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Biomedical subjects

B Gonen

Publications and source records attributed to B Gonen.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Effect of hyperglycemia and the aldose reductase inhibitor tolrestat on sural nerve biochemistry and morphometry in advanced diabetic peripheral polyneuropathy. The Tolrestat Study Group.

Tolrestat is a well tolerated nonhydantoin aldose reductase inhibitor that has been reported to improve nerve conduction in diabetic animals and humans. Its effects on nerve biochemistry and structure have not been studied in patients with diabetic neuropathy. Patients with advanced diabetic neuropathy treated with long-term open-label tolrestat were randomly assigned to continuation on drug treatment or to placebo-controlled drug withdrawal for 12 months. At the end of this period, sural nerve biopsies were obtained for measurement of glucose, sorbitol, and fructose content, and for detailed morphometric analysis. Tolrestat ameliorated the glucose-mediated increase in sorbitol and fructose in sural nerve tissue. No statistically significant differences in nerve morphometry emerged between the two groups; however, both treatment groups exhibited increased nerve-fiber regeneration and normalization of axo-glial dysfunction and segmental demyelination following long-term tolrestat treatment. These findings are similar to those previously reported in a placebo-controlled sequential nerve biopsy study with the aldose reductase inhibitor sorbinil. Thus tolrestat is a biochemically effective aldose reductase inhibitor in human diabetic nerve with potential therapeutic efficacy for diabetic neuropathy.

Aldehyde Reductase↗
PubMedDate not supplied

Withdrawal of the aldose reductase inhibitor tolrestat in patients with diabetic neuropathy: effect on nerve function. The Tolrestat Study Group.

A double-blind, placebo-controlled clinical trial was conducted to study the effects of discontinuing tolrestat, an aldose reductase inhibitor, on peripheral sensorimotor diabetic neuropathy. After an average of 4.2 years of continuous tolrestat use, 372 patients were randomly assigned to either placebo or continued tolrestat therapy and were followed for 52 weeks. After 3 months, patients who perceived worsening of symptoms of neuropathy were allowed to switch once to the alternate treatment group while maintaining the double-blind. Patients assigned to placebo had significant deterioration in motor nerve conduction velocity (MNCV) while those maintained on tolrestat did not (p < 0.05). The 28 patients who were randomly assigned to tolrestat and elected to switch to placebo had a significant deterioration in MNCV while the 36 assigned to placebo who switched to tolrestat had a significant improvement (p < 0.05). Treatment differences in favor of tolrestat were observed for sensation in the toes as well as for pain (p < 0.05). These data indicate that withdrawal from long-term treatment with tolrestat has a detrimental effect on several measures of diabetic neuropathy, whereas continuation of treatment is associated with stabilization of these measures, suggesting a continued role for polyol pathway activity in late neuropathy.

Aldehyde Reductase↗
PubMedDate not supplied

Hyperinsulinism complicating control of diabetes mellitus by an artificial beta-cell.

Serum free insulin concentrations were measured in diabetic subjects given insulin intravenously by a glucose-controlled insulin infusion system ("closed-loop" artificial beta-cell) in two experimental situations: hourly during the day while given their usual diet and at short intervals after administration of a standardized test meal. Three of four subjects showed sustained hyperinsulinism when compared with matched controls during a day on their usual diet. In two of the subjects, the insulin levels also exceeded those seen in those subjects on their usual dose of subcutaneous insulin. The glucose levels were not completely normalized in the three hyperinsulinemic subjects, and the insulin levels were significantly correlated with plasma glucose levels. After the test meal, all six diabetic subjects studied showed a delayed rise in insulin levels, when compared with six normal subjects, followed by an abrupt rise in insulin levels to peak levels more than seven times those seen in normal subjects. We conclude that significant hyperinsulinism may accompany feedback-controlled intravenous insulin administration. This should be considered in interpreting studies done with such systems, and in design of control algorithms for future systems.

Basophils↗
PubMedDate not supplied

Effect of filter setting on the electromyographic parameters of muscles contracting to fatigue.

The effects of various filter settings on the electrophysiological behavior of the development of muscular fatigue were studied. Eleven healthy volunteers were examined during isometric contraction of biceps brachii and rectus femoris against a constant load until fatigue occurred. The electrical activity was taped and computer processing was carried out at the basic setting of 15-5000 cycles and at low (15-200 Hz) and high (200-5000 Hz) frequence filter. The results support the hypothesis that in the low range of frequencies there is a high density of large slow motor units, while in the high range of frequencies there are numerous small fast motor units.

Action Potentials↗