Edward R. Smith

Treatment of menopausal hot flashes with transdermal administration of clonidine

A randomized prospective double-blind study was performed to evaluate the efficacy of a transdermal therapeutic system delivering clonidine in the treatment of menopausal hot flashes. Frequency, severity and duration of the flushing attacks before and during the 8-week treatment period were evaluated. The reduction in the number of hot flashes was highly significant in patients receiving the clonidine transdermal therapeutic system. On subjective comparison of flushing attacks before and during treatment, of the 15 patients who received the clonidine transdermal therapeutic system, 80% reported fewer hot flashes; 73% a decrease in severity; and 67% a decrease in duration. Among the 14 patients who were treated with placebo only, 36% reported fewer hot flashes; 29% a decrease in severity; and 21%, shorter duration (frequency, p less than 0.04; severity, p less than 0.04; and duration, p less than 0.03). Reported side effects were minimal, and no significant effect was observed on blood pressure or pulse rate. Transdermal clonidine therapy had no effect on the pulsatile luteinizing hormone secretion.

Physical, metabolic, and hormonal effects on men of long-term therapy with medroxyprogesterone acetate

Twenty-three men were treated with injectable medroxyprogesterone acetate (MPA) for sex-offending behavior. The physical, hormonal, and metabolic effects were monitored. The patients had significant (P less than 0.001) weight gain and increases (P less than 0.0001) in systolic blood pressure independent of weight gain. MPA therapy decreased testosterone (P less than 0.0001), luteinizing hormone (P less than 0.005), and testicular size (P less than 0.001), but not follicle-stimulating hormone. MPAs suppression of total sperm count was not consistent, but MPA significantly reduced sperm motility (P less than 0.001) and percent normal morphology (P less than 0.005). Statistically insignificant increases in insulin response without changes in glucose tolerance occurred in all patients, but only one patient developed overt diabetes mellitus. Three men developed gallstones, but none had significant changes in liver function. Patients receiving high-dose MPA therapy should be carefully monitored for blood pressure changes, diabetes mellitus, and gallbladder dysfunction.

Plasma and pituitary concentrations of LH, FSH, and Prolactin in aging C57BL/6 mice at various times of the estrous cycle ☆

Plasma and pituitary concentrations of LH, FSH, and prolactin (Prl) were measured by RIA in 2-4, 7-8, 12-13 and 16-20 month-old female C57BL/6 mice during various stages of the estrous cycle. In general, gonadotropin concentrations tended to rise with increasing age and Prl concentrations tended to decline. Pronounced differences existed, however, between the four age groups around the time of the LH surge. LH secretion declined progressively with increasing age at 21.00 hr of proestrus. Aged mice, 16-20 months old, had significantly lower plasma concentrations of LH than did other age groups. It is not known whether age-related changes in the ovary, pituitary, or hypothalamus are largely responsible for differences in the secretion of LH, FSH and Prl in aging C57BL/6 mice.

Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to formaldehyde

A battery of monitoring tests that could indicate genetic damage was used to investigate occupational formaldehyde exposure in a population of a hospital autopsy service workers. 11 exposed individuals and 11 matched controls were evaluated for sperm count, abnormal sperm morphology and 2F-body frequency. Subjects were matched for sex, age and customary use of alcohol, tobacco and marijuana. Additional information was collected on health, medications and other exposures to toxins. 10 subjects were employed for 4.3 months (range 1-11 months) prior to the first sample and 1 was employed for several years. Formaldehyde exposures were episodic but with a time weighed average between 0.61 and 1.32 ppm (weekly exposure range 3-40 ppm X h). Exposed and control subjects were sampled 3 times at 2-3 month intervals. Sperm morphology was also evaluated in B6C3F1 mice after 5 daily oral doses of 100 mg/kg formalin. No increase in abnormal morphology was detected in the treated animals. In humans, no statistically significant differences were observed between the exposed and control groups for the observed variables. Reduced sperm count correlated with increased abnormal morphology and 2F-body frequency in the exposed group but not in the control group. Evaluation of the impact of incidental exposures suggests a reduced count with marijuana use and increased abnormal morphology with medications used by controls. No effects on sperm were seen from formaldehyde or its metabolites in this population after occupational exposure, nor in mice following a high acute exposure. It is possible that minor effects might have occurred. The lack of an effect in this study may be due to a lack of statistical power to detect effects at this exposure level.

