41

asopis Drutva doktora medicine Republike Srpske

Journal of the Medical Society of the Republic of Srpska

Godina: 41. Broj 2 oktobar 2010.

asopis Drutva doktora medicine
Republike Srpske
Vol. 41 No 2 October 2010.
Medical Society of the
Republic of Srpska

UVODNICI
Nov izgled i sadraj asopisa UREDNICI
Znaajna prekretnica D. VASI
SPECIAL ARTICLES/SPECIJALNI LANCI
Evaluative Measures for Resource Quality: Beyond the Impact Factor
E. GARFIELD

Komentar lanka S. MILOEVI

Arthur C. Guyton J. E. HALL, A. W. COWLEY JR, V. S. BISHOP, AND OTHERS
Alon P. Winnie C. D. FRANCO
Medikalizacija u drutvu i psihijatriji T. KAI
ORIGINAL ARTICLE
Outpatient Utilization of Antibiotics in the Republic of Srpska,
in 2007 and 2008 V. MARKOVI-PEKOVI, S. STOISAVLJEVI-ATARA
REVIEW ARTICLE
Implementation of Secondary Prevention Methodologies in Ischemic Heart Disease
N. D. WONG, D. B. VULI, AND M. OBOT

CLINICAL PROBLEM-SOLVING
Redo Surgery After Multiple Coronary Endarterectomy
. S. JONJEV, Z. KONSTANTINOVI, V. TORBICA, AND OTHERS

CASE REPORT/PRIKAZ SLUAJA

Cor triatriatum sinister u odraslog bolesnika sa plunom hipertenzijom
A. M. LAZAREVI, S. LAZAREVI

Cardiac Papillary Fibroelastoma as a Cause of Recurent Stroke

. S. JONJEV, M. I. ROSI, V. TORBICA, AND OTHERS

IMAGES IN CLINICAL MEDICINE

Twenty Eight-Year-Old Man With Palpitations P. G. IGI
CONTINUING EDUCATION
Questions & Answers M. STOJILJKOVI, L. SOKOLOVA-OKI, S. PENCHAS
PROIRENI APSTRAKTI RADOVA PUBLIKOVANIH NA STRANIM JEZICIMA
www.scriptamedica.com

Scripta Medica
Vol. 41 No 2 October 2010.

Scripta Medica (Banja Luka)

asopis Drutva doktora medicine Republike Srpske
UREIVAKI ODBOR
EDITORIAL BOARD

MEUNARODNI UREIVAKI ODBOR

INTERNATIONAL A DVISORY BOARD

Glavni urednik
Editor-in-Chief

Pavle Anus, Belgrade, Serbia

Shigetoshi Chiba, Matsumoto, Japan
Ervin G. Erds, Chicago, Il, USA
Igor Franceti, Zagreb, Croatia
Faruk Hadiselimovi, Basel, Switzerland
Zoran Ivanovi, Bordeaux, France
Vladimir Kanjuh, Belgrade, Serbia
Tomislav Kau, Belgrade, Serbia
Neboja Lali, Belgrade, Serbia
Kafait U. Malik, Memphis, USA
Momir Mikov, Novi Sad, Serbia
Goran Milainovi, Belgrade, Serbia
Satoshi Nakatani, Osaka, Japan
Dragoslav Nenezi, Podgorica, Montenegro
Aleksandar Nekovi, Belgrade, Serbia
Momir Ninkovi, Munich, Germany
Miodrag . Ostoji, Belgrade, Serbia
Miralem Pai, Berlin, Germany
Shmuel Penchas, Tel Aviv, Israel
Boina Radevi, Belgrade, Serbia
Goran Stankovi, Belgrade, Serbia
Ksenija Vitale, Zagreb, Croatia
Vladan Vukevi, Belgrade, Serbia
Nathan D. Wong, Irvine, USA

Rajko Igi
Urednici
Senior Editors

Aleksandar Lazarevi
Slobodan Milovanovi
Milo P. Stojiljkovi
lanovi
Members

Dejan Bokonji
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IZDAVAKI SAVJET/PUBLISHING COUNCIL

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Web site Editor: Zdravko Gruba

Tehniki sekretar: Biljana Radii
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Tira: 1.000 primjeraka

75

76

Scripta Medica
Vol. 41 No 2 October 2010.

Sadraj

29 REVIEW ARTICLE

Implementation of Secondary Prevention

Methodologies in Ischemic Heart Disease

Contents

NATHAN D. WONG, DUKO B. VULI,

MARKO OBOT
36 CLINICAL PROBLEM-SOLVING

Nov izgled i sadraj asopisa UREDNICI

Znaajna prekretnica D. VASI
7

Redo Surgery After Multiple Coronary Endarterectomy

UVODNICI

IVOJIN S. JONJEV, ZORAN KONSTANTINOVI,

VLADIMIR TORBICA, MILENKO I. ROSI
39 CASE REPORT

Cor triatriatum sinister u odraslog bolesnika sa

plunom hipertenzijom

SPECIAL ARTICLE

Evaluative Measures for Resource Quality: Beyond the

Impact Factor
EUGENE GARFIELD

14

ALEKSANDAR M. LAZAREVI, SANDRA LAZAREVI

41

CASE REPORT

Cardiac Papillary Fibroelastoma as a Cause of

Recurrent Stroke

SPECIAL ARTICLE

Arthur C. Guyton

IVOJIN S. JONJEV, MILENKO I. ROSI, VLADIMIR

TORBICA, SLAVICA MAJDEVAC, NATAA GOCI

JOHN E. HALL, ALLEN W. COWLEY JR., VERNON S.

BISHOP, D. NEIL GRANGER, L. GABRIEL NAVAR,
AUBREY E. TAYLOR

43 IMAGES IN CLINICAL MEDICINE

17

SPECIAL ARTICLE

Twenty Eight-Year-Old Man With Palpitations

PETAR G. IGI

Alon P. Winnie

CARLO D. FRANCO

19

44 CONTINUING EDUCATION

SPECIJALNI LANAK

Questions & Answers

MILO P. STOJILJKOVI, LILJANA SOKOLOVA-OKI,

SHMUEL PENCHAS

Medikalizacija u drutvu i psihijatriji

TOMISLAV KAI

22 ORIGINAL ARTICLE

Outpatient Utilization of Antibioticis in the Republic of

Srpska, in 2007 and 2008
VANDA MARKOVI-PEKOVI,
SVJETLANA STOISAVLJEVI-ATARA

51

PROIRENI APSTRAKTI RADOVA PUBLIKOVANIH

NA STRANIM JEZICIMA

63 UPUTSTVO AUTORIMA
67 INSTRUCTIONS FOR CONTRIBUTORS

Scripta Medica
Vol. 41 No 2 October 2010.

EDITORIAL

Reporting statistics in
medicine
The need for quantitative evidence in medical judgments
was recently formalized as evidence based medicine [1,
2]. This concept was recognized a long time ago when, in
the second century AD, Galen noted that
A thing seen but once cannot be accepted nor regarded
as true Something can only be accepted and considered
true, if it has been seen very many times, and in the same
manner every time.
Galens words were almost entirely ignored until modern
biological and medical statistics emerged. Thanks to an
English statistician, Ronald Fisher (1890-1962), the advent
of powerful statistical methods made a great impact on
studies related to health. Statistical methods continued to
develop, and today we can improve study design, estimate
adequate sample size and provide reliable analysis of the
results.
This issue of the journal presents an abbreviated paper
from the J BUON (Journal of Balkan Union of Oncology)
devoted to descriptive statistics [3]. The authors indicate
frequent errors in various publications, including use of
the mean and standard error of the mean (SEM) instead
of the mean and standard deviation (SD) to report variations of sample data. Unfortunately, some editors and peer
reviewers frequently fail to indicate such shortcomings.
Nagele [4] noted mistakes in several papers published in
anesthesia journals (Table 1), but similar mistakes likely
occur in many other journals as well.
Table 1. Standard error of the mean (SEM) instead of standard
deviation (SD) used to indicate data variation.*

Journal

Number of articles using

SEM instead of SD/total

Anesthesia and Analgesia

112/405 (27.7%)

Brit Journal of Anesthesia

31/137 (22.6%)

Anesthesiology

48/257 (18.7%)

European Journal of
Anesthesiology

7/61 (11.5%)

*This table is an abbreviation of the original [3].

** Percent of total indicated in parentheses)

Researchers and clinicians depend upon accurate and descriptive statistics along with the correct use of inferential statistics to adequately summarize collected sample
data. They apply these tools to characterize features of
data distributions and estimate population characteristics.
As clinicians, we can gain information from carefully executed studies that provide convincing evidence. We need
to know how such conclusions can influence our practice
of medicine. For example, when it is shown that a certain
drug or technique is better than another, we may use that
information to the advantage of the patient.
In the former Yugoslavia, medical researchers have long
lacked published guidance about methods for effectively
collecting and reporting their statistical data. The paper
from the J BUON [3] now brings some specific and detailed
help, but researchers would be well advised, as well, to consult several recently published books on medical statistics
in English [5-8].
Darko Goli, MD, PhD
Head, Department of Anesthesiology and Intensive Care
Clinical Center Banja Luka
78000 Banja Luka, Republic of Srpska,
Bosnia & Herzegovina
Ranko krbi, MD, PhD.
Head, Department of Clinical Pharmacology
Faculty of Medicine,
University of Banja Luka
78000 Banja Luka, Republic of Srpska,
Bosnia & Herzegovina
Gennadiy Voronov, MD
Chairman, Department of Anesthesiology and Pain
Management
J. H. Stroger Hospital of Cook County
Chicago, IL 60612, USA

References
1. www.clinicalevidence.com
2. Anonimous. Clinical evidence handbook. London: BMJ, 2009.
3. Igic R, Stoisavljevic-Satara S. Statistical presentation of data in
biomedical publications. J BUON 2010;15:182-7.
4. Nagele P. Misuse of standard error of the mean (SEM) when
reporting probability of a sample. A critical evaluation of four
anesthesia journals. Br J Anesth 2003;90:514-6.
5. Campbell MJ, Swinscow TDV. Statistics at square one. London,
2009.
6. Campbell MJ. Statistics at square two: Understanding modern
statistical applications in medicine. London, 2006.
7. Lang TA, Sesic M. How to report statistics in medicine.
Philadelphia, American College of Physicians, 1997.
8. Myles PS, Gin T. Statistical methods for anesthesia and
intensive care. Edinburgh, Butterworth, 2000.

77

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Scripta Medica
Vol. 41 No 2 October 2010.

UVODNIK

Prikaz knjige

Prikaz knjige je opis njenog sadraja, kritika analiza, procena kvaliteta i ukazivanje na znaaj te publikacije. Engleski izraz book review se kod nas ponekad krivo prevodi
kao recenzija knjige, a ne prikaz knjige. Recenziranje
knjiga se vri pre njihovog objavljivanja, a prikaz knjige se
pie nakon to je knjiga objavljena.
Postoje dva pristupa pisanju ovih prikaza: deskriptivni i
kritiki. Za razliku od deskriptivnog prikaza, u kom autor istog uglavnom daje osnovne podatke o knjizi, kritiki
prikazi, pored opisa knjige, sadre procenu knjige kojom
prikaziva informie itaoca o kvalitetu dela. Kritiki prikazi imaju za cilj da izvre procenu kompetentnosti autora
knjige i kvaliteta informacija u njoj, te obaveste itaoca
moe li to delo, i u kojoj meri, podsticati donoenje boljih
odluka u datom domenu zdravstva. Uz to, kritika kojom se
izraava neslaganje i ukazuje na nedostatke knjige ili nekog
strunog dela, predstavlja glavnu pokretaku snagu koja
vodi napretku u svim naunim i strunim oblastima, ali i
podizanju akademskog nivoa. (1) Imajui u vidu injenicu
da je veima naih biomedicinskih asopisa, donedavno,
mahom publikovala deskriptivne prikaze knjiga, Scripta
Medica e podsticati kritike prikaze koje nameravamo
povremeno objavljivati u naem asopisu. Razlog za publikovanje ovih prikaza je, izmeu ostalog, i u tome to
itaoci radije itaju prikaze knjiga nego druge lanke u
asopisu. (2)
Kratka instrukcija o tome kako se piu prikazi knjiga data
je 1980. godine. (3) Ona je i danas aktuelna pa je u nastavku taj tekst dat u celini.
Mnogi asopisi objavljuju prikaze knjiga. U nekim
asopisima to se vri u redovnim kraim rubrikama, a
ponekad se pojavljuju svesci asopisa koji znatno vie prostora posveuju prikazima knjiga kao to to, na primjer,
ini Nature. Pisac prikaza knjige analizira sadraj djela i
obavjetava itaoce kakve je namjere imao autor djela, kakav je uspjeh i kakve propuste nanio prilikom postizanja
svojih ciljeva, kakav je jezik i stil, koja je centralna tema,
ta obuhvata, a ta ne obuhvata knjiga i koje su najjae i
najslabije strane knjige. Poeljno je da pisac prikaza knjige
komparira knjigu sa srodnim djelima, ali i sa ostalim
knjigama koje je napisao isti autor. U naim biomedicinskim asopisima se izuzetno retko sreu paralelni prikazi
vie knjiga koje obrauju isti predmet. Takvi prikazi su
osobito korisni kada je u pitanju udbenika literatura jer
pomau studentima i postdiplomcima za koju knjigu da se

opredijele pri izuavanju odreenog predmeta. Poeljno je

da asopisi takve prikaze knjiga objavljuju u vidu suplementa, kao to to u vie navrata svake godine ini pomenuti Nature.
Obino se prikazi knjiga piu na stranici-dvije teksta kucanog s proredom, ali ima i opirnijih prikaza. Obim prikaza odreuje redakcija asopisa i autor prikaza. Dobro
ine one redakcije koje prema znaaju djela daju prostor za
prikaz knjige.
Ne postoji jedinstvena formula o tome kako pisati prikaze
knjiga; oni znaajno variraju od jednog do drugog autora.
Miljenje o vrednosti knjige je, takoe, lino. Na asopis
prihvata kratke (oko 100 rei) i due (do 700 rei) prikaze
na srpskom jeziku, a samo izuzetno na engleskom. Vano je
da pisac prikaza bude ekspert za dato podruje medicine.
U veini sluajeva, prikaze e pisati strunjaci po narudbi,
a urednici e, po potrebi, skraivati preopirne tekstove i
redovno traiti da vide knjigu koja se predstavlja.
Veoma vaan doprinos ovom anru naune i strune komunikacije u biomedicinskim disciplinama, odskora pruaju i
lingvistika istraivanja. lanak dr Bojane Petri, (2) koji u
ovom broju objavljuje Scripta Medica, predstavlja pionirski korak u tom pravcu na prostorima Balkana.
Rajko Igi, MD, PhD
Reference
1.

Petri B. Scholarly criticisms in a small academic community:

A diachronic study of book reviews in the oldest Serbian scholarly journal. In F Salager-Meyer and BA Lewin (Eds). The word
and the sword: Criticism in the academy. Bern, Peter Lang (u
tampi).
2. Petri B. Prikazi knjiga u Srpskom arhivu i Vojnosanitetskom
pregledu: istorijska perspektiva. Scripta Medica 2010;41: DOPISATI STRANU OD DO.
3. Hall GM (Ed). How to write a paper. London, BMJ Publishing
Group, 1994.
4. Igi R. Kako se piu saoptenja o medicinskim istraivanjima.
Sarajevo, Veselin Maslea, 1980.

REVIEW ARTICLE

Faruk Hadziselimovic

Cryptorchidismpathophysiology,
treatment concept and long-term
follow up results

Kindertagesklinik Liestal
Switzerland
Oristalsstrasse 87a 4410 Liestal
Schweiz
0041619220525,
praxis@kintertagesklinik.ch

ABSTRACT
Unescended testes (cryptorchidism), incomplete descent at birth of one or both
testes affects 1-3% of boys and is the most common endocrine disease in
childhood. If untreated, the undescended testis may develop progressive failure
of spermatogenesis and has a higher incidence of carcinoma that may manifest
in adolescence and adulthood. Endocrine and primary end organ failures are the
two etiological factors most frequently held responsible for the increased incidence
of infertility in unilateral and bilateral cryptorchidism. The cryptorchid testis has
a typical histology showing depletion of germ cells and impaired maturation of
gonocytes accompanied by intestinal brosis and Leydig cell atrophy. In 70% of
males with isolated cryptorchidism, hypogonadotropic hypogonadism is the cause
of undescended testes. The number of Ad spermatogonia that develop in infancy
during the period of mini puberty (the stem cells for mature spermatozoa) is severely
reduced . The ultimate aim of all therapy for cryptorchidism is to have both testes
in the scrotum and to achieve normal fertility. Hormonal treatment is recommended
for all patients prior to orchidopexy and those at high risk of infertility (no Ad
spermatogonia). Treatment includes Kryptocur for inducing epididymo-testicular
descent and Buserelin (LH-RHa) for prevention of infertility. If unsuccessful surgery
should be performed before patients second birthday.

Seventy percent of cryptorchid patients exhibit hypogonadotropic hypogonadism. In boys with unilateral cryptorchidism, testicular pathology caused by hormonal imbalance
was bilateral; 71% of scrotal testes had a reduced number
of germ cells, and 75% had impaired transformation of
gonocytes into Ad (Adult dark) spermatogonia. Evidence
of a relative post-pubertal gonadotropin deficiency became
even more pronounced when LH plasma values were correlated with Ad spermatogonia. While both high infertility risk (HIR) and intermediate infertility risk groups had
normal basal LH levels, the low infertility risk group had
LH levels in the hypogonadotropic range.
Our long term, prospective follow-up study used hormonal
analyses to confirm a previously observed inverse correlation between FSH and sperm count [1.2]. Furthermore,
we established that patients with bilateral cryptorchidism
had higher FSH plasma values than those with unilateral
cryptorchidism [2]. At first glance, these findings suggest
that primary testicular failure causes the hypergonadotropic hypogonadism. However, we find that gonadotropin
levels are more highly correlated with the presence or absence of Ad spermatogonia than with the number of un-

descended testes. Patients with the greatest impairment

to mini-puberty and who exhibited failed transformation
of gonocytes into Ad spermatogonia had the most severe
infertility. [2]
The extent of testicular pathology observed in the high-risk
infertility group was comparable to that observed in males
with Klinefelter syndrome or idiopathic Sertoli cell only
syndrome [2]. However, testicular failure in XXY males or
idiopathic Sertoli cell only syndrome resulted in FSH levels 3 to 5 times higher than in the controls [2]. In contrast,
despite identical severity of testicular pathology in cryptorchid patients with a high risk of infertility, we observed
only marginal FSH elevation, indicating a relative FSH insufficiency. At least 70 % of our patients had relative FSH
deficiency. The finding of relative FSH and LH deficiencies
in most of our patients indicates that hypogonadotropic
hypogonadism is the primary etiologic factor in cryptorchidism [2,3,4,5]. Furthermore, the normal plasma testosterone values in our cohort do not support the hypothesis
of Toppari et al. [6] that mild Leydig cell dysfunction and
subsequent end organ dysgenesis are etiologic factors in
cryptorchidism.

