Prof. Sven Kurbel MD, PhD – personal web pages
Dept. of Physiology, Osijek Medical Faculty
J. Huttlera 4, 31000 Osijek, Croatia
e-mail: sven@jware.hr
41. Ultrasound measurement in defining the regional distribution of subcutaneous fat tissue.
Radić R, Nikolić V, Karner I, Kurbel S, Selthofer R.
Coll Antropol. 2002 Dec;26 Suppl:59-68.
Department of Anatomy, School of Medicine, J. J. Strossmayer University of
Osijek, Osijek, Croatia.
The aim of this research is to determine the significance of ultrasound
diagnostics in measuring the thickness of subcutaneous fat tissue as well as to
point out sex and age differences in regional distribution of subcutaneous fat
tissue. The research included 37 men and 33 women with different body mass
indexes. Ultrasound measuring of subcutaneous fat tissue was conducted on 16
measuring points. The thickness of subcutaneous fat tissue measured by ultrasound
and estimated proportion of fat tissue obtained by comparative methods coincided
mostly on the back side of the upper arm, lower abdominal region in interspinal
line and the front side of the forearm. Analysis of the subcutaneous fat tissue
distribution indicates that there is more equal accumulation of fat tissue in
women than in men. BMI limit value for obesity is not the same for men and women
because the point at which abdominal region becomes the main storage of
subcutaneous fat in body depends on sex. That BMI value represents the
physiological beginning of obesity since it marks the change in distribution
pattern of subcutaneous fat tissue in different body regions.
PMID: 12674836 [PubMed – indexed for MEDLINE]
42.Amoxycillin, clarithromycin and either sucralfate or pantoprazole for eradication
of Helicobacter pylori in duodenal ulcer (a randomized controlled trial).
Vcev A, Vceva A, Kurbel S, Takac B, Stimac D, Ivandić A, Ostojić R, Barbir A,
Hovat D, Mihaljević S.
Wien Klin Wochenschr. 2001 Dec 17;113(23-24):939-41.
Internal Clinic, Clinical Hospital Osijek. btakac@gmx.net
BACKGROUND: Sucralfate enhances the anti-Helicobacter pylori activity of
antimicrobials and has an inhibitory effect on H. pylori.
AIM: To evaluate the efficacy and safety of one-week sucralfate-based eradication
therapy for H. pylori infection in patients with duodenal ulcers, compared with
treatment based on pantoprazole, in a randomized controlled multicenter study.
METHODS: One hundred and twenty patients with active duodenal ulcers and H.
pylori infection were treated with amoxycillin 1 g b.d. plus clarithromycin 500
mg b.d. for the first 7 days. Patients were randomly assigned to receive either
sucralfate 1 g t.d.s. for 4 weeks (SAC group; n = 60) or pantoprazole (PAC group;
n = 60) 40 mg b.d. for the first 7 days and 40 mg o.d. for the next 3 weeks. The
patient’s H. pylori status was determined by a urease test and histological
investigation before the treatment, and again 4 weeks after cessation of all
medication.
RESULTS: One hundred and eleven patients completed the study. H. pylori infection
was eradicated in 76.4% (42/55) of patients in the SAC group (ITT analysis: 70%,
95% CI: 58-80%) vs. 85.7% (48/56) of patients in the PAC group (ITT analysis:
80%, 95% CI: 70-89) (N.S.). All ulcers had healed. There were no significant
differences between the two regimens regarding the occurrence of adverse effects.
CONCLUSION: Our study shows that one-week triple therapy with amoxycillin,
clarithromycin and either pantoprazole or sucralfate are effective regimens to
cure H. pylori infection in patients with duodenal ulcer.
PMID: 11802510 [PubMed – indexed for MEDLINE]
43. Model of interstitial pressure as a result of cyclical changes in the capillary
wall fluid transport.
Kurbel S, Kurbel B, Belovari T, Marić S, Steiner R, Bozíć D.
Med Hypotheses. 2001 Aug;57(2):161-6.
