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Biomedical subjects

W Berger

Publications and source records attributed to W Berger.

At least 199 records · Page 11Linked to original sources

[The relatively frequent incidence of severe sulfonylurea-induced hypoglycemia in the last 25 years in Switzerland. Results of 2 surveys in Switzerland in 1969 and 1984].

In 1969 and 1984 all emergency wards in Switzerland were asked to report on the incidence of severe episodes of hypoglycemia (HE) during treatment with sulfonylureas. Each of the two surveys referred to a ten-year period (period A 1960-1969, period B 1975-1984). The number of HE reported was 78 for period A and 116 for period B. The number of diabetics treated with sulfonylurea preparations was established on the basis of tablet consumption, which amounted to 35,000 in period A and 47,500 in period B. The incidence of hypoglycemia in each period was comparable (period A 0.22, and period B 0.24 per 1000 patient years), but differed with regard to the sulfonylurea preparations used. In period A hypoglycemic episodes occurred more frequently under chlorpropamide than under tolbutamide and carbutamide. In period B the incidence of episodes under chlorpropamide and glibenclamide was comparable, but was significantly higher than under tolbutamide and glibornuride. The risk of hypoglycemia occurring is thus significantly higher under glibenclamide and chlorpropamide than under glibornuride and tolbutamide. 6.5% of HE were fatal in period A, compared with 4.3% in period B. Advanced age proved to be a risk factor in HE: 77% of patients with HE were over 69 years of age, whereas only 50% of all diabetics treated with sulfonylurea preparations were in this age group. Further risk factors were impaired renal function (21%) and possible drug interactions (27%). There was less likelihood of recurrence of a hypoglycemic episode in period B than in period A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stumbling reactions in man: release of a ballistic movement pattern.

Four different modes of perturbation were applied during gait, either alone or in combination, in order to determine the extent to which compensatory reactions in the leg are released as fixed patterns or, alternatively, are generated by feedback mechanisms. The first agonist burst of the usually triphasic pattern evoked by a perturbation was unchanged in amplitude and timing when a second disturbance of an opposite sense was induced a short time later. Following this burst, the remainder of the response evoked by the second disturbance appeared time locked to the second stimulus and was unchanged in form. It is concluded, that the first agonist burst induced by a perturbation is stimulus specific and immutable after release, while the appearance of the following bursts of the triphasic pattern is dependent on the actual conditions. This suggests that a similar mechanism as assumed for ballistic hand and finger movements is operative, with the difference that the compensatory reactions following gait perturbations are induced by peripheral signals.

Adult↗

Albumin-directed antibodies in diabetes: demonstration of human serum albumin-directed IgM autoantibodies.

Sera of 406 individuals, 174 Type 1 (insulin-dependent) diabetic patients, 125 non-diabetic family members and 107 unrelated control subjects, were screened for the presence of antibodies against glycated albumin. In none of these sera could such antibodies be detected. However, antibodies directed towards monomeric, unmodified human serum albumin were detected in 13 sera. These albumin autoantibodies were of the IgM class, and occurred in sera from nondiabetic persons (0.9-1.6%) and with a five-fold higher frequency in sera from diabetic patients (5.2%). The presence of albumin antibodies was neither related to the presence of diabetic late complications, islet cell antibodies, HLA-status nor duration of diabetes. The albumin antibodies were also found in sera from persons carrying antibodies against mumps (17%) or Epstein-Barr virus.

Autoantibodies↗

Motor unit involvement in spastic paresis. Relationship between leg muscle activation and histochemistry.

In 4 patients with spastic hemiparesis the electromyograms (EMG) of leg muscles were recorded during walking and the gastrocnemius medialis on both sides was investigated by histochemistry and morphometry. During walking a reciprocal mode of muscle activation was preserved on the spastic side, but the EMG amplitude was reduced. In one patient the discharge behaviour of single motor units was investigated during stance. The mean discharge rate on both the spastic and the unaffected side amounted to about 5.5 Hz. Modification of this rate over a wider range by manoeuvres of the trunk was only observed on the unaffected side. Histochemistry and morphometry of the spastic muscle revealed: Increased levels of muscle fibre atrophy (especially type II); A predominance of type I fibres during later stages, when spasticity was established; Structural changes, such as the appearance of target fibres, mainly in type I fibres. These results suggest that the low level of tonic activation in spastic muscle develops tension enough during the stance phase of gait to support the body. The histopathological profile of the spastic gastrocnemius muscle is considered to be indicative of denervation, due to the combined effects of an impaired supraspinal control of the lower motoneurone and a concurrent transsynaptic muscle membrane dysfunction, muscle cell atrophy and fibre type transformation.

