The absence of the vomer in the first and early second trimester of pregnancy - a new marker of trisomy 21 and trisomy 13.

PURPOSE: The aim of this study was to measure the two frontomaxillo-facial (FMF) angles: the FMF-vomer (FMF-v) and the FMF-palate (FMF-p), and to visualize the vomer in the 1(st) and early 2(nd) trimester, in order to ascertain whether they can be used as markers for trisomy 21 and trisomy 13. MATERIALS AND METHODS: A 2D ultrasound scan was performed in the 340 normal and 12 abnormal pregnancies, using the linear, convex and endovaginal probes. RESULTS: We visualized the FMF angles within 1 to 5 minutes in 253 (72 %) of cases by using the linear probe. FMF-v angle was significantly smaller that the FMF-p angle (79.8° vs. 89.7°, 71.5° vs. 84.5° for the two trimesters, respectively), and that the value of both angles decreased in the second trimester. There was not one single case of trisomy in which vomer could be identified in the 1 (st) and early 2 (nd) trimester. The FMF-p angle failed to present difference between normal cases and the ones with trisomy (89.5°). There was not one single case of trisomy (21 or 13) in which vomer or FMF-v could be identified in the first or early second trimester. The diagnostic accuracy of vomer as a marker for trisomy was 0.985. CONCLUSION: If the vomer cannot be visualized in the 1 (st) and early 2 (nd) trimester, it is important to check the karyotype, and it is not necessary to measure the FMF-p angle. The high resolution probe (L 12 - 5 Mhz) enables easier assessment of the vomer.

Prediction of fetal macrosomia with ultrasound parameters and maternal glycemic controls in gestational diabetes mellitus.

PURPOSE OF INVESTIGATION: Evaluation of ultrasound measurements of fetal adipose subcutaneous tissue (ASCT), abdominal circumference (AC), liver length (LL), and amniotic fluid index (AFI) in prediction of fetal macrosomia (FM) and gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In a prospective clinical trial, 280 pregnant women underwent 100 g oral glucose tolerance test (oGTT) at 28th week of gestation (wg) and measurements ofAC, LL, AFI, and ASCT at 32nd, 34th, 36th, and 38th wg. RESULTS: For GDM, the best sensitivity was achieved by ACST at 32nd and 34th wg, the best specificity by LL at 32nd wg (90.6%), the best area under the curve (AUC) by LL at 34th wg (0.944). For FM the best sensitivity was achieved by AC at 32th, 34th, 36th, and 38th wg and by ASCT at 34th wg (94.2%), and the best AUC at 38th wg for AC (0.974). CONCLUSION: Ultrasound parameters of glycemic control were good predictors of FM and GDM.

Total ghrelin levels during acute insulin infusion in patients with polycystic ovary syndrome.

Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 nonobese patients with PCOS [body mass index (BMI): 20.52+/-1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36+/-6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74+/-25.69 vs 108.36+/-52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71+/-14.18 vs 98.77+/-40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance.

Immunological resistance to human biosynthetic insulin--effects of immunosuppression and plasmapheresis.

A 55-year-old gentleman, after being treated for a short time with a diet and with Chlorpropamide, was switched to purified porcine insulin due to ketonuria and ketoacidosis. After a year the patient developed immunological insulin resistance (mean daily insulin dose: 3.72 U/kg body weight; anti-insulin antibodies 78%). In order to lower anti-insulin antibodies human recombinant DNA insulin was introduced into further therapy. Contrary to expectations, the patient did not reduce whatsoever his anti-insulin antibodies and his daily insulin dose increased up to 5.63 U/kg body weight. Introduction of combined immunosuppressive therapy (prednisone plus azathioprine) together with plasmapheresis resulted in rapid lowering of daily insulin requirement and reduction in anti-insulin antibodies. Immunosuppressive therapy was continued with 10 mg of prednisone and a year later the patients insulin daily requirement was 0.66 U/kg BW while his antibodies were 18%. The possible causes of insulin resistance to human recombinant DNA insulin are discussed as well as the advantage of combined immunosuppressive therapy together with plasmapheresis that was used for rapid lowering of insulin daily requirement and anti-insulin antibodies titer.

Impact of Conception Method on Twin Pregnancy Course and Outcome.

