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There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP]. Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort. The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri. 122 men and 206 women, age 60.2 ± 4.3 years. Retrospective analysis. Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes. Serum total 25(OH) D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD. Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

OBJECTIVE The inappropriate use of acid-suppression therapy (AST) in non-intensive care unit patients contributes to inappropriate polypharmacy, drug interactions, community- and hospital-acquired pneumonia, and increased health care expenditures for institutions and individuals. The purpose of this study was to determine whether clinical pharmacist interventions significantly decreased the rate of inappropriately used AST. DESIGN A single group, pre-test post-test. SETTING The Geriatric Evaluation and Management unit in the St. Louis Veterans Affairs Medical Center. PATIENTS All patients admitted between July 1, 2006, through April 30, 2007 (control group), and May 1, 2007, through February 28, 2008 (PharmD group), were evaluated. All patients with a minimum length of stay of seven days were eligible for inclusion. Data were obtained from the Computerized Patient Record System regarding the use of proton-pump inhibitors, histamine-2 receptor antagonists, sucralfate, and the indication for these therapies. INTERVENTIONS A clinical pharmacist was present during the weekly interdisciplinary team rounds to make recommendations in the intervention group, compared with a nonpharmacist control group. OUTCOME MEASURES The percent of patients on these therapies without an appropriate indication (International Classification of Diseases, 9th Revision) were identified from the chart review, and comparisons were made between the control and PharmD groups. RESULTS A total of 142 and 151 patients were admitted during the control and PharmD arms, respectively. Of these patients, 117 in each group were eligible for inclusion in the analysis. The primary outcome, the number of patients receiving AST prior to discharge without an appropriate indication, occurred 46.2% (54/117) versus 23.9% (28/117) (P = 0.001) in the control and PharmD groups, respectively. CONCLUSIONS This study examined the impact of pharmacists' active participation in interdisciplinary team rounds compared with a nonpharmacist control group. These results demonstrate pharmacist participation associated with potential cost savings and improved patient care.

Background. Different factors may predict loss of appendicular muscle mass (LossAMM) and loss of muscle strength (LossMS). We investigated the relationship between LossAMM or LossMS and baseline anthropometric measures, lifestyle habits, hormones, lipid profiles, and inflammatory markers in 49 healthy postmenopausal women (54.1 6 4.3 years) in a 24–36-month prospective study. Methods. We measured parameters of lifestyle habits, anthropometry, lipid profiles, and blood levels of testosterone, estrone, estradiol, cortisol, dihydroepiandrostenedione, luteinizing hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, thyroxine, leptin, adiponectin, C-reactive protein (CRP), and interleukin-6 and interleukin-2 receptors. Percentage of loss per year of isometric knee extensor strength defined LossMS, and percentage of loss of AMM per year (dual x-ray absorptiometry) defined LossAMM. Results. The means (standard deviation) for LossMS and LossAMM were 1.17%/y (2.03) and 0.60%/y (0.74) and did not correlate (r ¼� 0.001; p ¼ .99). LossMS correlated negatively with level of physical activity (r ¼� 0.28), femoral BMD (r ¼� 0.30), alcohol consumption (r ¼� 0.30), and luteinizing hormone (r ¼� 0.32) and positively with estrone (r ¼ 0.29) and iPTH (r ¼ 0.32) (each at p , .05). LossAMM correlated negatively with AMM (r ¼� 0.41; p , .01). Stepwise regression analyses showed that LossMS was significantly predicted by baseline physical activity (beta ¼� 0.39) with an explanation of variation of the model (R 2 ) of 6%, body mass index (BMI) (� 0.40; 3%), high-density lipoprotein cholesterol (� 0.29; 3%), estrone (0.32; 6%), iPTH (0.27; 7%), and interleukin-2 receptor (0.32; 5%). LossAMM was predicted by baseline height (0.56; 47%), body mass index (1.04; 83%), AMM (� 0.92; 76%), thyroxine (� 0.33; 8%), estrone (� 0.61; 30%), and dihydroepiandrostenedione (0.44; 28%). Conclusions. LossMS and LossAMM in young postmenopausal women were not correlated with one another, and were determined by different factors.

