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The scientific article analyzes modern theoretical ideas about the essence of the concepts of ‘permission’ and ‘permission system’, on the basis of which the author's definition of the concept of ‘permission system’ is formulated, its essence and main features are revealed. Based on the study and analysis of scientific sources and the legal framework, the place of the permit system in the activities of public administration bodies is determined. It was found that the concept of ‘permissive system’ must be considered in two aspects: in a broad and narrow sense. It is substantiated that the concept of a permit system in a narrow sense actually reveals the essence of the exercise of control by an authorized body of public administration over the circulation of objects, materials and substances that pose an increased danger to human life and health and for which special rules or procedures have been established. As we can see, a common feature among the presented definitions of the term "permit" is the mandatory presence of a separate official document from an authorized entity that grants the corresponding right to something, as well as the definition of the objects and subjects of this permit, "...that is, who, to whom , where, under what conditions and during what period provides the opportunity to carry out this or that activity, to use these or that individual objects, substances or materials". The permissive system does not "permit" to have this or that right, but creates an appropriate procedural format for its proper (adequate, compliant with the requirements of the law) implementation. This applies to many other human and citizen rights. They are quite real and inalienable, but for their appropriate implementation, it is necessary to "deploy" (initiate and carry out) procedures prescribed by law, to go through all stages of the process prescribed by law. Legal implementation is procedural by nature, it is difficult to imagine any complex legal relations (and human rights are their embodiment) that could be implemented without procedural design. Considering the fact that the authority to implement the permit system in this area is entrusted to the police authorities, it was concluded that the permit system in the narrow sense should be considered as the permit system of the National Police of Ukraine.

Background. The use of targeted sequencing panels makes it possible to optimize and personalize the treatment strategy for cancer patients. Given the lack of a clear «portrait of the patient», the role of large panels (200 or more genes) in the treatment of a patient has not yet been determined.Aim. Assessment of the relationship between the results of targeted sequencing of tumor tissue or ctDNA and the treatment carried out after obtaining these data in patients with various solid tumors.Materials and methods. We retrospectively evaluated the NGS results and the treatments, provided to the 184 patients after NGS testing between 06.2016 and 06.2021. For analysis, one of two methods is used: a histological sample or the patient’s blood plasma. Evaluation of the results and determination of treatment tactics were carried out within the framework of a multidisciplinary commission. The frequency of detection of molecular disorders, the number of mutations in each sample, and the frequency of detection of targets for targeted therapy were assessed.Results. Molecular disorders were detected in 88.5 % (n = 163). The average number of mutations in one sample was 6. The maximum was detected in colorectal cancer patients; their average value was 8. The minimum was determined in non-small cell lung cancer and ovarian cancer patients, the average number of mutations was 3 in each localization. The average time from the moment the material was received by the laboratory to the generation of the report was 11 days. Targeted targets were identified in 25 (13.6 %) patients and therapy was started. Therapy with tyrosine kinase inhibitors of the first – third generations were performed in 12 (48 %) patients, PARP inhibitors – in 3 (24 %), BRAF and MEK inhibitors – in 2 (8 %), anti-HER2 therapy – in 1 (4 %). Targeted therapy within international clinical trials was initiated in 4 (16 %) patients. Immunotherapy was recommended in 3 (12 %) patients. In multivariate analysis, the chance of prescribing therapy based on the results of FM1 analysis was influenced by: mRAS (odds ratio 0.08; 95 % confidence interval 0.01–0.65; p = 0.018) and mEGFR (odds ratio 4.8; 95 % confidence interval 1.4–16.3; p = 0.012).Conclusion. The effectiveness of the FM1 test in real clinical practice in the Russian Federation corresponds to international data. In the presence of a mutation in the RAS genes, an additional FM1 test determines a low chance of detecting clinically significant disorders for which personalized treatment can be prescribed. The high frequency of prescription of therapy based on the results of blood plasma tests is due to the cohort of patients with non-small cell lung cancer and the detection of a mutation in the EGFR gene.

