Search PubMed⌕ Search

Biomedical subjects

D J Handelsman

Publications and source records attributed to D J Handelsman.

At least 145 records · Page 8Linked to original sources

The effect of salicylates on nonenzymatic glycosylation and thermal stability of collagen in diabetic rats.

The effects of glucose on the nonenzymatic glycosylation and thermal rupture time of rat tail collagen were examined by (1) in vitro incubation of collagen fibers in glucose and (2) in vivo in diabetic rats. In vitro, glucose caused a dose-dependent rise in both nonenzymatic glycosylation and thermal rupture time and there was a good correlation between these two parameters (r = 0.68, P less than 0.0001). Aspirin, a known inhibitor of nonenzymatic glycosylation, was effective in preventing the glucose-induced rise in nonenzymatic glycosylation and thermal rupture time when present at concentrations of 0.78, 1.56, and 3.12 mM. Sodium salicylate at concentrations of 1.56 and 3.12 mM was also effective. In vivo, the nonenzymatic glycosylation and thermal rupture time of collagen fibers were both increased by 2-3-fold in rats with streptozotocin-induced diabetes of 4 wk duration. Aspirin or sodium salicylate treatment for 4 wk (240 mg/kg/day) from the onset of diabetes was able to prevent the rise in thermal rupture time without affecting nonenzymatic glycosylation of collagen or glycosylated hemoglobin levels. Aspirin or sodium salicylate treatment did not have detectable effect on properties of collagen in normal rats. The in vitro findings are consistent with the hypothesis that nonenzymatic glycosylation leads to the increased thermal stability of collagen fibers. The significance of nonenzymatic glycosylation in vivo is less certain, as thermal rupture time can be altered independently. The action of aspirin and sodium salicylate in vivo suggests new therapeutic options in the prevention and treatment of diabetic complications.

Animals↗

Testicular function after renal transplantation: comparison of Cyclosporin A with azathioprine and prednisone combination regimes.

Testicular function was assessed in 24 men after renal transplantation who were on either Cyclosporin A (CSA) (8 men) or a combination of azathioprine and prednisone (AZP) (16 men) as immunosuppressive therapy. The different regimes were not associated with any differences in clinical or hormonal (LH, FSH, prolactin, testosterone, estradiol) indices of testicular function although adrenal androgen (dehydroepiandrosterone sulphate) was suppressed in prednisone-treated men. Overall, however, poor graft function was associated with abnormal testicular function. Renal allograft function rather than immunosuppressive regime was the major determinant of gonadal function.

Adult↗

The compliance of diabetic patients: relationship between subjective assessment by physicians and objective measurement of patient performance.

During a survey period of 9 months, diabetic patients attending an outpatient clinic were asked routinely by the nursing staff to produce their home urine/glucose monitoring charts and diet charts. If they could not do so, the importance of bringing these charts was explained and they were instructed to bring their charts at subsequent visits. In addition, the individual responses of 109 consecutive patients were monitored as index cases. The physicians of these 109 patients were asked to grade each patient according to their estimate of the patient's compliance. This subjective rating was correlated with the actual performance of the patients in bringing charts. During the survey the overall number of patients attending the clinic who brought urine/blood charts increased from 31% to 59%. The corresponding figures for diet charts were 6% and 21%. Before intervention, the group rated "high compliance" was more likely than the "low compliance" rated group to bring urine/glucose charts. However, after adjustment for this baseline difference the subsequent performances of the high and low rated groups were comparable. These two groups of patients also performed similarly with respect to diet charts. It is concluded that patients judged subjectively to have poor compliance were able to modify their behaviour similarly to those assessed as having good compliance.

Adult↗

The thermal stability of collagen in diabetic rats: correlation with severity of diabetes and non-enzymatic glycosylation.

The thermal stability of collagen fibres from rat tail tendon was studied in both normal and diabetic rats. Results were correlated with the age of the animals, glycosylated haemoglobin level and the degree of non-enzymatic glycosylation of the collagen. Age was found to be the most important single determinant of the thermal rupture time of collagen fibres (r = 0,87, p less than 0.005). Thermal rupture time was also increased in diabetes and showed good correlation with glycosylated haemoglobin (r = 0.69, p less than 0.005) and non-enzymatic glycosylation of collagen (r = 0.51, p less than 0.005). The correlation of glycosylated haemoglobin level and thermal rupture time was significant, independent of age and non-enzymatic glycosylation of collagen. Experiments in vitro showed that incubation of collagen fibres with glucose increased the thermal stability of collagen. These results demonstrated an independent effect of severity of diabetes on the physical properties of collagen. The role of non-enzymatic glycosylation in causing the changes in collagen properties in diabetes remains to be fully elucidated.

