Prophylaxis against HIV-1 infection in chimpanzees by nevirapine, a nonnucleoside inhibitor of reverse transcriptase.

Chimpanzees were challenged with HIV-1IIIB while receiving a short regimen of nevirapine (Viramune), a nonnucleoside inhibitor of HIV-1 reverse transcriptase. The untreated, control chimpanzee developed an infection characterized by seroconversion, viremia in peripheral blood mononuclear cells (PBMCs), and plasma positive for viral RNA. In contrast, the three nevirapine-treated chimpanzees remained negative for all viral markers with the exception of nested polymerase chain reaction (PCR) analysis of PBMCs for viral DNA. Although PBMCs from the three nevirapine-treated chimpanzees tested intermittently positive for viral DNA, this PCR signal disappeared and remained negative for the final five months of the study. These data indicate that orally administered nevirapine provided protection from HIV-1 infection in the chimpanzee model.

A first-in-human study of DS-1040, an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor, in healthy subjects.

Essentials DS-1040 inhibits the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa). Infusion of DS-1040 was safe and well tolerated in healthy young and elderly subjects. DS-1040 substantially decreased TAFIa activity but had no impact on bleeding time. DS-1040 may provide an option of safer thrombolytic therapy. SUMMARY: Background Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue-type plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding. DS-1040 is a novel low molecular weight compound that inhibits the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa), and was developed as a fibrinolysis enhancer for the treatment of thromboembolic diseases. Objectives This first-in-human, randomized, placebo-controlled, three-part, phase 1 study was conducted to evaluate the safety, pharmacokinetics and pharmacodynamics of DS-1040 in healthy subjects. Subjects/Methods Young (18-45 years) or elderly (65-75 years) subjects (N = 103) were randomized to receive single ascending doses of DS-1040 ranging from 0.1 mg to 40 mg, or placebo, administered either as a 0.5-h intravenous infusion or as a 24-h continuous infusion. Results All doses of DS-1040 were tolerated, and no serious adverse events (AEs) or discontinuations resulting from AEs occurred during the study. Bleeding time remained within the normal range for all doses tested in all subjects. Plasma exposure of DS-1040 increased proportionally with increase in dose. Elderly subjects had higher exposures to DS-1040 and prolonged elimination times, probably because of decreased renal clearance. DS-1040 caused a substantial dose-dependent and time-dependent decrease in TAFIa activity and in 50% clot lysis time. The levels of D-dimer, indicative of endogenous fibrinolysis, increased in some individuals following DS-1040 treatment. No effects of DS-1040 on coagulation parameters or platelet aggregation were observed. Conclusions The novel fibrinolysis-enhancing agent DS-1040 has favorable pharmacokinetic/pharmacodynamic properties and a favorable safety profile, warranting further clinical development.

Inordinately high levels of serum immunoreactive insulin in monoclonal immunoglobulinemia (on the problem of "big, big insulin").

1. A patient with occasional attacks of hypoglycemia had levels of serum immunoreactive insulin persistently fifty to one-hundred times the normal value. Immunoelectrophoresis revealed presence of monoclonal IgG in his serum. The patient's diagnosis was established as paraproteinemic lymphoid and plasmocytic reticulosis proximate to multiple myeloma; insuloma was not found. 2. On gel filtration of native serum, only part of the total immunoreactivity was found in the elution position of crystalline insulin; the major part emerged in the early fractions together with the large proteins. After acidification of the serum, however, practically the entire immunoreactivity was recovered in ethanol extracts and proved to be "little insulin" on gel filtration. Only, "little insulin" was also detected after gel filtration of serum incubated with urea. 3. It is suggested that the large component with insulin immunoreactivity obtained in gel filtration of native serum is an insulin-protein complex. The nature of the presumed complex is not clear. It is not a complex of the antigen-antibody type. Insulin "trapping" by monoclonal gamma globulin is considered.

A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006).

