[A 65-year-old patient with acromegaly, recent appearance of dyspnea and tibial edema].
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Biomedical subjects
Publications and source records attributed to G Müller-Esch.
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Counterregulatory effect following administration of biosynthetic human proinsulin (BHPI) and human insulin (BHI) were compared during hypoglycemia standardized by means of a glucose controlled insulin infusion system (GCIIS). A total of 0.148 +/- 0.010 U/kg of BHPI had to be given by the GCIIS in order to obtain a minimal blood glucose (BG) of 26 +/- 2 mg/dl (means +/- SEM) at 43 +/- 2 min. In contrast, 0.083 +/- 0.004 U/kg of BHI were sufficient to produce a minimal BG of 21 +/- 1 mg/dl (n.s.) at 35 +/- 1 min. (P less than 0.005). Moreover, BHPI infusion resulted in prolonged hypoglycemia and delayed blood glucose recovery. On a molar basis, the acute BG lowering effect of BHPI was about 13% that of BHI (BHPI 3.94 +/- 0.27 vs. BHI 0.51 +/- 0.03 nmol/kg). Serum proinsulin after BHPI reached its maximum of 19.4 +/- 2 pmol/ml at 20 min. and still exceeded basal values markedly at the end of the test period at 240 min. Serum insulin peaked at 10 min. (162 +/- 47 microU/ml) and had already returned to basal values (7.5 +/- 1 microU/ml) after 45 min. No severe side effects were observed and there was no need for glucose administration, but clinical symptoms of hypoglycemia were more pronounced after BHPI. Compared to BHI, BHPI produced a higher cortisol peak (252 +/- 16 vs. 168 +/- 10 ng/ml), a more pronounced secretion of ACTH and GH as well as a stronger decline of serum potassium (3.20 +/- 0.06 vs. 3.58 +/- 0.08 mmol/l). Counterregulatory prolactin secretion did not differ significantly. Urinary epinephrine secretion following hypoglycemia after BHPI exceeded that after BHI (10.3 +/- 4.8 vs. 3.0 +/- 0.5 ng/120 min.). Serum lactate increase after BHPI was more prolonged (1.68 +/- 0.24 vs. 0.37 +/- 0.14 mmol/l at 120 min.). BHPI-induced inhibition of lipolysis, as determined by free fatty acid patterns, was delayed and less pronounced. Our results indicate that the observed more distinct glucose counterregulation is due to prolonged hypoglycemia rather than to any specific BHPI action on the hypothalamic-pituitary axis. We regard this as a consequence of the prolonged circulating and biological half-life. A preferential proinsulin action on the liver may play an additional role. Whether this "depot effect" may be beneficial in the treatment of diabetes mellitus remains to be established.
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Human insulin (BHI, recombinant DNA) and pork insulin (PI) were compared in 10 healthy volunteers. Using a glucose controlled insulin infusion system for the performance of the insulin hypoglycemia test (IHT), a comparable dosage of both insulins had to be infused (BHI 0.129 +/- 0.007 vs PI 0.115 +/- 0.01 U/kg; mean +/- SEM). Blood glucose slopes and nadirs did not differ significantly (BHI 30 +/- 2 vs PI 29 +/- 2 mg/dl). There was no difference in C-peptide inhibition (minimum for BHI 0.50 +/- 0.08 vs PI 0.42 +/- 0.08 micrograms/l). Maximum hormone responses were identical for ACTH (BHI 78.4 +/- 11.3 vs PI 76.0 +/- 8.7 pg/ml), cortisol (BHI 246 +/- 20 vs PI 252 +/- 15 ng/ml) and GH (BHI 43.8 +/- 7.3 vs PI 49.4 +/- 6.7 ng/ml). Peak levels of prolactin did not differ significantly (BHI 1,335 +/- 315 vs PI 1,766 +/- 614 microU/ml). The urinary excretion pattern of epinephrine in three 120 min periods before, during and after IHT was identical (before IHT: BHI 0.9 +/- 0.2 vs PI 0.6 +/- 0.1 micrograms/120 min; during IHT: BHI 12.6 +/- 2.2 vs PI 13.4 +/- 2.5 micrograms/120 min; after IHT: BHI 2.5 +/- 0.7 vs PI 3.7 +/- 1.3 micrograms/120 min). No differences in the minima of serum potassium levels were observed (BHI 3.38 +/- 0.04 vs PI 3.33 +/- 0.05 mmol/l). We conclude that the biological effects of human insulin and pork insulin are comparable. Our data do not support the assumption of a different hypothalamic handling of human insulin (recombinant DNA) and porcine insulin.