To investigate the relationships between blood levels of leptin or adiponectin and lifestyle habits, hormones, and inflammatory markers, we measured parameters of alcohol intake, smoking, physical activity, and blood levels of leptin, adiponectin, testosterone, estrone, estradiol, cortisol, dihydroepiandrostenedione, luteinizing hormone, thyroxin, C-reactive protein (CRP), and interleukin 6 and interleukin 2 receptor in 76 healthy middle-aged postmenopausal women. Anthropometric measures and body composition (evaluated by dual-energy x-ray absorptiometry) and lipid profiles were also assessed. By simple regression, leptin correlated positively with fat and lean masses, glucose, triglycerides, low-density lipoprotein cholesterol, and total cholesterol, and negatively with high-density lipoprotein cholesterol. Adioponectin correlated negatively with fat and lean masses and low-density lipoprotein cholesterol, and positively with high-density lipoprotein cholesterol. Leptin concentration was correlated inversely with adiponectin (r = -0.26, P < .05) and positively with CRP (r = 0.56, P < .01). Adiponectin concentration was negatively correlated with time since last alcoholic drink (r = -0.24, P < .05) and CRP (r = -0.27, P < .05) and positively with testosterone level (r = 0.23, P < .05). By multiple regression analysis, leptin concentration was predicted by age (P < .05), testosterone (P < .05), adiponectin (P < .05), CRP (P < .01), and interleukin 6 receptor (P < .01). Adiponectin concentration was predicted by the time since last alcoholic drink (P < .05), testosterone (P < .05), leptin (P < .05), and C-reactive protein (P = .05). Similar results were found when leptin or adiponectin concentration was adjusted for fat mass. These results suggested that levels of leptin and adiponectin in middle-aged postmenopausal women are partially determined by sexual hormones and inflammatory marker levels, and both predicted one another. Moreover, adiponectin level may be modulated by alcohol intake.

The treatment of primary and secondary hypogonadism with testosterone is well established. Recently, there has been increased awareness that low testosterone levels also occur in chronically ill persons and aging males. Because of sex hormone binding globulin changes, it is more appropriate to make the diagnosis using either free or bioavailable testosterone. A small number of controlled studies have suggested that testosterone replacement in older men improves libido, quality of erections, some aspects of cognition, muscle mass, muscles strength, and bone mineral density. It also decreases fat mass and leptin levels. A number of screening questionnaires for the andropause have been developed. Insufficient numbers of older men have been treated with testosterone to characterize the true incidence of side effects. There is a desperate need for well designed, large controlled trials to establish the value or otherwise of testosterone treatment in older males.

Methods. A retrospective chart review of 833 discharged older home care patients was performed. These patients were consecutive discharges from a single home care agency who either (a) returned to independent self-care or care of the family (S/F Care group) or (b) were admitted to the hospital (Hospitalized group). Medication assessment within these two groups included total number of medications (prescription and nonprescription); degree of polypharmacy (percentage of patients taking 5 or more, 7 or more, and 10 or more medications); and prevalence for different types of medications, including different types of inappropriate medications. Inappropriate medications were designated according to a list that was previously developed through a modified Delphi consensus technique by a panel of 13 experts in geriatric pharmacology and has been utilized in other studies. Student’s t test was used for continuous variables and chi-square test was used for categorical variables to evaluate for differences between the S/F Care group and the Hospitalized group ( p , .05). For comparisons of types of medications, p , .01 was used for significant differences, because of the high number of comparisons made. Results. Of 833 discharges, 644 (77.3%) returned to self-care or care of the Family (S/F Care group) and 189 (22.7%) were hospitalized. The Hospitalized group, compared with the S/F Care group, was taking a higher number of medications (mean 6 SD : 6.6 6 3.9 vs 5.7 6 3.4, p 5 .004), and had a higher percentage of patients taking 7 or more medications (46% vs 26%, p 5 .002) and 10 or more medications (21% vs 10%, p 5 .005), but not 5 or more medications. Only three types of medications were more commonly used among patients in the Hospitalized group than among patients in the S/F Care group: clonidine (4.2% vs 1.1%, p 5 .004); mineral supplements (23.8% vs 14.8%, p 5 .003); and metoclopramide (5.8% vs 2.0%, p 5 .006). The Hospitalized group had a lower percentage of patients taking inappropriate medications than did the S/F Care group (20% vs 27%, p 5 .040), but none of the types of inappropriate medications was used more often in either group. Conclusions. This study shows a relationship between high levels of polypharmacy and hospitalization. Although it cannot be determined from this study whether a higher number of medications was an indicator of sicker patients at risk for hospitalization, or whether a higher number of medications might have directly led to hospitalization, polypharmacy should still be considered a marker for older home care patients for whom prevention of hospitalization is the goal.