Osijek Medical Faculty, University JJ Strossmayer, 31000 Osijek, Croatia.
sven.kurbel@public.srce.hr
Reported interstitial pressures range from -8 to +6 mm Hg in different tissues
and from <-20 mm Hg in burned tissue or more than +30 mm Hg in tumors. We have
tried to link interstitial pressure to the here proposed cyclical changes in the
fluid transport across the capillary wall. In the presented model interstitial
pressure is considered as an average of pressures in numerous pericapillary
spaces. A single pericapillary pressure is a dynamic difference between the net
outward (hydraulic pressure+interstitial colloid osmotic pressure) and inward
(plasma colloid oncotic pressure) forces. Hence, dominating net outward forces
would result in a positive pericapillary interstitial pressure, while stronger
inward forces would produce negative pressures in the pericapillary space. All
interruptions of blood flow leave some blood in capillaries with a normal oncotic
pressure and no hydrostatic pressure that might act as a strong absorber of
interstitial fluid until the blood flow is reestablished. Model assumptions for
the systemic circulation capillaries include (a) precapillary sphincters can
almost entirely stop the capillary flow, (b) only a minority of sphincters are
normally open in the tissue, and (c) hydrostatic pressures in unperfused
capillaries are similar to the pressures at their venous ends. The key proposal
is that capillaries with closed precapillary sphincters along their entire length
have low hydrostatic pressure of 10 to 15 mm Hg. This pressure cannot force
filtration, so these capillaries reabsorb interstitial fluid from the
pericapillary space along their entire length. In the open capillaries,
hydrostatic pressure filtrates fluid to the pericapillary space along most of
their length. Fluid enters, moves some 20 or 30 micrometers away and back to be
reabsorbed at the same point. Closed periods are periods of intense fluid
reabsorption, while the short open periods refill the space with fresh fluid. It
can be calculated that subcutaneous tissue interstitial pressure values might
develop if the closed periods are 1.14 to 2.66 times longer than the open
periods. Positive interstitial pressures observed in some organs might develop if
open periods are longer than the closed periods. High interstitial colloid
pressure in lungs makes both perfused and unperfused capillaries absorptive,
resulting in more negative values of lung interstitial pressure. The same model
is used to explain interstitial pressure values in tumors, burned tissue and
intestinal villi.
Copyright 2001 Harcourt Publishers Ltd.
PMID: 11461165 [PubMed – indexed for MEDLINE]
44. A model of the gastric gland ejection cycle: low ejection fractions require
reduction of the glandular dead space.
Kurbel S, Kurbel B, Dmitrović B, Vcev A.
J Theor Biol. 2001 Jun 7;210(3):337-43.
Osijek Medical Faculty, University JJ Strossmayer, Osijek, Croatia.
sven.kurbel@public.srce.hr
This paper was inspired by the reported results of authors from Uppsala and Lund
that gastric glands in rats rhythmically contract 3-7 cycles per minute and
develop luminal pressures more than 10 mmHg. To ensure that pepsinogen is not
retained in the acid-rich section of the gland, ejection fractions would need to
be more than 50% of the gland volume. We have tried to calculate the ejection
fraction of such contractions. Dimensions of human gastric glands were measured
on the fresh frozen samples of macroscopically and histologically normal gastric
mucosa. In total, 18 specimens (from nine persons) were measured under the
microscope. The density of glands was 135 +/- 11 (mean +/- S.D.) glands per mm(
2) of gastric mucosa. A typical gastric gland is a tubular structure 1.2 +/- 0.22
mm long and 0.03-0.05 mm wide. We have used 1 mm for length and 0.03 mm for the
gland diameter to calculate that each gland approximates a volume of 707 pl,
suggesting that the total glandular volume for 15 million glands reaches 10.6 ml.
