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.

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.

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.

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.

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.

[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.

[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.

[Post-traumatic pulmonary and systemic fat embolism in forensic practice. Prospective histological study]. / Posttraumska plucna i sistemska masna embolija u forenzijskoj praksi. Prospektivna histologijska studija.

INTRODUCTION: The more or less subclinical presence of fat emboli in the lungs and other vital organs, without ischaemic changes in them, whose presence could be postmortem established only by microscopic examination, is termed in forensic medicine systemic fat embolism. On the other hand, Fat Embolism Syndrome (FES) is a clinical manifestation of the presence and influence of fat emboli in organs, with clearly defined neurological, respiratory and cutaneous signs and various symptoms, grouped in the so called major and minor signs [8-11]. PURPOSE: The purpose of this paper is to establish the frequency of post-traumatic occurrence of fat emboli in capillaries of the lungs and other organs in cases where the cause of death was not related to pulmonary or systemic fat embolism, but where the typical fat depot injury was established. MATERIAL AND METHOD: A prospective autopsy histological study was carried out. The sample included 56 cases. The clinical and autopsy data were analyzed and compared in order to establish the value of injury Severity Score--ISS. Histological samples of all vital organs were stained by special technique (Sudan III) and the findings in the lungs and kidneys were graded according to Sevitt's criteria [12]. All data were statistically analyzed (chi 2 test, ANOVA). RESULTS AND DISCUSSION: The sample included 38 males (average age 53.10 years) and 18 females (average age 54.84 years). The older (ANOVA; p = 0.0017) males (chi 2 = 7.14; p < 0.01), injured as pedestrians (ANOVA, p-->0) were statistically significantly more represented. The most common determined causes of death were: cerebral contusions (30), exsanguination (22), respiratory disorders (9), combustion (6), spinal cord contusions (1), and others (complication of injuries, such as inflammations or sepsis--4). These causes were singular or competitive plural. The average value of ISS was 34.59 (SD = 13.16) and that of outliving period 3.70 days (SD = 5.88). The distribution of outliving period was log-normal. Pulmonary fat embolism was established in all cases: in 14 cases pulmonary fat embolism of the first degree; in 16 of the second grade and in 26 of the third degree. Pulmonary fat embolism of the third degree could be the precipitate singular or concurrent cause of death. The presence of fat emboli in glomeruli was established in 39 cases: in 30 cases the kidney fat embolism of the first degree was established, in 6 of the second degree and in 3 cases of the third degree. In 11 cases the presence of fat globules in brain capillaries was established and in 3 cases in the capillaries of other organs (heart, liver, spleen). By analyzing the clinical and autopsy data, as well as microscopic findings, we concluded that in four cases the cause of death was associated with systemic fat embolism, what previously had been missed. CONCLUSION: In all our sample cases pulmonary fat embolism was verified, and in a great number of them systemic fat embolism. According to medicolegal principles, pulmonary and systemic fat embolism that develop a few hours after trauma can be considered as a consequence of typical body fat depot injury. The later developed FES could be considered as the complication of such an injury. Pulmonary and systemic fat embolism could complicate the basic trauma, e.g. craniocerebral, abdominal or thoracic, and could be considered as the precipitating cause of death. Because of non-specific and non-characteristic macroscopic autopsy findings, pulmonary and systemic fat embolism could be missed as the cause of death.

[Post-traumatic systemic fat embolism syndrome. Retrospective autopsy study]. / Posttraumski sindrom sistemske masne embolije. Retrospectivna autopsijska studija.