The concept that the testes contain some magical substance that enhances vigor has existed since ancient times. Galen wrote in Peri-Spermatos : "What is, therefore, the cause that castrates slow down in their whole vital capacity?" 10 Ayruvedic medicine advocated ingestion of testes to treat impotence and obesity, and more than 2000 years ago, Pliny prescribed eating testicles to improve sexual vigor. In 1889, Brown-Sequard 8 reported that he had reversed his own age-related problems by injecting himself with testicular extracts. In his carefully written report, he acknowledged that the effect could have been a placebo one. Brown-Sequard's report unleashed a flurry of testicular extract treatment that continued throughout the end of the nineteenth century and the early part of the twentieth century. The leading proponent of this approach was Voronoff, who in the 1920s charged up to $5000 for a chimpanzee testicular transplant into the rich of Europe. 23 A human-to-human testicular transplant was performed by Lespinasse in Chicago. 10 Stanley at San Quentin prison transplanted fresh testicles from executed inmates into other prisoners. The physicians who popularized testicular extract transplants became renowned as the erector doctors. By the end of World War II, testicular transplants had led to a backlash, and Pincus, a leading American endocrinologist, 26 wrote that testes transplants had been "obnoxiously publicized in the late nineteenth and twentieth centuries" and, in his opinion, had derailed the development of endocrinology by "the exploitation of the idea of rejuvenation by hormones." In 1935, Laqueur of Organon reported successful extraction of pure testosterone from bulls' testicles. 12 In the same year, Butenandt and Hanish 9 and Ruzicka and Wettstein 49 both reported a method to synthesize testosterone from cholesterol. For their work, they received the Nobel Prize in 1939. In 1940, Thomas and Hill 53 reported successful treatment of the male climacteric with testosterone propionate. This report was followed in 1944 by one in the Journal of the American Medical Association on the use of testosterone to treat the male climacteric. 25 In some of their 20 cases, Heller and Myers 25 used sesame oil as a placebo to rule out the placebo effect. Between this time and the 1970s, many physicians treated the male climacteric with testosterone. A leading proponent of this therapy was Reiter, a German physician. 47 Only in the last few years has sufficient scientific evidence been accumulated to begin to satisfy the medical establishment that testosterone levels decline with age and that testosterone replacement therapy may play a role in enhancing functional capacity as well as increasing libido as men age.

Background. The impact of diabetes on disability and physical functioning in older African Americans and potential causes of the excessive disability associated with diabetes in other studies have been inadequately investigated.Methods. A population-based survey was performed comparing 116 self-reported diabetic inner-city African Americans aged 70 years and older to 522 nondiabetic persons from the same population. A subsample (n = 168) received a physical examination focused on body habitus, upper and lower body strength, balance, and timed physical performance tasks. Blood tests were obtained from 173 subjects.Results. Diabetic individuals reported worse general health (p = .01), instrumental activities of daily living (p = .02), and modified versions of the Rosow-Breslau scale (p < .001) and the Stanford Health Assessment Questionnaire (p = .002). Diabetic persons also reported more falls (0.59 per person vs 0.20, p = .019) and injurious falls (12% vs 6%, p = .025). There were minimal differences in the strength, balance, and timed performance measures (analyzed separately by gender). In multivariable analyses, impairments in visual function and pain and light touch perception appeared to explain some of the association between diabetic status and poor general health, disability, and falls, with lesser contribution from the number of medical problems, number of medications, and glycemic control.Conclusions. Older inner-city diabetic blacks demonstrated worse general health, excess disability, and more falls compared to controls, although deficits in strength, balance, and timed performance could not be demonstrated. The cause of decreased functional status in diabetic elders deserves additional investigation, focusing especially on sensory function, glycemic control, and contribution from specific medical problems and medications.

We have examined the relationship between self-reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none-to-moderate intake had

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p 8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.

