Frederick T. Murray

Serum aminoglutethimide levels: studies of serum half-life, clearance, and patient compliance.

Serum aminoglutethimide was measured in 13 women with mastastatic breast carcinoma who were treated with 1.0 Gm aminoglutethimide and 40 mg hydrocortisone daily over a period of one year. Serum concentrations of aminoglutethimide were used to evaluate drug half-life, clearance, and patient compliance. Mean half-life and clearance rates were determined in six patients. The mean half-life of aminoglutethimide prior to therapy was 13.3 +/- 2.65 (S.D.) hours and fell significantly (P less than 0.01) to 7.3 +/- 2.14 hours after six to 32 weeks of therapy. The mean clearance rate prior to therapy was 2.58 +/- 0.33 (S.D.) 1./hour and increased significantly (P less than 0.01) to 5.29 +/- 1.4 1./hour after therapy. The mean serum concentration was 11.5 +/- 3.6 microgram/ml in seven patients. No significant variation of mean aminoglutethimide concentration from the overall mean was noted during the course of therapy. We conclude that serum aminoglutethimide concentrations are useful in evaluating patient compliance. Our data also suggest that aminoglutethimide increases its own metabolism, which may explain the absence of toxicity symptoms seen late in the treatment period.

Gonadal dysfunction in the spontaneously diabetic BB rat

Diabetes which occurs spontaneously in the BB Wistar rat is associated with reduced fertility, predominantly in breeding males. In the first month of diabetes, there is a significant (p less than 0.05) reduction in serum testosterone associated with a transient decrease of serum LH and the accumulation of lipid in Leydig cells. Between one and three months of diabetes, there is an increase in both serum testosterone and LH and a further deposition of lipid droplets in Leydig cells. From three to six months of diabetes, there is a reduction of serum testosterone similar to age-matched controls, but high serum LH levels persist. Similar levels of LH and testosterone are noted after six months of diabetes, and all BB rats show marked changes in seminiferous tubules. These morphological changes in tubules consist of increased tubular wall thickness, severe germ-cell depletion, and Sertoli-cell vacuolization. Similar morphological changes of testes associated with generalized atrophy are noted in all control rats after 16 months of age. Decreased fertility in the BB rat appears to be associated with a primary disorder of Leydig cells, which precedes changes in seminiferous tubules consistent with accelerated aging. Preliminary data in impotent diabetic men suggest that the BB rat may be a valuable model for investigating human diabetic impotence and infertility.

Reduced sensitivity of penile mechanoreceptors in aging rats with sexual dysfunction

Male sexual activity gradually declines with age in most mammalian species and may be associated with a decrease in vibrotactile sensitivity of the penis. This study was designed to determine if the penile mechanoreceptors in aging rats exhibit reduced sensitivity to vibrotactile stimuli. Electrophysiological and behavioral data was obtained from mature adult (9 months) and old (23 months) rats. Single penile mechanoreceptor afferent fibers from aging animals exhibited a decrease in the ability to transduce high-frequency vibratory stimuli when compared to afferents from mature adult animals. In addition, there was a reduction in single-fiber and sensory nerve conduction velocity. Copulatory performance was reduced in the aging animals as determined by the inability to ejaculate with a receptive female. The results of this study demonstrate that the male rat exhibits an age-related decrease in penile vibrotactile sensitivity mediated by mechanoreceptor afferents which may be partly responsible for the decrease in parameters of sexual activity.

Reliability and validity of the Florida Sexual History Questionnaire

The Florida Sexual History Questionnaire (FSHQ) is a brief 20-item questionnaire designed to assess male sexual dysfunction. The validity and reliability of the scale were examined in 33 diabetic impotent males and 58 nondiabetic, age-equivalent nonimpotent males. The FSHQ was found to have high internal consistency and split-half reliability and significantly discriminated between nonimpotent and impotent subjects. Among diabetic impotent subjects, some of the test items were correlated significantly with physiological measures of sexual functioning. However, the FSHQ failed to discriminate between diabetics diagnosed as having organic or psychogenic impotence. This latter finding is discussed within the context of recent suggestions that it may not be possible to draw a clear dichotomy between organic and psychogenic impotence.