INTRODUCTION: The obstruction of blood vessels or heart chambers with fat globules, reached by circulation, is fat embolism [1, 2]. Clinical manifestation of the presence of fat emboli in vital organs is Fat Embolism Syndrome (FES). This syndrome is characterized by neurologic, respiratory and cutaneous signs and different symptoms [5-8], grouped in major and minor signs by Gurd and Wilson. PURPOSE: The purpose of this paper is to analyze and compare the autopsy findings and clinical data in cases where FES is emphasized as the single or concurrent cause of death after performed autopsy. MATERIAL AND METHOD: This retrospective study includes the autopsy material of the Institute of Forensic Medicine in Belgrade, over the period 1985-1998 when FES is pointed out as a cause of death. The severity of trauma for each case was determinated by Injury Severity Score (ISS). The microscopical findings, which are incorporated in autopsy reports, were separately analyzed. The sample was statistically prepared (chi 2 test, ANOVA). RESULTS: The sample included 56 patients: 43 males (average age 51.65 years) and 13 females (average age 65.07 years). The proportion of men was more significant (chi 2 test = 8.98; p < 0.01) as well as the persons aged 60-80 years (ANOVA, p = 0.0017). In our sample there were more pedestrians (32 patients) (Anova, p-->0) than other injured persons. Fractures of the femur, tibia and/or pelvic bones were typical injuries in each examined patient. The authors combined the clinical and autopsy data in order to get the ISS value. The mean ISS value was 20.65 (SD = 7.47). The mean value of the surviving period was 5.8 days (SD = 3.6). The sample distribution of surviving period was normal (Gauss distribution). The latent period from injury to the onset of the first major FES signs was about 24 hours (32 patients had one of the major FES signs during the first 24 hours after admission; 8 patients after 24-48 hours and 10 after 48 hours after admission). Six patients who were admitted in deep coma were not analyzed. DISCUSSION: The most common first major FES sign refers to the sudden onset and rapid progressive qualitative or/and quantitative disturbance of conciousness (deep coma developed after a short period, without obvious causes) in 40 cases. In six patients ophthalmological characteristic retinal blood vessels changes were found: they pointed to FES. The second major FES sign was respiratory disturbance alone (manifested at first as chest pain and spitting of blood, and later as disturbances in artery blood gas analysis), or in combination with disturbed conciousness--in 15 cases The characteristic later developed cutaneous chest and axillary rush as the only specific FES sign was established in 11 cases (surviving period was from 5 to 12 days), but clinically only in one case. In addition to objective difficulties, in most cases, one of the minor FES signs was established: in 22 cases haematological disturbances (i. g. low value of haematocrit, haemoglobin, number of platelets or/and coagulation factors); in 13 cases hyperpirexia, and other minor FES signs only occasionally. The postmortem diagnosis of FES could be established only microscopically (Sudan III staining). Bronchopneumonia (24 cases), hyaline membranes (7 cases), as well as lung oedema and alveolar haemorrhages (in almost two thirds of the sample) were the most common microscopical findings in the lung as complications of FES. The most characteristic postmortem brain findings in FES are dotted perivascular haemorrhages, mostly in the white matter. These changes were not established in 7 cases (surviving period was 1 to 2 days), but the especially stained sections pointed to FES as the cause of death. In addition to various chronic pathological changes, only intestinal haemorrhages and/or oedema of solid organs could be established microscopically. CONCLUSION: In the analyzed sample of 56 patients who died of FES, FES was clinically established onl

[Treatment of postmenopausal osteoporosis with 1-alpha(OH)D3]. / Lecenje postmenopauzne osteoporoze sintetskim analogom vitamina de-tri.

To evaluate the efficacy and safety of 1-alpha(OH) vitamin D3 in the treatment of postmenopausal osteoporosis, we conducted a six month prospective, double blind study in 20 postmenopausal women. Women were randomly divided into two groups. One group (n=12) received 1-alpha(OH) vitamin D3 (0.25 mcg twice a day), the other (n=8) received placebo. At the same time both groups received one calcium tablet (500 mg daily). In the group treated with 1-alpha(OH) vitamin D3, there was a significant increase in serum calcium (p<0.01), urinary excretion of calcium (p<0.05), and serum 1.25(OH)2 vitamin D3 concentracion (p<0.01), while parathyroid hormone levels showed tendency to fall without statistical significance. In the group treated with placebo and calcium, after treatment there was only a significant increase in serum calcium (p<0.01). In the placebo group occurrance of one new vertebral fracture was recorded. There were no side effects during treatment in both groups. It was concluded that the administration of 1-alpha(OH) vitamin D3 is a safe and potentially efficient drug in the treatment of postmenopausal osteoporosis.

[Effects of amiodarone on the thyroid gland: appearance of microlesions in follicles of hyperplastic rat thyroid after chronic amiodarone treatment]. / Dejstva amiodarona na tireoidnu zlezdu--pojava mikrolezija u folikulima hiperplasticne tireoidne zlezde pacova posle hronicnog tretmana amiodarom.

