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Background The educational beliefs of medical educators influence their teaching practices. Insight into these beliefs is important for medical schools to improve the quality of education they provide students and to guide faculty development. Several studies in the field of higher education have explored the educational beliefs of educators, resulting in classifications that provide a structural basis for diverse beliefs. However, few classification studies have been conducted in the field of medical education. We propose a framework that describes faculty beliefs about teaching, learning, and knowledge which is specifically adapted to the medical education context. The proposed framework describes a matrix in which educational beliefs are organised two dimensionally into belief orientations and belief dimensions. The belief orientations range from teaching-centred to learning-centred; the belief dimensions represent qualitatively distinct aspects of beliefs, such as ‘desired learning outcomes’ and ‘students’ motivation’. Methods We conducted in-depth semi-structured interviews with 26 faculty members, all of whom were deeply involved in teaching, from two prominent medical schools. We used the original framework of Samuelowicz and Bain as a starting point for context-specific adaptation. The qualitative analysis consisted of relating relevant interview fragments to the Samuelowicz and Bain framework, while remaining open to potentially new beliefs identified during the interviews. A range of strategies were employed to ensure the quality of the results. Results We identified a new belief dimension and adapted or refined other dimensions to apply in the context of medical education. The belief orientations that have counterparts in the original Samuelowicz and Bain framework are described more precisely in the new framework. The new framework sharpens the boundary between teaching-centred and learning-centred belief orientations. Conclusions Our findings confirm the relevance of the structure of the original Samuelowicz and Bain beliefs framework. However, multiple adaptations and refinements were necessary to align the framework to the context of medical education. The refined belief dimensions and belief orientations enable a comprehensive description of the educational beliefs of medical educators. With these adaptations, the new framework provides a contemporary instrument to improve medical education and potentially assist in faculty development of medical educators.

Approximately two out of three adult Americans are overweight or obese. Despite widespread recognition of this disorder, there has been little progress in the past 20 years in finding effective noninvasive treatments for weight loss. The consequences of obesity are increasingly well recognized and include increases in blood pressure, plasma lipids, the onset of type 2 diabetes, sleep apnea, asthma, osteoarthritis and a variety of cancers. Obesity can increase the rate of pregnancy complications and fetal malformations in normoglycemic women. Current medical approaches to obesity, including intensive lifestyle interventions and drug therapies, have been successful in achieving modest weight loss of 4–7%, less than the 1998 NIH Guidelines target of 10%. Surgical approaches, including laparoscopic adjustable gastric banding, vertical banded gastroplasty and Roux-en-Y gastric bypass, are much more successful, achieving weight loss of 15–50%. A treatment gap therefore exists in the management of obese and overweight patients, because many patients desire and would receive great health benefits by achieving weight loss of 7–15%. This review will discuss the dilemma of the treatment gap and explore possible ways by which it may be filled in the future by the use of innovative approaches.

OBJECTIVES The development of patient-centred attitudes by health care providers is critical to improving health care quality. A prior study showed that medical students with more patient-centred attitudes scored higher in communication skills as judged by standardised patients (SPs) than students with less patient-centred attitudes. We designed this multicentre study to examine the relationships among students' demographic characteristics, patient-centredness and communication scores on an SP examination. METHODS Early Year 4 medical students at three US schools completed a 12-item survey during an SP examination. Survey items addressed demographics (gender, ethnicity, primary childhood language) and patient-centredness. Factor analysis on the patient-centredness items defined specific patient-centred attitudes. We used multiple regression analysis incorporating demographic characteristics, school and patient-centredness items and examined the effect of these variables on the outcome variable of communication score. RESULTS A total of 351 students took the SP examination and 329 (94%) completed the patient-centredness questionnaire. Responses indicated generally high patient-centredness. Student ethnicity and medical school were significantly associated with communication scores; gender and primary childhood language were not. Two attitudinal factors were identified: patient perspective and impersonal attitude. Multiple regression analysis revealed that school and scores on the impersonal factor were associated with communication scores. The effect size was modest. CONCLUSIONS In a medical student SP examination, modest differences in communication scores based on ethnicity were observed and can be partially explained by student attitudes regarding patient-centredness. Curricular interventions to enhance clinical experiences, teaching and feedback are needed to address key elements of a patient-centred approach to care.