Background. Hemobilia is the excretion of blood alongside with bile through intra- and extrahepatic bile ducts. Despite the use of new methods of diagnosis and treatment, the mortality rate from hemobilia remains high (20-40%). Objective. To demonstrate a clinical case and some methods of diagnosis and treatment of a patient with hemobilia. Material and methods. The article presents our own clinical observation of a patient with a penetrating knife wound of the abdominal cavity with liver injury complicated by hemobilia. Two-stage treatment was performed including upper midline laparotomy, cholecystectomy, and biliary tract sanitation with external drainage of the common bile duct according to Pikovsky in combination with angioembolization of the damaged artery of the 4th liver segment. Results. The analysis of the clinical case shows X-ray endovascular methods to be one of the promising ways of increasing surgical management efficiency of traumatic hemobilia. Conclusions. This observation shows the possibility of developing hemobilia without signs of intra-abdominal bleeding in penetrating abdominal wounds with liver injury. The use of X-ray endovascular diagnostic methods can improve treatment outcomes of patients with hemobilia of traumatic origin.

Введение. Гемобилия – выделение крови с желчью через внутри- и внепеченочные желчные пути. Несмотря на применение новых методов диагностики и лечения, летальность при гемобилии остается достаточно высокой (20-40%). Цель исследования – продемонстрировать клинический случай, методы диагностики и лечения пациента с гемобилией. Материал и методы. В статье представлено собственное клиническое наблюдение пациента с проникающим ножевым ранением брюшной полости с повреждением печени, осложненным гемобилией. Проведено двухэтапное лечение с выполнением верхнесрединной лапаротомии, холецистэктомии, санации билиарных путей с наружным дренированием общего желчного протока по Пиковскому в комбинации с ангиоэмболизацией поврежденной артерии 4-го сегмента печени. Результаты. Проведенный анализ клинического случая показывает, что рентгенэндоваскулярные методы являются одним из перспективных направлений повышения эффективности хирургического лечения гемобилии травматического генеза. Выводы. Данное наблюдение показывает возможность развития гемобилии без признаков внутрибрюшного кровотечения при проникающих ранениях живота с повреждением печени. Применение рентгенэндоваскулярных методов диагностики позволяет улучшить результаты лечения пациентов с гемобилией травматического генеза.

Goal. To improve the results of surgical treatment of chronic pancreatitis complicated by vascular pathology of the parapancreatic zone. Materials and methods. On the basis of the "Grodno University Clinic" in the department of X-ray Endovascular Surgery of the period 2010 to April 2020, were performed 16 embolizations of the arteries of the parapancreatic zone due to complications of chronic pancreatitis. Among the patients there were 13 (81.25%) men and 3 (18.75%) women. They had a history of chronic pancreatitis, which was confirmed using instrumental and laboratory research methods. One of the patients (6.25%) had a stationary aneurysm.15 (93.75%) patients had a bleeding clinic, which required urgent surgical interventions. Results. Angioembolization of the parapancreatic arteries was effective in 15 (93.75%) patients, which was confirmed by the results of control angiograms. Conclusions. The use of intraluminal embolization for vascular pathology of the parapancreatic zone in treatment of chronic pancreatitis complications is a minimally invasive and effective method.

