[Prevalence and clinical aspects of cardiovascular vegetative neuropathy in a diabetic population].
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Biomedical subjects
Publications and source records attributed to R Gomis.
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The Ca2+-responsive enzyme transglutaminase, which catalyzes the cross-bridging of proteins, is present in pancreatic islet cells, but its participation in the process of insulin release remains to be documented. Glycine methylester (1.0-10.0 mM) inhibited, in a dose-related manner, transglutaminase activity in rat pancreatic islet homogenates, decreased [14C]methylamine incorporation into endogenous proteins of intact islets, and caused a rapid and reversible inhibition of insulin release evoked by D-glucose, while failing to affect D-[U-14C]glucose oxidation. Glycine methylester also inhibited insulin release induced by other nutrient or nonnutrient secretagogues. Sarcosine methylester failed to affect transglutaminase activity, [14C]methylamine incorporation, and insulin release. Both methylesters mobilized 45Ca from prelabeled intact islets, from membranes of islet cells, liver or brain, and from artificial lipid multilayers, this Ca mobilization being apparently unrelated to changes in transglutaminase activity. It is proposed that, in the pancreatic B cell, transglutaminase participates in the machinery controlling the access of secretory granules to the exocytotic sites.
The authors have transferred the posterior part of the deltoid muscle to the triceps in 21 tetraplegics. A modification of Moberg's technique has been employed utilising a strip of fascia lata reinforced by Dacron sutures to allow rehabilitation after only 3 weeks. Despite limited active extension of the elbow and diminished power, results were considered to be satisfactory by the patients. They benefited from a greater range of movement of the hand, an improved possibility of bearing weight, improvement in the use of wheelchairs and better ability to express their bladder.
The metabolic and secretory effects of methylamine in rat pancreatic islets were investigated. Methylamine accumulated in islet cells, was incorporated into endogenous islet proteins, and inhibited the incorporation of [2,5-3H] histamine into either N,N-dimethylcasein or endogenous islet proteins. Methylamine (2 mM) did not affect the oxidation of glucose or endogenous nutrients or the intracellular pH in islet cells. Glucose did not affect the activity of transglutaminase in islet homogenates, the uptake of 14C-methylamine by intact islets or its incorporation into endogenous islet proteins. Methylamine inhibited insulin release evoked by glucose, other nutrient secretagogues, and non-nutrient insulinotropic agents such as L-arginine or gliclazide. The inhibitory effect of methylamine upon insulin release was diminished in the presence of cytochalasin B or at low extracellular pH. Methylamine retarded the conversion of proinsulin to insulin. Trimethylamine (0.7 mM) was more efficiently taken up by islet cells than methylamine (2.0 mM), and yet caused only a modest inhibition of insulin release. These findings suggest that methylamine interferes with a late step in the secretory sequence, possibly by inhibiting the access of secretory granules to their exocytotic site.
Methylamine (2 to 10 mM) caused a dose-related inhibition of insulin release evoked in rat pancreatic islets by nutrient or non nutrient secretagogues. Trimethylamine exerted comparable effects upon insulin release. Methylamine (2 mM) inhibited insulin secretion but failed to affect 45Ca uptake and efflux in response to a rise in extracellular K+ concentration, suggesting that methylamine acts, to a certain extent at least, at a distal site in the secretory sequence. Methylamine, however, also exerted untoward ionic effects. First, methylamine (2 to 10 mM) apparently caused a dose-related increase in cellular pH. Second, methylamine (2mM) augmented 86Rb outflow from islets perifused either in the absence or presence of glucose or gliclazide, and inhibited Ca2+ inflow (as judged from the net uptake or efflux of 45Ca) in islets stimulated by D-glucose, L-leucine or 2-ketoisocaproate. This multiplicity of ionic and other effects may account for the fact that, in the presence of distinct secretagogues, the secretory process appeared more or less sensitive towards methylamine, depending on the relative importance of changes in cellular pH, K+ permeability and intracellular Ca2+ distribution as determinants of the secretory response.