Abraham Flexner's 1910 report is credited with promoting critical reforms in medical education. Because Flexner advocated scientific rigor and standardization in medical education, his report has been perceived to place little emphasis on the importance of public health in clinical education and training. However, a review of the report reveals that Flexner presciently identified at least three public-health-oriented principles that contributed to his arguments for medical education reform: (1) The training, quality, and quantity of physicians should meet the health needs of the public, (2) physicians have societal obligations to prevent disease and promote health, and medical training should include the breadth of knowledge necessary to meet these obligations, and (3) collaborations between the academic medicine and public health communities result in benefits to both parties. In this article, commemorating the Flexner Centenary, the authors review the progress of U.S. and Canadian medical schools in addressing these principles in the context of contemporary societal health needs, provide an update on recent efforts to address what has long been perceived as a deficit in medical education (inadequate grounding of medical students in public health), and provide new recommendations on how to create important linkages between medical education and public health. Contemporary health challenges that require a public health approach in addition to one-on-one clinical skills include containing epidemics of preventable chronic diseases, reforming the health care system to provide equitable high-quality care to populations, and responding to potential disasters in an increasingly interconnected world. The quantitative skills and contextual knowledge that will prepare physicians to address these and other population health problems constitute the basics of public health and should be included throughout the continuum of medical education.

Web-based clinical cases ("virtual patients", VPs) provide the potential for valid, cost-effective teaching and assessment of clinical skills, especially clinical reasoning skills, of medical students. However, medical students must embrace this teaching and assessment modality for it to be adopted widely.We examined student acceptance of a web-based VP system, Web-SP, developed for teaching and assessment purposes, in a group of 15 second-year and 12 fourth-year medical students.Student acceptance of this web-based method was high, with greater acceptance in pre-clinical (second-year) compared with clinical (fourth-year) medical students. Students rated VPs as realistic and appropriately challenging; they particularly liked the ability of VPs to show physical abnormalities (such as abnormal heart and lung sounds, skin lesions, and neurological findings), a feature that is absent in standardized patients.These results document high acceptance of web-based instruction and assessment by medical students. VPs of the complexity used in this study appear to be particularly well suited for learning and assessment purposes in early medical students who have not yet had significant clinical contact.

Context Achieving competence in ‘practice-based learning’ implies that doctors can accurately self- assess their clinical skills to identify behaviours that need improvement. This study examines the impact of receiving feedback via performance benchmarks on medical students' self-assessment after a clinical performance examination (CPX). Methods The authors developed a practice-based learning exercise at 3 institutions following a required 8-station CPX for medical students at the end of Year 3. Standardised patients (SPs) scored students after each station using checklists developed by experts. Students assessed their own performance immediately after the CPX (Phase 1). One month later, students watched their videotaped performance and reassessed (Phase 2). Some students received performance benchmarks (their scores, plus normative class data) before the video review. Pearson's correlations between self-ratings and SP ratings were calculated for overall performance and specific skill areas (history taking, physical examination, doctor−patient communication) for Phase 1 and Phase 2. The 2 correlations were then compared for each student group (i.e. those who received and those who did not receive feedback). Results A total of 280 students completed both study phases. Mean CPX scores ranged from 51% to 71% of items correct overall and for each skill area. Phase 1 self-assessment correlated weakly with SP ratings of student performance (r = 0.01–0.16). Without feedback, Phase 2 correlations remained weak (r = 0.13–0.18; n = 109). With feedback, Phase 2 correlations improved significantly (r = 0.26–0.47; n = 171). Low-performing students showed the greatest improvement after receiving feedback. Conclusions The accuracy of student self-assessment was poor after a CPX, but improved significantly with performance feedback (scores and benchmarks). Videotape review alone (without feedback) did not improve self-assessment accuracy. Practice-based learning exercises that incorporate feedback to medical students hold promise to improve self-assessment skills.

