Biomedical subjects

D J Handelsman

Publications and source records attributed to D J Handelsman.

156 records · Page 9Linked to original sources

PubMedDate not supplied

Diabetes in the Melanesian and Indian peoples of Fiji: a study of risk factors.

Epidemiological risk factor patterns for diabetes mellitus determined by hemoglobin A1 and fasting blood glucose criteria were compared in the biethnic (Melanesian and Indian) nation of Fiji. The 2 diagnostic criteria elicited essentially similar risk factor patterns in Indians but ranking of predictors was altered in Melanesians. By either criterion age was a dominant risk factor for diabetes in both ethnic groups with age2 a predictor in Indians of elevated hemoglobin A1 (chi 2 = 7.8, P less than 0.005) and fasting blood glucose (chi 2 = 25.3, P less than 0.0001). Age- and sex-adjusted prevalence of diabetes was higher in Indians than in Melanesians [RR = 2.5 (1.9-3.3)]. A positive family history was associated with increased risk of diabetes in both ethnic groups by the hemoglobin A1 criterion [pooled RR = 2.3 (2.0-2.6)] but was not significant in Melanesians under the fasting blood glucose criterion. A positive family history was a strong predictor of severe hyperglycemia in both ethnic groups. The relative risk for diabetes was greater in females [1.5 (1.2-9.1)], with no ethnic difference. There was no urban-rural difference in either ethnic group. The similar risk factor patterns for diabetes diagnosed by hemoglobin A1 and severe hyperglycemia suggest that elevated hemoglobin A1 may constitute a useful screening test for 'high risk' diabetic subjects.

Adult↗

PubMedDate not supplied

Testicular function and glycemic control in diabetic men. A controlled study.

We have investigated testicular function in 28 insulin-dependent diabetic men under the age of 50 years and 119 age-matched controls. Diabetics had reduced testicular volume, semen volume, total and total motile sperm output while plasma LH and FSH levels were elevated. Reduction in semen volume and impotence were more common in long-standing complicated diabetes. Glycosylated hemoglobin (GHb) levels were positively correlated with plasma LH levels (r = 0.46, p less than 0.02) but there was no direct correlation of glycemic control and spermatogenesis. The differences in testicular function were due to decreased spermatogenesis and could not be explained by other forms of testicular pathology or the presence of diabetic neurovascular complications. We conclude that the function of the hypothalamic pituitary testicular axis is impaired in diabetic men, that this impairment is at least partly related to the degree of preceding glycemic control and that multiple levels of the axis may be dysfunctional.

Adult↗

PubMedDate not supplied

The split ejaculate: assessment of fertility potential using two in vitro test systems.

Semen samples (split & whole ejaculates) were obtained from 12 normal men (group A) and 8 oligospermic infertile men with sperm concentrations of less than 20 x 10(6) sperm/ml (group B). All samples were evaluated by standard semen analysis, bovine cervical mucus penetration assay (CMPT), and, in all cases with sufficient sperm, in the human spermatozoa zona-free hamster in vitro penetration assay (SPA). In group A the motile sperm concentration was significantly higher in the ejaculated material of the first two contractions (fraction I or FI) than in the remainder of the ejaculate (fraction II or FII) (p less than 0.02). No significant differences were observed in sperm penetration into zona-free hamster ova or bovine cervical mucus by sperm from FI, FII or the whole ejaculate. Motile sperm concentration was significantly correlated with sperm penetration into bovine cervical mucus (r = 0.65, p less than 0.01), but not into zona-free hamster ova (r = 0.01 NS). In the samples collected by group B, the mean sperm concentration and motile sperm concentration were higher in the first (FI) than in the second (FII) fractions of the split ejaculate or the whole ejaculate (p less than 0.05). No significant differences were found among the FI, FII and the whole ejaculate semen samples for penetration of sperm into bovine cervical mucus. Sperm concentration and motile sperm concentration were significantly correlated with sperm penetration into bovine cervical mucus (r = 0.58, p less than 0.01 and r = 0.57, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Cervix Mucus↗

PubMedDate not supplied

Testicular function and fertility in men with homozygous alpha-1 antitrypsin deficiency.