Abstract —There is continuing uncertainty about whether morbidity and mortality of treated hypertensive patients depends on the drug(s) used to treat or only on the level of blood pressure achieved. This study was undertaken in a sample of special Veterans Administration hypertension clinics to determine which antihypertensive drugs were selected by the involved healthcare providers and how effective they were in achieving normotension. Hypertensive veterans (n=6100) were followed in six VA Hypertension Screening and Treatment Program clinics for 46 months beginning in May 1989. Their average age was 60.7 years; 53% lived in the Stroke Belt; 46% had target organ damage, 36% were black, 23% smoked, and 10% had diabetes mellitus. Antihypertensive regimens were divided into 12 all-inclusive categories. Blood pressures were averaged at the last study visit for all patients on a regimen. The regimens of diuretic or diuretic plus β-blocker gave the lowest average pressures (140.6/82.3 mm Hg) and calcium antagonist the highest (149.0/86.5 mm Hg). ANOVA indicated that differences between seven common regimens and also between the four single drug regimens were highly significant ( P

Falls following a meal occur commonly in older persons. These falls have been related to a decrease in postprandial blood pressure due to carbohydrates in the meal. The mechanism by which this occurs is not known. In this study, we examined the possible role of a vasodilatory peptide, calcitonin gene-related peptide (CGRP), which is released following carbohydrate loading in the pathophysiology of postprandial hypotension. Levels were assessed in 29 community-dwelling individuals aged 20-83 years during an oral glucose tolerance test, and heart rate and blood pressure were measured. Five subjects exhibited a postprandial reduction in systolic blood pressure (SBP) greater than 15 mmHg (mean reduction -30 +/- 4 mmHg). Four were aged over 60 (40% of the individuals in that group) and one was middle aged (11%). One individual in the older group was temporarily symptomatic, complaining of light-headedness. Linear regression analysis showed a significant association between the changes in CGRP and in blood pressure: SBP (r = 0.39, P = 0.037), and mean blood pressure (MBP) (r = 0.356, P = 0.06) in the oldest group. Individuals in this group with a greater than 15 mmHg drop in blood pressure, exhibited significantly greater changes in CGRP (SBP: P = 0.001, diastolic blood pressure (DBP): P = 0.05, MBP: P = 0.006). This association of log CGRP delta and BP change was not present in young or middle aged individuals. Thus, increases in CGRP levels were associated with blood pressure reduction, with older individuals more susceptible to these changes than younger individuals. CGRP may play a role in the pathogenesis of postprandial hypotension.

Osteoporosis is an important public health problem. Over the next few years the health-care demands of osteoporosis and hip fractures are expected to increase ten-fold. In this article, the pathogenesis and classification of age-related osteoporosis are analyzed. Treatment options are examined and a rational management plan for this entity is discussed.

Objective: To determine the effects of long-term use of the thiazide diuretic chlorthalidone on serum bone-related biochemical variables in older persons. Design: Cross-sectional comparison. Setting: Community-dwelling subjects who had participated in the Systolic Hypertension in the Elderly (SHEP) program. Participants: Sixty-six Caucasians (36 male and 30 female), age range 70 to 89 years, of whom 23 were taking a thiazide diuretic. Measurements: 25-hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, calcitonin, and serum bioavailable testosterone. Results: In both groups, there was a high prevalence of low 25 (OHD) levels (30%). Log 25OHD showed a significant inverse relationship to parathyroid hormone (r = .33, P < 0.05). Thiazide users had lower levels of osteocalcin (P < 0.05) and parathyroid hormone levels (P < 0.05) compared with non-thiazide users. Male thiazide users had decreased bioavailable testosterone levels compared with non-thiazide users (P < 0.05). Serum osteocalcin was significantly related to bioavailable testosterone in men not on thiazide (r = .43, P < 0.05). Conclusions: Hypovitaminosis D is a common finding in older individuals with associated elevations in parathyroid hormone. Parathyroid hormone and testosterone concentration (in men) are correlated with serum osteocalcin, a measure of osteoblastic activity. Long-term thiazide use alters these relationships and produces a biochemical profile suggestive of decreased bone formation. Reduced bioavailable testosterone may also play a role in these biochemical changes.