Objective: The aim of the study was to investigate the course and outcomes of twin pregnancies conceived by different methods of assisted reproduction (ART) compared to those conceived spontaneously. Methods: The study involved patients with twin pregnancies who delivered at the Ob/Gyn Clinic of the Clinical Center of Serbia over a period of three years. Patients were differentiated according to method of conception and type of ART. Age, parity, etiology of infertility, pregnancy complications, time of membrane rupture and type of delivery was recorded for each patient. Gestational week at delivery, presentation, birth weight, Apgar score, chorionicity and accompanying disorders were separately recorded for each twin. The data were analyzed statistically. Results: A total of 431 patients were included in the study. Although more twins were conceived by ART, the difference was not statistically significant (p = 0.092). The most common ART procedure was IVF/ICSI (p = 0.001). ART procedures, particularly IVF/ICSI, were significantly correlated with more advanced maternal age, fewer previous pregnancies and delivery by cesarean sections, usually planned (p = 0.001). Preterm membrane rupture was more common after ICSI, but preterm delivery and pregnancy complications were infrequent, irrespective of the method of conception (p = 0.001). ART twins were mostly dichorionic (p = 0.036). Monochorionic twins were conceived either spontaneously or with ICSI. Conception by ART was not correlated with twins' outcome (weight, Apgar score, disorders). Conclusions: ART procedures do not have a negative impact on twin pregnancy course and outcome. Twin pregnancies conceived spontaneously or by ART have similar outcomes.

Impact of Phytoestrogens on Serum Lipids in Postmenopausal Women.

Objectives: The aim of the study was to assess the impact of soy- and red clover-derived isoflavones on serum lipid levels in postmenopausal women and to compare the effects to the lipid levels of healthy postmenopausal women without phytoestrogen supplementation. Materials and Methods: Blood levels of triglycerides, total cholesterol and cholesterol fractions were assessed. Measurements were performed before treatment and at 6-month intervals over a period of 18 months. The investigation included 74 healthy postmenopausal women randomized into three groups according to treatment. The first group of 23 patients received soy-derived isoflavones, the second group (26 patients) was given red clover-derived phytoestrogens, while the third control group (25 patients) received no supplements. Results: Mean triglyceride, cholesterol and LDL levels of patients in the control group were significantly higher than in both the soy and the red clover groups (p < 0.001) at all three time points, while mean values did not differ significantly between the soy and the red clover groups. The mean HDL levels of patients in the control group was significantly lower than in both the soy and the red clover groups (p < 0.001). Conclusions: Phytoestrogen supplementation had a positive metabolic effect on serum lipid levels in postmenopausal women. The impact on serum lipids levels was similar for soy and red clover.

Concentration of carbon-monoxide in carbonized bodies--forensic aspects.

The aim of this paper is to determine the correlation between carbonized fire victims' carbon-monoxide (CO) blood concentration and the cause of death. We have reevaluated and analyzed the causes of death over a 10-year period regarding CO concentrations and atherosclerosis. We have considered the possible usefulness of low CO concentrations as a vital sign in smokers and non-smokers. The study included the retrospective analyzes of 73 autopsy reports of carbonized bodies. All the autopsies were carried out in the Institute of Forensic Medicine in Belgrade over a 10-year period (1990-1999). The investigation included 53 men and 20 women (chi(2)=19.83, p<0.001) with an average age of 41.40+/-21.35 years. We found 10 cases of deadly carbon-monoxide poisoning, but further analysis of CO concentrations revealed 6 more cases in which CO poisoning could be considered. We found a statistically significant relationship between carboxyhaemoglobin concentration above 10% and the aspiration of soot (chi(2)=6.41, p<0.01). In five cases with serious atherosclerosis, the concentration of carboxyhaemoglobin was above 20%, although these concentrations can be accepted as the cause of death. Half of the deceased, in the moment of death were under the influence of alcohol and 19 of them had a blood alcohol concentration above 1 pro mille.

[The role of myomectomy in female infertility].

The aim was to examine which is the role of myoma in women infertility. We analyzed 100 patients with infertility that underwent classic abdominal myomesctomy from 2000. to 2003. year. Frequency of conception was 46%. Most patients were over 30-years-old. Conception happened in 80% patients aged 30-39 years. In 69,6% patients with secundar infertility happened conception. Pregnancies occured more often in infertility shorter than 36 months, in front wall myoma and in intramural-subserose or subserose type. In 11 patients with intramural-submucose myomas, uteral cave was opened and only two of them got pregnant. Recidives of myoma happened in 18%, and postoperative adhesions in 29% of pacients. Age, duration of pre-operative infertility and characteristics of myoma did not have statistically significant influence on the conception. Miomectomy is the important method in treatment of infertility, especially if the other possible causes were excluded.

[Beta blockers in the treatment of hyperthyroidism]. / Beta blokatori u lecenju hipertireodizma.