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Scripta Medica
Vol. 41 No 2 October 2010.

Cryptorchid testis: histology.

The appearance of the cryptorchid testis is easily recognized, even under low magnification. It is characterized by
wide, empty intercellular spaces and small seminiferous
tubules with reduced numbers of germ cells. Histological
sections of undescended testes show circular tubules with
central spherical bodies and secondary regions with degenerated tubules [7,8].
As early as the second year of life, approximately 22% of patients with unilateral cryptorchidism are destined to lack
spermatogonia in their tubules [2,9]. Qualitative changes
of spermatogonia can be seen as well. For example, there
is an increase in the number of spermatogonia with two
nuclei, and the observed spermatogonia are mostly fetal,
sometimes with bizarre nuclear structures [9, 10].
The marked reduction in spermatogonia in a 6-year-old
cryptorchid patient includes immature forms, e.g. fetal and
Ap spermatogonia. Ad spermatogonia are rarely seen and
primary spermatocytes are never observed [2, 8, 9, 10,].
Most of the observed spermatogonia show signs of incipient degeneration [2, 8, 9].

Normal

Mini-puberty and Ad spermatogonia

Development of male fertility depends upon successful
mini-puberty [2,11] and the transformation of gonocytes
into Ad spermatogonia [12]. During mini-puberty, which
occurs between 30 and 90 days of postnatal life in male
infants, a substantial increase in GnRH secretion induces
an increase in gonadotropin and testosterone production
[13]. Testicular changes during mini-puberty are further
characterized by a slight increase in testicular weight [14]
and volume [15]. As a result, gonocytes transform into Ad
spermatogonia. Ad spermatogonia have a characteristic
nuclear feature that distinguishes them from other germ
cells, e.g. fetal, transient, and Ap spermatogonia [16]. The
Ad spermatogonium is a flat cell with a long oval nucleus;
this is the only form that has a region of rarefaction within
the nucleus (Fig. 1.) [16].
Adult dark (Ad) spermatogonia appear at 3 months of age
and remain for life [16]. Therefore, transformation of gonocytes into Ad spermatogonia, either directly or through intermediate stages, is not simply another developmental step
but a major transformation. This transformation involves
the switch from the fetal reservoir of stem cells (gonocytes)
to the adult reservoir of stem cells (Ad spermatogonia)
from which all future germ cells are replenished. Based on
results from our previous work, we know that development
of Ad spermatogonia depends upon LH and T secretions.
[17] The expression pattern of prepubertal germ cells indicates that genes involved in meiosis and post-meiotic germ
cell development are already up regulated before puberty
[9]. Boys with cryptorchidism lack Ad spermatogonia and
have low plasma concentrations of both basal and stimulated gonadotropin, as expected in hypogonadotropic hy-

cryptorchid
Figure 1. Histology of testicular tissue: normal and cryptorchid
testes.

pogonadism [18]. If transformation of gonocytes into Ad

spermatogonia fails during infancy, infertility is inevitable
[2,19,20]. We [2,20] along with others [21] confirmed this
finding, which was first reported in 2001[19]. Kim and coworkers analyzed the histology of testicular biopsies from

Hadziselimovic

patients with bilateral cryptorchidism and established the

prognostic importance of Ad spermatogonia for fertility
[21]. Furthermore, there is strong evidence that boys with
cryptorchidism will develop infertility, despite early and
successful orchidopexy [2].
EGR4 master gene for fertility in cryptorchidism
Whole genome profiling analysis of cryptorchid testes indicates abnormalities in several developmental testicular
genes. Expression of MBD2, FOXG1, TGFBR1, FDGFR1,
TDRDS, CTAS, MAGEs, GAGEs, SSXs, and Spa17 were
found to be lacking or under-expressed in boys in the high
infertility risk group [22].
The key observation from our current work is that the early
growth response gene, EGR4, was not expressed in boys
in the HIR group [9]. Since EGRs are pivotal for LH secretion, this provides indirect evidence that EGR 4 is important for Ad formation and that the LH-T axis is involved in
this developmental process. Patients in the HIR group had
severely reduced EGR4 expression, and their testicular
histology showed severe tubular and Leydig cell atrophy
identical to that of Egr1/Egr4 double mutant infertile mice.
As in Egr mutant mice, treating boys with cryptorchidism
and HIR with buserelin (a GnRH receptor agonist) normalized sperm parameters in 86% of patients who otherwise
would develop infertility, despite successful orchidopexy
[27]. Therefore, our results suggest that EGR4 is the master
gene that controls fertility development.
Although all of the patients we studied had isolated cryptorchidism in comparable undescended position and identical age, the HIR group had significantly lower EGR4
expression, indicating that descent of the epididymo-testicular unit does not require intact EGR4 function. This
new observation calls into question current dogma that
the undescended position itself is the cause of infertility.
In this regard, we found that an RNA helicase involved in
gene-specific mRNA export and protein translation during spermatogenesis was significantly down regulated in
the HIR group, which coincides the decreased expression
of EGR4, DDX25/GRTH. LH/HCG stimulates DDX25 via
cyclic-AMP-induced androgen formation in testicular Leydig cells (27).
Hormonal treatment and possible side effects
One of the therapeutic options in treatment of cryptorchidism is hormonal therapy with luteinizing hormone (LH),
or human chorionic gonadotropin (hCG) [2]. Induction of
testicular descent in this manner [2,28,29,30] improves
the potential for fertility from poor to good in up to 75% of
the individuals treated [31,32]. There are increasing concerns about the safety of hormonal therapy [33.34]. More
apoptotic spermatogonia were found in patients who underwent unsuccessful hCG therapy prior to orchiopexy
compared to the patients who underwent orchiopexy alone
[33]. However, in follow-up spermiograms there was no

difference in sperm concentration, motility or percentage

of normal morphology between the two groups of patients.
Maturation of spermatogonia and a decrease in a number
of Sertoli cells are anticipated effects of hormonal therapy,
thus degeneration of Sertoli cells may be noted. In a retrospective, nonrandomized study, Cortes et al [34] found
fewer germ cells per tubule in 1-3 year old patients, who
were treated unsuccessfully with gonadotropin releasing
hormone or hCG. The number of germ cells per tubule in
patients treated with orchiopexy alone was 0.14 (range =
0-0.86), while in patients previously treated with gonadotropin releasing hormone or hCG the numbers were significantly lower, 0.07 (range = 0-0.31) and 0.06 (range =
0.0025-0.21). Although these values differ statistically,
they are all low enough to predict future infertility. Since
this study was not randomized, there is a possibility that
some patients treated with orchiopexy alone might benefit
from hormonal therapy as well.
The effects of hormonal therapy on the contralateral descended testis have been studied only sporadically [35].
Bergada et al. [35] found stimulated maturation of germ
cells in treated patients and directly related the number
of mature cells to both the dose and duration of the treatment. We showed that hormonal treatment did not harm
the histology of the contralateral testis but rather improved
it. Patients treated with orchiopexy alone had an average of
1.33 1.0 mature cells/per tubule while hormonally treated patients had 2.05 1.1 germ cells per tubule. (p<0.05).
Hormone therapy increased the number of Ad spermatogonia per tubule as well [36].
Hormonal treatment following orchidopexy
Infertility induced by cryptorchidism is an endocrine disease of impaired mini-puberty. Treatment with LH-RHa
following successful orchiopexy before the age of six years
normalizes sperm parameters in the vast majority of patients. Normalization of the sperm counts in 86 % of males
with cryptorchidism following LH-RHa treatment further
refutes the hypothesis of end organ dysgenesis [27]. Since
50% of patients with unilateral cryptorchidism do not belong to the high infertility risk group, they will profit from
early surgery without the need for subsequent LH-RHa
treatment. Testicular biopsy is the only diagnostic procedure capable of identifying patients who need to be treated
with LH-RHa following successful surgery. Because of its
important prognostic value, a testicular biopsy should be
performed routinely during the orchiopexy.
Treatment recommendations (age <2 years)
1. LH-RH 1.2 mg/ day for 28 days; if no success,
2. 500 IU HCG/ week for 3 weeks; if no success,
3. orchidopexy and bilateral biopsy, if no Ad;
4. LH-RHa, 10 g on alternate days /for 6 months.

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1.
2.

3.
4.

5.

6.

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8.
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10.
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18.

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Hadziselimovic F, Herzog B. Hodenerkrankungen im Kindesalter. Stuttgart, Georg Thieme Verlag, 1990.

Hadziselimovic F, Hoecht B. Testicular histology related to
fertility outcome and postpubertal hormone status in cryptorchidism. Klin Padiatr 2008;220:302-7.
Hadziselimovic F. Pathogenesis and treatment of undescended
testes. Eur J Pediatr 1982;139:255-65.
Job JC, Toublanc JE, Chaussain JL, Gendrel, Roger M, Canlorbe
P. The pituitary-gonadal axis in cryptorchid infants and children. Eur J Pediatr 1987;146 (Suppl 2):25.
Hamza AF, Elrahim M, Elnagar, Maaty SA, Bassiouny E, Jehannin B. Testicular descent: when to interfere? Eur J Pediatr Surg
2001;11:1736.
Toppari J, Kaleva M, Virtanen HE, Main KM, Skakkebaek NE.
Luteinizing hormone in testicular descent. Mol Cell Endocrinol
2007;269:347.
Kleintech B, Hadziselimovic F, Hesse V, Schreiber G. Kongenitale Hodendystopien. Leipzig, VEB Georg Thieme, 1979.
Nistal M, Paniagua R, Diez-Pardo JA: Histological classification
of undescended testes. Hum Pathol 1980;11:666-74.
Hadziselimovic F. Cryptorchidism. Adv Anat Embryol Cell Biol
1977;53:3-71.
Hadziselimovic F. Cryptorchidism; Management and Implications. Berlin Heidelberg, Springer Verlag, 1983.
Hadziselimovic RF, Zivkovic D, Bica DTG, Emmons LR. The importance of mini-puberty for fertility in cryptorchidism J Urol
2005;174:1536-9.
Hadziselimovic F, Thommen L, Girard J, Herzog B. The significance of the postnatal gonadotropin surge for testicular development in normal and cryptorchid testes J Urol 1986;136:274-6.
Forest MG, Sizonenko PC, Cathland AM, Bertrand J. Hypophyseo-gonadal function in humans during the first year of life. J
Clin Invest 1974;53:819-28.
Siebert JR. Testicular weight in infancy (letter). J Pediatr
1982;100:835-6.
Cassorla FG, Golden SM, Johsonbaugh RE, Hermon WM, Loriaux DL, Sherins RJ. Testicular volume during early infancy. J
Pediatr 1981;99:742-3.
Seguchi A, Hadziselimovic F. Ultramikroskopische Untersuchungen am Tubulus seminiferous bei Kindern von der Geburt
bis zur Pubertat I. Spermatogonienentwicklung. Verh Anat Ges
1974;68:133-48.
Zivkovic D, Hadziselimovic F. Relationship between the adult
dark spermatogonia and secretory capacity of Leydig cells in
cryptorchidism. BJU 2007;100:1147-9.
Hadziselimovic F, Herzog B, Girard J Lack of germ cells and
endocrinology in cryptorchid boys from one to six years of life.
Cryptorchidism. In: Biereich, Giarola A. (eds.) Cryptorchidism
New York, London, Academic Press, 1979.
Hadziselimovic F, Herzog B. The importance of both an early
orchiopexy and germ cell Maturation for fertility. Lancet
2001;358:1156-7.
Hadziselimovic F, Emmons LR, Buser MW: A diminished
postnatal surge of Ad spermatogonia in cryptorchid infants is an
additional evidence for hypogonadotropic hypogonadism. Swiss

Med Wkly 2004;134:381-4.

21. Kim SS, Kolon T, Casale P, Carr M, Zderic SA, Canning DA, Huff
DS, Snyder HM The positive predictive value of prepubertal
testis biopsy on adult sperm density in patients with bilateral
undescended testes. J Urol 2008;179:144-5.
22. Hadziselimovic F, Hadziselimovic N, Demougin Ph, Krey G,
Hoecht B, Oakeley E EGR4 is a master gene responsible for fertility in Cryptorchidism. Sex Dev 2009;3:253-63.
23. Hadziselimovic F, Seguchi H. Ultramikroskopische Untersuchungen an Tubulus Seminiferous bei Kindern von der Geburt
bis zur Pubertt. II. Entwicklung und Morphologie der Sertolizellen. Verh Anat Ges 1974;68:149-61.
24. Cortes D, Mller J, Skaekkebaek E: Proliferation of Sertoli cells
during development of the human testis assessed by stereological methods. Int J Androl 1987;10:589-96.
25. Cortes D: Cryptorchidism Scand J Urol Nephrol (Suppl)
1998;196:1-54.
26. Zivkovic D, Hadziselimovic F. Development of the Sertoli cells
during mini-puberty in normal and cryptorchid testes. Urol Int
2009;82:71-82.
27. Hadziselimovic F. Successful treatment of unilateral cryptorchid
boys risking infertility with LH-RH analogue. Int Braz J Urol
2008;34:319-26.
28. Bica DT, Hadziselimovic F. Buserelin treatment of cryptorchidism: a randomized, double-blind, placebo-controlled study. J
Urol 1992;148:617-21.
29. Pyorala S, Huttunen N, Uhari M. A review and meta-analysis
of hormonal treatment of cryptorchidism. Clin Endocrinol
1995;80:2795-9.
30. Esposito C, De Lucia A, Palmieri A, Centonze A, Damiano R,
Savanelli A, Valerio G, Settimi A. Comparison of five different
hormonal treatment protocols for children with cryptorchidism.
Scand J Urol Nephrol 2003;37:246-9.
31. Hadziselimovic F, Herzog B. Treatment with luteinizing hormone releasing hormone analogue after successful orchiopexy
markedly improves the chance of fertility later in life. J Urol
1997;158:1193-95.
32. Huff DS, Snyder HM, Rusnack SL, Zderic SA, Carr MC, Canning
DA. Hormonal Therapy for the Subfertility of Cryptorchidism.
Horm Res 2001;55:38-40.
33. Dunkel L, Taskinen S, Hovatta O, Tilly JL, Wikstrm S. Germ
Cell Apoptosis after Treatment of Cryptorchidism with Human
Chorionic Gonadotropin is associated with Impaired Reproductive Function in the Adult. J Clin Invest 1997;100:2341-6.
34. Cortes D, Thorup J, Visfeldt J. Hormonal treatment may harm
the germ cells in 1-3-year-old boys with cryptorchidism. J Urol
2000;163:1290-2.
35. Bergada C, Mancini RE. Effects of gonadotropins in the induction of spermatogenesis in human prepubertal testis. J Clin
Endocrinol Metab 1973;37:935-43.
36. Zivkovic D, Hadziselimovic F. Effects of hormonal treatment on
the contralateral descended testis in unilateral cryptorchidism.
J Pediatr Urol 2005;2:468-72.

Garfield

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Miloevi

85

CASE REPORT

Partial Transurethral Prostatectomy

In Patient With Congenital Factor VII
Deciency

Ljuba Stojiljkovic*, David

Boldt and Dragan Gastevski
*Department of Anesthesiology
Northwestern University Feinberg
school of Medicine, Chicago, IL
60611, and Department of Anesthesiology and Pain Management, JHS
Hosopital of Cook County, Chicago,
IL 60612, USA
Correspodence
Ljuba Stojiljkovic, MD, PhD
Associate Professor of Anesthesiology, Northwestern University Feinberg School of Medicine
Feinberg Pavilion, Suite 5-704
251 East Huron St, Chicago, IL 60611
Phone: 312-926-8369
Fax: 312-926-8341, e-mail:
l-stojiljkovic@northwestern.edu

Gross hematuria is an uncommon first presentation of

benign prostatic hyperplasia (BPH), with a prevalence of
about 2.5% (1). Here we report a patient with intractable
hematuria and congenital factor VII (FVII) deficiency who
was presented for partial transurethral resection of prostate (TURP).
Case Report
A 56-year-old African-American male (height 182 cm,
weight 77 kg) was presented for cystoscopy and partial
TURP. History of the present illness was significant for
gross hematuria, for which he was transfused with 4 units
packed red blood cells (PRBC) and the bladder irrigation
was performed at an outside institution. Hematuria could
not be controlled and he was therefore transferred to our
hospital for further care. Vital signs upon arrival were
stable: temperature 37 0C, blood pressure 118/77 mmHg,
pulse 77 /min, respiratory rate 19 /min, and O2 saturation
was 96% on room air. The patient was a well developed,
well nourished male in no acute distress.
History was significant for the fact that, although the patient reported no personal history of significant bleeding,
he did note that his father was a bleeder. The patient reported no allergies and no other significant past medical
history. The physical exam was unremarkable and laboratory workup revealed a hemoglobin of 10.0, hematocrit of
28.3, prothrombin time of 18.2, International Normalized
Ratio (INR) of 1.54, and partial thromboplastin time of
32.1. Hematology consult was obtained. Mixing hematological laboratory studies were ordered to determine the

presence or absence of heparin or direct thrombin inhibitors, and they were all negative. The diagnosis of FVII deficiency was confirmed by measuring FVII activity, which
was only 2% of normal. In preparation for surgery, two
units of fresh frozen plasma (FFP) were transfused and
recombinant factor VIIa (Novosoven) was requested from
a pharmacy.
The patient was taken to the operating room, and 90 mcg/
kg of Novoseven intravenously (IV) was given prior to
surgical incision. Subsequently, a partial TURP was performed under general anesthesia. The patients intraoperative course was uneventful. Estimated blood loss was 200
ml and he received 1200 ml of crystalloids. The patient
was extubated without complications and then taken to
the postoperative anesthesia care unit (PACU) in a stable
condition.
Following extubation, the patient was noted to have moderate facial edema. Respirations were unlabored and breath
sounds were clear to auscultation bilaterally. The patient
quickly developed hypertension with systolic blood pressures in the low 200s. Other vital signs including heart
rate remained stable. It was feared that the patient may
have had either an allergic reaction to the recombinant
Factor VII or fluid overload. The hypertension was treated
with furosemide and antihypertensive hydralazine and
labetalol IV. Diphenhydramine and corticosteroids were
given IV in the event that this was an allergic reaction.
The patient responded to the treatment and was eventually discharged from the PACU with stable vital signs in-

Stiljkovic et al.

cluding systolic blood pressures in the 130-140 mmHg. He

remained stable on the floor and the edema gradually resolved. He was discharged home six days later.

voseven was used effectively in a patient with congenital

FVII deficiency for the treatment of intractable hematuria
associated with BPH and TURP.