Undergraduate (i.e., baccalaureate) premedical students have limited exposure to clinical practice before applying to medical school-a shortcoming, given the personal and financial resources required to complete medical training.The Stanford Immersion in Medicine Series (SIMS) is a program that streamlines the completion of regulatory requirements for premedical students and allows them to develop one-on-one mentor-mentee relationships with practicing physicians. The program, offered quarterly since 2007, is an elective available for Stanford University sophomores, juniors, and seniors. Participants apply to the program and, if accepted, receive patient rights and professionalism training. Students shadow the physician they are paired with at least four times and submit a reflective essay about their experience.SIMS program coordinators administered surveys before and after shadowing to assess changes in students' perceptions and understanding of medical careers.The authors observed, in the 61 Stanford premedical students who participated in SIMS between March and June 2010 and completed both pre- and postprogram questionnaires, significant increases in familiarity with physician responsibilities and in understanding physician-patient interactions. The authors detected no significant changes in student commitment to pursuing medicine. Student perceptions of the value of shadowing-high both pre- and post shadowing-did not change.Physician shadowing by premedical baccalaureate students appears to promote an understanding of physician roles and workplace challenges. Future studies should identify the ideal timing, format, and duration of shadowing to optimize the experience and allow students to make informed decisions about whether to pursue a medical career.

Purpose: A retrospective analysis of the MUSE* *VIVUS, Inc., Menlo Park, California. clinical trial was performed to evaluate the efficacy and safety of transurethral alprostadil in patients with erectile dysfunction after radical prostatectomy.Materials and Methods: Patients received doses of transurethral alprostadil in the clinic and those for whom a suitable dose was determined were treated at home with active drug or placebo for 3 months. Patients had undergone radical prostatectomy no less than 3 months before study entry.Results: Of the 384 patients in whom radical prostatectomy was identified as a cause of erectile dysfunction 70.3% had an erection believed sufficient for intercourse in the clinic and 57.1% on active medication had sexual intercourse at least once at home. The product of clinic and home success rates (70.3 x 57.1%) was an overall success rate (the likelihood of active treatment to lead to intercourse at home) of 40.1%. The frequency of most adverse effects of radical prost...

The occurrence of central hypothyroidism in previously euthyroid children during GH therapy has been reported with widely varying incidence. We monitored the acute effects on the hypothalamic-pituitary-thyroid axis in 15 euthyroid children with classic GH deficiency during the first year of GH therapy. All were initially euthyroid, as assessed by normal baseline TSH, T4, free T4, and T3 levels and negative antithyroid antibodies. A thyroid profile (T4, free T4 index, T3, rT3, and TSH) was performed at baseline and 1, 3, 6, 9, and 12–15 months after GH therapy began; a TRH stimulation test was performed at baseline and after 1, 3, and 9 months of therapy. By 1 month, there were significant decreases in T4, free T4 index, and rT3, and significant increases in T3 and the T3/T4 ratio. The changes from baseline values were greatest at 1 month, were almost universal for all thyroid values, and showed a gradual return to baseline from 3–12 months. There were no clinical signs of hypothyroidism and no change in baseline or TRH-stimulated TSH levels or in cholesterol levels, and all patients grew at velocities expected for the treatment schedule. There is little evidence for the development of clinically significant hypothyroidism in the great majority of initially euthyroid patients after GH therapy is begun. T4 supplementation is seldom needed in such patients.

