58 results on '"Neil Gesundheit"'
Search Results
2. Stanford University School of Medicine
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Daniel Bernstein, Cynthia A. Irvine, Preetha Basaviah, James N. Lau, Bahij Austin, Paul J. Utz, and Neil Gesundheit
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General Medicine ,Education - Published
- 2021
3. Medical educators’ beliefs about teaching, learning, and knowledge: development of a new framework
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Marleen Ottenhoff- de Jonge, Iris van der Hoeven, Neil Gesundheit, Roeland van der Rijst, and Anneke Kramer
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BackgroundThe 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’.MethodsWe 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.ResultsWe 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. ConclusionsOur 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.
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- 2021
4. From critic to inspirer: four profiles reveal the belief system and commitment to educational mission of medical academics
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Neil Gesundheit, Willem J. J. Assendelft, Anneke W. M. Kramer, Roeland M. van der Rijst, Friedo W. Dekker, Albert J. J. A. Scherpbier, Lianne N. van Staveren, Marleen W. Ottenhoff de Jonge, Fac. Health, Medicine and Life Sciences, RS: SHE - R1 - Research (OvO), and Onderwijs instituut FHML
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Male ,Value (ethics) ,020205 medical informatics ,Teaching beliefs ,lcsh:Medicine ,Identity (social science) ,02 engineering and technology ,Teacher qualities ,Professional Competence ,0302 clinical medicine ,Conceptions of teaching and learning ,Pedagogy ,0202 electrical engineering, electronic engineering, information engineering ,Cluster Analysis ,INTERVIEWS ,Teacher attributes ,030212 general & internal medicine ,Qualitative Research ,lcsh:LC8-6691 ,Class (computer programming) ,Education, Medical ,Professional development ,General Medicine ,Teacher identity ,Variety (cybernetics) ,Teacher profiles ,SATURATION ,Female ,Curriculum ,Faculty development ,Psychology ,Research Article ,Theme (narrative) ,Adult ,Medical education ,Faculty, Medical ,Teacher mission ,Context (language use) ,Education ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Interviews as Topic ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,TEACHER ,Humans ,CONCEPTIONS ,ENVIRONMENT ,lcsh:Special aspects of education ,lcsh:R ,United States ,CONTEXT ,IDENTITY ,Total Quality Management - Abstract
Background: The educational beliefs of medical academics influence how they act in class and thus influence student learning. One component of these are beliefs academics hold about the qualities of teachers themselves. These teacher qualities range from behaviours and competencies to more personal attributes such as the teacher's identity and mission. However, it is unclear what medical academics believe to be key teacher qualities. Therefore, this study explored the variety of medical academics' beliefs about 'teacher qualities', aiming to identify and characterise profiles of academics with similar beliefs.Methods: We interviewed 26 expert academics from two medical schools to explore their beliefs about teacher qualities. A concentric onion-model focusing on teacher qualities was used to analyse and categorise the data deductively. Within each theme we developed subthemes inductively. To gain insight into the variety of beliefs we then clustered the participants into teacher profiles according to the themes. To better understand each of the profiles we carried out a quantitative study of the differences between profiles regarding subthemes, contextual and personal factors, and analysed statistical significance using Fisher's exact- and Student's t-tests for categorical and continuous data, respectively.Results: Four profiles of medical academics were identified, corresponding to the most central theme that each participant had reflected on: the 'Inspirer', 'Role-model', 'Practitioner', and 'Critic'. The focus of the profiles varied from external constraining factors within the 'Critic' profile to affective personal qualities within the 'Role-model' and 'Inspirer' profiles. The profiles could be regarded as hierarchically ordered by inclusiveness. Educational institute was the only significant factor related to the profiles.Conclusions: Besides the relevance of affective teacher qualities, the 'Inspirer' profile demonstrates the importance of developing a clear mission as a teaching academic, centred around student learning and professional development. In our view, academics who inspire their students continue to be inspired themselves.The practical implications are described for faculty development programmes, and for the potential value of using these profiles within medical schools. In the discourse on educational beliefs, the authors argue that more attention should be paid to affective qualities, in particular to explicating the educational mission of academics.
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- 2019
5. In Reply to Tallia et al
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Neil Gesundheit
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General Medicine ,Psychology ,Education - Published
- 2020
6. Filling the treatment gap in the weight management of overweight and obese patients
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Neil Gesundheit
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Pregnancy ,Pediatrics ,medicine.medical_specialty ,treatment ,Proceedings Article ,business.industry ,Sleep apnea ,General Medicine ,Type 2 diabetes ,Overweight ,medicine.disease ,Obesity ,unmet need ,Surgery ,Blood pressure ,Weight loss ,Weight management ,overweight ,Medicine ,medicine.symptom ,business - Abstract
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.
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- 2012
7. Impact of student ethnicity and patient-centredness on communication skills performance
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Christy Boscardin, Alicia Fernandez, Andrew Nevins, Karen E. Hauer, Malathi Srinivasan, and Neil Gesundheit
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business.industry ,education ,Perspective (graphical) ,Psychological intervention ,Ethnic group ,Regression analysis ,General Medicine ,Education ,Patient centredness ,Health care ,Communication skills ,business ,Psychology ,Social psychology ,Clinical psychology ,Health care quality - Abstract
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.
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- 2010
8. Engaging Students in Dedicated Research and Scholarship During Medical School: The Long-Term Experiences at Duke and Stanford
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Patricia C. Cross, Robert P. Drucker, Daniel T. Laskowitz, Julie Parsonnet, and Neil Gesundheit
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Medical education ,Research program ,Student population ,Biomedical Research ,Students, Medical ,Time Factors ,Education, Medical ,Medical school ,MEDLINE ,General Medicine ,California ,Education ,Scholarship ,Basic research ,North Carolina ,ComputingMilieux_COMPUTERSANDEDUCATION ,Curriculum ,Sociology ,Schools, Medical ,Period (music) - Abstract
For more than 40 years, the faculties of Duke University School of Medicine (SOM) and Stanford University SOM have encouraged or required students to engage in scholarship as a way to broaden their education and attract them to careers in academic medicine. A dedicated period of research was first integrated into the Duke curriculum in 1959 to provide an opportunity for students to develop into physician leaders through a rigorous scholarly experience in biomedically related research. Originally designed to foster experience in laboratory-based basic research, the third-year program has evolved in response to the changing landscape of medicine and shifting needs and career interests of the medical student population. Stanford University SOM also has a long-standing commitment to biomedical research and currently requires each student to complete an in-depth, mentored "scholarly concentration." In contrast to Duke, where most of the scholarly research experiences take place in an immersive third year, the Stanford program encourages a longitudinal, multiyear exposure over all four (or five) years of medical school. Although the enduring effects of embedding a rigorous research program are not yet fully known, preliminary data suggest that these experiences instill an appreciation for research, impart research rigor and methodologies, and may motivate students to pursue careers in academic medicine. The authors discuss the histories, evolution, logistics, and ongoing challenges of the research programs at Duke University SOM and Stanford University SOM.
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- 2010
9. Medical Education for a Healthier Population: Reflections on the Flexner Report From a Public Health Perspective
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Ian Johnson, Evelyn T. Ho, Ann Banchoff, Lloyd F. Novick, Neil Gesundheit, David Butler-Jones, Denise Koo, M. Marie Dent, Jonathan A. Finkelstein, Jean Parboosingh, Stephen A. McCurdy, Denise Donovan, Lily Velarde, Jan K. Carney, Barbie Shore, Laurence Cohen, Rika Maeshiro, and Nancy M. Bennett
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Canada ,medicine.medical_specialty ,education.field_of_study ,Medical education ,Education, Medical ,business.industry ,Public health ,education ,Population ,MEDLINE ,General Medicine ,Population health ,United States ,Rigour ,Education ,Cause of Death ,Health Care Reform ,Health care ,medicine ,Humans ,Public Health ,Health care reform ,Flexner Report ,business - Abstract
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.
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- 2010
10. The use of virtual patients to assess the clinical skills and reasoning of medical students: initial insights on student acceptance
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Patricia Youngblood, Uno Fors, Neil Gesundheit, Pauline Brutlag, William T. Gunning, and Nabil Zary
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Students, Medical ,Medical psychology ,Teaching method ,education ,MEDLINE ,Pilot Projects ,Education ,Humans ,Medicine ,Computer Simulation ,Neurological findings ,Consumer behaviour ,Internet ,Medical education ,Modality (human–computer interaction) ,business.industry ,Teaching ,Clinical reasoning ,Problem-Based Learning ,General Medicine ,Consumer Behavior ,Clinical Competence ,business ,Clinical skills ,Computer-Assisted Instruction ,Education, Medical, Undergraduate ,Clinical psychology - Abstract
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.