Discussion
Congenital FVII deficiency is a rare bleeding disorder
with high phenotypic variability, and the incidence is approximately 1:500,000 (2). In the majority of patients,
FVII deficiency is associated with only mild hemorrhagic
disorder. However, surgery may be associated with severe
bleeding, and preoperative FVII replacement is advocated
(3). FVII replacement has traditionally been achieved with
FFP, protrombin complex concentrates or plasma-derived
FVII concentrates. However, in 2005, a recombinant FVIIa (Novoseven) was FDA approved for the prevention and
treatment of bleeding in patients with congenital FVII deficiency undergoing surgical procedures. In this case, No-

References
1.

Hunter DJW, Berra-Unamuno A, and Martin-Gordo A. Prevalence of Urinary Symptoms and Other Urological Conditions in
Spanish Men 50 Years Old or Older. J Urol 1997;155:1965-70.
2. Mariani G, Konkle BA, and Ingerslev J. Congenital Factor VII
Deficiency: Therapy with recombinant Activated Factor VII a
Critical Appraisal. Haemophilia 2006;12:19-27.
3. Mariani G, Dolce A, Marchetti G, et al. Clinical Picture and
Management of Congenital Factor VII Deficiency. Haemophilia
2004;10:180-3.

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CASE REPORT

Anesthesia For An Intoxicated

Parturient With A Cervical Collar

Jaw Donkoh, Ihuma Ofoma,

Ned Nasr, Zerin Dadabhoy,
Bozana Alexander
Department of Anesthesiology and
Pain Management, J. H. Stroger
Hospital of Cook County, Chicago,
Illinois 6012, USA
Correspodence
Bozana Alexander, MD
Anesthesia Research, Room 520
Chicago, IL 60612, USA
Phone: (312) 864 4632

Substance abuse has crossed social, economic and geographic borders and presents significant problem that is
facing society today. The prevalence of cocaine abuse in
young adults (including women) is markedly increased
over the past two decades. Approximately ninety percent
of cocaine-abusing women are of childbearing age. Thus,
it is not surprising to find pregnant women who abuse
this drug. During the early months of pregnancy, cocaine
abuse may increase the risk of miscarriage. When the drug
is used late in pregnancy, it triggers premature labor and
may cause an unborn baby to die or to have a stroke, which
can result in irreversible brain damage. [1] Thus, prenatal
cocaine exposure may affect infant development. [2]

as a restrained passenger, with chest injury due to air bag

deployment. She had a history of rheumatoid arthritis
managed with high daily dose of steroids. Initial work up
for chest and abdomen was negative. There was concern
about a widened mediastinum on chest x-ray, which was
cleared by the radiologist after CT scan. C-spine instability could not be excluded and a cervical collar was placed
by the trauma service. A toxicology report was positive for
heroine and cocaine. The Anesthesiology on call team was
consulted shortly after the patients arrival to the labor
and delivery unit. We were informed that the patient was
demonstrating changes in mental status including periodic
drowsiness.

The diverse clinical manifestations of cocaine abuse combined with physiologic changes of pregnancy, and pathophysiology of coexisting pregnancy-related disease might
lead to life-threatening complications and significantly
impact the practice of obstetric anesthesia. A complete understanding of the physiology of pregnancy, pathophysiology of pregnancy-specific disorders and anesthetic implications of cocaine abuse in pregnancy is essential for safe
anesthetic plan for this high-risk group of patients. [3]

We found distressed female in labor pain demanding a csection. She revealed that she had general anesthesia once
for a cesarean section. She denied food ingestion in the last
five hours. On inspection the airway appeared manageable
despite the presence of a cervical collar, which necessitated meticulous planning of airway management. After discussing the situation with the obstetrical team a decision
was made to allow labor to progress, with surgical intervention if necessary. Aspiration prophylaxis was administered accordingly. Availability of an emergency airway cart
in the operating room was verified. The anesthesia team
was summoned again three hours later for emergency cesarean section due to failure of labor to progress. Patient
was placed supine in the LUD position with a roll under her
shoulders and pre-oxygenated with her head at a 20-degree elevation. She underwent uneventful rapid sequence
induction and was subsequently intubated with c-collar in
place and in line neck stabilization. A stress dose of steroids was administered. Anesthesia was maintained with
sevoflurane in nitrous oxide and oxygen.

A third-term pregnant woman involved in a traumatic

event presents several unique challenges for anesthetic
management. We present a-37-week pregnant substance
abuser who went into labor after sustaining blunt trauma
to the chest. In this instance a decision to provide general
anesthesia was complicated by several factors, including
a history of rheumatoid arthritis, further compounded by
a c-spine that could not be cleared due to her intoxicated
condition. The alternative option of regional anesthesia
was not practical in a setting of recent traumatic event and
inebriated state.
Case Presentation
A-38-year-old G6P5 parturient presented to the emergency department after involvement in a vehicle collision

A male infant was delivered with APGAR scores 8 and 9.

At the end of the procedure patient met criteria for extubation, which was uneventful, as was the immediate recovery
period.

Donkoh et al.

Discussion
When selecting an anesthesia technique each case must be
analyzed individually and particular issues addressed accordingly [3]. For instance, the airway tends to be more
edematous and vascular during pregnancy, and rheumatoid arthritis may affect synovial joints in the c-spine.
Even in the absence of a c-collar, avoidance of neck extension would still be prudent and a smaller size tube recommended. Cocaine abuse is known to have effects on
hemodynamic status and possibly hemostasis [4]. In our
intoxicated pregnant trauma patient, we chose balanced
general anesthesia, which led to a favorable outcome for
both the mother and the fetus.

References
1.

Slutsker, L. Risks associated with cocaine use during pregnancy.

Obstet Gynecol 1992;778-89.
2. Richardson GA, Goldschmidt L, Willford J. The effects of prenatal cocaine use on infant development. Neurotoxicol Teratol
2008;30:96-106.
3. Kuczkowski KM. Cocaine abuse in pregnancyanesthetic implications. Int J Obstet Anesth 2002;11:204-10.
4. Chang A. Trauma in pregnancy. Emerg Med Clin N Amer
2009;16:209-28.

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Vol. 41 No 2 October 2010.

CASE REPORT

Bilateral Vocal Cord Palsy After

Mediastinoscopy

Since its introduction by Carlens in 1959, [1] mediastinoscopy has become an important tool for diagnosis of mediastinal lesions and staging of mediastinal malignancies. It
is more accurate at staging lung cancer than the computed
tomographic scans or positron emission tomography scans.
(2). From all the complications only less then 0.5% have
clinical significance, the worst is a massive hemorrhage,
which requires a trained team and well equipped operating
theatre for thoracic, vascular and cardiac surgery (3). The
rate of recurrent nerve paralysis or vocal cord palsy after
mediastinoscopy has been reported at less than one percent. These complications are more common in redo neck
surgery. Some other causes of operative injury to the vocal cords include intubation and placement of esophageal
stethoscopes, pacemaker placement, medial sternotomy,
carotid surgery, internal mammary artery harvest, and
esophagectomy.
We present a patient with mediastinal mass, who developed transient recurrent laryngeal nerve paresis and airway compromise after this procedure.
Case Presentation
A-55-year-old, 168 cm tall, weighing 60 kg, a smoker with
one-week history of neck swelling and hoarseness presented to emergency department with chest pain. Patient was
found to have mediastinal lymphadenopathy, and superior
vena cava syndrome. No wheezing or stridor was observed
during deep breathing. Diffuse neck edema was present
with distended veins on the left side. Rest of the airway
exam was favorable. Second IV was inserted on the lower
extremity and patient was taken to the operating room. Inhalation induction was facilitated with dexmedetomidine
and ketamine. Intubation with 7.5 size ETT, was smooth
and atraumatic. Direct laryngoscopy view was grade one.
Cuff was inflated with 5 ml of air to control the air leak.
General anesthesia was maintained with sevofluraine in
oxygen and air. Cisatracurium was administered before
surgical stimulation. At the end of the procedure patient
met criteria for extubation and was transferred to PACU
in stable condition with oxygen via facemask. During the
recovery room stay he developed dyspnea and stridor with
deep breathing. He was treated with warmed, humidified
oxygen, nebulized racemic epinephrine IV hydrocortisone

Anthony Joseph, Tadeush

Konefal, Gennadiy
Voronov, Bozana
Alexander
J. H. Stroger Hospital of Cook County,
Chicago, Illinois 60612, USA
Fax No. +1-312-864-9641

and furosemide. Patient had only minimal improvement

with the treatment and sitting posture. ENT consult was
obtained. Direct laryngoscopy showed bilateral vocal cord
paralysis with cords in the para-median position (Fig. 1).

Figure 1. Vocal cords in the paramedian position.

Patient was transferred to intensive care unit for further

observation and symptoms gradually improved. He was
discharged home after two days in stable condition. Two
weeks later pathology results came back positive for malignancy in multiple paratracheal stations. The tumor was
inoperable and patient was referred to medical oncology.
Discussion
Traction of the recurrent nerve causes the greatest stimulation to nerves. The traction on both nerves may frequently
occur with dissection along the trachea. Thus, it is as important as a biopsy or cautery injury (5). Unilateral paralysis may be asymptomatic. However, bilateral paralysis is
almost always manifested by stridor and different degree
of dyspnea. The severity of dyspnea depends on the vocal
cord position. Hoarseness occurs when paralysis is of sudden onset. The extent of recurrent laryngeal nerve damage, paresis or paralysis, is important for the vocal cord
paralysis. A vocal cord lies in the midline when paralysis is
complete. The paramedian position is the most common; it
is seen slightly lateral to the midline. In bilateral paralysis
the vocal cords are flaccid and seldom in the midline position at first.
To prevent this complication, it is worth considering possible measures, such as monitoring the cuff pressure, and
to release it after retractor placement or improve image by
using a video mediastinoscope. More visualization contributes that the surgeon puts less traction on the nerve.

Joseph et al.

Usage of electromyography for recurrent nerve monitoring

during mediastinoscopy may be useful when bulky nodes
in the left paratracheal grove that must be harvested, but
such monitoring is not indicated for standard cervical mediasctinoscopy. (5)
References
1.

Carlens EL. Mediastinoscopy: A method for inspection

and tissue biopsy in the superior mediastinum. Dis Chest
1959;36:343-52.

2. Cerfolio RJ, Ojha B, Bryant AS, Bass CS, et al. The role of FDGPET scan in staging patients with non-small cell carcinoma.
Ann Thorac Surg 2003;76:861-6.
3. Carlens E, Hambraeus GM. Mediastinoscopy. Indications and
limitations. Scand J Respr Dis 1967;48:1-10.
4. Widstrom A. Pulsy of the recurrent nerve following mediastinoscopy. Chest 1975;67:365-6.
5. Roberts J R and Wadsworth J. Recurrent laryngeal nerve monitoring during mediastinoscopy: predictors of injury. Ann Thorac
Surg 2007;83:388-91.

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Scripta Medica
Vol. 41 No 2 October 2010.

SPECIJALNI LANAK

Tomislav Kai

Lini stav: preporuke i praksa

Beograd, Srbija

APSTRAKT
Moderna medicina se tokom poslednjih decenija transformie u nauku zasnovanu
na dokazima. A do dokaza o ekasnosti novih lekova se dolazi naunim metodima i
oni su u rezultatima randomiziranih klinikih studija (RTC), pa se unose u Preporuke
za dijagnostiku i terapiju, koje publikuju sva profesionalna udruenja: amerika,
evropska pa i nacionalna. Preporuke bi trebalo da olakaju snalaenje lekara i
stimuliu ih da bre prihvataju novine u terapiji i bolje lee svoje bolesnike. Meutim,
jedna inae dobra ideja nosi u sebi protivrenosti koje usporavaju planirani proces.
Probleme otvara injenica da farmaceutska industrija nansira RTC, nansira i
istraivae i komitete za pisanje preporuka, zbog ega jasni konikti interesa stvaraju
atmosferu kojoj nedostaje transparentnost i poverenje. Tako dolazi do sukoba izmeu
preporuka i prakse. Poueni prisustvom konikta interesa (mita i korupcije) na svim
nivoima do SZO, lekari u praksi vrlo uzdrano ili skeptino gledaju na preporuke koje
im stalno nude nove lekove, u iju vrednost oni argumentovano sumnjaju, mada su
svesni da ne mogu stalno leiti svoje bolesnike znanjima sa studija medicine. Politika
u zdravstvu trebalo bi da promovie kontinuiranu medicinsku edukaciju, zasnovanu
na naunim dokazima. To je teko izvedivo, jer pritisak novca dovodi do apsurdnog
izjednaavanja naune medicine s alternativnom tj. tradicionalnom, i svi oni napori za
promociju RCT-a bivaju obesmiljeni. Bolesnicima nikada nije bilo lako, ali sada nije
lako ni lekarima.

Klinika farmakologija stavlja u centar svojih aktivnosti

racionalizaciju terapije, zasnovanu na svim pozitivnim i
negativnim iskustvima pretklinikih i klinikih ispitivanja, kao i praenju upotrebe lekova posle putanja u promet.
Randomizirane klinike studije su postale instrument
pomou kojeg se objektivizuju dotada subjektivni utisci
velikih autoriteta o tome da je neki novi lek efikasniji od
starog, ili da je jedan nain leenja bolji od drugog. Cilj
njihovog izvoenja jeste da se pribave dokazi o efikasnosti
lieni svake pristrasnosti, jer su dobijeni primenom duplo
slepe metodologije, i zato dovoljno ubedljivi da se mogu
preneti u redovnu praksu. Farmaceutska industrija je prihvatila pravila igre u koju su ukljueni elitni akademski
krugovi, institucije i pojedinci.

Korespodencija
Prof. dr Tomislav Kai
tkazic@eunet.rs

Njihovi rezultati dokazi su odluujue uticali na

promenu terapijskih protokola u najvanijim oblastima
medicine. Tako je nastao novi talas u terapiji, poznat kao
Evidence based medicine (EBM) tj. Medicina zasnovana
na dokazima. U tom kontekstu se periodino analiziraju
rezultati velikih klinikih studija i periodino donose
optevaee Preporuke ili Smernice (engl. Guidelines) za
izbor najboljih lekova kod pojedinih indikacija, s obzirom
na to da se na tritu esto nalazi preveliki broj lekova
neujednaene efikasnosti i podnoljivosti. Meunarodna
udruenja za aterosklerozu, kardiologiju, hipertenziju i
druga, donose detaljne preporuke algoritme za stratifikaciju bolesnika i racionalan izbor lekova.

Tabela 1. Klase Preporuka

Klasa I

Dokaz i/ili opta saglasnost da je data terapijska ili dijagnostika procedura povoljna, korisna, i
efektivna

Klasa II

Kontradiktorni dokazi i/ili divergentna miljenja o korisnosti/efikasnosti terapije

Klasa IIa

Teina dokaza/miljenja je u korist terapije ili postupka

Klasa IIb

Korisnost/efikasnost je slabije ustanovljena dokazima/miljenjima

Klasa III*

Dokaz ili opta saglasnost da terapija ili popstupak nisu korisni/efektivni, a neki mogu biti i tetni

*ESC ne preporuuje III klasu

Kai

Tabela 2. Nivo dokaza

Podaci iz veeg broja randomiziranih klinikih studija ili meta-analiza

Podaci iz samo jedne randomizirane klinike studije ili velikog broja nerandomiziranih studija

Konsenzus miljenja eksperata i/ili mali broj malih studija: retrospektivne analize i registri

Preporuke formuliu vielani predstavniki komiteti koji

klasiraju vrednosti dokaza o efikasnosti lekova ili procedura i nivoe dokaza na nain koji je prikazan na Tabeli 1 i 2.

pojedinana ili grupna miljenja, svesni jakih uticaja industrije i na njihovo formiranje i promociju kao eksperata i
na formiranje i objavljivanje njihovih miljenja.

Medicina zasnovana na dokazima

Efikasnost se potvruje rezultatima randomiziranih, kontrolisanih klinikih studija (engl. randomized clinical trials RCT). One su postale glavni oslonac EBM-a, jer se
u njima stvaraju dokazi koji se ugrauju u Preporuke za
kliniku praksu. U sadanje vreme, sredinom 2010. godine,
verovatno ima preko 1.000 preporuka za razne dijagnoze,
odnosno indikacije ako ih je 2004. bilo 927 [1].

Konikt interesa i kriza poverenja

Konflikti interesa (novi eufemizam za mito i korupciju) ozbiljno nagrizaju kvalitet dokaza.

