Search

Objective: To assess differences in insulin sensitivity and beta-cell function between nondiabetic premenopausal or early perimenopausal non-Hispanic white women and African American, Chinese American, Japanese American, and non-Mexican-American Latino women.Research Design and Methods: Homeostasis model assessments (HOMAs) of insulin sensitivity (HOMA%S) and beta-cell function (HOMA%beta) were used. Stepwise multivariable ethnic-specific ANCOVA models were used to compare HOMA%S and HOMA%beta between non-Hispanic whites and each of the four ethnic groups.Results: HOMA%S was lower in African Americans, Chinese Americans, and Japanese Americans when compared with non-Hispanic white women after correcting for waist circumference, presence of impaired fasting glucose, and site. Significant differences persisted only between African Americans and non-Hispanic whites after inclusion of triglycerides in the model. Triglycerides indirectly corrected for the differences in HOMA%S in the other two groups. There were no differences in HOMA%S between the non-Mexican-American Latinos and the non-Hispanic whites. Japanese Americans and Chinese Americans had lower HOMA%beta than non-Hispanic whites, whereas African Americans had higher HOMA%beta than non-Hispanic whites after correcting for confounders. HOMA%beta was similar between non-Mexican-American Latinos and non-Hispanic whites.Conclusions: These data suggest that type 2 diabetes prevention strategies for African-American women should initially target decreased insulin sensitivity, whereas strategies for Japanese-American and Chinese-American women may initially need to target both decreased insulin sensitivity and beta-cell function. Previous studies of Mexican-American populations may not apply to non-Mexican-American Latino women. [ABSTRACT FROM AUTHOR]

The shortage of organs for transplantation by its nature prompts ethical dilemmas. For example, although there is an imperative to save human life and reduce suffering by maximising the supply of vital organs, there is an equally important obligation to ensure that the process by which we increase the supply respects the rights of all stakeholders. In a relatively unexamined practice in the USA, organs are procured from unrepresented decedents without their express consent. Unrepresented decedents have no known healthcare wishes or advance care planning document; they also lack a surrogate. The Revised Uniform Anatomical Gift Act (RUAGA) of 2006 sends a mixed message about the procurement of organs from this patient population and there are hospitals that authorise donation. In addition, in adopting the RUAGA, some states included provisions that clearly allow organ procurement from unrepresented decedents. An important unanswered question is whether this practice meets the canons of ethical permissibility. The current Brief Report presents two principled approaches to the topic as a way of highlighting some of the complexities involved. Concluding remarks offer suggestions for future research and discussion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The specific objective of this study was to test the clinically derived hypothesis associating a high prevalence of depression in young men with nonclassical hypogonadism. We studied the entire population of men aged 18 to 40 years who had an outpatient visit at an academic health system in the years 2013 to 2015. The study group comprised 186 patients with a diagnosis of eugonadotropic hypogonadism and a testosterone value below 10.4 nmol/L with no apparent cause. We compared their demographic factors, other diagnoses, and treatments with those of (i) the entire population, (ii) a matched population of 930 controls, and (iii) 404 controls with normal testosterone determinations, and no hypogonadism diagnosis. Depression, defined as either an International Classification of Diseases, Ninth Revision ( ICD-9 ) diagnosis or treatment with an antidepressant medication, was found in 22.6% of cases vs 6.6% of population controls [ P < 0.001; OR: 1.13 (1.09 to 1.17); 95% CI]. Obesity was also higher in the cases ( P < 0.001). The matched controls had a depression rate of 13.4% compared with the case rate of 22.6% [ P < 0.002; OR 1.14 (1.08 to 1.17)]. Controls with normal testosterone determinations had a depression rate of 16.8% [ P = 0.121; OR: 1.04 (0.96 to 1.12)], suggesting that clinicians may have ordered a testosterone determination because of symptoms consistent with both depression and hypogonadism. The high incidence of depression in nonclassical hypogonadism in young men, although only associative, supports a depression evaluation and treatment as appropriate as well as investigation of the proximate causes of this form of hypogonadism.

