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Biomedical subjects

A Pernet

Publications and source records attributed to A Pernet.

18 recordsLinked to original sources

[Human insulin and hypoglycemia].

It has been reported over the last few years that transferring diabetic patients from animal to human insulin can lead, in some of the patients, to a diminution of the classical hypoglycaemic symptoms, as hunger and sweating, and to the more frequent occurrence of neuroglycopenic symptoms, as the first manifestation of hypoglycaemia. These changes seem to involve a fraction of patients estimated between 8 and 36%, depending on the type of selection of the patients. A decrease in the adrenergic counterregulatory response to hypoglycaemia has also been shown in some studies with human insulin. Similar changes in the sequence of hypoglycaemic symptoms are also described in various clinical conditions--as intensive insulin therapy with tight glycaemic control, long diabetes duration and presence of autonomic neuropathy, thus acting as confounding factors. According to these facts, a few recommendations are proposed: briefly, human insulin should only be prescribed to new patients who are able to learn from the very beginning the sequence of hypoglycaemic symptoms with human insulin; patients already treated with porcine insulin should not be transferred to human insulin. On the whole, studies available to date have not shown an increased frequency of severe hypoglycaemia with human insulin; however, this important matter still has to be conclusively clarified through well-designed prospective studies.

Autonomic Nervous System

Effect of gangliosides on diabetic peripheral neuropathy.

The effect of subcutaneously injected gangliosides on diabetic peripheral neuropathy was assessed in 26 diabetic patients with neuropathy, 20 of whom received 100 mg daily 5 days per week for 12 weeks in a randomised single-blind cross-over placebo-controlled study and six of whom, with painful neuropathy, received the same quantity of gangliosides for the same length of time but no placebo. Subjective symptoms of lower limb neuropathy improved on gangliosides but not on placebo (P = 0.01). The amplitude of the peroneal nerve muscle action potential increased on gangliosides and declined on placebo (P = 0.05), but no other significant changes were observed in nerve conduction or in any other measurable sign of lower limb somatic nerve function or of cardiovascular autonomic function.

Adult

[Shock].

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Humans

[Nyctohemeral arterial pressure profile and heart rate in autonomic diabetic neuropathy].

Autonomic failure reduces the physiological nocturnal decline of blood pressure (BP) and heart rate (HR). To assess the effect on circadian hemodynamic rhythms of sympathetic (s) and parasympathetic (ps) impairment in diabetic autonomic neuropathy (DAN), we measured BP automatically every 15 min and HR continuously for 24 hour in 11 diabetic patients. They were divided into 3 groups according to the results of cardiovascular reflex tests: a) DAN s + ps, b) DAN ps, c) no DAN. Nine of the patients were hypertensive. Eleven non-diabetic hypertensives served as controls. The disturbance of the circadian BP profile was related to the severity of the DAN, nocturnal BP tending to rise in group a, to fall in group b, and falling markedly in group c and in the control group. FC fell to a similar extent in all the groups. We conclude that the circadian BP profile is more affected by DAN than the FC profile, and that study of the circadian BP profile could reveal the presence of predominantly nocturnal hypertension.

Adult

[Intensified insulin therapy by multiple injections or by pump].

A relationship exists between metabolic control and the development of late complications of diabetes. Recently, new strategies of insulin therapy have been developed to normalize blood glucose control, with a view to preventing late complications of diabetes and increasing patients' well-being. Intensified insulin therapy can be performed by multiple insulin injections or by continuous subcutaneous insulin infusion with a pump; regular self-monitoring of blood glucose is mandatory with these types of treatment. Results obtained with both forms of insulin therapy are comparable, although in some cases pump treatment is superior. Intensified insulin therapy is principally aimed at young, motivated and compliant diabetic patients without advanced complications, and at diabetic women before and during pregnancy. The potential risks of intensified insulin therapy are reviewed.

Adult

Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency.

The metabolic responses to 4-h infusions of adrenaline (3 micrograms kg-1 h-1) and cortisol (10 mg m-2 h-1 for 2 h followed by 5 mg m-2 h-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 micrograms h-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg-1 h-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11.4 +/- 0.4 mmol l-1, P less than 0.001; somatostatin plus cortisol 6.7 +/- 0.3 mmol l-1, P less than 0.05; somatostatin alone 4.9 +/- 0.4 mmol l-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9.3 +/- 0.4 mmol l-1 v. 7.2 +/- 0.5 mmol l-1 at 45 min, P less than 0.001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0.55 +/- 0.04-1.82 +/- 0.11 mmol l-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2.30 +/- 0.11 mmol l-1 at 60 min, P less than 0.01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The metabolic response to insulin deprivation in idiopathic brittle diabetes.