Objective: To study the immunologic effects of recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor type 1 (rhIGF-1), or the combination, in patients with moderately advanced HIV infection. Design: Randomized but not blinded trial. Setting: Government medical research center. Patients: Twenty-four HIV-infected patients with CD4 cell counts of 100–400 × 106/l who were receiving nucleoside antiretroviral therapy. Interventions: Either rhGH, rhIGF-1, or the combination was administered subcutaneously for 12 weeks. Main outcome measures: Immunologic parameters, including T-cell subsets and assays of in vitro interleukin (IL)-2 production in response to antigens and mitogens, and safety profile. Results: Plasma IGF-1 levels were low or low-normal prior to treatment and increased with all three therapies. There were no significant changes in CD4 cell counts, RA/RO CD4 cell subsets, natural killer cell function, immunoglobulin levels, or in vitro IL-2 production in response to mitogen or alloantigens. However, there was an upward trend (and for p18IIIB a statistically significant increase) in the in vitro IL-2 production in response to each of five HIV envelope peptides. Potential toxic effects included fatigue, arthralgia, edema, myalgia, and headache. Patients also were noted to have weight gain averaging 4 kg early in the course of treatment. Conclusions: These results suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that modest improvement in HIV-specific immune function was attained. Further studies will help clarify the therapeutic potential of rhGH/rhIGF-1 as an immunostimulator in the setting of HIV infection.

OBJECTIVE To examine if dual replacement with insulin and rhIGF-I, recombinant human insulin-like growth factor I (rhIGF-I) may be safe and result in improved metabolic control and reduced insulin usage. RESEARCH DESIGN AND METHODS Forty-three patients with IDDM were randomized to receive a daily injection of rhIGF-I (80 mcg/kg s.c.) or placebo while on conventional insulin therapy for 4 weeks. Insulin was adjusted in the attempt to achieve predetermined goal glycemic values. Free and total IGF-I, four daily blood glucoses, and HbA1c were measured. RESULTS Before randomization, placebo and rhIGF-I groups exhibited low plasma levels of free and total IGF-I, which increased toward normal levels during the treatment period only in the rhIGF group. The regression curve obtained from the average of daily blood glucose measurements indicated that the glycemic profile, overlapping in the lead-in period, exhibited a downward trend in the rhIGF-I group during the treatment period. Mean blood glucose level during the last 10 days of treatment was lower in the rhIGF-I groups (174 ± 37 vs. 194 ± 32 mg/dl). HbA1c level was reduced by more than one-half percent more in the rhIGF-I group (−1.85%) than in the control group (−1.3%). The dose of regular insulin was significantly lower in the rhIGF-I group (0.2 ± 0.1 vs. 0.28 ± 0.1 U · kg−1 · 10 days−1 in the placebo group; P < 0.05). CONCLUSIONS rhIGF-I in combination with conventional insulin treatment ameliorated the low plasma total and free IGF-I levels and was well tolerated in IDDM. There was a trend toward improved glycemic control, while the regular insulin dose was significantly decreased.

Background Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. Methods Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 μg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. Results During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P

Pharmacokinetics of insulin-like growth factor-1 in advanced chronic renal failure. Information regarding the impact of chronic renal failure (CRF) on IGF-1 serum clearance is limited. Thus we evaluated the pharmacokinetics of insulin-like growth factor-1 (IGF-1) in six normal adults and six adults with advanced CRF (serum creatinine 7 ± 0.8 mg/dl). All subjects were given 80 µg/kg recombinant human IGF-1 s.c. and blood was sampled over 48 hours. Baseline total serum IGF-1 levels were similar in both groups, but peak levels were elevated significantly in CRF; this was apparently related to the reduced distribution volume in CRF subjects. CRF did not affect the metabolic clearance rate (MCR) of total serum IGF-1. Immunoreactive IGF binding protein-3 (IGFBP-3) levels were greater in CRF. Western immunoblots revealed that the apparent increase in IGFBP-3 was largely due to an increase in immunoreactive fragments. IGFBP-3 protease activity was not increased. Thus IGFBP fragment accumulation likely reflects reduced fragment clearance. Western ligand blots revealed elevated 30 and 34kDa IGFBP levels and IGFBP products in CRF serum. Serum acid labile subunit levels were unchanged in CRF. Peak free IGF-1 levels and the MCR of free IGF-1 did not differ between groups. In both groups the MCR of free IGF-1 exceeded the MCR of total IGF-1 by approximately 30-fold. These data suggest that in CRF patients receiving s.c. IGF-1: (a) total serum IGF-1 levels are increased as a result of elevated circulating IGFBPs that may restrict the distribution of IGF-1 beyond plasma; (b) serum free IGF-1 levels are not altered; and (c) the IGF-1 MCR is unchanged in CRF. Thus, in advanced CRF, apart from a reduction in the total IGF-1 volume of distribution the pharmacokinetics of IGF-1 are largely unaltered.