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- 2009
11. Does feedback matter? Practice-based learning for medical students after a multi-institutional clinical performance examination
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Malathi Srinivasan, Michael S Wilkes, Claudia Der-Martirosian, Karen E. Hauer, and Neil Gesundheit
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medicine.medical_specialty ,Students, Medical ,Evidence-based practice ,Teaching method ,education ,Physical examination ,Feedback ,Education ,Cohort Studies ,Humans ,Medicine ,Medical history ,Medical History Taking ,Physical Examination ,Competence (human resources) ,medicine.diagnostic_test ,business.industry ,Communication ,Teaching ,General Medicine ,Physical therapy ,Normative ,Observational study ,Clinical Competence ,business ,Education, Medical, Undergraduate ,Cohort study - Abstract
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.
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- 2007
12. Is a career in medicine the right choice? The impact of a physician shadowing program on undergraduate premedical students
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David M. Fetterman, Neil Gesundheit, Patricia Y. Lewis, Jennifer Y. Wang, and Hillary Lin
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Education, Premedical ,Male ,medicine.medical_specialty ,Medical education ,Career Choice ,business.industry ,MEDLINE ,General Medicine ,Choice Behavior ,California ,Education ,Clinical Practice ,Undergraduate methods ,Family medicine ,Physicians ,Surveys and Questionnaires ,Students, Premedical ,Medicine ,Humans ,Female ,business ,Career choice ,Education, Medical, Undergraduate ,Retrospective Studies - Abstract
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.
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- 2015
13. EFFICACY AND SAFETY OF TRANSURETHRAL ALPROSTADIL IN PATIENTS WITH ERECTILE DYSFUNCTION FOLLOWING RADICAL PROSTATECTOMY
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Kara L.M. Weldon, Ridwan Shabsigh, Raymond A. Costabile, Marianne Spevak, Irving J. Fishman, Joshua L. Rapport, Kerry J. Nemo, Peter Y. Tam, Fred E. Govier, Neil Gesundheit, and Wayne J.G. Hellstrom
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medicine.medical_specialty ,Chemotherapy ,Prostatectomy ,business.industry ,medicine.medical_treatment ,Urology ,Placebo ,medicine.disease ,Surgery ,Clinical trial ,Sexual intercourse ,Erectile dysfunction ,medicine ,business ,Adverse effect ,Complication - Abstract
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...
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- 1998
14. Changes in Thyroid Hormone Levels during Growth Hormone Therapy in Initially Euthyroid Patients: Lack of Need for Thyroxine Supplementation1
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Neil Gesundheit, Barry M. Sherman, and David T. Wyatt
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endocrine system ,medicine.medical_specialty ,Triiodothyronine ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,Incidence (epidemiology) ,Biochemistry (medical) ,Clinical Biochemistry ,Thyroid ,Biochemistry ,Endocrinology ,TRH stimulation test ,medicine.anatomical_structure ,Internal medicine ,Toxicity ,medicine ,Central hypothyroidism ,Euthyroid ,business ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
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.
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- 1998
15. Pilot study of the immunologic effects of recombinant human growth hormone and recombinant insulin-like growth factor in HIV-infected patients
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Dan L. Longo, Samuel Broder, Sergio Bauza, Bach Yen Nguyen, David Venzon, Neil Gesundheit, Michael Baseler, William J. Murphy, Mario Clerici, Gene M. Shearer, and Robert Yarchoan
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Adult ,Male ,Cellular immunity ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,HIV Core Protein p24 ,Immunoglobulins ,HIV Infections ,Pilot Projects ,Immunostimulant ,Insulin-like growth factor ,Immune system ,T-Lymphocyte Subsets ,Immunopathology ,medicine ,Humans ,Immunology and Allergy ,Insulin-Like Growth Factor I ,Human Growth Hormone ,business.industry ,Recombinant Insulin-Like Growth Factor ,Body Weight ,Interleukin ,T-Lymphocytes, Helper-Inducer ,Immunotherapy ,Middle Aged ,Recombinant Proteins ,CD4 Lymphocyte Count ,Killer Cells, Natural ,Infectious Diseases ,Leukocytes, Mononuclear ,Interleukin-2 ,Female ,business - Abstract
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.
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- 1998
16. Adjunctive Growth Hormone during Ovarian Hyperstimulation Increases Levels of Insulin-Like Growth Factor Binding Proteins in Follicular Fluid: A Randomized, Placebo-Controlled, Cross-Over Study*
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Pramila V. Dandekar, Mary C. Martin, Jaron Rabinovici, Sharron E. Gargosky, Neil Gesundheit, Stephen M. Rosenthal, and Nicholas A. Cataldo
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Adult ,endocrine system ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,medicine.medical_treatment ,Clinical Biochemistry ,Radioimmunoassay ,Stimulation ,Ligands ,Biochemistry ,Insulin-like growth factor-binding protein ,Placebos ,Endocrinology ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Ovulation ,media_common ,Cross-Over Studies ,In vitro fertilisation ,biology ,Human Growth Hormone ,Growth factor ,Ovary ,Biochemistry (medical) ,Follicular fluid ,Stimulation, Chemical ,Follicular Fluid ,Insulin-Like Growth Factor Binding Proteins ,Insulin-Like Growth Factor Binding Protein 3 ,Theca ,biology.protein ,Female ,Menotropin - Abstract
GH increases circulating insulin-like growth factor I (IGF-I), which can promote the growth and differentiated function of ovarian granulosa and theca cells. Reported studies of GH as an adjunct to menotropin stimulation in women, largely those with ovarian dysfunction, have not consistently shown a benefit of GH, despite increases in serum and follicular fluid IGF-I. We hypothesized that changes in intrafollicular IGF-binding proteins (IGFBPs), which can antagonize IGF actions on granulosa cells, may underlie the inconsistent effects of GH. In the present study of GH, administered in double-blind, placebo-controlled, cross-over fashion to regularly cycling women undergoing in vitro fertilization, we found that follicular fluid levels of IGFBP-1, -3, and -4 and serum levels of IGFBP-3, as well as follicular fluid and serum IGF-I, were significantly increased in the GH-treated cycles, when compared with the placebo cycle of the same patient. We suggest that the net increase in intrafollicular IGFBPs in GH cycles may mitigate the potential beneficial effect of increased IGF-I.
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- 1997
17. Dual Hormonal Replacement With Insulin and Recombinant Human Insulin-Like Growth Factor I in IDDM: Effects on glycemic control, IGF-I levels, and safety profile
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Teresa Quattrin, Kathryn Thrailkill, Lester Baker, Jean Litton, Karen Dwigun, Melissa Rearson, Mary Poppenheimer, David Giltinan, Neil Gesundheit, Paul Martha, and null Jr
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Blood Glucose ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Placebo ,Internal medicine ,Blood Glucose Self-Monitoring ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Insulin-Like Growth Factor I ,Child ,Pancreatic hormone ,Glycemic ,Advanced and Specialized Nursing ,business.industry ,medicine.disease ,Recombinant Proteins ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Endocrinology ,Metabolic control analysis ,Regular insulin ,Drug Therapy, Combination ,Female ,Safety ,business - Abstract
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.