Further calculations based on one to five contractions per minute on an average
and on the total volume of gastric glands of 10 ml showed that only ejection
fractions less than 10% deliver daily volumes less than 3 l. The presented model
of the gastric gland activity is based on the idea that the low ejection
fractions require a reduction of the glandular dead space. The reduced luminal
pressure during the gland relaxation might cause backflux of hydrophobic
viscoelastic mucus through the gland aperture. Repeated glandular contractions
and relaxations would move the mucus all the way to the gland bottom, filling the
gland cavity below the neck with an axial semisolid mucous cylinder. This filling
would reduce the gland dead space. During contractions, the gland would eject
mainly the peripheral, the more liquid part of its content. The decreasing
luminal pressure in the relaxing gland would pull the outlet mucus inside,
protecting gland apertures from the gastric juice.
Copyright 2001 Academic Press.
PMID: 11397134 [PubMed – indexed for MEDLINE]
45. A model of hydraulic interactions in liver parenchyma as forces behind the
intrahepatic bile flow.
Kurbel S, Kurbel B, Dmitrovic B, Wagner J.
Med Hypotheses. 2001 May;56(5):599-603.
Physiology, Osijek Medical Faculty, University JJ Strossmayer, Osijek, Croatia.
sven.kurbel@public.srce.hr
The small diameters of bile canaliculi and interlobular bile ducts make it hard
to attribute the bile flow solely to the process of secretion. In the model liver
within its capsule is considered a limited space in which volume expansions of
one part are possible only through the shrinking of other parts. The liver
capsule allows only very slow volume changes. The rate of blood flow through the
sinusoides is governed by the Poisseuill-Hagen law. The model is based on a
concept of circulatory liver units. A unit would contain a group of acini sharing
the same conditions of arterial flow. We can imagine them as an acinar group
behind the last pressure reducer on one arterial branch. Acini from neighboring
units compose liver lobules and drain through the same central venule. One lobule
can contain acini from several neighboring circulatory units. The perfusion cycle
in one unit begins with a transient tide in the arterial flow, governed by local
mediators. Corresponding acini expand, grabbing the space by compressing their
neighbors in the same lobules. Vascular resistance is reduced in dilated and
increased in compressed acini. Portal blood flows through the dilated acini,
bypassing the compressed neighbors. The cycle ends when the portal tide slowly
diminishes and acinar volume is back on the interphase value until the new
perfusion cycle is started in another circulatory unit. Each cycle probably takes
minutes to complete. Increased pressures both in dilated and in compressed acini
force the bile to move from acinar canalicules. Both up and down changes in
acinar volume might force the acinar biliary flow. In cases of arterial
vasoconstriction, increased activity of vasoactive substances would keep most of
the circulatory units in the interphase and increased liver resistance can be
expected. Liver fibrosis makes all acini to be of fixed volume and result in
increased resistance. Because of that, low pressure portal flow would be more
compromised, as reported. In livers without arterial blood flow, although some
slow changes in the portal flows can be expected, acinar volume changes should be
reduced. In acute liver injury, enlarged hepatocytes would diminish sinusoidal
diameter and increase acinar resistance. In liver tumors, areas of
neovascularization with reduced resistance would divert the arterial flow from
the normal tissue, while in the compressed perifocal areas, increased vascular
resistance should diminish mainly the portal flow.
Copyright 2001 Harcourt Publishers Ltd.
PMID: 11388774 [PubMed – indexed for MEDLINE]
46. Cancer incidences in the digestive tube: is cobalamin a small intestine cytoprotector?
Kurbel S, Kovacic D, Radic R, Drenjancevic I, Glavina K, Ivandic A.
Med Hypotheses. 2000 Mar;54(3):412-6.
