Ambiguous Genitalia and Lissencephaly in A 46,XY Neonate with a Novel Variant of Aristaless Gene.

Introduction: Disorders of sexual development can present isolated or as a part of complex genetic syndromes. Case presentation: A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent. Conclusions: The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia.

An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2-18.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n=1) and impaired glucose regulation in 15.9% (n=48) of the subjects. Isolated IFG was detected in 4.3% (n=13), isolated IGT in 8.3% (n=25) and combined IFG and IGT in 3.3% (n=10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.

HELLP syndrome as a cause of unexpected rapid maternal death--a case report and review of the literature.

Unexpected rapid death after delivery due to HELLP syndrome (HS) may become the subject of a forensic expertise. Since this syndrome is rarely encountered in forensic pathology, our objective was to point to some specific findings which might present forensic aspects of HS. These include unexpectedness, suddenness and fulminant course of this syndrome, which may confuse physicians, and on the other hand these characteristics cast doubt on violent injury, diagnostic oversights or iatrogenic injuries. Absence of classical signs of preeclampsia and non-specific clinical symptoms cause considerable differential diagnostic problems leading to a diagnostic delay or initial wrong non-obstetric diagnosis. A definitive postmortem diagnosis of HS in questionable cases of maternal death and consecutive forensic expertise of suspected medical malpractice should be based on accepted laboratory criteria and characteristic histopathological alterations.

"Cognac alibi" as a drunk-driving defense and medico-legal challenge.

Some drivers with positive forensic ethanol analyses, offer an explanation that they consumed alcohol a short time before a traffic accident or after driving. In medico legal practice this is commonly known as hip-flask defense, but to us as "cognac alibi" defense. In these cases, the lawyers require the medico legal experts to offer as much information as possible so that the court may come to the most reliable conclusions about the driver's blood alcohol concentration at the moment of the traffic accident (BAC(Acc)). At the Institute of Forensic Medicine our own analytical approach was established to study this medico legal problem. It consists of three inter-related phases in which it combines the obtained BAC values, with testimonies of the drunk driving suspect andalso witnesses. A specific algorithm was designed for calculating absorption and elimination of consumed alcohol. All the above-mentioned elements and blood-ethanol values calculated according to Widmark's method were inserted into appropriate cells of MS Excel software in order to calculate BAC in the function of time. The result is a relevant analysis of the drunk driving suspect's BAC in 5-minute intervals, as well as a graphic representation in chart form.

[Analysis of ischemic lesions of the liver after various periods of warm and cold ischemia]. / Analiza ishemijskih lezija jetre u razlicitim intervalima tople i hladne ishemije.

Liver and sinusoidal wall cells become swollen very fast due to ischemia in liver allograft, with Eurocollins preservation solution. This process consequently narrows the sinusoidal lumen and significantly disturbs the "functional structure" of Rapaport microcirculation units. Advanced changes on "functional structure" microcirculation liver units can cause outflow block phenomenon of the liver and a consequential primary graft dysfunction. In order to avoid this unfavorable consequence of transplantation, it is necessary to assess the potential allograft vitality in advance. The assessment can be based on measuring values of sinusoidal volume, increase of the serum glutaminpyruvic transaminaze (SGPT) level per mass unit of liver tissue in the preservation solution and increase of necrotizing hepatocytes' number in liver lobules. During the first 8 hours of cold ischemia these values do not change significantly, so we can conclude that in this interval of cold ischemia liver is suitable for transplantation, which is not the case with warm ischemia where changes occur much earlier. Practically, the intensity of lesions with 4 hour period of warm ischemia equals the intensity of lesions with 16 hour period of cold ischemia.

[Morphologic characteristics of the liver allograft in experimental warm ischemia]. / Morfoloske karakteristike alografta jetre u eksperimentalnoj toploj ishemiji.

Thirty-minute normothermic liver ischemia causes swelling of the hepatocytes and sinusoid wall cells, their individual necrosis and discharge of the glycogen supply in the hepatocytes. The swelling of the hepatocytes and of the sinusoid wall cells causes a significant reduction of the liver lobe sinusoid volume which decreases from 27.6% to 5.4%, representing, actually, one fifth of the normal value. Such finding was recorded as a critical vascular liver volume, because any further decrease of the sinusoid volume would inevitably lead toward manifest and persisting portal hypertension which evidently interferes with Bernoulli trial of the hepatitic perfusion. The obtained data determine morphofunctional relevancy of the liver allograft for transplantation and are useful for all other surgical interventions requiring partial resection of this organ or time limited regional and total ischemia.

[Morphologic analysis of damage in renal grafts in various preservative solutions]. / Morfoloska analiza ostecenja renalnog grafta u razlicitim prezervacionim tecnostima.

In this study experimental research was conducted concerning the morphology of renal lesions, in the function of time (12, 24, 36 and 48 hours) on potential renal allografts, which were stored in various cooled preservative fluids. A physiological solution was used, Euro-Collins and modified Euro-Collins, where dextrose was substituted with mannitol in the quantity of 35 g/l. With the modification of the Euro-Collins solution, in other words by the substitution of dextrose with mannitol, better results were achieved, and the differences grow in the function of time. The electrolytic content of this solution successfully maintains the intracellular ionic balance, and mannitol, as a highly osmotically active substance, offers better protection of the cells of the nephron complex from intracellular water penetration, which immediately results in the prolongation of preservation time and better quality of cadaveric renal graft.

[Experimental study of liver allograft damage during cold ischemia]. / Eksperimentalna istrazivanja ostecenja alografta jetre u toku hladne ishemije.

Changes on the majority of structural complexes were observed in livers that underwent the influence of the preservant and cold ischemia. Cellular architecture of a such liver is disturbed. Hepatocites are with granular and vacuolar degeneration: focal cariolyzes and piasmolyzes are present, partial destruction of cellular membrane is noticeable. The dilatation of sinusoidal spaces is very emphasized and followed by the severe loss of endothelium. These changes along with the disturbed cellular architecture represent the findings of Pelosis hepatis. It is important to emphasize the significance of changes observed on liver sinusoids and endothelium especially since their intensity is much greater than of those changes observed on parenchim. We assume that these angioarchitectural damages play an important role in the onset and development of cardiopulmonal and coagulopatic components of the postreperfusional syndrome. The fact that the postreperfusional syndrome was also observed in cases with heterotopic transplantation could support this assumption.

[Damage in the hemato-enteral barrier in experimental liver transplantation]. / Problematika ostecenja hematoenteralne barijere kod eksperimentalne transplantacije jetre.

Semiquantitative analyzes of intestinal mucous lesion graduating from 0 (normal) to V (necrotic) were done in the experimental model, 6-12h alter the heterotopic liver transplantation in dogs. All degrees of mucous damages were found in intestinal samples (mean value was 2.60). The most dominant were the lesions of III (31%) and IV (25%) degree while in 4% complete destruction of mucousal villious was observed. Success of liver transplantation besides the presence of the lesions of hepatic alograft during the phases of the warm and cold ischemia or immunological responses, depends on the changes in functionally connected regions. In that sense the damages of mesenterial department lead a very important role. Lumenal infective agents and cardiodepressive macromolecules, passing trough the hematoenteral barrier, cause local hepatic damages and central cardiovascular failure.