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- 1997
18. Treatment of Men with Erectile Dysfunction with Transurethral Alprostadil
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Harin Padma-Nathan, Wayne J.G. Hellstrom, Fran E. Kaiser, Richard F. Labasky, Tom F. Lue, Wolfram E. Nolten, Paul C. Norwood, Craig A. Peterson, Ridwan Shabsigh, Peter Y. Tam, Virgil A. Place, Neil Gesundheit, Christy Cowley, Kerry J. Nemo, Alfred P. Spivack, Darby E. Stephens, and Leslie K. Todd
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medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Urology ,General Medicine ,Placebo ,medicine.disease ,Effective dose (pharmacology) ,Surgery ,Clinical trial ,chemistry.chemical_compound ,Urethra ,medicine.anatomical_structure ,Erectile dysfunction ,chemistry ,medicine ,Prospective cohort study ,Prostaglandin E1 ,business - Abstract
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
- Published
- 1997
19. Changes in body composition of human immunodeficiency virus-infected males receiving insulin-like growth factor I and growth hormone
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Philip D.K. Lee, Neil Gesundheit, James M. Pivarnik, Kenneth J. Ellis, and Julie G. Bukar
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Opportunistic infection ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Biology ,Biochemistry ,Cachexia ,Insulin-like growth factor ,Absorptiometry, Photon ,Endocrinology ,Double-Blind Method ,Acquired immunodeficiency syndrome (AIDS) ,Weight loss ,Internal medicine ,Immunopathology ,Weight Loss ,medicine ,Humans ,Insulin-Like Growth Factor I ,Acquired Immunodeficiency Syndrome ,Anthropometry ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,Adipose Tissue ,Growth Hormone ,Body Composition ,Etiology ,Regression Analysis ,Drug Therapy, Combination ,medicine.symptom ,Body mass index - Abstract
Weight loss is a common, persistent characteristic of long term human immunodeficiency virus (HIV-1) infection; its full etiology remains unknown. Because treatment with GH has induced nitrogen retention in various catabolic conditions, we designed this study to determine whether a moderate dose of insulin-like growth factor I (IGF-I) combined with a low GH dose could impede the catabolic response seen in HIV-1 infection. A double blind, placebo-controlled study design was used. Subjects in the GH/IGF-I treatment group (n = 44) and control group (n = 22) continued to receive their routine stable antiretroviral therapy. No patient had a recent history of opportunistic infection, malignancy, or Kaposi's sarcoma and had dietary intakes of at least 25 Cal/kg weight.day at study entry. During the 12-week study period, dietary instruction was given, and subjects were encouraged to maintain an intake of 35 Cal/kg and 1 g protein/kg. All subjects had a body mass index of 19.8 kg/m2 or less at the time of study entry or a weight loss of 10% or more of their premorbid weight and a body mass index below 26.1 kg/m2. The treatment group received 0.34 mg (0.68 mg/day) GH, twice daily, and 5.0 mg (10 mg/day) IGF-I, twice daily. Changes in body composition of total body potassium (TBK), total body nitrogen (TBN), fat-free mass (FFM), and body fat (Fat) were examined at 6 and 12 weeks during the treatment period. TBK, TBN, FFM, and Fat for the treatment and placebo groups were, on the average, below normal at study entry. At 6 weeks, the GH/IGF-I group showed a significant increase in FFM (P0.0001), a minimal increase in TBK (P0.05), and a substantial decrease in Fat (P0.01) compared with baseline values. The loss of body fat continued to be significant (P0.01) in the GH/IGF-I group treatment at 12 weeks, whereas the increase in FFM was minimal (P0.05). No significant changes in the mean body composition occurred at 6 or 12 weeks in the placebo group. By 12 weeks, neither TBK (body cell mass) nor TBN (total protein mass) had significantly increased relative to the values at baseline, although the FFM remained elevated. Thus, the combined GH and IGF-I doses used in this study in adult males with HIV-associated weight loss were ineffective in producing a sustained anabolic response and, in fact, resulted primarily in a significant loss of body fat.
- Published
- 1996
20. Pharmacokinetics of insulin-like growth factor-1 in advanced chronic renal failure
- Author
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John O. Ike, Andrew R. Hoffman, Raymond L. Hintz, Duane C. Bloedow, Neil Gesundheit, Fernando C. Fervenza, Ralph Rabkin, Helen Maidment, and Frances Liu
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Blotting, Western ,law.invention ,Insulin-like growth factor ,chemistry.chemical_compound ,Pharmacokinetics ,Pregnancy ,law ,Internal medicine ,Humans ,Medicine ,Distribution (pharmacology) ,Insulin-Like Growth Factor I ,Volume of distribution ,Creatinine ,business.industry ,Blood Proteins ,Middle Aged ,Blood proteins ,Blot ,Kinetics ,Endocrinology ,chemistry ,Nephrology ,Recombinant DNA ,Kidney Failure, Chronic ,Female ,business ,hormones, hormone substitutes, and hormone antagonists ,Protein Binding - Abstract
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.
- Published
- 1996
21. Mutations of the Growth Hormone Receptor in Children with Idiopathic Short Stature
- Author
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Neil Gesundheit, Lena M. S. Carlsson, Robin Covello, Kenneth M. Attie, James A. Wells, Shiuh-Ming Luoh, Audrey Goddard, Amy Chen Rundle, and Tim Clackson
- Subjects
Mutation ,medicine.medical_specialty ,General Medicine ,Growth hormone receptor ,Biology ,medicine.disease ,medicine.disease_cause ,Short stature ,Growth hormone secretion ,Idiopathic short stature ,Endocrinology ,Internal medicine ,medicine ,Growth Hormone Insensitivity Syndrome ,medicine.symptom ,Receptor ,Gene - Abstract
Background Short stature in children who are not deficient in growth hormone (GH) is probably caused by a variety of defects. Some children with idiopathic short stature have low serum concentrations of GH-binding protein, which is derived from the GH receptor. The possibility that low serum concentrations of GH-binding protein might indicate partial insensitivity to GH led us to investigate possible defects in the gene for the GH receptor in children with idiopathic short stature and low serum concentrations of GH-binding protein. Methods We studied 14 children with idiopathic short stature who were selected on the basis of normal GH secretion and low serum concentrations of GH-binding protein. Analysis of single-strand conformation polymorphisms and DNA sequencing were both used to identify mutations in the GH-receptor gene. Results Mutations in the region of the GH-receptor gene that codes for the extracellular domain of the receptor were found in 4 of the 14 children, but in none of 24 normal subjects...
- Published
- 1995
22. Dynamic changes of growth hormone—binding protein concentrations in normal men and patients with acromegaly: Effects of short-term fasting
- Author
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Roberta Demott Friberg, Sherleen H. Huang, Ariel L. Barkan, P. Jean Ho, Neil Gesundheit, and Wai Lee Wong
- Subjects
Adult ,Male ,Chronic exposure ,medicine.medical_specialty ,Calorie ,Endocrinology, Diabetes and Metabolism ,Endogeny ,Biology ,Cohort Studies ,Eating ,Endocrinology ,Reference Values ,Growth hormone-binding protein ,Internal medicine ,Acromegaly ,medicine ,Humans ,Circadian rhythm ,Aged ,Analysis of Variance ,Fasting ,Middle Aged ,medicine.disease ,Growth Hormone ,Female ,Carrier Proteins ,Quantitative analysis (chemistry) ,Federal state - Abstract
Plasma concentrations of growth hormone (GH) and GH-binding protein (GHBP) were measured at hourly intervals in five healthy men and five patients with acromegaly during the fed state and after a 5-day fast. GHBP concentrations (both total and complexed with endogenous GH) were analyzed by the ligand-mediated immunofunctional assay (LIFA). Total GHBP was similar in both groups during the fed state (104.4 +/- 5.2 and 101.6 +/- 10.3 pmol/L), did not exhibit a diurnal rhythm, and was unchanged by fasting (91.9 +/- 5.4 and 109.9 +/- 10.5 pmol/L, respectively). However, the GHBP/GH complex concentration was significantly higher in acromegalics than in controls (41.0 +/- 2.8 v 18.0 +/- 2.2 pmol/L, respectively; P.05), closely followed diurnal GH rhythm in normals, and was significantly correlated with mean 24-hour GH concentrations (r = .86, P.01). We conclude that plasma concentrations of GHBP are stable throughout the day and are unchanged either by short-term calorie deprivation or by chronic exposure to high levels of endogenous GH. In contrast, GHBP/GH complex concentrations are altered both acutely and chronically by ambient GH.
- Published
- 1995
23. Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults
- Author
-
Susan D. Boulware, N J Rennert, Neil Gesundheit, R. S. Sherwin, and William V. Tamborlane
- Subjects
Adult ,medicine.medical_specialty ,Glucose uptake ,medicine.medical_treatment ,Fatty Acids, Nonesterified ,Carbohydrate metabolism ,Biology ,Glucagon ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Insulin ,Insulin-Like Growth Factor I ,Pancreatic hormone ,Aged ,C-Peptide ,Dose-Response Relationship, Drug ,C-peptide ,Age Factors ,General Medicine ,Middle Aged ,Glucose clamp technique ,Recombinant Proteins ,Glucose ,Endocrinology ,chemistry ,Basal (medicine) ,Research Article - Abstract
The actions of recombinant human insulin-like growth factor-I (rhIGF-I) and insulin were compared in 21 healthy young (24 +/- 1 yr) and 14 healthy middle-aged (48 +/- 2 yr) subjects during 3-h paired euglycemic clamp studies using one of three doses (rhIGF-I 0.2, 0.4, and 0.8 micrograms/kg.min and insulin 0.2, 0.4, and 0.8 mU/kg.min, doses chosen to produce equivalent increases in glucose uptake). In younger subjects, rhIGF-I infusions suppressed insulin by 19-33%, C-peptide by 47-59% and glucagon by 33-47% (all, P < 0.02). The suppression of C-peptide was less pronounced with insulin than with rhIGF-I (P < 0.007). The metabolic responses to rhIGF-I and insulin were remarkably similar: not only did both hormones increase glucose uptake and oxidation in a nearly identical fashion, but they also produced similar suppression of glucose production, free fatty acid levels, and fat oxidation rates. In contrast, rhIGF-I had a more pronounced amino acid-lowering effect than did insulin (P < 0.004). In middle-aged subjects, basal IGF-I levels were 44% lower (P < 0.0001) whereas basal insulin and C-peptide were 20-25% higher than in younger subjects. Age did not alter the response to rhIGF-I. However, insulin-induced stimulation of glucose uptake was blunted in older subjects (P = 0.05). Our data suggest that absolute IGF-I and relative insulin deficiency contribute to adverse metabolic changes seen in middle age.