Physiology, University ‘JJ Strossmayer’, Osijek Medical Faculty, Osijek, Croatia.
sven.kurbel@public.srce.hr
Malignancies are common in the digestive tube, although with unequal distribution
among segments. The aim of this paper was to compare available interpretations of
the low cancer incidence in the small bowel and high in the large bowel. Supposed
mechanisms include relatively small bacterial population, large secretion of
liquid and rapid transit in the small bowel. Small bowel mucosa is the main
absorptive part of the digestive tube with absorption rates for various nutrients
so high that they can even be considered as clearances from the intestinal
content. Consequently, these nutrients are not present in the large bowel. An
alternative explanation is that an absorbable protective substance from the
intraluminal content, might protect the mucosa from malignant transformations. It
can be speculated that if there are any cytoprotective substances in the digested
food their effect would be expressed mostly in the absorptive small intestine,
leaving the large bowel mucosa unprotected. Vitamin B12 might be a possible
candidate for this role. Cobalamin molecules are initially bound to haptocorrin
(Hc) in the stomach, but in the small intestine B12 is transferred to intrinsic
factor (IF) after the action of pancreatic trypsin on Hc. Cobalamin-IF complexes
are absorbed in the terminal ileum leaving only a small fraction of B12 to enter
the large bowel. We have tried to summarize available data regarding cancer
incidences in digestive tube, segmental length and transit times of tube content.
Cancer density is calculated as incidence per length and transit speed as length
per transit time. Cancer incidences for seven intestinal segments were considered
low if they were below one case per 100 000 inhabitants annually, while the low
cancer density meant less than six cases per 100 000 inhabitants per metre. For
instance, transverse colon was considered as a high cancer incidence place (2.15
cases), with low cancer density (4.3 cases/m). Transit speed more than 0.3
metre/hour was associated with low cancer incidences (accuracy 0.85) and low
cancer density segments (accuracy 1.00). Cobalamin availability showed similar
distribution, available in low incidence segments and unavailable in high
incidence segments. Experimental studies are needed to quantify B12 availability
in the large bowel and to determine whether small amounts of B12-IF or, perhaps,
B12-haptocorrin complexes are absorbed by the small bowel mucosa. Without that,
no cytoprotective effects of B12 in the digestive tube can be expected.
Copyright 2000 Harcourt Publishers Ltd.
PMID: 10783476 [PubMed – indexed for MEDLINE]
47. Histochemical changes in the rectal mucosa of diabetic patients with and without
diarrhea or constipation.
Ivandić A, Prpic-Krizevac I, Dmitrović B, Vcev A, Kurbel S, Peljhan V, Bacun T.
Wien Klin Wochenschr. 2000 Jan 14;112(1):21-6.
Department of Internal Medicine, Osijek University Hospital, Croatia.
Sixty-four diabetic patients, 35 with diarrhea, 15 with constipation and 14
without stool problems, and forty healthy subjects, were subjected to
rectosigmoidoscopy. During rectosigmoidoscopy, rectal biopsy specimens for
histological and histochemical analysis were obtained. Histological findings of
nonspecific colitis in 25 out of 64 diabetic patients were uniformly distributed
among the three groups (p = 0.959). However, the finding was slightly more common
in diabetic patients than in controls (eight out of 40 control subjects, p =
0.043). A positive PAS reaction was observed in 30 out of 64 diabetic patients
and was also uniformly distributed among the three groups (p = 0.508), but was
significantly more common among diabetic patients than controls (three out of 40,
p < 0.001). A positive reaction to cholesterol was found in 46 out of 64 diabetic
patients, also uniformly distributed among the three groups (p = 0.773). It was
significantly more common in diabetic patients than in controls (nine out of 40,
p < 0.001). Reactions of the rectal mucosa histological specimens to glycogen and
triglycerides were negative, both in diabetic patients and in controls. In
conclusion, it appears that stool problems among our diabetic patients were not
related to the positivity of PAS or to the positive cholesterol reaction in the
rectal mucosa histological specimens. Since positive findings of both reactions
were more common in specimens taken from diabetic patients than in controls,
positive reactions might be related to metabolic disturbances in diabetic
patients.
PMID: 10689736 [PubMed – indexed for MEDLINE]
48. Intracranial infection after missile brain wound: 15 war cases.
Hećimović I, Dmitrović B, Kurbel S, Blagus G, Vranes J, Rukovanjski M.