Adult↗

Sulfonylurea therapy fails to diminish insulin resistance in type I-diabetic subjects.

To assess whether extrapancreatic effects of sulfonylureas in vivo are detectable in the absence of endogenous insulin secretion, insulin sensitivity was determined in six insulin-deficient type 1-diabetic subjects. Peripheral uptake and hepatic production of glucose and lipolysis were measured during hyperinsulinemia using the euglycemic clamp technique and 3-3H-glucose infusions twice, once during a period with glibornuride treatment (50 mg b.i.d.), and once without. Hepatic glucose production decreased in diabetic subjects during hyperinsulinemia (insulin infusion of 20 mU/m2 X min; plasma free insulin levels of 40 +/- 4 mU/l) from 2.9 +/- 0.6 mg/kg min to 0.2 +/- 0.1 mg/kg X min after 120 min, and plasma free fatty acid (FFA) concentrations decreased from 1.33 +/- 0.29 to 0.38 +/- 0.08 mmol/l. Hepatic production, peripheral uptake of glucose and plasma FFA concentrations before and during hyperinsulinemia were not influenced by pretreatment with glibornuride. Compared to 8 non-diabetic subjects, type 1-diabetics demonstrated a diminished effect of hyperinsulinemia on peripheral glucose clearance (2.4 +/- 0.04 vs 4.2 +/- 0.5 ml/kg X min, P less than 0.01), whereas hepatic glucose production and plasma FFA levels were similarly suppressed by insulin. The data indicate that sulfonylurea treatment did not improve the diminished insulin sensitivity of peripheral glucose clearance in type 1-diabetic subjects; insulin action on hepatic glucose production and lipolysis was unimpaired in diabetics and remained uninfluenced by glibornuride. Thus, extrapancreatic effects of sulfonylureas in vivo are dependent on the presence of functioning beta-cells.

Adult↗

HLA-DR3 and DRw6: prognostic factors for the incidence of hypothyroidism in Graves' disease after radioiodine treatment.

Several studies demonstrated a relationship between HLA-B8 and -DR3 and the early course of thyroid function after treatment of thyrotoxicosis. However, the association between certain DR antigens and the outcome of thyroid function years after radioiodine treatment for Graves' disease remains unclear. We therefore determined the HLA pattern in 2 groups of female patients with different severity of hypothyroidism. From a total of 45 patients, 27 had developed pre-clinical hypothyroidism (normal serum levels of T4, FT4 and T3, normal or elevated basal TSH levels, but an exaggerated TSH response to TRH, Group A). Mean follow-up was 111 months (range 36-360 months) for this group. Eighteen patients had become overtly hypothyroid (T4 and FT4 levels in the hypothyroid range and an elevated basal TSH concentration, group B) after a mean interval of 51 months (range: 4-132 months) following treatment. Eighty-seven healthy blood donors served a controls. Positive plasma antibody titres (tanned red cell haemagglutination technique) were observed in 67% of all patients with a preponderance in group B (83% versus 56% in group A, n.s.). The whole group of Graves' disease patients showed the antigens B8, DR3 and Drw6 in 37.8%, 33.3% and 35.6%, respectively (P less than 0.02, less than 0.05, and less than 0.04 vs controls). In patients with pre-clinical hypothyroidism there was a significantly increased prevalence of antigen B8 (P less than 0.01) and DR3 (P less than 0.05) compared to the control group. In contrast, the overt hypothyroid group showed an augmented frequency of HLA-DRw6 (P less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

[Dependence of the action potential amplitude of motor units on the recruitment threshold: implications for electromyography].

The relationship between the action potential amplitude and the threshold force of recruitment of 275 motor units (MU) recorded from the first dorsal interosseus muscle of 15 healthy subjects was analysed. The number of newly recruited MU decreased exponentially with increasing muscular force. Action potential amplitudes showed a highly significant positive linear correlation with threshold force of recruitment. This relationship is in accordance with the size principle of MU recruitment. Applying the rank correlation method, 88.6 +/- 2.0% (mean +/- standard deviation) of paired comparisons between all MU of one subject followed the normal activation sequence of MU with an increasing action potential amplitude. It is shown that small variations of the distance between the leading-off surface of the electrode and the MU recorded do not affect these findings. These results demonstrate that the force at which a MU is recruited is the most important factor influencing MU action potential amplitude in normal subjects. So far this fact has not been adequately appreciated in clinical electromyography although it is of significance for the assessment of pathological conditions.