Efektivnost se potvruje u uslovima svakodnevne klinike

ili ambulantne prakse, a ekonomska isplativost se utvruje
farmakoekonomskim analizama.
Analiza medicinske prakse ukazuje da su ogromne razlike
izmeu efikasnosti i efektivnosti, da se u realnoj praksi
ne mogu ponoviti rezultati klinikih studija ne samo kod
nas na Balkanu, ve ni u najbogatijim i najrazvijenijim
sredinama Evrope i Amerike. Nad time lamentira direktor NIH (engl. National Insitutes of Health) C. Lenfant,
istiui kao eklatantne primere nedovoljnog propisivanja
beta blokatora, ACE inhibitora, aspirina i statina, iako
su mnoge klinike studije pokazale da ti lekovi smanjuju
kardiovaskularni (KV) i ukupni morbiditet i mortalitet,
smatrajui da je tako velika razlika izmeu efikasnosti
i efektivnosti bar delom posledica nedovoljne edukacije
lekara [2]. Medicina se zato okree raznim vidovima poslediplomske edukacije od kurseva, seminara, specijalizacija
do testova preko Interneta (CME).

Usporavanje tempa razvoja novih i efikasnih lekova, i medikalizacija odnosno komercijalizacija ivota uinili su da
se pritisak industrije na medicinu pojaava i preko granica
prihvatljivih za otvoreno, kritino drutvo. Medicinski
akademski krugovi su previe ukljueni u marketing novih
lekova i terapijskih procedura, u perpetuiranje mitova o
lekovima kao maginim mecima koji ciljaju na bolest.
Kao veliki uspesi promoviu se marginalne i nategnute razlike u efikasnosti u odnosu na efikasnost lekova koji su
decenijama u upotrebi, pa se posle esto izraava uenje
zato lekari opte prakse ne prihvataju rezultate klinikih
studija.
Nove analize ozbiljno dovode u pitanje i osporavaju napore
i intervencije za smanjenje zdravstvenog rizika u dve najmasovnije oblasti: hipertenziji i dislipidemijama.
Hipertenzija konstatuje se fijasko terapije osim za bolesnike sa vrlo visokim krvnim pritiskim, jer vai pravilo
polovine: polovina bolesnika ne zna da ima hipertenziju,
polovina od onih koji znaju se ne lei, polovina od onih koji
se lee, ne lee se pravilno, samo 10 - 30% leenih dostie
ciljne vrednosti, a analiza nesponzorisanih studija kod
bolesnika sa blagom i umerenom hipertenzijom ukazuje
da terapija koja traje 30 godina produava ivot za samo 24
dana.[4]

Pitanje zato se u praksi ne mogu ponoviti uspesi iz RCT-a?,

moe imati vie odgovora, koji se za ovu priliku mogu saeti
u jedan: Zato to su dokazi efikasnosti sve tanji! Naime,
dokazi se esto dobijaju pod pritiskom, na ovaj nain: [3]
Primenom kriterijuma za ukljuivanje; bolesnici se
vetaki homogenizuju, veina ih se ne ukljuuje u
studije, ve se posebnim kriterijuma iskljuuje, a
ukljui se tek svaki trei ili sedmi bolesnik, to ne odgovara realnoj situaciji u praksi;
Izborom visokih doza koje izabrani bolesnici dobro
podnose, a koje se teko mogu primenjivati u praksi;
Intenzivnim praenjem koje je neizvodljivo u praksi;
Prejakim uticajem sponzora studija na rezultate i interpretaciju.

Kod starih osoba PROSPER studija pokazuje da statini

sniavaju lipide i smanjuju broj infarkta, ali ne i ukupni
mortalitet (22 smrti manje od infarkta i loga, a 24 vie
od raka); ishod je isti samo se menjaju dijagnoze [5]. Deluje neverovatno da autori ove studije i urednici asopisa
Lancet olako prelaze preko poveanja incidence karcinoma
makar to bile i osobe starije od 70 godina.

Dakle, nije sluajno to su u Tabeli 2, eksperti u komitetima stavili na poslednje mesto po verodostojnosti svoja

Bode oi neprikriveni konflikt interesa prisutan na vie

nivoa od istraivaa, asopisa do najviih institucija. Ve-

Hiperlipidemija Kod ena u primarnoj prevenciji

snienje lipida ne smanjuje ni KV ni ukupni mortalitet, a
u sekundarnoj prevenciji smanjenje lipida prati smanjenje
incidence infarkta i KV mortaliteta, ali ne smanjuje ukupni
mortalitet.

93

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Scripta Medica
Vol. 41 No 2 October 2010.

like klinike studije od kojih treba da zavise globalni terapijski stavovi, industrija finansira direktno ili indirektno.
Direktno, kada to ini eksplicitno, a indirektno, kada jedna
velika firma voenje studije u kojoj se ispituje njen lek formalno poveri nekoj uglednoj instituciji, a ona sama odredi
vei deo tima eksperata koji rukovode istraivanjem. Po
zavrenom ispitivanju, kada dobijene rezultate treba ugraditi u preporuke, arogantno ispoljava svoju snagu nalazei
naina da njeni tienici budu najuticajnije linosti u
timovima za pisanje preporuka. Onda je normalno da
se takvi komiteti zalau za sve nie normalne vrednosti
krvnog pritiska, to se desilo 2003. godine, kad su i niske
vrednosti od 120-139 mm Hg bile oznaene kao prehipertenzija. Princip je isti kod komiteta u drugim forumima
i za druge dijagnoze, mada nije uvek jasno kako se stie taj
status, ko ih postavlja niti koliki je njihov realni uticaj na
medicinsku praksu.
Prava senzacija je dola s vrha britanske medicine: 2004.
je British Medical Journal (BMJ) objavio da vie od 50%
lanaka o efikasnosti lekova koje publikuju Lancet, New
England Journal of Medicine i BMJ piu autori-duhovi

iz industrije, a samo potpisuju najugledniji profesori s

najprestinijih univerziteta [6]. Kako se posle toga moe
verovati dokazima i preporukama nastalim pod takvim
okolnostima.
Lekari u praksi takoe nisu aneli niti su manje otporni
od drugih profesija na poklone i beneficije koje im prua
industrija i, direktno ili indirektno, utie na njihove
propisivake navike. To je bilo otilo predaleko, da su morali
da interveniu pravnici i za svako profesionalno udruenje
lekara, farmaceuta, pa ak i studenata, formuliu posebne
moralne kodekse koji do detalja opisuju kvalitet i kvantitet
poklona od industrije koji su drutveno prihvatljivi i koji
nee menjati propisivaku praksu lekara, tako da bi neka
uspena terapija bila zamenjena neuspenom ili sumnjivom.
Za bolesnike takva situacija u eri medikalizacije ivota u
kojoj skupi lekovi budu nueni za ostvarenje malih koristi,
ostavlja previe prostora da pomo za svoje tegobe potrae
u raznim vidovima alternativne terapije: fitoterapije, homeopatije, akupunkture ili se okreu ostalim modernim vidovnjacima i izbaviteljima. Medicina je poela molitvama
za spas od bolesti, a ini se da se krug zatvara.
Preporuke od oboavanja do osporavanja
Preporuke su edo globalizacije i sudbina im je zajednika.
Za sada, je odnos prema njima varijabilan: jedni ih potuju
jer im to odgovara, drugi ih potuju jer moraju, neki ih ne
potuju jer su svesni nedostataka, neki ih ne potuju jer
nemaju sredstava itd. [3]
Ipak, Preporuke imaju svoje proponente i oponente.
Proponenti su: industrija, profesionalna udruenja kao
ESC, ACC/AHA i sl., komiteti, autoriteti i apologeti global-

izacije.
Oponenti su: istraivai, individualci, kritini duhovi, lekari koji hoe da misle svojom glavom, i antiglobalisti.
Meu oponentima je dosta starih lekara, profesora i
naunika najvieg ranga, od kojih su neki ogoreni, drugi
zabrinuti, a njihovi stavovi zasluuju panju.
Attilio Maseri, veliko ime italijanske kardiologije, je jedan
od ogorenih i sa te pozicije kae na inauguralnom predavanju za visiting profesora Medicinskog fakulteta u Beogradu da Preporuke najvie odgovaraju: apotekarima,
koji nisu uili kliniku medicinu, lekarima koji su suvie
leerni da bi mislili, lekarima koji su proseni, posluni i
pokorni, lekarima koji misle politiki korektno.

Nisam studirao medicinu da bih sprovodio Preporuke!,

kae prof. Masseri.
Desmond Julian, profesor emeritus kardiologije u UK, argumentovano upozorava kolege u SAD na njihovom kongresu 2007. na rezultate GRACE studije: Zasnivati prognozu rizika na karakteristikama bolesnika koji su bili
ukljueni u studije je vrlo opasno! jer neukljueni umiru
dva puta vie, na primer, od akutnog infarkta miokarda
nego ukljueni [7].
Stav rukovodstva ESC-a je racionalan i umeren, kao i
stav naeg Udruenja kardiologa. Preporuke treba slediti
jer medicinska praksa se ne moe zasnivati na znanju
steenom na studijama niti samo na stavovima autoriteta;
preporuke treba smatrati vanim izvorom za kontinuiranu
edukaciju lekara [8].
Stavove eminentnih srpskih kardiologa znate iz prve ruke.
Danas se zalagati da medicina bude zasnovana na bolesniku izgleda staromodno na prvi pogled, ali se od toga
ne moe pobei! Bolesnik jeste u prvom planu. Bolesnik je
unikat i svaki unosi u proces leenja svu varijabilnost svoje
linosti i iskustva. Lekar ne moe da bira da li hoe ili nee
da lei svakog bolesnika koji doe u ambulantu.
Preporuke treba potovati u meri koju zasluuju, jer su
one samo saveti visokih strunih tela koja treba da lekaru
olakaju izbor leka i doze, a ne dogma koja se bespogovorno sprovodi; one ga ne oslobaaju individualne odgovornosti za odluke koje donosi, traei meru adekvatnu potrebi pojedinog bolesnika [3]. Posebno bi za ovu priliku bio
stimulativan nedavni kritiki osvrt u asopisu JAMA, koji
ukazuje na unutranje nedostatke kardiolokih preporuka ograniavajui se na ACC/AHA, ali kako su oni esto
zajedniki sa evropskim (ESC) i naim u Srbiji, i te kako
imaju vanost i za nau praksu. Sutina kritike jeste da su
dokazi slabi, da samo 11% preporuka ima najveu snagu
tj. klasu IA (vidi tabele 1 i 2), dok ak 48% ima uporite na
nivou C (miljenja eksperata, prikazi sluajeva i standardi
prakse)[9]. Prema tome, stav autora u prethodnom tekstu
ne treba olako oceniti kao kritizerstvo jednog frustriranog
Balkanca, ve kao priliku da se ukae na iskuenja pred ko-

Kai

jima se danas u vreme informatike revolucije nalaze

lekari i bolesnici.
Preporuke i praksa u Srbiji
Neki dogaaji postaju jasni tek kad se doe do apsurda u
koje nas sve uvodi politika. A period tzv. tranzicije daje
mnogo primera za to te medicina ne moe biti izuzetak.
Pod pritiskom kapitala raznih stepena istoe dolazi
stupnjevito do izjednaavanja moderne medicine s tradicionalnom medicinom, do izjednaavanja naunih dokaza
i praznoverja.
Nedavno, novembra 2009, publikovane su dozvole Ministarstva zdravlja Republike Srbije o obavljanju tradicionalnih metoda leenja, tako da je sada mogue da se polaganjem ruku na pacijenta kanalie energija iz okoline
dlanovima na delove tela koji su energetski oslabljeni.
Leenje iglicama, energijom, biljkama, mirisima vie
nije rezervisano iskljuivo za privatne ordinacije sve vie
dravnih kua trai dozvolu da, uz konvencionalnu medicinu, primenjuje i alternativne metode leenja. Domovi
zdravlja Stari grad i Zemun, Specijalna bolnica Sveti
Sava, Institut za reumatologiju, Klinika za rehabilitaciju
Dr Miroslav Zotovi i Zavod za zatitu elezniara su
prve ustanove koje su dobile dozvole Ministarstva zdravlja
za obavljanje tradicionalnih metoda leenja i to u okviru
dopunskog rada. Zainteresovani mogu da se podvrgnu
tretmanima iz alternativne medicine onim metodama koje
je drava priznala kao ravnopravne.
A priznato ravnopravne metode leenja su: ajurveda, akupunktura, tradicionalna kineska terapija, homeopatija,
fitoterapija, kvantna medicina, hiropraktika i primenjena
kineziologija, makrobiotika, tradicionalna domaa medicina, refleksologija, segmentna terapija, suoku, tuina i
ijacu. Dozvoljene su i metode rehabilitacije za unapreenje
zdravlja: apiterapija, aromaterapija, igong vebe, duhovna
energetska medicina, reiki, deteksija tetnih zraenja, joga
vebe, porodini raspored i taii uan vebe.
Alternativnom medicinom u naim domovima zdravlja i
bolnicama mogu da se bave iskljuivo zdravstveni radnici
koji su proli odgovarajuu obuku. Medicinari ne smeju da
budu osuivani i moraju imati zdravstveno uverenje. Osim
iskustva, rukovodstvo ustanove duno je da izdvoji poseban prostor za alternativne naine leenja.

Tako izgleda tranziciona medicina u Srbiji: Jedni te isti

eksperti piu ili prevode Preporuke evropskih udruenja
za kardiologiju, endokrinologiju, gastroenterologiju i druge specijalnosti i subspecijalnosti, sve zasnovane na dokazima iz randomiziranih kontrolisanih klinikih studija i
njima ravnopravne proglaavaju metode tradicionalne i/ili
alternativne medicine.
Srbija je ovde uzeta kao paradigma, zbog nedavnog ilustrativnog primera, ali da nije nita bolje u svetu ukazuje primer blamae Svetske zdravstvene organizacije koja je skoro
u isto vreme lansirala nepostojeu pandemiju svinjskog,
meksikog ili novog gripa i spasonosne vakcine a
sve zbog velikih profita grupacije BigPharma i insajdera u
SZO.
Ima li svemu tome kraja?
Literatura
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3.

4.
5.

6.
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8.

9.

Heneghan C. EBM Guidelines: Evidence based medicine. Evidence Based Medicine 2004;9:61 doi:10.1136/ebm 9.2.61
Lenfant C. Clinical research to clinical practice Lost in translation. N Engl J Med 2003;349;868-76.
Kai T. Terapija kao spoj nauke i prakse. U Kai T i Ostoji M
(urednici), Klinika kardiovaskularna farmakologija, 5. izdanje,
Integra, Beograd 2009:1-23.
Sturman MF. The medicalising of America, part I. Easy Diagnosis 2005a;2(8): Augus 2, online.
Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly
individuals at risk of vascular disease (PROSPER): a randomized controlled trial. Lancet 2002;360:1623-30.
Abbasi K.Transparency and trust. BMJ 2004;329: doi:10.1136/
bmj 329.7472.0-g
Steg PG, Lopez-Sendon J, Lopez de Sa E et al. For the GRACE
investigators. Arch Int Med 2007;167:68-73.
Bassand JP, Priori S, Tendera M. Evidence-based v impressionist medicine. How best to implement guidelines. EHJ
2005;26:1155-8.
Tricoci PL, Allen JM, Kramer JM et al. Scientific evidence
underlying the ACC/AHA clinical practice guidelines. JAMA
2009;301:831-41.

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Vol. 41 No 2 October 2010.

KOMENTAR

Traganje za dokazima
o ekasnom i sigurnom
leenju

Pri razmatranjima efektivne farmakoterapije, glavno nastojanje kliniara je usmereno na procenu efektivnosti i sigurnosti leka ili drugih terapijskih procedura. Kako lekar
moe biti siguran u dokaze koji se nalaze u literaturnim
izvorima (knjigama i asopisima)?
Nivo dokaza se moe uproeno svesti na to kako su
vrena istraivanja kojima se dolo do odgovarajue tvrdnje. Hijerahija dokaza se obino predstavlja ovim redosledom: (I) zakljuci dobijeni na osnovu prikaza i analize vie
randomiziranih klinikih studija (engl. systematic review
of randomized clinical trials - RTC) i tzv. meta-analize
su najsnaniji izvor, a slede (II) randomizirana klinika
studija, (III) opservaciona studija (cohort study, casecontrolled study ili cross-sectional survey), (IV) prikaz
sluajeva i na kraju (V) lino miljenje autoriteta. (1)
Baze podataka
Velika baza izvornih podataka je Medline. Ona obuhvata
preko 5.000 asopisa koji izlaze u vie od 70 zemalja. Besplatno je dostupna online na World Wide Web (WWW)
putem PubMed. Ostale baze podataka su AMED, CINHAL,
Current Contents, Embase, Health Star, Medicine, Premedicine, Psychinfo, ali i Google Scholar i MSN.com.
Pri traenju vieg nivoa dokaza, a posebno randomiziranih
klinikih studija i drugih kvalitetnih klinikih ispitivanja,
dobro je pored Medline i drugih izvornih baza podataka,
kombinovati pretrage s filtriranim i sintetisanim bazama podataka. Primeri za prvu grupu izvora su; Cocharne
Controlled Clinical Trials Register ili Evidence-Based Digests (npr. Evidence-Based Cardiology, Evidence-Based
Eye Care, Evidence-Based Medicine, Evidence Based
Mental Health), Health Technology Assessment Database
i NHS Economic Evaluation Database, a za drugu grupu:
American College of Physicians PIER, Clinical Evidence,
Cocharne Database of Systematic Reviews (DARE), Database of Abstracts of Reviews of Effectiveness, EvidenceBased on Call.
Cocharne Library sadri korisne informacije iz razliitih
baza podataka koje se mogu pretraivati zajedno. Zato
mnogi kliniari poinju pretragu unutar Cocharne Li-

brary. Ovde vredi navesti re-dve o nazivu tog izvora.