В роботі запропоновано апарат формалізації знань щодо оцінки ступеня небезпеки ситуації обстановки для системи підтримки прийняття рішень в автоматизованих системах управління повітряним рухом, з урахуванням сучасних досягнень розробки та впровадження систем підтримки прийняття рішень в складних організаційно-технічних системах. Удосконалення ситуаційного аналізу обстановки для управління процесом інформаційної підтримки прийняття рішень оператором автоматизованих систем управління повітряним рухом передбачає підвищення рівня автоматизації і інтелектуалізацію низки задач до яких відносяться оцінка ступеню небезпеки ситуації обстановки, яка складається в зоні відповідальності органу управління; для розв'язання поставленого завдання щодо формалізації знань про ступень небезпеки обстановки, в якості базового обрано апарат теорії нечітких множин, а саме застосовано метод обробки результатів експертизи, що дозволяє перейти до бінарних відношень строгої переваги та до ядра нечіткого відношення строгої переваги; проведено експертизу для формування множини небезпечних факторів, які треба виявити. Результати даного дослідження дозволять особі, що приймає рішення у першу чергу враховувати значення визначених чинників, які найбільш суттєво впливають на ступень складності обстановки при підготовці прийняття рішень по управлінню повітряним рухом.

The paper suggests ways of transition from a machine-centric to an anthropometric approach in the design of automated air traffic control systems, taking into account modern achievements in the development and implementation of decision support systems in complex organizational and technical systems. Improvement of situational analysis of the situation for managing the process of information support for decision-making by operators of automated air traffic control systems provides for increasing the level of automation and intellectualization of a number of tasks. These include the assessment of the situation that forms in the area of responsibility of the management body; development of methods for presenting knowledge about problems of detecting abnormal situations in airspace; choice and development of methods and procedures for formalizing knowledge about the situation that develops; the development of procedures for the interpretation of modal knowledge; the development of methods for solving the problems of assessing the situation, which develops; development of methods for solving problems of recognition and assessment of extraordinary situations in airspace; Assessment of the degree of danger of situations occurring within the area of responsibility of the management body. As a result of this research, directions for the development and improvement of intellectual models and information processing methods for managing the process of information support in decision-making in automated air traffic control systems have been determined. The proposed approach, which involves the need to develop methods for automated decision of problems assessment of the situation, as well as changes in the structure of information models and methods of managing them. In this case, the circumstances of the situation should be classified and the task of preparing for the decision should be considered as a task of recognition.

Using stable constitutive expression of retinoblastoma gene product (pRb) in polypotent mesenchymal 10T1/2 cells we obtained stable cell lines hyperexpressing functionally active or inactive mutant pRb. The cells producing active exogenous pRb demonstrated high sensitivity to adipocyte differentiation inductors, whereas production of inactive form of the exogenous protein suppressed adipocyte differentiation. The obtained lines can serve as the experimental model for studying the role of pRb in determination of adipocyte differentiation.

Method of calculating the relative sensitivity for X-ray television systems based on X-ray screens, CCD cameras and impulse x-ray devices was proposed. To visualize the images formed by the pulsed X-ray radiation, an adjustable duration of accumulation on the CCD camera was used. The relative sensitivity of the control is determined by the intersection of dependences of the luminance and threshold contrast on the size of the defect. The comparison of calculated and experimental values of the relative sensitivity of control is made in this paper.

We have studied photoluminescence in two CdTe / Cd 1− x Mn x Te multiple quantum-well samples with well thicknesses from 9.7 A to 100 A and with barrier compositions x = 0.5 and x = 0.68. The following effects have been observed after hydrostatic pressure up to 3 GPa was applied: (i) decrease of the luminescence intensity from wider wells, which can be related to the stress-induced deterioration of initially strained CdTe layers; (ii) transfer of photoexcited electrons from thinner wells into the barriers where Mn-related recombination occurs; (iii) large negative pressure coefficient (≈ −80 meV/GPa) of the Mn-related photoluminescence; (iv) positive pressure coefficients for CdTe well luminescence, which do not practically depend on the well thickness, while their magnitude decreases with increasing Mn concentration in the barriers (75 meV/GPa for Cd 0.50 Mn 0.50 Te and 60 meV/GPa for Cd 0.32 Mn 0.68 Te).