Background. This cohort of "late middle-aged" African Americans has an excess of disability. We aimed to determine associations of circulating cytokine receptors (sTNFR1, sTNFR2, and sIL-6R) and C-reactive protein (CRP) with disability, physical function, and body composition. Methods. Stratified sampling of two socioeconomically diverse strata of St Louis, Missouri, occurred in 2000-2001. Inclusion criteria were self-reported black or African American race, born 1936-1950 inclusive, and Mini-Mental State examination score of 16 or greater. In-home evaluations of handgrip strength, lean body mass percentage (LBM%), physical performance, upper and lower body functional limitations (UBFLs and LBFLs), and basic and instrumental activities of daily living (BADLs and IADLs) were collected. Of the 998 participants, 368 had blood sampled at baseline. Serum was stored and assayed in 2006. Results. Absolute risks were LBFLs of 2 or more, 46%; UBFLs of 1 or more, 23.5%; BADLs of 2 or more, 20.6%; and IADLs of 2 or more, 22.5%. Independent of age, sex, and underlying comorbid conditions, higher CRP and sTNFR were associated with poorer physical performance ( b = −1.462, p < .001 and b = −0.618, p = .003), UBFLs (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.1-4.64 and OR 1.39, 95% CI 0.96-2.02), LBFLs (OR 2.30, 95% CI 1.19-4.45 and OR 1.91, 95% CI 1.26-2.91), BADLs (OR 2.79, 95% CI 1.03-5.96 and OR 1.66, 95% CI 1.11-2.46), and IADLs (OR 2.13, 95% CI 1.03-4.41 and OR 1.43, 95% CI 0.99-2.08). higher CRP ( b = −3.251, p

Nearly 50% of individuals with type II diabetes mellitus are over the age of 65 years. There are numerous reasons to maintain blood glucose levels below 11.1 nmol/L (200 mg/dl) in older persons, and there are a number of changes often seen with advancing age that persons, and there are a number of changes often seen with advancing age that may interfere with the management of diabetes mellitus, e.g. hypodipsia, anorexia, visual disturbance, altered renal and hepatic function, depression, impaired basoreceptor response and multiple medications. Hyperglycaemia appears to produce cognitive impairment which may lead to poor compliance. It is often difficult to manipulate diet in older people, and in fact dietary changes can lead to severe protein energy malnutrition. High maximum voluntary oxygen intake has been correlated with increased glucose disposal, but there is little evidence that physical exercise can improve diabetic control in the elderly. Oral sulphonylurea hypoglycaemic agents are extremely useful in the treatment of diabetes in these patients, but it should be remembered that they are more liable to develop hypoglycaemia than are younger diabetics. The role of metformin in the management of older diabetic patients is poorly studied. Many older persons can cope well with insulin therapy, but those with visual disturbances often make errors when drawing up insulin and require special attention. Combination therapy of insulin with oral hypoglycaemic agents is not recommended in this group of patients, and serum fructosamine is preferred to glycated haemoglobin to monitor control. Successful management of elderly diabetic patients thus requires an interdisciplinary team approach.

There are few reported data on biochemical and functional correlates of androgen levels in African-American men. This study aimed at reporting physical and biochemical correlates of serum total testosterone (total T), bioavailable testosterone (BT) and dehydroepiandrosterone-sulphate (DHEAS) levels in community-dwelling, African-American men aged 50-65 years. Home-based physical examinations and health status questionnaires were administered to randomly sampled men. Body composition (dual-energy X-ray absorptiometry), lower limb and hand-grip muscle strength, and neuropsychological functions were assessed. Levels of serum total T, BT, DHEAS, oestradiol (E2), adiponectin, leptin, triglycerides and glucose were measured. Multiple linear regression models were constructed to identify factors independently associated with androgen levels. DHEAS levels declined from age 50 to 65 years (p < 0.0001), but total T and BT levels remained constant. Independent of other associated factors, higher total T levels were associated with lower serum triglyceride levels (beta = -0.142, p = 0.049); higher BT was associated with better performance on the trail-making tests (TMT-B:TMT-A ratio: beta = -0.118, p = 0.024) and higher DHEAS levels were associated with lower adiponectin (beta = -0.293, p = 0.047) and higher mini-mental state examination (MMSE) score (beta = 0.098, p = 0.008). Multiple regression models predicted 21, 18 and 29% of variance in total T, BT and DHEAS, respectively. Higher total T levels were associated with serum metabolic markers, particularly lower triglycerides, whereas higher BT was associated with better cognitive and muscle function and DHEAS with lower adiponectin and higher MMSE scores.