Objective: To describe an exceedingly rare case of parathyromatosis in pregnancy and the limited medical treatment options available for such cases that are refractory to surgery., Methods: Case presentation and description of clinical course with brief review of the literature., Results: A 21-year-old woman with a history of 3.5 gland parathyroidectomy presented with severe hyperemesis during her first trimester of pregnancy and was found to have primary hyperparathyroidism attributable to parathyromatosis. We describe the diagnostic and management dilemmas associated with this case, which included localization of the culprit lesions, a technically challenging surgical resection and subsequent medical management with cinacalcet when symptomatic hypercalcemia recurred during the third trimester. To our knowledge, this is only the third report of the successful use of cinacalcet during pregnancy, and the first case report of parathyromatosis presenting during pregnancy., Conclusion: Cinacalcet was used safely and effectively during the third trimester of pregnancy to treat symptomatic hypercalcemia due to parathyromatosis.

The most common cause of hypercalcemia in hospitalized patients is malignancy. Primary hyperparathyroidism most commonly causes hypercalcemia in the outpatient setting. These two account for over 90% of all cases of hypercalcemia. Hypercalcemia can be divided into PTH-mediated and PTH-independent variants. Primary hyperparathyroidism, familial hypocalciuric hypercalcemia, familial hyperparathyroidism, and secondary hyperparathyroidism are PTH mediated. The most common PTH-independent type of hypercalcemia is malignancy related. Several mechanisms lead to hypercalcemia in malignancy-direct osteolysis by metastatic disease or, more commonly, production of humoral factors by the primary tumor also known as humoral hypercalcemia of malignancy that accounts for about 80% of malignancy-related hypercalcemia. The majority of HHM is caused by tumor-produced parathyroid hormone-related protein and less frequently production of 1,25-dihydroxyvitamin D or parathyroid hormone by the tumor. We report the rare case of a patient with hypercalcemia and diagnosed primary hyperparathyroidism. The patient had persistent hypercalcemia after surgical removal of parathyroid adenoma with recorded significant decrease in PTH level. After continued investigation it was found that the patient also had elevated 1,25-dihydroxyvitamin D and further studies confirmed a large spleen mass that was later confirmed to be a lymphoma. This is a rare example of two concomitant causes of hypercalcemia requiring therapy.

A recent large-scale meta-analysis of genome-wide studies has identified 95 loci, 59 of them novel, as statistically significant predictors of blood lipid traits; we tested whether the same loci explain the observed heterogeneity in response to lipid-lowering therapy with fenofibrate. Using data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 861) we fit linear mixed models with the genetic markers as predictors and high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, and triglyceride concentrations as outcomes. For all four traits, we analyzed both baseline levels and changes in response to treatment with fenofibrate. For the markers that were significantly associated with fenofibrate response, we fit additional models evaluating potential epistatic interactions. All models were adjusted for age, sex, and study center as fixed effects, and pedigree as a random effect. Statistically significant associations were observed between the rs964184 polymorphism near APOA1 (P-value≤0.0001) and fenofibrate response for HDL and triglycerides. The association was replicated in the Pharmacogenetics of Hypertriglyceridemia in Hispanics study (HyperTG, n = 267). Suggestive associations with fenofibrate response were observed for markers in or near PDE3A, MOSC1, FLJ36070, CETP, the APOE-APOC1-APOC4-APOC2, and CILP2. Finally, we present strong evidence for epistasis (P-value for interaction =  0.0006 in GOLDN, 0.05 in HyperTG) between rs10401969 near CILP2 and rs4420638 in the APOE-APOC1-APOC4-APOC2 cluster with total cholesterol response to fenofibrate. In conclusion, we present evidence linking several novel and biologically relevant genetic polymorphisms to lipid lowering drug response, as well as suggesting novel gene-gene interactions in fenofibrate pharmacogenetics.

Objective: To assess the efficacy, with respect to participant understanding of information, of a computer-based approach to communication about complex, technical issues that commonly arise when seeking informed consent for clinical research trials., Design, Setting and Participants: An open, randomised controlled study of 60 patients with diabetes mellitus, aged 27-70 years, recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne., Intervention: Participants were asked to read information about a mock study via a computer-based presentation (n = 30) or a conventional paper-based information statement (n = 30). The computer-based presentation contained visual aids, including diagrams, video, hyperlinks and quiz pages., Main Outcome Measures: Understanding of information as assessed by quantitative and qualitative means., Results: Assessment scores used to measure level of understanding were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task (82% v 73%; P = 0.005). More participants in the group that completed the computer-based task expressed interest in taking part in the mock study (23 v 17 participants; P = 0.01). Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement (21 in the computer-based task group, 18 in the paper-based task group)., Conclusions: A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research, and may reduce costs and improve efficiency in recruiting participants for clinical trials.