Beta blockers are widely used as adjuvant therapy in the treatment of hyperthyroidism. They are usually combined with antithyroid drugs, iodine, in the period before the effect of radiotherapy occurs and in patients during preparation for partial surgical resection of the thyroid gland. In exceptional situations, in mild form of hyperthyroidism, when it is not possible to use other drugs, it may be useful to apply propranolol as a single drug. Oral doses are 40 to 80 mg every 6 or 8 hours. For intravenous application more useful are short-acting drugs. Drug is applied until remission of all symptoms of the disease. In this kind of therapy propranolol almost does not produce any untoward effects. Containdications for the application of beta blockers are: asthma, chronic obstructive pulmonary disease and congestive heart insufficiency.

[The Mallory-Weiss syndrome as an unrecognized cause of death]. / Malori-Vajsov sindrom kao u uzrok neznana smrti.

Longitudinal tears in the esophagus at the esophageogastric junction are termed Mallory-Weiss syndrome. They are encountered most commonly in alcoholics, attributed to episodes of excessive vomiting. These lacerations could be the cause of massive and severe external and/or internal fatal bleeding. Bleeding from upper gastrointestinal parts could be caused by this syndrome, as well as by ulcers, inflammations, esophageal varices, tumours, blunt abdominal injuries, etc. Such unclear deaths could be of interest to law authorities because they are suspicious, sudden and/or obscure. In daily forensic medical practice, this syndrome is relatively rare, and therefore it, it should be recognized. In this paper, the authors present the case of a single male, aged 54, a chronic drinker, who was found dead in his flat. During the previous day, he was observed medically in the Trauma Centre in Belgrade for nonspecific gastrointestinal symptoms (nausea, vomiting and diarrhea). The mucous tears of esophageogastric junction had been established by autopsy, as well as the massive internal gastrointestinal bleeding. On the basis of autopsy and microscopic findings, clinical data and circumstances, the established cause of natural death was fatal exsanguination from esophageogastric mucous tears due to Mallory-Weiss syndrome.

[Correlation between survival time and severity of injuries in fatal injuries in traffic accidents]. / Korelacija izmedju vremena nadzivljavanja i tezine traume kod smrtno stradalih osoba u saobracaju.

INTRODUCTION: In forensic pathology, only trauma systems based on disintegration of anatomic structure of organs and tissues, could be used for objectivization, comparison and establishing of severity of injuries. Trauma systems based on pathophysiological values are useless. The Abbreviated Injury Scale (AIS) and its derivate Injury Severity Score (ISS) are the most common. AIS coded injuries are divided into six body regions and injuries are assigned a six-digit score in relation to their severity. ISS results the sum of the squares of the highest AIS values from the three most severely injured body regions. In this way, the ISS values are discontinued and vary from 0 (absence of injuries) to 75 (incompatible-with-life injury). PURPOSE: The purpose of this paper is to establish the correlation degree between outliving period and trauma severity in persons fatally injured in traffic accidents, and according to this finding to point out the ISS value of critical injury. MATERIAL AND METHOD: A retrospective autopsy study was performed; it included the material of the Institute of Forensic Medicine in Belgrade of 1998. The autopsy reports and accessible clinical medical data were analyzed for persons over the age of 18, fatally injured in traffic accidents who survived trauma less than 15 days. The sample was statistically prepared (chi 2-test, t-test, correlation coefficient, regression line). RESULTS AND DISCUSSION: The sample included 272 persons: 193 males and 79 females. The proportion of men was more significant (chi 2 = 4.76; 0.01 < p < 0.05). Average age was 51.08 years (SD = 18.08): males 49.84 +/- 17.41 and females 54.09 +/- 19.38. The most frequently injured persons in our sample were pedestrians (134). The authors combined the autopsy and accessible clinical data in order to obtain the ISS value for each case. They considered that all persons found dead on the spot or died ante portam did not outlive trauma. The sample distribution by ISS values showed three peaks: for ISS--75, 41-50 and 26-35. Peaks indicated the number of the injured body regions and trauma severity in these persons. In 87 persons who did not survive, the ISS value was 75. There were 73 persons without outliving period with ISS values less than 75: their mean ISS value was 31.87 (SD = 11.30). In 112 cases the mean outliving period was 4.79 days (SD = 3.77) and their mean ISS value was 18.05 (SD = 15.33), which was a statistically significant lower ISS value than in previous group (t = 7.015; p < 0.001). A weak negative correlation between outliving period and ISS values in our sample was noted (coefficient of linear correlation r = -0.452). Our sample is representative (t = 8.37). Coefficient of a determination (r2 = 0.20), pointed to the fact that direct correlation outliving period-trauma severity was only about 20% and the rest of correlation i.e. 80% depended on other factors (e.g. effective emergency medical system and triage, prompt and correct diagnosis, adequate medical treatment and care, etc.). The calculated linear regression was as follows: outliving period approximately 52-3 ISS. This regression pointed out that critical and potentially fatal injury, in our sample, was injury with ISS of 17. There were 22 persons with ISS < or = 7. Six of them died on the spot as car passengers; they died due to mechanical asphyxia (thoracoabdominal pressure) or respiratory and/or circulation failure due to critical chest injury (flail chest, contusions and rupture of the lungs with consequent haemopneumothorax). The rest of 16 persons survived trauma in an average of 8.56 days (SD = 3.88), and the causes of death were pneumonia, thrombus and fat embolism, sepsis, etc. CONCLUSION: By anaylzing our sample of fatally injured persons in traffic accidents (unpenetrated blunt trauma), there was a negative weak correlation between the outliving period and severity of injury based on ISS. This correlation was partly direct but mostly depended on other factors (e.g. effective emergency medical system and triage, prompt and correct diagnosis, adequate medical treatment and care, etc.). Establishment of these factors could be possible through state medical projects in big medical trauma centres. Prospect registration, evaluation and scoring of all injuries in hospitals and dissecting rooms, and comparison of the obtained results, can give valid data on mortality of injured people, bad diagnosis, and appropriate medical treatment. The autopsy of injured persons dead on the spot can point out what kind of injuries are incompatible with life, as well as with their severity. The autopsy of injured persons who survived trauma can point to the most frequent injury complications, clinical diagnosis and preventable deaths. According to this paper, the critical injury by ISS is 17. In such cases, the forensic pathologist must answer the following questions: whether the death was due to trauma; whether the precipitated cause of death was the consequence or complication of injury; what were the mechanism and mode of dying; whether the death was preventable; if there were possible malpractice and negligence, etc.

