Search PubMed⌕ Search

Biomedical subjects

W Berger

Publications and source records attributed to W Berger.

At least 217 records · Page 12Linked to original sources

Incidence of severe sideeffects during therapy with sulfonylureas and biguanides.

The most important side-effect of sulfonylureas is hypoglycaemia. According to surveys in Switzerland and in Sweden it occurs at a frequency of about 2 cases per 10,000 treatment years. Mortality is high, about 10%. The syndrome of inappropriate ADH-secretion has been observed almost exclusively during treatment with chlorpropamide. Asymptomatic cases of SIADH-syndrome are quite frequent, hyponatraemia has been observed in 6-10% of diabetics treated with chlorpropamide. The most dangerous side-effect of biguanides is lactic acidosis. It occurs significantly more frequent during treatment with phenformin compared to metformin. Metformin has been reported to lead to lactic acidosis in 0.4 cases per 10,000 treatment years; mortality is about 30%. Mortality of phenformin-associated lactic acidosis is even higher, 70%. Both biguanides, phenformin and metformin, cause relatively frequently vitamin B12-malabsorption (in about 1/3 of the cases). However, symptomatic vitamin B12-deficiency is extremely rare.

Acidosis↗

The contact phase of blood coagulation in diabetes mellitus and in patients with vasculopathy.

The contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also alpha 2-macroglobulin are significantly elevated in diabetics with complications, for alpha 2-macroglobulin especially in patients with nephropathy, 137.5% +/- 36.0 (p less than 0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 +/- 22.1 (p less than 0.01). Prekallikrein (PK) is increased in all patients' groups (Table 2) as compared to normals. PK is particularly high (134% +/- 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

Blood Coagulation↗

Platelet aggregation, beta-thromboglobulin and platelet factor 4 in diabetes mellitus and in patients with vasculopathy.

We have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of beta-TG and the stages of either retinopathy or macroangiopathy or nephropathy. The difference is more marked between normals and diabetics with neuropathy (p = 0.026). The aggregation response to ADP and platelet activating factor (PAF) is enhanced at lower stimulator concentration. Using the beta-TG, PF4 and aggregation values the discriminant analysis allows a distinction of several subgroups especially with nephropathy and neuropathy (Table 6).

Blood Platelets↗

[Nocturnal hypoglycemia in type-I diabetics, an underestimated risk?].

In 22 type I labile diabetics aged 20-64 years, various nighttime blood sugar (BS) values were obtained. Although 13 patients in 15 of 43 nights investigated measured below 2.8 mmol/l (50 mg%) for many hours, two thirds remained symptomless while the remainder suffered from minor hypoglycemic symptoms. The lowest BS values were obtained at about 3 a.m. Prospective as well as retrospective estimation of the hypoglycemic risk was performed with the aid of fasting and bed time BS. Causes and measures for prevention of the unexpectedly large number of episodes of nighttime hypoglycemia are discussed. Additionally, 18 healthy volunteers aged 24-61 years were investigated during 22 nights in regard to BS-values for comparative purposes: the lowest measured BS was 3.7 mmol/l (66 mg%) with an average nighttime BS of 4.9 +/- 1.1 mmol/l (86 +/- 5 mg%).

Adult↗

Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy.

Fifteen haemostasis parameters have been measured in 48 normal persons, 36 diabetic without and 44 with complications and 27 with peripheral arterial disease. Since the patient groups are older than normals, part of the differences are due to age. However, the differences are significant between normals and patients. They become highly significant for the diabetics with complications and nephropathy (Table 7). In diabetics without complications factor VIII functions, fibrinogen and thrombin time are related to age whereas there is a negative correlation for the fibrinolytic activity and antithrombin III. The diabetic complications shade off the correlations, which subsist only for VIIIR:CoF, VIIIR:Ag, ATIII and lysis before stasis. With Hbalc as dependent variable VIIIR:CoF is the only significant predictor variable in diabetics (Table 9).

Adult↗

Cerebral evoked potentials associated with the compensatory reactions following stance and gait perturbation.

We have studied the gastrocnemius electromyographic (EMG) responses and the cerebral potentials evoked in normal subjects by perturbations of stance and gait in the form of short treadmill acceleration impulses. In the stance condition a small EMG response (LM1; latency around 40 ms) was followed by a strong muscle activation (LM2; latency 75-90 ms). Following perturbation during gait, LM1 was lacking and LM2 appeared a little earlier (65-75 ms). In the stance condition, the cerebral potentials appeared with shorter latency (42 ms as compared to 83 ms) and a larger amplitude (41 microV as compared to 21 microV) than those seen in the gait condition. These changes can be explained by a presynaptic inhibition of group I afferent signals during gait, which are assumed to be responsible for the early EMG and EEG responses. It is suggested that the LM2 and the cerebral responses evoked by gait perturbation are mediated by signals from group II and III afferents.

