.0)
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and other
complication
13 (12.5)
91 (87.5)
104 (100.0)
6 (100.0)
24 (100.0)
18 (100.0) 0.274*
246 (100.0)
3 (100.0)
Medication
consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
1 (16.7)
3 (12.5)
1 (5.5)
20 (8.1)
-
5 (83.3)
21 (87.5)
17 (94.5)
226 (91.9)
3 (100.0)
6 (100.0)
24 (100.0) 0.552*
18 (100.0)
246 (100.0)
3 (100.0)
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and other
complication
Medication
consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
3 (50.0)
6 (25.0)
3 (16.7)
83 (33.7)
-
3 (50.0)
18 (75.0)
15 (83.3)
163 (66.3)
3 (100.0)
Chi-square (*Pearson)
Chi-square (*Fisher exact)
variable among the three ethnics. Table 2 showed

the distribution pattern of mean S.D of age among
genders and also among the study population.
Mean age comparison among genders showed
females have high mean age (59.04 years) as
compared to males (58.23 years). While comparing mean age difference among ethnics revealed Chinese mean age is 62.75 years followed
by Indians with 56.53 years and least age to disease response among Malays 53.61 years. Mean
weight of the study population was 66.29kg but
upon analysis among genders it is found that
males mean S.D (70.34 15.185) is extensively
higher as compared to females (62.37 13.382).
Further analysis by cross tabulation showed Malay
males mean weight at the time of diagnosis significantly higher (p<0.001, one way ANOVA) as compared to other ethnics, same results found among
Malay females (p<0.001, one way ANOVA). Table
3 showed cross-tabulation of mean weight distribution among gender and ethnics at the time of diagnosis. At the time of diagnosis body mass index
(BMI) has been collected and results showed the
mean BMI of the study population was 25.39 (297,
100%), among them females have higher BMI 25.79

as compared to males 24.97 at the time of diagnosis.
The Figure 1 presents the percentage distribution of
clinical risk factors among study population. Clinical risk factors are the individual parameters that
might lead to increase long-term complications
or co morbidities. More the clinical risk factors
among the study population, it will give increase
possibility to get higher complications. Findings
suggested increased number of risk factors among
the study population. Finding also showed that
hypertension found among all the classes of diagnosis. Significant variable are diagnosis class and
medication consideration. Table 4 provides the descriptive information about the RF-2 hypertension
during the study duration among selected patients.
Risk factor analysis results showed that hyperlipidemia have significant association among gender.
Further analysis revealed that about 95 (32%) of
our study population carrying this risk factor and
majority of them 83 (87.4%) on the oral medication. Table 5 presented the finding of the analysis.
Similarly smoking findings are presented in Table 6.
Age above then 45 years for male and >55 years
108
TABLE 7. Characteristic determination of RF5-Male>45

years (N=114/150) among male in study population
Characteristic
Ethnic
Malay
Chinese
Indian
N (%)
p-value
27 (23.7)
65 (57.0)
22 (19.3)
0.000
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and other complication
1 (0.9)
27 (23.7)
43 (37.7)
43 (37.7)
Medication consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
1 (0.9)
12 (10.5)
5 (4.4)
94 (82.5)
2 (1.7)
0.000
0.000
TABLE 9. Characteristic determination of RF7-Hypoglycaemia in study population

Characteristic
RF4-Hypoglycaemia
Total N(%) p-value
TABLE 8. Characteristic determination of RF6-Female > 55

years (N=90/147) among female in study population
Characteristic
Ethnic
Malay
Chinese
Indian
N (%)
p-value
16 (17.8)
58 (64.4)
16 (17.8)
0.000
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and other complication
1 (11.1)
15 (16.7)
32 (35.5)
42 (46.7)
Medication consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
3 (33.3)
6 (6.7)
1 (1.1)
79 (87.8)
1 (1.1)
0.000
0.000
TABLE 10. Characteristic determination of RF8-No Exercise

(3x/week>20 min) in study population
Characteristic
Yes N (%) No N (%)
RF8-No Exercise
(3x/week>20 min)
Total N (%) p-value
Yes N (%) No N (%)
Gender
Male
Female
14 (9.3)
8 (5.4)
136 (90.7) 150 (100.0) 0.457

139 (94.6) 147 (100.0)
Gender
Male
Female
41 (27.3)
38 (25.9)
109 (72.7) 150 (100.0) 0.730

109 (74.1) 147 (100.0)
Ethnic
Malay
Chinese
Indian
7 (9.2)
7 (4.5)
8 (12.3)
69 (90.8) 76 (100.0)
149 (95.5) 156 (100.0) 0.317
57 (87.7) 65 (100.0)
Ethnic
Malay
Chinese
Indian
21 (27.6)
38 (24.4)
18 (27.7)
55 (72.4) 76 (100.0)
118 (75.6) 156 (100.0) 0.032
47 (72.3) 65 (100.0)
2 (66.7)
9 (10.1)
7 (6.9)
1 (33.3)
80 (89.9)
94 (93.1)
33 (37.1)
18 (17.8)
3 (100.0)
56 (62.9)
83 (82.2)
3 (100.0)
89 (100.0) 0.001*
101 (100.0)
4 (3.8)
100 (96.2) 104 (100.0)
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and other
complication
27 (26.0)
77 (74.0)
104 (100.0)
4 (66.7)
20 (83.3)
17 (94.4)
233 (94.7)
3 (100.0)
Medication
consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
3 (50.0)
4 (16.7)
4 (22.2)
63 (25.6)
-
3 (50.0)
20 (83.3)
14 (77.8)
183 (74.4)
3 (100.0)
6 (100.0)
24 (100.0)
18 (100.0) 0.037*
246 (100.0)
3 (100.0)
Diagnosis
IDDM
Diabetes
Diabetes and HPT
Diabetes and other
complication
Medication
consideration
Insulin
Insulin and oral
BIDS
Oral
Diet and exercise
2 (33.3)
4 (16.7)
1 (5.6)
13 (5.3)
-
3 (100.0)
89 (100.0) 0.016*
101 (100.0)
6 (100.0)
24 (100.0)
18 (100.0) 0.033*
246 (100.0)
3 (100.0)
Chi-square (*fisher exact)
Chi-square (*fisher exact)
for females is important factor for complications

and long-term medical problems. Upon analysis of this variable we find similar results of significant association with ethnic, diagnosis class
and medication consideration. Results showed

that 114 (76%) of our study males are > 45 years
while 90 (61.2%) of females were > 55 years. Detailed descriptive data is presented in Table 7 & 8.
109
Hypoglycemic evidence has an association with

diagnosis class and medication consideration,
no significant differences has been found among
gender and ethnicity of the study population (Table 9). Majority of the patients having no social
habit of exercise, table 10 describes the relation
and association of no-exercise risk factors with
characteristic variables among study population.
trolling the blood pressure is a commendable goal

of antihypertensive therapy, treating hypertensive
cardiovascular disease in the diabetic patient is
more complex than simply achieving blood pressure targets. Recent studies have shown that antihypertensive drug classes have differing effects on the
risk of new onset diabetes, on metabolic endocrine
surrogate endpoints and possibly on outcome (32).
Discussion
The World Health Organization projects that by
the year 2025 more than 5% of the world population, i.e. 300 million people will suffer from diabetes. A patient who suffers from type 2 diabetes has
a 24 times greater risk of death from cardiovascular causes than the patient without diabetes (27).
The most Hypertension and Diabetes 83 common
cause of dying in the diabetic patient is heart disease. In addition, peripheral vascular disease, endstage renal disease, blindness and amputations
are common co-morbidities in diabetic patients.
Hypertension has been identified as a major risk
factor for the development of diabetes. Patients
with hypertension are at a 23 times higher risk
of developing diabetes than patients with normal
blood pressure (28). Hypertension by itself is, of
course, a powerful risk factor for cardiovascular
morbidity and mortality as established by data
from the Framingham cohort more than three
decades ago. For any given level of systolic blood
pressure, the occurrence of diabetes distinctly
increases cardiovascular mortality. Stamler et
al. (29) have documented that diabetes in the
normotensive patient confers greater risk than a
systolic blood pressure between 160 and 170mm
Hg. This observation provoked Haffner and Cassells (30) observation that the prognosis of diabetes is just as grim as the one of a patient who
has suffered an acute myocardial infarction. Of
note, while this is true for overall cardiovascular mortality, it does not necessarily mean that
diabetes and hypertension are synonymous in
affecting the individual components of cardiovascular system. Also, it does by no means follow that specific cardiovasculardrugs are equally
protective in diabetes and coronary artery disease.
Blood pressure control remains unacceptably low
in the general population, but is even lower in the
diabetic hypertensive patient (31). Although con-
Clinical finding in cardiovascular problems

in Diabetes patients
Diabetes mellitus is associated with a high risk of
cardiovascular disease and is the leading cause
of end-stage renal disease, blindness, and nontraumatic amputations in western countries (33).
Elevated but nondiabetic levels of fasting glucose
also carry a higher risk of cardiovascular disease
(34). As a cardiovascular risk factor, glycemia is
a continuous variable with no sudden increase
in risk (35). The extreme state is the metabolic
syndrome that is associated with a 2- to 3-fold
increase in cardiovascular morbidity and mortality (36-38). Hypertension by itself is a powerful risk factor for cardiovascular morbidity and
mortality. Although the effects of diabetes mellitus and hypertension on the cardiovascular
system vary somewhat and are often distinct,
their combined presence in the same patient is
destructive (39). The common denominator of
hypertensive/ diabetic target organ disease is the
vascular tree, which is affected by both disorders.
The Vascular Tree. Both hypertension and diabetes are well-identified risk factors for atherogenesis. Several mechanisms acting together mediate
the damage to the vascular tree in the diabetic
hypertensive patient (39). Metabolic abnormalities that often present in diabetic hypertensive
patients accelerate atherosclerosis. Plasma levels
of lipoprotein have been noted to be elevated in
diabetic individuals, particularly those with poor
glycemic control. Augmented oxidation of lowdensity lipoprotein cholesterol and formation of
glycated low-density lipoprotein, which enhance
foam cell formation, have been observed in diabetic states. Anatomic and functional abnormalities of the vascular endothelium have been described in diabetes mellitus and hypertension (39).
Hyperglycemia activates protein kinase C in endothelial cells, which may enhance vascular tone, per-
110
meability, and atherosclerosis. Elevated circulating

levels of insulin as exist in type 2 diabetes and in
many patients with essential hypertension may
contribute either directly or in conjunction with
insulin-like growth factor (IGF) to the accelerated
atherosclerosis associated with these conditions.
Insulin and IGF-1 may exert their atherogenic effects through influences on both vascular endothelial cells and vascular smooth muscle cells (39).
Diabetes mellitus and hypertension are also associated with hematologic abnormalities that encourage thrombosis. Enhanced platelet adhesion and
aggregation as well as higher than normal levels
of some coagulation factors contribute to the procoagulation state in diabetic hypertensive patients
(39). Diabetes seems to be a specific risk factor for
small vessel disease. In contrast, hypertension, at
least in its nonmalignant form, seems to affect predominantly the large arteries. Together, the two
disorders synergistically damage the arterial tree.
Heart and Coronary Artery Disease. Diabetes mellitus is associated with a markedly increased prevalence of coronary artery disease. The prevalence
of coronary artery disease as assessed by various
diagnostic methods is as high as 55% among adult
patients with diabetes mellitus as compared to
24% of the general population (40). Moreover,
the cardiovascular mortality rate is more than doubled in men and more than quadrupled in women
who have diabetes mellitus compared to those
without. The restenosis rate after coronary balloon angioplasty is about 2-fold higher in diabetic
than nondiabetic patients (41). Due to autonomic
neuropathy diabetic patients have a decreased perception of ischemic pain, which contributes to a
high prevalence of silent ischemia (42). Diabetic
patients without previous myocardial infarction
have as high a risk of myocardial infarction as
nondiabetic patients with previous myocardial
infarction (43). Myocardial ischemia is common
in patients with hypertension (44) and caused by
several pathogenic mechanisms. (a) Hypertension
accelerates arteriosclerosis of the coronary arteries. (b) Elevated blood pressure increases left ventricular wall stress, wall tension, and stroke work.
(c) Resistance of the coronary microvasculature is
abnormally elevated in hypertensive patients even
in the absence of left ventricular hypertrophy. (d)
Long-standing hypertension causes left ventricular
hypertrophy that increases the diffusion distance,

compromises the vasodilator reserve of the coronary circulation and increases the oxygen demand
of the myocardium (27, 45). It should be noted that
hypertensive patients, especially those with left
ventricular hypertrophy, are as susceptible to silent
myocardial ischemia as patients with diabetes (46).
Coronary artery disease is much more common in diabetic hypertensive patients than in
patients suffering from hypertension or diabetes
alone (47). For all 2,681 men in the PROCAM
trial who had none of the three risk factors (i.e.
hypertension, diabetes, or hyperlipidemia), the
coronary artery disease incidence was 6/1,000
in 4 years. In contrast, the incidence of coronary
artery disease in those participants who were suffering from hypertension or diabetes was 14 and
15 per 1,000 in 4 years, respectively. When both
risk factors were present in the same patient, the
incidence rate increased to 48 per 1,000 (47).
Diabetes, and to a lesser extent hypertension, may
alter the perception of ischemic pain, leading to
a high prevalence of silent ischemia. Melina et al.
(35) found a high prevalence of asymptomatic ST
segment depression in diabetic patients with essential hypertension. The number of ST segment
depression episodes was significantly related to
glycosylated hemoglobin levels, left ventricular mass, and ambulatory systolic and diastolic
blood pressure variability and hypertensive peaks.
Hyperlipidemia
Lipoprotein Pattern in Diabetes. The most typical lipoprotein pattern in diabetes, also known as
diabetic dyslipidemia or atherogenic dyslipidemia,
consists of moderate elevation in triglyceride levels, low HDL cholesterol values, and small dense
LDL particles. This lipoprotein pattern is associated with insulin rsistance and is present even before the onset of diabetes. LDL cholesterol levels
in type 2 diabetic subjects are generally similar
to those found in the general population. Small
dense LDL particles are highly atherogenic because of their enhanced susceptibility to oxidative
modification and increased uptake by the arterial
wall. At triglyceride levels > 132 mg/dl, small LDL
particles become common (49). Overall, 3040%
of patients with diabetes have triglyceride levels >
200 mg/dl, and 10% have triglycerides > 400 mg/
111
dl (50). However, in the U.K. Prospective Diabetes Study, despite a high frequency of modestly elevated baseline triglyceride levels (mean baseline
159 mg/dl), a multivariate analysis showed that
triglyceride levels did not predict CHD events.
LDL cholesterol was the strongest independent
predictor of CHD followed by HDL cholesterol,
(51) supporting current national guidelines in
which LDL lowering is the primary lipid target.
Diabetes management
Improving glycemic control in individuals with
moderate to severe hyperglycemia regardless of
type of treatment is associated with improvement
in lipid values. Among the available oral therapeutic options for type 2 diabetes, treatment with
metformin and thiazolidinediones has been associated with beneficial effects on lipids. Metformin has been associated with modest reduction
in triglyceride levels in hyperlipidemic and hypertensive patients (52). In a head-to-head comparison study, (53) pioglitazone was associated with
significant triglyceride reduction, whereas there
was no net triglyceride change with rosiglitazone.
Although both agents increased HDL cholesterol
and LDL cholesterol, pioglitazone was associated
with a greater increase in HDL cholesterol and
less LDL cholesterol increase than rosiglitazone.
Smoking
Smokers with Type 1 and Type 2 diabetes are at increased risk of illness and premature death, mostly
through development of cardiovascular disease,
but other disease processes associated with diabetes may also be made worse by smoking (5455). Smokers with Type 1 diabetes in particular
may have a higher risk of developing kidney disease, and possibly eye and nerve damage as well,
whereas smokers with Type 2 diabetes are more
likely to increase their risk of coronary heart disease, stroke and peripheral vascular disease (56).
Evidence is also accumulating that shows that
smoking is associated with an elevated risk of developing Type 2 diabetes (57-62). A major review
and meta-analysis of published data has found
that current smokers are more likely to develop
diabetes than ex-smokers and never smokers, and
that smokers of 20 or more cigarettes a day are
at greater risk than lighter smokers (63). Overall,
112
current smokers are estimated to have a 44% greater risk, and ex-smokers a 23% greater risk of developing Type 2 diabetes than people who have never
smoked (63). Plausible biological mechanisms for
this association include increased insulin resistance, altered insulin secretion and other impairments to pancreatic function noted in smokers
(63). According to the authors of this review, 'the
relevant question should no longer be whether
this association exists, but rather whether this established association is causal.'(63 p2660) If further research proves a causal relationship between
smoking and Type 2 diabetes, it can be expected
to have a major impact on future estimates of tobacco-caused morbidity and mortality in Australia and globally. Smokers experience a poorer level
of overall general health than non-smokers (64).
Taking into account possible confounding factors
such as alcohol use, socioeconomic background,
age and gender, smokers also report higher levels of tiredness or fatigue, reduced wellbeing and
satisfaction with life, slightly lower self-reported
measures of mental wellbeing, and increased incidence of psychological symptoms such as depressed mood and anxiety. In the elderly, smoking is associated with accelerated declines in
physical function, and increased levels of clinical
illness and physical and cognitive impairment
(64). Smokers are also more likely to report a
history of pain during health examinations (65).
It is understood that the circulation throughout
the body of toxic constituents of tobacco smoke
causes a number of diseases of many organs, as
detailed in the preceding sections. The widespread
distribution of tobacco smoke components may
also be responsible for a more general decrement
in health, through altered inflammatory/immune
processes, oxidative stress and subclinical organ
injury (64). Smokers are also more likely to experience sleep disturbances, including taking longer to
fall asleep, being less likely to stay asleep, and having less total sleep time than non-smokers (66-67).
Smoking and absence from work due to illness.
Smokers are more likely to miss work due to illhealth, have longer duration of absence from work,
and access all levels of medical care more frequently. Work absences are reportedly higher in smokers resulting from a broad range of symptoms,
including problems with the digestive tract, neck,

back and upper limbs. These effects are evident
in younger smokers, before the effects of major
tobacco-caused disease become apparent during
middle age and later years.5 There is also substantial evidence that smokers are more likely to suffer
injury in the workplace than non-smokers (64).
Australian data show that men who smoke are
66% more likely to be absent from work than
male never-smokers, and that female smokers are
23% more likely to miss work than female neversmokers (68). This in turn has a major quantifiable
economic impact on the nation's productivity (69).
Hypoglycaemia
Low blood sugar, also called hypoglycemia, is a
condition that occurs when the amount of sugar in
a patient's blood is lower than normal. Blood sugar
levels less than 70 mg/dL are considered to be dangerously low and may cause damage to the patient's
tissues, reports MedlinePlus, a National Institutes
of Health website (70). Hypoglycemia can cause
a variety of long-term effects or complications.
Deficiencies in Neurodevelopment
Newborn babies, or neonates, who suffer from
recurrent episodes of low blood sugar levels can
develop deficiencies in neurodevelopment, states
an article in the April 1999 issue of the Journal
of Pediatrics (72). Neurodevelopment pertains
to the growth and maturation of the brain and
other aspects of the nervous system. Neonates,
especially premature babies, who have been affected by hypoglycemia, may have reduced
head circumferences and score lower on psychometric tests. These effects can last up to five
years after birth. Even mild to moderate cases
of hypoglycemia in neonates should be treated
promptly to avoid these long-term complications.
Coma
Coma, or chronic loss of consciousness, may be
a long-term effect of hypoglycemia, according to
MedlinePlus (70). Hypoglycemia that results in
coma is commonly called insulin shock. Without adequate levels of blood sugar, the brain is
unable to obtain enough energy to function. Decreased brain function over a long period of time
typically results in coma. Patients in a coma are
unresponsive to external stimuli and may need assistance breathing and ingesting nutrients. Comas
may last between a few hours to several months.
Treating the hypoglycemic disorder usually
brings the patient back to a conscious state (71).
Death
Without sugar, or glucose, the body is unable to
function. Glucose provides much of the energy
the body needs to survive. As blood sugar levels
fall, multiple organs, especially the brain, begin
to fail, warns MayoClinic (71). If left untreated, this condition may lead to death. Patients
must recognize the early signs of hypoglycemia in order to avoid this dreaded outcome (72).
Physical Activity
The possible benefits of physical activity for the
patient with type 2 diabetes are substantial, and
recent studies strengthen the importance of longterm physical activity programs for the treatment
and prevention of this common metabolic abnormality and its complications. Specific metabolic effects can be highlighted as follows (73).
Glycemic control several long-term studies have
demonstrated a consistent beneficial effect of
regular physical activity training on carbohydrate
metabolism and insulin sensitivity, which can
be maintained for at least 5 years (74-75). These
studies used physical activity regimens at an
intensity of 5080% Vo2max three to four
times a week for 3060 min a session (74).
Improvements in HbA1c were generally 1020%
of baseline and were most marked in patients with
mild type 2 diabetes and in those who are likely
to be the most insulin resistant (76). It remains
true, unfortunately, that most of these studies suffer from inadequate randomization and controls,
and are confounded by associated lifestyle changes
(77). Data on the effects of resistance exercise are
not available for type 2 diabetes although early
results in normal individuals and patients with
type 1 disease suggest a beneficial effect (73, 75).
It now appears that long-term programs of regular physical activity are indeed feasible for patients with impaired glucose tolerance or uncomplicated type 2 diabetes with acceptable
adherence rates (79). Those studies with the
best adherence have used an initial period of su113
pervision, followed by relatively informal home