OBJECTIVE: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. DESIGN: An open label phase I/II study. SETTING: Tertiary care hospital, Kampala, Uganda. PATIENTS AND INTERVENTIONS: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. OUTCOMES: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. RESULTS: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. CONCLUSION: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.

Comparison of N-acetyl-beta-glucosaminidase and albuminuria with clinical finding of microangiopathy in type I diabetes mellitus.

N-acetyl-beta-Glucosaminidase activity in serum and urine and microalbuminuria were measured in 70 type-I diabetics and compared with glycated serum protein as well as with the finding of diabetic retinopathy. A significantly increased N-acetyl-beta-glucosaminidase activity in serum correlated positively with glycated protein but not with the development of retinopathy. Urinary N-acetyl-beta-glucosaminidase activity and albuminuria were significantly increased in diabetics with (p less than 0.001) or without (p less than 0.01) retinopathy as compared to healthy controls. A significant positive correlation was observed between urinary N-acetyl-beta-glucosaminidase activity and albuminuria (r = 0.73, p less than 0.01) as well as between blood pressure and albuminuria (r = 0.51, p less than 0.05).

HPLC-UV method for the quantitation of nevirapine in biological matrices following solid phase extraction.

Nevirapine (VIRAMUNE) is a non-nucleoside reverse transcriptase inhibitor with activity against human immunodeficiency virus type 1 (HIV-1), currently marketed for the treatment of HIV-1 infected adults. A reverse phase HPLC-UV method was optimized and validated for the determination of nevirapine in human plasma, serum, milk and cerebrospinal fluid. The analyte was extracted from 250 microl of biofluid using a bonded silica solid phase extraction column, and resolved chromatographically on a reversed-phase, 15x0.46 cm i.d. 5 microm particle Supelco LC-8 analytical column with an isocratic mobile phase of 63% phosphate buffer (0.025 M, pH 6.0) with 1-butanesulfonic acid as anion-pair reagent: 21.5% methanol: 15.5% acetonitrile. The peaks were detected at a flow rate of 1.0 ml min(-1), at a wavelength of 280 nm, with a run time of 10 min. The assay was linear over a range of 25 to 10000 ng ml(-1). This method has been used for the clinical development of nevirapine.

Risk calculation of type 2 diabetes.

The paper presents an analysis of the risk of developing Type 2 diabetes according to family history and anthropometric variables. The age of diabetes onset was analysed in 2024 diabetics. We obtained several groups according to family history. In each group taken separately, the data describing the cumulative percentage of diabetes onset was fitted by logistic curve F(x) = p1/(1 + p2*p3((x/10)-p4)). Comparing these curves we see that cumulative age-dependent risk increases from the group of randomly chosen persons through the group of first degree relatives to the children of diabetics. The highest risk of diabetes onset is determined by the curve representing the group of known diabetics. Another analysis was performed in a different group of 390 obese subjects (34 diabetics among them). Male diabetics had significantly higher body mass index (BMI) and weight than male non-diabetics. Female diabetics showed significantly higher weight, body mass index, waist to hip ratio (WHR) and age than female non-diabetics. Elimination of factors with randomization and matching showed a complicated relationship between diabetes, age and anthropometric variables. Using stepwise logistic regression we obtained the model for prediction of diabetes risk based on age, BMI, WHR: probability of diabetes = exp(u)/(1 + exp(u)), where u = -13.9 + 0.05431*age + 6.789*WHR + 0.07881*BMI for obese women, u = -11.84 + 10.01*WHR for obese men. In conclusion, genetic factors are the most important and can be exactly quantified in Type 2 diabetes. The importance of anthropometric variables for prediction of diabetes risk is also presented.

