Safer drug therapy for the elderly: progress has started.
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Biomedical subjects
Publications and source records attributed to R N Butler.
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As zinc status may influence susceptibility to colon cancer, we examined the effect of dietary zinc deficiency on the proliferation of epithelial cells (colonocytes) in the large bowel of rats. When compared to feed-restricted rats, those with zinc deficiency showed a significant reduction in proliferation in the distal colon as assessed by accumulated metaphase arrest and crypt cell production rates in vivo. Zinc deficiency had no apparent effect on thymidine kinase activity in colonocytes but was accompanied by minor changes in fecal mass and fecal pH. In rats, zinc deficiency is associated with a reduction in the rate of proliferation of colonocytes in the distal colon.
Several methods were used to assess proliferation of colonocytes in the proximal and distal colon of the rat after fasting and refeeding. Those applied in vivo included metaphase arrest, labelling with bromodeoxyuridine and uptake of tritiated thymidine. The latter two techniques were also applied after isolation of colonocytes in vitro. Methods applied in vivo showed similar proliferation in the proximal and distal colon after fasting and enhanced proliferation in both regions after refeeding. However, the degree of enhancement was greater in the distal colon than in the proximal colon. In vitro, proliferation was enhanced in both the proximal and distal colon after refeeding but the degree of variability was greater than after assessment in vivo. Methods applied in vivo are preferred for assessment of proliferative activity in the rat colon, and major changes in proliferation in both proximal and distal colon can be induced by fasting-refeeding.
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Aging is the third great antecedent to all disease, along with genetic factors and the environment. Yet, the role of aging in the genesis of the conditions of old age constitutes relatively new territory that has not been adequately explored in terms of education, the health care system, and research. A commitment to these areas was made in 1982 when the Mount Sinai Medical Center established the nation's first and only medical school department of geriatrics--the Gerald and May Ellen Ritter Department of Geriatrics and Adult Development. Recognizing that aging of the population constituted a major global public health challenge, leaders of the medical center turned to Robert N. Butler, MD, who was then director of the National Institute on Aging, for guidance in setting up an institute of gerontology and geriatrics. Because only a full-fledged academic department would have a claim on resources, curriculum, and clerkship time, Dr Butler recommended that such a department be developed at Mount Sinai. The Ritter Department of Geriatrics and Adult Development emphasized the wide scope of this new discipline through educational programs, clinical services, health policy studies, and research projects.
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A delay of left ventricular isovolumic relaxation and decrease in myocardial compliance may result in a decline of measured early filling rates in elderly subjects. Previous studies of diastolic function, however, have not excluded coronary artery disease or addressed the contribution of atrial contraction to diastole. The present study evaluated radionuclide-derived diastolic variables in 13 healthy elderly volunteers aged 75 +/- 6 years without symptoms or risk factors for coronary disease who had normal findings on the stress electrocardiogram, stress gated blood pool imaging and two-dimensional echocardiogram. Results were compared with those of a group of 10 healthy young volunteers aged 26 +/- 5 years. High count, 32 frame, double-buffered gated blood pool acquisitions were obtained at rest in the left anterior oblique view with an RR interval variation less than 5%. Left ventricular time-activity curves were analyzed and flow-volume loops for each group were constructed. In the healthy elderly: peak early diastolic filling rate is decreased, time of peak early filling and time to first third of diastolic filling are delayed, and peak late left ventricular filling rate and percent of atrial filling volume are augmented, suggesting an adaptive response of the atria to diminished left ventricular compliance.
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Post-prandial serum levels of gastrin, the main hormonal stimulator of acid secretion, have been shown to be significantly elevated after HSV compared with controls. The mechanism for this elevation is not known but could be secondary to an increased antral gastrin concentration (AGC). In this study AGCs were measured in endoscopic biopsies before and at intervals of 6 and 32 weeks after HSV in 12 patients with duodenal ulcer. Results were compared with 13 normal controls and 12 duodenal ulcer patients treated with cimetidine for 6 weeks. Blood was taken for fasting serum gastrin concentration at each endoscopy. In the HSV group AGC significantly increased on both postoperative occasions when compared with pre-operative values (P less than 0.01). AGC also showed a significant correlation with time after HSV (r = 0.71; P less than 0.01). Only one patient, who had a persistent duodenal ulcer, failed to show an increase in AGC. Cimetidine failed to increase AGCs in duodenal ulcer patients after 6 weeks of treatment. However, a subgroup (n = 7) of cimetidine-treated patients with low pretreatment AGCs, below 10 ng/mg, did show a significant rise at 6 weeks (P less than 0.05). Fasting serum gastrin levels did not change significantly in any of the three groups. It is concluded that HSV causes a significant increase in AGC with time.