Fertility and testicular function were studied in eight men with severe homozygous (Pi ZZ variant genotype) alpha-1 antitrypsin (AAT) deficiency. Age- and marital duration standardized fertility, clinical androgenic features, mean testicular volume, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and semen analysis were all normal apart from a reduction in semen volume. Mean plasma total and free testosterone were elevated and the percentage free testosterone reduced compared with age-matched, healthy fertile controls indicative of increased sex-hormone binding globulin (SHBG) levels representing an early marker for subclinical hepatic dysfunction associated with AAT-deficiency. In view of the preservation of normal fertility and testicular function despite chronic respiratory disease and premature death with deleterious AAT gene variants, it is proposed that the high prevalence of genetic polymorphism in the AAT protein may be maintained by the chronological asynchrony of the periods of maximal male reproductive activity (40 years) and the late onset (greater than 40 years) of symptoms in severe AAT deficiency rather than by any balance between reduced reproductive fitness of homozygotes and heterozygote advantage.

Fertility↗

PubMedDate not supplied

Hypothalamic-pituitary adrenal function in end-stage non-alcoholic liver disease.

Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n = 8) or who were unable to complete the investigations (n = 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 micrograms tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r = -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r = -0.597, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Androgen effects on bioactive and immunoreactive gonadotrophin levels during puberty in male baboons.

The effect of androgens on changes in circulating LH and FSH during pubertal development was examined longitudinally in a 3 year study in male hamadryas baboons. Baboon LH and FSH were measured by a species-specific radioimmunoassay and bioactive LH (B-LH) was measured by the mouse in vitro Leydig cell bioassay. Control baboons (n = 5) progressed normally through puberty. Eight baboons were castrated prepubertally; of these four received testosterone implants at the chronological age (CA) of clinical puberty (4.0 +/- 0.1 yr, mean +/- SEM). The timing of the postcastration rise in B-LH levels ranged between 1 and 15 months later (median 3.5 months) (CA 3.5 +/- 0.2 yr) thus supporting the hypothesis that central activation of gonadotrophins occurs at the time of puberty, independent of gonadal influences. Similar results were seen for immunoreactive-LH (IR-LH) and IR-FSH levels. IR- and B-LH levels continued to rise with age (P < 0.0003) in the untreated castrated baboons, associated with an increased LH B/I ratio. Administration of testosterone resulted in temporary suppression of B-LH, IR-LH and IR-FSH levels; however gonadotrophin levels subsequently rose with age despite increased testosterone levels. Thus the mechanisms initiating puberty involve both gonad-independent events as well as alterations in negative androgenic feedback sensitivity on gonadotrophin secretion.

Animals↗

PubMedDate not supplied

Development of the diabetes knowledge (DKN) scales: forms DKNA, DKNB, and DKNC.

The Diabetes Knowledge Assessment (DKN) scales were developed to meet a specific need for rapid and reliable knowledge assessment in diabetic patients. Item format and item selection from an initial pool of 89 items were determined by pilot-testing over 300 diabetic subjects. Reliability analysis of the resulting 40 multiple-choice items, with a further sample of 56 subjects, gave a Cronbach's alpha coefficient of 0.92. Parallel forms DKNA, DKNB, and DKNC, each of 15 items selected from the parent set, had alpha coefficients above 0.82 and correlated 0.90 with each other. A full clinical trial, using DKNA, DKNB, and DKNC in randomized order of presentation, was conducted with 219 subjects attending a 2-day diabetes education program. Overall DKN scores improved from 7.6 (51%) to 11.3 (75%). Analysis of variance confirmed that DKNA, DKNB, and DKNC were equivalent forms at pretest. Mean posttest scores on DKNB were lower than the other scales (P less than 0.001), but variances were equivalent for all three. A specific local change in the education program format was found to account for this discrepancy in the DKNB posttest mean. In situations where comprehensive assessment of diabetes knowledge would be time-consuming and unnecessary, these results indicate that rapid and reliable assessment is possible with a scale of only 15 validated items. The development of parallel forms of the scale extends the range of retesting possibilities for diagnosis and research.

Diabetes Mellitus↗

PubMedDate not supplied

Stereological evaluation of mouse prostate development.

A stereological study of the development of the mouse prostate was undertaken between the second week of postnatal life and maturity. The aim was to quantify the progressive changes in the size and areal density of the ventral prostate gland components during development. Male mice were studied at weekly intervals from days of life 15 to 49 for organ and body weights, ductal branching, diameters of ventral prostate ducts and lumen and volume densities of epithelium, lumen, and stroma. Ductal branch-tip numbers were maximal at 35 days of age, while prostate weights increased linearly with age and did not reach a plateau at 49 days. Prostatic glandular and luminal diameters both showed a continuous increase until day 49. At 5 weeks of age, there was a decrease in the volume density of prostatic epithelium accompanied by a simultaneous increase in the volume density of the lumen. This study indicates that prostate-branching morphogenesis is complete by the fifth week in mice but that further growth of the prostate continues due to the increase in ductal dimensions. Qualitatively, the ventral prostate in mice is fully mature by 5 weeks, and this histological maturity coincides with the completion of branching morphogenesis.