To test the hypothesis that frequent episodes of ketoacidosis and severe hyperglycaemia in brittle diabetes result from an exaggerated response to insulin withdrawal, the metabolic response to insulin deprivation in 16 severely brittle female diabetics has been compared with that in 6 C-peptide negative stable female diabetic patients of similar age and body weight. 4 hr after stopping insulin infusion, blood glucose was significantly higher in the brittle diabetics (22.8 vs 17.0 mmol/l, p less than 0.001) but blood 3-hydroxybutyrate was not different (1.8 vs 1.6 mmol/l). Concentrations of free insulin and counter-regulatory hormones were similar, basally and during the deprivation. Insulin antibody levels were significantly elevated in the brittle patients (11.2 vs 5.2 mmol/l, p less than 0.05) and there was no relationship between glucose or ketone body response and antibody level. Blood lactate, pyruvate, alanine and glycerol were significantly elevated basally in the brittle diabetic patients, but did not respond differently to insulin deprivation. Basal lactate and pyruvate concentrations were significantly correlated with overnight insulin requirements (lactate, rs 0.62, p less than 0.05; pyruvate, rs 0.70, p less than 0.05) suggesting that the elevated basal concentrations resulted from the higher peripheral insulin delivery rates required to maintain overnight normoglycaemia in the brittle patients. We conclude that although there are demonstrable abnormalities of intermediary metabolism in brittle diabetics, neither elevated levels of counter-regulatory hormones, nor an exaggerated response to insulin withdrawal explains the frequent episodes of ketoacidosis in these patients.

3-Hydroxybutyric Acid

Sulfonylureas in insulin-dependent (type I) diabetes: evidence for an extrapancreatic effect in vivo.

The effect of glibenclamide treatment on insulin-mediated glucose disposal was studied in eight C-peptide-negative type I diabetic patients. The patients were studied twice by the euglycemic insulin clamp technique. One of the two experiments was preceded by glibenclamide treatment at the dose of 5 mg, three times daily for 15 days; half of the patients had the first test before and the second test after sulfonylurea treatment, and vice versa. Insulin was infused for four periods of 2 h each sequentially at 0.5, 1.0, 2.0, and 5.0 mU kg-1 min-1; for each insulin infusion period, the steady state plasma free insulin levels were comparable with or without glibenclamide. The mean +/- SEM plasma glucose concentration was 88 +/- 2 mg/dl in both experiments. The insulin-mediated glucose disposal rate was greater with glibenclamide during the first insulin infusion period (which generated plasma free insulin levels within the physiological range) 2.68 +/- 0.32 mg kg-1 min-1 with glibenclamide vs. 1.97 +/- 0.20 mg kg-1 min-1 without glibenclamide (P less than 0.005). However, glucose disposal rates did not differ in the diabetic patients with or without glibenclamide treatment during the second, third, and fourth insulin infusion periods, which generated plasma free insulin levels in the supraphysiological range. These results provide evidence for an extrapancreatic effect of glibenclamide at low insulin concentrations during euglycemic clamping in patients with insulin-dependent diabetes mellitus. However, this effect was not reflected clinically in either an increased rate of hypoglycemic reactions or decreased insulin needs during the short term period of treatment.

Adult

[Schistosomiasis. Apropos of 5 cases of Swiss citizens having traveled in endemic countries].

Among a series of 35 cases of schistosomiasis diagnosed in Geneva between 1961 and 1975 on biopsies (bladder, rectum and liver), the cases of 5 Swiss citizens who had lived in endemic countries are reported. Since the clinical manifestations are often misleading or hardly typical, the diagnosis rests above all on biopsy. After recall of the epidemiologic and pathologic features, the diagnostic steps are reviewed. The object of this study is to call the practiontitioner's attention to the increasing incidence of imported schistosomiasis among the inhabitants of temperate countries.

Adult

Antibacterial agents specifically inhibiting lipopolysaccharide synthesis.

The spread of antibiotic resistance in Gram-negative bacteria has sustained a continuing search for new agents with antibacterial activity against this important class of bacterial pathogen. Because the biosynthesis of lipopolysaccharide (LPS) is unique to Gram-negative bacteria and required by them for growth and virulence, attempts have been made to discover or design antibacterial agents acting at this site; however, no such agents have so far been developed. We now present definitive experimental data documenting design of the first member of the class of antibacterial compounds which specifically inhibit LPS synthesis. The target enzyme is 3-deoxy-D-manno-octulosonate cytidylytransferase (CMP-KDO synthetase), a cytoplasmic enzyme which activates 3-deoxy-D-manno-octulosonate (KDO) for incorporation into LPS. A specific inhibitor of CMP-KDO synthetase, alpha-C-(1,5-anhydro-7-amino-2,7-dideoxy-D-manno-heptopyranosyl)-carboxy late was designed using results of our studies of the purified enzyme. LPS synthesis ceased and lipid A precursor accumulated, causing growth stasis and perturbation of outer membrane structure and function, following delivery of the inhibitor to the intracellular target by a peptide carrier. Antibacterial action required an intact oligopeptide permease system and specific intracellular aminopeptidase activity to release inhibitor from the peptide prodrug.

Aldehyde-Lyases