- Published
- 1994
24. Impact of student ethnicity and patient-centredness on communication skills performance
- Author
-
Karen E, Hauer, Christy, Boscardin, Neil, Gesundheit, Andrew, Nevins, Malathi, Srinivasan, and Alicia, Fernandez
- Subjects
Male ,Students, Medical ,Attitude of Health Personnel ,Communication ,Patient-Centered Care ,Surveys and Questionnaires ,Ethnicity ,Humans ,Female ,Clinical Competence ,Factor Analysis, Statistical ,Education, Medical, Undergraduate - Abstract
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.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.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.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.
- Published
- 2010
25. Empowerment evaluation: a collaborative approach to evaluating and transforming a medical school curriculum
- Author
-
Neil Gesundheit, David M. Fetterman, and Jennifer Deitz
- Subjects
Medical education ,Models, Educational ,Faculty, Medical ,Feedback, Psychological ,General Medicine ,United States ,Education ,ComputingMilieux_COMPUTERSANDEDUCATION ,Empowerment evaluation ,Humans ,Medical school curriculum ,Sociology ,Curriculum ,Power, Psychological ,Needs Assessment ,Schools, Medical ,Education, Medical, Undergraduate ,Program Evaluation - Abstract
Medical schools continually evolve their curricula to keep students abreast of advances in basic, translational, and clinical sciences. To provide feedback to educators, critical evaluation of the effectiveness of these curricular changes is necessary. This article describes a method of curriculum evaluation, called "empowerment evaluation," that is new to medical education. It mirrors the increasingly collaborative culture of medical education and offers tools to enhance the faculty's teaching experience and students' learning environments. Empowerment evaluation provides a method for gathering, analyzing, and sharing data about a program and its outcomes and encourages faculty, students, and support personnel to actively participate in system changes. It assumes that the more closely stakeholders are involved in reflecting on evaluation findings, the more likely they are to take ownership of the results and to guide curricular decision making and reform. The steps of empowerment evaluation include collecting evaluation data, designating a "critical friend" to communicate areas of potential improvement, establishing a culture of evidence, encouraging a cycle of reflection and action, cultivating a community of learners, and developing reflective educational practitioners. This article illustrates how stakeholders used the principles of empowerment evaluation to facilitate yearly cycles of improvement at the Stanford University School of Medicine, which implemented a major curriculum reform in 2003-2004. The use of empowerment evaluation concepts and tools fostered greater institutional self-reflection, led to an evidence-based model of decision making, and expanded opportunities for students, faculty, and support staff to work collaboratively to improve and refine the medical school's curriculum.
- Published
- 2010
26. Integrating collaborative population health projects into a medical student curriculum at Stanford
- Author
-
Lisa J. Chamberlain, Neil Gesundheit, N. Ewen Wang, Clarence H. Braddock, Evelyn T. Ho, and Ann Banchoff
- Subjects
medicine.medical_specialty ,Students, Medical ,education ,Population health ,Health Promotion ,California ,Education ,Nursing ,Health care ,Medicine ,Humans ,Community Health Services ,Cooperative Behavior ,Curriculum ,Health policy ,Schools, Medical ,Medical education ,HRHIS ,business.industry ,Public health ,Teaching ,International health ,General Medicine ,Health promotion ,Public Health ,business ,Education, Medical, Undergraduate - Abstract
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.
- Published
- 2008
27. Acute Hepatitis Associated With the Use of an Herbal Supplement (Polygonum Multiflorum) Mimicking Iron-overload Syndrome
- Author
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Bharathi Avula, Neil Gesundheit, Emil M. deGoma, Ashley R. Laird, Nina Ramchandani, and Ikhlas A. Khan
- Subjects
Polygonum ,Constipation ,food.ingredient ,biology ,Traditional medicine ,business.industry ,Gastroenterology ,Prostatitis ,biology.organism_classification ,medicine.disease ,Ingredient ,food ,Herb ,Immunology ,medicine ,medicine.symptom ,business ,Herbal supplement ,Acute hepatitis - Abstract
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
- Published
- 2008
28. Hemodynamic effects of transurethral alprostadil measured by color duplex ultrasonography in men with erectile dysfunction
- Author
-
PETER Y. TAM, TINA KELLER, ROBERTA POPPITI, NEIL GESUNDHEIT, and HARIN PADMA-NATHAN
- Subjects
Adult ,Male ,Erectile Dysfunction ,Regional Blood Flow ,Urology ,Vasodilator Agents ,Hemodynamics ,Humans ,Alprostadil ,Middle Aged ,Ultrasonography, Doppler, Color ,Aged ,Penis - Abstract
We evaluated the hemodynamic effects of transurethral alprostadil in 21 patients with erectile dysfunction using color duplex ultrasonography.Penile arterial diameter, peak flow velocity and end diastolic velocity were compared following intraurethral administration of 500 microg. alprostadil and intracavernosal injection of 10 microg. alprostadil.A dose of 500 microg. transurethral alprostadil resulted in significant increases in corporeal blood flow comparable to those achieved with intracavernosal injection of 10 microg. alprostadil as measured by duplex ultrasonography in men with erectile dysfunction. Transurethral alprostadil resulted in statistically significant increases in arterial diameter and peak flow velocity comparable to those achieved with intracavernosal injection. End diastolic velocities were higher after transurethral alprostadil than intracavernosal injections. Color ultrasonography following transurethral alprostadil showed arterial and venous hyperemia of the corpus spongiosum and corpora cavernosa. Furthermore, color ultrasonography revealed communicating vessels between the corpus spongiosum and corpora cavernosa following administration of transurethral alprostadil.The visualization of communicating vessels between the corpus spongiosum and corpora cavernosa after transurethral alprostadil suggests local mechanisms of drug transfer from one to the other. In addition to potential clinical benefits, transurethral alprostadil may be useful to visualize the vascular anatomy of the penis and to test for patient responsiveness to local vasoactive agents.
- Published
- 1998
29. Body composition of HIV/AIDS males: effects of treatment with insulin-like growth factor (IGF-I) and growth hormone (GH)
- Author
-
Neil Gesundheit, Kenneth J. Ellis, Julie G. Bukar, Phillip D.K. Lee, and J.M. Pivarnik
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,HIV Infections ,Growth hormone ,Body Mass Index ,Insulin-like growth factor ,Absorptiometry, Photon ,Acquired immunodeficiency syndrome (AIDS) ,Bone Density ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Acquired Immunodeficiency Syndrome ,Radiation ,Anthropometry ,business.industry ,Human Growth Hormone ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Endocrinology ,Adipose Tissue ,Body Composition ,Potassium ,Regression Analysis ,Scintillation Counting ,Composition (visual arts) ,business - Published
- 1998
30. Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations
- Author
-
Peter Y. Tam, Neil Gesundheit, Wayne J.G. Hellstrom, John E. Morley, Kerry J. Nemo, Fran E. Kaiser, John C. Varady, Craig A. Peterson, Leslie K. Todd, Alan H. Bennett, J. Joseph Prendergast, Harin Padma-Nathan, Virgil A. Place, and Emil A. Tanagho
- Subjects
Adult ,Male ,Urology ,medicine.medical_treatment ,Vasodilator Agents ,Placebo-controlled study ,Placebo ,law.invention ,Randomized controlled trial ,Double-Blind Method ,Erectile Dysfunction ,law ,medicine ,Prazosin ,Humans ,Alprostadil ,Adrenergic alpha-Antagonists ,Aged ,Aged, 80 and over ,Chemotherapy ,Dose-Response Relationship, Drug ,Vascular disease ,business.industry ,Penile Erection ,Middle Aged ,medicine.disease ,Clinical trial ,Erectile dysfunction ,Anesthesia ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
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.