An evaluation of the minnesota multiphasic personality inventory as a discriminator of primary organic and primary psychogenic impotence in diabetic males

The ability of the MMPI to discriminate between primary psychogenic impotence and primary organic impotence in males with diabetes mellitus was assessed. In order to provide the MMPI with the optimal situation to discriminate between the two groups, we attempted to form a homogeneous sample in terms of physical conditions. Thirty impotent diabetic males were classified as primary organic or primary psychogenic based on nocturnal penile tumescence data. Beutler et al.s MMPI decision rules yielded a 63% misclassification of the two groups. Possible explanations for the lack of discriminative power of the MMPI with this sample of diabetic males were discussed in relation to previous findings. The power of nocturnal penile tumescence to classify men as having primary organic or primary psychogenic impotence was examined with reference to other vascular and endocrine variables.

Assessment of proteinuria and neuropathy in the nonimmunosuppressed BB diabetic rat after abdominal intratesticular islet transplantation.

Only limited studies are available that assess diabetic complications following islet cell transplantation. Our objectives were to quantitate urine total protein, sural nerve morphometry, and sexual function in the diabetic BB/WOR male rat following islet cell transplantation into the abdominal testis. Success of islet cell transplantation was determined by nonfasting, morning, twice-weekly serum glucose and 12-hr fasting glucose, total glycosylated hemoglobin, and HbA1c after six months of diabetes and prior to death. Results showed that 9 of 16 rats were transplanted successfully for a period of at least six months. Pretransplant glucose was 21.9 +/- 4.67 (SD) mM/L and posttransplant glucose was 6.44 +/- 72 mM/L. The 12-hr fasting glucose ranged from 4.61 to 9.28 mM/L in animals prior to death, and glycosylated hemoglobins were not different from controls. Total urinary protein was significantly (P < 0.01) less than untreated diabetic rats (5.66 +/- 1.96 vs. 16.6 +/- 3.7 mg/24 hr) and not different from controls. Penile reflexes and serum testosterone remained normal in islet cell-transplanted animals. Sural nerve morphometry was normal, with 29.2% fewer abnormalities (paranodal swelling, paranodal demyelination, myelin wrinkling, Wallerian degeneration, and segmental demyelination) than untreated diabetic BB/WOR rats. We conclude that abdominal, intratesticular islet transplantation normalizes fasting blood glucose and glycosylated hemoglobin. In addition, the improvement in metabolic control at six months of diabetes was associated with normal total urinary protein, sural nerve morphometry, and sexual function.

Sertoli Cells Maintain Spennatid Vibility in Vitro

It is clear that intimate structural interactions between Sertoli cells and developing germ cells are essential for the completion of intratesticular germ cell maturation. Although there is experimental evidence suggesting that Sertoli cells may enhance the viability of some germ cells in uitrd and that germ cells may have effects on Sertoli cell physiology,*J the demonstration of specific SertoWspermatid interactions in vitro is lacking. Likewise, the mechanism(s) involved in the interactions is unknown. A longstanding concern in trying to interpret data from Sertoli cell experimentation in uitro is that, in culture, the cell loses its unique differentiated phenotype and possibly its unique spermatogenic-related funct i ~ n . ~ ~ ~ Recently, Byers et ~ 1 . ~ showed that when Sertoli cells were plated on a reconstituted basement membrane (Matrigel), they demonstrated in vivo-like structural polarity and performed polarized functions in virro. Using this substrate, we have developed a coculture method to further evaluate interrelationships between Sertoli cells and spermatids, assuming that the more differentiated Matrigel-supported Sertoli cell may express activity heretofore unrecognized and provide an appropriate environment for spermatid survival.

The integrated gonadotrophin test.

Excerpt The pulsatile nature of luteinzing hormone (LH) and, to a lesser extent, follicle-stimulating hormone (FSH) secretion requires that integrated gonadotrophin concentrations be ascertained to...