Zentralbl Neurochir. 2000;61(2):95-102.
Division of Neurosurgery, University Hospital Osijek, Osijek University Medicine
School.
OBJECTIVES: The present study describes 15 cases of intracranial infections
developed in a group of in patients with missile brain wound (MBW), during the
war in Croatia in the region of East Slavonia.
METHOD: The retrospective study included 88 MBW casualties. There were 11 females
and 77 males aged 2-80 years. The projectile penetration of the cranial dura was
confirmed and the presence of intracranially retained foreign bodies was
evaluated with computerized tomography (CT) in all the patients. The wounded were
treated according to the modern recommendations of neurotrauma care. However, we
extracted only accessible bone/metallic fragments during intracranial
debridement. All intracranial infections were documented by cultures, CT, surgery
or autopsy. The mean follow-up period of wounded with intracranial infections was
2.4 years (range, 10 days to 7 years).
RESULTS: Intracranial infection developed in 14 patients (17%) as “early
intracranial infections”. Among 14/15 cases, infection developed within the first
8 weeks, and in 1 case 5 months after wounding. We recorded 4 cases of isolated
bacterial meningitis, whereas in 9 cases brain abscess had developed. In 6 cases
brain abscess was associated with concomitant meningitis and epidural empyema.
Local cerebritis developed in one case, as well as subdural empyema with the
concomitant meningitis in one case. There were 8 deaths in total of 15 cases.
Glasgow Outcome Score 3 was observed in 2 and good outcome in 5/15 cases. The
infectious organisms were isolated in 8 cases. Gram-positive bacteria were found
in 12 different specimens. Gram-negative bacteria were found in 9 specimens. The
most frequently isolated organism was Staphylococcus aureus. beta-hemolytic
streptococcal and clostridial infections were not observed. Among the 15 patients
with intracranial infection, just one did not have intracranially retained bone
and/or metallic fragments. However, among the 73 head injuries without
intracranial infections only 10 did not have retained fragments. CSF fistula
and/or dehiscence developed in 13/15 patients with intracranial infection. In
67/73 wounded without intracranial infections, wound complications were not
registered.
CONCLUSIONS: The liberal use of post-contrast CT of the brain within the first 2
months after injury, especially if performed early in the clinical course, can
lead to a prompt diagnosis of most of “early intracranial infections”. The
surgical procedures in order to prevent wound CSF fistula/dehiscence development
are absolutely necessary. The immediate scalp and dural wound repair in case of
wound complications are absolutely indicated and if needed, the procedures can be
repeated. However, it seems that retained fragments are not responsible for an
increased rate of intracranial infection.
PMID: 10986758 [PubMed – indexed for MEDLINE]
49. Minoxidil and male-pattern alopecia: a potential role for a local regulator of
sebum secretion with vasoconstrictive effects?
Kurbel S, Kurbel B, Zanić-Matanić D.
Med Hypotheses. 1999 Nov;53(5):402-6.
Department of Physiology, Osijek Clinical Hospital, Croatia.
sven.kurbel@public.srce.hr
Regulation of the hair cycle takes place at the pilo-sebaceous unit with the
sebaceous gland as a sex hormone-dependent part. Although minoxidil stimulates
proliferation of follicular cells and activation of prostaglandin endoperoxide
synthase-1, it was suggested that other mechanisms, such as an increase in the
local blood flow, might mediate the drug effect on hair growth. If that is the
case, it is possible that minoxidil counteracts some vasoconstrictive mediator of
male-pattern alopecia. This hypothetical vasoconstrictive mediator X would have
to meet some criteria: (I) vasoconstriction both in the general circulation and
in the hair-growing skin; (II) local vasoconstrictive activity in the hair
growing skin should be related to the circulating testosterone level; (III) only
an increase in the local mediator X activity causes male-pattern alopecia, since
hypertensive patients are not balder than expected. The sebaceous gland is a
possible place of the mediator X secretion since it is a sex-hormone-dependent
part of the pilo-sebaceous unit. ET-1 might be a suitable candidate for the
mediator X, since male hormones raise ET-1 plasma levels and female hormones
lower them. The speculation presented here is that ET-1, beside vasoconstriction
in the general circulation, might also regulate the sebum secretion, by
triggering contractions of the myoepithelial cells. This hypothetical mechanism
would normally remain confined to the sebaceous gland. During puberty, sex
hormones stimulate growth of sebaceous glands in both sexes. In women
hypertrophied sebaceous glands under estrogen control would not increase its ET-1
content, while in men, testosterone would increase ET-1 secretion that might
affect the neighboring arterioles. Induced vasoconstriction might reduce the hair
growth and promote hair loss. If ET-1 plays the described role, then an ET-1
antagonist, i.e. bosentane, should also have some hair-growing properties.