- Published
- 1998
31. Effects of alprostadil and prazosin on motility, viability and membrane integrity of human sperm
- Author
-
Craig A. Peterson, Wayne J.G. Hellstrom, Neil Gesundheit, Suresh C. Sikka, John C. Varady, and Run Wang
- Subjects
Male ,medicine.medical_specialty ,Cell Survival ,Urology ,Vasodilator Agents ,Motility ,Semen ,Polyethylene glycol ,Pharmacology ,chemistry.chemical_compound ,Internal medicine ,medicine ,Prazosin ,Prazosin Hydrochloride ,Humans ,Alprostadil ,Sperm motility ,Adrenergic alpha-Antagonists ,business.industry ,Cell Membrane ,Sperm ,Spermatozoa ,Membrane integrity ,Endocrinology ,chemistry ,Sperm Motility ,business ,medicine.drug - Abstract
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.
- Published
- 1998
32. Intravenous insulin-like growth factor-I (IGF-I) in moderate-to-severe head injury: a phase II safety and efficacy trial
- Author
-
Mark S. Luer, Kenneth A. Kudsk, Robert P. Rapp, Sharon A. Chen, Craig J. McClain, Byron Young, Julie G. Bukar, Rex O. Brown, Jimmi Hatton, Neil Gesundheit, and Robert J. Dempsey
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Resuscitation ,Nitrogen balance ,Randomization ,Adolescent ,Diet therapy ,Nitrogen ,medicine.medical_treatment ,Nervous System ,Intensive care ,medicine ,Craniocerebral Trauma ,Humans ,Glasgow Coma Scale ,Prospective Studies ,Insulin-Like Growth Factor I ,business.industry ,Head injury ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Intravenous therapy ,Anesthesia ,Injections, Intravenous ,Female ,Neurology (clinical) ,business ,Energy Metabolism - Abstract
✓ 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.
- Published
- 1997
33. Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women
- Author
-
Leah Holloway, Neil Gesundheit, Gail E. Butterfield, Robert Marcus, and Raymond L. Hintz
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Lipoproteins ,Clinical Biochemistry ,Placebo ,Biochemistry ,Bone and Bones ,Phosphorus metabolism ,Excretion ,chemistry.chemical_compound ,Endocrinology ,Bone Density ,Internal medicine ,medicine ,Humans ,Insulin ,Insulin-Like Growth Factor I ,Aged ,Aged, 80 and over ,Glucose tolerance test ,medicine.diagnostic_test ,biology ,business.industry ,Cholesterol ,Biochemistry (medical) ,Phosphorus ,Glucose Tolerance Test ,Middle Aged ,Recombinant Proteins ,Insulin-Like Growth Factor Binding Proteins ,chemistry ,Estrogen ,Growth Hormone ,Osteocalcin ,biology.protein ,Body Composition ,Calcium ,Female ,business ,Carrier Proteins ,Hormone - Abstract
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)
- Published
- 1994
34. Does the Duration of a Scholarly Concentration Affect Medical Studentsʼ Productivity?
- Author
-
Neil Gesundheit, Daniel T. Laskowitz, and Robert P. Drucker
- Subjects
Toxicology ,business.industry ,Medicine ,General Medicine ,Duration (project management) ,business ,Affect (psychology) ,Productivity ,Education - Published
- 2011
35. Ligand-mediated immunofunctional assay for quantitation of growth hormone-binding protein in human blood
- Author
-
Lena M. S. Carlsson, Ross G. Clark, Ann M. Rowland, Wai Lee T. Wong, and Neil Gesundheit
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Antibodies, Heterophile ,Biology ,Monoclonal antibody ,Ligands ,Biochemistry ,Sensitivity and Specificity ,law.invention ,Microtiter plate ,Endocrinology ,Drug Stability ,law ,Growth hormone-binding protein ,Internal medicine ,Blood plasma ,Bone plate ,medicine ,Humans ,Binding site ,Binding protein ,Biochemistry (medical) ,Receptors, Somatotropin ,Growth Hormone ,Recombinant DNA ,Immunologic Techniques ,Carrier Proteins ,Blood Chemical Analysis ,Chromatography, Liquid - Abstract
Human serum contains a high affinity GH-binding protein (GHBP) whose amino-terminal sequence is identical to the extracellular domain of the GH receptor. Current methods that measure GHBP are laborious, require size or charcoal separation of the GH/GHBP complex, and may be influenced by ambient GH concentrations. We have developed a novel assay method that allows quantitation of the total amount of functional GHBP in serum or plasma. The assay can also be used to measure the concentration of the circulating GH/GHBP complex. An anti-GHBP monoclonal antibody, which recognizes both free GHBP and GH-bound GHBP, is used to capture the GHBP on a microtiter plate. Recombinant human GH is added to saturate all binding sites, and an anti-GH antibody conjugated with horseradish peroxidase is used to detect the amount of GH (endogenous and exogenous) bound to the GHBP. The same procedure, but without incubation with GH, allows measurement of the endogenous GH/GHBP complex. The assay is sensitive (detection range, 31-2000 pmol/L), with average inter- and intraassay precisions of 11.3% and 7.3%, respectively. Measurements in random blood samples from 16 healthy adults showed that all subjects had clearly detectable GHBP concentrations (range, 65.8-305.6 pmol/L). In contrast, GHBP levels were undetectable in samples from 2 patients with Laron-type dwarfism. We believe that this ligand-mediated immunofunctional assay, which combines the simplicity and specificity of an enzyme-linked immunosorbent assay with the ability to detect only biochemically active binding protein, will be useful for studies of the role of the GHBP in health and disease.
- Published
- 1991
36. Changes in the sialylation and sulfation of secreted thyrotropin in congenital hypothyroidism
- Author
-
Bethel Stannard, Bruce D. Weintraub, Peter W. Gyves, G S DeCherney, N R Thotakura, and Neil Gesundheit
- Subjects
medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Oligosaccharides ,Thyrotropin ,Peptide hormone ,Fetus ,Hypothyroidism ,Pregnancy ,Reference Values ,Internal medicine ,medicine ,Congenital Hypothyroidism ,Endocrine system ,Animals ,Chromatography, High Pressure Liquid ,G alpha subunit ,chemistry.chemical_classification ,Glucosamine ,Multidisciplinary ,Methimazole ,Chemistry ,Primary hypothyroidism ,Rats, Inbred Strains ,medicine.disease ,Congenital hypothyroidism ,Rats ,Endocrinology ,Glycoprotein Hormones, alpha Subunit ,Pituitary Gland ,Sialic Acids ,Female ,Glycoprotein ,hormones, hormone substitutes, and hormone antagonists ,Endocrine gland ,Hormone ,Research Article - Abstract
We have examined the oligosaccharide structure of secreted thyrotropin (TSH) in perinatal and mature rats with congenital primary hypothyroidism. Rat pituitaries from euthyroid control animals and those rendered hypothyroid by methimazole treatment were incubated with [3H]glucosamine in vitro. Secreted TSH was purified, and oligosaccharides were enzymatically released and characterized by anion-exchange HPLC. In perinatal hypothyroid animals compared with control animals, oligosaccharides from TSH alpha and beta subunits contained more species with three or more negative charges. Moreover, perinatal hypothyroid animals demonstrated a dramatic increase in the ratio of sialylated to sulfated species within oligosaccharides of the same negative charge (2.9- to 7.4-fold increase for TSH-alpha; 15.1- to 25.5-fold increase for TSH-beta). In mature hypothyroid 9-week-old animals compared with control animals, changes were less pronounced, suggesting that endocrine regulation of oligosaccharide structure is dependent upon the maturational state of the animal. These changes were specific for TSH because glycosylation of free alpha subunit (synthesized by the thyrotroph and gonadotroph) and of total glycoproteins was minimally altered by hypothyroidism. Together, these data provide direct evidence and characterization of specific changes in the structure of a secreted pituitary glycoprotein hormone occurring as a result of in vivo endocrine alterations during early development. Moreover, they provide a potential structural basis to explain the delayed clearance of both TSH and the gonadotropins with end-organ deficiency, which may have important implications for the in vivo biological activities of these hormones. Specifically, such posttranslational changes may be an important adaptive response to prevent the consequences of endocrine deficiency during early development.