Context: Reproductive hormones are incompletely characterized during the menopause transition (MT)., Hypothesis: Increased anovulation and decreased progesterone accompany progress through the MT., Design: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr., Main Outcome Measures: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables., Results: Ovulatory-appearing cycles declined from 80.9% at baseline to 64.7% by the third assessment (H3). Cycles presumed anovulatory and not ending with bleeding by 50 d (anovulatory/nonbleeding) increased from 8.4 to 24% by H3 and were associated with progress to early perimenopause [odds ratio (OR) = 2.66; confidence interval (CI) = 1.17-6.04] or late perimenopause (OR = 56.21; CI = 18.79-168.12; P < 0.0001), African-American ethnicity (OR = 1.91; CI = 1.06-3.43), and less than high school education (OR = 3.51; CI = 1.62-7.62). Anovulatory cycles ending with bleeding remained at about 10% from baseline to H3; compared with ovulatory cycles, they were associated with obesity (OR = 4.68; CI = 1.33-16.52) and more than high school education (OR = 2.12; CI = 1.22-3.69; P = 0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pregnanediol glucuronide decreased 6.6% for each year on study. Insulin sensitivity measures did not relate strongly to menstrual cycle hormones., Conclusions: Anovulation without bleeding represents progression of the MT. A small but detectable decrease in luteal progesterone excretion occurs as women progress through the MT.

We report data from 60 patients with polycystic ovary syndrome (PCOS) who had undergone assessment of insulin resistance, pancreatic beta-cell function, obesity, and androgen levels to elucidate the complex relationships among these traits. Homeostasis model assessment was used to quantify insulin resistance and beta-cell function. A reference population was derived from the National Health and Nutrition Examination Study (NHANES III, 1988-1994). Indices of insulin resistance, insulin secretion, bioavailable testosterone, and body mass index all exhibited significant pairwise correlations. Multiple regression analysis clarified the phenotypic relationships, demonstrating that insulin resistance and bioavailable testosterone were independent predictors of beta-cell function; beta-cell function and obesity were independent predictors of insulin resistance; and beta-cell function was an independent predictor of bioavailable testosterone. Of note, comparison with normal women from NHANES revealed a significantly stronger relationship between beta-cell function and insulin resistance in PCOS, raising the possibility of an intrinsic defect in beta-cell function whereby increasing insulin resistance leads to a greater insulin response in PCOS than normal. The altered relationship of beta-cell function and insulin resistance coupled with the fact that beta-cell function, not insulin resistance, was a predictor of hyperandrogenemia suggests that beta-cell dysfunction may be a key pathogenic determinant in PCOS.

Following the landmark Massachusetts Male Aging Study (MMAS) that provided the first relatively unbiased study of the epidemiology of erectile dysfunction (ED), a number of additional studies were carried out in the U.S. and around the world. The studies vary in quality because they used different definitions of ED, different assessment instruments, different and sometimes biased sources of populations, inadequate response rates to questionnaires and interviews, cultural disparities in willingness to discuss sexual issues, and differing interpretations of the results. Nevertheless, the studies demonstrated similar levels of ED by age and an exponential rise with age. They also generally confirmed the conditions that correlated with ED in the MMAS, namely, diabetes, hypertension, coronary artery disease, prostate cancer therapy, and depression. These were exacerbated by cigarette smoking., (Copyright 2004 Humana Press Inc.)