Animals↗

PubMedDate not supplied

Effects of liver disease and transplantation on the human prostate.

A major determinant of late-life prostate diseases is hormonal exposure during earlier life, but the effects of androgens in midlife on the human prostate have been little studied. In order to identify hormonal effects on the prostate during the long latent period of midlife, we studied the effects of chronic androgen deficiency on the prostate during midlife by examining men with severe liver disease before and after liver transplantation. Patients (n = 15, median 57, range 38-65 years old) with severe liver disease but no known prostate disease being evaluated for liver transplantation underwent 21 prostate ultrasound studies, 12 prior to and 9 after liver transplantation, with six men undergoing both studies. Controls were 42 prostate ultrasound studies (2:1 matching) from age-matched healthy men. Total- and central-prostate volumes were measured with a 7.5-MHz biplane transducer planimetrically at 2.5-mm intervals with a stepper device from base to apex of the prostate. Overall, total- and central-prostate volumes were not significantly different between patients with chronic liver disease before and after liver transplantation and age-matched healthy controls. This appeared to be due to a bimodal distribution, with most men (12 men, 17 studies) having smaller prostate volumes and a minority (3 men, 4 studies) having previously undiagnosed, macroscopic, benign prostatic hyperplasia. The reduction in prostate volume prior to transplantation was significantly correlated with severity of liver disease (Child-Pugh score). Before liver transplantation, prostate-specific antigen (PSA) concentrations were significantly lower and prostatic acid phosphatase increased, and both were normalized after liver transplantation. Plasma testosterone concentrations were decreased before transplantation and remained low after transplantation. Sex hormone-binding globulin level was significantly elevated before and reduced to subnormal after liver transplantation. Estradiol concentrations were unchanged by liver disease or transplantation. We conclude that prostate volumes, particularly that of the central zone, are usually reduced by the functional androgen deficiency of chronic liver disease and tend to be restored toward normal by liver transplantation, depending on the degree of rectification of circulating plasma testosterone concentrations. Prostate glands with established benign prostatic hyperplasia may be less responsive to these hormonal changes.

Adult↗

PubMedDate not supplied

Androgen receptor gene polymorphism and prostate zonal volumes in Australian and Chinese men.

Prostate diseases are age and androgen dependent. The evolution of clinically overt pathology requires decades of exposure to adult male levels of circulating testosterone, but the precise relationship between age and androgen circulation remains poorly understood. A marker of integrated androgen action over prolonged periods would therefore be a valuable tool for clinical and epidemiologic research into the origins of prostate disease. In order to evaluate these 2 factors, we have studied the CAG-repeat length polymorphism of the androgen receptor gene and the size of the total, central, and peripheral zones of the prostate, estimated by planimetric ultrasound in 2 populations with widely different susceptibility to death from invasive prostate cancer. From a larger epidemiologic study of the effects of ethnicity and migration on the origins of prostate disease, a nested-case control study was undertaken with 50 Chinese men living in Yue Yang, China and 50 non-Chinese men living in Sydney, Australia. All men had undergone planimetric transrectal prostate ultrasound together with blood sampling to determine CAG-repeat length by polymerase chain reaction and immunoassay of plasma testosterone, estradiol, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), and prostate-specific antigen (PSA). Australian men had larger central (7.9 +/- 0.4 vs 3.3 +/- 0.3 mL) and total (29.8 +/- 1.2 vs 25.5 +/- 1.1 mL) but not peripheral (22.0 +/- 0.9 vs 22.2 +/- 0.8 mL) prostate volumes compared with Chinese men. Even after adjustment for differences in body size (the Australian men were taller and heavier), the central-zone volume remained lower by approximately 50% in Chinese men (P < 0.001), whereas testis and total-prostate volumes were no longer significantly different. The length of CAG repeats was no different between Australian men (22.5 +/- 0.5 repeats) and Chinese men (22.5 +/- 0.5 repeats), and there was no correlation within or between populations in CAG repeats or any measure of prostate volume or hormones. DHT concentration was 20% lower in Chinese men compared with Australian men (1.6 +/- 0.1 vs 2.0 +/- 0.1 nmol/L, P = 0.005), a difference that persisted after age adjustment (P = 0.039) but that was removed by adjustment for differences in total-prostate size (P = 0.12). Blood testosterone, estradiol, SHBG, and PSA concentrations were not different between the 2 populations. Hence, the hypothesis is refuted that the CAG repeat polymorphism in the androgen receptor gene (within the nonpathologic range) and the central-prostate zone volume might be markers of long-term androgen sensitivity. Whether either factor alone may constitute a marker of androgen sensitivity remains to be established by other means, and a long-term marker of integrated androgen action suitable for clinical and epidemiologic research is still lacking.