Action Potentials↗

Compensatory reactions to gait perturbations in man: short- and long-term effects of neuronal adaptation.

Short- and long-term changes in the cerebral potentials and the electromyographic (EMG) responses in the arms and legs evoked by gait perturbations were followed up over repeated trials in healthy subjects. Two different modes of muscle activation could be discerned. The first adapted to the specific motor task within a few trials and remained constant during the remaining experiments. This 'hard wired' and complex leg muscle reaction was shown to be task specific and necessary for an adequate compensation for the displacement. It was supposed that this reaction is mediated via a spinal pathway. The other mode, which included an early arm extension, disappeared successively as the motor task became familiar. These flexible EMG responses represent the 'protective' part of the reaction and are suggested to be mediated via a transcortical pathway, due to their close relationship to the cerebral potentials evoked by the perturbations.

Adaptation, Physiological↗

Neuronal control of ballistic finger movements in man: task specific electromyographic patterns.

The electromyographic (EMG) patterns of finger flexor and extensor muscles have been studied during ballistic finger movements in three different conditions: (1) rapid isotonic finger flexion; (2) throwing and (3) catching a tennis ball. In 1 and 2 a three-burst pattern was observed. In the latter, the first agonist burst was shorter and of higher amplitude compared to condition 1. Catching a ball was connected with a coactivation of extensor and flexor muscles prior to and during ball contact and a contribution of segmental stretch reflexes to the flexor activation. The finger flexion movement was 10-15 times faster than in conditions 1 and 2. After ischaemic blocking of group I afferents and in patients with rigidity, a short inhibition of the increased extensor activation became predominant and was the basic mechanism underlying finger flexion for catching a ball. It is concluded that in natural ballistic finger movements, other neuronal mechanisms are of functional significance than those seen in the usual experimental paradigms.

Biomechanical Phenomena↗

[HLA-antigens and islet cell antibodies in type-1 diabetics of various age groups and their first-degree relatives].

140 type 1 diabetics from Basle and vicinity were HLA-typed. 89% had HLA-haplotypes DR3, DR4, or DR3/DR4. The frequency of these antigens was significantly increased compared to normal controls. The HLA antigens DR2 and DR5 were significantly diminished in diabetics. The increase in diabetes-associated HLA antigens differed within the diabetics according to the age of diabetes manifestation. Diabetes onset before age 40 was associated with increased frequency of HLA DR4 and HLA DR3/DR4. In contrast, patients with diabetes onset after age 40 exhibited an increased prevalence of HLA DR3. The combination HLA B7/DR4 was only observed when diabetes onset was below age 20. Islet cell antibodies (ICA) were determined in 124 of the 140 type 1 diabetics. ICA were found in 40% of patients who had had diabetes for less than 2 years, but in only 21% when diabetes had lasted more than 10 years. There was no association between certain HLA haplotypes and presence of ICA. HLA antigens and the presence of ICA were also investigated in 117 first-degree relatives of the type 1 diabetics. Compared to the latter, the relatives had a significantly diminished prevalence of the HLA DR3/DR4 combination. Compared to healthy controls, these relatives had a significantly increased frequency of positive ICA (in 12% compared to 2% in nondiabetic controls). These findings demonstrate that the genetic (HLA-antigens) and immunological (ICA) background of type 1 diabetes is heterogenous. A clinical feature of the genetically determined subtypes is the age of diabetes onset.

Adolescent↗

Afferent control of human stance and gait: evidence for blocking of group I afferents during gait.