physical activity programs with regular, frequent
follow-up assessments (80). A number of such
programs have demonstrated sustained relative
improvements inVo2max over many years with
little in the way of significant complications (81).
Exercise and Type 1 Diabetes
All levels of physical activity, including leisure
activities, recreational sports, and competitive
professional performance, can be performed
by people with type 1 diabetes who do not have
complications and are in good blood glucose
control (note previous section) (76-78). The
ability to adjust the therapeutic regimen (insulin and medical nutrition therapy) to allow safe participation and high performance
has recently been recognized as an important
management strategy in these individuals (77).
In particular, the important role played by the
patient in collecting self-monitored blood glucose data of the response to physical activity and
then using these data to improve performance
and enhance safety is now fully accepted (73-75).
Hypoglycemia, which can occur during, immediately after, or many hours after physical activity, can be avoided. This requires that the patient
has both an adequate knowledge of the metabolic
and hormonal responses to physical activity and
well-tuned self-management skills (76). The increasing use of intensive insulin therapy has
provided patients with the flexibility to make appropriate insulin dose adjustments for various
activities (79). The rigid recommendation to use
carbohydrate supplementation, calculated from
the planned intensity and duration of physical
activity, without regard to glycemic level at the
start of physical activity, the previously measured
metabolic response to physical activity, and the
patients insulin therapy, is no longer appropriate.
Such an approach not infrequently neutralizes
the beneficial glycemic lowering effects of physical activity in patients with type 1 diabetes (80).
General guidelines that may prove helpful in
regulating the glycemic response to physical
activity can be summarized as follows (73-76):
1. Metabolic control before physical activity
- Avoid physical activity if fasting glucose levels are _250 mg/dl and ketosis is present, and
114
use caution if glucose levels are _300 mg/dl

and no ketosis is present. Ingest added carbohydrate if glucose levels are _100 mg/dl.
2. Blood glucose monitoring before and after physical activity - Identify when
changes in insulin or food intake are necessary. Learn the glycemic response to
different
physical
activity
conditions.
3. Food intake - Consume added carbohydrate as needed to avoid hypoglycemia.
Carbohydrate-based foods should be readily available during and after physical activity.
Because diabetes is associated with an increased
risk of macrovascular disease, the benefit of
physical activity in improving known risk factors
for atherosclerosis is to be highly valued. This is
particularly true in that physical activity can improve the lipoprotein profile, reduce blood pressure, and improve cardiovascular fitness (76).
However, it must also be appreciated that several
studies have failed to show an independent effect
of physical activity training on improving glycemic
control as measured by the A1C test in patients
with type 1 diabetes. Indeed, these studies have
been valuable in changing the focus for physical activity in diabetes from glucose control to that of an
important life behavior with multiple benefits (76,
80). The challenge is to develop strategies that allow individuals with type 1 diabetes to participate
in activities that are consistent with their lifestyle
and culture in a safe and enjoyable manner (78).
In general, the principles recommended for dealing with physical activity in adults with type 1
diabetes, free of complications, apply to children, with the caveat that children may be prone
to greater variability in blood glucose levels. In
children, particular attention needs to be paid to
balancing glycemic control with the normalcy of
play, and for this the assistance of parents, teachers,
and athletic coaches may be necessary. In the case
of adolescents, hormonal changes can contribute to the difficulty in controlling blood glucose
levels (3,54, 70). Despite these added problems,
it is clear that with careful instructions in selfmanagement and the treatment of hypoglycemia,
physical activity can be a safe and rewarding experience for the great majority of children and adolescents with type 1 diabetes (15, 27, 31, 54, 72).
Exercise in the Elderly
Evidence has accumulated suggesting that the

progressive decrease in fitness and muscle mass
and strength with aging is in part preventable by
maintaining regular physical activity (81). The
decrease in insulin sensitivity with aging is also
partly due to a lack of physical activity. Lower levels of physical activity are especially likely in the
population at risk for type 2 diabetes (1, 81). A
number of recent studies of exercise training have
included significant numbers of older patients
(49, 78). These patients have done well with good
training and metabolic responses, levels of adherence at least as good as the general population, and
an acceptable incidence of complications (49). It
is likely that maintaining better levels of fitness

in this population will lead to less chronic vascular disease and an improved quality of life (57).
Conclusion
Majority of patients are at high risk of long-term
complications and comorbidies. It has been
found that increased rate of risk factors have
been found among the study population and
non-significant to sociodemographic differences.
Competing interests
The authors declare no conflicts of interest.
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117
www.jhsci.ba
Dietary calcium intake and osteoporosis

in postmenopausal women living
in Sarajevo area
Amila Kapetanovi1, Dijana Avdi2
Medical Rehabilitation Center Fojnica, Fojnica, Bosnia and Herzegovina. 2 Clinic for orthopedics and traumatology, University
of Sarajevo Clinical Center, Bolnicka 25, Sarajevo, Bosnia and Herzegovina
Abstract
Introduction: Osteoporosis is a multifactorial polygenetic disease of which the genetic determinants are
modulated by hormonal, environmental and nutritional factors. Identification of the risk factors for osteoporosis related to nutrition is important in the prevention and treatment of this disease, considering that these
factors can be modified. The aim of this study was to examine influence of dietary calcium intake on bone
mineral density in postmenopausal women who hadnt a deficit of estrogen in their menstrual history.
Methods: A total of 100 postmenopausal women living in Sarajevo area, aged 50-65 years, without estrogen
deficiency in menstrual history were included in the study. Mineral bone density was measured at the lumbar
spine and proximal femur by DualEnergy Xray Absorptiometry using Hologic QDR-4000 scanner. Examination and control group were formed based on mineral bone density values. The women in the examination
group had osteoporosis. The women in the control group had osteopenia or normal mineral bone density.
Estimates of daily dietary calcium intake were performed based on a Food Frequency Questionnaire.
Results: The average daily intake of dietary calcium among women who had osteoporosis was 967.32 mg,
and in women who hadnt osteoporosis 1195.12 mg. The difference between two groups was statistically significant (p<0.001). There was registered significant correlation between intake of dietary calcium and mineral
bone density in examination (p<0.01) and in control group (p<0.01).
Conclusion: The results of this study have shown that adequate daily intake of dietary calcium in postmenopausal women aged 50-65 years living in Sarajevo area, which hadnt estrogen deficiency in their menstrual
history (in the group of women without osteoporosis amounted to 1195.12 mg) has a positive impact on bone
mineral density.
Keywords: dietary calcium intake, osteoporosis
Introduction
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural
deterioration of bone tissue with a consequent
increase in bone fragility and higher fracture risk
(1). It is considered a multifactorial polygenetic
disease of which the genetic determinants are
modulated by hormonal, environmental and nutritional factors (2). Postmenopausal osteoporosis is related to the loss of gonadal function. The
* Corresponding author: Amila Kapetanovi
Medical Rehabilitation Center Fojnica,
Fojnica, Bosnia and Herzegovina
E-mail: nermin1a@bih.net.ba
Tel: +387 30 838 800; Fax: +387 30 838 848
Submitted: 10 July 2012 / Accepted: 20 August 2012.
118
quantity and quality of the bone after menopause

decreases rapidly resulting in an increased risk
of fractures (3,4). Estrogens are known to play
an important role in regulating bone homeostasis and preventing postmenopausal bone loss (1).
Research results regarding the effect of nutritional,
environmental and lifestyle factors on bone mineral density and on the risk of bone fractures are
not consistent, implying the need for further research which would contribute to providing relief
for this problem. Calcium and vitamin D have received most of the attention directed to diet and
bone health, but there are continuing questions
about their benefits for bone health (5). People in
some geographical areas with low calcium intakes
(Japan) have a low incidence of osteoporotic fracJOURNAL OF HEALTH SCIENCES 2012; 2 (2)
AMILA KAPETANOVI, DIJANA AVDI: DIETARY CALCIUM INTAKE AND OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN LIVING IN SARAJEVO AREA
FIGURE 1. The average age of women without estrogen

deficiency in menstrual history. t = 0.746, no statistically significant
FIGURE 2. Average daily intake of dietary calcium among

women without estrogen deficiency in menstrual history. p<
0.001
tures, in contrast to some populations (Scandinavian countries) where average calcium intakes are
high, have a high incidence of osteoporosis (5, 6).
The recommendations for calcium intake vary
widely among regional agencies. Variability in
calcium intake recommendations can be explained partly by the discrepant results obtained
in observational and interventional studies (7).
Identification of the risk factors for osteoporosis
that are related to nutrition is important in the prevention and treatment of this disease, considering
that these are factors that can be modified. In addition to differences in the incidence of osteoporosis
and osteoporotic fractures among racial groups,
differences within the same race have also been determined as well as differences in conjunction with
age and gender (8-13). Therefore, the importance
of conducting research on osteoporosis within
certain population groups has been confirmed.
The aim of this study was to examine influence
of dietary calcium intake on bone mineral density in postmenopausal women who hadnt a
deficit of estrogen in their menstrual history.
spine and proximal femur by DualEnergy Xray

Absorptiometry using Hologic QDR-4000 scanner.
Estimates of daily dietary calcium intake were performed based on a Food Frequency Questionnaire.
Statistical processing and analysis of data was
conducted. The difference in results was tested by
using appropriate statistical tests of significance
difference (Chi square test, t-test). The coefficient
of linear correlation between dietary calcium intake and bone mineral density was calculated.
Methods
A total of 100 postmenopausal women living in
Sarajevo area (Sarajevo Canton), aged 50-65 years,
without estrogen deficiency in menstrual history
were included in the study. Examination and control group were formed based on mineral bone density values. The women in the examination group
had osteoporosis. The women in the control group
had osteopenia or normal mineral bone density.
Mineral bone density was measured at the lumbar
Results
The average age of women without estrogen deficiency in their menstrual history, in the examination group was 58.64 years, and in the control group
was 57.9 years. There was no statistically significant
differences between these two groups, t = 0.746.
Average daily intake of dietary calcium among
women without estrogen deficiency in menstrual history was, in the examination group
967.32 mg, and in the control group 1195.12
mg. The difference in the average daily intake of dietary calcium between the two
groups was statistically significant, p < 0.001
The coefficient of linear correlation between
T scores and daily intake of dietary calcium
among women without estrogen deficiency
in menstrual history in the examined group
was statistically significant, r = 0.677, p < 0.01.
The coefficient of linear correlation between
T scores and daily intake of dietary calcium
among women without estrogen deficiency
in menstrual history in the control group was
statistically significant, r = 0.615, p < 0.01.
119
TABLE 1. The coefficient of linear correlation between T

score and daily intake of dietary calcium among women without estrogen deficiency in menstrual history
Parameters
Coefficient of linear
correlation
Examination group
Control group
r = 0.677
p < 0.01
r = 0.615
p < 0.01
Discussion
The female reproductive system plays a major role
in regulating the acquisition and loss of bone by the
skeleton from menarche through senescence (14).
Estrogen deficiency (e.g., after menopause) increases the rate of remodeling and the volume of
bone that is resorbed and decreases the volume of
bone that is formed resulting in bone loss and structural decay after menopause (15). Kapetanovi
et al. found a significant association between
menstrual factors (years between menarche and
menopause, years since menopause) and bone
mass loss in Bosnian postmenopausal women (16).
Research results regarding the effect of calcium
intake on bone mineral density and on the risk of
bone fractures are not consistent. Park et al. found
in their research that a high intake of dietary calcium, especially calcium from plant foods reduces
the risk of osteoporosis and increase bone mineral
density in Korean postmenopausal women (17).
Napoli et al. studied the importance of sources of
calcium intake on estrogen metabolism and bone
mineral density in healthy postmenopausal women of white race. Intake of calcium form dietary
sources was associated with higher bone mineral
density than suplement calcium intake. The authors concluded that calcium from dietary sources
may produce more favorable effects in bone health
in postmenopausal women than will calcium from
supplements (18). Ilic et al. have shown that there is
significant correlation between bone mineral density in healthy Caucasian postmenopausal women
and certain nutrients including calcium (19).
Although the antifracture effect of calcium alone
120
is questionable, several observations justify the

recommendation to avoid calcium deficiency in
this age (20). Results of the Feskanich et al. study
showed that total calcium intake in postmenopausal women (through diet and supplementation) was not associated with risk of hip fracture
and that consumption of milk is not associated
with lower risk of hip fracture (compared was intake of 1200 mg / day or more with calcium intake
below 600 mg / day), and that consumption of
milk is not associated with lower risk of hip fracture. Conclusion of their study is that neither milk
nor a high-calcium diet appears to reduce risk
of hip fracture in postmenopausal women (21).
Fardellone et al. have not found a difference in the
average daily calcium intake between women with
and without a diagnosis of osteoporosis or with
and without fractures. The study involved postmenopausal women aged 45 years and over (22).
The results of this study have shown that adequate daily intake of dietary calcium in order
to preserve and promote bone health in postmenopausal women, aged 50-65 years, living in
the Sarajevo Canton, which hadnt estrogen deficiency in their menstrual history, was 1195.12
mg (the group of women without osteoporosis).
Average daily intake of dietary calcium in postmenopausal women which hadnt estrogen deficiency in their menstrual history in the group
of women with osteoporosis was 967.32 mg.
Conclusion
The results of this study have shown that adequate daily intake of dietary calcium in postmenopausal women aged 50-65 years living in
Sarajevo area, which hadnt estrogen deficiency in
their menstrual history (in the group of women
without osteoporosis amounted to 1195.12 mg)
has a positive impact on bone mineral density.
Conflict of interest
Authors declare no conflict of interest
References
(1) World Health organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a
WHO Study Group. WHO Technical Report Series 843; 1994.
(2) Gennari L, Merlotti D, De Paola V,
Calabro A, Becherini L, Martini G,
et al. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J
Epidemiol. 2005;161(4):307-20.
(3) Delaney MF. Strategies for prevention and treatment of osteoporosis during early postmenopause.
Am J Obstet Gynecol, 2006;194(2
Suppl):S12-23
(4) McClung MR. The menopause and
HRT. Prevention and management
of osteoporosis. Best Pract Res Clin
Endocrinol Metab, 2003;17(1):5371
(5) Gueldner SH, Grabo TN, Newman
ED, Cooper DR. Osteoporosis
Clinical Guidelines for Prevention, Diagnosis and Management.
Springer Publishing Company,
2008.
(6) FAO / WHO. Human vitamin and
mineral Requirments. Report of a
joint FAO/WHO expert consultation 2002.
(7) Roux C. The living skeleton. Wolters Kluwer Health France, 2007.
(8) Barrett-Connor E, Siris ES, Wehren
LE, Miller PD, Abbott TA, Berger
ML, et al. Osteoporosis and fracture risk in women of different
ethnic groups. J Bone Miner Res.
2005;20(2):185-94.
(9) Kanis JA, Johnell O, De Leat C,
Jonsson B, Oden A, Ogelsby AK.
International variations in hip fracture probabilities: implications for
risk assessment. J Bone Miner Res.
2002; 17(7):1237-44.
(10) Sambrook P, Kelly P, Eisman J. Bone
mass and ageing. Baillieres Clin
Rheumatol. 1993;7(3):445-57.
(11) Nelson HD, Morris CD, Kraemer
DF, et al. Osteoporosis in postmenopausal women: diagnosis
and monitoring. Evidence Report/
Technology Assessment No.28.
AHRQ Publication No. 01-E032.
Rockville, MD: Agency for Healthcare Research and Quality. January
2001.
(12) Looker AC, Orwoll ES, Johnston
CC, Jr., Lindsay RL, Wahner HW,
Dunn WL, et al. Prevalence of low
femoral bone density in older U.S.
adults from NHANES III. J Bone
Miner Res. 1997;12(11):1761-8.
(13) Looker AC, Melton LJ 3rd, Harris TB, Borrud LG, Shepherd JA.
Prevalence and trends in low femur bone density among older US
adults: NHANES 2005-2006 compared with NHANES III. J Bone
Miner Res. 2010;25(1):64-71.
(14) Clarke BL, Khosla S. Female reproductive system and bone. Arch Biochem Biophys. 2010;503(1):118-28.
(15) Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N
Engl J Med. 2006;354(21):2250-61.
(16) Kapetanovi A, Avdi D, Markovi