- Published
- 1990
37. EFFICACY OF MUSE [R] (ALPROSTADIL) IN PATIENTS WITH ERECTILE DYSFUNCTION WHO FAILED VIAGRA [TM] (SILDENAFIL) THERAPY
- Author
-
Wayne J.G. Hellstrom, Kerry J. Nemo, Raoul S. Concepcion, Peter Y. Tam, Neil Gesundheit, George J. Dechet, André T. Guay, Ajay Nehra, and Michael P. O'Leary
- Subjects
chemistry.chemical_compound ,medicine.medical_specialty ,Erectile dysfunction ,chemistry ,Sildenafil ,business.industry ,Urology ,medicine ,In patient ,medicine.disease ,business - Published
- 1999
38. DOES RENEWED SEXUAL ACTIVITY INCREASE CARDIAC MORBIDITY? META-ANALYSIS OF THE EXPERIENCE WITH MUSE [R] (ALPROSTADIL)
- Author
-
Richard F. Labasky, Raymond A. Costabile, Robert P. Nelson, Alfred P. Spivack, Ronald W. Lewis, James H. Barada, Ajay Nehra, Arnold Melman, and Neil Gesundheit
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,Meta-analysis ,medicine ,Intensive care medicine ,business - Published
- 1999
39. Recombinant Human Growth Hormone, Insulin-like Growth Factor 1, and Combination Therapy in AIDS-Associated Wasting
- Author
-
Neil Gesundheit, Frederick Koster, Jeff Danska, David S. Schade, Kevin Hardy, Donna Nickell, Durwood Watson, Clifford Qualls, Stephen D. Nightingale, and Debra L. Waters
- Subjects
Adult ,Male ,medicine.medical_specialty ,Patient Dropouts ,Placebo-controlled study ,HIV Wasting Syndrome ,Weight Gain ,Placebo ,law.invention ,Cachexia ,Placebos ,Body Water ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,Internal Medicine ,Humans ,Medicine ,Insulin-Like Growth Factor I ,Muscle, Skeletal ,Wasting ,Human Growth Hormone ,business.industry ,Proteins ,General Medicine ,Middle Aged ,medicine.disease ,Endocrinology ,Body Composition ,Quality of Life ,Lean body mass ,Drug Therapy, Combination ,Female ,medicine.symptom ,business ,Weight gain - Abstract
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.
- Published
- 1996
40. Characterization and Charge Distribution of the Asparagine-Linked Oligosaccharides on Secreted Mouse Thyrotropin and Free α-Subunits
- Author
-
Neil Gesundheit, G. Stephen Decherney, Peter W. Gyves, Bethel Stannard, Bruce D. Weintraub, and R. Leigh Winston
- Subjects
medicine.medical_specialty ,Glycosylation ,Macromolecular Substances ,Protein subunit ,Thyroid Gland ,Oligosaccharides ,Thyrotropin ,Mannose ,Mice, Inbred Strains ,In Vitro Techniques ,Chromatography, Affinity ,Mice ,chemistry.chemical_compound ,Endocrinology ,Sulfation ,Hypothyroidism ,Internal medicine ,medicine ,Animals ,Asparagine ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,biology ,Chemistry ,Oligosaccharide ,Chromatography, Ion Exchange ,Amino acid ,Biochemistry ,Concanavalin A ,Pituitary Gland ,biology.protein - Abstract
Mouse hemipituitaries in vitro secrete TSH, composed of an alpha-beta heterodimer, as well as excess (free) alpha-subunits. By dual metabolic labeling with [35S]sulfate and [3H]mannose, we have characterized oligosaccharides from secreted TSH alpha, TSH beta, and free alpha-subunits released from the apoprotein by enzymatic deglycosylation. Oligosaccharides from each subunit displayed a distinct anion exchange HPLC profile due to a specific pattern of sialylation and sulfation. Six species were obtained from TSH alpha (with two glycosylation sites), including neutral oligosaccharides as well as those with one or two negative charges. For TSH beta (with one glycosylation site) at least eight oligosaccharide species were noted, representing nearly every permutation of sialylation and sulfation; approximately 30% contained three or more negative charges. Analysis of [3H]mannose-labeled oligosaccharides on Concanavalin-A-agarose showed 85% binding for those from TSH alpha, 70% for free alpha, and 50% for those from TSH beta. These data demonstrate that oligosaccharides from secreted TSH beta were more sialylated and sulfated, consistent with a more complex branching pattern, than those from TSH alpha. Oligosaccharides from free alpha-subunit were more sialylated than those from TSH alpha, and the net negative charge was intermediate between those of TSH alpha and TSH beta. Although great microheterogeneity is present even at the single glycosylation site on the beta-subunit of secreted TSH, a pattern of sialylation and sulfation could be discerned. If one assigns probabilities of sialylation [p(N)] and sulfation [p(S)] based on the observed distribution within monoacidic (charge -1) species, the proportion of diacidic (charge -2) oligosaccharides could be predicted for each subunit by [p(N)]2, 2[p(N)] [p(S)], [p(S)]2, corresponding to species containing two sialic acid, one sialic acid and one sulfate, and two sulfate residues, respectively. This suggests that the probability of sialylation or sulfation at a second site on these oligosaccharides is similar to that at the first and that anionic oligosaccharides in secreted TSH and free alpha are distributed binomially with regard to sialic acid and sulfate residues.
- Published
- 1989
41. Tight Linkage between the Syndrome of Generalized Thyroid Hormone Resistance and the Human c-erbAβ Gene
- Author
-
Robert W. Lash, Bruce D. Weintraub, O.W. McBride, Stephen J. Usala, A.E. Bale, Neil Gesundheit, C. Weinberger, and Fredric E. Wondisford
- Subjects
Genetics ,Receptors, Thyroid Hormone ,Thyroid hormone receptor ,Genetic Linkage ,Drug Resistance ,Locus (genetics) ,Syndrome ,General Medicine ,Biology ,medicine.disease ,Thyroid Diseases ,Pedigree ,Gene product ,Thyroid hormone resistance ,Endocrinology ,Nuclear receptor ,Proto-Oncogene Proteins ,Generalized Thyroid Hormone Resistance ,medicine ,Humans ,Triiodothyronine ,Gene family ,Molecular Biology ,Gene ,Polymorphism, Restriction Fragment Length - Abstract
Multiple cDNAs belonging to the c-erbA gene family encode proteins that bind T3 with high affinity. However, the biological functions of these multiple thyroid hormone receptors have not yet been clarified. Generalized thyroid hormone resistance (GTHR) refers to a human syndrome characterized by tissue refractoriness to the action of thyroid hormones; several studies have suggested quantitative or qualitative defects in T3 binding to nuclear receptors in certain kindreds. To investigate the biological functions of the c-erbA genes, c-erbA alpha and c-erbA beta, we tested the hypothesis that an abnormal c-erbA gene product is present in GTHR by examining these genes in members of one kindred. Restriction enzyme analysis failed to identify an abnormal pattern in affected individuals suggesting no rearrangements or large deletions. However, we demonstrated that the gene conferring the GTHR phenotype is tightly linked to the c-erbA beta locus on chromosome 3. This linkage strongly suggests that the c-erbA beta gene is important in man as a thyroid hormone receptor and identifies a putative c-erbA beta mutant phenotype with central nervous system, pituitary, liver, metabolic, and growth abnormalities.
- Published
- 1988
42. Alterations in the Glycosylation of Secreted Thyrotropin during Ontogenesis
- Author
-
Neil Gesundheit, Peter W. Gyves, G S DeCherney, Bruce D. Weintraub, and Bethel Stannard
- Subjects
chemistry.chemical_classification ,Glycosylation ,biology ,Peptide ,Cell Biology ,Pronase ,Carbohydrate ,Biochemistry ,chemistry.chemical_compound ,Sulfation ,chemistry ,Affinity chromatography ,Concanavalin A ,biology.protein ,Glycoprotein ,Molecular Biology - Abstract
We have examined the carbohydrate structure of thyrotropin (TSH) secreted in vitro by pituitaries from prenatal, perinatal, and mature rats using concanavalin A (ConA)-agarose chromatography and anion-exchange high performance liquid chromatography (HPLC). [3H]Glucosamine-labeled TSH was immuno-precipitated and treated with either Pronase to generate glycopeptides or a mixture of endo-beta-N-acetyl-glucosaminidase F and peptide:N-glycosidase F to release oligosaccharides. The percentage of secreted TSH glycopeptides not bound to ConA was greater in mature animals (47 +/- 3%) than in either prenatal (29 +/- 3%) or perinatal animals (29 +/- 6%), suggesting more multiantennary oligosaccharides in the older animals. These structural changes were characterized further by performing anion-exchange HPLC on released oligosaccharides. Secreted TSH from prenatal rats predominantly contained oligosaccharides with 1 and 2 negative charges, while TSH from mature rats contained these structures as well as 15% with 3 negative charges. In addition, the ratio of sialylated to sulfated oligosaccharides was greater in mature compared to prenatal animals for species with 1 negative charge (1.9-fold) as well as for species with 2 negative charges (4.3-fold). We also correlated the structural alterations noted by ConA analysis with anion-exchange HPLC. Oligosaccharides that bound to ConA and were eluted with alpha-methylglucoside, when analyzed by anion-exchange HPLC, consisted of species with 1 and 2 negative charges, whereas oligosaccharides that were unbound to ConA were predominantly species with three negative charges. Together, these data suggest that with maturation of the hypothalamic-pituitary-thyroid axis secreted TSH contains more negatively charged multiantennary oligosaccharides with increased sialylation and decreased sulfation.