Aging↗

Hypogonadism and massive testicular infiltration due to amyloidosis.

We report a case of infertility with bilateral testicular enlargement and hypogonadism due to amyloidosis. Testicular biopsy revealed complete replacement with amyloid and subsequent investigation demonstrated primary hypogonadism with marked elevation of gonadotropins, azoospermia, mild renal failure and lack of progression of generalized amyloidosis during 2 years.

Adult↗

Testicular damage after radioactive iodine (I-131) therapy for thyroid cancer.

Testicular damage was evaluated in twelve men by determination of sperm counts, serum FSH, LH, and testosterone up to 3 1/2 years after treatment with radioactive iodine (131I) therapy for thyroid cancer. Dose-dependent spermatogenic damage with elevation of serum FSH was evident. Full recovery in one and partial recovery in another patient was documented during 2 1/2 years of follow-up. Serial study in two patients documented a small but significant effect of 50 mCi 131I on serum FSH levels and clinically important effects appear to be restricted to men having multiple doses totalling over 100 mCi.

Adult↗

Prevalence, testicular function and seminal parameters in men with sperm antibodies.

A prospective survey of 289 unselected men, attending a male infertility clinic (200 subjects) or as donors presenting for an artificial insemination programme (89 subjects) was performed. High titres of sperm agglutinating antibodies (greater than 1/32) were present only in a group of (6.5%) of infertile men but not in volunteer donors. Low titres occurred with similar frequencies (12%) in both groups. The sperm immobilizing antibody test was less sensitive and more specific but of no additional diagnostic benefit. Patients with high titres of sperm antibodies had evidence of testicular damage with decreased testicular volumes, elevated serum FSH and LH levels and reduced sperm density and motility whereas low titres were not associated with any testicular or seminal pathology. These data suggest a sub-group of infertile men have evidence of spermatogenic damage and impaired sperm function associated with high titres of sperm antibodies. Immunologic infertility in these men may reflect either an underlying autoimmune orchitis or a secondary immune reaction following testicular damage of various causes.

Adult↗

Heterozygote detection in congenital adrenal hyperplasia.

Detection of heterozygote carriers for congenital adrenal hyperplasia by use of a modified tetracosactide (a synthetic corticotropin) stimulation test with prior overnight dexamethasone suppression proved to have a diagnostic accuracy of 95%. Discrimination of heterozygotes from normals was best when we used a criterion based on the ratios of 17 alpha-hydroxyprogesterone to cortisol at baseline and at 30 min after intravenous administration of 250 micrograms of tetracosactide.

17-alpha-Hydroxyprogesterone↗

Dexamethasone suppression of adrenocortical function.

To investigate the potency of dexamethasone in suppressing adrenocortical function, we gave various evening doses to laboratory staff members. Plasma corticotropin, cortisol, and dehydroepiandrosterone sulfate concentrations were measured the following day, to quantitate the degree of suppression after both short- and long-term treatments. We found that the minimum amount for effective suppression was 1 mg for a single evening dose, 0.5 mg per day for a long-term evening dose. On these regimens plasma corticotropin and cortisol were consistently suppressed, but plasma dehydroepiandrosterone sulfate was suppressed only with long-term treatment.

Adrenal Cortex↗

Testicular function after renal transplantation.

Gonadal function was assessed in seventeen adult male renal transplant recipients, with well established good homograft function, for a mean of 4.9 years. Patients were assessed clinically and by measurement of basal concentrations of FSH, LH, prolactin, testosterone and oestradiol, FSH and LH responses to bolus injections of LHRH and semen analysis. Retrospectively all had symptoms consistent with marked hypogonadism prior to transplantation but in nine out of sixteen this was reversed with transplantation. Residual hypogonadism was evident in seven of sixteen patients and correlated with duration of haemodialysis longer than 1 year (P less than 0.01). Even among patients with clinically normal gonadal function, defects in the hypothalamic--pituitary--testicular axis remained. Elevated basal serum FSH, excessive FSH responses to LHRH and lowered basal serum testosterone were found. In the group with residual hypogonadism more marked changes, including elevated basal LH and excessive LH responses to LHRH, were also found. Fertility was recorded in two men on three occasions since transplantation. Sperm counts were normal in five and abnormal in four patients. Testicular volume and sperm density were inversely correlated with basal and stimulated FSH and LH levels.