K. Uticaj menstrualnih faktora
na gubitak kotane mase kod bosanskih ena u postmenopauzi.
HealthMed, 2007; 1(2): 2-9
(17) Park HM, Heo J, Park Y. Calcium
from plant sources is beneficial to
lowering the risk of osteoporosis
in postmenopausal Korean women.
Nutr Res. 2011;31(1):27-32.
(18) Napoli N, Thompson J, Civitelli R,
Armamento-Villareal RC. Effects of
dietary calcium compared with calcium supplements on estrogen metabolism and bone mineral density.
Am J Clin Nutr. 2007;85(5):1428-33.
(19) Ilich JZ, Brownbill RA, Tamborini
L. Bone and nutrition in elderly
women: protein, energy, and calcium as main determinants of bone
mineral density. Eur J Clin Nutr.
2003;57(4):554-65.
(20) Burckhardt P. Calcium supplementation in the menopause-unnecessary, advisable, or necessary? Ther
Umsch. 2007;64(5):259-63.
(21) Feskanich D, Willett WC, Colditz GA. Calcium, vitamin D, milk
consumption, and hip fractures:
a prospective study among postmenopausal women. Am J Clin
Nutr. 2003;77(2):504-11.
(22) Fardellone P, Cott FE, Roux C,
Lespessailles E, Mercier F, Gaudin
AF. Calcium intake and the risk
of osteoporosis and fractures in
French women. Joint Bone Spine.
2010;77(2):154-8.
121
www.jhsci.ba
Analysis of lipid status, body mass index and

waist-hip ratio in post-menopausal women
Lejla Meali1, Edhem Haskovi2
Women and pregnant women health protection service, Health center Tuzla, Albina Herljevia 1, 75000 Tuzla, Bosnia and
Herzegovina. 2 Department of Biology, Faculty of Science University of Sarajevo, Zmaja od Bosne 33, 71000 Sarajevo, Bosnia
and Herzegovina.
Abstract
Introduction: Menopause is the absence of menses in the period longer that one year. It is widely accepted
that menopause leads to changes in hormonal status, metabolism and lipid profile. The aim of this study was
to analyze the influence of menopause on the concentrations of lipids, lipoproteins and also the influence of
body mass index (BMI) and waist-hip ratio (WHR) on lipid profile in post-menopausal women.
Methods: Sixty post-menopausal women of average age of 52.82 years were compared to a group of 34
pre-menopausal women average age of 47.92 years.
Results: Post-menopausal women had higher, but non significant (p>0.05) concentrations of total cholesterol, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and triglycerides than pre-menopausal women. The concentration of high density lipoproteins (HDL) was significantly lower in post-menopausal
women than pre-menopausal (p<0.05). The concentration of apolipoprotein B was also significantly higher
in post-menopausal women (p<0.05), but the concentrations of apolipoprotein and lipoprotein (a) were lower
but without significance (p>0.05). There was no difference between body mass index (BMI) and waste-hip
ratio (WHR), but the WHR has shown as a significant predictor of the LDL and cholesterol concentrations in
post-menopausal women.
Conclusion: We can conclude that menopause leads to changes in lipid profile by lowering of HDL and
increasing the levels of apolipoprotein B, that increases the risk for cardiovascular disease. The WHR is the
significant predictor of cardiovascular risk in post-menopausal women.
Keywords: menopause, lipid status
Introduction
Menopause is cessation of menstruation in a period longer than one year, and begins with changes
in ovarian function. After menopause, changes in
lipid profile of a woman occur, but not all of those
mechanisms have been explained. One of the important factors in that mechanism is change in adipose tissue distribution. Higher levels of cholesterol, triglycerides, LDL, apolipoprotein B and lower
levels of HDL and apolipoprotein A are characteristic in menopause. The increase of LDL level
is not the only indicator; the composition of LDL
molecules also changes. Participation of low density lipoproteins in menopause rises for 30-40% (1).
* Corresponding author: Lejla Meali, Women and pregnant
women health protection service Health center Tuzla
Albina Herljevia 1, 75000 Tuzla, Bosnia and Herzegovina
Phone: +38761 146 698; Fax: +38735 282 161;
E-mail: lejlamesalic@yahoo.com
Submitted: 15 May 2012 / Accepted: 1 August 2012
122
During menopause, concentration of triglycerides also increases, which is linked to abdominal fat amount increase and insulin resistance.
Menopause causes decrease of HDL concetration
and also changes in HDL structure. The concentration of HDL2 decreases and concentration
of HDL3 increases. HDL concentration is in inverse proportion with level of abdominal fat (2).
Adipose tissue is not just a passive depot of fat
which contains energetic balance and termoregulation, but is also an important endocrine
organ (3). According to contemporary knowledge, adipose tissue cells adipociytes are
multiplying and proliferating during lifetime.
Aside from having different kinds of receptors
and participating in processes of lipogenesis and
lipolysis, adipocytes have high levels of P 450
aromatase enzyme and 17--hydroxysteroid
dehydrogenase, which catalyze processes of
aromatization of androgens into estrogens.
LEJLA MEALI, EDHEM HASKOVI: ANALYSIS OF LIPID STATUS, BODY MASS INDEX AND WAIST-HIP RATIO IN POST-MENOPAUSAL WOMEN
Adipose tissue also produces other hormones

which have autocrine and paracrine functionS, but
mechanisms of autonomous production of hormones in adipose tissue are not yet fully explained.
One of the important adipose tissue hormones is
leptin, with polypeptide structure, which shows
differences in concentration depending on sex
(it is higher in women, especially obese women).
It informs hypothalamus about adipose tissue
amounts in organism and also has influence on
activity of neuropeptide Y and somatostatin. By
decreasing the somatostatin concentration it decreases appetite, regulates the activity of frontal
lobe of hypophysis and also affects metabolism
and energy homeostasis. During menopause, not
only leptin, but also decreased level of growth hormone, estradiol and androgenes, cause changes
in lipogenesis and lipolysis mechanisms, which
leads to characteristic distribution of adipose tissue in menopause (centripetal weight gaining).
These changes increase the risc of cardiovascular
diseases, endometrium cancer and breast cancer.
The increase of body mass in menopause and different distribution of adipose tissue is the result of
changes in estrogen and androgen level in circulation, but also is a result of changes in lipid and
carbohydrates metabolism, reduction of energetic needs and physical activity. Galanin, GnRH,
endogenous opoids and neuropeptide Y have an
important role in stimulating the need for lipid
and carbohydrate intake, while holecystokinin,
glucagon, TRH and calcitonin reduce appetite.
There is small number of studies which investigate relations between lipoprotein concentrations
and different antropometric parameters in postmenopausal women. This study represents an attempt of clarifying this problem by investigating
of a lipid profile in post-menopausal women and
comparison it with a lipid profile in pre-menopausal women. Next, the aim is to investigate what
is the influence of body mass index and waist-hip
ratio on lipid profile in post-menopausal women.
Methods
Patients
This prospective research has been done from September 2000 to September 2004. The sample was a
group of sixty women of average age (52.828.22)
with average menopause length of 49.5635.65

months. Inclusion criteria were: hormone therapy, medications affecting lipid profile, smoking
more than twenty cigarettes per day, body mass
index greater than 35 kg/m2 . Considering that
all women included in study had somatic and
psychological changes related to menopause and/
or painful syndromes related to osteopenia and
osteoporosis, all of them were regularly sent to
gynecological and neuropsychiatric examinations.
Control group was composed of 34 pre-menopausal women with average age of 47.921.66,
who havent been taking any hormone therapy or
medicaments which could affect the lipid profile.
Procedures
Blood sampling was done in Medical Biochemistry Institute at University Clinical Center Tuzla
(UKC Tuzla). Blood was taken from cubital vein.
Total cholesterol concentration, triglyceride concentration, LDL, HDL and VLDL
concentrations
were
determined
determined on Dimension RxL instrument.
Evaluation of gained weight was made on the
basis of Qeuetelet index (Devenport-Kamp
modification) or Body Mass index. On the basis of measurements of waist circumference on
the narrowest area and hip circumference on
the widest area, waist-hip ratio was calculated, according to this formula: WH ratio = waist
circumference (cm) / hip circumference (cm).
Statistical analysis
Calculated values were processed by: arithmetic
mean, standard deviation, Mann Withney U test,
Students test, Pearsons test, Spearman-Ranks
test of correlation, and multiple regression. Statistical significance was established on the level
of differences smaller than 5% and 1%. Statistic
program Data Desk version 6.0 (1997, Data Description, Inc,.USA) was used for data processing.
Results
Total
values
of
cholesterol,
triglyceride, LDL, HDL and VLDL levels in woman of both groups are shown in Table 1.
Total cholesterol concentration in post-menopausal women is a little higher than in premenopausal women, which wasnt statistically
123
TABLE 1. Total values of cholesterol, triglyceride, LDL, HDL

and VLDL levels in blood of post-menopausal and control
group of pre-menopausal women.
important (p>0.05). Triglyceride concentration

in post-menopausal women also wasnt significantly higher (p>0.05). There werent statistically
important differences in LDL concentration between two groups (p>0.05). But, HDL concentration in post-menopausal women was significantly
lower than in pre-menopausal women (p<0.05).
VLDL concentration difference between two
groups wasnt statistically important (p>0.05).
Apolipoprotein A, apolipoprotein B and Lp(a)
concentrations in post-menopausal women and
in pre-menopausal women are shown in Table 2.
Apolipoprotein A concentration in post-menopausal women was lower than in pre-meno-
pausal women , but the difference isnt statistically important (p>0.05). Apolipoprotein
B concentration was significantly higher in
post-menopausal women (p=0.003). Lp(a) concentration in post-menopausal women was
higher than in pre-menopausal women, but statistical difference was not significant (p>0.05).
In group of post-menopausal women BMI
values were 2.55 0.38, and in group of premenopausal women 2.47 0.30, which wasnt
statistically significant difference (p>0.05).
15 women (25%) in menopause had a BMI from
25 to 29.9kg/m2 (which reflects increased risk of
cardiovascular diseases) and 4 women (6.67%)
had BMI from 30 to 34.9 kg/m2 (high risk of cardiovascular diseases). In group of pre-menopausal
women , 11 women (18.33%) had BMI from 25 to
29.9kg/m2. Different adipose tissue distribution
and centripetal weight gaining are characteristic
somatic changes in menopause and are recognized
risk of cardiovascular diseases in women (11).
WHR in post-menopausal women was 0,78
0,05, while in pre-menopausal women it was
0,81 0,07, so there wasnt a significant difference between the groups (p>0,05). In the group
of women in menopause, 2 (3,33%) had WHR
bigger than 0,85 and in the group of women with
regular menstruation, 4 (6,66%) women. Sultan
and associates stated that WHR can be used as
screening for identification of postmenopause
women with increased cardiovascular risk (14).
There wasnt a significant correlation between BMI
and lipid and lipoprotein concentration, as well
as apoilipoprotein and Lp(a), while there was a
FIGURE 1. Correlation between cholesterol concentration

and WHR in post-menopausal women.
FIGURE 2. Correlation between LDL concentration and WHR

in women in menopause
Cholesterol
Triglyceride
LDL
HDL
VLDL
POST-MENOPAUSE
mmol/L SD
6.08 1.14
1.64 0.68
4.12 1.11
1.44 0.41
0.69 0.68
CONTROL
mmol/L SD
5.99 1.44
1.56 0.74
3.99 1.46
1.69 0.50
0.58 0.39
TABLE 2. Total values of apolipoprotein A, apolipoprotein

B and Lp(a) levels in blood of post-menopausal and control
group of pre-menopausal women.
Apolipoprotein A
Apolipoprotein B
Lp(a)
124
POST-MENOPAUSE
g/L SD
1.52 0.27
1.24 0.33
0.28 0.30
CONTROL
g/L SD
1.61 0.28
1.02 0.17
0.24 0.23
FIGURE 3. Correlation between apolipoprotein B concentration and WHR in post-menopausal women.
highly significant positive correlation between

waist-hip ratio and cholesterol concentration
(p<0.01), LDL concentration (p<0.01) and apolipoprotein B concentration (p<0.05) (Figure 1, 2, 3).
The influence of BMI, waist-hip ratio and menopause length on LDL and apolipoprotein concentrations in women in menopause, was examined
by multiple regression analysis. It was established
that waist-hip ratio is statistically the best predictor
(p=0.072). WHR is statistically significant predictor
of LDL and total cholesterol concentration in relation to BMI in the same group of women (p<0.05).
In the group of pre-menopausal women, there is
a highly significant negative correlation (p<0.01)
between WHR and HDL and apolipoprotein A
concentrations, while there was no correlation
between BMI and some lipoprotein fractions.
Discussion
Main findings of our study were: post-menopausal
women have significantly lower HDL concentration in raltion to pre-menopausal women, apolipoprotein B concentration is significantly higher
in women in menopause, WHR is an important
predictor of cholesterol and LDL concentration in
women in menopause, in relation to BMI, which has
not effect on lipid profile of women in menopause.
In contrast to our observations, many other stud-
ies have proved significant deviations in lipid and

lipoprotein concentrations in post-menopausal
women (4- 8). It is important to emphysize that
Lp(a) synthesis is genetically determined and, in
contrast to other lipoproteins, its concentration is
not changed by diet, workout or under influence of
drugs which decrease the concentration of lipids (9).
Lp (a) concentration reduction has been described
in women who used hormone therapies (10).
According to the results of this research, there
wasnt a difference in BMI and WHR between postmenopausal women and pre-menopausal women ,
but WHR appeared to be statistically important
predictor of LDL and cholesterol concentration in
relation to BMI, in women in menopause. Some
similar observations are already published (12, 13).
In the group of pre-menopausal women, there was
a significantly negative correlation between WHR
and HDL and apilipoprotein A concentrations.
Having in mind roles of these two lipoproteins
in causing the cardiovascular diseases, previously
mentioned correlation tells that pre-menopausal
women but higher WHR also are in higher risk of
cardiovascular diseases. By analysing the influence
of centripetal weight gaining in post-menopausal
women and pre-menopausal women but same
BMI, Ozbey and colleagues. have established a
fact that accumulating adipose tissue in abdominal area is an independent risk factor for cardiovascular diseases in both groups of women (15).
Conclusion
Post-menopausal women have significantly
lower HDL concentration in raltion to premenopausal women while apolipoprotein B concentration is significantly higher in women in
menopause. WHR is an important predictor of
cholesterol and LDL concentration in women in
menopause, in relation to BMI, which has not
effect on lipid profile of women in menopause.
125
References
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Dagenais GR, Lupien PJ, Despers
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Y. Small lowdensity lipoprotein
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(6) Goholke-Barwolf C. Coronary artery disease-is menopause a risk

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(7) Guthrie JR, Taffe JR, Lehert P, Burger HG, Dennerstein L. Association between hormonal changes at
menopause and the risk of a coronary evenz: a longitudinal study.
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(8) Berg G, Mesh V, Boero L, Sayegh
F, Prada M, Royer M, Muzzio ML,
Schreier L, Sisele N, Benanacia
H. Lipid and lipoprotein profile in
menopausal transition. Effects of
hormones, age and fat distribution.
Horm Metab Res 2004; 36(4): 215220.
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cardiovascular disease. Atherosclerosis 1994; 108: 111-126.
(10) Esplendad MA, Bush TL, MebaneSims I, Stefanik ML, Johnson S,
Sherwin R, Waclawiw M. Rationale
design and conduct of the PEPI trial. Control Clin Trials 1995; 16:3-19.
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Guo SS, Zeller C, Chunmlea C,
Siervogel RM. Aging, body composition and lifestyle: the Fels Longitudinal Study. Am J Clin Nutr 1999;
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www.jhsci.ba
Does wound infiltration of tramadol reduce

postoperative pain in laparoscopic or open
herniorrhaphy?
Remziye Svac1*, Erol Eroglu2, Lutfi Yavuz2, Fusun Eroglu2, Yaar Svac3
Department of Anesthesiology and Reanimation, Kocatepe University, School of Medicine, Afyon, Turkey. 2 Department of
General Surgery, Suleyman Demirel University, School of Medicine, Isparta, Turkey. 3 Hospital of Pulmonary Disease, Afyon,
Turkey,
Abstract
Introduction: The laparoscopic approach may be associated with more postoperative pain initially. The aim
of this study was to evaluate the effects of administered tramadol at wound closure on postoperative pain
and analgesic requirements under spinal anesthesia in laparoscopic inguinal herniorrhaphy (LH) or tension
free open inguinal herniorrhaphy (TFOH).
Methods: Twenty patients were randomly divided into two groups (n= 10 in each) as LH or TFOH. Patients
received infiltration of 200 mg tramadol with 40 mL of 0.9% saline solution at wound closure procedure.
Postoperative pain was assessed with a Visual Analog Scale (VAS) at 3, 6, 12, and 24 hours postoperatively.
Additional requirements of tramadol for postoperative pain releif were registered.
Results: VAS scores at postoperative 12 and 24 hours were significantly higher according to 3rd hour VAS
scores in both groups. The VAS scores at 12 hours after operation significantly lower in LH group than in
TFOH group (1.5 0.97 vs 5.1 0.99). Additional requirements of tramadol for postoperative pain releif were
significantly lower in LH group.
Conclusion: We conclude that wound infiltration of 200 mg tramadol reduce postoperative pain in LH group.
Keywords: laparoscopy herniorrhaphy, postoperative pain, tramadol
Introduction
Pain after laparoscopic surgery may vary in quality
and localization and is reported in several studies
to be incisional, intraabdominal, or referred (1).
The etiology is complex, including damage to abdominal wall structures, the induction of visceral
trauma and inflammation and peritoneal irritation
because of CO2 entrapment beneath the hemi diaphragms. Pain after laparoscopic procedure is significantly less and shorter than that caused by the
same surgical procedure made possible by open
surgery (2). Compared with open procedures, laparoscopic surgery, a minimally invasive technique,
* Corresponding author: Remziye Sivaci, MD.
Dumlupinar Mh. Turabi Cd. Tutuncu Apt.
B Blok NO: 2/1 D:9 03200 AFYON- TURKEY
Tel: + 90 272 2145511; Fax: + 90 272 2158281
E-mail: remziyesivaci@gmail.com
Submitted 18 May 2012 / Accepted 15 July 2012
is associated with reduced surgical trauma (3).

Anti-inflammatory drugs decrease postoperative
pain as local anesthetics and opioids when administered at the surgical site at time of wound closure.
Tramodol is a centrally acting synthetic analgesic
with -opioid receptor agonist activity. Infiltration of tramadol into the surgical wound reduces
postoperative pain with very few side effects (4).
Patients benefit from laparoscopic extraperitoneal
hernia repair because this allows earlier mobilization than the more classical open surgical approach (5). Laparoscopic inguinal herniorrhaphy
(LH) provides distinct advantages over open herniorrhaphy and it is the treatment of choice for
many patients. LH is associated with less pain and
disability without increasing mortality or overall
morbidity (6-8). Although the effect of wound
infiltration of tramadol following LH provides
better postoperative analgesia than open herni127
REMZIYE SIVACI ET AL.: DOES WOUND INFILTRATION OF TRAMADOL REDUCE POSTOPERATIVE

PAIN IN LAPAROSCOPIC OR OPEN HERNIORRHAPHY?
orrhaphy, this issue is not well documented yet.

The aim of this study was to evaluate postoperative pain relief effects and analgesic
requirements of locally administered tramadol after LH and tension free open herniorrhaphy (TFOH) under spinal anesthesia.
Methods
Twenty ASA physical status I or II patients were
randomized for elective unilateral either LH or
TFOH (n=10 in each). Informed consent was
obtained from each patient. Patients were evaluated as primary inguinal hernia type II-a,b and
III-a according to Nyhus Classiffication. Patients
with renal disease, active peptic ulceration, a history of drug or alcohol abuse, chronic pain states,
or daily intake of non-steroidal anti-inflammatory drugs or opioids were excluded from the
study. Any kind of complications were explained
to all of the patients and informed consent was
provided. All patients were instructed preoperatively about the use of a visual analog pain scale
(VAS) (0= no pain to 10= excruciating pain).
The patients didnt receive any analgesic premedication. Age (year), height (cm) and weights
(kg) were recorded and all patients had received
IV saline infusion (0.09% NaCl, 10 mL kg1) in
the operating room about 20 min before spinal
anesthesia. Standard monitors were included an
electrocardiogram, non-invasive blood pressure
device, and pulse oxymetry. Oxygen was administered to all patients via nasal catheters at rate 2
mL/min. Spinal anesthesia was made with a 26 G
Quincke point needle in the lateral position at the
L4-L5 interspaces. After clear, free flow of cerebrospinal fluid was obtained, 3 mL heavy 0.5% bupivacaine (*Marcaine heavy, Astra Zeneca, England)
was administered intratecally. Patients were then
placed with a supine horizontal position until the
end of the study. Any decrease or increase in baseline systolic blood pressure of more than 20% was
treated and excluded from the study. When a bradycardia or tachycardia occurs then atropine 0.5
mg was given. Data were recorded on a chart recorder. No opioids were given during the operation.
The extra peritoneal laparoscopic hernia repairs
were performed by the same surgeon. A subumblical incision was made and the rectus sheath
was retracted to create a plane between the pos128
terior aspect of the rectus muscle and the peritoneum. A space-maker balloon trochar apparatus
was then introduced and inflated with isotonic
sodium chloride solution (1000 mL) before deflation. The dissection exposed the hernial defect
and allowed placement of the mesh. At the end of
surgical procedure, Tramadol 200 mg in 40 mL of
0.9% saline was injected to the wound locally by
the surgeon. The patients were placed in a 30o sitting position to keep the injected volume in the
ilioinguinal dependent area of the fascial plane.
Data collected that included to time intervals
(minute) duration of spinal anesthesia (bupivacain injection to loss of sensorial level of L2) and
duration of surgery (incision to end of surgery).
Patients were transferred to the recovery room and
observed by nursing staff and have not received
any other analgesics during the study. Postoperative pain was assessed by using a VAS during unassisted mobilization at 3, 6, 12 and 24 hour after
operation. When VAS value was 3, tramadol was
given intramuscularly for postoperative analgesia
and total amount of tramadol were documented
for each patient. Postoperative complications
included nausea and vomiting were also noted.
Statistical analysis
The results were expressed as mean values standard deviation. Mann-Whitney-U was used to
compare VAS scores and total amounts of tramadol as additional analgesic postoperatively
for each patient between two groups. Friedman
test and Wilcoxon test were used for repeated
and related measures. P values less than 0.05 was
considered as statistically significant. The study
was conducted in accordance with the ethical
standards of the Helsinki Declaration of 1975.
Results
Age, height, weight, duration of anesthesia and
surgery were similar in two groups (Table 1).
VAS scores on postoperative periods in the groups
and levels of statistical significance changes according to 3th hour VAS scores were shown in
Table 2. VAS scores at postoperative 12 and 24
hours were significantly higher in both groups.
The significant is greater in TFOH group. The
VAS scores were reduced significantly in LH
group than in TFOH group at 12 hours after

TABLE 1. Patients demographic data and duration of anesthesia and surgery in two groups
Age (yr)
Height (cm)
Weight (kg)
Duration of anesthesia (min)
Duration of surgery (min)
LH (n=10)
49.3 9,8
168.9 7.0
71.2 5.2
80.7 9.1
64.4 8.2
TFOH (n=10)
49.6 8.3
169.1 3.8
75.7 4.9
78.6 9.5
62.6 8.2
LH; laparoscopic herniorrhaphy group, TFOH; tension free open

herniorrhaphy group
TABLE 2. Visual analog scale (VAS) scores on postoperative periods in two groups and levels of statistical significance
changes according to 3th hour VAS scores.
Hours
3
6
12
24
LH (n=10)
TFOH(n=10)
VAS
p
VAS
p
0.8 0.78 (1 [0-2])
1.0 0.94 (1 [0-3])
1.0 0.81 (1 [0-2]) 0.317 1.3 0.67 (1 [0-2]) 0.429
1.5 0.97 (2 [0-3]) 0.020 5.1 0.99 (5 [4-7]) 0.005
5 1.33 (4.5 [3-6]) 0.005 6.4 1.34 (6 [5-9]) 0.005
Data was shown as median [min - max] standard deviation.

p: levels of statistical significance changes according to 3th hour
(Wilcoxon signed ranks).
herniorrhaphy group
TABLE 3. Tramadol requirements in two groups

Tramadol use
None
1 time
2 time
p
LH
n
5
5
0
0.001
TFOH
n
0
3
7
62.6 8.2

herniorrhaphy group
TABLE 4. Nausea and vomiting
Never
Nausea
Vomiting
p
LH
n
9
1
0
0.218
TFOH
n
6
1
3
62.6 8.2

herniorrhaphy group
operation (1.5 0.97 and 5.1 0.99) (Table 2).