The impact of structured student debates on critical thinking and informatics skills of second-year medical students.

Among its many facets, the field of medical informatics encompasses the use of technology to access and manage scientific information. The Association of American Medical Colleges (AAMC), through the Medical Informatics Objectives of the Medical School Objectives Project (MSOP) has identified five informatics-related roles of the physician and has established objectives for each of these roles. The lifelong learning role incorporates skills relating to information retrieval, evaluation, and reconciliation. Without activities specifically targeting these skills, it is an act of faith that students will graduate with adequate preparation in these areas. To explicitly address these curricular goals, second-year students in Endocrinology and Reproduction Course at the University of Texas Medical Branch in Galveston were required to participate in debates on controversial topics in these fields. This exercise provided a structured task for developing and improving skills in literature searching, critical thinking, including evaluation of the quality of studies, reconciling results of conflicting studies, teamwork, formal presentation and communication, and spontaneous scholarly discussion. A search of the Medline database produced only one article describing the use of student debates for acquiring content and developing critical thinking and communication skills in health science education. The paper describes a first-year pharmacy curriculum that incorporated debates on socioeconomic topics relevant to pharmacy practice. While these debates required critical analysis of issues, the primary focus was on content rather than cognitive or informatics-related skills. Published accounts of debates in a college chemistry course and business school provide qualitative descriptions of the beneficial effects of such exercises on critical thinking, updating knowledge, and communication skills. In a more quantitative approach, Allen et al. conducted a meta-analysis of the impact of formal instruction in communication skills (including debates) on critical thinking ability. Such training resulted in 44% increase in scores on tests of critical thinking. Compared with training in other communication skills, participation in ‘‘forensics’’ (i.e., competitive debates) produced the greatest improvement, although the differences did not achieve statistical significance. Finally, Johnson et al. performed a meta-analysis of the effects of a method they call ‘‘academic controversy’’ on a variety of cognitive outcomes. This method, which shares many features of the debates described in the current report, has produced ‘‘increased achievement and retention, higher-quality problem-solving and decision-making, more frequent creative insight, more thorough exchange of expertise, and greater task involvement’’ by students. The current report describes the implementation of structured debates and the evaluation by students and faculty of the degree to which the informatics objectives were accomplished. Method

Physical and hormonal evaluation of transsexual patients during hormonal therapy

The optimal hormonal therapy for transsexual patients is not known. The physical and hormonal characteristics of 38 noncastrate male-to-female transsexuals and 14 noncastrate female-to-male transsexuals have been measured before and/or during therapy with various forms and dosages of hormonal therapy. All patients were hormonally and physically normal prior to therapy. Ethinyl estradiol was superior to conjugated estrogen in suppression of testosterone and gonadotropins but equal in effecting breast growth. The changes in physical and hormonal characteristics were the same for 0.1 mg/d and 0.5 mg/d of ethinyl estradiol. The female-to-male transsexuals were well managed with a dose of intramuscular testosterone cypionate of 400 mg/month, usually given 200 mg every two weeks. The maximal clitoral length reached was usually 4 cm. Higher doses of testosterone did not further increase clitoral length or suppression of gonadotropins; lower doses did not suppress the gonadotropins. Based on the information found in this study, we recommend 0.1 mg/d of ethinyl estradiol for the noncastrate male-to-female transsexual and 200 mg of intramuscular testosterone cypionate every two weeks for the noncastrate female-to-male transsexual.

