[Intensified insulin therapy in Type-I diabetes].
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Biomedical subjects
Publications and source records attributed to W Berger.
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The leg muscle electromyographic responses induced during stance by impulsive displacements of a treadmill belt (directed forward or backward and at different rates) were studied in a group of patients with Parkinson's disease and a group of age-matched healthy subjects. Young normal subjects were also studied both before and after intake of a dopamine antagonist (haloperidol). Compensatory gastrocnemius electromyographic responses resulting from backward-directed displacements were significantly smaller in both the patients and the young normal subjects following intake of haloperidol. The reduced sensitivity of the gastrocnemius muscle to stretch correlated with an inability to compensate for the perturbations. In the patients, the gastrocnemius response was followed by enhanced activation of the tibialis anterior muscle. This was not the case in the normal subjects after intake of dopamine antagonist and is probably not, therefore, the consequence of acute dopamine deficiency. In the patients the angular rotation at the ankle joint induced during faster backward-directed displacements was slower than that in normal subjects, despite identical amounts of gastrocnemius electromyographic activity. This supports earlier findings of changes in intrinsic muscle stiffness in Parkinson's disease. None of these differences were seen when the tibialis anterior muscle was stretched. This differential behavior of the antagonist leg muscles can best be explained by the different function fulfilled by these muscles in regulation of stance and gait.
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Sudden tilts of the head to the front or rear were induced during stance, balancing, gait and during perturbations of gait. The most prominent response in the leg muscle electromyogram (e.m.g.) to head tilt occurred in the tibialis anterior muscle (latency about 55 ms) following a backward tilt induced during balancing. During stance and gait, the e.m.g. activity related to head tilt was only a minor component of the leg muscle activity normally occurring during gait. When the head tilt was induced shortly after a perturbation of gait (treadmill acceleration impulse), the compensatory reaction in the leg muscles did not significantly differ from that seen after the gait perturbation alone. In addition, the rate of acceleration of the head was tested against the compensatory e.m.g. responses: No correlation of influence could be discerned. The results indicate that sudden head tilts and the resulting head acceleration have little influence on the e.m.g. patterns that occur during gait and perturbations of gait. It is assumed that these patterns are regulated by central programs, and that the compensation for leg perturbation is achieved mainly by spinal reflex mechanisms. It is discussed whether the lack of head tilt responses is the result of an antagonistic vestibular-neck interaction, or whether it indicates a reduced effectiveness of vestibulo- and cervico-spinal reflexes during gait.
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Leg muscle EMG responses evoked by short treadmill acceleration impulses applied during stance were analysed in patients with spastic hemiparesis. The compensatory reactions on the unaffected side consisted of a diphasic pattern of leg muscle activation. The first response could best be described as a polysynaptic spinal stretch reflex response. This response was absent on the spastic side, except for its later, declining component. This remainder of the first response and the following activation of the antagonistic muscle was identical on both the unaffected and the spastic side. This part of the pattern is assumed to be centrally programmed (at the spinal level) and triggered by the termination of the acceleration impulse.
To assess mechanisms leading to the 'dawn phenomenon' in type 1 diabetes mellitus, overnight insulin clearance, hepatic blood flow and insulin sensitivity of glucose metabolism were determined in 9 type 1 diabetic subjects treated with continuous subcutaneous insulin infusions. Glucose clamp studies were performed twice, once after midnight (from 24.00 to 02.00 h), and once in the early morning (from 06.00 to 08.00 h) during insulin infusion at 15 mU/m2/min. Insulin clearance was 482 +/- 57 ml/m2/min during the first, and 528 +/- 56 ml/m2/min during the second clamp (nonsignificant). Hepatic plasma flow assessed by measuring indocyanine green clearance was 984 +/- 115 and 1,040 +/- 163 ml/min, after the first and after the second clamp, respectively (nonsignificant). Glucose uptake during the two clamps was not significantly different. Since hepatic blood flow is known to influence insulin clearance and hepatic glucose metabolism, the data demonstrate that overnight changes in hepatic blood flow and insulin clearance do not contribute to the previously described early morning increase in insulin requirements in type 1 diabetic subjects (dawn phenomenon).