Fifteen patients received additional tramadol
postoperatively. There was statistically significant difference between groups for the time to
the first request for tramadol between LH group
and TFOH group; the patients in the TFOH
groups needed additional tramadol earlier than
the patients in the LH group. Tramadol requirements were significantly lower in LH group
while 5 patients never received and 5 patients
received only once after operation (Table 3).
The highest frequency of postoperative nausea and
vomiting (PONV) coincided in early postoperative
period. There were not statistically significant differences between groups in means of PONV (Table 4).
Discussion
Laparoscopic surgery, compared with open procedures, may be associated with diminished surgical trauma response and shortened recovery
time; early postoperative pain after laporoscopic
procedure which is a frequent complaint (9). Saff
et al showed that laparoscopic extraperitoneal
hernia repair with bupivacaine resulted in a lack
of pain-relieving efficacy (5). There are different reasons for pain in extraperitoneal laparoscopic hernia repair based on the afferent source
of pain signals. There is a significant contribution of visceral pain fibers that are more diffuse
in distribution and innervation (5). These fibers
are more refractory to blockade with local anesthetics and nonsteroidal anti-inflammatory drugs
than somatic fibers (2,10). The latter are related to
stimulation of neuronal serotonin release and inhibition of presynaptic reuptake of norephinephrine and serotonin (11). Tramadol is a synthetic
and centrally acting analgesic. It has both opioid
and non-opioid properties. Tramadol has been
shown to have a similar potent effect on pain as
morphin (12). In clinical trials, tramadol has not
displayed the serious side effects typically seen
with the use of opioid analgesics or non-steroidal
anti-inflammatory drugs (13-15). Direct infiltration into the wound is a common form of postoperative analgesia in the surgery because of reduced side effects of the drugs on cardiovascular
and central nervous system (16). Relieving pain in
patients with herniorrhaphy can be problematic.
Inadequate analgesia may delay discharge or pro129

long hospital stay (6). Concerns over the safety of

analgesics often lead physicians to use small doses
of these drugs with consequent sacrifices in efficacy; the respiratory depression, together with the
prevalent nausea and vomiting, caused by opioids.
There is no available literature concerning the
magnitude of pain in LH and TFOH after wound
infiltration of tramadol postoperatively. It is a
general belief that most surgeons thought that
LH causes less postoperative pain than TFOH (2).
We have found that VAS scores at postoperative 12
and 24 hours were significantly higher according
to 3th hour VAS scores in both groups. The VAS
scores were reduced significantly in LH group than
in TFOH group at 12 hours after operation (1.5
0.97 and 5.1 0.99). Pain and postoperative tramadol requirements decreased in group LH. This difference is significant; it also may bias the results toward less pain and need for analgesics in LH group.
Fifteen patients received tramadol postoperatively.
There was statistically significant difference between groups for the time to the first request for
tramadol between LH group and TFOH group;
the patients in the TFOH groups needed additional tramadol earlier than the patients in the LH
group. Tramadol requirements were significantly
lower in LH group while 5 patients never received
and 5 patients received only once after operation.
The recommended systemic dose of tramadol for
postoperative pain is 50 mg intramuscular injection. Morphine produces a prolonged postoperative analgesia, but is associated with major side
effects such as postoperative nausea and vomiting,
in particular the potential of delayed respiratory
depression (15). Clonidine, an alpha 2 adrenergic
agonist, has been shown to potentate postoperative analgesia. Although, clonidine improved the
efficacy of analgesia, it was associated with prolonged sedation. Of all the agents used, wound
infiltration of tramadol seems to show promise
because of the absence of the side effects (18).
Inadequate pain treatment causes discom-
130
fort, prevents sleep and thereby contributes to

postoperative fatigue, delays discharge, and
limits activity, prolong recovery period, and
may induce nausea and vomiting. There were
not statistically significant differences between
groups in means of PONV in this study also.
Yndgaard S. et al., have been shown that analgesic
effect of subfascial infiltration with local analgesic
was observed on postoperative pain after herniorrhaphy. Therefore, using tramadol may provide
better effect is the postoperative pain and less side
effects (19). The results of the VAS score indicate
a negligible effect with a significant level for longlasting period postoperatively when wound infiltration of tramadol was used in LH group. The effect of tramadol is clear: it lasts for a longer period
and is evident during the mobilization. At postoperative 12 and 24 hour, the median VAS score in
LH group decreased than TFOH group. Most of
the patients in the group had not needed analgesic requirements but only a few patients was given
analgesic drug for pain and with low VAS scores
remained in the group. The nausea, vomiting and
sedation, which are frequently associated with the
administration of parenteral opioids and similar
drugs such as tramadol. But, wound infiltration of
these drugs has been found more suitable for use in
a day care setting and postoperative analgesia (20).
Concluson
We conclude that wound infiltration of 200 mg
tramadol provides more long lasting effect for
pain management in LH group without respiratory depression, PONV or other side effects
Acknowledgements
We thank the department of pulmonary medicine in our hospital for the support of statistically
analysis.

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131
www.jhsci.ba
Smoking and BMI as a risk factor of cardiovascular disease at a doctors in Tuzla canton
Merisa Imamovi-Kulugli1*, Fatima Jusupovi2
Health Centre Tuzla, Albina Herljevia 2, 75000 Tuzla, Bosnia and Herzegovina. 2 Faculty of Health Studies, University in
Sarajevu, 71000 Sarajevo, Bosnia and Herzegovina
Abstract
Introduction: Cardiovascular diseases are becoming the leading social and medical problem of civilization,
given the trend indicates an increase of morbidity, disability and mortality from this diseases. The aim of
our study was to determine the frequency of smoking and increased BMI, as a risk factor for cardiovascular
disease in doctors in the Tuzla Canton and correlate values of BMI by the doctor smokers and nonsmokers.
Methods: The study was conducted in 13 medical centers in the area of Tuzla canton in the second quarter
of 2009. Two groups were formed by randomization of 150 doctors non-smokers and 150 doctors smokers
from a total of 366 doctors of both sexes, age over 25 years. The study involved doctors who smoke tobacco
5 or more years. The methods of anthropometric measurements and questionnaires were used in study.
Results: The results showed that the total number of doctors surveyed, 44.81% were smokers, with more
women smokers (28.7%) than men (21.3%) smokers (p=0.011). We found that there is a significant statistical difference between subjects with BMI higher than 25 and subjects with normal weight, in the group of
smokers (p = 0.0001).
Conclusion: It can be concluded that the frequency of smoking in the total number of surveyed doctors, is
significant. The increased value of BMI (over 25) is present in large number of subjects (with the larger percentage subjects of smokers).
Keywords: smoking, BMI, cardiovaskcular disease.
Introduction
Chronic non-infectious diseases, including the
cardiovascular and cerebrovascular diseases are
the leading cause of morbidity and mortality, in
addition to cancer (1). They are a significant cause
of invalidity, loss of working ability, early death
(before 65 years of age) and increasing health care
costs, especially in countries where a high percentage of the population is represented by older
people (2). For these the trend of increasing morbidity, mortality and invalidity from diseases of
circulatory system, it is clear that these diseases
are becoming major public health problem of civilization. According to the World Health Organization, cardiovascular diseases cause 16.7 million
deaths annually (29% of all deaths), more than one
* Corresponding author: Merisa Imamovi-Kulugli,
Health Centre Tuzla, Albina Herljevia 2, 75000 Tuzla,
Bosnia and Herzegovina; Phone: +38761785549
E-mail: merisa.k@bih.net.ba, fatimajusupovic@yahoo.com
Submitted 2 May 2012 / Accepted 28 June 2012
132
third of cardiovascular deaths happens in persons

of middle age (3). According to the reports of the
Public Health Federation (4), in Bosnia and Herzegovina rates of mortality and morbidity of cardiovascular disease is rapidly growing from 60 of last
century, and the indicators for year 2004 and 2005
show that in Bosnia and Herzegovina mortality
rate from cardiovascular disease dominates about
50% of all causes of death and in women and men.
During the 2008 diseases of circulatory system in
Tuzla Canton, participate with 53.5% of total mortality. The mortality rate because of circulatory
diseases in 2008 was 80.55 / 100.000 population
younger than 65 years. Leading disease population
of Tuzla Canton during 2002 to 2008 was headed
the chronic non-infectious diseases, among which
the first are cardiovascular diseases (5). Harming effects of smoking for cardiovascular disease
depends on the quantity of cigarettes smoked per
day and duration of smoking habit (6). The risk
for cardiovascular disease is higher if the start
MERISA IMAMOVI-KULUGLI, FATIMA JUSUPOVI: SMOKING AND BMI AS A RISK FACTOR

OF CARDIOVASCULAR DISEASE AT A DOCTORS IN TUZLA CANTON
smoking before the age of 15. More cohort studies

shows that smokers have two to three times higher
risk for cardiovascular disease than non-smokers
(7). Stopping smoking reduces the risk of cardiovascular disease by about 50% per year, and equal
to the risk of nonsmokers after 5-15 years (8).
From 50th to 90th year's 19th century in many
European countries, the rate (%) doctors of smokers is constantly decreased (9). Fifties of the 19th
century in the U.S. is 55% of doctors smoked,
while in 1993 rate doctors of smokers was only
5% (10). In England, since 1951th to 1994th rate
doctors of smokers dropped from 68% to 7% (11).
Northern European countries is characterized low
frequency of smoking among doctors, on average
7-23% men and 3-15% women doctors of smokers, while the values in the general population
ranged between 30-45%. Countries of Central
Europe was characterized rate doctors of smokers
some higher (20-28% men and 16-25% women),
while the countries of eastern and north-eastern
Europe have had even greater rate doctors of
smokers, almost as general population (30-54%
of men and 40% of women doctors smokers) (9).
Masironi and Arciti (12) have showed, in studies, that 80-85% doctors who do not smoke
or have stopped smoking, always give anti
smoking advice to patients, while less than
50% doctors who smoke also, give advice.
Overweight is one of the biggest public health
problem in the 21 century, especially in some parts
of the world, including the European Region of the
World Health Organization. The risk of disease in all
segments of the population increases progressively
with increasing body mass index (BMI). Since the
1980, prevalence of obesity has increased in many
European countries more than three times (13).
Obesity is no more a problem only of the developed countries, it was become an increasing
problem in developing countries. It is estimated
that today the world's 1.1 billion adults and 10%
of children have an increased body weight (14).
Increased BMI is connected with increased risk of
coronary heart disease (15) and hypertension (16).
Aim of the study is determine frequency smoking among doctors in Tuzla Canton, and
to determine the frequency of increased
BMI as a risk factor of cardiovascular disease in smokers and nonsmokers doctors.
Methods
The research was conducted in 13 health centers
in Tuzla Canton in second quarter of 2009. From
a total of 366 doctors of both sexes, aged over 25
years, method of free chose formed group from
150 doctors smokers and 150 doctors nonsmokers.
In the study involved doctors who smoke tobacco
5 years and over, every day a certain number of
cigarettes (at least 10 cigarettes a day), and excluded doctors who smoke tobacco occasionally,
every second or third day, two to three cigarettes.
The research was a prospective, cross-sectional.
Risk factors were evaluated: smoking and overweight - obesity. It was processed with questionnaire and anthropometric measurements.
Data on risk factors were obtained by the survey. A modified questionnaire referred in part
to general directories, and second part consisted of general information, general relation for smoking, smoking duration, number of cigarettes smoked per day (17, 18).
Body height (cm) was measured by anthropometry,
three times and was calculated as the mean value.
Body weight (kg) was measured by the decimal
scale (100 grams of tolerance), which calibrated before the measurement. The measurement was done
with minimum clothes, three times and calculated
the mean value. Body mass index (BMI) was calculated based on the relation measured body mass
(kg) and body height (cm), as follows: BMI = BW
(kg) / TV (m) 2, whereby as the increased body
weight taken BMI value equal to or greater than
25.0 according to the World Health Organization.
After the survey, made is appropriate encryption
and controls to ensure proper data entry. Data
were entered into the table in Excel, and then
transported into the statistical software package
SPSS17.0. where the after definition of the variables were statistically processed data, and with
the help program Arcus QuickStat completed.
For testing the statistical significance between
groups, we used proportions, Chi square test,
Student's t-test. Statistically significant results we considered those in which the p <0.05.
Results
Of the total number of surveyed doctors
(366) them 202 or 55.19% were non-smokers, and 164 or 44.81% were smokers, a sta133

tistically significant difference (p = 0.005).

Method of random choice formed group
from 150 doctors smokers and 150 doctors
nonsmokers. In the sample from 150 smokers, was 86 or 28.7% women of smokers and 64
or 21.3% men of smokers, as shown in Table 1.
The total number of observed subjects most of
them in the age group between 46 and 55 years
(98 or 32.7%), while the smallest number in the
age group over 65 years (5 or 1.7%). The highest number doctors of smokers in the age group
between 36 and 45, it is 49 or 16.3% of all respondents doctors of smokers, a statistically
significant difference compared to nonsmokers of the same age group (p = 0.0001) (Table 2) .
The mean age of smokers is about 42 (+ -9)
years. The youngest doctor is a smoker aged 25 years and the oldest 73 years.
The total number subjects of smokers largest
number of them is a smoker for 20 years and
TABLE 1. The gender structure of subjects in the sample of
over, in the age group between 46 and 55 years
smokers and nonsmokers
(19 or 12.7%), while at the same age group of 3
or 2% smoked 5 years. Of the total number of
GENDER
smokers, 37 subjects or 24.7% is a smoker 10
Women
Men
Total
years and 33 or 22% is smoke 20 or more years,
Nonsmokers N 90
60
150
% 30.0%
20.0%
50.0%
no statistically significant difference (p = 0.58).
Smokers
N 86
64
150
The total number subjects of smokers most of
% 28.7%
21.3%
50.0%
them women with smoking period of 10 years (30
Total
N 176
124
300
or 20%), and the smallest number of men with
% 58.7%
41.3%
100.0%
smoking period of 10 years (7 or 4.7%), a statistically significant difference (p = 0.0001). Of the
Statistically significant differences by gender in subjects smokers
total number women who smoke 20 or more
(p = 0.011).
years, 19 of them or 12.7% and men
14 or 9.3%, while in the group who
TABLE 2. Age structure in a sample of smokers and nonsmokers
declared to smoked 20 years, women 12 or 8%, while men 19 or 12.7%.
AGE OF SUBJECTS
Th
e total number subjects of smokers
25-35 36-45 46-55 56-65 over 65 No data TOTAL
most
them, in the age group between
Non
N 28
22
53
10
4
33
150
25 and 35 years old, smokes 10 cigasmokers % 9.3% 7.3% 17.7% 3.3% 1.3%
11.0% 50.0%
rettes a day (23 or 15.3%). Of the total
Smokers N 40
49
45
6
1
9
150
number subjects of smokers, them 63
% 13.3% 16.3% 15.0% 2.0% .3%
3.0%
50.0%
or 42% smoked an average of 10 cigaTotal
N 68
71
98
16
5
42
300
% 22.7% 23.7% 32.7% 5.3% 1.7%
14.0% 100.0%
rettes a day and 2 or 1.3% smoked 40 or
more cigarettes a day, which is statistically significant difference (p = 0.0001).
TABLE 3. Distribution of cigarettes smoked per day by sex subjects
A statistically significant difference in
the number subjects who smoked an avwomen men
TOTAL
erage of 10 cigarettes a day (63 or 42%)
not has pleaded N 19
2
21
% 12.7%
1.3%
14.0%
compared to subjects who smoked an av10
N 37
26
63
erage of 40 cigarettes per day (2 or 1.3%)
% 24.7%
17.3%
42.0%
(p = 0.0001), while there was no statisti20
N 28
29
57
cally significant differences among sub% 18.7%
19.3%
38.0%
CIGARETTES
jects who smoked an average of 10 (63 or
PER DAY
40
N 2
5
7
42%) and 20 cigarettes a day (57 or 38%)
% 1.3%
3.3%
4.7%
(p = 0.47). Among subjects who smoke
40 and more
N 0
2
2
an average of 10 cigarettes a day more
% .0%
1.3%
1.3%
is a woman, 37 or 24.7% (men 26 or
TOTAL
N 86
64
150
17.3%), which was significantly higher
% 57.3%
42.7%
100.0%
134