We developed a 24 hour intravenous dexamethasone suppression test for the differential diagnosis of Cushing's syndrome. Basal ACTH and cortisol levels were measured at 8 and 9 AM; a bolus of 8 mg dexamethasone phosphate (in children 5 mg/m2) was administered intravenously, and cortisol levels were measured hourly until 3 PM, then every 2 hours until midnight, and the next morning at 8 and 9 AM. We studied 13 patients with an ACTH-secreting pituitary adenoma, four with an autonomous adrenal adenoma, a 10 year-old girl with primary adrenocortical nodular dysplasia, one male with an ACTH-secreting medullary carcinoma of the thyroid, and one male with an ACTH-secreting non-small cell carcinoma of the lung, and compared their results to those obtained in 8 lean and 12 obese normal individuals (controls). The clinical diagnosis was first ascertained by the response to the oral administration of dexamethasone in low and high doses (standard Liddle test), then by the intravenous dexamethasone suppression test, and finally confirmed surgically. Although both controls and patients with an ACTH-secreting pituitary adenoma significantly suppressed their cortisol levels within hours after the injection (50% reduction of basal value at 2 hours, and 75% at 4 hours, p < 0.0001), levels remained suppressed the next morning only in the controls, while in the patients they returned to basal values. No suppression was observed in any of the patients with an adrenal adenoma and the child with primary adrenocortical nodular dysplasia (whose ACTH levels were low), or in the patients with ectopic ACTH secretion tumors (whose ACTH levels were high).(ABSTRACT TRUNCATED AT 250 WORDS)

A 65-year-old man was admitted because of severe cervical pain radiating to both shoulders and bouts of fever, which followed pneumonia. Bone scan showed increased focal uptake in C6-7, while computerized tomography showed destruction of the 7th intervertebral disk, with bone sequesters and soft tissue swelling. Fine needle aspiration drew purulent material with gram-positive bacteria on direct staining. Culture grew Staphylococcus aureus, coagulase positive. Treatment with IV cloxacillin for 3 weeks, followed by oral treatment for another 3, resulted in complete remission.

A decline in plasma insulin and an increase in glucagon are known to occur during intense and/or prolonged exercise. However, it is not established whether changes in insulin and glucagon secretion are involved in the precise matching of hepatic glucose production to the enhanced glucose uptake by muscle during brief, low intensity exercise. We studied the effects of 30-min cycle exercise at 40% of maximal aerobic capacity in healthy subjects and C-peptide-deficient subjects with type 1 diabetes (IDDM) using [3-3H]glucose to estimate glucose turnover. Diabetic subjects were studied during continuous iv insulin infusion, which normalized glucose kinetics before experimental perturbations. In control (saline-infused) experiments, endogenous glucose appearance (Ra) increased by 80-90% above baseline to match the increase in glucose disappearance in both normal and IDDM subjects, even though the latter exercised at fixed levels of plasma free insulin, averaging 203 +/- 19 pmol/L. In other experiments, somatostatin was infused, and glucagon (1.0 ng/kg.min) and insulin (at two different rates) were maintained at constant levels. Infusion of insulin in normal subjects at doses sufficient to maintain constant peripheral plasma insulin was associated with no apparent effect on glucose turnover (plasma insulin, 80 +/- 21 pmol/L, compared to 52 +/- 5 pmol/L during saline; P = NS). However, insulin infusion at doses that normalized the portal insulin concentration (approximately 208 pmol/L) together with glucagon replacement inhibited the rise in glucose production in both normal and IDDM subjects. There were similar 45-55% reductions (P less than 0.03) of the increase in Ra seen with exercise in control experiments. When peripheral plasma free insulin (and presumably portal levels as well) were increased by about 20% in this experimental setting in IDDM (278 +/- 43 pmol/L), the suppression of Ra was even more profound, and Ra failed to increase at all with exercise. We conclude that the hormonal regulation of Ra in brief duration exercise in man does not necessitate the decrements in portal venous insulin observed under more intense exercise conditions as long as an exercise-induced glucagon secretory response can occur. Glucagon secretion alone cannot prevent hypoglycemia when portal venous insulin concentrations are increased by minimal amounts, such as in insulin-treated diabetics.