Adaptation, Physiological↗

Corrective reactions to stumbling in man: functional significance of spinal and transcortical reflexes.

Stumbling reactions were studied in terms of bilateral leg muscle electromyographic (EMG) responses during locomotion on a treadmill. At random times, but fixed points in the stepping cycle, short impulses were applied to the treadmill, either accelerating or decelerating its progress. It was found that acceleration was compensated for by a strong ipsilateral gastrocnemius and contralateral tibialis anterior activation, and deceleration by a bilateral tibialis anterior activation. In both muscles the responses appeared with a latency of about 70 msec and lasted for about 150 msec. It is concluded that sudden displacements induced by acceleration or deceleration during gait are compensated for by a polysynaptic spinal pathway, with an associated depression of monosynaptic responses.

Acceleration↗

Single K+ channels in membrane evaginations of smooth muscle cells.

Attempts have been made to apply the patch-clamp technique to enzymatically dispersed smooth muscle cells of frog and toad stomach. The rate of successful gigaseal formation has been extremely low, but better results can be obtained when patches are taken from membrane evaginations which develop on single cells after mechanical agitation and incubation in Ca2+-containing solutions at 25 degrees C. Also ball-shaped single cells formed by the confluence of membrane evaginations were found to be equally useful for patch-clamp studies. Giga-seal formation was obtained in more than 80% of all attempts. Electron micrographs indicate that the myofilaments in membrane evaginations and in ball-shaped cells are separated from the cell membrane. Channel activity in membrane patches of such "myoballs" or evaginations is similar to the channel activity as found in intact cells. Two types of K+ channels (100 and 200 pS) have been observed that can be blocked by tetraethylammonium. Channels with the conductance of 200 pS are activated by intracellular Ca2+. The formation of evaginations has also been observed in other cells and may help to apply the patch-clamp technique to cells contaminated with surface coats.

Animals↗

Comparison of the effect of semisynthetic human insulin and porcine insulin on glucose kinetics, plasma free fatty acid and amino acid levels in man.

The effect of semisynthetic human insulin on hepatic glucose output, peripheral glucose clearance, plasma levels of C-Peptide, free fatty acids and amino acids was compared with purified pork insulin using the glucose clamp technique. 8 normal overnight-fasted subjects received intravenous infusions of either human or porcine insulin at 20 mU/m2.min(-1) during 120 min achieving plasma insulin levels of approximately equal to 50 mU/l. Plasma glucose levels were maintained at euglycaemia by variable rates of glucose infusion. Hepatic glucose production measured by continuous infusion of 3-(3) H-glucose was similarly suppressed by both insulins to rates near zero. The metabolic clearance rate of glucose increased during infusion of human insulin by 120%, C-peptide levels decreased by 41% and plasma FFA concentrations fell by 74%. The respective changes during infusion of pork insulin were similar, 118%, 48% and 72%. Both insulins decreased the plasma levels of branched-chain amino acids, tyrosine, phenylalanine, methionine, serine and histidine similarly. Thus, the results demonstrate that semisynthetic human and porcine insulin are aequipotent with respect to suppression of hepatic glucose output, stimulation of glucose clearance, inhibition of insulin secretion, lipolysis and proteolysis.

Aged↗

Interlimb coordination of posture in patients with spastic paresis. Impaired function of spinal reflexes.

Activation of leg musculature on both sides following a unilateral displacement was studied during stance on separate see-saws, or on stable force-measuring platforms, in patients with spastic hemiparesis and paraparesis. During balancing the movements on the spastic side were damped and the degree of muscle activation reduced. Whereas in healthy subjects the tibialis anterior muscles of both sides were activated, following a unilateral displacement, with the same strength and latency (see-saws 55 ms, platforms 85 ms), in hemispastic patients the EMG responses were delayed (by about 20 to 30 ms) and of reduced strength on the spastic leg, irrespective of whether the unaffected or the spastic side was displaced. In addition, the compensatory movements on the spastic side were damped in both conditions, although the amplitude of displacement was the same bilaterally. Although there was no correlation between the delay and the reduction in EMG response, the latter was correlated with the severity of paresis. In patients with spastic paraparesis quite similar results were obtained with delayed and reduced EMG responses on both sides. It is concluded that in spasticity the impaired regulation of quick compensatory movements is due to a dysfunction of a spinal interneuronal system by which the early EMG responses are mediated. This could be explained by loss of supraspinal control. In addition to the impaired neural activation of leg muscles, changes in the mechanical properties of muscle can be assumed to contribute to the damped movements on the spastic side.