- Published
- 1989
43. Changes in Thyrotropin (TSH) Carbohydrate Structure and Response to TSH-Releasing Hormone during Postnatal Ontogeny: Analysis by Concanavalin-A Chromatography*
- Author
-
John B. Butler, Peter W. Gyves, Bruce D. Weintraub, Neil Gesundheit, and Terry Taylor
- Subjects
Male ,Aging ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Thyrotropin ,Endogeny ,Pronase ,Biology ,Peptide hormone ,Chromatography, Affinity ,chemistry.chemical_compound ,Endocrinology ,Affinity chromatography ,Glucosamine ,Internal medicine ,Concanavalin A ,medicine ,Animals ,Thyrotropin-Releasing Hormone ,Chromatography ,Rats, Inbred Strains ,Carbohydrate ,Glycopeptide ,Rats ,chemistry ,Pituitary Gland ,biology.protein ,hormones, hormone substitutes, and hormone antagonists - Abstract
We have studied the carbohydrate structure of TSH as well as its response to TRH during postnatal ontogenesis in the rat using Concanavalin-A (Con A)-Sepharose chromatography of labeled glycopeptides. Pituitaries from neonatal (5-day-old) rats with low levels of endogenous TRH and mature (56-day-old) rats were incubated for 24 h in medium containing [3H] glucosamine in the presence or absence of 10(-7) M TRH. Both intracellular and secreted TSH were immunoprecipitated, treated with Pronase to generate glycopeptides, and analyzed by chromatography on Con A-Sepharose. The total amount of [3H]glucosamine-labeled TSH was greater per pituitary in mature rats compared to that in neonatal rats (P less than 0.05), while there was no significant difference between the groups in the concentration of total labeled TSH per microgram pituitary DNA. RIA determination of total TSH was greater in the older animals than in the younger animals when normalized both per pituitary and per microgram pituitary DNA (P less than 0.01 and P less than 0.02, respectively). However, for both labeled and unlabeled TSH the percentage of TSH secreted was greater in mature rats than in neonatal rats (P less than 0.02 and P less than 0.01, respectively), indicating a less active hormonal secretory process in the younger animals. In control animals, the proportion of labeled TSH glycopeptides that did not bind to Con A was greater in 56- than in 5-day-old animals for both intrapituitary and secreted forms (P less than 0.01), reflecting a shift toward more multiantennary and/or bisected biantennary complex carbohydrate structures in the older animals. In response to TRH in vitro, the total amount of labeled secreted TSH was increased more than 2-fold in both 5-day-old (P less than 0.05) and 56-day-old (P = NS) animals. However, there was a marked difference in the glycopeptide distribution between these two ages. Five-day-old animals showed a small but not significant decrease in the percentage of secreted TSH glycopeptides that bound to Con A-Sepharose, while 56-day-old animals had a specific increase in the glycopeptide fractions that bound and corresponded to biantennary complex and/or unusual hybrid forms (P less than 0.01). These studies in the rat suggest differences in TSH carbohydrate structure and secretion as well as a differential response to TRH during postnatal ontogenesis.
- Published
- 1987
44. Differential Sulfation and Sialylation of Secreted Mouse Thyrotropin (TSH) Subunits: Regulation by TSHReleasing Hormone*
- Author
-
Neil Gesundheit, James A. Magner, Bruce D. Weintraub, and Thomas Chen
- Subjects
endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Macromolecular Substances ,Thyrotropin ,Mannose ,Mice ,chemistry.chemical_compound ,Methionine ,Endocrinology ,Sulfation ,Hypothyroidism ,Pituitary Hormones, Anterior ,Internal medicine ,medicine ,Animals ,Pituitary Neoplasms ,Thyrotropin-Releasing Hormone ,G alpha subunit ,chemistry.chemical_classification ,Sulfates ,Hexosamines ,N-Acetylneuraminic Acid ,Peptide Fragments ,Sialic acid ,Hexosaminidases ,Secretory protein ,chemistry ,Biochemistry ,Glycoprotein Hormones, alpha Subunit ,Pituitary Gland ,Sialic Acids ,Glycoprotein ,N-Acetylneuraminic acid ,hormones, hormone substitutes, and hormone antagonists - Abstract
To determine whether sulfate and/or sialic acid are present on secreted mouse TSH, thyrotropic tumor minces and hypothyroid pituitaries were incubated with [3H]methionine and [35S]sulfate, or [35S]methionine and [3H]N-acetylmannosamine. The metabolically labeled TSH and free alpha-subunits were then analyzed by gel electrophoresis. [3H]N-Acetylmannosamine was a specific precursor (greater than 80%) for the sialic acid [3H]N-acetylneuraminic acid, as established by HPLC characterization of tritium label released by acid hydrolysis. Each of the three secreted subunits (TSH alpha, TSH beta, and free alpha) incorporated both sulfate and sialic acid. The incorporation of these labels was confirmed by the release of [35S]sulfate by endoglycosidase F and of [3H]N-acetylneuraminic acid by neuraminidase. Differential labeling of newly synthesized secreted TSH subunits was observed. In secreted TSH dimer, TSH beta incorporated 1.3 times more [35S]sulfate (P less than 0.05) and 2.5 times more [3H] N-acetylmannosamine (P less than 0.02) per carbohydrate chain than did TSH alpha. Secreted free alpha-subunit incorporated more [3H]N-acetylmannosamine, but less [35S]sulfate, then did secreted TSH alpha. To investigate the effect of TRH on TSH sulfation and sialylation, thyrotropic tumor minces and hypothyroid pituitaries were incubated with [35S]sulfate or [3H]N-acetylmannosamine, with or without 10(-7) M TRH; labeling was then normalized in each case to incorporation of [3H]mannose, a marker of the inner core sugars. TSH secreted in the presence of TRH had a lower sulfate to mannose ratio [28 +/- (+/- SE) 4% of control; P less than 0.05] and a lower sialic acid to mannose ratio (63 +/- 8% of control; P less than 0.05). TSH alpha and TSH beta were affected equally. No change was seen in the labeling of non-TSH secretory proteins. Differential glycoprotein sulfation and sialylation may, in part, explain the previously observed variability in isoelectric point, bioactivity, and MCR of TSH in different physiological states and may represent a point of regulation by TRH.
- Published
- 1986
45. Effect of TRH on TSH Glycosylation and Biological Action
- Author
-
Neil Gesundheit, Bruce D. Weintraub, Peter W. Gyves, and Terry Taylor
- Subjects
medicine.medical_specialty ,Glycosylation ,General Neuroscience ,Thyrotropin ,Thyrotropin-releasing hormone ,Second Messenger Systems ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Endocrinology ,History and Philosophy of Science ,chemistry ,Post translational ,Action (philosophy) ,Internal medicine ,Protein processing ,Second messenger system ,medicine ,Animals ,Protein Processing, Post-Translational ,Thyrotropin-Releasing Hormone - Published
- 1989
46. Differential carbohydrate processing and secretion of thyrotropin and free alpha subunit. Effects of 1-deoxynojirimycin
- Author
-
Bruce D. Weintraub, Neil Gesundheit, Catherine Ronin, Bethel Stannard, and J Burnside
- Subjects
medicine.medical_specialty ,Protein subunit ,Alpha (ethology) ,Cell Biology ,Carbohydrate metabolism ,Biology ,Biochemistry ,Prolactin ,Endocrinology ,Secretory protein ,Internal medicine ,medicine ,Secretion ,Molecular Biology ,Intracellular ,G alpha subunit - Abstract
In pulse-chase experiments we compared the kinetics of early carbohydrate processing and subsequent secretion of thyroid-stimulating hormone (TSH) and free alpha subunit under control conditions and after treatment with 1-deoxynojirimycin, an inhibitor of glucosidases I and II. Under control conditions TSH achieved resistance to endo-beta-N-acetylglucosaminidase H (endo H) more rapidly than free alpha (t1/2 0.3 h versus 0.9 h); however, free alpha was secreted more rapidly than TSH (t1/2 2.2 h versus 3.4 h). With 1-deoxynojirimycin, oligosaccharides co-migrating with G3Man9GlcNAc and G2Man9GlcNAc were demonstrated on TSH for the first time, suggesting that previous pulse-chase studies did not disclose these intermediates due to rapid removal of glucose residues from the common G3Man9GlcNAc2 precursor. 1-Deoxynojirimycin delayed the rate of attainment of endo H resistance for both TSH and free alpha, but there was no effect on subunit combination. With 5 mM 1-deoxynojirimycin the amount of secreted free alpha was reduced to 65% of control; secreted TSH was reduced markedly to 17% of control without intracellular accumulation, suggesting increased intracellular degradation. There was no significant toxicity from these doses of 1-deoxynojirimycin on the production or secretion of the two major nonglycosylated pituitary proteins, growth hormone and prolactin, or on at least 10 other secretory proteins. Basal differences in the relative rates of TSH and free alpha processing and secretion as well as differential sensitivity to 1-deoxynojirimycin suggest separate secretory pathways for these two closely related proteins.