Using the rat and guinea-pig as an experimental animal model, the effect of amiodarone (Cordarone) on normal of hyperplastic thyroid was investigated in eu- or hypothyroid animals. Following short- or long-term treatments with different doses of amiodarone (5-50 mg/day) and amiodarone-equivalent amounts of stable iodine, serum thyroid hormones were assayed, followed by determination of thyroid uptake of radioiodine, the weight of the thyroid gland and its histological structure. Having received amiodarone chronically, euthyroid rats showed decreaed levels of serum T3 and T4, in contrast to euthyroid guinea-pigs in which no appreciable differences between amiodarone-treated and untreated animals were observed. However, the weight of the thyroid decreased in both species after amiodarone treatment. A similar effect was seen after the treatment with excessive iodine, but only in euthyroid rats, while the guinea-pigs showed increased gland weight and activation of the follicular epithelium, as seen on histological sections. These differences obeserved in thyroid glands of rats and guineapigs were probably associated with the facts that the normal dietary iodine intake was lower in guinea-pigs and their thyroid glands were more sensitive to excess of iodine than that of rats. After chronic amiodarone treatment, hypothyroid rats with hyperplastic thyroids showed a much greater increase of serum T4 than the control rats, while the T3 increase was appreciably smaller. After several months (5 and 6.5) of amiodarone treatment, the appearance of various lesions was observed in the thyroid follicular epithelium of these animals. These microlesions probably resulted in a direct toxic effect of amiodarone on the hyperplastic gland. The results of the present investigation suggest that amiodarone effects on the thyroid may not be associated with excessive iodine exclusively, but also with the specific effects of amiodarone on this gland.

Modulation by glucocorticoids of growth hormone secretion in patients with different pituitary tumors.

The acute administration of glucocorticoids is a new stimulus of growth hormone (GH) secretion in man. In order to ascertain its point of action, and also the suitability of this new test as a diagnostic tool in GH pathological states, 33 subjects were studied. Eight of them were normal controls, and 25 were patients with tumors affecting the hypothalamopituitary area. A glucocorticoid stimulus, dexamethasone 4 mg i.v. was administered at 0 min and GH levels (means +/- SEM, microgram/l) were measured during the following 5 h. In addition, GH-releasing hormone (GHRH) and clonidine were employed as either pituitary or hypothalamic GH stimuli. Dexamethasone administration to normal subjects did not alter GH levels in the first 2 h of the test. Afterwards, a GH peak was observed around the third hour, GH levels returning to basal ones thereafter. The dexamethasone-induced GH peak (6.7 +/- 1.5) and area under the curve (526 +/- 137) were lower than after GHRH (14.0 +/- 4.5 and 1,070 +/- 369, respectively). In the 14 acromegalic patients studied, the GHRH-induced GH net increase was similar to that observed in controls, while the placebo did not alter GH basal levels. An absence of hypothalamic control was evident because clonidine did not stimulate GH release. On the other hand, and contrary to normal subjects, dexamethasone strongly inhibited GH secretion, the values being significantly lower when calculated either as mean GH peak, or maximum GH increment (delta). The delta GH was -2.5 +/- 3.1 after placebo, +3.7 +/- 4.5 after clonidine, +17.0 +/- 3.3 after GHRH and -13.4 +/- 4.5 following dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Further evidence for differential regulation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH): increased FSH and decreased LH levels in a patient with familial pure gonadal dysgenesis.

There is experimental evidence that a portion of follicle-stimulating hormone (FSH) secretion is independent of hypothalamic influences. A 29 year old woman with familial pure gonadal dysgenesis developed myelodysplastic syndrome. Endocrine investigations showed discrepancy between serum FSH and luteinizing hormone (LH) levels. FSH levels remained elevated while LH levels decreased. The FSH to LH ratio was 10 (normal 2-2.5). The fall in LH is likely to be due to factor(s) involved directly and specifically in LH synthesis and release. Exogenous LH releasing hormone administration as well as hormonal replacement treatment increased LH levels. The FSH to LH ratio decreased to 7. This case supports the hypothesis of differential regulation of FSH and LH, and that FSH secretion is at least partly autonomous.

Belgrade virus: a new hantavirus causing severe hemorrhagic fever with renal syndrome in Yugoslavia.

Two biologically and genetically distinct hantaviruses were isolated from blood and urine specimens collected from four Yugoslavian patients with clinically severe hemorrhagic fever with renal syndrome (HFRS). Viral isolates from three patients, designated strains Belgrade 1-3, were distinct from Hantaan, Seoul, Puumala, and Prospect Hill viruses as determined by plaque-reduction neutralization tests and restriction analysis of enzymatically amplified M-segment fragments. The fourth isolate, called Kraljevo, was indistinguishable from Hantaan virus. Strains Belgrade 1 and 2, like the Kraljevo strain, caused a fatal meningoencephalitis in newborn mice inoculated with 100 pfu of virus intracerebrally and intraperitoneally. Strain Belgrade 3 was much less neurovirulent, requiring 30,000 pfu of virus to cause fatal disease in mice. These data indicate that two distinct hantaviruses, one of which constitutes a new serotype, cause clinically severe HFRS in Yugoslavia.