Kada je A. Cocharne bio student medicine 1938. godine,
nosio je ulicama Londona plakat s natpisom: Svi efektivni
naini leenja treba da budu besplatni. Njegova knjiga
Efektivnost i efikasnost (2) imala je mali odjek, ali je u njoj
bila sutina dananje medicine zasnovane na dokazima.
Baze podataka o citiranju lanaka su takoe vaan izvor
informacija, jer radovi koji su citirali neki lanak pokazuju
potvrdu, neslaganje ili dopunu citiranog, lanka. Traganje
o citiranju nekog lanka je mogue od ranih ezdesetih godina prolog veka, kada je Eugene Garfield osnovao Institute for Scientific Information. Najpre je publikovan Science Citation Index (SCI), zatim Social Science Citation
Index (SSCI) i Arts and Humanities Citation Index (AHCI).
Kasnije je nastala elektronska verzija za traenje citiranosti, Web of Science, koja ukljuuje SCI, SSCI i AHCI. Noviji
indeksi citiranja su OVID Medline citation track function i
Scopus, kojim se pretrauju asopisi, patenti, Web podaci i
praenje citiranosti.
Kada e prezauzet lekar praktiar traiti ove podatke?
Traganje za dokazima o efikasnosti i sigurnosti leenja
on obino trai kada naie na neki problem u praksi i eli
da se o njemu obavesti kako bi eventualno planirao svoje
istraivanje, drugim reima, kada planira istraivaki projekat. Pored toga, lekar ponekad eli da proveri da li vredi
uvesti nov, drugaiji terapijski postupak ili prihvatiti Preporuku o leenju koju je primio od nekog strunog tela.
Meutim, za seriju terapijskih inovacija, lekar obino koristi moderne prirunike (3), poput ovih koji su prikazani
u ovom broju naeg asopisa u rubrici Prikazi knjiga.
Saveti koji se nalaze u takvom priruniku imaju za cilj da
se postojee filtrirano znanje, tj. dokazi o efikasnosti i
sigurnosti leenja iznesu od strane eksperta, kako bi bili
iroko diseminirani i lako dostupni. Zato je i depno izdanje ovakvih knjiga primereno toj svrsi.
Lekarima se esto daju farmakoterapijske preopruke.
Njih piu eksperti za razna podruja medicine ispred
raznih sekcija lekarskih drutava, osguravajuih drutava,
dravnih organa, meunarodnih strunih organizacija,
Svetske zdravstvene organizacije itd. Te preopruke mogu
biti veoma korisne, ali ih uvek treba kritiki usvajati. (3)
Odnosi sa rmama
Farmaceutska industrija je veoma zainteresovana da utie
na lekare, pa ak i pacijente, da se lekovi koje oni proizvode
koriste to vie. Ne ale se znaajna novana sredstva da se
lek reklamira. Najefektivniji nain kojim se postie promena propisivake navike kliniara je lini kontakt saradnika
farmaceutske firme s lekarom. Taj saradnik putuje s tanom
u kojoj su dokazi da taj lek ima prednost nad drugima. (4)
Najbolje je za farmaceutsku kuu da njen saradnik pokae
kontrolisanu kliniku studiju u kojoj je taj lek uporeen s
placebom, a ne s nekim paralelnim lekom. Ako je taj lek
ba morao da se poredi s paralelnim, saradnik farmaceu-

Igi

tske kue obino pokae podatke koji porede lek koji bude
reklamiran s konkurentskim koji je davan u subterapijskim dozama. Nee taj saradnik saoptiti smrtne sluajeve
ili teke neeljene efekte leka. On, usput, obino navede
nekoliko uticajnih lokalnih lekara koji primenjuju taj lek.
Biete takoe ubeivani da se na lek, mada je skuplji od
konkurentskog, ipak, zbog svega drugog vie isplati.

nepublikovane materijale, pitajte ga kakva je sigurnost tog

leka, njegova tolerancija, efikasnost, cena, a neka vas ne
impresionira to je lek nov, jer to mu moe biti i mana.
Reference
1.
2.

Iskusni farmakolozi savetuju lekare(4): Primite predstavnika farmaceutske kue samo onda kada mu zakaete
prijem i to uradite ako vas dotini proizvod interesuje, ne
dozvolite da vam on deklamuje nauen tekst, pitajte ga ono
to vas interesuje, traite da vam pokae nezavisne publikovane dokaze o tom leku iz poznatih asopisa, ne pridajte znaaj promotivnim brourama jer one esto sadre

3.
4.

Greenhalgh T. How to read a paper. The basis of evidencebased medicine, third edition. London: BMJ, 2006.
Cocharne A. Effectiveness and efficiency. London: Nuffield
Provincial Hospitals Trust, 1972.
Kai T. Lini stav: Preporuke i praksa. Scripta Medica,
2010;41:
Anonymous. Getting good value from drug reps. Drug Ther
Bull 1983;21:13-5.

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Scripta Medica
Vol. 41 No 2 October 2010.

SPECIJALNI LANAK

Bojana Petri

Prikazi knjiga u Srpskom arhivu i

Vojnosanitetskom pregledu: Istorijska
perspektiva

University of Essex
United Kingdom

Prikazi naunih knjiga su odnedavno uli u fokus

lingvistikih istraivanja kao marginalan, ali ipak vaan
anr naune komunikacije u svim disciplinama. Prikazi
knjiga su krai tekstovi, obino locirani na poslednjim
stranicama asopisa, iji cilj je da informiu naunu javnost o novim naslovima i daju sud o njihovoj vrednosti i
doprinosu. U engleskoj literaturi postoje dva tipa ove vrste
teksta: prikaz knjige (book review), koji podrazumeva informacije o sadrini publikacije i njenu kritiku evaluaciju,
i obavetenje o novim knjigama (book notice), koje ukratko
predstavlja nova izdanja bez detaljne analize i procene.

Osim uloge kritike u prikazima knjiga, i sam nain kritikovanja naunih dela se menjao tokom istorije. Dok se
u 19. veku prikazivai nisu ustezali da kritikuju ne samo
delo, ve i autora lino, pa i da iznose ironine i sarkastine
primedbe, takav nain kritikovanja je ustupio mesto odmerenoj i konstruktivnoj kritici, koja radije bira indirektna sredstva izraavanja. Ovakav razvoj izraavanja
naune kritike konstatovan je u razliitim naunim disciplinama, ukljuujui medicinu, na engleskom, francuskom
i panskom jeziku (4-6), pa i na srpskom jeziku u oblasti
knjievnih nauka (7).

Istorijska prouavanja pokazuju da su prvi prikazi knjiga, objavljeni u engleskim asopisima u 17. veku, sluili
prvenstveno kao obavetenje o sadrini novih knjiga i da
su se esto sastojali iz obimnih citata iz dela sa vrlo malo
prateeg komentara; meutim, sa sve intenzivnijim objavljivanjem novih naslova, pojavila se potreba da se knjige
kritiki ocenjuju kao orijentir itaocima na koje knjige da
obrate panju (1,2). Kritiko procenjivanje tako postaje nezaobilazni element prikaza knjiga.

Postavlja se pitanje da li se slina razvojna putanja moe

nai u prikazima knjiga u medicinskim asopisima na
srpskom jeziku, to je bila polazna osnova za istraivanje
istorijskog razvoja prikaza knjiga u dva asopisa na srpskom jeziku, Srpskom arhivu za celokupno lekarstvo (SA)
i Vojnosanitetskom pregledu (VSP). Oba asopisa imaju
dugu tradiciju i uivaju veliki ugled u medicinskoj periodici na srpskom jeziku. SA je osnovan 1872. godine, a VSP
1944. godine. Oba asopisa su referisana u Web of Science
i svrstana u kategoriju M24, i predstavljaju jedine asopise
tog ranga koji objavljuju lanke i prikaze i na srpskom (a ne
iskljuivo na engleskom) jeziku.

Prouavanja strukture prikaza knjiga pokazuju da je evaluacija prisutna u svim segmentima teksta. Tako u studiji
prikaza knjiga iz hemije, ekonomije i lingvistike MottaRoth (3) otkriva etiri opta elementa strukture koji se
pojavljuju u gotovo svim prikazima knjiga, pri emu svaki
moe da sadri evaluaciju. Prvi segment je uvodno predstavljanje knjige, koje definie optu oblast kojom se knjiga
bavi, daje napomene o autoru, navodi koju vrstu italake
publike bi knjiga mogla posebno zanimati, i smeta knjigu
u iru oblast u odnosu na druga slina dela. Drugi segment
daje opti prikaz knjige s osvrtom na njenu organizaciju i
teme svakog poglavlja. Trei segment se detaljnije bavi delovima ili aspektima knjige koji zasluuju posebnu panju,
bilo zbog svojih vrlina ili mana. Konano, u etvrtom segmentu, knjiga se preporuuje itaocima zbog svoje vrednosti ili uprkos navedenim manjkavostima, ili se izrie
opta negativna evaluacija celog dela. Iako je ovaj model
nastao na osnovu prouavanja prikaza na engleskom jeziku, pokazalo se da vai i za druge jezike. Na primer, uputstvo za pisanje prikaza knjiga u oblasti medicine na srpskom
jeziku (4) sadri sve elemente ovog modela.

Ne ulazei u detaljnu lingvistiku analizu, ovde dajem

pregled najznaajnih optih promena u nainu izraavanja
kritike tokom tri istorijska perioda koji mogu zanimati
itaoce asopisa Scripta Medica. Uzorkovani su tekstovi iz
tri dekade, u razmacima od 50 godina: 1900 - 1909, 1950 1959 i 2000 - 2009.

Prikazi knjiga u prvoj dekadi 19. veka

U periodu od 1900. do 1909. godine, knjige se prikazuju
kroz kratka obavetenja, ali i duge i detaljne tekstove, u
kojima se mogu nai i otre kritike primedbe. U skladu s
ustaljenom praksom naune kritike toga doba (6), kritiki
ton se esto granii s omalovaavanjem autora, kao to se
vidi iz sledeeg, danas nezamislivog, primera:
Gde je pisac, po Bogu, itao da se crvena krvna zrnca i to
jo poto su izila iz krvnih sudova pretvaraju u levkocite

Petri

i gigantske elije? Izgleda mi da je pisac dotino mesto u

kakvoj patologiji ravo proitao, a jo gore razumeo. (SA,
1903, sv.1, str. 49)
Ipak, u veini prikaza prevladava pozitivna ocena, pogotovo kada se radi o knjigama stranih, uglavnom nemakih
autora, dok su prikazivai skloniji kritici kada piu o tada
dosta retkim knjigama domaih autora.

Prikazi knjiga sredinom 20. veka

Tokom pedesetih godina, dolazi do ogromnog porasta broja prikaza knjiga i prikazivaa. U odnosu na prethodni period, prikazuje se mnogo vei broj knjiga domaih autora,
to je razumljivo s obzirom na razvoj medicinske nauke
kod nas. to se stranih knjiga tie, zanimljivo je da se
prikazuju uglavnom originalna izdanja na svim svetskim
jezicima, a ree prevodi, to svedoi o aktivnom praenju
strane literature iz razliitih zemalja. U lingvistikom
smislu, prikazi postaju standardniji u smislu duine i
strukture teksta. Prikazi su mahom evaluativni, a sudovi i
pohvalni i kritiki. Ne izostaje ni nauna polemika kao to
je, na primer, kritiki dijalog izmeu autora Ratne hirurgije objavljene 1953. godine i njenog prikazivaa, koji je
voen tokom nekoliko brojeva Srpskog arhiva tokom 1953
i 1954. godine. Stie se utisak dinamine naune zajednice
koja kritiki prati i diskutuje najnovija dostignua u svojoj
oblasti.
Meutim, nain izraavanja kritike se bitno razlikuje od
prethodnog perioda, jer se, umesto kritike same linosti
autora, sada prvenstveno kritikuje delo, kao u sledeem
primeru:
U poglavlju o oteenju zracima, povrede koje oni prouzrokuju navedene su samo sumarno, kratko i nepotpuno.
(VSP, 1955, br. 5-6, str. 317).
Osim toga, u odnosu na prethodni period, primetna je
vea upotreba jezikih sredstava koja ublaavaju kritiku
otricu, kao to je kombinovanje kritikih i pohvalnih komentara u istoj reenici, kao u sledeem primeru:
U poglavlju o trovanjima skoro potpuno nedostaju
praktina uputstva za vetaka (izuzev praktino lepo
obraenog trovanja alkoholom). (VSP, 1955, br 5-6, str.
316).
Kritika se takoe ublaava optom pozitivnom evaluacijom
na samom kraju teksta, kao to je I pored navedenih manjkavosti, knjiga predstavlja znaajan doprinos, iako ima
i primera gde krajnja ocena ostaje u potpunosti negativna
(detaljnije o nainima ublaavanja kritike moe se nai u:
Hyland (1), za primere na srpskom vidi: Petri (7).

Prikazi knjiga u prvoj dekadi XXI veka

U periodu od 2000. godine do danas dolazi do velikih
promena. Pre svega, broj prikaza knjiga znatno opada,
tako da neki brojevi SA i VSP-a ne sadre nijedan prikaz.
Prikazuju se uglavnom knjige domaih autora, u manjoj
meri prevodi sa engleskog jezika, a jo ree originalna
strana izdanja. Promene su vidljive i u izboru knjiga za
prikazivanje: Dok su u prethodnom periodu prevladavale
naune publikacije, univerzitetski udbenici i prirunici,
sada su predmet prikaza u znatnoj meri i knjige iz istorije
medicine kod nas. Meutim, najznaajnija promena tie se
kritike, koja praktino nestaje sa stranica naih medicinskih asopisa. Od ukupno 40 prikaza objavljenih u SA
i VSP-u, uz dodatak kontrolnog uzorka od 10 tekstova iz
Medicinskog pregleda, samo dva teksta sadre kritike
primedbe. Ogromna veina prikaza se uglavnom fokusira
na predstavljanje sadrine na neutralan ili pohvalan nain,
bez udubljivanja u detaljniju ocenu. Drugim reima, veina
tekstova su obavetenja o novim knjigama (book notice),
a ne prikazi u uem smislu rei (book reviews). Zanimljivo je da je slian trend uoen i u prikazima knjiga u oblasti nauke o knjievnosti, na uzorku iz ista tri perioda iz
Letopisa Matice srpske (7).
Iako ogranieni tekstualni prostor donekle objanjava
odsustvo kritike, jer se radi mahom o kraim tekstovima,
ipak se postavlja pitanje o uzroku ove promene. Istina je da
je slian trend uoen i u prikazima knjiga na drugim jezicima, prvenstveno panskom, francuskom i bugarskom
(5,8,9), mada ni priblino u tolikoj meri kao na srpskom. U
asopisima na engleskom jeziku, meutim, kritika i dalje
ostaje nezaobilazan element u prikazima knjiga. Jedno od
objanjenja koje se navodi u literaturi kao razlog znatnijeg
izbegavanja kritike u naunom diskursu na nekim malim
jezicima u odnosu na engleski jeste veliina naune zajednice (8-11). U malim naunim zajednicama, kao u ovom
sluaju, postoji vea verovatnoa da se autori i prikazivai
knjiga lino poznaju, te je potreba za izbegavanjem mogueg
konflikta mnogo vea nego u meunarodnoj zajednici. Ovo
objanjenje deluje logino i sigurno je da bar u nekoj meri
objanjava ovu pojavu i u sluaju prikaza na srpskom jeziku,
ali ne bi moglo da objasni postojanje kritike poetkom 20.
veka, kada je nauna zajednica u oblasti medicine bila takoe
mala, tavie, mnogo manja nego danas. Drugo mogue
objanjenje jeste potreba za podrkom i solidarnou meu
lanovima naune zajednice, koje je naroito izraeno u periodima kada je nauna delatnost u krizi. Na delu su takoe
i drugi faktori, kao to su nepostojanje motivacije za pisanje prikaza poto se ne vrednuju u evaluaciji naune delatnosti, pisanje na molbu kolega autora, ogranien prostor
za prikaze knjiga u asopisima, to vodi skraivanju teksta,
a samim tim i pomanjkanju prostora za detaljniju procenu,
kao i injenica da se u dananjem brzom razvoju nauke nova
saznanja objavljuju prevashodno u naunim radovima, a ne
knjigama, te je mogue da prikazi knjiga vie nemaju takav
znaaj kakav su imali ranije.

99

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Scripta Medica
Vol. 41 No 2 October 2010.

Sigurno je da e urednici i autori u oblasti medicine imati

na umu i druga objanjenja, koja nisu poznata lingvistima,
te ovim putem elim da pozovem itaoce na diskusiju o
ovoj temi.
Reference
1.
2.

3.

4.
5.

Hyland, K. Disciplinary discourses. Social interactions in academic writing. London: Longman, 2000.
Salager-Meyer, F., Alcaraz Ariza, MA., Pabn Berbes, M. Collegiality, critique and the construction of scientific argumentation in medical book reviews: A diachronic approach. Journal of
Pragmatics, 2007, 39/10:1758-74.
Motta-Roth, D. 1998. Discourse analysis and academic book
reviews: A study of text and disciplinary cultures. In: Fortanet,
I., Posteguillo, S., Palmer, JC., Coll, JF. editors. Genre studies in
English for academic purposes. Castell: Universitat Jaume I,
1998, pp 29-58.
Igi, R. Kako se piu saoptenja o medicinskim istraivanjima.
Sarajevo: Veselin Maslea, 1980.
Salager-Meyer, F., Alcaraz Ariza, MA. Negative appraisals in
academic book reviews: A cross-linguistic approach. In: Candlin, C., Gotti, M. editors. Intercultural aspects of specialised
communication. Frankfurt: Peter Lang, 2004, pp 149-72.

6. Salager-Meyer, F. 2010. Academic book reviews and the construction of scientific knowledge (1890-2005). In: Posteguillo,
S., Gea Valor, ML., Garca Izquierdo, I., Esteve, MJ. editors.
Linguistic and translation studies in scientific communication.
Bern: Peter Lang.
7. Petri, B. Scholarly criticism in a small academic community: A
diachronic study of book reviews in the oldest Serbian scholarly
journal. In: Salager-Meyer, F., Lewin, BA. editors. The word
and the sword: Criticism in the academy. Bern: Peter Lang (u
tampi).
8. Lors Sanz, R. (Non-)critical voices in the reviewing of history
discourse: A cross-cultural study of evaluation. In: Hyland, K.,
Diani, G. editors. Academic evaluation. Review genres in university setting. Basingstoke: Palgrave Macmillan, 2009, pp 143-60.
9. Shaw, P., Vassileva, I. Co-evolving academic rhetoric across culture: Britain, Bulgaria, Denmark, Germany in the 20th century.
Journal of Pragmatics, 2009, 41:290305.
10. Duszak, A. editor. Culture and styles of academic discourse.
Berlin: Mouton de Gruyter, 1997.
11. Moreno, AI., Surez, L. A study of critical attitude across English and Spanish academic book reviews. Journal of English for
Academic Purposes, 2008, 7/1: 15-26.