Pancreatic islet homogenates display Ca2+-dependent transglutaminase activity. Methylamine inhibits the enzyme activity, accumulates in intact islet cells, is incorporated in endogenous islet proteins, and inhibits glucose-stimulated insulin release. The inhibition by methylamine of both enzyme activity and insulin release is inversely related to the ambient Ca2+ concentration. Dimethylamine also inhibits transglutaminase activity and glucose-stimulated insulin release. However, trimethylamine, which does not affect transglutaminase activity, again inhibits glucose-stimulated insulin release, the latter inhibition being also inversely related to the Ca2+ concentration. It is concluded that the impairment of insulin release by methylamines is not necessarily linked to inhibition of transglutaminase activity.
Eighty cases of peritrapezial arthritis of the thumb treated by Swanson's trapezial implant have been reviewed by the authors. They advocate a slightly modified technique and emphasize the importance of "varisation" of the implant and of correct resection of the greater multangular bone. Follow-up was at least one year in all cases, maximum 10 years, the mean being 3 1/2 years. Results were judged as very good in 75% of the cases, fair in 20% and poor in 5%. This study emphasized the cases of failure by implant instability and its causes. In 8 cases, abnormal wear of the implant or of the scaphoid bone raises the question of long-term tolerance of silicone implants.
The authors stress the prevalence and severity of wrist involvement in rheumatoid disease. Improved knowledge of aetiopathogenesis and deformities had led to identification of the importance of the distal consequences on the digital joints of decentralization of the wrist. Synovectomy retains an important place at the onset of the disease. This may be completed by stabilization procedures (tendon transfer and partial arthrodesis). At the advanced stage of the disease, arthroplasty is currently overtaking arthrodesis. Interposition arthroplasty, with its rare indications, is now well developed. Although the solution of the future, arthroplasties lack sufficient follow up in terms of their results. The Swanson implant offers limited mobility but ensures freedom from pain and a good wrist axis. The ideal treatment of the rheumatoid wrist is oriented towards early conservative surgery and later, at an advanced stage, towards arthroplasty, the ideal technique of which remains to be discovered.
The possible contribution of hepatocellular damage and portal-systemic shunting to hyperinsulinism in cirrhosis was studied in 23 cirrhotics, 8 of whom had a surgical portacaval shunt, and 16 controls by measuring insulin and the connecting peptide (C-peptide) concentrations in simultaneous samples of peripheral arterial and hepatic venous blood. The fractional hepatic insulin extraction (0.48 +/- 0.06, mean +/- SE) was normal in cirrhosis. The hepatic insulin elimination rate was directly related to arterial insulin levels (r = 0.91, P less than 0.001) even at very high circulating levels. Extrahepatic insulin metabolism was measured across the kidney and lower limb. There were no significant differences between cirrhotics and control subjects in relation to renal (0.25 +/- 0.05 vs. 0.23 +/- 0.04) and lower limb insulin extraction (0.14 +/- 0.07 vs. 0.19 +/- 0.04). While in the control group hepatic venous insulin (0.143 +/- 0.018 pmol/ml) markedly exceeded the peripheral insulin concentration (0.083 +/- 0.009 pmol/ml, P less than 0.01), the contrary was found in cirrhotics with end-to-side portacaval shunt in whom all the pancreatic venous effluent is shunted to the systemic circulation (hepatic venous insulin, 0.130 +/- 0.028 pmol/ml; peripheral, 0.234 +/- 0.037 pmol/ml; P less than 0.01). Portal-hypertensive cirrhotics without a surgical portacaval shunt also had hepatic venous insulin levels (0.132 +/- 0.029 pmol/ml) below peripheral arterial insulin concentrations (0.205 +/- 0.041 pmol/ml, P less than 0.01). The study suggests that hyperinsulinism in cirrhosis is not the result of an intrinsic defect of hepatic insulin metabolism but of the spontaneous shunting of portal blood to the systemic circulation.