Depletion and reaccumulation of follicular thyroglobulin (TG) in guinea-pig thyroid gland after short- and long-term administration of thyrotropin (TSH).

The relationships among the content and composition of soluble iodoproteins in thyroid gland, the serum Tg concentration and the morphological structure of gland were investigated in guinea-pigs during short-term and long-term TSH administration (2 I.U. per day for 1 to 28 days). A significant decrease in the content of Tg in the gland (from 6.50 mg to 1.32 mg/100 mg tissue), disappearance of 12 S iodoprotein, hypertrophy and hyperplasia of the follicular cells were observed in guinea-pigs treated with TSH up to 7 days. Later on, after depletion of follicular colloid, reaccumulation of colloid in the preexisting and newformed follicles (a marked increase of Tg and 12 S protein) and partial involution of the structural changes occurred. The serum Tg concentration increased during the whole period of TSH treatment (mean values from 100 to 500 micrograms/l). A marked positive correlation between serum Tg concentration and thyroid weight was found. Serum T3 and T4 concentrations increased transiently with maximal values on the 1st day (T3, from 0.86 to 3.26 nmol/l, T4, from 44 to 138 nmol/l) and decreased thereafter. The results imply that different regulatory mechanisms exist which control thyroid hormone secretion and transfer of Tg from the gland into blood circulation. The serum Tg level is directly dependent on the total bulk of thyroid tissue, but is considerably less dependent on the structure of the gland. The reaccumulation of colloid (Tg) in thyroid follicles of guinea-pigs treated with TSH is a result of the reduction of the stimulatory effect of TSH on the process of Tg degradation during chronic hormone application. Several different factors may be responsible for the appearance of refractoriness or desensitization of the thyroid to prolonged exogenous TSH stimulation.

Reduced acid protease activity in vitro of lysosomes from thyroid gland of rats chronically treated with propylthiouracil and perchlorate.

We have recently demonstrated that proteolytic activity of lysosomal acid proteases from papillary carcinoma is significantly higher than in morphologically normal thyroid tissue. In the present study the activity of lysosomal acid proteases from parenchymatous proliferated thyroid epithelium, induced by action of antithyroid substances, has been examined in an in vitro system using 125I-labelled rat thyroglobulin as a substrate. Thyroid lysosomes were isolated from rats treated chronically for 3-4 weeks with propylthiouracil (PTU, 0.1% in drinking water) and perchlorate (NaClO4, 200 mg/rat/day) by centrifugation between 800 and 20,000 x g. It was observed that, in contrast to human malignant thyroid tissue, the proteolytic activity of lysosomal acid proteases from antithyroid substance-induced hyperplastic goitre was markedly reduced in comparison with control thyroid tissue (29-50%). Since reduced activity of total lysosomal proteases was found both per unit of wet weight thyroid tissue and per unit of lysosomal proteins, the results suggest that changes in lysosomal enzymes may probably have more quantitative than qualitative nature.