Adult↗

Corrective reactions to stumbling in man: neuronal co-ordination of bilateral leg muscle activity during gait.

Electromyogram (e.m.g.) responses of lower leg muscles, and corresponding movements were studied following a perturbation of the limb during walking, produced by either (a) a randomly timed, short acceleration or decelerating impulse applied to the treadmill, or (b) a unilateral triceps surae contraction induced by tibial nerve stimulation. Bilateral e.m.g. responses following the perturbation were specific for the mode of perturbation and depended on the phase of the gait cycle in which the perturbation occurred. Treadmill deceleration evoked a bilateral tibialis anterior activation; acceleration evoked an ipsilateral gastrocnemius and contralateral tibialis anterior activation (latency in either condition and on both sides was 65-75 ms, duration about 150 ms). Tibial nerve stimulation at the beginning of a stance phase, was followed by an ipsilateral tibialis anterior activation; during the swing phase it was followed by an ipsilateral tibialis anterior and contralateral gastrocnemius activation (latency about 90 ms, duration about 100 ms). These patterns differed from the response seen after a unilateral displacement during static standing, which evoked a bilateral tibialis anterior activation. These early responses were in most cases followed by late ipsilateral responses, but the e.m.g. pattern of the next step cycle was usually unchanged, or affected only at its onset. The e.m.g. responses were unaltered by ischaemic nerve blockade of group I afferents, by training effects or by pre-warning of the onset of perturbation (randomly or self-induced). Despite the different e.m.g. responses following a perturbation during gait, the same basic functional mechanism was obviously at work: the early ipsilateral response achieved a repositioning of the displaced foot and leg, while the early contralateral and late ipsilateral responses provided compensation for body displacement. It is suggested that the e.m.g. responses may be mediated predominantly by peripheral information from group II and group III afferents, which modulate the basic motor pattern of spinal interneuronal circuits underlying the respective motor task.

Adult↗

Tension development and muscle activation in the leg during gait in spastic hemiparesis: independence of muscle hypertonia and exaggerated stretch reflexes.

In 15 patients with spastic hemiparesis the development of tension of calf muscles in relation to their electrical activation and their stretching period was studied on both sides during locomotion. Only in the spastic leg did isolated small biphasic potentials appear in the gastrocnemius E.M.G. with monosynaptic latency at the beginning of the stance phase, while the remaining gastrocnemius activation was reduced compared to the unaffected side. Perturbations of gait were followed in the spastic leg by a large monosynaptic response, while the polysynaptic reflex response was reduced. In the unaffected leg only a strong polysynaptic response appeared, which suggests a reciprocal modulation of monosynaptic and polysynaptic reflex responses. Tension development paralleled the gastrocnemius E.M.G. in the unaffected leg, while in the spastic leg tension was more closely correlated to muscle stretch. It is concluded that in spasticity the exaggerated monosynaptic reflexes represent only a small part of leg extensor activation during gait and that the tension development does not depend on these reflexes.

Adult↗

Quantitation of glycosylated hemoglobin by boronate affinity chromatography.

Total hemoglobin glycosylation and the contribution of glycosylation at the N-terminus of the beta-chains and at "non"-beta-N-terminal positions were quantitated by use of boronate affinity and ion exchange chromatography. Glycohemoglobin (y) was found to correlate linearly (y = 1.92x + 0.53; r = 0.96) with HbA1c (x) and to contain approximately 50% beta-N-terminally glycosylated hemoglobin. This result is in agreement with the binding on boronate agarose of the various hemoglobin components resolved by cation exchange chromatography. An amount of glycohemoglobin similar to that of HbA1c was isolatable from HbA. A slope of less than 2 results because HbA1c is retained only to 93% and the intercept of the regression line reflects the partial adherence (65%) of HbA1a + b to the resin. These results confirm the occurrence of significant "non"-beta-N-terminal glycosylation and show that under optimal chromatographic conditions total glycohemoglobin can be determined with boronate affinity chromatography.