(p = 0.05), while among subjects who smoked an

average of 20 cigarettes day more men 29 of them,
or 19.3% (women 28 or 18.7%), which was not statistically significant difference (p = 0.85) (Table 3).
On the basis of measured height and
weight, we performed recalculation of BMI,
by doctors of smokers and nonsmokers.
Larger number of subjects had a higher BMI
values (over 25), these 170 or 56.7%, of which
90 or 30% doctors of smokers and 80 or 26.7%
doctors of nonsmokers, which is not a significant difference between groups (Table 4).
By doctors of smokers in the highest percentage
(22.3%) was measured higher BMI values. In subjects of smokers with a BMI 25-30 was found to have
more women smokers (28.7%) than men (21.3%)
smokers (p = 0.011). In the same group of subjects
raised the value of BMI from 30-35 was 6.3% of subjects, and 1, 3% of subjects had a BMI from 35-40.
In doctors nonsmokers is similar, with a slightly
smaller percentage, 21.3% of the measured value of higher BMI in the range of 25-30, 4.3% in
the range 30-35 and 1% in the BMI range of 3540. In the group of subjects smoking more subjects with a BMI over 25, 90 of them or 29.9%,
while a BMI of less than 25, were 57 or 19%, a
statistically significant difference (p = 0.0001).
While in the group subjects of non-smokers with
a BMI over 25 were 80 or 26.6%, and of them
65 or 21.7% with a BMI less than 25, it is not

statistically significant difference (p = 0.0781).
Not determined connection frequency between of
obesity-BMI (CHI2 = 0.86, p = 0.35) at tested group.
Mean values of BMI in both groups of patients
were higher, but the test of significance showed
that there was no significant difference among the
groups. Correlating groups subjects of smokers and
nonsmokers in relation to the value of BMI showed
the existence of minor correlation (pc = 0.084).
Discussion
Analyzing, in our study, the frequency of smoking and increased BMI values as risk factors for
cardiovascular disease in 366 doctors in primary
care, both sexes, aged over 25 years, we have found
that smoking among doctors is present in a significant percentage (44.81% ). By Masironu (9) from
50's to 90's of the 19th century in many European
countries, the rate (%) doctors of smokers has
constantly decreased. In the study group of health
workers in the department of pediatrics, gynecology, community health services, and home treatment in Belgrade, smokers were more than in the
our study (58.5%), and 23% nonsmokers (19). In
the total investigated sample of smokers in our
study, it was found that there are more women
smokers (28.7%) than men (21.3%) smokers (p =
0.011), the larger the percentage of survey frequency of smoking in late last century in the
northern countries of Europe (9). In this
TABLE 4. BMI values of doctors smokers and doctors of non-smokers
study characterized the low frequency of
smoking among doctors, an average of
SUBJECTS
7-23% men and 3-15% women doctors
NONSMOKERS SMOKERS TOTAL
of smokers, while the values in the gen17-20
N 5
4
9
eral population ranged between 30-45%.
% 1.7%
1.3%
3.0%
By the same study, the countries of Cen20-25
N 60
53
113
tral Europe is characterized by the rate
% 20.0%
17.7%
37.7%
doctors of smokers slightly higher (2025-30
N 64
67
131
28% men and women 16-25%), which
% 21.3%
22.3%
43.7%
is close to our study, while the countries
30-35
N 13
19
32
BMI
of eastern and north-eastern Europe
% 4.3%
6.3%
10.7%
have had higher rate doctors of smok35-40
N 3
4
7
ers, which is greater than our study and
% 1.0%
1.3%
2.3%
was 30-54% men and 40% women docThere is not N 5
3
8
% 1.7%
1.0%
2.7%
tors of smokers. According to statistical
TOTAL
N 150
150
300
data British Heart Foundation (20) in
% 50.0%
50.0%
100.0%
England in 2004 were 26% men and 23%
of women aged 16 years and over who
(According to WHO BMI over 25 = obesity)
135

smoke cigarettes, which is also similar to our results. Testing that was done in Croatia, in the general population group, it was found that smoking is
more frequent among men than in women, which
is different from our study where a larger percentage of smokers among women (21). Results of
our study confirm that most patients who smoke,
with smoking period of 10 years (24.7%), including more women than men, less is subjects with
smoking period of 20 years and over (20 %). From
the aspect of the amount of cigarettes smoked per
day, we found that most subjects smokers (42%)
smoked 10 cigarettes a day, significantly more
women, slightly less (38%) smoked 20 cigarettes a
day, and 1.3% of those smoking 40 or more cigarettes a day , which is worrying from the aspect
unwanted effects on cardiovascular disease, which
depends on the amount of cigarettes and smoking
period, as showed De Backe et al (6) Manson and
colleagues (22). Among subjects who smoked 20
cigarettes a day slightly leading men than women,
which was not statistically significant difference (p
= 0.85), and is risk of negative effects is present for
both population groups. Our study shows that the
largest number of smokers in the older age group
between 36 and 45 years, which is different from research Kovacic and colleagues (21) which was carried in Croatia in which smoking is most common
in the younger age group between 18 and 25 years.
Results of ATTICA study, conducted in Greece,
confirmed earlier research that obesity is connected with various cardiovascular risk factors such
as diabetes, hypertension and hipercholesteronemia (23), and we have the purpose of estimating
potential risk to our subjects wanted to look and
value BMI. In our study, the increased values of
BMI (over 25) are present in a significant number
subjects (56.7%). In the study in Slovenia, ZaletelKragelj and Fras (24) showed that among the subjects was 40.1% overweight and 38.5% were normal
weight, which is slightly smaller than our results.
Increased levels of BMI in the subjects were smokers in the percentage of 30% and in nonsmokers
26.7%, which is not a significant difference between groups. There was no connection between
the frequency of obesity-BMI (CHI2 = 0.86, p =
0.35) in the investigated group. Values of BMI over
30, in our study had 13% subjects, which is less
than the research was conducted in Croatia by
136
Heim and colleagues (25). In their study showed

that in the adult population has more than 1/5
subjects in whom there a BMI over 30. In our
study the subjects of smokers was measured by
higher BMI values in the range of 25-30, in the
highest percentage (22.3%), while the value the
subjects of nonsmokers the BMI range of 25-30 is
similar, with slightly smaller percentage (21.3 %).
This differs from large epidemiological studies that
show an inverse relationship between smoking
and body mass - smokers are less heavy than nonsmokers (26). From study conducted in Slovenia, it
is clear that among smokers less obesity than nonsmokers. This difference is statistically significant
(27), which differs from the results of our research.
In this research found that there is a significant
statistical difference among to subjects with
higher BMI and those who had a BMI lower than
25, in the group of smokers (p = 0.0001). While
in the group nonsmokers we no found statistically significant difference among to subjects
with higher BMI and less than 25 (p = 0.0781).
Towards WHO data in Europe have obesity 1/3
of adults. The average BMI is 26.5, while the index in Croatia in 2003. totaled 29.9 (25), and in
our study the mean BMI is 26.3 in the group of
smokers and 25.6 in the group nonsmokers. Primary prevention and early detection of risk factors for cardiovascular diseases and their control
are essential. Health workers need to, not only
quit smoking, than to be a major health educators, obliged to actively publish the risk of harmful effects of smoking and other risk factors,
and to transfer knowledge about keeping and
improving health, still from the earliest youth.
Conclusions
This study has shown that the frequency of smoking in the total number of surveyed doctors (N =
366) present in a significant percentage. Smoking is frequently in women than in men, the
majority of doctors smokers in the age group of
36-55 years. Increased levels of BMI (over 25)
are present in a significant number subjects of
both groups (56.7%), of which in most percentage of subjects smokers. In relation to BMI in the
group of smokers there is a significant statistical
difference between those who have an increased
BMI and a satisfactory weight. There was no conJOURNAL OF HEALTH SCIENCES 2012; 2 (2)

nection between the frequency of obesity-BMI

(CHI2 = 0.86, p = 0.35) in the investigated group.
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www.jhsci.ba
The possible role of tumor antigen CA 15-3,

CEA and ferritin in malignant and benign
disease
Nafija Serdarevi1,2, Samira Mehanovi2
1
2
Department of biochemistry, Clinical Center University of Sarajevo, Bolnicka 25, 71000 Sarajevo, Bosnia and Herzegovina.
Faculty of health sciences, University of Sarajevo, Zmaja od Bosne 33, 71000 Sarajevo, Bosnia and Herzegovina.
Abstract
Introduction: Serum CA15-3 has been one of the most reliable tumor markers used in monitoring of breast
cancer patients. To increase its sensitivity, the combined measurement of other tumor markers (CEA and ferritin) with CA15-3 was investigated. The aim of this study was determination of CA 15-3, CEA and ferritin in
female patients with breast cancer, lung cancer and mastitis
Methods: 300 patients with carcinoma, hospitalized at Department of Gynecologic Oncology and Department for Oncology at the University Clinics Center of Sarajevo and 200 healthy subjects were compared.
Results: In patients with breast cancer the mean value of tumor markers were CEA 155.61 ng/mL, CA 15-3
106.38 U/mL and ferritin 197.03 ng/mL. In patients with lung cancer CEA was 58.97 ng/ml, CA 15-3 40.62 U/
mL and ferritin 544.16 ng/mL. Patients with mastitis had CEA 5.17 ng/mL, CA 15-3 112.67 U/mL and ferritin
174.92 ng/mL. The control group had values of tumor markers CEA 1.62 ng/mL, CA 15-3 11.72 U/mL and ferritin 85.35 ng/mL. We found good correlation between CA 15-3 and CEA correlation coefficient was r = 0.750.
There was a low correlation between CA 15-3 and ferritin with correlation coefficient r = 0.274.
Conclusions: The CA 15-3 and CEA are useful markers in patients with confirmed diagnosis of breast and
lung cancers. The ferritin concentration has not increased in patients with breast cancer but it increased in
lung patients. The future study has to make investigations of tumor markers and ferritin in different stage of
breast cancer.
Keywords: CA15-3, CEA and ferritin
Introduction
Although the measurement of tumor markers
in breast cancer has been studied for nearly 20
years, their usefulness remains unclear. In patients with metastatic breast carcinoma, tumor
markers appear to be useful during follow-up,
but a wide range in rates of marker positivity has
been reported: 50%80% (1-3). Breast cancer is
the most common malignancy in women. Successful treatment of breast cancer relies on a better understanding of the molecular mechanisms
involved in breast cancer initiation and progres* Corresponding author: Nafija Serdarevi
Department of biochemistry, Clinical Center University of Sarajevo,
Bolnicka 25, 71000 Sarajevo, Bosnia and Herzegovina,
Tel: +387 33 29 70 00; Fax: +387 33 44 18 15
E-mail: serdarevicnafija@yahoo.com
Submitted 14 June 2012/ Accepted 8 August 2012
138
sion (4). The CA 15-3 concentrations increase was

observed in various malignant tumors, but this is
a useful marker for breast cancer metastasis and
is determined in monitoring disease progression
and success of therapy. It is not used as screening
test or as a test for primary diagnosis because it
has low diagnostic sensitivity (5). CA 15-3 alone,
however, is not recommended as a marker for either diagnosis or detection of early recurrence of
breast cancer according to the American Society
of Clinical Oncology (ASCO) guidelines (6). Because of insufficient data, the ASCO also does not
recommend the use of CA 15-3 alone as a marker
for monitoring response. It should be noted that
the elevation of CA 15-3 between 4 and 6 weeks
after initiation of a new therapy, i.e. spurious early
rise (surge), indicates poor prognosis. The proportion of patients exhibiting a surge in CA 15-3 level
NAFIJA SERDAREVI, SAMIRA MEHANOVI: THE POSSIBLE ROLE OF TUMOR ANTIGEN CA 15-3,
CEA AND FERRITIN IN MALIGNANT AND BENIGN DISEASE
after chemotherapy initiation was reported to be

4.8%, and patients with surge may respond more
poorly to chemotherapy than those without surge
(7). CEA is also not recommended as a marker for
diagnosis or routine surveillance after primary
therapy, and a surge in CEA level may also occur
between 4 and 6 weeks after initiation of primary
treatment. The ASCO does not recommend CEA
measurement in patients with positive CA 15-3;
thus, the CEA level provides only supplementary
information. However, if sufficient data regarding
other factors are available, rising CEA level can
be a useful indicator of treatment failure in patients without measurable disease (8). Efforts are
directed to identify new markers of breast cancer,
which might be used for early detection, staging
and prognosis, and prediction of therapy response.
Ferritin is a large macromolecule (450 kDa) which
is synthesized in the liver, spleen, myocardium,
placenta and other tissues and plays a major role
in iron storage. It consists of 24 subunits which
form protein shell (apoferritin) around an insoluble core of stored iron. There are two types
of subunits, the basic L and acidic H type. Different isoferritins have different proportions of
these two subunits (9). Ferritin is a sensitive indicator of iron deficiency, thus the main clinical
application of serum ferritin measurement is in
differential diagnosis of anaemia. Ferritin concentration may increase in case of iron overload
(haemochromatosis or haemosiderosis), infection
or inflammation, neurodegenerative disorders,
malignancies and destruction of liver tissue (10).
Ferritin is one of the proteins whose concentration
may be altered due to breast cancer presence. Recent studies have suggested a crucial role of perturbations in ferritin levels and tightly associated
with this, the deregulation of intracellular iron
homeostasis; however, the underlying molecular
mechanisms for the cancer-linked ferritin alterations remain largely unknown and often with conflicting conclusions (11). Therefore, this study was
undertaken to define the role of ferritin in breast
cancer. We have make determination of CA 15-3,
CEA and ferritin at patents with breast or lung
cancer and patients with diagnosis of mastitis. At
our investigation we try to find a possible correlation between tumor marker CA 15-3 with tumor
marker CEA and ferritin in patients with cancer.
Methods
Patients
The investigation included patients (n= 500) in period from February till October in 2011. It was retrospective study ant we included female patients
with diagnosis breast cancer, lung cancer or with
diagnosis of mastitis. All of 300 patients were hospitalized at Department of Gynecologic Oncology
and Department for Oncology at the University
Clinics Center of Sarajevo and 200 healthy subjects. The mean age of patients with cancer was
45.32-/+ 9.23, patents with mastitis 35.24 +/- 5.64
and mean age of control group was 43.45 -/+ 2.85.
The patient samples of blood were collected in
serum separation Vacutainer test tubes (Beckton
Dickinson, Rutherford, NJ 07,070 U.S.) in volume of
3.5 mL. We used test tubes with gel. Serum samples
were obtained by centrifugation at 3000 rpm using
centrifuge (Sigma 4-10). After centrifuging, serum
concentration of CEA, CA 15-3 and ferritin was
determined. The investigation was done respecting ethical standards in the Helsinki Declaration.
Chemiluminescent microparticle immunoassay
CMIA
All immunoassays require the use of labeled material in order to measure the amount of antigen or antibody. A label is a molecule that will
react as a part of the assay, so a change in signal
can be measured in the blood after added reagent solution. CMIA is noncompetitive sandwich assay technology to measure analytes. The
amount of signal is directly proportional to
the amount of analyte present in the sample.
Architect ferritin, CEA and CA 15-3 assay is twostep immunoassay to determine the presence
antigen in human serum using CMIA technology. In the first step, sample, assay diluent and
anti-antibody-coated paramagnetic particles are
combined. Ferritin, CEA or CA 15-3 present in
the sample binds to the anti-coated micro particles. After incubation and wash, anti-acridiniumlabeled conjugate is added in the second step. Following another incubation and wash, pre-trigger
and trigger solutions are then added to the reaction mixture. The pre-trigger solution (hydrogen peroxide) performs the following functions:
Creates an acidic environment to prevent
139
early release of energy (light emission).

Helps to keep microparticles from clumping.
Splits acridinium dye off the conjugate bound
to the microparticle complex. This action
prepares the acridinium dye for the next step.
The trigger solution (sodium hydroxide) dispenses to the reaction mixture. The acridinium
undergoes an oxidative reaction when exposed
to peroxide and an alkaline solution. This reaction causes the chemiluminescent reaction to occor. N-methylacridone forms and releases energy
(light emission) as it returns to its ground state.
The resulting chemiluminescent reaction is measured as relative light units (RLU). A direct relationship exists between the amount of ferritin,
CEA or CA 15-3 in the sample and RLU detected
by Architect System optics (8). The normal serum
range of CA 15-3 between 0. 0 31.3 U/mL, CEA
0-5.00 ng/mL and ferritin 4.63 204.00 ng/mL.
Statistical
analysis
The results were statistically analyzed using NCSS
and statistical software SPSS version 12.0 software.
Determined by the average value ( ), standard
deviation (SD), Pearson correlation coefficient
(r), equations of linear regression and Student t
test with statistical significance level of p <0.05.
Results
The CA 15-3 is cancer antigen that is used in the
management of some patients with breast cancer. It is most effective at monitoring metastatic
breast cancer, but has not had high success at
detecting early stage breast cancers. Many studies are still conducted with the purpose of finding markers that could be used for early diagnosis and/or serve as possible reliable prognostic
or predictive parameters, but with conflicting
results. At present, no markers are available for
an early diagnosis of breast cancer. The surveillance of patients with diagnosed breast cancer
the most widely used serum markers are CA 15-3
and CEA which, in combination with other clinical parameters, could have clinical significance.
The raised of serum ferritin concentrations in
breast carcinoma patients might be attributed to
stromal reaction rather than to tumor synthesis.
In our study we have a female patients with diagnosis of breast and lung cancer. The patients with
lung cancer have a primary cancer in breast. The
140
FIGURE 1. The patient diagnosis involved in the study
patients with cancer were hospitalized in Department of Gynecologic Oncology and Department
for Oncology at the University Clinics Center of
Sarajevo. The patients with mastitis were hospitalized in Department of Gynecologic at the
University Clinics Center of Sarajevo. The percent of patients in our study is show in Figure 1.
Abnormal CEA (>5 ng/mL) or CA 15.3 (>30 U/
mL) serum concentrations were found in 15.4%
and 27.2 % of the patients studied, respectively. In
patients with breast cancer the mean value of tumor
markers were CEA 155.61 ng/mL, CA 15-3 106.38
U/mL and ferritin 197.03 ng/mL. Our study have
got results in patient with lung cancer CEA 58.97
ng/ml, CA 15-3 40.62 U/mL and ferritin 544.16
ng/mL. The results of our study have shown that
the patients with mastitis have CEA 5.17 ng/mL,
CA 15-3 112.67 U/mL and ferritin 174.92 ng/mL.
The control groups have value of tumor markers
CEA 1.62 ng/mL, CA 15-3 11.72 U/mL and ferritin 85.35 ng/mL. Serum levels for the three tumor
markers in patients with metastatic diseases were
significantly higher than those in patients without
metastasis. This suggests that serum CA15-3 is the
most reliable monitoring marker in patients with
metastatic diseases. The CEA and ferritin were
high in patients with lung cancer then CA 15-3 and
it could be explain that CEA is more specific for
lungs then CA 15-3. The raises serum ferritin in tumors might be due to tumor synthesis because the
ferritin is reactant of acute phase. The mean value
of tumor marker in our study is shown in Figure 2.
We compared CA 15-3 and ferritin in patients with
FIGURE 2. The mean concentration of CEA. CA 15-3 and

ferritin in patients with tumor and benign disease
cancer in 200 blood samplers (r = 0.274), results is

shown in Figure 3. Regression equation revealed
a slope of 0.5597 and a y axis intercept of 264.64.
The difference between the tumor marker CA 15-3
and ferritin was statistically significant for p <0.05
according Student t-test. The low correlation (r =
0.274) was found between CA 15-3 and ferritin.
The results of our comparison CA 15-3 and CEA are
shown in Figure 4. Regression equation revealed
a slope of 1.4334 and a y axis intercept of 118.39,
correlation coefficient was r = 0.75. The difference
between the tumor markers was statistically significant for p <0.05 according Student t-test. The
coefficient of correlation was r = 0.75, so we have
good found correlation between CA 15-3 and CEA.
FIGURE 3. Comparison of CA 15-3 and ferritin in serum measured by Architect CMIA. The correlation coefficient r = 0.274.
FIGURE 4. Comparison of CA 15-3 and CEA in serum measured by Architect CMIA. The correlation coefficient r = 0.75.
141
Discussion
The results of this study indicate that of the three
tumor markers tested, serum CA15-3 is the most
sensitive and specific in terms of the detection of
breast cancer metastases. In our study the average
concentration of CEA and CA 15-3 was higher
in patients group with primary breast cancer, a
results are shown in Figure 2. The CA 15-3 was
higher in breast cancer but lower than CEA in
lung cancer. The patients with mastitis diagnosis the have higher concentration of CA 15-3 but
normal concentration of CEA. Serum CA15-3
has been one of the most reliable tumor markers used in monitoring breast cancer patients. It
has been reported that the sensitivity and specificity of serum CA15-3 for detecting metastatic
diseases are higher than those of CEA (12,13).
In our study the concentration of CEA was mostly
elevated in patients with breast and lung carcinoma. The recent study has reported that serum
levels of CEA were high at patients with adenocarcinoma and squamous carcinoma (14). The
other investigator has shown that CEA is significantly related to differential degree of lung
cancers (15). The different staining patterns and
positive rates and intensities of CEA may be
helpful for the pathological classification of lung
cancers. The CEA concentration was in reference rage in patients with mastitis and controls.
In this study patients with cancer particularly with
lung cancer have higher concentration of ferritin. This might be due to the potential additional
regulators involved in ferritin synthesis. Iron is
the main, but not the only regulator of ferritin
expression. Hypoxia, often present in neoplastic tissue, is also one of the factors that promote
ferritin increase independently of the iron status
(16, 17). The ferritin concentrations may be a

prognostic indicator in some patients with lungs
and breast cancer. In this study the highest levels
of ferritin were obtained in the group of patients
with advanced disease, which was in agreement
with previous reports (18). The other study groups
have found that ferritin has been previously associated with breast cancer. Still, there is no consistent conclusion regarding its role or relevance in
breast cancer (19). The possible limitation of our
study is that we do not have information about
ferritin level in patients before cancer or mastitis.
Linear regression analysis of the values for the tumor markers revealed that serum CA 15-3 values
were not correlated with serum ferritin values (r =
0.274) but it was good correlation with serum CEA
values (r =0.750). The correlation results are shown
in Figure 3 and 4. In other investigation groups it
was found that good correlation between CA 15-3
and CEA with coefficient of correlation r = 0.96 (20).
Conclusion
Serum concentrations of CEA, CA 15-3, are related to tumor extent, with significantly higher
values seen in patients with breast cancer. The
CA 15-3 is only specific in patients with metastasis because we have got high concentration in
patients with mastitis. The serum value of CEA
was higher in patients with lung cancer. Further
prospective studies, of a large number of subjects
premenopausal and postmenopausal women,
are required to confirm such a statement and to
validate the usefulness of ferritin determination
in the serum of lung or breast cancer patients.
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Measurement of Serum Sialyl Lewis X with
143
www.jhsci.ba
Minimally invasive treatment of iatrogenic

complete left ureter obstruction after
hysterectomy
Yigit Akin1*, Isil Basara2, Aliseydi Bozkurt2
Department of Urology, School of Medicine, Erzincan University, 24040, Erzincan, Turkey. 2 Department of Radiology, Harput
State Hospital, 23050, Elazig, Turkey.
Abstract
The iatrogenic ureter injuries are rare complications and may have serious consequences. The treatment options depend on situations. Pelvic surgeons, keep in mind that this kinds of complications, is very important
for diagnosis and treatment, during the surgery. This report presents a case of a patient with iatrogenic left
ureteral injury during hysterectomy. The patient visited emergency department of our hospital with the chief
complaints of left lomber pain on the 17th day of hysterectomy. After evaluation in emergency clinic, the patient had an endoscopic treatment for iatrogenic ureter injury. The patient is still in follow-up period. We also
review the literature and discuss diagnose, treatment, prognosis of iatrogenic ureter injuries. The treatment
options are still developing by technology.
Keywords: hysterectomy, minimally invasive, surgical procedures, ureteral obstruction, wounds, injuries.
Introduction
The iatrogenic ureteral injuries are rare; this
complication is the one of the most important
complication in gynecological surgery (1). The
injuries almost locate in the distal part of ureter
(2). Quick diagnosis and treatment decrease complication rates (3). Also early diagnosis provides
the best results for treatment (3). There are a lot
of treatment options. When this rare complication applies our clinics, we may prefer minimally invasive treatment options (4-6). Herein, we
present a 62-year-old woman with a complete
left ureter obstruction which was formed by a suture in her ureter with a previous hysterectomy.
clinic. She had big submucous myoma uteri and

after diagnosis, she had a hysterectomy operation
for myoma uteri. On the 17th day of surgery, she
had visited emergency department of our hospital
with the chief complaints of left lumbar pain and
dysuria. Then, physical, laboratory and radiological evaluations were performed. In physical examination she had left lumbar tenderness and pain.
Case report
On April 2011, a 62-year-old woman with complaints of abdominal pain was admitted to our hospital. She was evaluated in gynecology outpatient
* Corresponding author: Yigit Akin,
Department of Urology, School of Medicine,
Erzincan University, Erzincan/Turkey
Tel: +90-506-5334999
e-mail: yigitakin@yahoo.com
Submitted: 15 May 2012/ Accepted: 4 August 2012
144
FIGURE 1. In gray scale US examination, there are dilatations in all calyx system. The level of dilatation is grade 2-3
hydronephrosis.
YIGIT AKIN ET AL.: MINIMALLY INVASIVE TREATMENT OF IATROGENIC COMPLETE LEFT URETER OBSTRUCTION AFTER HYSTERECTOMY
FIGURE 4. Ureteroscopic view of ureter after ureterotomy

was performed. Guide wire is also in the ureter.
FIGURE 2. In IVU, there is complete obstruction in the lower

part of left ureter. Additionally, there is mild dilatation in the
proximal part of ureter.
FIGURE 3. Endoscopic view of the suture (arrow).