Compensated hypothyroidism was diagnosed in a 36-year-old female who presented with breast tenderness and mild galactorrhoea. T4 was 5.8 mcg dl-1 and T3RU was 22.5%, while TSH and prolactin were very mildly elevated (6.5 mU ml-1 and 26.1 ng ml-1, respectively). The TRH test showed an exaggerated response. TSH increased to 43 mU ml-1, and prolactin levels reached 161 ng ml-1. Treatment with T4 decreased the TSH and prolactin levels to within the normal range, and prevented the galactorrhoea. The case presented here demonstrates that galactorrhoea can be present even with mild hypothyroidism.

This is a general review of the use of mullet in polyculture systems in the Israeli fish-farms for the past 10–15 years. Two species of mullets are reared in Israel in fresh- and brackishwater ponds as well as in Lake Tiberias: Mugil cephalus and Mugil capito . The data collected in this work deals with the following subjects. 1. (1) Annual and bi-annual rearing of mullets as a component in a polyculture system. 2. (2) The density of mullet stocking and the effect of the initial weight on both individual growth and total yield of mullets in ponds. 3. (3) The inter-relationships between carp and mullets in fish ponds and the effect of additional feeding on mullets.

We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

An improved chromatic rotatable refraction test for simultaneous spheric and astigmatic refraction is described. Its new features are interposition of a bright yellow stripe between the conventional red and green fields and a pair of parallel test lines, which traverse vertically all colored fields. Thereby astigmatic errors become easily visible.

PRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 micrograms) and LHRH (100 micrograms). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non-responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean +/- SD basal PRL levels were 68.5 +/- 29.9 ng/ml in Group I and not different in Group II (40.6 +/- 12.0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2.4 +/- 0.7 microU/ml to a peak of 5.9 +/- 2.7 microU/ml (P less than 0.005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide. In Group II females, PRL responsiveness to metoclopramide was associated with TSH non-responsiveness. In Group I females, PRL levels failed to rise, whereas TSH increased. The PRL and TSH profile in Group I females is typical of a prolactinoma. It is concluded that PRL as well as TSH determinations following metoclopramide are useful indices in the assessment of hyperprolactinaemia and may be of value in differentiating the functional state from that of a pituitary tumour.

This study has evaluated the effect of the estrogen antagonist clomiphene citrate on the exaggerated PRL response to TRH and the dopaminergic antagonist metoclopram-ide (MET) in 16 patients with primary testicular failure and elevated basal and peak gonadotropin responses to LRH. Subjects were challenged with LRH (100 µg), TRH (200 µg), and MET (10 mg), given iv at 30-min intervals in the basal state and after clomiphene citrate, administered as a daily dose of 100 mg for 4 weeks (10 subjects), 200 mg for 4 weeks (3 subjects), and 100 mg for 8 weeks (3 subjects). The patients were subdivided into 2 groups on the basis of the PRL response to TRH and MET, which was exaggerated in 12 subjects (group I) and similar to the controls in 4 subjects (group II). Mean basal LH, FSH, and LH (but not FSH) responses to LRH were increased post clomiphene treatment in both groups. Testosterone levels were normal in both groups, but 17β-estradiol (E2) levels were in)creased in group I. After clomiphene administration, bot...

A patient with methimazole-induced aplastic anemia is described. Despite severe pancytopenia and the complete disappearance of hemopoietic elements from the bone marrow, recovery of hemopoiesis has been observed within 14 days of discontinuing methimazole therapy. In vitro studies of CFU-C inhibition of peripheral mononuclear cells harvested in remission, were performed by incubation with autologous sera collected at earlier phases of the disease. These studies provide evidence in favor of a humoral, and most probably autoimmune mechanism as the cause of transient bone marrow aplasia.