The authors describe the population health curriculum at the Stanford University School of Medicine from 2003 to 2007 that includes a requirement for first-year medical students to engage in community-based population health projects. The new curriculum in population health comprises classroom and experiential teaching methods. Population health projects, a key component of the curriculum, are described and classified by topic and topic area (e.g., health education; health services) and the intended outcome of the intervention (e.g., establishing new policies; advocacy). During the past four years, 344 students have entered the curriculum and have participated in 68 population health projects. The projects were determined both by students' interests and community needs, and they represented diverse topics: 51% of the 68 projects addressed topics in the area of disease prevention and health promotion; 28% addressed health care access; 15% addressed health services; 4% addressed emergency preparedness; and 1% addressed ethical issues in health. Each project had one of three targets for intervention: community capacity building, establishing policies and engaging in advocacy, and bringing about change or improvement in an aspect of the health care system. Projects represented diverse stages in the evolution of a community-campus partnership, from needs assessment to planning, implementation, and evaluation of project outcomes. Experience to date shows that classroom-based sessions and experiential learning in the area of population health can be successfully integrated in a medical school curriculum. When contextualized in a population health curriculum, population health projects can provide future physicians with an experiential counterpart to their classroom learning.

To the Editor:A Chinese herb, Polygonum multiflorum, known as Shou Wu Pian and He Shou Wu root, is an ingredient of many herbal supplements promoted to treat balding, dizziness, prostatitis, and constipation. Five patients with acute hepatitis associated with the use of Polygonum multiflorum have pr

Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder.In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales.Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination.Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

We evaluated the effects of alprostadil, prazosin hydrochloride, and alprostadil/prazosin hydrochloride, agents used in the clinical treatment of male erectile dysfunction, on the motility, viability and membrane integrity of human sperm.Ten healthy volunteers provided semen samples that were incubated with 0.4 mg./ml. alprostadil, 0.1 and 0.2 mg./ml. prazosin hydrochloride and 0.4 mg./ml. alprostadil plus 0.1 mg./ml. prazosin hydrochloride for 2 hours. Control incubations included polyethylene glycol 1450, the formulation vehicle for the clinical use of alprostadil and prazosin, and Ham's F-10 buffer. Serial evaluations of percent sperm motility, percent viability, membrane function (by hypo-osmotic swelling test) and several computer generated measurements of sperm motion, including straight line velocity, curvilinear velocity, linearity and amplitude of lateral head displacement, were made.None of the agents had a significant impact on the percentage of motile or viable sperm or on sperm membrane function. Incubation with 0.2 mg./ml. prazosin reduced straight line velocity and curvilinear velocity significantly compared with the other agents. These changes were most likely a direct result of the viscosity of the 0.2 mg./ml. prazosin solution and not a cellular or metabolic effect on the sperm.Alprostadil and prazosin hydrochloride at doses used in transurethral therapy for erectile dysfunction have no effect on the motility, viability and membrane integrity of human sperm.