A computerized method for artefact handling, which occurs during recording and evaluation of data from glucose controlled insulin infusion systems (GCIIS) is demonstrated: Recording phase: "Interrupt"-Mode: Restoring of the original linear data-time relation is achieved by using an additional time channel. Analogous treatment of time- and parameter files allows correct correlation. "Communication I/O error": An error-handling subroutine prevents break of program caused by lead characters which occur during restarting the GCIIS thereby disturbing GCIIS-microcomputer communication. Risk of data loss caused by breakdown of electric current is minimized by an appropriate interaction between intermediate store and floppy disk for data transfer. Evaluation phase: Implausible data: Obstruction of double lumen catheter as well as loss of glucose sensor sensitivity result in inappropriate data with consecutive incorrect computation of glycemic indices such as MAGE and M-value. Zero-values: During "HOLD"-mode, all blood glucose values are set to zero by the GCIIS causing forbidden arithmetic operations. These artefact periods are marked in the prepared time-file, deleted and interpolated subsequently. In conclusion, our method permits automatic artefact handling during the recording phase and complete correct data processing during the evaluation phase.
A 71-year-old woman with insulinoma was studied. Preoperatively, using the glucose controlled insulin infusion system (GCIIS) for glucose clamping at various blood glucose levels, autonomous insulin production was demonstrated and intravenous glucose needs for maintenance of normoglycaemia were evaluated. The results of a somatostatin suppression test, guided by the GCIIS, supported the postulation of a well differentiated beta cell adenoma with reduced storage capacity. These assumptions were later confirmed by histochemical and ultrastructural investigations. Hypoglycaemia during surgery was avoided by means of the GCIIS. Upon clamping of the plasma glucose at 90 mg/dl, 15.5 g dextrose had to be given until resection of the tumour. Immediately thereafter, a sharp rise in plasma glucose to 140 mg/dl together with a need for 4.1 U insulin showed that the insulinoma tissue had been removed completely.
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Insulin hypoglycaemia test (IHT) for assessment of hypothalamic-pituitary-adrenocortical (HPA) function in patients with pituitary tumours is usually performed by bolus injection of insulin, a procedure which includes the risk of overdosage and/or the need of repeated administration. This study describes that a glucose controlled insulin infusion system (GCIIS) permits to perform the IHT with standardized hypoglycaemia. Ten healthy volunteers and 10 patients with pituitary tumours were studied using the GCIIS (Biostator) on static control (Mode 1:1, BI 35, QI 10, RI 20, FI 300). Insulin administration was discontinued and the GCIIS used only for monitoring of blood glucose (BG), when BG had fallen below 40 mg/dl and initial clinical symptoms for hypoglycaemia were observed. In controls, the GCIIS guided IHT achieved a sufficient degree of hypoglycaemia (BG 27.6 +/- 2.0 mg/dl; mean +/- SEM) and physiological responses for GH (peak 49.4 +/- 6.7 ng/ml), Prl (peak 1766 +/- 614 microU/ml), ACTH (peak 76.0 +/- 8.7 pg/ml) and cortisol (peak 252 +/- 15 ng/ml). The total amount of insulin given was 0.115 +/- 0.012 U/kg. In the patients with pituitary tumours however, the required insulin dose varied markedly from 0.090 (pituitary insufficiency) to 0.340 U/kg (Cushing's syndrome). Minimum BG obtained was 32.5 +/- 1.9 mg/dl. Partial impairment of hypothalamic-pituitary function and, in particular, patients requiring exogenous cortisol supplementation during stress, could be identified. In conclusion, special advantages of the GCIIS-guided IHT are: Optimal insulin dosage with standardized hypoglycaemia due to automatic adjustment to the individual insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
After inhaling a leather-impregnation spray in a confined space, coughing fits and dyspnoea occurred in a 40-year-old man and an 20-year-old woman, previously in good health. The cardinal symptoms on admission to an emergency ward were of interstitial pulmonary oedema in the X-ray but without increased pulmonary arterial pressure. Administration of corticosteroids both by aerosol and intravenously improved the acute symptoms within a few hours. Two subsequent chest X-rays demonstrated complete healing. The acute symptoms were caused by the impregnation spray producing an alveolitis or toxic lung oedema in both cases. The early topical administration of corticosteroids would appear to be the most important preventive and protective measure.
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