Adult↗

PubMedDate not supplied

The development of the baboon prostate: ultrasound methodology, modelling, and natural history.

In order to evaluate the potential of ultrasound for serial, nontraumatic estimation of prostate size in the hamadryas baboon (Papio hamadryas), we adapted the technique of planimetric ultrasound to study a captive-bred colony of 30 male baboons (median age 8.4 years, range 3.3-17 years) including 4 long-term castrates. Most (19) were studied on another two occasions (at 33-and 43-day intervals) to estimate reproducibility of the prostate size (dimensions, volume) measurement. Prostatic dimensions were measured with a B-mode sector ultrasound using a 7.5-MHz transrectal transducer by planimetry at 2.5-mm steps from base to apex as well as the maximum three dimensions of the prostate. The planimetric volume estimate was reproducible (intraclass coefficient 0.81) with coefficient of variation (CV) of 24.3% for all, and 16.0% for mature, baboons. The prostate dimensions were also reproducible (CVs 7.9-13.4%). Prostate volume estimates based on the general ellipsoidal model were reasonably reproducible (19.9% for all, 12.9% for mature) but were biased in relationship to the planimetric volume (0.57 +/- 0.19, P = 0.004). Using the independent estimates of prostate volume and dimensions, we developed an empirical power-function model of prostate shape based on the generalized ellipsoidal model that was robust and unbiased (-0.07 +/- 0.15, P = 0.64) with respect to the planimetric volume. This model provides a simpler and accurate formula for prostate volume based on its three maximal dimensional measurements. The natural history of prostate growth in the hamadryas baboon was illustrated by sigmoidal correlations with age (ED50 = 6.0 years, plateau ED95 = 8.3 years), body weight (ED50 = 14.6 kg, ED96 = 16.1 kg), and testis volume (ED50 = 7.8 ml, ED95 = 18.4 ml). Between-animal variability among mature baboons was greater for prostate weight (27%) than body weight (10%), raising the possibility that a subgroup of these baboons may develop spontaneous age-related prostatic hyperplasia. These findings suggest that ultrasonic evaluation of prostate size in the hamadryas baboon may constitute a suitable model for spontaneous benign prostatic hyperplasia and for experimental studies of prostate growth, development, and hormonal regulation.

Animals↗

PubMedDate not supplied

The effects of recombinant FSH on testosterone-induced spermatogenesis in gonadotrophin-deficient (hpg) mice.

In order to clarify the mechanism of synergism between follicle-stimulatory hormone(FSH) and testosterone (T) in the hormonal regulation of spermatogenesis, we studied the effects of recombinant human FSH (rhFSH) on the induction of spermatogenesis by testosterone in congenitally gonadotropin-deficient hpg mice. Weanling (day 21) homozygous hpg mice were administered daily subcutaneous injections of 1, 5, or 10 IU of rhFSH alone or in combination with a subdermal testosterone implant until day 70 of age. Spermatogenesis was quantitated by stereological estimation of germ cell populations and Sertoli cells as well as measurement of diameter of seminiferous tubules and their lumina in perfusion-fixed testes and by counting homogenization-resistant condensed testicular spermatids. Recombinant human FSH alone increased the absolute numbers of spermatogonia (x3.5-fold) and spermatocytes (x3-fold) compared with untreated hpg mice but did not significantly increase Sertoli cell numbers or form any condensed spermatids or tubular lumen. Relative to Sertoli cell numbers, rhFSH alone increased populations of spermatogonia (x2-fold) and spermatocytes (x2-fold). The addition of T to rhFSH further increased the absolute numbers of spermatogonia (x5-fold) and spermatocytes (x3.5-fold) compared with untreated hpg mice as well as increasing tubular diameter and forming tubular lumina. In addition administration of T allowed the completion of spermatogenesis in the presence of intratesticular T levels that were approximately 2% of non-hpg controls. All effects of the FSH + T combination were however no greater than the effects of the equivalent dose of T alone. The present study therefore indicates that rhFSH alone increases proliferation of premeiotic spermatogenic cells but has no effect on the completion of spermiogenesis or on Sertoli cell maturation. Furthermore we were unable to identify any additive effects of FSH with T in the hormonal regulation of spermatogenesis in the hpg mouse. This suggests that FSH or T both may stimulate initial spermatogenic development, but only T can complete spermiogenesis.

Animals↗