OBJECTIVE To determine the effect patient education has on osteoporosis prevention and calcium intake has on elderly men who are at risk for developing osteoporosis. DESIGN This was a prospective study in which subjects completed a Men's Osteoporosis Risk Questionnaire and watched a video on osteoporosis prevention. Subjects were then divided into groups based on osteoporosis status and contacted one month later to complete a telephone survey. SETTING Geriatric ambulatory care clinic in the St. Louis Veteran's Affairs Medical Center. PARTICIPANTS 35 men over the age of 65. INTERVENTION Subjects watched a video on osteoporosis prevention. OUTCOMES Primary outcome was change in calcium intake (total, dietary, and supplemental) in men at risk for osteoporosis. Secondary objectives were new diagnoses of osteoporosis; new fractures; effects on exercise, tobacco and alcohol use; and change from baseline calcium intake between at risk, diagnosed, and no risk for osteoporosis subjects. RESULTS After watching the educational video, 67% of the subjects increased the amount of calcium ingested, and 10% of the subjects began calcium supplementation. CONCLUSIONS There were significantly more subjects meeting the RDA of calcium after watching the educational video.

Three questionnaires, the St. Louis University Androgen Deficiency in Aging Male (ADAM), the Aging Male Survey (AMS) and the Massachusetts Male Aging Study (MMAS), have been developed as potential screening tools for hypogonadism in older males. We compared these questionnaires in 148 males aged 23-80 years using bioavailable testosterone as the "biochemical gold standard" for diagnosis of hypogonadism. The sensitivity for the ADAM was 97%, for the AMS 83% and the MMAS 60%. Specificity was 30% for the ADAM, 59% for the MMAS and 39% for AMS. Both bioavailable testosterone and the calculated free testosterone correlated significantly with a number of the individual questions. Total testosterone correlated poorly with most of the questions. In conclusion, the ADAM and AMS may be useful screening tools for hypogonadism across the adult lifespan, but both are relatively nonspecific.

This study compared the results of various testosterone assays in a cross-sectional study of 50 male subjects age 28 to 90 years. The purpose of the study was to determine the relationship of the various testosterone assays to one another. In addition, we determined week-to-week variability in testosterone and bioavailable testosterone in 16 subjects. The following assays were undertaken: total testosterone (T), free testosterone by equilibrium dialysis (FTD), bioavailable testosterone (BT), free testosterone by ultracentrifugation (FTU), and direct estimation of serum free T by an analog ligand radioimmunoassay (FTA). In addition, using total T and sex hormone-binding globulin (SHBG), we calculated the free androgen index (FAI = T/SHBG) and the free testosterone index (FTI) using the method of Vermeulen. In a second study, we measured the week-to-week variation in T and BT in a group of older males. Lastly, we demonstrated excellent stability of serum stored at [minus ]70[deg ]C for up to 7 years for T and BT. Correlations of the various assays to increasing age were significant for all assays except total T (r = [minus ].126). The best correlation was found with BT (r = [minus ].744, P [lt ] .001). All measures were statistically significantly correlated with FT. The best correlations were FTI (r = .807, P [lt ] .007) and BT (r = .670, P [lt ] .001). If T was used to classify hypogonadism in comparison to BT, it resulted in misclassification in 42% of cases. In addition, we demonstrated a marked week-to-week variability in T and BT in older men with the T and BT being in the eugonadal range some weeks and hypogonadal on other occasions. This occurred in 8 of 16 men for T and 10 of 16 men for BT. Based on these data, we suggest that the FTI or BT are the most practical methods to determine hypogonadism. There is a need for increased awareness that marked week-to-week variability within a single individual can occur for measurements of both T and BT.