The urine test and serum creatinine were normal.

In ultrasonography (US) examination, there was
grade 2-3 hydronephrosis with mild proximal
left ureter dilatation (Figure 1). After ultrasound
(US) examination, intravenous urography (IVU)
evaluation was performed in order to find out the
exact obstruction localization and the reason of
the obstruction (Figure 2). There was not a stone
image in the kidney ureter bladder x-ray examination. There was a complete obstruction in the distal part of left ureter, in nephrogram phase of IVU.
In the light of these findings, we concluded that there
was distal left ureter obstruction which was formed
iatrogenic after hysterectomy operation and we
performed endoscopic evaluation by ureteroscopy.
In ureteroscopy, we could reach the suture material at the left distal ureter (Figure 3). After
that, we cut the suture material with cold ureterotomy and we reached left kidney with semirigid ureteroscopy by using guide wire (Figure 4). Then double j stent was put into ureter.
She discharged at the 1st day after the surgery. We
took off the double j catheter after 1st month of
the surgery.
Discussion
Ureteral injury is one of the rare and serious
complications of gynecologic surgery. The frequency of ureteral injury following gynecologic
145
surgery is approximately 1%, with a higher percentage of injuries occurring during abdominal hysterectomies and partial vaginectomy
(1). Nevertheless, when a ureteral injury occurs,
quick recognition of the problem and a working
knowledge of its location and treatment are essential in providing patients with optimal care.
Ureter lies on anterior of psoas muscle and crosses
over the iliacs and also crosses anteriorly by the
gonadal vessels. Most of the iatrogenic injured
cases do not have any identifiable risk factors.
Endometriosis, uterus size larger than 12 weeks
gestation, ovarian cysts 4 cm or larger, pelvic radiation therapy, anatomic anomalies of urinary
tract, ovarian masses, inflammation of pelvis, pelvic malignancy are the some of the risk factors
which may disrupt of normal pelvic anatomy (2).
The reasons of iatrogenic ureter injury are, misapplication of a clamp, ligation with suture,
transection of ureter, ureteral ischemia form
electrocoagulation, resection of segmental ureter, secondary obstruction of ureter by angulation. Also the combination of all of these reasons may lead the iatrogenic ureter injury (5).
Ureteral injury may be divided as recognized or
unrecognized during surgery. When the iatrogenic injury was diagnosed during the surgery,
the time of urologist starts-up in operation. The
injury may be treated best by urologist with ureteral repair during the same operation. Unilateral
ureteral injuries are occurred nearly 75% of the
cases after the operation (7). If the injury of ureter has occurred and has not been recognized, it
may cause flank pain, chronic ureteral obstruction or formation of fistulas. In our case, the iatrogenic injury had occurred after the surgery.
Then, the injury was diagnosed quickly and it was
treated endoscopic minimally invasive surgery.
As a result of developing technology, laparoscopic and robotic-assisted surgery have been
included to the surgery modalities. Same as
open pelvic surgery, in laparoscopic and robotic-assisted surgery, surgeons should keep
in their minds the iatrogenic ureter injury (8).
If the ureteral injury can be diagnosed intraoperative, intravenous administration of indigo
carmine or methylene blue with furosemide may
help to localize a ureteral injury (1). Extravasation
of blue dye indicates ureteral discontinuity. Also
146
fluoroscopy may help us by administration of contrast substance in ureter and show us the injury or
obstruction zone in ureter. If the ureteral injury
has occurred after surgery, laboratory studies including complete blood count, a electrolyte panel
with serum creatinine and blood urea nitrogen
are needed to distinct for possible infection and
renal failure. In radiological evaluation, renal US,
if the patients serum creatinine levels are normal
IVU, abdominal and pelvic computed tomography
with intravenous contrast may be used. Although
renal US is the best non-invasive method to visualize the kidney and shows hydronephrosis it
cannot be used to assess kidney function or the
continuity of the ureter. Urologists use the IVU
to evaluate for continuity of the ureter in cases of
ureteral injury. Unlike renal ultrasonography and
a retrograde ureteropyelography, IVU is used to
assess for function of the ipsilateral kidney and
the drainage of the ureter in a series of sagittal
images. Hydronephrosis, ureteral integrity, and
any extravasation may usually be seen with IVU.
CT scan can also be used to assess for both function of the ipsilateral kidney and drainage of the
ureter. CT scanning has the advantage of imaging
for concomitant conditions at the same time (5).
The treatment options depend on situation of the
cases. There is no exact medical treatment options
for iatrogenic ureter injuries but some conditions
such as infection, renal failure which belongs to
ureteral injury should be treated medically. The
surgical treatments may range from minimally
invasive treatments to ureteroneocystostomy. The
most common open, laparoscopic or roboticassisted surgical treatments for ureteral injury
are simple removal of a ligature, ureteral stenting, ureteral resection and ureteroureterostomy,
transureteroureterostomy, and ureteroneocystostomy (9-11). Wolf et al. (12) reported long term
excellent results of endoureterotomy. In our case,
we simply removed the ligated suture by endouretetomy and put ureteral stent. If the patients
situation is not suitable for treatment of ureteral
injury the urinary diversion should be perform
by percutaneous nephrostomy catheter. This provides decompression of closed urinary system.
If the obstruction or injury is managed by minimally invasive endoscopic surgery and additionally ureteral stent is put in to ureter, the stent may
be put off 15th day of surgery after uretral healing

and regression of renal hydronephrosis. If psoas
hitch, boari flep, ureteroneocystostomy or other
open surgical procedure are performed, urethral
catheter may be taken off 10th day of surgery and
ureteral stent may be put off 15th-30th day of surgery. In 3rd month of the surgery, the upper urinary system imaging should be performed (11).
We conclude that, this case shows the importance of early diagnosis and treatment of iatro-
genic ureter injury which occurred after surgery. Also this case emphasizes the significance
of ureteroscopy which is a minimal invasive
and effective method in the diagnosis and treatment. In the future, the use of new minimally
invasive technologies will be able to change
the management of iatrogenic ureter injuries.
Competing interests
References
(1) Selzman AA, Spirnak JP. Iatrogenic
ureteral injuries: a 20- year experience in treating 165 injuries. J Urol
1996;155(3): 878-881.
(2) Payne CK. Ureteral injuries in the
female: fistulas and obstruction. In:
Raz S (ed). Female Urology. 2nd ed.
Philadelphia: W.B. Saunders, 1996.
pp. 507-20.
(3) Gilmour DT, Dwyer PL, Carey MP.
Lower urinary tract injury during
gynecologic surgery and its detection by intraoperative cystoscopy.
Obstet Gynecol 1999; 94(5): 883889.
(4) Mate-Kole MO, Yeboah ED, Affram
RK, Ghosh TS. Anuric acute renal
failure due to bilateral accidental
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Ghali AM, El Malik EM, Ibrahim
AI, Ismail G, Rashid M. Ureteric
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Mathews R, Marshall FF. Versatility
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Konigsberg H, Blunt KJ, Muecke EC.
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injuries. Urology. 1975;5(6):751755
Koo HP, Bloom DA. Lower ureteral
reconstruction. Urol Clin North
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Wolf JS Jr, Elashry OM, Clayman
RV. Long-term results of endoureterotomy for benign ureteral and
ureteroenteric strictures. J Urol.
1997;158(3):759-764.
147
www.jhsci.ba
Lebers hereditary optic neuropathy

- case report
Mirjana A. Janicijevic-Petrovic1*, Tatjana Sarenac Vulovic1, Nenad Petrovic1, Suncica Sreckovic1,
Svetlana Paunovic1,Katarina Janicijevic2, Dejan Vulovic2, Dragan Vujic3
Clinic of Ophthalmology Clinical Centre Kragujevac, Zmaj Jovina 30, 34000 Kragujevac, Serbia. 2 Medical Faculty of University
in Kragujevac, Svetozara Markovia 69, 34000 Kragujevac, Serbia. 3 State University of Novi Pazar, Vuka Karadia bb, 36300
Novi Pazar, Serbia.
Abstract
Lebers hereditary optic neuropathy is a neuro-ophthalmological entity characterized by acute or subacute
bilateral, not simultaneous visual loss with centro cekal scotoma and occasional further visual improvement.
This rare ophthalmological disease can be accompanied with dyschromatopsia. It is associated with a matrilineal inheritance pattern. Its diagnosis used to be solely clinical, aided by imaging and neuro-physiological
studies, until the advent of descriptions of mitochondrial biochemical abnormalities and genetic testing. We
describe a case of 24 year old male with progressive painless deterioration of visual acuity and positive family
history.
Keywords: optic neuropathy, Leber, visual acuity
Introduction
Lebers hereditary optic neuropathy is a neuroophthalmological entity characterized by acute
or subacute bilateral, not simultaneous visual
loss with centro cekal scotoma and occasional
further visual improvement. This rare ophthalmological disease can be accompanied with dyschromatopsia. It is associated with a matrilineal
inheritance pattern. Its diagnosis used to be solely
clinical, aided by imaging and neuro-physiological studies, until the advent of descriptions of
mitochondrial biochemical abnormalities and
genetic testing. Primary point mutations occur
at nucleotide positions 3460, 11778 and 14484
of the mitochondrial genome coding for protein
subunits of the respiratory chain complexes. The
11778 mutation is most frequently observed, accounting for 80-90% of described cases.2 Young
males are primarily affected (80-90%), usually in their third decade of life. Females, carriers of the disease, rarely express the symptoms.
* Corresponding author: Mirjana A. Janiijevi-Petrovi
Kneza Miloa 3-1, 34000 Kragujevac, Srbija
Phone: +38166013691
Fax:+38134370073
e-mail:mira.andreja@yahoo.com
Submitted 20 June 2012/Accepted 26 July 2012
148
Case report
A young man adult of 24 experienced a sudden
progressive, painless decreasing of visual acuity of
the right eye. The condition deteriorated over a few
days. He also noticed that the colors when viewed
with the right eye, were extremely pale. The left
on the first examination was with normal visual
acuity. For 22 days visual acuity of the left eye decreased. He had a healthy younger brother, with
no visual disturbances. His mother remembered
that his uncle (her brother) was 23 years old and
had similar problem The patient did not smoke,
nor did he consume any alcohol and was well
nourished. He was not exposed to heavy metals.
At the time of the referral, two months after the
onset of the disease, visual acuity was 0.01 in the
right eye, and 0.1 in the left. During visual field
testing, centrocoecal scotoma on the right eye and
central scotoma on the left eye were found (Figure
1). Subjectively present profound dyschromatopsia could not be objectively proved due to very low
central vision. Pupillary responses were normal,
and relative afferent pupillary defect could not be
detected. There were no signs of intraocular inflammation and intraocular pressure was normal.
Fundoscopic appearance was not impressive. The
only thing that could be seen was slightly tortuous
MIRJANA A. JANICIJEVIC-PETROVIC ET AL.: LEBERS HEREDITARY OPTIC NEUROPATHY CASE REPORT
papillary capillary network and very discrete dilatation and tortuosity of small peripapillary vessels,
more pronounced on the right eye. On fluorescein
angiography, the vessels were intact, with no leakage (Figure 2). Pattern visual evoked potentials
(VEP) were bilaterally almost extinct, with hardly

discernible P100. Retrobulbar part of optic nerve
showed no abnormalities on orbitalechography.
Standard imaging studies (CT, MRI) excluded the
presence of chiasmal or other intracranial mass lesion as well as foci of demyelinisation. The presence of
sarcoidosis, tuberculosis and
syphilis was also excluded
with the appropriate serological tests and chest radiography. Peripheral blood sample
was taken for mitochondrial
DNA (mt DNA) isolation
from leukocytes. A G11778A
mutation was found in leukocyte mtDNA and the mutation was homoplasmic. This
finding confirmed earlier presumptive diagnose of LHON.
Follow-up showed no improvement of central visual
acuity for almost a year, but
thereafter the left eye vision
started to improve. On the last
check-up, 14 months after the
onset of the disease, left eye
visual acuity recovered to 0.7
but the right eye stayed at 0.1.
On ophthalmoscopy, bilateral
profound optic atrophy with
empty, pale discs was found
(Figure 3). On control pattern
VEP there were no changes.
The mother`s leukocyte
mt DNA has already been
FIGURE 1. Centrocoecal scotoma on the right eye and central scotoma on the left eye
isolated and sent for analysis. We hope to get consent
from other family members to perform studies on
their mitochondrial genome.
During outpatient followup, his symptoms have not
increased or decreased, and
he has been medicated using
vitamin C (500 mg t. i. d.), vitamin B1 (5 mg), vitamin B2
(2 mg), vitamin B6 (2 mg),
vitamin PP (20 mg), vitamin
FIGURE 2. Intact vessels on fluorescein angiography
149
FIGURE 3. Bilateral profound optic atrophy with empty, pale discs on ophthalmoscopy
B5 (3 mg), in one tablet, t .i. d, and coenzyme

Q10 (100 mg b .i .d.). The purpose of this supplementation was to improve cellular ATP usage.
Discussion
Hereditary optic neuropathies are a group of diseases with defined clinical presentation and different inheritance patterns. The clinical setting may
be of acute, sub-acute or relentlessly progressive
painless visual loss, bilateral (simultaneous or sequential), with centro cecal scotoma, altered color
perception (dyschromatopsia) and optic atrophy.
The inheritance pattern may present as autosomal
dominant, recessive, X-linked or matrilineal (1).
In Lebers hereditary optic neuropathy, male individuals in their teens or twenties suffer acute
visual loss that is sequential in 78% of cases and
simultaneous in 22% (2). Fundus examination
in the initial stages shows papilledema and peripapillary microangiopathy, evolving to atrophy
of the nerve fiber layer of the retina and finally
leading to optic atrophy and centrocecal scotoma (3). Family history is suggestive of mater150
nal inheritance in 50% of patients, and in the

other 50% the disease seems to be sporadic (4).
Four main mutations of mitochondrial DNA
(mtDNA) encompass over 90% of patients with
Lebers hereditary optic neuropathy: 11778 (genetic subunit ND4), 14484 (ND6), 3460 (ND1) and
14459 (ND6). The mutation at 14459 corresponds
to the dystonia phenotype for Lebers hereditary
optic neuropathy (5). Mashima et al.6 assessed the
prevalence of different mutations in a sample of 80
individuals with Lebers hereditary optic neuropathy and showed that 87% carried the mutation at
11778, 9% at 14484 and 4% at 3460. Riordan-Eva
et al. 2 found prevalence for the same mutations
of respectively 75%, 15% and 8%. Oriental studies
demonstrate higher proportions of 11778 mutations than do Western studies (6,7). Biousse et al.
(8) reported the 14484 mutation on monozygotic
twins with distinct phenotypes (only one symptomatic sibling), while genetic testing in the mother
was negative, thereby suggesting de novo mutation.
Sadun et al. recently published that there is the
strong influence of environmental risk factors,
with smoking as the most common factor (9).