[Clinical examination of the blood of roe deer (Capreolus capreolus L.) and fallow deer (Dama dama L.) naturally invaded by parasites]. / Klinické vysetrení krve srnci zvere (Capreolus capreolus L.) a dancí zvere (Dama dama L.) prirozene invadované parazity

Roe-deer (Capreolus capreolus L. -- five animals) and fallow deer (Dama dama L. -- eleven animals) of both sexes and at different age were subject to blood examination. The deer were killed in several preserves in Bohemia during autumn and winter shootings in two years. The following blood values were determined: erythrocyte count, leucocyte count, hemoglobin content, hematocrit values, MCV, MCH, MCHC, white blood picture, total protein, its fractions (albumin, alpha-, beta-, and gamma-globulin) SGOT, SGPT, and alkaline phosphatase activities, and calcium, phoshporus, and magnesium levels. Examinations were performed in the blood collected from heart soon after the killing of the animals and the results were evaluated in relation to natural polyvalent invasions by parasites of the following species: Bicaulus sagittatus, Dictyocaulus viviparus, Paramphistomum sp., Haemonchus contortus, Ostertagia circumcincta, O. ostertagi, Trichostrongylus colubriformis, Bunostomum trigonocephalum, Nematodirus filicollis, Chabertia ovina, Oesophagostomum columbianum, Trichocephalus ovis, Eimeria auburnensis, E. faurei, and E. ninaekohlyakimovae, occurring in different intensities and species composition in individual animals of the deer tested.

[Clinical examination of the blood of red deer (Cervus elaphus L.) naturally infested with parasites]. / Klinick e vysetrení krve jelení zvere (Cervus elaphus L.) Prirozene invadované cizopasníky

In six animals hunted and four immobilized animals of red deer (Cervus elaphus L.) of both sexes and of different age, kept at three game preserves in Bohemia, the psychological values were ascertained: the number of erythrocytes and leucocytes, the hemoglobin content, the hematocrit, MCV, MCH, MCHC, the white blood count, the total serum protein, the fractions: albumin, alpha-, beta- and gamma-globulin, the activity of SGOT, and SGPT, the alkaline phosphatase and the metabolism of calcium, phosphorus, and magnesium in the blood serum. The blood from the heart shortly after killing of the animal was examined, and in immobilized animals the blood was taken from the vena jugularis. In the red deer, a variable intensity of the polyvalent infection of parasites of the species Dictyocaulus viviparus, Bicalulus sagittatus, Fascioloides magna, Paramphistomum spec., Haemonchus contortus, Ostertagia ostertagi, O. circumcincta, Trichostrongylus axei, Nematodirus filicollis, Chabertia ovina, and Trichocephalus globulosa was found. In the immobilized deer no marked deviations were found in the examined values of blood that had been taken within 10 minutes after the calming of the animals.

[Clinical examination of the blood of wild boars (Sus scrofa L.) naturally infested with parasites following administration of anthelminthics]. / Klinické vysetrení drve cerné zvere (Sus scrofa l.) priprozene invadované parazity po aplikaci anthelmintik

With 24 head of wild boars (Sus scrofa L.) of both sexes of the age of one to two years, kept in a game preserve and naturally infected with parasites of the species Mestastrongylus pudendotectus, M. elongatus, Ascarops strongylina, Physocephalus sexalatus, Ascaris suum, Globocephalus urosubulatus, Oesophagostomum dentatum, Trichocephalus suis, Eimeria debliecki, and E. perminuta, three experiments were performed with feeds premedicated with anthelmintics: pyrantel tartrate + diethylcarbamazine tartrate (a dose of 25 + 50 mg kg-1 of live weight), Mebendazole 5 p. c. premix and Mebendazole 50 p. c. premix (doses of 10 mg kg-1 and 40 mg kg-1 of live weight) administered for three consecutive days. According to the results of the helminthological dissections the effectiveness of pyrantel tartrate + diethylcarbamazine tartrate reached from 58.1 to 100 p. c. compared with the different species of nematodes, Mebendazole 5 p.c. premix from 47.8 to 100 p. c., and Mebendazole 50 p. c. premix reached the effectiveness of 85.4 to 100 p.c with the mentioned therapeutic doses. The results obtained from a coprological investigation showed the effectiveness, in the case of pyrantel tartrate + diethylcarbamazine tartrate, of 99.2 and 70.65 p. c. on the sixth and fifteeenth day after application, in the case of Mebendazole 5 p. c. premix 94.4 and 79.41 p. c. on the tenth and twentieth day after application, and in the case of of Mebendazole 50 p. c. premix it amounted to 96.0 and 100 p. c. on the tenth and twentieth day after application. In 22 head of wild boars of the total number of examined animals the minimum, maximum, and average values of the number of erythrocytes, leucocytes, of the hemoglobin content, of the hematocrit, MCV, MCH, MCHC, of the white blood count, of the protein total, of the fractions of albumin, alpha-, beta-, and gamma-globulin, of the activity of SGOT and SGPT, and of the metabolism of calcium, phosphorus, and magnesium were determined. The investigation was performed in the shortest possible time after the killing of the animals. In the examined values no marked deviations in 48 hours were found after the application had finished compared with the values determined in non-treated animals.