Polycystic ovary syndrome (PCOS) affects 5% to 7% of women of reproductive age. Insulin resistance and obesity are components of this important syndrome that may contribute to excess cardiovascular risk. We analyzed data from 69 patients with PCOS who had undergone quantitative assessment of insulin sensitivity, blood pressure, lipid profiles, and androgen levels to determine the impact of insulin resistance and obesity on parameters of cardiovascular risk. Homeostasis model assessment (HOMA) was used to stratify patients in terms of insulin resistance. To obtain a reference population, we used data from the National Health and Nutrition Examination Study (NHANES III, 1988 to 1994). The most insulin-resistant tertile of patients exhibited higher body mass index (BMI), androgen levels, systolic and diastolic blood pressure (DBP), triglyceride (TG) levels, and decreased high-density lipoprotein cholesterol (HDL-C) levels. Insulin resistance, not BMI, was the main determinant of HDL-C and TG levels and systolic blood pressure (SBP) in PCOS. Among normal women, both BMI and insulin resistance influenced cardiovascular risk factors. Insulin resistance was a more significant predictor of TGs in women with PCOS than in normal women (P =.008). In contrast to normal women, insulin resistance in PCOS appears to be the prime determinant of abnormal lipids, blood pressure, and androgens. Thus, early detection of insulin resistance, as well as weight reduction, should be emphasized for all patients with PCOS.

Background: We assessed the prevalence of mood disturbance among women with prospectively documented polycystic ovary syndrome (PCOS)., Methods: Thirty-two women with PCOS completed the Center for Epidemiological Studies-Depression Rating Scale (CES-D). Clinical and biochemical characteristics were assessed., Results: Sixteen women had CES-D scores indicative of depression. Depression was associated with greater insulin resistance (P=0.02) and higher body mass index (P=0.05). Women receiving oral contraceptives for the treatment of PCOS were less depressed than patients not receiving treatment (P=0.03)., Limitations: Possible selection bias, use of a screening tool alone without further diagnostic evaluation of depression, small samples size and lack of direct comparison with an age matched control group, should be considered in interpretation of these results., Conclusion: Findings suggest a high prevalence of depression among women with PCOS, and an association between depression and PCOS markers.

We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.

Background: Patients with elevated levels of serum triglycerides (TG) often have other associated lipid abnormalities (e.g., low levels of high-density lipoprotein cholesterol [HDL-C]) and are at increased risk of developing coronary heart disease. Although the therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in hypercholesterolemic patients have been well established, less is known about the effects of statins in patient populations with hypertriglyceridemia., Hypothesis: The purpose of this study was to evaluate the lipoprotein-altering efficacy of simvastatin in hypertriglyceridemic patients., Methods: This was a multicenter, randomized, double-blind, placebo-controlled study. In all, 195 patients with fasting serum triglyceride levels between 300 and 900 mg/dl received once daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks., Results: Compared with placebo, simvastatin treatment across all doses resulted in significant reductions (p < 0.05 - < 0.001) in serum levels of triglycerides (-20 to -31% decrease) and TG-rich lipoprotein particles. Significant (p < 0.001) reductions were also seen in low-density lipoprotein cholesterol (-25 to -35%) and non-HDL-C (-26 to -40%). Levels of HDL-C were increased (7-11%) in the simvastatin groups compared with placebo (p < 0.05 - < 0.001)., Conclusion: The results of this study demonstrate the beneficial effects of simvastatin in patients with hypertriglyceridemia.

We present the case of a young woman with treatment-resistant major depression, who presented to the Mood Disorders Clinic with a Hamilton Psychiatric Rating Scale for Depression (HAM-D-21) score of 28, after a year-long treatment with Effexor-XR. The patient also had untreated Polycystic Ovarian Syndrome (PCOS). The resolution of her depressive symptoms resulted from the treatment for PCOS with metformin and spironolactone. The patient remained euthymic 5 months after discontinuation of the antidepressant while continuing therapy for PCOS. We briefly overview of the pertinent literature of the pathophysiology of PCOS and affective disorders, highlighting an overlap in phenotypical presentations between these two disorders. Dysregulation of the hypothalamo-pituitary axis and various end organ systems are implicated in both PCOS and affective disorders. As such, several clinical and biochemical markers are common to both disorders, namely insulin resistance, obesity, and hyperandrogenism. In addition, these metabolic abnormalities are interrelated, causing women with PCOS or affective disorders to get caught in a "vicious cycle" of hormonal dysregulation. The case report presented here illustrates how treatment of symptoms such as insulin resistance and hyperandrogenism can lead to remission of major depressive disorder and PCOS. We suggest that through treatment of underlying metabolic defects, both the mood of the patient and the metabolic condition of PCOS can be assisted.