- Published
- 1988
47. Preoperative lateralization of pituitary microadenomas by petrosal sinus sampling: Utility in two patients with non-ACTH-secreting tumors
- Author
-
George R. Merriam, Bruce D. Weintraub, Stuart J. Frank, John L. Doppman, Donald L. Miller, Edward H. Oldfield, and Neil Gesundheit
- Subjects
Adenoma ,Adult ,Male ,endocrine system ,Pituitary gland ,medicine.medical_specialty ,endocrine system diseases ,Thyrotropin ,Lateralization of brain function ,Adrenocorticotropic Hormone ,Acromegaly ,medicine ,Humans ,Pituitary Neoplasms ,Bloodletting ,Petrosal Sinus Sampling ,business.industry ,Pituitary tumors ,General Medicine ,medicine.disease ,Surgery ,Inferior petrosal sinus sampling ,medicine.anatomical_structure ,Growth Hormone ,Pituitary hormones ,Cavernous Sinus ,Female ,Radiology ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
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
- Published
- 1989
48. Effects of in vivo bolus versus continuous TRH administration on TSH secretion, biosynthesis, and glycosylation in normal and hypothyroid rats
- Author
-
Neil Gesundheit, Bruce D. Weintraub, and Terry Taylor
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,Radioimmunoassay ,Thyrotropin ,Thyrotropin-releasing hormone ,Endogeny ,Sulfur Radioisotopes ,Tritium ,Biochemistry ,Methionine ,Endocrinology ,Bolus (medicine) ,TRH stimulation test ,Hypothyroidism ,Thyroid-stimulating hormone ,Pituitary Gland, Anterior ,In vivo ,Internal medicine ,medicine ,Animals ,Infusions, Parenteral ,Thyrotropin-Releasing Hormone ,Molecular Biology ,Saline ,Glucosamine ,Chemistry ,Rats, Inbred Strains ,Rats ,Kinetics ,Injections, Intravenous ,Protein Processing, Post-Translational ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
The effects of in vivo TRH administered either as bolus or continuous doses on TSH secretion, synthesis, and glycosylation were studied in normal and hypothyroid rats. Nine-week-old normal or 3-week postthyroidectomy rats were administered bolus doses of saline or TRH (0.5 mg/kg) twice daily or continuous saline or TRH (1 mg/kg/day) via an osmotic pump. After 5 days, pituitaries were removed and incubated with [35S]methionine (MET) and [3H]glucosamine (GLCN), with or without 10(-8) M TRH, for 6 and 24 h. Samples were precipitated with anti-TSH beta sera and then analyzed by gel electrophoresis. In normal rats, plasma TSH, T4 and T3 increased with continuous in vivo TRH but not with bolus TRH; in hypothyroid rats, plasma TSH, T4 and T3 were not altered by continuous or bolus doses of TRH. Additionally, in normal rats, continuous in vivo TRH increased incorporation of MET in secreted TSH (477 vs. 212 X 10(3) dpm/mg DNA; P less than 0.05) and intrapituitary TSH (5035 vs. 2124 X 10(3) dpm/mg DNA; P less than 0.05), and GLCN in secreted TSH (148 vs. 50 dpm/mg DNA; P less than 0.05) and intrapituitary TSH (2344 vs. 744 X 10(3) dpm/mg DNA; P less than 0.05). In contrast, in hypothyroid animals, continuous in vivo TRH did not alter MET or GLCN incorporation in TSH. Bolus TRH did not alter secreted or intrapituitary MET or GLCN incorporation into TSH in the normal rat. However, bolus TRH in the intrapituitary MET or GLCN incorporation into TSH in the normal rat.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1986
49. Effect of thyrotropin-releasing hormone on the carbohydrate structure of secreted mouse thyrotropin. Analysis by lectin affinity chromatography
- Author
-
Bruce D. Weintraub, L A Silverman, Neil Gesundheit, and D L Fink
- Subjects
chemistry.chemical_classification ,endocrine system ,endocrine system diseases ,Mannose ,Lectin ,Thyrotropin-releasing hormone ,Cell Biology ,Biology ,Biochemistry ,Fucose ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Anterior pituitary ,Glucosamine ,Concanavalin A ,medicine ,biology.protein ,Glycoprotein ,Molecular Biology ,hormones, hormone substitutes, and hormone antagonists - Abstract
Thyrotropin (TSH) is a glycoprotein hormone whose secretion from the anterior pituitary is regulated, in part, by the hypothalamic tripeptide thyrotropin-releasing hormone (TRH). We have used serial lectin affinity analysis to explore whether TRH, in addition to promoting TSH secretion, alters the carbohydrate structure of secreted TSH. Hypothyroid mouse hemipituitaries were incubated in medium containing [3H] mannose, [3H]glucosamine, or [3H]fucose either with or without 10(-7) M TRH. TSH was immunoprecipitated, proteolytically digested into glycopeptides, and chromatographed on serial lectin-Sepharose columns. Under basal conditions, 37% of secreted [3H]mannose-labeled TSH glycopeptides failed to bind to concanavalin A (ConA)-Sepharose, 55% bound and eluted with 10 mM alpha-methylglucoside, and 8% bound and eluted with 500 mM alpha-methylmannoside. Approximately 35% of glycopeptides not binding to ConA-Sepharose were bound by pea lectin-Sepharose, suggesting the presence of certain core fucosylated triantennary complex oligosaccharides. TRH caused a 2-fold increase in secretion of [3H]mannose-labeled TSH glycopeptides due almost exclusively to a specific increase in structures that bound to ConA-Sepharose and eluted with 10mM alpha-methylglucoside, corresponding to biantennary complex or unusual hybrid species. There was no change in the distribution of intrapituitary TSH glycopeptides with TRH. Acid hydrolysis of secreted proteins showed little metabolism of the tritiated sugar precursors, except for a 20% conversion of [3H]mannose to [3H]fucose. Moreover, ConA-Sepharose chromatography of secreted [3H]glucosamine- and [3H]fucose-labeled TSH glycopeptides showed similar increases in ConA-Sepharose binding with TRH as noted with [3H]mannose labeling. Subsequent lectin analysis of secreted [3H] mannose-labeled TSH glycopeptides on erythroagglutinating phytohemagglutinin-Sepharose and leukoagglutinating phytohemagglutinin-Sepharose disclosed no significant differences in TRH-treated versus control samples. These data suggest that secreted mouse TSH has greater carbohydrate heterogeneity than has been recognized previously. In addition, TRH in vitro promotes the secretion of specific TSH molecules apparently enriched in biantennary complex or unusual hybrid oligosaccharides.
- Published
- 1987
50. Enzymatic deglycosylation of thyroid-stimulating hormone with peptide N-glycosidase F and endo-beta-N-acetylglucosaminidase F
- Author
-
Kok-Onn Lee, Hao-Chia Chen, Neil Gesundheit, and Bruce D. Weintraub
- Subjects
PNGase F ,Glycoside Hydrolases ,Macromolecular Substances ,Biophysics ,Carbohydrates ,Thyrotropin ,Peptide ,Galactosamine ,Biochemistry ,Amidohydrolases ,Chaps ,Acetylglucosaminidase ,Animals ,Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase ,Amino Acids ,Molecular Biology ,Polyacrylamide gel electrophoresis ,G alpha subunit ,chemistry.chemical_classification ,Glucosamine ,Cell Biology ,Oligosaccharide ,Hydrogen-Ion Concentration ,Molecular Weight ,Enzyme ,Hexosaminidases ,Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase ,chemistry ,Cattle ,Electrophoresis, Polyacrylamide Gel ,Glycoprotein - Abstract
We investigated the ability of two enzymes, peptide N-glycosidase F (PNGase F) and endo-beta-N-acetylglucosaminidase F (Endo F), to deglycosylate microgram quantities of bovine TSH and its subunits under nondenaturing conditions. One oligosaccharide chain could be selectively removed from the alpha subunit by PNGase F, and all the oligosaccharide chains from both subunits could be removed by Endo F. These methods of enzymatic deglycosylation should permit study of the functional role of each N-linked carbohydrate chain of various glycoprotein hormones.
- Published
- 1986
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