The effect of bombesin-related peptides on the phagocytic function of mouse phagocytes in vitro

Bombesin (BBS) at doses of 0.1, 1.0, 10.0 and 100.0 nM stimulated chemiluminescence (CL) production by phagocytic cells (monocytes, macrophages and polymorphonuclear leucocytes) in mice in the presence of ZAP (opsonized zymosan particles containing luminol). These data suggest that BBS increased the phagocytic function of mouse phagocytes. BBS-related peptides, gastrin-releasing peptides (GRP)-27, GRP-14, GRP-10 and neuromedin B, also induced similar CL responses compared with BBS. The CL response elicited by BBS was depressed dramatically by various concentrations of EGTA (a Ca++ chelator), indicating that a Ca++ pathway may play a key role in the BBS-stimulated CL response.

Increased bioactive luteinizing hormone levels in postmenopausal women with endometrial cancer

Abstract OBJECTIVE: The purpose of our study was to investigate the secretion of immunoactive and bioactive luteinizing hormone in postmenopausal women with endometrial cancer. STUDY DESIGN: Seventeen postmenopausal women with endometrial cancer and nine without cancer were studied. Blood samples were collected at 15-minute intervals for 360 minutes. All samples were assayed for bioactive luteinizing hormone by rat interstitial cell testosterone assay and for immunoactive luteinizing hormone by radioimmunoassay. Serum pooled from 6-hour sampling was assayed for follicle-stimulating hormone, total estradiol, unbound estradiol, and estrone. RESULTS: Patients with endometrial cancer had significantly ( p \lt 0.01) higher bioactive luteinizing hormone levels (mean ± SE 276 ± 26 IU/L) as compared with those of control women (144 ± 18 IU/L). Bioactive/immunoactive ratios of luteinizing hormone were significantly higher ( p \lt 0.01) in women with cancer {5.8 ± 0.7) than in those without cancer (2.5 ± 0.5). There was a significant ( p \lt 0.001) positive correlation ( r = 0.582) between unbound estradiol levels and bioactive luteinizing hormone concentrations. CONCLUSIONS: There is an increase in bioactive luteinizing hormone secretion in postmenopausal women with endometrial cancer. This could lead to an increase in ovarian androgen production resulting in increased prehormone availability for estrogen formation from peripheral conversion. (AM J OBSTET GYNECOL 1992;167:1825-30.)

Plasma and pituitary concentrations of luteinizing hormone, follicle-stimulating hormone and prolactin in aged, ovariectomized CD-1 and C57BL/6 mice

Plasma and pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (Prl) were determined by radioimmunoassay in young (2-4 months-old) and aged CD-1 (14-18 months-old) and C57BL/6 (16-22 months-old) mice one month after ovariectomy. In young, ovariectomized mice, plasma and pituitary concentrations of LH and FSH were significantly higher, whereas concentrations of Prl were significantly lower than those in control mice (sham-operated). In contrast, plasma concentrations of LH, FSH and Prl were not statistically different in aged, ovariectomized mice and aged, control mice. There were also no differences in pituitary concentrations of the three hormones when comparing the same aged C57BL/6 mice, although the aged, ovariectomized CD-1 mice exhibited higher pituitary levels of each hormone than those of their controls. The pituitary of the aged mouse responds differently to ovariectomy than that of the young mouse because of age-related changes in the ovary and/or hypothalamic-hypophyseal complex.

Vitamin E levels in premenstrual syndrome

To determine whether changes in peripheral vitamin E levels are associated with symptoms of premenstrual syndrome, 10 patients with premenstrual syndrome and 10 control subjects were studied. They gave blood at 2- or 3-day intervals throughout three menstrual cycles. The vitamin E was measured by fluorometry after hexane extraction and luteinizing hormone was measured by radioimmunoassay. In the control group, vitamin E values were 854 +/- 45 micrograms/dl (mean +/- SE) during the luteal phase and 925 +/- 55 micrograms/dl during the follicular phase. No significant changes were noted between the two values. In the patients with premenstrual syndrome, the values were 849 +/- 53 micrograms/dl during the luteal phase, which was not significantly different from 858 +/- 48 micrograms/dl during the follicular phase. No significant changes were noted between the control group and the patients with premenstrual syndrome in either the luteal or the follicular phase. Vitamin E deficiency in patients with premenstrual syndrome was not shown by peripheral vitamin E levels in our study.