In this paper, we empirically explore some manifestations of norms for the conduct of science. We focus on scientific research ethics and report survey results from 606 scientists who received funding in 1993 and 1994 from the Division of Molecular and Cellular Biology of the Biology Directorate of the National Science Foundation. We also report results for 91 administrators charged with overseeing research integrity at the scientists' research institutions. Both groups of respondents were presented with a set of scenarios, designed by fractional factorial methods, describing different kinds of scientific conduct that in the eyes of some would likely be unethical. Respondents then were asked to evaluate each of these scenarios for how unethical the behavior might be and what kinds of sanctions might be appropriate. We use the responses to consider the nature of consensus around norms related to the practice of science and in particular, similarities and differences between scientists and science administrators. Implications for policy are also discussed.

Scientists, as professionals, have a responsibility to self-regulate. However, whistleblowing is rare. We investigated scientists' infrequent disclosure of unethical behavior by studying their responses to scenarios describing unethical research acts and compared their responses to those of research administrators. A cross-sectional survey was administered to National Science Foundation-funded principal investigators and their institutions' representatives (IRs) to the Office of Research Integrity. Both scientists and IRs proposed to respond to nearly all research behaviors that they rated as unethical. Scientists more often proposed responses limited to the research team (58% vs. 25% of cases, p < .001) whereas IRs more often proposed to inform an administrator or dean, journal editor, funding agency, professional society, or reporter. The prior behavior and academic rank of the scenario protagonist were associated with responses, but consequences of the unethical behavior were not. Scientists appear to perceive that they uphold their responsibility to respond to unethical behavior by disclosures within the research team, whereas administrators propose to report to externally accountable individuals, raising the question of whether scientists' behavior constitutes professional self-regulation or cover up.

Purpose: To investigate the perceptions of scientists and institutional representatives (IRs) to the National Institutes of Health's Office of Research Integrity concerning appropriate punishment for unethical research behavior., Method: In 1994-95, 606 scientists and 91 IRs rated the ethical behaviors of and suggested appropriate punishments for protagonists in randomly generated scenarios describing scientific research behaviors. The authors evaluated the relationships of the suggested punishments to the protagonists' behaviors and characteristics, and compared recommendations of the scientists and IRs., Results: The respondents suggested punishments for 80% of the scenarios that were rated unethical. Punishments were more often prescribed for behaviors rated more unethical and for repeat offenders. The type of punishment was related to the protagonist's academic status and the nature of the unethical behavior. IRs proposed more and different punishments than did scientists., Conclusion: Scientists and IRs proposed that most unethical research behaviors be punished. The decision to punish depended on the unethical level of the behavior. The type of punishment depended on the aims: correcting the wrong, rehabilitation, or sanction. Variation in the respondents' selections of punishments and the IRs' greater propensity to punish suggest that scientists committing similar ethical violations may receive different punishments. Explicit consideration of which punishment is merited under what circumstances should be undertaken by the scientific community.

Erectile dysfunction (ED) is the most common sexual problem in men, after premature ejaculation, affecting up to 30 million in the United States. In a society in which sexuality is widely promoted, ED impacts on feelings of self-worth and self-confidence and may impair the quality of life of affected men and their partners. Damage to personal relationships can ensue; and the anger, depression, and anxiety engendered spill over into all aspects of life. Patients are often embarrassed or reluctant to discuss the matter with their primary care practitioners. Unfortunately, many physicians fail to take the opportunity to promote open discussion of sexual dysfunction. They too, may avoid the topic through personal embarrassment. Since the National Institutes of Health (NIH) Consensus Conference on Impotence in 1992, the inadequate level of public and professional understanding of ED has begun to be addressed. As a first step in breaking down the communication barriers between patients and practitioners, it is important that physicians have a thorough understanding of the wide variety of conditions associated with ED and how the different risk factors for ED may be readily identified. This review addresses the diagnosis of ED and identifies diagnostic tests that can be used by primary care physicians to determine the patients most at risk and the treatments most suited to meet the patients' and their partners' goal for therapy.