Prolonged hypoglycaemia (serum glucose levels of 50 mg/dl and less, for more than 12 h in spite of treatment with periodic injections of hypertonic glucose) secondary to treatment with glibenclamide was found in 13 hospitalized patients. The mean daily dose of glibenclamide was 6.7 mg. In nine patients, the hypoglycaemia developed within 7 days of treatment. In two patients the tendency to hypoglycaemia lasted for more than 60 h in spite of continuous infusion of 5% or 10% glucose. Old age seems to be a crucial predisposing factor as none of the patients was under the age of 68 years. Contributing factors were renal failure and congestive heart disease. We feel that glibenclamide should be used with care in the elderly and in patients with renal or cardiac failure.

Hypophosphatemia in diabetic ketoacidosis is well recognized, but is believed to be usually of moderate severity. We describe 2 patients in whom acute hemolytic anemia secondary to severe (0.19-0.35 mmol/l) hypophosphatemia has developed 1-2 days following treatment for diabetic ketoacidosis. Our experience indicates that severe hypophosphatemia requiring phosphate supplementation does occur in diabetic patients, and calls for increased awareness for the clinical and laboratory manifestations of this complication of diabetic ketoacidosis.

Nine patients, six men and three women, 40 to 73 years of age, were included in the study. All of the patients had severe heart failure refractory to aggressive therapy including digitalis, diuretics, and vasodilators. Eight patients underwent one treatment of peritoneal dialysis while the remaining patient received two dialyses. The urine output was measured by an indwelling catheter; glomerular filtration rate (GFR) was determined by creatinine and inulin clearance, and renal blood flow (RBF) was determined by sodium paraamino hippurate (PAH) clearance. Following one peritoneal dialysis, the mean fluid loss/patient was 3,995 ml (range 3,200 to 5,100 ml). Dialysis was generally well tolerated. One patient, who had underlying hepatic cirrhosis and underwent two dialyses, developed hepatic failure and died 10 days after the second dialysis. At postmortem, peritonitis was discovered. All of the patients showed a marked subjective and objective clinical improvement. The mean plasma urea decreased from 154 to 71 mg/dl (P less than 0.005), and mean plasma creatinine decreased from 1.83 to 1.13 mg/dl (P less than 0.005). Blood pH was 7.30 before dialysis and increased to 7.37 (P less than 0.0125) after treatment. Mean urine output predialysis was 955 ml and increased to 1,472 ml post dialysis (P less than 0.0005). Creatinine clearance increased from 35 to 73 ml/min (P less than 0.0005). The mean inulin clearance increased from 33 ml/min predialysis to 69 ml/min post dialysis (P less than 0.0005), and mean PAH clearance increased from 96.7 to 362.5 ml/min (P less than 0.0005). Acute peritoneal dialysis is a safe and effective means for removing large quantities of excess fluid from patients with intractable heart failure.

The effect of prolonged treatment with chromium on glucose homeostasis was assessed in rabbits. Thirty-one male rabbits were divided into 6 groups. All were fed for 30 days with a standard ad libitum diet. Twenty-seven rabbits were injected daily during a further 120 days with different doses of potassium chromate (3-20 micrograms) while 4 rabbits served as controls. No significant rise in serum glucose levels was observed, insulin levels were the same in the different groups, and glycosylated hemoglobin concentration also did not change after the administration of chromium. Serum chromium levels increased proportionally to the dose injected to an almost a 14 fold increase in the 20 micrograms chromium treated group. Although others have shown that chromium may have a hyperglycemic effect with inhibition of insulin secretion, we have not been able to confirm this finding.