Naslov teksta maksimalmo dva reda, po potrebi povecati sirinu

tekst boksa da stane naslov, Etiam dapibus iaculis euismod

CONTINUING EDUCATION

Faruk Hadziselimovic,
Nela Raeta, 2Mirko
atara, 2Radoslav Gajanin,
2
Dejan Bokonji,
1

Questions & Answers

1. Kindertagesklinik Liestal
Switzerland

2. Medicinski fakultet, 75000

Banja Luka
Correspondence

Dejan Bokonji, MD, PhD

78000 Banja Luka
Republic of Srpska, Bosnia &
Herzegovina

Questions
1. A 6-year-old male undergoes an elective repair of inguinal
hernia. An undescended testicle is encountered in the inguinal canal. Thus, in addition to a high ligation repair of the indirect hernia sac, an orchiopexy is performed. Which of the
following statements is true?
a. Germ cell tumors are very rare type of testicular cancer.
b. Increased serum human chorionic gonadotropin (hCG)
level is almost always found in association with seminoma.
c. Orchipexy does not reduce the likelihood that this patient
will develop testicular cancer.
d. A biopsy of suspected testicular cancer may be safely performed under local anesthesia via a scrotal incision.
e. Seminomas are insensitive to radiation therapy.
2. Which tumor marker is most often associated with hepatocellular carcinoma?
a. Beta-hCG
b. Alpha-fetoprotein
c. CA 19-9
d. Carcinoembrionic antigen
e. CA 125
3. Gout is a syndrome caused by deposition of urate crystals.
It typically presents as an acute monoarthritis of rapid onset.
The first metatarrsophalangeal joint is the most commonly
affected joint (podagra). Diagnosis is usually made clinically.
Describe various treatments of acute attack of gout.
4. The Achilles tendon does not have a true synovial sheath. It
is surrounded by a paratendon (fatty areolar tissue that separates the tendon from its sheath). The early pain of Achilles
tendinitis is caused by injury to the paratendon rather than
to the tendon itself. Pain is greater when the patient gets up in
the morning and often improves with continued walking, as
the tendon moves more freely inside the paratendon. Similarly, pain increases when exercise is begun and often improves

as exercise continues. The Achilles tendon is tender when

squeezed between the fingers. If pain is ignored and running
continued, inflammation spreads to the tendon, and pain is
then constant and exacerbated by movement.
The diagnosis of ruptured tendon Achilles is often missed, perhaps because it is not realized that the foot can still be plantar
flexed by the toe flexors. The classic signs are a palpable gap
in the tendon, excessive active and passive dorsi-flexion of
the foot, and inability to stand on tiptoe on the affected foot.
However, these signs may be difficult to assess because of pain
and swelling at the time of injury. With the patient prone or
kneeling, the calf is firmly but gently squeezed just distal to its
maximal circumference. Where the tendon is intact the foot
plantar flexes. Where the tendon is ruptured, no plantar flexion occurs. This test will also differentiate ruptured tendon
Achilles from the other common injury to the calf.
How the Achilles tendon can be strengthened?
5. A 68-year-old male presents to your communitybased
health center with history of weight loss, chronic cough, and
hemoptysis. The patient has a 65-pack-per-year smoking history. You obtain a chest x-ray, which shows a mass near the
hilum of he lung. A CT scan confirms the presence of a centrally located 3 cm mass. Bronchoscopy with transbronchial
biopsy was done. When you receive the pathology report of the
biopsy, you determine the mass to be unresectable based on
the biopsy results. Which of the following tumor histologies
has the most aggressive natural history?
a. Squamous cell carcinoma
b. Adenocarcinoma
c. Small cell carcinoma
d. Large cell carcinoma
e. Hodgkins disease
6. A 64-year-old male was diagnosed with cirrhosis of the liver secondary to hepatitis C infection more than 10 years ago.

101

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Scripta Medica
Vol. 41 No 2 October 2010.

Which of the following is used in determining this patients

Childs classification?
a. Age
b. History of smoking
c. Encephalopathy
d. Hepatocellular enzyme elevation (ALT, AST)
e. PTT
7. A 6-week-old male infant is brought to the clinic because of
a 2-week history of emesis. The mother describes the emesis
as nonbilious and reports it has become projectile over the
last 48 hours. On physical exam, the infants abdomen is soft
and a palpable mass is detected in the right upper quadrant. A
contrast study is obtained. The images show the gastric outlet
obstruction. What is this childs most likely diagnosis?
8. What are the simple measures that may be tried to stop hiccup (singultus)?
9. How to read a paper?
10. What is qualitative research?

Answers
1. C. Testicular cancer is the most common solid tumor found
in young adult men. More than half of painless solid swellings
of the body of the testis are malignant, with peak incidence
in men aged 25-35 years. About half of testicular cancers are
seminomas, which tend to affect older men, and have a good
prognosis. Criptorchidism significantly increases the affected
individuals risk of testicular cancer. Orchiopexy (the placement of cryptorchid testicles back in the scrotum) does not
alter their malignant potential. Thus, examination for the tumor detection in such persons should be performed regularly.
a. Ninety-five percent of testicular tumors arise from germ
cells. These tumors include seminomas, non-seminomas, embrional cell carcinomas, choriocarcinomas, and teratomas.
b. Human chorionic gonadotropin (hCG) is found in almost
100% of choriocarcinomas, and teratomas.
d. Seeding of malignant cells can occur along the biopsy tract
site. Therefore, orciectomies should be approached trough an
inguinal incision.
e. Seminomas are highly sensitive to radiation therapy. (In
men with good prognosis non-stage 1 seminoma who have
had orchidectomy, radiotherapy may improve survival and be
less toxic than chemotherapy, except in men with large volume disease, in whom chemotherapy may be more effective.
Standard radiotherapy treatment comprises 30-36 Gy in 1518 fractions.)
2. B. Alpha fetoprotein (AFP) is associated with hepatocellular carcinoma. More than 70% of patients with an HCC larger
than 3 cm will have an elevated AFP level.

a. Beta-hCG is associated with intrauterine pregnancy, as well

as testicular and trophoblastic tumors.
c. CA 19-9 is associated with pancreatic cancer, but it may also
be elevated in colorectal and gastric cancers.
d. CEA is associated with colorectal cancer. It may also be elevated in HCC, pancreatic, brest, and testicular cancers.
e. CA 125 is associated with ovarian tumors.
3. The response to colchicine, oral (1 mg per every 2 h until a
response is obtained or until diarrhea or vomiting occur; no
more than 7 mg should be taken in 48 h) is often dramatic.
Joint pains generally begin to subside after 12 h of treatment
and cease within 36 to 48 h. Attention: Severe electrolyte
imbalance can accompany colchicine-induced diarrheal episodes with disastrous consequences, especially in elderly patients. The high incidence of adverse effects in patients taking
cochicine precludes its use as routine treatment.
NSAIDs are effective in acite attacks of established gout. Daily
doses are usually taken with food for 2 to 5 days. NAAIDs may
cause many complications, including GI upset, hyperkalemia (in
patients whose renal blood flow is prostaglandin E2-dependent),
and fluid retention. Elderly and dehydrated patients are at particular risk, especially if there is a history of renal disease. Two
equivalence studies found no difference in pain between etoricoxib and indomethacin, but found that indomethacin was associated with more adverse effects. The adverse effects of NSAIDs
include gastrointestinal ulceration and hemorrhage, and for at
least some COX-2 inhibitors, increased cardiovascular risk.
Gouty attacks may be treated by aspiration of affected joints,
following by instillation of corticosteroid esters. Prednisolone
tebutate 10 to 50 mg can be uses, with doses depending on the
size of the affected joint. Single dose of ACTH 80 U im is very
effective treatment and may be especially useful in treating
gouty attacks in postoperative patients who cannot take oral
medications. Prednisone may also be used in short courses
(20 to 30 mg/day) for polyarticular attacks.
In addition to specific therapy, rest and abundant fluid intake
are indicated. Treatment of drugs that lower the serum urate
concentration should be deferred until acute symptoms have
been completely controlled.
4. The athlete should stop running. Rearfoot control may
improve by inserting orthotics in shoes with tight, stiff heel
counters. Performing toe raises, if they are not painful, can
strengthen the Achilles tendon. The patient should avoid fast
uphill and downhill running until the tendon heals.
Instructions for toe raises
Stand, slowly rise on the toes, and then slowly descend
back on the heels. Perform this 10 times; followed by 1
min of rest, then two more sets of 10. When this exercise
feels easy, use progressively heavier hand weights.

Hadziselimovic et al.

5. C. Four types of primary lung tumors exist: adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and
large cell carcinoma. Small cell carcinoma usually originates
in the major bronchus near the hilum. It is known for its rapid
growth and early metastasis to both lymphatic and blood vessels. It is therefore considered by many to be metastatic at the
time of diagnosis.
a. Squamous cell carcinoma accounts for 30% of primary
malignant lung tumors. It occurs centrally in the segmental,
lobar, or mainstem bronchi. Slow growing and late to metastasize, this type of tumor lends itself to resection if diagnosed
early enough.
b. Adenocarcinoma accounts for 40% of malignant lung tumors. It is most often peripheral in location. Like squamous
cell carcinoma, adenocarcinoma is late to metastasize and
may be resectable.
d. Ten percent of malignant lung tumors involve large cell
carcinomas, which are also usually located in the periphery.
These tumors show rapid growth and early metastasis, but are
known to be less aggressive than small cell carcinomas. The
majority of large cell carcinomas are poorly differentiated adenocarcinomas.
f. Hodgkins disease is a lymphoma that usually presents asymptomatic adenopathy and constitutional symptoms of fever, night sweats, and weight loss. Hodgkins lymphomas are
highly responsive to radiation therapy and chemotherapy.
6. The Child-Pugh classification of cirrhosis is a method of
predicting operative mortality. Patients with cirrhosis are
at increased risk for associated morbidity and mortality for
any kind of surgery. The operative mortality associated with
Childs classes A, B, and C is 2%, 10%, and 50%, respectively.
Score A is 5-6, score B is 7-9, and score C is 10 points or higher.
Following Child-Pugh Classication Points are used for the
Relevant Calculation

Factor/Points

Serum bilirubin (mg/dl)

<2

2-3

>3

Serum albumin (g/dl)

>3.5

2.8-3.5

<2.8

Ascites

Absent

Mild

Moderate

Hepatic encephalopathy
None
(grade)

1, 2

3, 4

PT (INR)

1.7-2.3

>2.3

<1.7

a, b, d, e. Age, history of smoking, ALT and AST levels, and PTT

are not used to determine the Childs classication.

7. D. This is the classic description of hypertrophic pyloric stenosis. Patients present with history of projectile emesis and
often have a palpable, oliveshaped mass in the right upper
quadrant. The contrast study images show the gastric outlet
obstruction of pyloric stenosis. It is four times more common
in male infants and usually presents at 4 to 8 weeks of age.
Dehidratation is often seen with a hypokalemic, hypochloremic metabolic alkalosis. All resulting electrolyte abnormalities should be corrected prior to proceeding to the operating
room. Most patients resume oral intake within 12 hours of
surgery. (The Fredet-Ramstedt pyloromyotomy is the classic
operation performed.)
a. Duodenal atresia presents as bilious emesis in the newborn
and is associated with the classic double bubble sign on abdominal x-rays.
b. Cholangiocarcinoma is a tumor of the biliary tree; it is nor
typically seen in children.
c. Hirschprungs disease presents as a relative colonic obstruction and difficulty-passing stool due to an aganglionic
segment of the distal colon.
e. Intestinal malrotation is a surgical emergency and must be
considered. Infants with malrotation might vomit, however,
they would also have distension and pain, which are symptoms not usually found in children with pyloric stenosis.
8. Hiccup presents repeated involuntary spasm of the diaphragm, followed by sudden closure of the glottis, which
checks the inflow of air and produces the characteristic sound.
Hiccups follow irritation of afferent or efferent nerves or of
medullar centers that control the respiratory muscles, especially diaphragm. Swallowing hot or irritating substances may
stimulate afferent nerves. High blood CO2 inhibits hiccups,
while low CO2 stimulates them. Hiccups are more common in
men and often accompany diaphragmatic pleurisy, pneumonia, uremia, alcoholism, or abdominal surgery. The cause of
most prolonged or recurrent hiccups can be determined, but
the cause of other episodes may never become apparent.
Various simple measures may be tried, such as, increasing
PaCO2, and inhibiting diaphragmatic activity by series of deep
breath-holdings or by re-breathing deeply into a paper bag.
A plastic bag should not be used, because it may cling to the
nostrils. Vagal stimulation may work: drinking glass of water
rapidly, swallowing dry bread, or inducing vomiting. Inhalation of carbogen (5% CO2 and 95% O2) is of value, particularly in postoperative patients. Metoclopramide 10 mg p.o. bid
to qid may help to some patients. Sometimes even bilateral
phrenicotomy does not cure all cases.
9. Medical doctors and researchers spend a great deal of time
reading research papers. They must read papers for several
reasons: to review them for a conference or seminar, to keep
current in their field, or for a literature survey of a new field.

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However, this skill is rarely taught, leading to much wasted

effort.
The key idea is that one should read the paper in several passes. Each pass accomplishes a special goal and builds upon the
previous pass: The first pass gives to a reader a general idea
about the paper. The second pass lets him grasp the papers
content, but not its details. The third pass helps him to understand the paper in depth.
However, as clinical practice becomes busier, and time for
reading and reflection becomes more and more precious, the
ability effectively to peruse the medical literature and to become familiar with knowledge of best practice from modern
communication system will be essential skills for doctors.
Good instructions for search in the literature, papers that report drug trials, diagnostic or screening tests, etc., one can
find in journal articles or books dedicated to such education.
10. Question such as what proportion of smokers have tried
to give up? clearly need quantitative methods, but question
What stops people from giving up smoking? cannot be answered by leaping in and measuring the first aspect of the
problem that we (the outsiders) think might be important. After a while, we need to hang out, listen to what people come up
with. After a while, we may notice a pattern emerging, which
may prompt us to make our observations in a different way.
We may start with one of the methods (passive observation,
participant-observation, semi-structured interview, narrative
interview, focus groups), and go on to use a selection of others.
Qualitative or interpretative research was for years the territory of social scientists. It is now increasingly recognized as
being not just complementary to, but in many cases, a prerequisite for the quantitative research with which most of the
biomedical scientists are ore familiar.

The differences between the qualitative and quantitative research (the overstated dichotomy) in health care may be presented as follows:

Qualitative
Methods: observation, interview
Reasoning: inductive
Sampling methods: theoretical
Strength: validity

Quantitative
Methods: experiment, survey
Reasoning: deductive
Sampling method: statistical
Strength: reliability
If the objective of the research was to explore, interpret or
obtain a deeper understanding of a particular clinical issue,
qualitative methods were almost certainly the most appropriate ones to use. If, however, the research aimed to achieve
some other goal (such as determining the incidence of a disease or the frequency of an adverse drug reaction, testing a
cause-and effect hypothesis or showing that one drug has a
better risk-benefit ratio than other), qualitative methods are
clearly inappropriate!

Literature
1.

2.
3.

4.

Doctors have traditionally placed high value on numberbased data, which may in reality be misleading, reductionist
and irrelevant to the real issues. The increasing popularity
of qualitative research in the biomedical sciences has arisen
largely because quantitative methods provided either no answers, or the wrong answers, to important questions in both
clinical care and service delivery.

5.
6.
7.

(Short sections from the following books or articles were used

to prepare this educational section. Some of these parts were
modified according to the present knowledge. Main purpose of
this text is that our readers improve their medical English.)
BMJ Publishing Group. Clinical evidence handbook. London,
BMJ, 2008.
Greenhalgh T. How to read a paper. The basics of evidencebased medicine. Malden, Blackwell Publishing, 2006. (London,
BMJ, 2001.)
Keshav S. How to read a paper. ACM SIGCOMM Computer Communication Review 2007:37:83Lane KAG (ed.), The Merck manual, seventeenth edition. New
York: Merck, 1999.
Macleod J, ed. Clinical examination, sixth edition. Edinburgh,
Churchill Livingstone, 1983.
Nelson EW. Blueprints Q&A step 3 surgery, second edition.
Malden, Blackwell, 2005.

105

CASE REPORT

Cor triatriatum sinister u odraslog

bolesnika sa plunom hipertenzijom

Aleksandar M. Lazarevi,
Sandra Lazarevi
Specijalistika ordinacija interne
medicine Cardio, Banja Luka,
Republika Srpska
Bosna i Hercegovina
Adresa za korespondenciju:
Prof. Dr. Aleksandar M. Lazarevi
Specijalistika ordinacija interne
medicine Cardio
Pave Radana 17
78000 Banja Luka
Republika Srpska
Bosna i Hercegovina
Tel. 051 346 000
Fax: (+387) 51 346 001
E-mail: alazar@inecco.net

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Prikazi knjiga

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Scripta Medica
Vol. 41 No 2 October 2010.

Momir Mikov, Ranko krbi i John Paul

Fawcett: Sulphasalazine: past, present and
future challenges. Banja Luka, Medicinski
fakultet Univerziteta u Banjoj Luci, 2009. Knjiga
sadri 85 stranica, format 17x23 cm, tira 300
primeraka, ISBN 978-99938-42-40-8.