The prevalence of osteoporosis and the incidence of fractures are substantially lower in black than in white subjects, a finding generally attributed to racial differences in adult bone mass. Whether these racial differences are present in childhood is the subject of considerable interest, as the amount of bone gained during growth is a major determinant of future susceptibility to fractures. We measured the density and size of the vertebrae and femurs of 80 black and 80 white healthy children, 8-18 yr of age, matched for age, gender, height, weight, and stage of sexual development, using computed tomography. Race had a significant and differential effect on the bones in the axial and appendicular skeletons. In the axial skeleton, black children had greater cancellous bone density, but similar cross-sectional area of the vertebral bodies. In contrast, in the appendicular skeleton, black children had greater femoral cross-sectional area, but similar cortical bone area and cortical bone density. Compared to white children, vertebral bone density and femoral cross-sectional area at sexual maturity were, on the average, 10.75% and 5.7% higher, respectively, in black children. Such significant variations may contribute to the racial differences in the prevalence of osteoporosis between black and white adults.

Context: The professional integrity of scientists is important to society as a whole and particularly to disciplines such as medicine that depend heavily on scientific advances for their progress., Objective: To characterize the professional norms of active scientists and compare them with those of individuals with institutional responsibility for the conduct of research., Design: A mailed survey consisting of 12 scenarios in 4 domains of research ethics. Respondents were asked whether an act was unethical and, if so, the degree to which they considered it unethical and to select responses and punishments for the act., Participants: A total of 924 National Science Foundation research grantees in 1993 or 1994 in molecular or cellular biology and 140 representatives from the researchers' institutions to the US Department of Health and Human Services Office of Research Integrity., Main Outcome Measures: Percentage of respondents considering an act unethical and the mean malfeasance rating on a scale of 1 to 10., Results: A total of 606 research grantees and 91 institutional representatives responded to the survey (response rate of 69% of those who could be contacted). Respondents reported a hierarchy of unethical research behaviors. The mean malfeasance rating was unrelated to the characteristics of the investigator performing the hypothetical act or to its consequences. Fabrication, falsification, and plagiarism received malfeasance ratings higher than 8.6, and virtually all thought they were unethical. Deliberately misleading statements about a paper or failure to give proper attribution received ratings between 7 and 8. Sloppiness, oversights, conflicts of interest, and failure to share were less serious still, receiving malfeasance ratings between 5 and 6. Institutional representatives proposed more and different interventions and punishments than the scientists., Conclusions: Surveyed scientists and institutional representatives had strong and similar norms of professional behavior, but differed in their approaches to an unethical act.

Background: Little is known about scientists' views on normative research ethics and how these compare with the views of the institutional representatives (IRs) involved in matters of scientific conduct. We qualitatively evaluated scientist and IR perceptions of the norms of science, ethical violations and their harms, factors contributing to violations, and approaches to improve scientific conduct., Methods: Focus groups were conducted with National Science Foundation investigators and with IRs. Themes were extracted from observation, notes, and transcripts. Consensus and contrasts within and between groups were described., Results: Scientists described a rich set of norms including honesty, integrity, service, sharing, openness, mentoring, and meticulous work habits. Institutional representatives focused on good citizenship and abiding by administrative rules. Both groups listed similar ethical violations, though scientists felt that severe violations were rare, that science was self-correcting, and that the greatest harm from misconduct disclosure was the loss of public trust and funding. Institutional representatives called for increased and less confidential misconduct investigations. Reporting misconduct was strongly supported by IRs but rejected by scientists. Both scientists and IRs believed that formal research ethics education was needed for trainees., Conclusions: Scientists in these focus groups upheld a complex set of norms that mirror prior codes of science and exceed national misconduct rules. The sharply contrasting views of scientists and IRs concerning responsibility to report misconduct, the utility of misconduct investigation, and penalties for misconduct highlight areas where open discussion and constructive resolution are needed to formulate a functional mechanism to enhance the ethical conduct of science.

Five hyperthyroid patients (two men and three women) with typical features of subacute thyroiditis were treated with sodium ipodate (Oragrafin; 0.5 g, orally daily or every other day) for 15-60 days; the treatment was stopped when both serum T4 and T3 levels were normal. All patients studied demonstrated a prompt normalization of serum T3, improvement in clinical symptoms of hyperthyroidism, and/or weight gain. We observed no side-effects of treatment with sodium ipodate. Our data suggest that sodium ipodate is a safe and effective agent for management of hyperthyroidism in subacute thyroiditis.