To investigate prolactin (PRL) and thyrotropin-stimulating hormone (TSH) secretion in ovarian failure, 14 women with primary ovarian failure were challenged with luteinizing hormone-releasing hormone (LHRH) (100 micrograms) and thyrotropin-releasing hormone (TRH) (200 micrograms) given intravenously at 30-minute intervals. Responses were compared with those of 13 healthy female controls. In the patient group, basal follicle-stimulating hormone (FSH), LH, and peak gonadotropin responses to LHRH were higher and basal estrone and estradiol levels were lower than in the controls (P less than .001). Mean basal PRL levels were similar in the 2 groups. However, the mean peak and integrated PRL responses in the patients were greater than in the controls (P less than .05). Ten patients had a markedly exaggerated PRL response to TRH. The mean basal TSH levels and the peak TSH response to TRH were similar to those of the controls. Estrogens are known to stimulate PRL secretion. These subjects had increased PRL responses with low circulating estrogens. The mechanism underlying the findings is not known, but could be related to increased aromatization of androgens to estrogens in the hypothalamus. Alternatively, other factors could be responsible for the exaggerated PRL responses to TRH noted in these patients with primary ovarian failure.

A 30-year-old man who had 12 repeated hospital admissions within a period of 7 years for localized pain and swelling of the extremities is described. Excision biopsy of several subcutaneous lesions revealed histologic changes typical of polyarteritis nodosa (PN). Systemic disease was excluded because of a normal testicular biopsy, negative abdominal angiogram, and the lack of evidence for renal or other visceral involvement. Response to steroid therapy was excellent. Cutaneous PN is a distinct subset of polyarteritis with a chronic course and excellent prognosis. The present case underlines the need for a greater awareness, and for considering early biopsy of suspected lesions in patients with multiple episodes of apparent superficial thrombophlebitis.

Summary We studied two sisters who developed large non-toxic goitres in adolescence. Deiodinase deficiency was diagnosed by a rapid thyroid uptake of radioactive iodine (RAI) at 2 hours associated with a marked fall in thyroidal 131I by 24 hours. Serial RAI scans in the second patient documented evolution of the iodine-deficient state. Conservation of intra-thyroidal iodine stores was maintained by avid iodine uptake and failure to release organified 131I. With progressive loss of inorganic iodine, hypothyroidism developed, associated with a rise in serum TSH which further exacerbated the loss of iodine. Treatment with l-thyroxine resulted in an improvement of thyroid function, but normalization was achieved only after small doses of Lugol's iodine were administered. These studies illustrate the variable nature and late onset of an inborn error of thyroid metabolism. This family supports an autosomal recessive mode of inheritance for deiodinase deficiency. We have documented progression from a euthyroid to hypothyroid state resulting from decompensation of iodine conservation mechanisms.

Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.

A 55 year old woman in thyrotoxic crisis developed atrial fibrillation, atrioventricular block, and sinoatrial block in rapid succession. All of these abnormalities resolved completely after antithyroid treatment. This course of events illustrates the profound effect of thyroid hormones on cardiac function. In view of the potential aggravation of atrioventricular conduction disturbance by beta adrenergic blocking agents, thyrotoxic patients should be carefully screened for electrocardiographic evidence of conduction disturbance before the administration of such drugs.

The aim of the present study was to measure the PRL response to metoclopramide (MET) and chlorpromazine (CPZ) in seventeen patients with primary testicular failure and eight patients with isolated gonadotrophin deficiency (IGD). The responses were compared with those to TRH. Basal gonadotrophins and peak responses to LHRH were increased in testicular failure and reduced in IGD. Basal PRL levels were normal in both groups of patients. However, when compared with controls, the PRL response to both MET and CPZ as well as to TRH was exaggerated in primary testicular failure, whereas the responses wee decreased in IGD. In both patient groups, as well as in the controls, the PRL response to MET exceeded that to TRH and CPZ. It is suggested that alterations in the steroid milieu are responsible for the exaggerated PRL response to MET, CPZ and TRH in primary testicular failure and the reduced response observed in IGD.

An elevation of serum aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) may be produced in patients treated with i.v. full-dose HEPARIN. We studied the influence of low-dose s.c. HEPARIN (5,000 IU X 2) in 34 patients with acute myocardial infarction (AMI) and in 7 with cerebrovascular accidents or calf thrombophlebitis. Twelve patients (all males) with AMI showed a secondary elevation of GOT and GPT at about the sixth or seventh day after the commencement of therapy that persisted throughout the period of treatment. Four patients (two males and two females) with cerebrovascular accidents or thrombophlebitis showed similar increases of GOT and GPT.