[Effects of amiodarone on the thyroid gland in euthyroid and hypothyroid animals]. / Efekti amiodarona na tireoideju eutireoidnih i hipotireoidnih zivotinja.

Amiodarone is a benzofurane derivative which contains an appreciable amount of iodine (37%). It is used in cardiology as an antianginal and antiarrhythmic drug. Using guinea-pigs and rats as the animal model systems, the effects of amiodarone on normal and hyperplastic thyroid glands were investigated in eu- and hypothyroid animals. After the amiodarone treatment, considerable differences were observed in the levels of thyroid hormones and in the structure of the gland which proved dependent not only on the length of treatment, but also on animal species and the functional status of the gland before treatment. At extended amiodarone application, the rats with hyperplastic thyroid developed microlesions in epithelium of some follicles.

[Fatal therapeutic event after an injection of chlorpromazine]. / Fatalni terapijski zades posle injekcije hlorpromazina.

Accidental deaths after parenteral use of medicaments are usually very rare. The most common cause of death is allergic reaction. In literature, the most menacing medicaments are antibiotics. Taking into account that macroscopic and microscopic autopsy findings are uncharacteristic and poor clinical features and circumstances are more or less characteristic and objective, and that the establishing of cause and mode of death could be a problem for dissectors. Later, in forensic expertise, the questions about medical malpractice could arise. In this paper the authors report on the case of a male, aged 46, a chronic psychiatric patient with schizophrenia, treated by neuroleptics, who died about half an hour after intramuscular injection of chlorpromazine. On the basis of the autopsy, microscopical and toxicological findings, clinical features and circumstances, as well as exclusion of other possible violent and morbid causes of death, it was established that the unexpected and sudden death was caused by anaphylactic allergic reaction due to injected medicament--chlorpromazine.

[Iodine levels in salt for human consumption and aspects of iodine prophylaxis in Yugoslavia]. / Sadrzaj joda u soli za ljudsku upotrebu i neki aktuelni aspekti jodne profilakse u nasoj zemlji.

Iodine content of iodinated salt intended only for human consumption was eyamined in samples from all domestic manufacturers (salt mines in: Tuzla, Pag, Ulcinj, Ston, Nin, Seca-Portoroz). Sampling was made from commercially available packs (1 kg) or from food industries (large packs). It was established that iodine content of examined samples (57) varied considerably and ranged from 1.8 to 12.2 mg iodine/kg salt. Iodinated salt from the Tuzla and Pag salt mines contained iodine within the prescribed limits in both small and large packs. Similar finding of iodine content was in the small packs of the Ulcinj salt mines, however, their large packs (10 kg) had a markedly low level of iodine (1.8-4.7 mg). Lower iodine content was also noted in salts (1 kg) from the Nin, Ston and Seca-Portoroz mines. Of the 57 examined samples in 70% iodine content was lower than the prescribed dose (7.6 mg). In addition, some mines had low iodine content in all of the 100% of their respective samples. Ever since iodine prophylaxis was introduced in Yugoslavia a number of factors influenced the decrease of iodine intake by the organism to a considerable degree. The results of our investigations and some epidemiological data indicate that the issue of increasing the amount of iodine from the present 7.6 to 15 mg iodine/kg salt should be reconsidered. Besides, it is necessary to arrange the systematic quality control of iodinated salt.

[Clinical study of the use of LHRH (GnRH) analogs]. / Klinicka iskustva u primeni LHRH (GnRH) analoga.

We presented recent advances in the use of LHRH analogues, the structure, the route of administration and the indications. Reversible medical castration was achieved with LHRH analogues and LHRH analogues could be applied in endocrinology, gynaecology and oncology. The paper deals with our experience in Suprefact application (Hoechst) in PCOS patients; induction of ovulation with Suprefact and pulsatile s.c. LHRH, and Superfact with exogenous gonadotropins. The use of analogues in the treatment of hirsutism is discussed.

Effect of pentobarbital on the synaptosomal activity of acetylcholinesterase in Mongolian gerbils.

The influence of Na pentobarbital anesthesia on the activity of specific and nonspecific cholinesterase was studied in the synaptosomal fraction of Mongolian gerbils' brains. These studies have shown that this barbiturate inhibits the specific activity of acetylcholinesterase only.