Objective: To determine the incidence of remote testicular trauma and of possible related permanent hormonal and seminal changes in infertile men., Design: Retrospective clinical study of hormonal and seminal parameters in a subpopulation of infertile men., Setting: Andrology Clinic in an academic research environment., Participants: Infertile men, with and without history of remote testicular trauma, and fertile volunteers., Main Outcome Measures: Percentage of infertile men with history of blunt testicular trauma, concentrations of reproductive hormones, and semen parameters., Results: Significant remote blunt testicular trauma was reported by 16.8% of infertile men. This had occurred 2 to 17 years (mean, 16.4 years) before evaluation, mostly with contact sports at adolescent age. Estradiol concentrations after testicular trauma were 19% and 25% higher than in infertile men without history of testicular injury and in fertile controls. Elevated E2 levels did not correlate with T. Infertile men with and without history of testicular trauma showed changes in seminal parameters., Conclusion: The incidence of remote blunt testicular trauma in infertile men is unexpectedly high. After injury, FSH-stimulated aromatization of T may increase testicular E2 production, interfere with spermatogenesis, and cause infertility. Consistent use of protective devices in contact sports is recommended.

Background: As the United States becomes more multicultural, physicians face the challenge of providing culturally sensitive and appropriate health care to patients with differing health beliefs and values. While a few schools are providing cultural-sensitivity training in response to the changing patient population, the pervasiveness of such training has not been thoroughly reported., Method: In 1991-92, all 126 U.S. medical schools were surveyed regarding their implementation and plans for future implementation of cultural-sensitivity training. The t-test was used to compare data from those schools that offered separate, formal cultural-sensitivity courses with data from the schools that did not offer such courses., Results: Of the 126 schools surveyed, 98 (78%) responded. Only 13 of the responding schools offered cultural-sensitivity courses to their students, and all but one of these courses were optional. These 13 schools reported a greater perceived likelihood that their students would have contact with African-American patients (t = 2.88, p < .05). Despite the few courses offered and the common perception that recent graduates were only "somewhat prepared" to provide culturally sensitive clinical services, only 33 schools were planning to implement new courses., Conclusion: The results indicate needs for more cultural-sensitivity training and for further studies to determine the most effective type of training for students.

The author introduces questions about the commercialization of science, focusing on fairness and conflicts of interest, and suggests the bases for policy initiatives. First, is it fair for government-supported research to enrich research universities and individual scientists? The belief that it is unfair seems limited to biomedicine and is not shared by other fields and government research agencies. The main concerns, however, are conflicts of interest and of commitment (loss of objectivity, reordering of priorities, degradation of science as an open and collegial enterprise, conflicts of commitment, and exploitation of graduate students and postdoctoral fellows). The author outlines 11 principles that can be used in setting policies about conflict of interest and commitment, including the principles that these conflicts are inevitable, that technology transfer should be supported rather than hindered, that the type and amount of financial reward received by the faculty are not as important as the strings attached by the commercial sponsor, and that trainees must be protected from working in settings where they cannot discuss or promptly publish their work.

Objective: To evaluate the use of pentoxifylline to treat impotence in men with mild to moderate penile vascular insufficiency., Design: Double-blind randomized clinical trial., Setting: Sexual Dysfunction Clinic at VA Medical Center, Sepulveda, CA., Participants: Convenience sample of couples., Intervention: Twelve weeks of treatment with placebo or 400 mg tid of pentoxifylline., Measurements: (1) Report of patient verified by partner as to number of coital episodes per month; (2) penile-brachial pressure index determinations., Results: Pentoxifylline therapy regularly increased the PBPI in impotent men in comparison with the placebo, frequently into the normal range. Pentoxifylline therapy was particularly useful in restoring the PBPI in men with the pelvic steal syndrome; six of seven such subjects improved into the normal range. During the pentoxifylline treatment period, in contrast with the control period, nine men were able to reestablish coital function and three had no improvement. Six couples did not attempt intercourse despite a professed interest in sexual activity; however five out of the six men experienced erections during episodes of fantasy or attempts at masturbation during treatment. There were no complications of therapy., Conclusions: These promising preliminary results suggest a well tolerated alternative therapy for erectile dysfunction in patients with mild to moderate penile vascular disease.