From 1980 to 1985, 120 insulin-dependent diabetics were admitted to the emergency department of the Cantonal Hospital, Basle, for altogether 173 severe hypoglycemic attacks. Relating these numbers to a total of 700 insulin-dependent diabetics in Basle, this means an hypoglycemia incidence of 4.2 per 100 treatment years. The principal causes were: dietary error or increased physical activity (43.7%); increase in daily insulin dose by the patient or his doctor (14.6%); and other illnesses, mostly involving the gastrointestinal tract (10.9%). Age and duration of insulin treatment were risk factors for the occurrence of hypoglycemic episodes. Thus, comparing patients at the Cantonal Hospital with or without hypoglycemia, there were significantly more hypoglycemic attacks (p less than 0.05) in the group of patients aged over 60 years or who had been treated with insulin for more than ten years. Average daily dose of insulin was about the same in both groups (35.8 U daily with hypoglycemia; 39.6 U without). Regardless of the daily number of injections, hypoglycemia occurred most frequently between 10 and 13 h and before the evening meal between 17 and 19 h.
The cerebral potentials induced by an electrical stimulus (median nerve or finger) were recorded over the central region of the scalp and were analysed during falling onto the extended arms or during writing to investigate the influence of different motor tasks on the transmission of a synchronous afferent volley to the brain. During both falling (before landing) and writing, the first peaks (20-40 ms) were reduced. Later peaks (60-200 ms) were enhanced during writing but reduced during falling. A reduction of the first peak was also obtained after ischaemic blockade of group I afferents, suggesting that the cerebral transmission of group I afferents is inhibited during falling and writing. The subjects reported a corresponding reduction in the perception of the stimulus during falling. During writing, however, the large late waves indicate a task specific processing of the remaining afferent volley. Such a gating of sensory information to the brain is assumed to play a functional role in the respective motor tasks.
45 non-insulin dependent diabetic subjects with "secondary failure" of oral treatment were observed for 2 years; during this period 23 of the 45 became insulin requiring. Plasma C-peptide concentrations at study entry and several clinical parameters of the patients were analysed statistically using discriminant analysis to test their value in predicting the need for later insulin therapy. The results demonstrated the fasting C-peptide concentrations and, independently of this, the simultaneously measured glucose level had a significant predictive power, e.g. only patients with fasting glycemia of greater than 12 mmol/l and C-peptide concentrations exceeding 700 pmol/l did not require insulin during follow-up. Increased C-peptide concentrations pointed to a predominance of insulin resistance which correlated with an increased chance of being treatable without insulin. A further group of 44 elderly, insulin-treated diabetic subjects were examined for clinical markers of type 1 and type 2 diabetes when these patients were separated into type 1 and 2 diabetes according to their fasting C-peptide concentrations. It was demonstrated that age, weight and duration of diabetes did not significantly differ between the 2 types of diabetes in this group of patients. The studies demonstrate that determination of plasma C-peptide concentration is a valuable tool in distinguishing the two types of diabetes (type 1 and type 2). This distinction has clinical implications with regard to genetic counselling or the search for other endocrinopathies. In addition, fasting C-peptide measurement is a valuable tool, in conjunction with blood sugar determination, in deciding whether patients with secondary failure of oral antidiabetic treatment require long-term insulin therapy.
We have followed the segregation of the probes pJ3.11, 7C22, pB79a, and MET through cystic fibrosis families in the German Democratic Republic with two affected sibs. Two families with a crossover between MET and the CF phenotype were detected. In one of these families recombination was also observed between the DNA probe 7C22 and CF, and between the markers XV-2c and CF, which suggests that XV-2c, MET and 7C22 are all on the same side of CF. The other MET recombinant family is informative with XV-2c and does not recombine, which excludes the genetic order XV-2c--MET--CF if multiple recombinant events are disregarded. These two families together demonstrate that recombinations may occur in a very small genetic interval, which has important implications for prenatal diagnosis based on data from linked markers.