✓ The purpose of this study was to determine the effect of insulin-like growth factor-I (IGF-I) on the catabolic state and clinical outcome of head-injured patients. Thirty-three patients between the ages of 18 and 59 years with isolated traumatic head injury and Glasgow Coma Scale (GCS) scores of 4 to 10 were randomized to one of two groups. All patients received standard neurosurgical intensive care plus aggressive nutritional support; the patients in the treatment group also received intravenous therapy with continuous IGF-I (0.01 mg/kg/hour). During the 14-day dosing period, the control patients lost weight, whereas treated patients gained weight despite a significantly higher measured energy expenditure and lower caloric intake (p = 0.02). Daily glucose concentrations and nitrogen outputs were greater in control patients (p = 0.03) throughout the study period. During Week 1, only treated patients achieved positive nitrogen balance. Fifteen of 17 treated and 13 of 16 control patients survived the 1st week. No deaths occurred in patients whose serum IGF-I concentrations were higher than 350 ng/ml. Dichotomized Glasgow Outcome Scale scores for patients with baseline GCS scores of 5 to 7 improved from poor to good for eight of 12 treated patients but for only three of 11 control patients (p = 0.06). Eight of 11 treated patients with serum IGF-I concentrations that were at least 350 ng/ml achieved moderate-to-good outcome scores at 6 months, compared to only one of five patients with lower concentrations (p < 0.05). These findings indicate that pharmacological concentrations of IGF-I may improve clinical outcome and nitrogen utilization in patients with moderate-to-severe head injury.

We conducted a controlled trial of recombinant human GH (rhGH) in 27 healthy elderly women (66.7 +/- 3.0 yr), of whom 8 took a stable dose of replacement estrogen throughout the study (plus estrogen group). Hormone or placebo was given as a single daily injection. A total of 19 women were assigned to receive rhGH at an initial daily dose of 0.043 mg/kg BW. After several weeks, 50% dose reductions were necessitated by side-effects. The last 7 subjects to be enrolled began treatment at this reduced level. A total of 13 women assigned to rhGH and 14 women assigned to placebo completed 6 months of drug treatment. In the rhGH group, 6 women took estrogen; thus, the effects of rhGH were assessed separately by estrogen status. Circulating insulin-like growth factor-I (IGF-I) levels were similar at baseline (rhGH, 133 +/- 40.4 micrograms/L; placebo, 128 +/- 13). rhGH increased IGF-I and IGF-I-binding protein-3 (IGFBP-3) in all subjects [6 month IGF-I in plus estrogen women, 230 +/- 25.4 micrograms/L; in those not receiving estrogen (minus estrogen), 308 +/- 21.3]. No changes in IGF-I or IGFBP-3 occurred with placebo (IGF-I, 144 +/- 21.3 micrograms/L). Skinfold thickness measurements showed an 11% decrease in fat mass (P < 0.005) and a 9% decrease in percent fat after 6 months of rhGH treatment. No significant difference in nitrogen balance was seen in either group at 6 months, but rhGH increased creatinine clearance by 9.2% (P < 0.05). rhGH dramatically increased markers of bone turnover, with more pronounced effects in minus estrogen women. Hydroxyproline excretion increased by 20% and 80%, and pyridinoline excretion increased by 44% and 75% in plus and minus estrogen subgroups, respectively. Osteocalcin concentrations increased by more than 60% in minus estrogen women (P < 0.05), but did not change in the plus estrogen group. No changes were observed in circulating type I procollagen extension peptide in either group, and no change in any turnover marker was seen in the placebo group. rhGH did not alter blood pressure or circulating L-T4 levels, but a transient increase in serum T3 was observed in the minus estrogen group at 3 months. rhGH decreased low density lipoprotein cholesterol in the minus estrogen group, but otherwise no significant changes in circulating lipoproteins or fibrinogen were observed. Eight women assigned to rhGH and 14 placebo-treated women remained on blinded treatment through 12 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Objective : To increase lean body mass and improve health status in patients with wasting associated with the acquired immunodeficiency syndrome (AIDS) by treatment with recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor 1 (rhIGF-1), or both. Design : Randomized, double-blind, placebo-controlled clinical trial. Setting : University of New Mexico Clinical Research Center and University of Texas Southwestern Medical Center. Patients : 60 patients with AIDS and wasting as defined by the Centers for Disease Control and Prevention. Patients were divided into four groups of 15 patients each. Intervention : Group 1 received 1.4 mg of rhGH once daily plus placebo twice daily ; group 2 received 5 mg of rhIGF-1 twice daily plus placebo once daily ; group 3 received 5 mg of rhIGF-1 twice daily plus 1.4 mg of rhGH once daily ; and group 4 received placebo three times daily. Measurements : Body weight, body composition, muscle strength, protein catabolism, quality of life, and immune status were assessed at baseline, and changes in these variables were measured at 6 and 12 weeks. Results : At 6 weeks, lean body mass had increased and total fat mass had decreased in the groups receiving rhGH, rhIGF-1, or both. Group 3 had the greatest changes in lean body mass (mean ± SE, 3.2 ± 0.59 kg ; P < 0.001) ; only in this group were changes in body mass maintained at 12 weeks. Only patients in group 1 had improvement in muscular strength of the knees and upper body (P = 0.04) and quality of life (P = 0.01). Immunologic function did not improve in any group. Conclusions : Growth factor therapy had significantly increased lean body mass and decreased fat mass by 6 weeks, but these improvements persisted for 12 weeks only in group 3. Growth factor therapy at the dosages used in this study is not recommended because the magnitude of weight gain was modest and improvements in quality-of-life measures varied.