The cerebral potentials (c.p.) evoked by electrical stimulation of the tibial nerve during stance and in the various phases of gait of normal subjects were compared with the c.p. and leg muscle e.m.g. responses evoked by perturbations of stance and gait. Over the whole step cycle of gait the c.p. evoked by an electrical stimulus were of smaller amplitude (3 microV and 9 microV, respectively) than that seen in the stance condition, and appeared with a longer latency (mean times to first positive peak: 63 and 43 ms, respectively). When the electrical stimulus was applied during stance after ischaemic blockade of group I afferents, the c.p. were similar to those evoked during gait. The c.p. evoked by perturbations were larger in amplitude than those produced by the electrical stimulus, but similar in latencies in both gait and stance (mean 26 microV and 40 microV; 65 ms and 42 ms, respectively) and configurations. The large gastrocnemius e.m.g. responses evoked by the stance and gait perturbations arose with a latency of 65 to 70 ms. Only in the stance condition was a smaller, shorter latency (40 ms) response seen. It is concluded that during gait the signals of group I afferents are blocked at both segmental and supraspinal levels which was tested by tibial nerve stimulation. It is suggested that the e.m.g. responses induced in the leg by gait perturbations are evoked by group II afferents and mediated via a spinal pathway. The c.p. evoked during gait most probably reflect the processing of this group II input by supraspinal motor centres for the coordination of widespread arm and trunk muscle activation, necessary to restablish body equilibrium.

Adult↗

Cerebral potentials and leg muscle e.m.g. responses associated with stance perturbation.

In order to investigate the neuronal mechanisms underlying the compensatory movements following stance disturbance, leg muscle e.m.g. responses and cerebral potentials evoked by a treadmill acceleration impulse were analysed. It was found that the displacement was followed by a cerebral potential of a latency of 40-45 ms and EMG responses in the calf muscles at a latency of 65-70 ms. The e.m.g. responses represented specific compensatory reactions to the mode of perturbation (with a gastrocnemius activation following positive acceleration but a tibialis ant. activation following negative acceleration). The cerebral potentials, however, showed a common pattern to both conditions. In addition, the leg muscle e.m.g. reactions were not altered by learning effects and by forewarning of displacement onset, while the amplitude of the cerebral potentials was significantly smaller in these conditions compared to those produced in response to randomly induced perturbations. It was therefore concluded that the leg muscle e.m.g. reactions are mediated by a polysynaptic spinal reflex pathway which depends on a supraspinal control. The cerebral potentials seem to represent afferent signals which can be supposed to be subjected to modification and processing by supraspinal motor centres, according to the actual requirements.

Adult↗

Real and artefactual erythrocyte swelling in hyperglycaemia.

The mean erythrocyte volume of patients with acute diabetic decompensation was determined by Coulter measurement and found to be elevated above normal (mean increase 5.5 mu3). Experiments in vitro revealed this to be an artefact associated with Coulter determination. A more reliable estimate of in vivo erythrocyte volume can be obtained from centrifugated haematocrit and erythrocyte count. With this method, true erythrocyte swelling parallel to glucose concentration was observed when erythrocytes were exposed to isotonic glucose-NaCl solutions. This volume increase resulted from decreased sodium concentration and was in the order of 0.5-1.0 mu3 per mmol/l of sodium. Glucose was osmotically ineffective. Similar volume changes were documented in a diabetic patient parallel to his daily variations of blood glucose. In severe diabetic decompensation, dehydration usually prevents an increase in erythrocyte volume. We conclude that hyperglycaemia is associated with erythrocyte swelling if total serum tonicity remains within the normal range.

Adult↗

Stance and gait perturbations in children: developmental aspects of compensatory mechanisms.

The leg muscle EMG responses following perturbations during stance and gait were analysed in children between 1 and 8 years of age in order to study the development of those reflex systems responsible for the compensatory movements necessary to maintain body equilibrium. Single monosynaptic reflex potentials followed by a long-lasting (about 500 msec) polysynaptic gastrocnemius EMG response, along with coactivation of all antagonistic leg muscles, were characteristic of the EMG reactions following a treadmill acceleration impulse in early infancy. From 4 years of age on, the monosynaptic reflex potentials disappeared when perturbations were induced during gait. In addition, the polysynaptic reflex response became shorter (about 100 msec) and a reciprocal mode of leg muscle activation occurred, with a consequently more rapid and effective compensation of perturbation impulses. In older children with a disorder of the motor system acquired at an early age, a partial persistence of the immature motor responses could be observed, irrespective of whether the impairment was a cerebral lesion or a muscular dystrophy. It is concluded that the coactivation pattern is due to the immaturity of those nervous structures mediating afferent information necessary for the control of bipedal stance and gait. Furthermore, the existence of mutual inhibition of monosynaptic and polysynaptic spinal reflex responses, dependent on the function of supraspinal motor centres, can be assumed.

Cerebral Palsy↗