Multiple sclerosis (or MS-like disease) shares a
rather uncommon comorbidity with Lebers hereditary optic neuropathy. Some patients with Lebers hereditary optic neuropathy develop clinical
features that are phenotypically indistinguishable
from multiple sclerosis, and mutations for Lebers
neuropathy are considered to be a risk factor in
the pathophysiology of multiple sclerosis (10,11).
On the other hand, prevalence studies among
multiple sclerosis patients have failed to demonstrate primary mtDNA mutations (12,13). It
is currently recommended to proceed with mt
DNA analysis for all young male multiple sclerosis patients with initial neuro-ophthalmological
manifestations and peripapillary microangiopathy, especially those with bilateral symptoms
and a positive family history for visual los (14).
There is no specific treatment for Lebers hereditary
optic neuropathy. From an empirical standpoint,
most if not all patients will receive an initial diagnosis of optic neuritis and will be treated, without
any response, using steroid therapy at high doses.
In a case-control study with patients carrying mutations 14484, 3460 and 11778, combination therapy using idebenone / vitamin B2/vitamin C (which
improves ATP availability) shortened the time required for vision recovery in the group using this
therapy (11.1 months), in comparison with the

placebo group (17.4 months; p = 0.03) (15). A single-patient study backed by magnetic resonance
spectroscopy of the central nervous system (31PMRS) showed clinical and imaging improvement
When idebenone treatment was instituted (idebenone is not available in Brazil, but only in Argentina:
its action is similar to that of the coenzyme Q10) (16).
The prognosis for vision recovery depends on
the mutation reported. Good prognosis may be
found in up to 50% of patients bearing the 14484
mutation. Nevertheless, only 4% of patients with
the 11778 mutation have gradual improvement,
as we were able to observe in our patient (17).
Conclusion
A diagnosis of Lebers hereditary optic neuropathy should be suspected whenever young males
develop bilateral visual loss, usually sequential,
with a positive familial history. Neuro-ophthalmological examination may demonstrate suggestive signs of Lebers hereditary optic neuropathy. The mutation at the 11778 locus is the
most frequent mutation of mitochondrial DNA
in Lebers hereditary optic neuropathy patients.
References
(1) Kerrison JB. Hereditary optic neuropathies. Ophthalmol Clin North
Am. 2001;14(1):99-107.
(2) Riordan-Eva P, Sanders MD, Govan GG, Sweeney MD, Da Costa J,
Harding AE. The clinical features of
defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995;118(Pt 2):319-37.
(3) Huoponen K. Leber hereditary
optic neuropathy: clinical and molecular genetic findings. Neurogenetics. 2001;3(3):119-25.
(4) Yamada K, Mashima Y, Kigasawa K,
Miyashita K, Wakakura M, Oguchi
Y. High incidence of visual recovery
among four Japanese patients with
with the 14484 mutation. J Neuroophthalmol. 1997;17(2):103-7.
(5) Brown MD, Allen JC, Van Stavern

GP, Newman NJ, Wallace DC. Clinical, genetic, and biochemical characterization of a Leber hereditary
optic neuropathy family containing both the 11778 and 14484 primary mutations. Am J Med Genet.
2001;104(4):331-8.
(6) Mashima Y, Yamada K, Wakakura
M, et al. Spectrum of pathogenic
mitochondrial DNA mutations
and clinical features in Japanese
families with Lebers hereditary
optic neuropathy. Curr Eye Res.
1998;17(4):403-8.
(7) Yen MY, Wang AG, Chang WL,
Hsu WM, Liu JH, Wei YH. Lebers
hereditary optic neuropathy the
spectrum of mitochondrial DNA
mutations in Chinese patients. Jpn
J Ophthalmol. 2002;46(1):45-51.
(8) Biousse V, Brown MD, Newman NJ,

et al. De novo 14484 mitochondrial
DNA mutation in monozygotic
twins discordant for Lebers hereditary optic neuropathy. Neurology.
1997;49(4):1136-8.
(9) Sadun AA, Carelli V, Salomo SR,
et al. Extensive investigation of a
large Brazilian pedigree of 11778/
haplogroup J Leber hereditary optic neuropathy. Am J Ophthalmol.
2003;136(2):231-8.
(10) Chinnery PF, Andrews RM, Turnbull DM, Howell NN. Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance
and expression of the G11778A
mitochondrial DNA mutation? Am
J Med Genet. 2001;98(3):235-43.
(11) Vanopdenbosch L, Dubois B,
DHooghe MB, Meire F, Carton H.
151
Mitochondrial mutations of Lebers

hereditary optic neuropathy: a risk
factor for multiple sclerosis. J Neurol. 2000;247(7):535-43.
(12) Pnisson-Besnier I, Moreau C,
Jacques C, Roger JC, Dubas F,
Reynier P. Sclrose en plaques et
mutations de lADN mitochondrial
associes la maladie de Leber.
(Multiple sclerosis and Lebers
hereditary optic neuropathy mitochondrial DNA mutations). Rev
Neurol (Paris). 2001;157(5):537-41.
(13) Kalman B, Lublin FD, Alder H.
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Mitochondrial DNA mutations

in multiple sclerosis. Mult Scler.
1995;1(1):32-6.
(14) Mojon DS, Herbert J, Sadiq SA,
Miller JR, Madonna M, Hirano M.
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nucleotides 11778 and 3460 in multiple sclerosis. Ophthalmologica.
1999;213(3):171-5.
(15) Mashima Y, Kigasawa K, Wakakura
M, Oguchi Y. Do idebenone and
vitamin therapy shorten the time
to achieve visual recovery in Leber
hereditary optic neuropathy?

(16) J Neuroophthalmol. 2000; 20(3):
166-70.
(17) Cortelli P, Montagna P, Pierangeli G,
et al. Clinical and brain
(18) bioenergetics improvement with
idebenone in a patient with Lebers
hereditary optic neuropathy: a clinical and 31P-MRS study. J Neurol
Sci. 1997;148(1):25-31.
(19) Nakamura M, Yamamoto M. Variable pattern of visual recovery of
Lebers hereditary optic neuropathy.
Br J Ophthalmol. 2000;84(5):534-5.
www.jhsci.ba
Endocarditis lenta-patient survived septic

shock: a case report
Amra Maci-Dankovi1*, Nina Burina1, Mehmed Kuli2,Snjeana Mehani3
The Department of Internal Medicine - Cardiology, General Hospital ''Prim. Dr. Abdulah Naka'', Kranjevieva 12, 71000
Sarajevo, Bosnia and Herzegovina. 2 Heart Center,Clinical Center Sarajevo, Bolnika 25, 71000 Sarajevo. 3 Clinic for Infective
Diseases,Clinical Center Sarajevo, Bolnika 25, 71000 Sarajevo
Abstract
Infective endocarditis is defined as an infection of the endocardial surface of the heart. Its intracardiac effects
include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial
abscesses. This disease still carries a poor prognosis and a high mortality.
A severe case of infective endocarditis with its complications is presented. A man with aortic prosthetic
valve due to earlier aortic stenosis and corrected aortal coarctation and implanted pacemaker presented
with prolonged unexplained fever, malaise, sweating, weight loss (15 kg/4 months) and lumbar pain. He
was treated with broad-spectrum antibiotics prior IE diagnosis was considered. Echocardiogram showed
aortic vegetations and possible periaortal abscess formation. Nonspecific inflammation parameters were
high positive. Cultures were constantly negative. His condition had deteriorated suddenly, and he had presented with worsening of cutaneous vasculitis, subacute glomerulonephritis and subsequent acute respiratory distress syndrome and septic shock. This patient survived with residual bilateral necrosis of the feet and
toxic peroneal paresis. At the end transthoracic echocardiogram showed enlarged heart chambers, LV mild
dilated and concentric hypertrophy with ejection fraction about 40%, degenerative postinflammatory mitral
valve changes, mild mitral regurgitation and tricuspid regurgitation, postinflammatory aortic root fibrosis and
moderate aortic valve stenosis (AVPG max 50,9 mmHg, AVPG mean 24 mmHg) with no pericardial effusion.
Initial suspicion of Q fever was definitely excluded by serological testing showing nonspecific IgM positivity,
probably rheumatoid factor related.
Keywords: Endocardtitis lenta, prosthetic valve infection, septic shock, false positive Q-fever
Introduction
Infective endocarditis (IE) is an interesting disease because of its constant incidence and mortality rate despite advances in both diagnostic and
therapeutic procedures. The diverse nature and
evolving epidemiological profile of IE ensure it
remains a diagnostic challenge (1). Despite improvements in medical and surgical therapy, IE
is still associated with a severe prognosis and remains a therapeutic challenge (2). Different sets
of diagnostic criteria have been used to direct and
standardize case definitions both in clinical practice and in scientific work (3). The clinical history
of IE is highly variable according to the causative
* Corresponding author: Amra Maci Dankovic,
Department of of Internal medicine, General Hospital
Prim. Dr Abdulah Naka, Kranjevieva 12,
71000 Sarajevo, Bosnia and Herzegovina
Tel.: 061/177-743 E-mail: ifsa@bih.net. ba
Submitted: 14 June 2012 / Accepted: 1 August 2012
microorganism, the presence or absence of preexisting cardiac disease, and the mode of presentation. Thus, IE should be suspected in a variety of
very different clinical situations. It may present as
an acute, rapidly progressive infection, but also as
a subacute or chronic disease with low grade fever and nonspecific symptoms which may thwart
or confuse initial assessment. The current in-hospital mortality rate for patients with IE is 15% to
20% with 1-year mortality approaching 40% (3).
Once a disease of young adults with mostly
rheumatic valve disease, IE now has new predisposing factors valve prostheses, degenerative
valve sclerosis, intravenous drug abuse associated with increased risk for bacteriemia, resulting in health care-associated IE. Leading causative organism shifted from predominantly
streptococci to predominantly staphylococci.
According to microbiological findings, the following categories are proposed:
153
AMRA MACI-DANKOVI ET AL.: ENDOCARDITIS LENTA-PATIENT SURVIVED SEPTIC SHOCK: A CASE REPORT
1. IE with positive blood cultures (oral streptococci, enterococci, staphylococci)

2. IE with negative blood cultures because of
prior antibiotic treatment (oral streptococci or
coagulase-negative staphylococci)
3. IE frequently associated with negative blood
cultures (HACEK group Gram-negative bacilli)
4. IE associates with constantly negative blood
cultures (Coxiella burnetii, Bartonella, Chlamydia, Tropheryma whipplei) (1).
The true prevalence of Q fever may be underestimated because this disease can be asymptomatic
in infected individuals. Endocarditis is the most
common manifestation of chronic Q fever (4).
The risk of transformation from acute Q fever to
endocarditis is 40%. C. Burnetii anti-phase I IgG
titers of > 800 are considered to be a major criteria for the diagnosis of endocarditis (5). Most
cases of Q fever are initially misdiagnosed, which
directly results in patients' multiorgan involvement (6). Currently, treatment with long-term
tetracycline and quinolone regimen for at least 4
years is recommended. Patients are considered
cured when IgG antibodies to C. Burnetii phase I
are < 800 and IgM and IgA antibodies are < 50 (7).
According to Duke criteria evidence of endocardial involvement and typical blood culture are
regarded as major criteria, while a predisposing
cardiac condition or recent history of injecting
drug abuse, the presence of temperature of 38.0
or more, defined vascular and immunological
phenomena, blood cultures intermittently positive for microorganisms, and echocardiographic
findings consistent with IE but not meeting major criteria are regarded as minor criteria. The
disease is designated as definite IE if a combination of 2 major criteria, 1 major and 3 minor criteria, or 5 minor criteria is observed. The disease
is also categorized as definite IE if histopathologic
or microbiological evidence of IE is obtained
at surgery or autopsy. Furthermore, an episode
of suspected IE is rejected if a firm alternate diagnosis is found, the symptoms of the patient
resolve with antimicrobial therapy for 4 days or
less, or surgery or autopsy is performed within
4 days after commencing antimicrobial therapy
and no pathologic evidence of IE is obtained. Finally, the case is classified as possible if it can nei154
ther be rejected nor designated as definite IE (8).

Among IE caused by the most frequent microorganisms, IE caused by Staphylococcus aureus affecting left-sided valves carries the worst
prognosis and has a high prevalence of embolic episodes and neurologic involvement. It
is also well known that prosthetic valve IE has
a poorer prognosis than native valve IE (9).
Case report
In November 2011 a 51-year-old man was admitted to General Hospital Sarajevo because of high
fever, sweating, high erythrocyte sedimentation
rate and back pain. Three months prior to admission he has started complaining of pain around inferior scapula angle, profuse night sweats and prolonged fever ( about 38C) and has lost weight (15
kg during this time). He was given paracetamol
and antibiotics (he is allergic to penicillin).
The patient was born with a congenital heart
disease coarctation of the aorta(corrected
in 1980.y in Geneva) and he underwent to replacement of a stenotic bicuspid aortic valve
in 2007. and three years after he has been implanted a pacemaker. Six months prior to admission pacemaker revision was necessary because
of an inflammation at the generator pocket.
On admission to hospital he had no significant
symptoms and fever was not documented. He had
normal hemodynamics and had no peripheral or
renal signs of systemic infection. Transesophageal echocardiogram (TEE) examination ten days
prior to hospitalization showed no signs of prosthetic valve or electrode infections. Heart auscultation revealed mechanical aortic valve click.
Transthoracal echocardiogram (TTE) on admission showed vegetations on aortic prosthetic valve
and possible periaortic abscess formation (Figure
1). Laboratory investigation showed a total white
blood cell count of 9,5x109, hemoglobin level of
117 g/l, platelet count of 405x109, erythrocyte sedimentation rate was 97 mm/h, fibrinogen level and
C reactive protein concentration were constantly
elevated and rheumatoid factor (RF) was positive. Rheumatologic testing was conducted and
serological testing for Q fever was ordered. The
tests revealed positive anti-nuclear antibodies
(ANA) antibodies and F2-IgM Coxiella Burnetiiantibody. Initial therapy with Hiramycin 2x100mg
FIGURE 1. TTE: Suspected aortic abscessus formation
FIGURE 2. TTE: Postinflammatory mitral valve changes
was started and the patient was advised to return

for follow-up in two weeks and for retesting for
Q fever. In this period he was constantly afebrile
and that may led away from bacterial IE diagnosis.
In January 2012 the patient was admitted to
KCUS-Heart Center for reevaluation and repeated
fever . On admission he presented with difficulty
walking due to swollen ankles with petechialpurpuric rash and vesicular-bullous blister around
medial malleolus. INR was 2,75 and TTE revealed
vegetations on mechanical valve. Serologic testing for Q fever revealed F2-IgM and IgG positive.
The patient was redirected to Clinic for Infectious
Diseases. He was prescribed Vancomycin 2x1 g,
Gentamycin 2x80mg, Rifampycin 2x300 mg. TTE
showed diffuse partially mobile vegetations on
the ventricular and atrial side of the mitral valve
(MV) with mild mitral regurgitation (MR), aortic regurgitation (AR) and tricuspid regurgitation
(TR). TEE showed three mobile vegetations on the
ventricular side of the aortic valve (AV) and on the
atrial side of the anterior leaflet of the MV. Cardiosurgeon did not suggest any surgical treatment.
However, his condition deteriorated suddenly, and
he presented with worsening of cutaneous vasculitis, subacute glomerulonephritis and subsequent
acute respiratory distress syndrome (ARDS) and
septic shock. Chest auscultation was significant for
basal bilateral fine crackles. Chest x-ray showed
progressive bilateral infiltrative changes. He was
intubated and mechanically ventilated for six
days. Antibiotic therapy was changed to Doxicyclin 2x100 mg, Tienam 3x1 g, Funzol 1x400 mg
and finally Linezolid 2x600 mg. Third serologic
testing results showed F2-IgM positive, F1-IgG
i F2-IgG negative. It was concluded that it was a
false positive reaction and Q fever was deffinitely
exc luded. In addition our patient developed left
femoral vein thrombosis and lymphoedema in his
right arm with possible superficial vein thrombosis. TEE showed vegetation on artificial valve
but patient was hemodinamically insufficient
and no definitive surgical therapy was indicated.
After stabilization he was discharged from Intensive Care Unit and sent back to Heart Center. Subsequent laboratory investigation showed
high cytoplasmic (classical) antineutrophil cytoplasmic antibodies (c-ANCA) which led to
suspect Wegener's granulomatosis and corticosteroid therapy was administrated (Medrol
1x12 mg). It was not conclusive because of no
evidence of upper respiratory involvement.
At the end TTE showed enlarged heart chambers, LV mild dilated and concentric hypertrophy with ejection fraction about 40%, degenerative postinflammatory MV changes(figure
2), mild MR and TR, postinflammatory aortic
FIGURE 3. Postinflammatory moderate prostetic aortic valve

stenosis
155
FIGURE 4. TEE : Postinflammatory aortic root fibrosis
root fibrosis(figure 4) and moderate AV stenosis (AVPG max 50,9 mmHg, AVPG mean 24
mmHg)-(Figure 3) with no pericardial effusion.
Because of bilateral necrosis of the feet plastic surgeon recommended surgical treatment.
The patient was discharged with bilateral toxic peroneal paresis treated with gabapentin.
Discussion
We presented a case of culture-negative IE with
multiple episodes of recurrent fever, vegetation
formation on the prosthetic aortic valve, thromboembolic incidents through the whole body and
subsequent complication development. Initial suspicion of Q fever was definitely excluded by serological testing showing nonspecific IgM positivity,
probably RF related. Later Wegener's granulomatosis diagnosis was dismissed because no evidence
of upper respiratory tract involvement was found.
IE has showed to be a great challenge to diagnose
because of its non-specific symptomatology. Patients may therefore present to a variety of specialists who may consider a range of alternative diagnoses including chronic infection, rheumatologic
and autoimmune disease, or malignancy. Classic
textbook signs may still be seen in the developing world, although peripheral stigmata of IE are
increasingly uncommon elsewhere, as patients
generally present at an early stage of the disease.
However, vascular and immunological phenomena such as splinter hemorrhages, Roth spots, and
glomerulonephritis remain common, and emboli
156
to the brain, lung or

spleen occur in 30%
of patients and are
often the presenting feature (2). In a
febrile patient, the
diagnostic suspicion
may be strengthened
by laboratory signs
of infection, such as
elevated C-reactive
protein or sedimentation rate, leukocytosis, anemia, and microscopic hematuria.
TTE/TEE
are
now
ubiquitous
and their fundamental importance in diagnosis, management, and follow-up of IE is clearly
recognized. Echocardiography must be performed rapidly, as soon as IE is suspected. Three
echocardiographic findings are major criteria in the diagnosis of IE: vegetation, abscess,
and new dehiscence of a prosthetic valve (1).
The sensitivity of TTE ranges from 40 to 63% and
that of TEE from 90 to 100%. However, diagnosis may be particularly challenging in IE affecting intracardiac devices, even with use of TEE.
Identification of vegetations may be difficult in
the presence of preexisting severe lesions (mitral valve prolapse, degenerative calcified lesions,
prosthetic valves), if vegetations are very small
(,2 mm), not yet present (or already embolized),
and in non-vegetant IE. In cases with an initially
negative examination, repeat TTE/TEE must be
performed 710 days later if the clinical level of
suspicion is still high. Multislice computed tomography (CT) has recently been shown to give
good results in the evaluation of IE-associated
valvular abnormalities, as compared with TEE,
particularly for the assessment of the perivalvular extent of abscesses and pseudoaneurysms (1).
The American Heart Association encourages
acquiring blood cultures promptly when diagnosing infective endocarditis. In fact, a positive
blood culture is a major diagnostic criterion for
infective endocarditis. Most patients with infective endocarditis will yield a positive culture.
However, low-grade bacteremia (less than 50
colony-forming units per milliliter of blood)

is a common occurrence. In these cases of lowgrade bacteremia, the administration of antibiotics before obtaining blood cultures may affect
bacterial growth in the sample and hinder the
ability to appropriately tailor therapy to the offending pathogen (10). Bacterial culture is integral to microbiological practice, since it enables
empirical treatments to be refined to agents that
may be less toxic, cheaper, or more effective (11).
Blood culture negative infective endocarditis
(BCNIE) occurs in 2.531% of all cases of IE, often delaying diagnosis and the initiation of treatment, with profound impact on clinical outcome.
BCNIE arises most commonly as a consequence
of prior antibiotic administration, underlying the
need for withdrawing antibiotics and repeat blood
cultures in this situation. An increasingly common scenario is infection by fastidious organisms
with limited proliferation under conventional culture conditions, or requiring specialized tools for
identification. These organisms may be particularly common in IE affecting patients with prosthetic valves, indwelling venous lines, pacemakers,
renal failure, and immunocompromized states (1).
Cardiac device related infective endocarditis (CDRIE) is defined as an infection extending to the
electrode leads, cardiac valve leaflets, or endocardial surface. CDRIE must be suspected in the
presence of unexplained fever in a patient with a
cardiac device (CD). In the majority of patients,
CDRIE must be treated by prolonged antibiotic therapy associated with device removal (1).
Surgical treatment is used in approximately
half of patients with IE because of severe complications. Reasons to consider early surgery
in the active phase, i.e. while the patient is still
receiving antibiotic treatment, are to avoid
progressive heart failure (HF) and irreversible structural damage caused by severe infection and to prevent systemic embolism (1).
Perivalvular extension of IE is the most frequent
cause of uncontrolled infection and is associated
with poor prognosis and high likelihood of need
for surgery. Perivalvular complications include
abscess formation, pseudoaneurysms, and fistulae.
Surgery is indicated when fever and positive blood
cultures persist for several days (710 days) despite

an appropriate antibiotic regimen and when extracardiac abscesses (splenic, vertebral, cerebral, or
renal) and other causes of fever have been excluded.
Embolic events are a frequent and life-threatening complication of IE related to the migration
of cardiac vegetations. The decision to operate
early for prevention of embolism must take into
account the presence of previous embolic events,
other complications of IE, the size and mobility
of the vegetation, the likelihood of conservative
surgery, and the duration of antibiotic therapy (1).
Conclusion
Signs and symptoms of an IE can be very unspecific making the diagnosis, treatment and
prognosis challenging. The presented case of
a prolonged, initialy unexplained febrile state
was treated with broad-spectrum anibiotics without previously taking the appropriate
samples for cultures that reduced the chances of identifying causative microorganism.
We
believe
that
contamination
was
made
by
superfitial
dermal
Staphyllococcus at the time of CD implantation.
Good response to Linezolid therapy leads to
believe that probably causative organisam is
Staphyllococcus aureus which had spead hematogenously to most vulnerable prosthetic
aortic valve (PAV) and then on to MV giving
clinical presentation of endocarditis lenta. Metastatic abscesses and distal necrosis in an septic environment can be very serious subsequent events.
This interesting case of false positive Q fever can be explained with positive RF
which is also an IgM molecule and is positive in 50% cases of systemic infections.
Detailed early evaluation and interdisciplinary action is a key point to correct diagnosis and early
treatment of IE before metastatic and local serious
complications. Different course of action might
bring faster diagnosis and better survival rate
with patients' fewer consequences in the future.
157
References
(1) European Society of Cardiology.
Guidelines on the prevention, diagnosis, and treatment of infective
endocarditis (new version 2009).
ESC Guidelines. European Heart
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(2) Botelho-Nevers E, Thuny F, Casalta JP, Richet H, Gouriet F, Collart F et al. Dramatic reduction
in infective endocarditisrelated
mortality with a managementbased approach. Arch Intern Med.
2009;169(14):1290-1298.
(3) Murdoc D, Corey GR, Hoen B,
MiroJM, Fowler VG Jr, Bayer AS
et al. Clinical presentation, etiology,
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Arch Intern Med. 2009;169(5):463473.
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Landais C, Fenollar F, Thuny F,
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44:1337-1340.
Li-Juan Z, Xin-ping FU, Jing-shan
Z. Q fever endocarditis with multiorgan complication: a case report.
Chin Med J. 2006; 119 (18):15801582.
Raoult D, Houpikian P, Dupount HT, Riss JM, Arditi-Djiane J,
Brouqui P. Treatment of Q fever endocarditis. Arch Intern Med. 1999
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Heiro M, Nikoskelainen J, Hartiala
JJ, Saraste MK, Kotilainen PM. Diagnosis of infective endocarditis