PMID: 10616041 [PubMed – indexed for MEDLINE]
50. Endothelin-secreting tumors and the idea of the pseudoectopic hormone secretion in tumors.
Kurbel S, Kurbel B, Kovacić D, Sulava D, Krajina Z, Dmitrović B, Sokcević M.
Med Hypotheses. 1999 Apr;52(4):329-33.
Department of Oncology, Osijek Clinical Hospital, Croatia.
sven@systematics.fido.hr
Ectopic hormone secretion in tumor cells is here described as an amplification of
hormone production already present in normal, nonendocrine tumor-originated
tissue. This idea is tested on the available data regarding endothelin-1 (ET-1)
secreting tumors. The endothelins are ubiquitous regulatory peptides produced by
various tissues. The precursor cells of many tumor types secrete endothelins.
ET-1 protein expression was detected in situ in all tested prostate cancers as
well as in normal prostate tissue. The majority of hepatocellular carcinomas
produce ET-1, while ET-1 is secreted by the normal hepatic stellate cells. Human
breast cancer cells produce immunoreactive ET-1. Similar data exist for
pancreatic tissue, the thyroid and large bowel. We can conclude that tumor cells
might sustain endothelin secretions already present in the normal
tumor-originated tissue. The model that is presented of the pseudoectopic hormone
secretion consists of relations between a few parameters. The proportion of
hormone-secreting tumors (Th) among all tumors (T) of that organ depends on the
amount of the hormone-secreting cells (Ch) among all cells (C) susceptible to
malignant transformation. The corrective factor (k) was introduced in the
expression Th/T=Ch/C*k, to represent specific conditions altering the malignant
transformation probability for a certain normal hormone-secreting cell. In
prostate, breast and colon, the kvalue is predicted to be approximately 1,
suggesting that ET-1-secreting normal cells are not more prone to the malignant
transformation than their neighbours. In liver and pancreas, the incidence of
ET-1-secreting tumors outnumbers the proportions of normal ET-1-secreting cells
(k values >1). In these organs, normal ET-1-secreting cells seem more likely to
turn malignant in comparison to their neighbours, perhaps due to their function,
position and exposition to oncogenic factors, or even due to their ET-1
secretion. There are similar data for thyroid and adrenal glands. No ET-1
secretion was reported in kidney neoplasms. Normal renal ET-1 secreting cells
might be less prone to turn malignant than other renal cells. Unlse the normal
lung tissue, small cell lung cancers often secrete adrenocorticotrophic hormone
(ACTH). The pancreatic islet cells do not secrete gastrin, but their tumors often
do. Constant k would exceed 1 in both cases. We speculate that these tumors might
originate from a small subset of cells with the described feature. Tumor cells
sometimes lack features of the normal tissue, as in the cases of the steroid
receptor-negative breast cancer. These tumors might originate from the
hypothetical subset of receptor-free breast cells. Benign breast epithelial cells
lacking oestrogen receptors have been described in cases of megalomastia. These
cells might be constituents of normal breasts or, perhaps, present only in cases
of increased breast cancer risk.
PMID: 10465672 [PubMed – indexed for MEDLINE]