Pancreatic islet homogenates display calcium-sensitive transglutaminase activity, but the role of this enzyme in the process of insulin release remains to be elucidated. Tolbutamide, gliclazide, glisoxepide, glipizide and glibenclamide inhibited transglutaminase activity in islet homogenates. When the cationic response of islet cells to hypoglycaemic sulphonylureas was suppressed by exposing intact islets to quinine, tolbutamide, gliclazide and glibenclamide caused a rapid, sustained, reversible and dose-related inhibition of insulin release. The relative efficiency of distinct hypoglycaemic sulphonylureas as inhibitor of transglutaminase activity was in mirror image of their relative potency as insulin secretagogue. However, the dose-action relationship for the inhibitory action of these agents upon insulin release from quinine-treated islets was similar in response to either tolbutamide, gliclazide or glibenclamide. These results indicate that hypoglycaemic sulphonylureas may exert an inhibitory action upon insulin release, but suggest that such an effect is not tightly related to inhibition of transglutaminase.
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1. Pancreatic islet homogenates catalyze, in a Ca2+-dependent fashion, the incorporation of [2,5-3H]histamine, [1,4-14C]putrescine, [1,2-3H]agmatine, [14C]methylamine and L-[U-14C]lysine in N,N-dimethylcasein. 2. Using [2,5-3H]histamine as the amine donor, the Km for Ca2+ and histamine amounts to 90 microM and 0.7 mM, respectively. 3. The incorporation of [2,5-3H]histamine into N,N-dimethylcasein is inhibited by monodansylcadaverine, N-p-tosyl glycine, bacitracin and methylamine, the relative extent of inhibition depending on the respective concentrations of Ca2+, inhibitor and amine donor. 4. Bacitracin and methylamine, but not N-p-tosyl glycine, cause a dose-related inhibition of glucose-stimulated insulin release. 5. It is concluded that, in pancreatic islets, the Ca2+-responsive transglutaminase activity plays a critical role in the process of glucose-induced insulin release.
Two cases of rupture of the flexor tendons of the little finger associated with a fracture of the hook of the hamate bone are presented. The preoperative diagnosis had not been made. Excision of the fractured hook and repair of the tendons by a short graft from the palmaris longus in one case and by the transfer of the superficial flexor of the ring finger in the other case gave a good final result. The authors remark on the rarity of reports of this fracture in the literature, the frequent occurrence of nonunion and the two complications which are exceptional; rupture of the flexor tendons and compression of the deep branch of the ulnar nerve. The fracture is mainly encountered in sports that require the grasping of a handle (tennis, golf, hockey, squash). The diagnosis is often missed at the onset because of not using the correct X-ray positioning: special incidence for the carpal tunnel view and a 3/4 view with the wrist in 45 degrees of supination and forced radial deviation.
The authors report 19 cases of simple arthrolysis of the proximal interphalangeal joint for flexion rigidity. Their cases were limited to isolated lesions of the joint without any flexor or extensor tendon involvement. The technique is described, and the importance of postoperative physical therapy is stressed. The results in these cases, in contrast with those in complicated cases of rigidity, are very satisfactory. The etiology is primarily sprains and dislocations of the proximal interphalangeal articulation, immobilized for too long a time in flexion (in the so-called "functional position").
The authors used Hunter's technique to treat 16 cases of fixed-flexion deformity of the finger (with irreducible flexion of the joint greater then 70 degrees), secondary to lesions of the flexor tendons. The flexion deformity was corrected in 11 of the 16 cases, and active movement greater than 70 degrees was obtained in only 7 cases. Technical difficulties (particularly cutaneous problems), frequent complications, prolonged reeducation are the reasons that the indications for its use are exceptional, and why there is need for excellent cooperation by the patient.
To elucidate if there are alterations in insulin metabolic clearance in obesity under basal conditions, plasma insulin and C-peptide were measured in 22 obese patients and 8 normal subjects, and the plasma C-peptide to insulin molar ratio was used as an index of hepatic insulin extraction. In obese patients, the C-peptide to insulin molar ratio correlated indirectly with basal plasma insulin levels (r = 0.71; P less than 0.001), being low in the obese patients with higher insulin levels and within the normal range in obese patients in which insulin levels were similar to those of control subjects. It is suggested that hepatic insulin extraction is decreased in obesity, even under basal conditions, but this alteration is only manifested when plasma insulin levels are high.
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