[Thoughts on insulin therapy]. / Zamyslení nad lécbou inzulinem.

The submitted review concentrates on several important features of contemporary insulin treatment of diabetes (1). Only in the minority of cases, and only in insulin-dependent diabetes typical substitution treatment is involved. Even if it approaches physiological conditions, either by a permanent insulin supply beneath the skin by means of a pump, or using the tactics of several injections per day in the system called "basal bolus", it differs from the latter by the fact that it supplies insulin first into the peripheral circulation and not into the liver and does no imitate the pulsatile character of insulin secretion (2). Contemporary insulin preparations imitate only imperfectly the physiological rapid post-prandial rise of insulinaemia with a subsequent rapid drop. In an attempt to approach this as closely as possible various insulin analogues are used and substitution of amino acids in its molecules by others (3). The antibody formation against insulin was restricted to a great extent by the introduction of mono-component insulin but was not eliminated even when biosynthetic human insulin is used. The importance of these antibodies is, however, in common cases small and is manifested by a prolonged period of action (4). Non-substitutional insulin administration in non-insulin dependent diabetes is indicated where without it satisfactory compensation of diabetes is not achieved. There are favourable reports on combined treatment with insulin and oral antidiabetics in this type. The risk are in particular undesirable body weight increments.

[The development of theories on the mechanisms of insulin action]. / Vývoj teorií o mechanismu pusobení inzulínu.

In 1924 Laufberger formulated his block theory on the action of insulin. Its basic thesis that insulin prevents the new formation of glucose and its supply into the blood stream is still valid, although knowledge on the multiple action of insulin expanded substantially. The theory put forward in 1955 by Levine and Goldstein which ascribed all insulin actions to the influence on the cellular membrane permeability for glucose, could, however, not explain all data associated with insulin, the knowledge of which was expanded steadily. At present the mechanism of insulin action is explained most comprehensively by the concept based on the bond of insulin to its membrane receptor which by activation of tyrosine kinase it contains induces either cascade phosphorylation of intracellular protein kinases or (and) leads to the release of the "second messenger" from the cell membrane, i.e. of glycosyl-phosphatidyl inositol. In both instances activation of the glucose and amino acids transmitter from the medium into the cells results, as well as activation of enzymes catalyzing in the cell various degrees of carbohydrate, fat and protein metabolism.

[Evaluation of the status of diabetes mellitus during a 2-year period using traditional methods and determination of glycosylated hemoglobin A1c and fructosamine in the blood]. / Hodnoceni stavu cukrovky v prubehu dvou let tradicnim zpusobem a s pouzitim stanoveni glykovaného hemoglobinu A1c a fruktózaminu v séru.

In the course of two years the authors checked 23 diabetic patients (13 type 2, 10 type 1), using the traditional approach, by assessment of haemoglobin A1c and serum fructosamine. The patients were classified according to compensation into four and three groups resp. Assessment of haemoglobin A1c evaluated the patients, in the same group as the traditional evaluation in 57.7% into the best compensated group and in 62.5% into the worst compensated group. In fructosamine agreement with traditional evaluation in the best compensated group was in 84.2% and in the worst compensated group in 50.0%. In 40.2% the evaluation was in agreement for all three methods of evaluation, differences between evaluation according to haemoglobin A1c and serum fructosamine were recorded in 51.5%. Assessment of haemoglobin A1c and serum fructosamine improves information on the state of diabetes, concurrent estimation of both is, however, often associated with difficulties as regards interpretation. These problems are discussed in the presented paper.