Because osteoporosis and its attendant fractures are more common in women than in men, most studies have been performed in women. However, age-related osteoporosis and fragility fractures are also a major problem in men. Recent studies suggest that diagnosing men as osteoporotic when they fall more than 2.5 standard deviations below the mean for young men identifies a group at risk for fracture. Data suggest that many men with femoral fractures have age-related hypogonadism. Hypogonadism is associated with decreased lean body mass and bone mass. Most men with femoral fractures are reported to be hypogonadal. Testosterone replacement in hypogonadal older men improves bone mass and lean body mass. A therapeutic intervention to reduce fracture incidence in men with osteoporosis has been reported. No population-based study has examined the incidence or prevalence of hypogonadism with or without osteoporosis in men. Thus, osteoporosis in men probably exists with and without hypogonadism. Therapeutic interventions should be based on treatment of hypogonadism when present with osteoporosis.

Estrogen deficiency in women is associated with accelerated bone loss, and estrogen replacement therapy has been proven to be effective in preventing osteoporosis and fractures in postmenopausal women. The introduction of selective estrogen receptor modulators that have an estrogen-like effect on the skeleton but have a different pattern of effects on other tissues may have an important role in the management of osteoporosis in women in the near future. In men, androgen deficiency has been shown to be associated with osteoporosis. Although androgen replacement in hypogonadal men may decrease bone resorption and increase bone mass, long-term placebo-controlled trials are needed to better define the benefits and risks of such therapy before it can be recommended. Sex hormone deficiency is linked to the development of osteoporosis in both women and men. In women, hormonal replacement by estrogen or the newly developed selective estrogen receptor modulators may prevent the development of osteoporosis and its related fractures. In men, there is early evidence that testosterone replacement therapy may enhance bone mass in hypogonadal men.

ging is associated with a series of inexorable physiologic changes in men such as decline in libido, decreased potency, osteopenia, decreased muscle mass and strength, decreased food intake, and cognitive function. Many of these changes are similar to those seen with male hypogonadism. Recently it has become established that testosterone levels decline from the age of 30 years and this rate of decline parallels the rate of decline of the physiologic changes associated with aging (see below). This has led to the speculation that a lack of testosterone is responsible for some of these changes and that testosterone replacement therapy may retard or reverse some of these age-related “degenerations”. The concept that a decline in testosterone with aging is associated with a variety of physiologic age-related changes, similar to the role of estrogen deficiency in women, has been referred to by a variety of names, including male menopause, the climacteric, the viropause, the andropause, or most recently, ADAM. This article reviews the changes in androgen levels that occur with aging and the evidence that some of these changes may play a role in the physiology of the aging process. The putative benefits of testosterone replacement in older men are listed in Table I. The concept that testosterone replacement may reverse some of the deleterious effects of aging was first offered by the French neurologist Charles Edouard Brown Sequard. When he was 72 he conducted a series of animal experiments on the effects of testicular extracts and then injected himself, with the reported excellent results given in the quotation at the beginning of this article.1,2 In his article he recognized that the effect could be a placebo one. FROM THE CHICAGO MEETINGS

Cross-sectional studies have suggested that serum 25-hydroxyvitamin D (25OHD) levels decline with aging. We have examined this putative decline in a longitudinal study using participants in the New Mexico Aging Process Study. 25OHD levels were measured in participants in whom serum samples were available between 1980 to 1982 and 1989 to 1994 (37 men and 99 women). The available data for these visits included age, gender, and the date the sample was obtained. Questionnaires assessing physical activity and vitamin D intake were administered at the visits. A seasonal variation (r = .25, P < .05) in 25OHD was demonstrated in the whole group of subjects. In 25 subjects who were not receiving vitamin D supplementation at either time and had samples obtained in the same season, both serum 25OHD (P < .05) and physical activity (P < .05) decreased over a mean period of 11.4 years. In 23 subjects who had samples obtained in the same season but used vitamin D supplements at both times, there was no change in serum 25OHD. Mean summer 25OHD levels did not change with the duration of study. On the other hand, the mean serum 25OHD declined with the duration of study when measured from winter to winter or spring to spring. Multiple regression analysis demonstrated that the month, activity level, vitamin D supplementation, and gender (P < .001) were independent determinants of serum 25OHD levels. This study confirms that aging is associated with a reduction in serum 25OHD, and suggests that this decrease is a reflection of reduced sun exposure rather than aging per se. The reduction in serum 25OHD was the result of decreasing winter and spring 25OHD serum concentrations. It is clear that vitamin D supplementation can prevent the age-related decline in 25OHD levels.