Monografija o sulfasalazinu je vieautorsko delo, koje potpisuju prof. dr Momir Mikov i asist. mr pharm. Svetlana
Goloorbin-Kon s Medicinskog fakulteta Univerziteta u
Novom Sadu, prof. dr Ranko krbi i asist. mr sc. med.
Nataa Stojakovi sa Medicinskog fakulteta Univerziteta u
Banjoj Luci i prof. dr John Paul Fawcett i njegovi studenti
Elizabeth Yee, Marie Kong, Eugenie Huang, Pauline Hung,
Goldie Wong i Philip Tsai, svi sa Farmaceutskog fakulteta
Univerziteta Otago, Novi Zeland.
Pored tekstualnog dela, knjiga sadri est dijagrama, tri tabele i 244 reference. Pisana je odlinim engleskim jezikom,
lakog i razumljivog stila. Podeljena je u osam glavnih poglavlja: Otkrie, Fiziko-hemijske karakteristike, Farmakokinetika, Farmakodinamika i terapijska primena,
Neeljeni efekti, Farmaceutski oblici, Budunost sulfasalazina i Saetak, a na kraju slede reference.
Autori su ovim delom eleli da obelee sedamdesetogodisnjicu otkria sulfasalazina (1939 - 2009). Nanna Svartz
je dola na ideju da u jednu molekulu spoji sufapiridina
(jedan od sulfonamida) i 5-aminosalicilnu kiselinu (mesalazin; 5-ASA), poto su dotadanji pokuaji da se reumatoidni artritis lei pojedinanom primenom sulfonamida
ili salicilata ostali neuspeni.
Kao nastavnik farmakologije, moram da istaknem da je
posebna vrednost ove knjige u tome to se itaocu, a to bi
svakako trebalo da budu i nai dodiplomski studenti, daje
pogled na sulfasalazin koji znaajno odudara od onoga to
se nalazi u dostupnoj udbenikoj literaturi na naem jeziku. U tom smislu, sulfasalazin nije tek puki prolek ili nosa
za mesalazin, koji se iz njega oslobaa u distalnim partijama digestivnog trakta azo-redukcijom pod dejstvom enzima iz crevnih bakterija i proizvodi kompletan antiinflamatorni efekat, ve supstanca, koja per se, ali i preko drugog
metabolita sulfapiridina, proizvodi brojne povoljne terapijske efekte, koji nisu samo lokalni, tj. ogranieni na crevo,
ve i sistemski. Time se i predstava o mestu sulfasalazina u
savremenoj farmakoterapiji menja od starog, gotovo opsoletnog, leka koji moe da se koristi u inflamatornoj bolesti
creva, ali ga je bolje zameniti njegovim metabolitom mesalazinom, koja je sredstvo prvog izbora, u jo znaajan
lek koji zauzima svoje mesto u leenju niza bolesti, meu
kojima i reumatoidnog artritisa, ulcerativnog kolitisa,
Crohnove bolesti, psorijatinog artritisa, juvenilnog artri-

tisa, ankilozirajueg spondilitisa i ulkusa eluca. Autori,

meutim, istiu da je u nekim klinikim studijama jasno
pokazano da se terapijski efekat sulfasalazina odrava
samo tokom 8-12 nedelja, posle ega poinje da se gubi.
U svakoj od ovih indikacija - a to je ujedno i najsadrajnije
i najdue poglavlje u knjizi autori najpre objanjavaju
mehanizam delovanja sulfasalazina, a potom komentariu
rezultate klinikih studija. U zakljuku se istie da je sulfasalazin jedan od tzv. DMARD (Disease-Modifying AntiRheumatic Drugs) i da se kao takav koristi u drugoj liniji (nakon nesteroidnih antiinflamatornih lekova). Ova upotreba
moe da bude u obliku monoterapije ili, sa jo boljim rezultatima, u dvojnim (s metotreksatom ili hidrohlorohinom)
ili trojnim kombinacijama (s metotreksatom i hidroksihlorohinom). Kao monoterapija kod bolesnika s reumatoidnim artritisom, sulfasalazin je ekvivalentne efikasnosti s
terapijom zlatom, d-penicilaminom ili metotreksatom, s
tim to mu efekat nastupa bre.
Monografija nudi objektivnu sliku o racionalnoj primeni
sulfasalazina, poto se u njoj istie da je za leenje zapaljenjske bolesti creva distalne lokalizacije (ulcerativni kolitis
ili proktokolitis) preporuljivije leenje mesalazinom, i to
ili samo klizmama ili supozitorijima, ili njihovim kombinovanjem s peroralnim preparatima mesalazina. U tom
smislu se u pretposlednjem poglavlju panja posveuje i samom mesalazinu i olsalazinu kao konjugatu dve molekule
mesalazina i definie im se mesto u farmakoterapiji ulceroznog kolitisa i proktokolitisa.
U zakljuku bih istakao da ova obimom nevelika, ali
sadrajem veoma znaajna monografija predstavlja svake
hvale vredan internacionalni poduhvat, kojim se sistematizuje i na jednom mestu prezentuje savremeni pogled
na mesto jednog starog, ali jo veoma aktuelnog leka u
farmakolokom armamantarijumu koji nam stoji na raspolaganju za leenje itavog niza tekih inflamatornih
stanja u gastroenterologiji i reumatologiji. Uveren sam da
e publikacija naii na veoma povoljne reakcije svoje ciljne
publike dodiplomskih i poslediplomskih studenata medicine i farmacije, lekara opte prakse, klinikih farmakologa, internista, dermatovenerologa, kao i subspecijalista
gastroenterologije i reumatologije.
Prof. dr Milo P. Stojiljkovi

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Vineta Vuksanovi: Klinika mikrobiologija.

Podgorica, Univerzitet Crne Gore, 2009. Knjiga
sadri 258 strana, format 17x24 cm, tira 400
primeraka, ISBN 978-86-908751-5-3.

Mikrobiologija je predklinika i klinika medicinska disciplina koja se slua na medicinskom, stomatolokom i

drugim fakultetima unutar zdravstva. To su imali u vidu
tvorci Bolonjskog programa studija pa studenti medicine
izuavaju ovu medicinsku oblast u dva nastavna predmeta: na drugoj godini studija pod nazivom mikrobiologija i
na etvrtoj godini u okviru klinike mikrobiologije. Poto
klinika mikrobiologija, kao poseban predmet, u ranijem
periodu studiranja medicine nije postojao, nije kod nas ni
bilo udbenika koji je obraivao samo taj aspekt mikrobiologije. Ovaj nedostatak bio je motiv autora da napie udbenik koji e olakati izvoenje nastave iz tog predmeta.
Udbenik Klinika mikrobiologija sadri desetak kraih
uvodnih poglavlja posveenih uzimanju mikrobiolokih
uzoraka nosa, nazofarinksa, grla, uha, oka, ispljuvka, koe,
apscesa i peritonealne tenosti. Slede opirna poglavlja u
kojim su obraene infekcije uha, oka, koe, respiratirnog
i gastrointestinalnog trakta, genitalnih organa, urinarnog
trakta, centralnog nervnog sistema, kao i virusni hepatitisi
i retrovirusi. Posebno su prikazane mikrobioloke pretrage
krvi, mikrobioloki nalaz kod trudnica i bolnike infekcije.
Koncept ovog udbenika je savremen; akcenat je stavljen
ne samo na karakteristike mikroorganizama, ve i na patogene mehanizme koje dovode do infektivnih bolesti, a delom i na leenje. Zadatak autora bio je delikatan i zahtevan
jer je na nov i originalan nain trebalo da se sistematizuju,
analiziraju i prikau kompleksni odnosi izmeu mikroorganizama i domaina, te sve prezentuje prema organskim
sistemima. Infekcije pojedinih organskih sistema autor je
detaljno opisao i prikazao prema razliitim uzronicima
(bakterije, virusi, gljive, paraziti), te naveo novija saznanja
o sloenoj patogenezi infekcija i ukazao na faktore koji se
odnose na virulenciju mikroorganizama. Razraeni su i
dijagnostiki postupci koji su kritiki analizirani, a to je
dragoceno za pravilno tumaenje mikrobiolokih rezultata
u sklopu odreene klinike slike. Poglavlje Mikrobioloki
nalaz kod trudnica predstavlja poseban doprinos sadraju
i aktuelnosti udbenika. Tu autor znalaki i sistematino
prikazuje savremena saznanja i sopstvena iskustva o infekcijama koje esto ugroavaju zdravlje ena u tom stanju i
utiu na tok i ishod trudnoe.
Intrahospitalne infekcije su vaan problem u zdravstvu.
Zato im je autor posvetio panju, kako bi taj tekst bio vodi
za uspeno sprovoenje nunih hospitalih mera, ukljuujui i epidemioloki nadzor u stacionarnim zdravstvenim

ustanovama. Izneti podaci o virusnim hepatitisima i HIV

infekciji su danas sve znaajniji, jer ovi tipovi infekcije stalno prete. Zato su neophodna uputstva i znanje za rad u ovoj
oblasti sve potrebniji.
Udbenik je ilustrovan sa 72 tabele i slike u boji. Dato je
189 referenci domae i strane literature. Meutim, neke
reference su ispisane neujednaenim stilom i to bi trebalo
da bude ispravljeno u narednom izdanju udbenika. Uz to,
vredelo bi dati kratka uputstva o leenju pojedinih infekcija koja su zasnovana na dokazima i prirediti predmetni
indeks. Da bi nuni literaturni izvori bili lake dostupni
studentima i ostalim zainteresovanim, trebalo bi da bude
navedeno vie referenci koje su besplatno (free access) dostupne posredstvom Interneta.
Knjiga Klinika mikrobiologija e, pored osnovne uloge
u nastavi etvrte godine medicine, koristiti i kao dopunska literatura za studente drugih zdravstvenih usmerenja.
Knjigu preporuujem i lekarima raznih specijalnosti da im
poslui kao prirunik. Ona e svim itaocima biti vodi za
pravilno uzimanje uzoraka i tumaenje dobijenih laboratorijskih rezultata u oblasti klinike mikrobiologije.
Prof. dr Branislava Koci

Savo ibali: Antimikrobna sredstva i ljekar

praktiar, drugo izdanje. Tuzla, PrintCom, 2008.
ISBN 978-9958-633-82-9

Tomislav Kai: Antibiotici za kliniku praksu.

Beograd, Integra, 2010. ISBN 978-86-87907-01-0
Do 1935. godine nije bilo lekova za efikasno leenje sistemskih bakterijskih infekcija. Te godine je otkrie sulfonamida potvrdilo Erlihov koncept hemoterapije i oznailo
novu eru u medicini. To otkrie bio je veliki podsticaj za
pronalazak novih antibakterijskih lekova. Nakon otkria
penicilina i njegovog preiavanja, podstaknut je interes
za antibiotike - supstancije koje stvaraju mikroorganizmi
da bi inhibirali rast drugih mikroorganizama. Do danas
je pronaeno na stotine antibiotika i oni manje toksini su
uli u armamentarijum lekara kao efikasni antibakterijski
lekovi. Pored produkata bakterija i gljivica, to su sve ee
de novo sintetisane supstancije. Ovi lekovi deluju tako to
inhibiraju sintezu elijskog zida patogenog organizma, aktiviraju enzime koji razaraju elijski zid, poveavaju permeabilnost elijske membrane, ometaju sintezu proteina ili
metabolizam nukleinskih kiselina.
Od velikog broja antibiotika, lekar treba da odabere najsvrsishodniji za datog pacijenta. Izbor tog leka i njegovo

Scripta Medica
Vol. 41 No 2 October 2010.

doziranje ne zavisi samo od klinike dijagnoze, pa ni od

bakterioloke identifikacije i antibiograma ve i od niza
faktora koji se odnose na bolesnika (na primer, funkcija
bubrega i jetre, podnoljivost, uzrast, trudnoa, stanje
oboljenja). Zbog razvoja rezistencije bakterija na antibiotike, pogotovo zbog pojave multirezistentnih sojeva, sve
vie se vodi rauna o racionalnoj primeni ovih lekova. Uz
to, sainjavaju se liste rezervnih antibiotika kako bi se mogle efikasno leiti potencijalno fatalne infekcije. U nekim
situacijama, kombinovanje antibiotika poveava njihovu
efikasnost zbog sinergistikog delovanja, a kod meanih
infekcija iri se antibakterijski spektar. Meutim, ovo kombinovanje je esto nepotrebno i tetno zbog mogue pojave
superinfekcije ili antibiotikog antagonizma.
U nastojanju da se lekaru olaka izbor antimikrobnog leka,
objavljene su dve knjige (u Tuzli i Beogradu). Neke odlike
tih prirunika su navedene u Tabeli 1.
Tabela 1. Osnovni podaci o knjgama (S. ibalia i T. Kaia)

Tip podataka
Broj strana

Antimikrobna
sredstva
(S. ibali)
311

Antibiotici
(T. Kai)
207

Broj poglavlja

28

17

Tabele

45

Slike

Indeks pojmova

Ne

Da

Literatura

Da

Ne

Infekcije i izbor lekova

po sistemima

Ne

Da

Recenzenti

Broj reklamnih strana

Tira

500

Cena

500 din

Infektolog

Kliniki
farmakolog

Struni profil autora

Profesor S. ibali, u dva uvodna poglavlja, iznosi opte podatke koji se odnose na antibiotike, ukljuujui farmakokinetiku, metabolizam, sigurnost i efektivnost, rezistenciju,
kombinovanje antibiotika i mikrobioloko testiranje osetljivosti. Tu je lepo prikazan i istorijat otkria antibiotika.
Sledi deset poglavlja koja su posveena pojedinim grupama
antibiotika, a zatim su u zasebnim poglavljima obraeni
antimikotici, antivirusna sredstva, terapija lajmanijaze,
toksoplazmoze, anthemintici, i antiprotozoici. U tim
specijalnim poglavljima su date indikacije za primenu
leka, doziranje, farmakokinetika svojstva leka, neeljena

dejstva leka i registrovani preparati. Dimenzije ove knjige

(20 x 14 cm) zahtevaju malo vei dep belog mantila, zato
e ova knjiga pre nai mesto na stolu ili polici.
Potpuno drugaije je profesor Kai organizovao podatke
u svom priruniku. Nakon poglavlja Principi terapije
antibioticima, slede poglavlja o antibioticima za bakterijske infekcije, antigljivinim antibioticima i antivirusnim
lekovima. U jedanaest poglavlja su prikazane infekcije po
sistemima (na primer, infekcije CNS, krvi, kardiovaskularnog sistema, respiratornog trakta, mokranih puteva,
koe i mekih tkiva). Doziranje u renalnoj insuficijenciji je
prikazano u posebnom poglavlju, a na kraju prirunika,
od 139. do 204. strane, je poglavlje o lekovitim pripravcima, tj. preparatIma. Tu su abecednim redom navedeni
registrovani lekovi, njihovi proizvoai, sastav, dejstvo,
indikacije, doziranje, neeljena dejstva, pakovanje i paralele. Indeks pojmova, dat na kraju knjige, pomae itaocu
da lako pronae informacije o antibioticima, infekcijama i
lekovitim pripravcima. Ovaj prirunik prua obilje korisnih instrukcija onima koji provode i prate leenje infekcija,
a njegove dimenzije (17 x 11 cm) omoguavaju da se knjiga
lako smesti u dep belog mantila.
U ovim prirunicima potraio sam uputstva o antibiotikom
leenju akutnog sinuzitisa i njih sam uporedio s podacima
koji su dati u knjigama Clinical evidence handbook (London: BMJ, fall 2008) i Clinical evidence concise (London,
BMJ, winter 2005). Dve poslednje publikacije sadre objavljene klinike dokaze o delotvornosti lekova dobijene
kontrolisanim klinikim ispitivanjem (engl., randomized
controlled trial, skraeno RTC). Meutim, mora se imati
u vidu da u medicinskoj praksi te dokaze, kada postoje,
ne treba ba slepo prihvatati. Podaci o primeni antibiotika
kod akutnog sinuzitisa sumirani su u Tabeli 2.
Tabela 2. Preporuke za antibiotiko leenje akutnog sinuzitisa.

Akutni sinuzitis se definie kao prolazna inflamacija

sluznice paranazalnih sinusa koja traje manje od etiri
nedelje. Lekari opte prakse Evrope svake godine dijagnostikuju akutni sinuzitis u 1-5% odraslih stanovnika. Kod
50% tih osoba u pitanju je bakterijska infekcija sinusa;
najee patogene bakterije su Streptococcus pneumoniae
i Haemophilus influenzae, a ree Moraxella catarrhalis i
druge bakterije. Bakterijskoj infekciji esto prethodi virusna infekcija gornjeg respiratornog trakta, a 0,5% obinih
prehlada zavri kao akutni siunuzitis. U jednom kontrolisanom klinikom ispitivanju, dve treine osoba s akutnim
sinuzitisom spontano, bez ikakvog leenja, prevlada to zapaljenje. Rizik neleenja je hronini sinuzitis, a eventualno
i neka retka komplikacija (orbitalni celulitis i meningitis).
Nema publikovanih dokaza o efektivnosti antihistaminika, dekongestanata, inhalacije vodene pare ili ispiranja
fiziolokim rastvorom NaCl kod akutnog sinuzitisa. Veina
lekara smatra da je olakana evakuacija sekrecije iz sinusa
vana terapijska mera.

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Izvor

Antibiotik koji se preporuuje

ibali

amoksicilin, ampicilin, azitromicin,

sulbaktam, klaritromicin, telitromicin

Kai

(amoksicilin, amoksiklav, cefprozil,

azitromicin)* (amoksiklav)**
(doripenem, imipenem, meropenem,
ceftazidim+ vankomicin, cefoperazon +
vankomicin)***

Kliniki dokazi (prema knjigama koje je objavio BMJ)

Tri RTC-a su pokazala da amoksicilin, sa ili bez klavulanata, ne smanjuje i ne lei simptome akutnog sinuzitisa
bolje od placeba, ako je dijagnoza tog zapaljenja postavljena samo klinikim pregledom. Uz to, amoksicilin, sa ili
bez klavulanata, izaziva dijareju. U drugim TRC studijama
kotrimoksazol, cefalosporini, azitromicin ili eritromicin
se nisu pokazali efektivnijim od placeba.
Kod radioloki ili bakterioloki potvrenog akutnog sinuzitisa nisu raene RTC za cefalosporine ili makrolide. Jedan opsean revijski prikaz literature ukazuje da su amoksicilin, amoksicilin-klavulanat, cefalosporini i makrolidi
moda delotvorni kod ovako dijagnostikovanog akutnog
sinuzitisa i da meu tim lekovima nema znaajnije razlike
u efektivnosti. Meutim, cefalosporini i makrolidi imaju
manje neeljenih efekata od amoksicilina i amoksicilinklavulanat kombinacije.
Legenda: Indikacije za primenu lekova se u ovom priruniku
navode kod opisa veine antibiotika (ne navode se, na primer,
indikacije kod kombinacije tikarcilin + klavulanat) i zato je tee
nai preporuku za leenje akutnog sinuzitisa; uz to, nekada se
indikacije navode uopteno, na primer, infekcije gornjih respiratornih puteva pa nije jasno da li se to odnosi i na akutni
sinuzitis; *Bolesnik koji nije nedavno dobijao antibiotike; **Ako
je bolesnik nedavno dobijao antibiotike; ***Hospitalizovani
bolesnici + nazotrahealna ili nazogastrina intubacija; hospitalizovanim bolesnicima ti lekovi se daju i.v.