[Hyperlipoproteinemia and the genetic epidemiology of diabetes mellitus]. / Hyperlipoproteinémie a genetická epidemiologie diabetu mellitu.

Cardiovascular diseases are the most frequent cause of mortality in the sub-population of type II diabetics (cca 600,000 in the CSSR). Type II diabetics very frequently cumulate several very serious risk factors (hyperlipoproteinaemia, arterial hypertension, obesity, hyperuricaemia, smoking) for the manifestation of cardiovascular disease. Concurrent comprehensive treatment of all revealed risk factors is essential for primary prevention. Systematic application of methods of genetic epidemiology in families of affected diabetics helps to detect in time and to treat other affected members of the family. It is at the same time a rational way of primary prevention of cardiovascular disease in the highest risk sub-populations. The authors submit an algorithm of treatment of hyperlipoproteinaemic type II diabetics.

[Compensation in diabetes and serum insulin levels in type I diabetics during insulin pump therapy and after changing to treatment with a combination of short- and long-acting insulin]. / Kompenzace cukrovky a hladiny inzulínu v séru u diabetiku I. typu pri lécbe inzulínovou pumpou a po prevedení na lécbu kombinací inzulínu s krátkým a prodlouzeným úcinkem.

Twenty-one type diabetics previously treated in the conventional way with insulin with unsatisfactory results were admitted to hospital. The blood sugar level, serum insulin and non-esterified fatty acids in serum (NEFA) were assessed from 6 a.m. to 2 a.m. during treatment with an insulin pump and after changing the patients to insulins with varying length of action. Patients in the following groups were followed up separately: a) patients with antibodies against insulin treated either by two (n = 4) or three (n = 12) injections; b) patients with antibodies (n = 16) and without antibodies (n = 5), regardless of the number of insulin injections. Changes from the insulin pump regime implied an increased insulin requirement, (significant only in group b) and deteriorated compensation of diabetes which was more markedly manifested when evaluated by index M according to Schlichkrull with the exception of the group without antibodies, where M remained despite the increase in the range of satisfactory compensation. The NEFA profile behaved in a reversed manner, as compared with the serum insulin level. The results confirm the greater success of insulin pump treatment when attempting to maintain the blood sugar level as close as possible to normal values. From the analysis of the blood sugar and serum insulin profile recommendations for the tactics of treatment are derived, when the use of an insulin pump is not possible.

[A consulting system for insulin therapy in diabetes]. / Konzultacní systém pro inzulínovou lécbu cukrovky.

The authors describe a computer system which provides consultations on insulin treatment of diabetes. The intentions and aims of computer consultation and means for their implementation are described. The basic element of the system is the model of insulin pharmacodynamics. Two concepts are used to differentiate individual characteristics of the patient: the basal need and insulin sensitivity. The basal need is the amount of insulin which maintains the blood sugar level at the desired level in the course of the day, provided the subject adheres to a standard regime. The insulin sensitivity represents the sensitivity of the glucose metabolism to deviations from the basal requirement. These purely individual parameters are currently adapted by the "learning" module. The module compares the assessed and predicted blood sugar levels and corrects the parameters to achieve a minimum difference. The accuracy of approximation depends on the number of assessed blood sugar levels. The system foresees a minimum of two assessments per day. Individualized parameters are used for the prediction of the blood sugar level. The system visualizes predicted blood sugar levels for manually administered alternative insulin doses. The module of the automatic therapeutic plan is part of the module. The system recommends treatment with an "optimal" development of the predicted blood sugar level. As a criterium of the optimal profile of the blood sugar level the M-value was selected which is used for the evaluation of the daily blood sugar profile. The predictive capacity of the system was evaluated on the basis of retrospective data.(ABSTRACT TRUNCATED AT 250 WORDS)

[Variations in the dietary regimen in type I diabetes mellitus. I. Short-term use of a high-carbohydrate diet]. / Odchylky dietního rezimu u diabetu mellitu I. typu. I. Krátkodobé uzití diety s vysokým obsahem sacharidu.