SUMMARY Patients with primary testicular failure have increased basal TSH levels and an exaggerated TSH response to TRH in the presence of normal circulating levels of thyroid hormones. In order to evaluate if this TSH profile is an oestrogenrelated phenomenon, sixteen patients with primary testicular failure were challenged with 200 μg TRH prior to and after the administration of clomiphene citrate. The latter was given in a dose of 100 mg/day for 4 weeks to ten patients; 200 mg/day for 4 weeks to three patients and 100 mg/day for 2 months to the final three patients. The patients demonstrated increased mean basal TSH levels with an exaggerated TSH response to TRH. Following the administration of clomiphene citrate, there were no changes in T4, T3 sephadex or total T3 levels and in basal or stimulated TSH levels. Clomiphene did produce an increase in oestradiol, testosterone, basal gonadotrophins and LH response to LHRH. Since the oestrogen antagonist, clomiphene citrate, had no effect on TSH secretion, it is unlikely that the exaggerated TSH response to TRH is mediated by oestrogens.

Summary Iodine-induced hyperthyroidism can develop even in the presence of an otherwise normal gland. One of the less common sources of iodine is tablets of seaweed, sold over the counter without prescription. We report the case of a 72 year old female who developed clinical and laboratory evidence of hyperthyroidism while ingesting sea-kelp (Vitalia) tablets. Six months after stopping the tablets, the symptoms and laboratory evidence of hyperthyroidism had disappeared. No evidence of pre-existing thyroid disease was found.

We examined the role of the plasma glucose concentration per se in the secretion of counterregulatory hormones during exercise. Ten men (average age, 24 yr; maximal aerobic capacity, 31.8 mL/kg.min) were studied during two 50-min bicycle exercise periods at either normal glucose [87 +/- 1 (+/- SE) mg/dL (4.8 +/- 0.1 mmol/L)] or low glucose [59 +/- 1 mg/dL (3.3 +/- 0.1 mmol/L)]. The plasma glucose targets were achieved by exogenous insulin and variable glucose infusions. These results were compared to studies in which saline was infused. Exercise at normal glucose was associated with significant increments in plasma epinephrine (maximum 3- to 5-fold above baseline) and norepinephrine (2-fold), comparable to those that occurred during saline administration. Plasma GH increased only at the most intense exercise level, while plasma cortisol and glucagon did not increase significantly. In low glucose-exercise studies, the increase in plasma epinephrine during exercise was significantly greater than that at normal glucose (P less than 0.01), although proportional to basal preexercise levels (r = 0.73; P less than 0.001). Plasma glucagon increased almost 100%, and plasma cortisol and GH increased by 150% and 400%, respectively. Compared to the effect of the same degree of hypoglycemia in the absence of exercise, only plasma epinephrine (P = 0.002) and norepinephrine (P less than 0.001) displayed effects independent of hypoglycemia during exercise. When low glucose was reversed to normal at the midpoint of exercise, plasma epinephrine and glucagon returned to the levels obtained for the same duration of exercise at normal glucose, while norepinephrine, GH, and cortisol were only partially responsive to the rise in plasma glucose. These data suggest that 1) moderate exercise is a stimulus for a sympathoadrenal and GH response, but not a peripheral glucagon response; 2) during exercise and hypoglycemia, plasma epinephrine and norepinephrine are enhanced, while the glucagon response is entirely glucose dependent; and 3) the epinephrine response to hypoglycemia can be dissociated from that to exercise, suggesting differing control mechanisms. We conclude that the activation of counterregulatory hormones during exercise is regulated by glucose-independent mechanisms, although these responses may be augmented by concurrent hypoglycemia.