We now report successful preoperative lateralization by simultaneous bilateral inferior petrosal sinus sampling of the relevant pituitary hormones in two patients with non-ACTH-secreting microadenomas. The patients were a 23-year-old woman with a mixed pituitary tumor secreting TSH and causing hyperthyroidism and a 44-year-old man with acromegaly. Both had high-resolution CT scans without evidence of adenoma; the patient with acromegaly also had a normal MRI scan of the pituitary

While more than 40 cases of TSH-secreting pituitary adenomas have been reported in the medical literature (1,2), little attention has been devoted to structural variability—in particular that due to carbohydrate microheterogeneity—of thyrotropin molecules derived from different tumors and distinct physiological states. We recently evaluated two patients representing extremes within the spectrum of TSH-secreting pituitary adenomas and have contrasted several biochemical features of these tumors.

The effects of hypothalamic hypothyroidism vs. primary hypothyroidism on TSH carbohydrate structure were studied in the rat. Adult male rats with bilateral paraventricular nuclear lesions (n = 10), sham lesions (n = 10), and thyroidectomies (n = 6) were studied 2 weeks postoperatively and compared to normal animals without surgery (n = 6). Pituitaries were incubated in medium containing [3H]glucosamine for 24 h. TSH was immunoprecipitated from medium and pituitary sonicates using anti-TSH beta serum, digested with pronase to obtain TSH glycopeptides, desalted, then analyzed by Concanavalin-A (Con-A) chromatography. Compared to sham controls, hypothalamus-lesioned animals contained a greater proportion of secreted TSH glycopeptides that bound weakly to Con-A, indicating a shift from bisecting and/or multiantennary structures in control animals to biantennary and/or truncated hybrid forms in hypothalamus-lesioned animals. In contrast, thyroidectomized animals, compared to normal and lesioned animals, contained a greater proportion of secreted TSH glycopeptides that did not bind to Con-A, indicating a shift from biantennary and/or truncated hybrid forms to bisecting and/or multiantennary forms. The characteristics of the carbohydrate chains on secreted TSH differed markedly in hypothalamic vs. primary hypothyroidism despite equally low thyroid hormone levels in vivo. Thus, in addition to regulating TSH secretion, hypothalamic hormones alter TSH carbohydrate structure, which may affect its bioactivity and MCR.

TSH-secreting pituitary tumors represent one major group of the syndrome of inappropriate secretion of TSH (1). This syndrome is defined as inappropriately measurable or elevated concentrations of TSH in the presence of increased total and free serum thyroid hormones, and is comprised of both neoplastic and non-neoplastic variants. Neoplastic TSH production by a pituitary tumor may occur in the setting of either a microadenoma or macroadenoma and may be associated with the production of other hormones, particularly growth hormone and prolactin. Because of increased awareness of physicians, these tumors are being recognized with increasing frequency. Currently, over 40 cases have been reported in the literature, and we have seen or are aware of several additional unreported cases.