sensitivity of the Duke vs von
Reyn criteria. Arch Intern Med.
1998;158:18-24.
(9) Tornos P, Almirante B, Mirabet
S, Permanyer G, Pahissa A, SolerSoler J. Infective endocarditis due
to Staphylococcus aureus: deleterious effect of anticoagulant therapy.
Arch Intern Med. 1999;159:473475.
(10) Shands at the University of Florida.
Drugs & Therapy Bulletin. 2006
Nov/dec; 20 (10). Available from:
http: //www.shands.org/professionals/druginfo/bulletins/1006.pdf.
(11) Varley AJ, Jumoke Sule, Absalom
AR. Priciples of antibiotic therapy.
BJA:CEACCP. 2009; 9 86). Available from: http: // ceaccp.oxfordjournals.org/content/9/6/184.full.
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International System of Units (SI).
www.jhsci.ba
UPUTSTVO AUTORIMA
Upute i smjernice autorima za pripremu i predaju rukopisa u Journal of Health Sciences
Ciljevi i okvir asopisa
The Journal of Health Sciences (JHSci) je internacionalni asopis
na engleskom jeziku, koji objavljuje orginalne radove iz oblasti fizikalne terapije, medicinsko-laboratorijske dijagnostike, radioloke
tehnike, sanitarnog inenjerstva, zdravlja i ekologije, zdravstvene
njege i terapije, te drugih srodnih oblasti.
Vrste znanstvenih radova koje se mogu poslati za objavljivanje
u JHS
Orginalni radovi: orginalne laboratorijske eksperimentalne i klinike studije ne bi trebao prelaziti 4500 ukljuujui tabele i reference.
Prikaz sluajeva: prezentacije klinikih sluajeva koji mogu sugerisati kreiranje nove radne hipoteze, uz prikaz odgovarajue literature. Tekst ne bi trebao prelaziti 2400 rijei.
Pregledni lanci: lanci afirmiranih znanstvenika, pozvanih da ih
napiu za asopis. Redakcija e, takoer, razmatrati i samostalne
aplikacije.
Uvodnici: lanci ili kratki uvodniki komentari koji predstavljaju
miljenja prepoznatih lidera u medicinskim istraivanjima.
Podnoenje rada za objavljivanje
Rad koji se alje u JHSci mora biti u skladu sa propozicijama o sadraju, izgledu i kvalitetu, koje je urnal propisao u ovim instrukcijama za autore i na web stranici urnala, www.jhsci.ba. Propozicije
o sadraju, izgledu i kvalitetu naunog rada u skladu su sa meunarodnim propozicijama i preporukama datim od strane International Committee of Medical Journal Editors. Uniform Requirements
for Manuscripts Submitted to Biomedical Journals New Engl J
Med 1997, 336:309315 (www.icmje.org), te preporuka meunarodnih radnih grupa za standardizaciju izgleda i kvaliteta naunih
radova: STROBE (www.strobe-statement.org) , CONSORT (www.
consort-statement.org), STARD (www.stard-statement.org) i drugih.
Predloci
JHSci je pripremio predloke (engl. template) za izgled i sadraj
naunog rada. Predloci sadre sve neophodne podnaslove i obogaeni su uputama o sadraju svakog poglavlja naunog rada, te e
autorima znatno olakati proces pisanja rada. JHSci preporuuje
koritenje predloaka za pisanje naunih radova koji se nalaze na
web stranici urnala www.jhsci.ba u dijelu Information for authors.
autori ele predstaviti rukopis, pismo ili dijelove koji ne mogu biti
poslani elektronski, ili je to zatraeno od urednitva. Za autore koji
nemaju mogunost elktronskog slanja rada, potrebno je poslati
potom jedan primjerak rada, zajedno s elektronskom verzijom na
CD-u ili DVD-u na sljedeu adresu: za Journal of Health Sciences,
Fakultet zdravstvenih studija Univerziteta u Sarajevu, 71000 Sarajevo, Bolnika 25, Bosna i Hercegovina.
Pravila redakcije
Autorstvo
Svi autori morati potpisati formular za podnoenje rada (Manuscript Submission form). Potrebno je da svi autori potpisom potvrde
da: su zadovoljili kriterije za autorstvo u radu, utvreno od strane
International Committee of Medical Journal Editors; vjeruju da
rukopis predstavlja poteni rad i da su u mogunosti potvrditi valjanost navedenih rezultata. Autori su odgovorni za sve navode i
stavove u njihovim radovima. Vie informacija se moe dobiti na
(http://bmj.com/cgi/collection/authorship).
Plagijarizam ili dupliciranje objavljenog rada
Od autora se zahtjeva da svojim potpisom potvrde da u momentu
podnoenja rad nije objavljen u sadanjem obliku ili bitno slinom
obliku (u tampanom ili elektronskom obliku, ukljuujui i na web
stranici), da nije prihvaen za objavljivanje u drugom asopisu ili
razmatran za objavljivanje u drugom asopisu. Meunarodni odbor urednika medicinskih asopisa dao je detaljno objanjenje ta
jeste, a ta nije duplikat (www.icmje.org). Vie informacija moe se
nai i na stranici www.jhsci.ba.
Formular saglasnosti bolesnika
Zatita prava pacijenta na privatnost je od iznimnog znaaja. Autori trebaju, ako redakcija zahtjeva, poslati kopije formulara Suglasnosti bolesnika iz kojih se jasno vidi da bolesnici ili drugi subjekti
eksperimenata daju doputenje za objavljivanje fotografija i drugih
materijala koji bi ih identificirali. Ako autori nemaju potrebnu saglasnost za istraivanje, moraju je dobiti ili iskljuiti podatke koji
identificiraju subjekte, a za koje nisu dobili saglasnost.
Odobrenje Etikog komiteta
Autori moraju u formularu za podnoenje rada i u dijelu rada
Metode jasno navesti da su studije koje su proveli na humanim
subjektima, odnosno pacijentima, odobrene od strane odgovoarajueg etikog komiteta. Vie informacija moete nai u najnovijoj verziji Helsinke deklaracije (http://www.wma.net/e/policy/
b3.htm). Isto tako, autori moraju potvrditi da su eksperimenti koji
ukljuuju ivotinje provedeni u skladu sa etikim standardima.
Pismo za podnoenje rada

Svi autori rada moraju potpisati formular za podnoenje rada. On
sadri odobrenje za publiciranje poslanog rada, izjavu o sukobu
interesa, izjavu potivanju etikih principa u istraivanju i izjavu o
prijenosu autorskih prava na JHSci. Ovaj formular se mora preuzeti
sa web stranice www.jhsci.ba u dijelu Information for authors, te
odtampati, popuniti i skenirati. Ukoliko se skeniranjem dobiju dva
ili tri fajla, moraju se pretvoriti u jedan ZIP fajl.
Izjava o sukobu interesa

Od autora se zahtjeva da navedu sve izvore finansijske pomoi koje
su dobili za istraivanje (grantovi za projekte, ili drugi izvori finansiranja). Ako ste sigurni da nema sukoba interesa, onda to i navedite kratko. Za vie informacija pogledajte uvodnik u British Medical
Journal, 'Beyond conflict of interest' (http://bmj.com/cgi/content/
short/317/7154/291).
Slanje rada
Vri se iskljuivo preko web stranice www.jhsci.ba preko predvienog web formulara. Web formular sadri etiri stranice na kojima
se nalazi: 1. popis stavki koje treba ostvariti prije podnoenja rada;
2. informacije o autoru za korespondenciju; 3. informacije o naunom radu; 4. dio za slanje fajlova. U web formularu autori su duni
ispravno popuniti informacije, unijeti ispravnu e-mail adresu za
korespondenciju, te poslati 2 fajla: 1. Pismo za podnoenje rada;
2. Nauni rad. NIJE POTREBNO slati tampanu verziju, osim ako
Izdavaka prava
U okviru Pisma za podnoenje rada od autora se zahtjeva da prenesu izdavaka prava na Fakultet zdravstvenih studija. Prijenos izdavakih prava postaje punovaan kada i ako rad bude prihvaen
za publiciranje. ira javnost ima prava reproducirati sadraj ili listu
lanaka, ukljuujui abstrakte, za internu upotrebu u svojim institucijama. Saglasnost izdavaa je potrebna za prodaju ili distribuciju
van institucije i za druge aktivnosti koje proizilaze iz distribucije,
ukljuujui kompilacije ili prijevode. Ukoliko se zatieni materijali
161
UPUTE I SMJERNICE AUTORIMA ZA PRIPREMU I PREDAJU RUKOPISA U JOURNAL OF HEALTH SCIENCES
koriste, autori moraju dobiti pismenu dozvolu izdavaa i navesti

izvor, odnosno referencu u lanku.
Formatiranje (izgled) rada
Predloci (engl. template) za pisanje radova
JHSci je na svojoj web stranici www.jhsci.ba dao predloke (engl.
Template) prema kojima treba formatirati radove. Predloci, takoer, sadre i upute preuzete od strane radnih grupa za standardiziranje formata u pisanju naunih radova i objektivno i potpuno
prikazivanje rezultata studija. Vie informacija o strukturi naunih
radova moe se nai na web stranici www.jhsci.ba i na web stranicama radnih grupa: www.consort-statement.org, www.strobe-statement.org, www.stard-statement.org, i drugih. Predloci se mogu
preuzeti na sljedeem linku: http://jhsci.ba/information-for-authors.html
Skraenice i simboli
Skraenice se moraju definisati prilikom njihovog prvog pojavljivanja u tesktu. One koje nisu internacionalno i generalno prihvaene
trebaju se izbjegavati. Koristiti standardne skraenice. Potrebno je
izbjegavati skraenice u naslovu rada i u saetku.
Kljune rijei
Nakon abstrakta treba staviti 3-10 kljunih rijei ili kratkih fraza
koje e pomoi u indeksiranju rada. Uvijek kada je to mogue, treba koristiti termine iz Medical Subject Headings liste Nacionalne
Medicinske Bibiloteke (MeSH, NLM). Vie informacija na:
(http://www.nlm.nih.gov/mesh/meshhome.html).
Tekst rada
Tekst rada mora biti standardnog naunog formata. Vie informacija dobiete preuzimanjem predloaka sa web stranice urnala:
http://jhsci.ba/information-for-authors.html
Pregledni lanci mogu imati drugaiju strukturu.
Uvod je koncizan dio rada. U njemu se predstavlja problem kojim
se rad bavi i to kreui od ireg konteksta problema i trenutnog
stanja i dosadanjih dostignua u vezi konkrtnog problema, prema
specifinom problemu koji e obraditi ova studija. Na kraju uvoda
je potrebno jasno istaknuti svrhu, ciljeve i/ili hipoteze ove studije.
Metode. Ovaj dio ne treba biti kratak. U predlocima koje je JHSci dao na web stranici nalazi se vie informacija o sadraju ovog
poglavlja.
Rezultati. Dati prednost grafikom prikazu rezultata studije u odnosu na tabelarni, kada je god to primjenjivo. Koristiti podnaslove
radi postizanja vee jasnoe radova. Vie informacija nai u predlocima.
Diskusija. U ovoj sekciji treba dati smisao dobivenim rezultatima,
ukazati na nova otkria do kojih se dolo, ukazati na rezultate drugih studija koje su se bavile slinim problemom. Uporediti svoje
rezultate sa drugim studijama i naglasiti razlike i novine u svojim
rezultatima. U ovom poglavlju treba interpretirati, sveobuhvatno
sagledati dobijene rezultate, te sintetizirati novo znanje iz analize.
Zakljuak. Treba da bude kratak i da sadri najbitnije injenice do
kojih se dolo u radu. Navodi se zakljuak, odnosno zakljuci koji
proizilaze iz rezultata dobivenih tokom istraivanja; treba navesti
eventualnu primjenu navedenih ispitivanja. Treba navesti i afirmativne i negirajue zakljuke.
Zahvala
U ovom dijelu se mogu navesti: (a) doprinosi i autori koji ne zadovoljavaju dovoljno kriterija da budu autori, kao npr. podrka kolega
ili efova institucija; (b) zahvala za tehniku pomo; (c) zahvala za
materijalnu ili finansijsku pomo, obrazlaui karakter te pomoi.
Izjava o sukobu interesa
Autori moraju navesti sve izvore finasiranja svoje studije i bilo koju
finansijsku potporu (ukljuujui dobijanje plae, honorara, i drugo) od strane institucija iji finansijski interesi mogu zavisiti od
162
materijala u radu, ili koji bi mogli uticati na nepristranost studije. Ako ste sigurni da ne postoji sukob interesa, navedite to u radu.
Jo informacija se moe nai ovdje: (http://bmj.com/cgi/content/
short/317/7154/291).
Reference
Reference se trebaju numerisati prema redoslijedu pojavljivanja u
radu. U tekstu, reference je potrebno navesti u zagradama, npr. (12).
Kada rad koji citirate ima do 6 autora, navesti sve autore. Ukoliko
je 7 ili vie autora, navesti samo provih 6 i dodati et al. Reference
moraju ukljuivati puni naziv i izvor informacija (Vancouver style).
Imena urnala trebaju biti skraena kao na PubMedu. http://www.
ncbi.nlm.nih.gov/journals
Primjeri referenci:
Standardni rad: Meneton P, Jeunemaitre X, de Wardener HE,
MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev.
2005;85(2):679-715
Vie od 6 autora: Hallal AH, Amortegui JD, Jeroukhimov IM, Casillas J, Schulman CI, Manning RJ, et al. Magnetic resonance cholangiopancreatography accurately detects common bile duct stones in
resolving gallstone pancreatitis. J Am Coll Surg. 2005;200(6):86975.
Knjige: Jenkins PF. Making sense of the chest x-ray: a hands-on
guide. New York: Oxford University Press; 2005. 194 p.
Poglavlje u knjizi: Blaxter PS, Farnsworth TP. Social health and
class inequalities. In: Carter C, Peel JR, editors. Equalities and
inequalities in health. 2nd ed. London: Academic Press; 1976. p.
165-78.
Internet lokacija: HeartCentreOnline. Boca Raton, FL: HeartCentreOnline, Inc.; c2000-2004 [cited 2004 Oct 15]. Available from:
http://www.heartcenteronline.com/
Osobne komunikacije i nepublicirani radovi ne bi se trebali nai u
referencama ve biti navedeni u zagradama u tekstu. Neobjavljeni
radovi, prihvaeni za publiciranje mogu se navesti kao referenca sa
rijeima U tampi (engl. In press), pored imena urnala. Reference moraju biti provjerene od strane autora.
Tabele
Tabele se moraju staviti iza referenci. Svaka tabela mora biti na posebnoj stranici. Tabele NE TREBA grafiki ureivati.
Broj tabele i njen naziv pie se IZNAD tabele. Tabela dobija broj
prema redoslijedu pojavljivanja u tekstu, a naziv treba biti jasan i
dovoljno opisan da je jasno ta tabela prikazuje. npr Table 3. Tekst
naziva tabele..... U radu prilikom pozivanja na tabelu treba napisati
broj tabele u zagradi, npr. (Table 3). Za skraenice u tabeli potrebno
je dati puni naziv ispod tabele. Poeljno je ispod tabele dati objanjenja i komentar, koji su neophodni da se rezultati u tabeli mogu
razumjeti. Prikazati statistike mjere varijacije, kao to je standardna devijacija i standardna greka sredine, gdje je primjenjivo.
Slike
Slike staviti iza referenci i tabela (ako postoje). Svaka slika mora biti
na posebnoj stranici. Slika dobija broj prema redoslijedu pojavljivanja u tekstu. Naziv i broj se piu ISPOD slike, npr. Slika 3. Tekst
naziva slike... U radu, prilikom pozivanja na sliku treba napisati
broj slike u zagradi, npr (Slika 3). Neophodno je da slika ima jasan
i indikativan naziv, a u tekstu ipod slike objasniti sliku i rezultat
koji ona prikazuje, sa dovoljno detalja da ona moe biti jasna bez
pretrage teksta koji je objanjava u radu. Slika mora biti kvaliteta
najmanje 250-300 dpi, formata JPG, TIFF ili BMP.
Jedinice mjere
Mjere duine, teine i volumena trebaju se pisati u metrikim jedinicama (meter, kilogram, liter). Hematoloki i biohemijski parametri se trebaju izraavati u metrikim jedinicama prema International System of Units (SI).

JHSCI 2012 v2 I2 September

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UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

UNIVERZITET U SARAJEVU FAKULTET ZDRAVSTVENIH STUDIJA

Journal of Health Sciences

Dijana Avdi (BiH)

Demal Pecar (BiH)

Aida Rudi (BiH)

Jasmina Berbi-Fazlagi (BiH)

Fatima Jusupovi (BiH)

Mirsad Mufti (BiH)

Budimka Novakovi (SRB)

Borut Poljak (SI)

Isabelle Rishard (F)

Sandra Vegar-Zubovi (BiH)

Journal of Health Sciences

Volume 2, Number 2, September 2012

Journal of Health Sciences

Volume 2, Number 2, September 2012

The autumn brings the fruits

Dijana Avdic, MD, PhD

JOURNAL OF HEALTH SCIENCES 2012; 2 (2)

Journal of Health Sciences

Volume 2, Number 2, September 2012

Etiological factors as predictor of rehabilitation

ing one side of the body, hemiparesis if it has

ommended in first two or three weeks after CVI.

The KolmogorovSmirnov statistic test with a

FIGURE 2. Box plot of LOH (days) in both groups

sion was 8.0 (IQR=2 to 15), in group B was 5.0

In our study, the most patients (78/89 or 87.6%)

completion of first phase of treatment (2,11,12).

JOURNAL OF HEALTH SCIENCES 2012; 2 (2)

Saunders company: 1996: 1053-79.

Journal of Health Sciences

Volume 2, Number 2, September 2012

Risk factors for long term complications

lifetime of coping with the disease (1). Type 1

their signature, thumbprints were used instead.

Age mean (S.D.)

JOURNAL OF HEALTH SCIENCES 2012; 2 (2)

TABLE 2. Mean age gender distribution among ethnic

TABLE 3. Mean weight in kg at diagnosis gender distribution

TABLE 4. Characteristic determination of RF2 hypertension

62 (41.3) 150 (100.0) 0.417

35 (33.7) 104 (100.0)

males and rest 147 (49.5%) females. Mean age

TABLE 5. Characteristic determination of RF3 - hyperlipidemia in study population

TABLE 6. Characteristic determination of RF4-Smoking in

107 (71.3) 150 (100.0) 0.0215

122 (81.3) 150 (100.0) 0.000

Chi-square (*Fisher exact)

variable among the three ethnics. Table 2 showed

100%), among them females have higher BMI 25.79

JOURNAL OF HEALTH SCIENCES 2012; 2 (2)

TABLE 7. Characteristic determination of RF5-Male>45

TABLE 9. Characteristic determination of RF7-Hypoglycaemia in study population

Total N(%) p-value

TABLE 8. Characteristic determination of RF6-Female > 55

TABLE 10. Characteristic determination of RF8-No Exercise

Yes N (%) No N (%)

Total N (%) p-value

Yes N (%) No N (%)

136 (90.7) 150 (100.0) 0.457

109 (72.7) 150 (100.0) 0.730