Adult↗

Clinical trial of an aldose reductase inhibitor in diabetic neuropathy.

A single-blind, nonrandomized, placebo crossover clinical trial of an aldose reductase inhibitor, Alrestatin (AY 22, 284) was performed over a 4-mo period in nine patients with diabetic peripheral neuropathy. Most patients had subjective benefit, but objective measures of conduction were essentially unchanged. Substantial toxicity was evident, particularly photosensitive skin rash.

Action Potentials↗

Detection of varicocele by radionuclide blood-pool scanning.

Varicocele is a common and treatable cause of male subfertility. The authors describe a new technique for varicocele detection using radionuclide blood-pool imaging of the scrotum. Of 83 patients studied, 29 had a clinically palpable varicocele of various sizes, and 26 of them were demonstrated by this technique. Two of the false negatives were bilateral varicoceles. In the 41 patients with no clinically detectable varicocele, there were 10 positive and 10 marginally asymmetric studies. The results indicate that this technique detects unilateral varicoceles with high sensitivity, including some which are subclinical. There may be significant implications for treatment of infertility.

Adult↗

Testicular size: the effects of aging, malnutrition, and illness.

Paired testicular volumes and weights, as well as age, height, and weight, were recorded from a series of 1056 consecutive necropsies on adult males ranging in age from 18 to 96 years. These data were analyzed to examine the effects of age, nutritional state (standardized body weight), and illness on testicular size. Testicular volume and weight were related by a constant density of 1.038 g/ml, regardless of testicular size, age or illness. Mean testicular volume was correlated with height (r = 0.470), weight (r = 0.504), body surface area (r = 0.549) and standardized body weight (r = 0.152). Advancing age, malnutrition, alcoholism, malignancy, and a chronic, terminal illness were each individual risk factors for reduced testicular size, whereas diabetes, narcotic or other drug usage, and pelvic injury were not associated with reduced testicular volume. Since advancing age, reduced standardized body weight, and some disease states were all associated with diminution of testicular size, the interaction of age, malnutrition, and illness on testicular size were examined by statistical modeling, using multivariate logistic regression and covariance analysis. The associations of alcoholism, malignancy, and chronic, terminal illness with decreased testicular volume were independent of aging or nutritional state. The effects of chronic, terminal illness were mostly explained by the concurrent effects of reductions in standardized body weight (malnutrition). After exclusion of men with diseases shown to be associated with decreased testicular size, he specific effects of age alone demonstrated a reduction in testicular volume only in the 8th decade of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Glycosylated hemoglobin as an index of the prevalence and severity of diabetes in biethnic Fiji.

Glycosylated hemoglobin was compared with fasting blood glucose as a screening test for diabetes mellitus and as an index of the severity of diabetes in biethnic (Melanesian and Indian) Fiji. Age-adjusted diabetes prevalence in the test sample was higher in Indians by either criterion. According to the hemoglobin A1 criterion, Melanesians had prevalence rates of 8.2% (males) and 15.8% (females) compared to 17.0% (males) and 24.3% (females) in Indians. In contrast, fasting blood glucose criteria (WHO) gave higher rates in each group. Hemoglobin A1 levels were higher overall in Indians and females. The predictive value of an elevated fasting blood glucose test for an elevated hemoglobin A1 was 20.0% in Melanesians and 60.7% in Indians while that of a normal fasting blood glucose test for a normal hemoglobin A1 was 89.4% in Melanesians and 89.3% in Indians. The proportion of Indians with elevated hemoglobin A1 who were severely hyperglycemic was almost 7 times higher (40.9% vs. 5.8%) than that of Melanesians. The ethnic difference in the predictive value of fasting blood glucose levels for hemoglobin A1 levels appears to be related to the greater severity of hyperglycemia of diabetic Indians compared to diabetic Melanesians. Hemoglobin A1 levels provide information on both the qualitative as well as quantitative differences in diabetes between ethnic groups.

Adult↗