Borohydrides↗

Normal and impaired development of children's gait.

The development of bipedal locomotion was studied electrophysiologically in 50 children, ages varying between 6 months and 7 years. The typical features of the immature gait were: A co-activation of antagonistic leg muscles during the stance phase. With the development of free walking the activity pattern gradually became more reciprocally organized. Up to an age of 4 years, large solitary biphasic potentials in gastrocnemius with segmental latency after the muscle was stretched as the forefoot reached the ground. A reduced magnitude of gastrocnemius-EMG at the early stages of stepping. While the magnitude of tibialis anterior EMG did not change substantially with the maturation of gait, the final magnitude of gastrocnemius activity was established around 4-5 years. In the early stages of gait development, preprogrammed leg muscle EMG in form of the co-activation, and segmental stretch reflex activity appear separately. It is conjectured that during the course of maturation, the integration of the stretch-reflex activity into the preprogrammed leg muscle EMG corresponds to an increase of gastrocnemius activity with optimal adaptation to the environment. The locomotor pattern of older children with cerebral palsy showed a striking similarity to the early stages of gait development in healthy children.

Adolescent↗

[Profile of autoimmune antibodies in idiopathic hypothyroidism and hypothyroidism following radio-iodine treatment in Basedow's disease: comparison with a group of normal subjects from the female population of Switzerland].

Prevalence of thyroid microsomal antibodies (MCHA) and thyroglobulin antibodies (TGHA), as well as frequency of other autoantibodies (parietal cell antibodies [PZA], adrenal antibodies [NNA], islet cell antibodies [IZA], smooth muscle antibodies [SMA], mitochondrial antibodies [MitA] and antibodies to nuclear antigens [ANF]), are reported for three different female groups in Switzerland in 91 euthyroid controls (group A), in 58 patients with idiopathic hypothyroidism (group B) and in 55 patients with hypothyroidism after administration of radioactive iodine for Graves' disease (group C). Prevalence of MCHA in the three groups was 14.5%, 90%, and 72%, respectively, and TGHA were positive in 6.5%, 56%, and 28%, respectively. Simultaneous occurrence of both thyroid antibodies and their appearance in higher titers were significantly more frequent in group B than in the other two groups. Goitrous forms of idiopathic hypothyroidism show higher MCHA titers than the atrophic forms. There was no association between thyroid antibodies and the presence of endocrine ophthalmopathy in group C. PZA were frequently found in groups B and C (26% and 13.6%, respectively; 4.7% in controls). The higher frequency of other autoantibodies was even more pronounced for ANF (52.1% in group B, 29.7% in group C, and 12.5% in controls). NNA and SMA were also more frequent, but not to a statistically significant degree. Two patients (both in group B) had positive islet cell antibodies. MitA were equally distributed in the three groups. These results suggest a relatively high proportion of asymptomatic autoimmune thyroiditis in the female population of Switzerland, with possible progression to overt hypothyroidism. Determinations of PZA and NNA are mandatory in both Graves' disease and idiopathic hypothyroidism. Cases with positive PZA must be closely monitored in view of the association with autoimmune atrophic gastritis and pernicious anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

The influence of dimethylbiguanide on phenprocoumon elimination and its mode of action. A drug interaction study.

This study was based on the clinical observation of a higher phenprocoumon requirement in these diabetic patients simultaneously treated with phenprocoumon (Marcoumar) and dimethylbiguanide (DMB), and of a drug interaction observed in a patient. These higher requirements of phenprocoumon, suggesting an increased elimination, could have been due to an enhancement of liver microsomal enzyme activity and/or an increase in liver blood flow. Various studies were performed to test this hypothesis. The clinically suggested higher phenprocoumon requirement was proven by a drug observation study. Hence a higher tablet consumption of phenprocoumon and a diminished anticoagulatory effect was found after treatment with DMB in doses of between 1 and 3 g. An increased elimination of phenprocoumon following DMB administration was also found in a pharmacokinetic study. The activity of the liver microsomal enzyme system, investigated in animal and man, showed no changes in the liver microsomal enzymes in animal studies or the in vivo parameters of liver microsomal enzyme activity in patients. Measuring liver blood flow in dogs, utilizing the indocyanine green clearance method, an increased flow of about 33% was observed. As changes in liver blood flow can increase the metabolism of some highly lipid soluble drugs, the increased metabolism of phenprocoumon during DMB treatment could be related to the increase in liver blood flow and not to changes in liver microsomal enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Hydroxycoumarins↗