Brojni podaci u priruniku S. ibalia bili bi lake dostupni

kada bi postojao dobar indeks pojmova, ukljuujui indikacije za primenu leka. Vredelo bi da autor u narednom
izdanju knjige napie poglavlje o primeni antimikrobnih
lekova kod raznih infekcija. Tako bi lekar praktiar lake
doao do informacije koju trai. Manje greke u ispisivanju
referenci treba korigovati i moda smanjiti njihov broj jer
su lanci na koje se itaoci upuuju mahom objavljeni u
stranim asopima, a oni nisu lako dostupni.
Prirunik T. Kaia je prvenstveno namenjen medicinskom osoblju koje vri kliniku praksu. U naem jeziku
klinika praksa se uglavnom poistoveuje s bolnikom
praksom i s praksom u stacionarnim zdravstvenim ustanovama. Poto kod tekih infekcija (na primer: meningitis,
sepsa i septiki ok) rano davanje antibiotika moe spasiti
ivot, vredi dati odgovarajue savete lekarima koji rade u
primarnoj zdravstvenoj zatiti. Ukoliko autor namerava da
priredi novo izdanje, trebalo bi da ga dopuni i s dodatnom
literaturom. Bez obzira na laku dostupnost raznih podataka putem Medline (PubMed) i drugih izvora putem Interneta, dobro je da autori prirunika ukazuju na domau literaturu (knjige i asopisi) koja se odnosi na tematiku koju
obrauju.
Oba prirunika sadre korisne informacije o antibioticima i nekim drugim antiefektivnim lekovima. Knjiga S.
ibalia je kompletna i dobro obraena zbirka podataka
o najznaajnijim antimikrobnim lekovima, a knjiga T.
Kaia je izvor podataka o antibioticima i antivirusnim
lekovima, ali i o njihovoj primeni kod pojedinih infekcija,
s naglaskom na one koje su bolesnika dovele na leenje u
bolnicu ili neku drugu stacionarnu ustanovu.
Rajko Igi

Scripta Medica
Vol. 41 No 2 October 2010.

Samir Delibegovi: Kako pisati medicinski

znanstveni lanak. Interliber, Sarajevo, 2008.
Knjiga sadri 88 strana, format 17x24 cm, tira
500 primjeraka, ISBN: 9789958400100

Prirunik je napisan na 88 strana A4 formata, sa jednostrukim proredom i dobro odabranim naslovima, koji itaocima kao kljune rijei omoguavaju da lagano pronau
pomo u svakoj fazi pisanja rada. Poglavlja u knjizi Zato
i kako pisati (Impact factor, Citiranost lanaka, Pretraivanje baze podataka, Autorstvo i raspored autora, Dozvole, Uputstvo autorima, Kako zapoeti), lanak (Naslov,
Imena autora, Apstrakt/Saetak, Kljune rijei), IMRaD
Struktura lanka (Uvod, Pacijenti i metode, Rezultati,
Diskusija), Zahvala, Citiranje i reference (Sistem citiranja
referenci citat-niz i Sistem citiranja referenci prezimegodina), Pismo urednitvu asopisa, Recenzije, te Praktini primjeri, objanjavaju svaku fazu pisanja naunog
lanka. Prirunik je nastao iz elje autora da studentima
medicinskih fakulteta na junoslovenskim jezicima budu
pribliene osnove medicinskog pisanja. Prirunik se, dakle, bavi samim pisanjem, a ne metodologijom istraivanja, o kojoj postoji vie izvrsnih knjiga na naim jezicima.
Sistematinost i pedagoka optimalnost su na zavidnoj
visini. Tanost definicija i pojmova, klasifikacija i metodinost su tako precizne da se moe predvidjeti redosljed
odjeljaka u tekstu, tako da se tekst lako pamti. Izbor sugerisane literature objanjava ozbiljnost ovog rada.
Knjiga je, u prvom redu, namijenjena studentima medicine koji po Bolonjskom programu studija izuavaju vjetinu
naunog pisanja u toku redovnog studija. Umijee pisa-

nja naunog lanka je vjetina koju treba uiti i koja slijedi odreena pravila. Sam proces uenja nije kratak, ve je
pun potekoa i greaka. Meutim, udbenik poput ovog
olakava poetniku mukotrpni put objavljivanja sopstvenih medicinskih istraivanja.
U drugom dijelu Prirunika, autor prezentira cjelokupni
sadraj korespondencije autora i urednika (a posredno i recenzenata) tokom procesa peer-review recenzije lanka,
u jednom uglednom asopisu (Current Contents; IF-3.6),
od inicijalne submisije do konanog prihvatanja lanka za
publikovanje. Primjer je dobro odabran i edukativan jer
prezentira vrlo izbalansiran nain komunikacije izmeu
autora, urednika i recenzenata koji je vrlo vaan, a nekada i kljuan za konanu odluku urednika da lanak bude
publikovan u asopisu. Dodatni znaaj daje injenica da se
u prvoj recenziji jedan od recenzenata izjanjava o lanku
relativno pozitivno, a drugi relativno negativno. Autor je
cijeli proces recenzije prezentirao in extenzo bez, ini se,
potrebnih skraivanja koja bi olakala itanje teksta, vjerovatno elei u cjelosti prezentirati nain komunikacije u
toku peer-review procesa.
Globalno gledano, smatram da ovaj prirunik po organizaciji, sadraju i pedagokoj sistematinosti znaajno prevazilazi primarnu namjenu, a to je da bude prirunik za
studente medicine. Naravno da je za studente medicine
najvaniji, jer se kua gradi od temelja. Meutim, i pored
oigledne skromnosti autora, ja ovaj prirunik iskreno preporuujem ne samo studentima medicine, ve i svim ljekarima, i to ne samo onim u akademskoj zajednici, nego
i ljekarima praktiarima, jer ako ne objavite ta ste radili,
nakon izvjesnog vremena, niko nee znati da ste bilo ta
radili.
Prof. dr Enver Zerem

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Scripta Medica
Vol. 41 No 2 October 2010.

Naslov teksta maksimalmo dva reda, po potrebi povecati sirinu

tekst boksa da stane naslov, Etiam dapibus iaculis euismod

Proireni apstrakti radova publikovanih

na stranim jezicima

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Scripta Medica
Vol. 41 No 2 October 2010.

Diethyldithiocarbamate potentiates the effects

of protamine sulphate in the isolated rat
uterus
Zorana Oreanin-Dusi1, Slobodan Milovanovi2, Duko Blagojevi1,
Aleksandra Nikoli-Koki1, Ratko Radojii3, Ivan Spasojevi4, Mihajlo Spasi1
1

Department of Physiology, Institute for Biological Research, Belgrade, Serbia

Faculty of Medicine, University of Eastern Sarajevo, Foa, Bosnia and Herzegovina
3
Faculty of Biology, University of Belgrade, Belgrade, Serbia
4
Institute for Multidisciplinary Research, University of Belgrade, Belgrade, Serbia
2

Oreanin-Dusi i sar. Dietilditiokarbamat potencira

efekte protamin sulfata u izolovanom uterusu
pacova. Redox Report 14(2) 48-54.
Cilj: Protamin sulfat (PS) ima irok spektar dejstva, posredovan razliitim mehanizmima. U naim predhodnim
eksperimentima je pokazano da PS uzrokuje K-kanalima
posredvanu relaksaciju spontanih i Ca indukovanih kontrakcija izolovanih uterusa pacova. Dietilditiokarbamat
(DDC) je poznati helirajui agens za Cu i Fe i koristi se
kao inhibitor CuZn-SOD u in vivo i in vitro uslovima. Mehanizam DDC posredovane inhibicije CuZn-SOD podrazumeva dva molekula DDC-a, jedan ekstrahuje bakar iz
aktivnog centra, dok drugi molekul zamenjuje jon bakra
u aktivnom centru, to vodi ka inhibiciji enzima. U ovoj
studiji smo ispitivali efekat DDC-a (2.5 mM and 5 mM) na
relaksantni efekat PS-a na izolovanim uterusima nevinih
enki pacova u estrusu.
Eksperimentalni pristup: Uterusi su izolovani iz nevinih enki Wistar pacova i suspendovani u kupatila za izolovane organe. Praena je spontana i Ca indukovana aktivnost uterusa tretiranih rastuim koncentracijama PS-a
do totalne relaksacije. Aktivnost antioksidativnih enzima
(mangan superoksid dismutaze - MnSOD, bakar-cink superoksid dismutaze CuZn-SOD, katalaze - CAT, glutation peroksidaze - GSHP-x i glutation reduktaze GR) kod
H2O2-tretiranih uterusa je poreena sa uterusima zam-

rznutim odmah nakon izolovanja i uterusima (sa spontanom i/ili Ca2+ - indukovano aktivnou) inkubiranim 2h u
vodenom kupatilu bez tretmana PS-om. Ispitivan je efekat
DDC-a (2.5 mM and 5 mM) na PS posredovanu relaksaciju.
Rezultati: DDC potencira relaksantni efekat protamin
sulfata. Tretman sa 5 mM DDC znaajno je inhibirao
CuZn-SOD, dok je aktivnost MnSOD-a rasla. Mehanizam
delovanja DDC-a je postuliran na bazi njegove interakcije
sa dvovalentnim jonima gvoa i CuZn-SOD. DDC helira
dvovalentne jone gvoa, formirajui Fe-DDC komplekse.
Fe-DDC formira stabilne NO-Fe-DDC2 komplekse putem
NO eliminacije i procesa denitrozilacije, to u kombinaciji
sa DDC-om (5 mM) uzrokuje inhibiciju CuZn-SOD. U
miinoj eliji Fe-DDC kompleksi mogu da denitroziluju
tiol grupe unutar K kanala vodei ka efluksu K+ jona. To
dalje vodi ka otvaranju K-kanala, hiperpolarizaciji membrane, inhibiciji Ca2+ influksa i finalno, relaksaciji glatkog
miia.
Zakljuak: Kako Fe-DDC i NO-Fe-DDC2 kompleksi
iskljuuju ulogu dvovalentnog gvoa u generisanju hidroksil radikala u Fentonovoj reakciji, DDC takoe moe
da sprei patofizioloke promene uzrokovane gvoem.
Ovakva uloga DDC-a otvara mogunost upotrebe njegovog farmakolokog oblika (disulfiram) u irokom spektru
patolokih promena vezanih za glatke miie.

Scripta Medica
Vol. 41 No 2 October 2010.

Journal of BUON 15: 182-187, 2010

2010 Zerbinis Medical Publications. Printed in Greece

SPECIAL ARTICLE

Statistical presentation of data in biomedical publications

R. Igi1,2, S. Stoisavljevic-atara2
1

Department of Anesthesiology and Pain Management, Stroger Hospital of Cook County, Chicago, IL, USA; 2Department of Pharmacology and Toxicology, Medical Faculty, University of Banja Luka, Banja Luka, Republic of Srpska, Bosnia and Herzegovina

Igi R., Stoisavljevi-atara S. Statistical

presentation of data in biomedical publications. J.
BUON 2010;15:182-7.
Veina biomedicinskih i klinikih istraivanja se izvodi
na malom uzorku koji se uzima iz neke populacije, a nalazi dobijeni na uzorku se ekstarpoliraju za tu populaciju
uz odreen stepen pouzdanosti. Statistiari i urednici
asopisa ukazuju da podatke koji su normalno distribuirani (Gaussova distribucuja) treba prikazivati tako da
se uz srednju vrednst koristi standardna devijacija (SD),
a za ishod studije standardna greka srednje vrednosti
(SEM) ili confidence interval (CI). Meutim, pogreno je
koristiti SEM za opis dobijenih podataka.
Postoji puno razloga za varijabilnost podataka jer svaki
uzorak, uzet sluajnim izborom iz populacije, nije identian.
Varijabilnost tih podataka je mogue opisati na nekoliko
naina, ukljuujui mere centralne tendencije (srednja
vrednost, medijan, mod). Medijan i mod su pogodni pokazatelji kod prikaza podataka koji sadre ekstremne vrednosti (outliers) i kada je u pitanju bimodalna distribucija.
B



















 

 

 

 

Figure 1. Data display as a dot plot (A) and box-whisker plot (B).
The median for each set of the data is marked both at the dot plots
and box-whisker plots. The box is marked by the first and third
quartile. The whiskers show the range.

Ne-normalno distribuirane podatke je najbolje prikazati

tako to se isti podele u etiri kvartila i da se naini boxwhisker plota, ako bi takasto nanoenje (dot plot) bilo
nepraktino zbog velikog uzorka. Medijan se u oba sluaja
naznai (Figure 1).
Kada se u lanku prikazuju dobijeni podaci, obino treba
navesti broj subjekata (n), raspon rezultata, centralnu tendenciju (srednja vrednost i SD) i CI za srednju vrednost.
Numerike mere disperzije (SD i SEM) se odnedavna prikazuju na dva naina. Tako, na primer, visina sistolnog pritiska se kod kolske dece moe prikazati ovako:
120 mmHg (SD=6, n=100) ili
120 +6 mmHg (SD, n=100).
Mnogi asopisi jo u ovu svrhu koriste + simbol. Meutim,
sve je vie asopisa koji ga eliminiu i postupaju prema
uputstvu koje je dato od strane Councila of Science Editors
(Scientific style and format: The CSE manual for authors,
editors, and publishers. Reston, The Council, 2006.).
Mnogi autori gree i umesto SD koriste SEM kod prezentacije podataka. Verovatno je za to razlog to je SEM manja
vrednost od SD (SEM=SD/n) pa ta manja cifra nekako
izgleda prihvatljivija. Meutim, ta greka esto promakne
recenzentima i urednicima asopisa.

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Scripta Medica
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Scripta Medica
Vol. 41 No 2 October 2010.

Izvetaj sa Internacionalnog
simpozijuma ziologa u
Beogradu

SAD, Slovake, Slovenije, Srbije, panije, vedske, i Ukrajine. Na skupu su prikazani i brojni posteri. Glavne teme
skupa bile su: (1) Neuroendokrina regulacija fiziolokih
procesa, (2) Fiziologija termogeneze, mitohondrija i redoks regulacija, (3) Neurofiziologija u zdravlju i bolesti i
(4) Biofizika u fiziologiji. Na zavrnoj ceremoniji je najpre
odrano predavanje pod naslovom Veliki naunici iz male
zemlje u ratu i miru, a zatim su dodeljene dve nagrade
mladim istraivaima: Ivan aja i Akademik Radoslav
K. Andjus.

Od 10. do 14. septembra 2010. godine, odran je

Meunarodni simpozijum One hundred years of Ivan Djajas (Jean Giaja) Belgrade School of Physiology [Sto godina
kole fiziologije Ivana aje u Beogradu].
Ivan aja je roen 1884. godine u Avru, Normandija.
Njegov otac Boidar, pomorski kapetan, je bio Srbin
iz Dubrovnika, a majka Delfin Depoa bila je Francuskinja. aja je bio Srbin katolike vere. Kada je imao
est godina, prelazi s porodicom u Srbiju. U Beogradu
pohaa osnovnu kolu i gimnaziju, studira u Francuskoj na Sorboni (1909. godine) dobija titulu doktora
nauka iz fiziologije. Vraa se u Beograd, gde osniva
prvi institut za fiziologiju na Balkanu. Tu , uz prekide
tokom dva svetska rata, radi sve do svoje smrti, 1957.
godine. aja je u svetu poznat po istraivanjima metabolizma, termoregulacije i hipotermije. Zbog svojih
otkria biran je za lana Francuske akademije nauka
kada se ukazalo mesto nakon smrti Aleksandra Fleminga, pronalazaa penicilina. Mnogi nai naunici
i studenti pamte njegovu frazu: Nulla dies sine experimento, [Nijedan dan bez eksperimenta], do koje
je aja nadoao parafrazirajuci uvenu Leonardovu:
Nulla dies sine linea.
Na Simpozijumu u Beogradu usmene referate je podnelo
preko 60 istrazivaa iz Austrije, Engleske, Francuske,
Holandije, Hrvatske, Italije, Nemake, Poljske, Rusije,

Odluka Francuske akademije nauka o izboru Ivana aje umesto Aleksandra Fleminga.

Skup je odran na engleskom jeziku, a za brojnu domau

publiku, organizatori su obezbedili primerke dva separata koji su objavljeni u ediciji Srpske akademije nauka i
umetnosti ivot i delo srpskih naunika (Vol. 11, sekcija
II, knjiga 11, 2008): Ivan aja (1884-1957) i Radoslav K.
Andjus (1926-2003). Autori ovih priloga su Pavle R. Andjus, odnosno Stanko S. Stojilkovi.
Uesnici Simpozijuma su prihvatili predlog prof. dr Rajka
Igia da se prie pripremi knjige posveene istoriji domae
fiziologije i farmakologije, dvema bliskim naunim disciplinama. Raniji pokuaj da se priredi knjiga o istorijatu tih
disciplina na nivou Jugoslavije, koju je Prof. Igi pokrenuo
zajedno s akademikom Nikom Alegrettijem, nije uspeo
zbog smrti prof. Alegrettija, ali i raspada drave.
Dr Nedeljka arovi

ajin dijagram termoregulacije, 1938

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