Repeated estimation of plasma protein glycation by the fructosamine assay gave more variable results than expected from analytical variability (coefficient of variation approximately 2%). Fructosamine results obtained on plasma samples drawn at different times of the day differed by up to 1 mmol/l, corresponding to a coefficient of variation of greater than 10%. As a consequence, the information concerning averaged glycaemia of a fructosamine determination is subject to an uncertainty of 7.8 mmol/l. Fructosamine concentrations were linearly related to the protein concentration. Correction for the protein concentration decreased this variability; however, factors other than protein concentration, such as lipid content, also influence results of fructosamine determinations.
Comparisons were made between the cerebral potentials (CPs) and EMG responses of leg muscles evoked by perturbation impulses during stance and gait in normal children aged from 1 to 10 years. Changes in the efferent arm of the reflex systems during development were reflected in parallel changes with age of the afferent system, expressed in the CP: in the youngest children (1-2 years of age) monosynaptic stretch reflex potentials appeared following perturbations during both stance and gait, together with a reduced level of longer latency EMG responses. The CP, too, had a profile that did not, at this early stage, differ in either condition. In children from 6 to 10 years of age, the adult pattern was reached, with the suppression of monosynaptic stretch reflexes and the early part of the CP during gait perturbation. This is interpreted as an inhibition of group I afferents at both segmental and supraspinal levels, involving suppression of both segmental stretch reflexes and group I signals to supraspinal centres. This control of afferent information had yet to be established in early infancy. The age group from 2 to 6 years showed progressive changes, with an increase in both the level and phasic nature of polysynaptic EMG responses and a corresponding transformation of the latency and shape of the CP. It is suggested that maturation of compensatory EMG responses during gait is achieved by the establishment of descending inhibition of group I afferents and facilitation of polysynaptic spinal reflexes via group II afferents.
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Procedures resorted to in building up a questionnaire for assessing adolescent's Mental Health are submitted. Questions were selected from DSM-III diagnosis categories and from Goldberg's General Health Questionnaire (GHQ) as well. The following variables were considered: socioeconomic characteristics, developmental level, and normal vs. psychopathologic criteria. The main results may be summarized as follows: a) Reliability and validity of data obtained allow the researchers to infere that this is an apt test for discriminating between normal and psychopathologic adolescents, b) Factorial analysis results confirm the constructional validity of the questionnaire, c) The most relevant variable was normal vs. psychopathological criteria even though the developmental level variable was also of significance. No significative differences were obtained in connection with socioeconomic level, d) As demonstrated in previous papers, psychopathology in adolescents is a mixed syndrome, and e) In similar questionnaires, adolescents got higher scores than adults.
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We have investigated bilateral leg muscle activation following an obstruction of the forward swinging leg during gait. When the holding impulse was released at the beginning of the swing phase, weak gastrocnemius (GM) and biceps femoris (BF) responses appeared in the contralateral, standing leg. When the holding impulse was released at the end of the swing phase, strong tibialis anterior (TA) and rectus femoris (RF) responses appeared in the swinging leg, and GM and BF responses in the standing leg. In the latter condition the TA response was followed by a premature impact associated with a GM activation. The latency between onset of impulse and appearance of the responses was 65-70 ms in both legs. While in the first condition the duration of GM and BF response corresponded to the duration of the impulse, it was independent for the duration of GM and BF response in the latter. It is concluded that different strategies for compensation are at work. In the first condition, body stability is maintained during the obstruction by the standing leg. In the second condition, body support is provided by a premature touchdown of the swinging leg. It is suggested that the appropriate pattern is, in part, released by a spinal generator.
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