For a period of two days, while maintaining compensation of diabetes mellitus type I (treated by insulin pump), the authors replaced the usual diabetic diet by a bland carbohydrate diet (2.6 +/- 0.6 MJ/24 h, practically without amino nitrogen). This resulted in a negative energy and nitrogen balance with an indicated adaptation reaction on the second day of administration--reduced amount of catabolic urinary nitrogen, concentration of non-esterified serum fatty acids suggested a slightly increased lipolysis. The insulin consumption per 24 h was significantly reduced, as compared with the control day. A low energy carbohydrate diet is, when administered for a short period under careful control of compensation of diabetes type I, relatively safe and can be used e. g. during intercurrent digestive diseases.

[Changes in the dietary regimen during treatment of type I diabetes mellitus with continuous insulin infusion. II. Omitting food]. / Vliv zmen dietního rezimu pri lécbe diabetu mellitu I. typu kontinuální podkozní infúzí inzulínu. II. Vynechání jídla.

UNLABELLED: The authors investigated in 11 type diabetics the effect of omission of a meal on the compensation of diabetes during treatment with an insulin pump IP 1003. After stabilization of treatment by the pump, the patients were left on the 5th day without breakfast, while the basal operation of the pump was maintained and the patient received their insulin bolus in the morning. The test was terminated as planned after 180 mins. in 6 patients, in 5 it was terminated early because of typical signs of clinical hypoglycaemia. The course of the blood sugar curves revealed differences between patients from abrupt drops of hyperglycaemic values to hypoglycaemia to balanced low blood sugar levels. For the rest of the day till the following morning after the test the blood sugar was elevated, as compared with the control level of the 4th day. CONCLUSIONS: the tests revealed the relatively small drop of the blood sugar level after omission of the meal, hypoglycaemia develops in the majority of diabetics only after 120 to 180 mins. The danger of early hypoglycaemia within 60 minutes was recorded only in patients with a known history of severe hypoglycaemic states. Posthypoglycaemic hyperglycaemia influences the compensation of diabetics during the rest of the day.

[The Biostator in the diagnosis and therapy of organic hyperinsulinism]. / Biostator v diagnostice a terapii organického hyperinzulinismu.

In 12 patients with the diagnosis of organic hyperinsulinism the authors examined the carbohydrate metabolism on a Biostator, using the method of stabilized glycaemia. They found a highly significantly reduced tissue sensitivity to insulin at the same time a reduced metabolic insulin turnover as compared with healthy subjects (p less than 0.001). Simultaneously they examined the acute action of diazoxide (Proglicem) treatment to which the patients responded in two ways. In one group a decline of the insulin level occurred and the tissue sensitivity to insulin rose, while patients in the second group responded by a rise of serum insulin but there was no response in the insulin sensitivity. In this second group diazoxide treatment obviously does not eliminate hypoglycaemic attacks. Examination on the Biostator thus makes it possible to decide whether conservative treatment is indicated in organic hyperinsulinism.

[Hypoglycemia and modern treatment of diabetes]. / Hypoglykémie a soucasná lécba cukrovky.

During insulin treatment, when the objective is to achieve blood sugar levels as close as possible to normal values by an intensified regime, hypoglycaemia is three times as frequent as compared with the conventional regime. The author discusses in the submitted review the relationship between a reduced blood sugar level and associated symptoms, he describes the counterregulation reparative response and draws attention to its changes in conjunction with prolonged duration of diabetes and mentions short-term as well as long-term consequences of hypoglycaemia. In the conclusion he mentions possible ways how to prevent this complication of insulin treatment.