Purpose: To evaluate the use of a vacuum tumescence device in the treatment of impotence in couples wishing to restore coital function, whose male partners had unsatisfactory results from penile implants or in whom the man was impotent following treatment for prostate or colon carcinoma., Subjects: Convenience sample of seventeen couples seeking treatment of male factor sexual dysfunction., Methods: After completion of a comprehensive diagnostic evaluation of the male partner, couples who expressed a wish to restore coital function were instructed in the use of the vacuum tumescence device. Partners each filled out and initialled a daily diary of sexual activity and returned to clinic for followup at 3 and 6 months., Results: Sixteen patients were able to obtain firm to hard erections lasting an average of 14.9 minutes and had satisfactory coitus with vaginal ejaculation an average of 3.9 times per month. There were no significant complications., Conclusion: The vacuum tumescence device can be effective in the treatment of impotence after penile prosthesis explantation, in enhancement of inadequate erections with a prosthesis in place, and after surgical or radiation therapy for prostate or colon carcinoma.

The relation of the reproductive endocrine system to impotence in older men was examined by measuring the concentrations of testosterone (T), bioavailable testosterone (BT), LH, and PRL and body mass index (BMI) in 57 young controls (YC), 50 healthy potent older controls attending a health fair (HF), and 267 impotent patients (SD). The SD and HF had markedly reduced mean T and BT values compared to YC. When adjusted for age and BMI there was no difference in BT between potent and impotent older men. The percent BT was much higher in YC than in the older groups. While the percent BT rose significantly with increased T in YC, it was inversely related to T in the older subjects, suggesting that increased sex hormone-binding globulin binding was a primary event leading to a low BT. Forty-eight percent of HF and 39% of SD were hypogonadal, as defined by a mean BT of 2.5 SD or more below the mean of YC (less than or equal to 2.3 nmol/L). Ninety percent of these had LH values in the normal range, suggesting hypothalamic-pituitary dysfunction. Thirty-four SD and six each of YC and older control volunteers (OC) underwent GnRH testing. Older subjects showed impaired responsiveness to GnRH compared to YC. A low basal LH level correlated very highly with hyporesponsiveness to GnRH. Thus, secondary hypogonadism and impotence are two common, independently distributed conditions of older men.

This study evaluated the use of a vacuum tumescence device in the treatment of impotence in older men. Twenty couples with sexual dysfunction due to erectile impotence and who were interested in restoration of sexual function were treated by providing them with both a vacuum tumescence device to engorge the penis and an obstructing band to impede venous return. Nineteen patients established firm to hard erections lasting an average of 16 minutes and were able to have satisfactory coitus with vaginal ejaculation an average of three times per month. The penile-brachial pressure index, supine and after exercise (a measure of the adequacy of penile arterial flow), exhibited a significant increase following six month's use of the vacuum tumescence device. The only significant complications were mild, self-limited hematomas on three occasions of use. Thus in this limited series the vacuum tumescence device provided a well-accepted, relatively inexpensive therapeutic approach to impotence.

Hypogonadal men usually have diminished libido and erectile dysfunction, and testosterone replacement therapy in these men increases sexual activity, erotic thoughts, and self-reported nocturnal erections. The polygraphic assessment of nocturnal penile tumescence (NPT) provides an objective index of erectile capability and is useful for differentiating psychogenic from organic erectile dysfunction. In this study we evaluated NPT in six hypogonadal adult men during and after termination of androgen therapy. Multinight sleep studies were conducted within 1 week and 7-8 weeks after each man received 20 mg testosterone cypionate, im. The mean serum testosterone level 4-7 days after testosterone injection was 35.9 +/- 3.4 (+/- SE) nmol/L, and it fell to 2.3 +/- 0.9 nmol/L after 7-8 weeks. Significant declines (P less than 0.05) in the number of NPT episodes (3.7 to 2.0), maximum penile circumference increase (24 to 13 mm), and total tumescence time (107 to 55 min) accompanied the fall in the serum testosterone level. No androgen-related changes in the amount or integrity of rapid eye movement sleep were found. Finally, the mean penile rigidity (buckling pressure) decreased from 770 +/- 98 to 590 +/- 81 g (P less than 0.05). Comparison of these results to those in normal men revealed that none of these men met all diagnostic criteria for organic impotence, even 7-8 weeks after discontinuation of testosterone administration. While men with androgen deficiency may have normal NPT, sleep-related erections increase in response to testosterone administration.