To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women.A cross-sectional study.The Sac and Fox Nation in rural OklahomaSerum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry.A total of 77 Native American women aged 19 to 85 years.Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P.05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P.001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P.001). BMD was lower (P.001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (ror = -0.48, P.001) and body mass index (BMI) (ror = 0.41, P.005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P.05) and femoral (r = .41, P.01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P.05) in premenopausal Native American women, and lower (P0.05) in postmenopausal subjects, compared with white women.In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years.A randomized controlled trial.Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension.Reduction in average weekly self-reported alcohol intake was significantly greater (P.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44).The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.

Leptin is a recently isolated peptide hormone released from adipocytes that has been postulated to play a role in appetite regulation and energy metabolism. Aging affects both food intake and body composition. Body composition is also affected by ethnicity. We have evaluated the relationships between serum leptin levels, age, body composition (by dual-energy x-ray absorptiometry), and hormonal parameters in a cross-sectional study of 94 women, 53 African-American (AAF) and 41 Caucasian (CF). Our hypotheses were as follows: (1) changes in body composition would be related to age in a sinusoidal pattern, (2) changes in serum leptin would parallel changes in body fat, (3) serum leptin levels would be influenced by body fat distribution, and (4) serum leptin would be related to serum concentrations of sex hormones. Serum leptin paralleled changes in body fat and body mass index (BMI) with age. In the entire group, serum leptin correlated closely with measures of body fat, including BMI and total fat mass, and there was no difference in leptin levels between the two ethnic groups. In simple regression analysis, serum leptin was related to both serum estradiol and testosterone. The relationship between serum leptin and trunk fat was linear in both groups, but significantly different in AAF and CF (P = .014). Serum leptin was associated with the trunk to lower-extremity fat ratio in CF (r = .67, P = .001) but not in AAF. Body fat was increased with advancing age until about 65 years and then declined. Measures of lean body mass declined linearly with age in the entire group, as well as both subgroups. In the entire group, total lean body mass and lean body mass corrected for BMI (lean body mass/BMI) were inversely related to age. In subjects aged less than 60 years AAF were stronger (P < .05) and had both a larger BMI and fat mass (P < .05) than CF. However, the patterns of age-related changes in fat body mass, lean body mass, and BMI were similar in both groups. In the entire group, multiple regression analysis indicated that the age, free thyroxine index (FTI), and leptin concentration were predictors of the body composition and distribution of trunk to lower-body fat. These observations indicate that there is a sinusoidal relationship between body fat and age, with a decline in body fat in extreme old age in both AAF and CF, and that serum leptin concentrations are more closely related to body fat and BMI than to age or ethnicity.

A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population. Fifteen hypogonadal men (mean age 68 ± 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65± 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone Testosterone improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean ± sem: −2.0 ± 0.9 ng/dL vs. 0.8 ± 0.7 ng/dL; P < 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit. Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.

There is limited information concerning bone mineral density (BMD) and its determinants across a wide spectrum of ages in African American females (AAF). Therefore, we have performed a cross-sectional study of 54 AAF and 39 Caucasian females (CF), aged 20-90 yr, to quantify femoral and lumbar bone mineral density, total body calcium, as well as the potential determinants of bone density. BMD decreased with age in all sites after age 40 yr in both racial groups. Bone density was greater in AAF than in CF, although there was considerable overlap between the two groups. There was no significant difference in the rate of age-related bone loss between the two groups. At the femoral neck, BMD was below the fracture threshold in 28% of the postmenopausal AAF compared to 47% of postmenopausal CF. L1-L4 BMD was below the fracture threshold in 8% of postmenopausal AAF and 11% of postmenopausal CF. Serum-25 hydroxyvitamin D (25OHD) was inversely related to age in both othnic groups and lower (P0.05) in premenopausal AAF than CF. Twenty-four percent of the AAF and 22% of the CF had serum 25OHD levels of 8 ng/L or less. Serum PTH was directly related to age (r = 0.43; P = 0.003 in AAF and r = 0.55; P = 0.002 in CF), and 25OHD was inversely related to age (r = -0.43; P = 0.003 in AAF and r = -0.65; P0.001 in CF). PTH was higher (P0.05) in postmenopausal AAF than in CF. Serum testosterone was greater in AAF than in CF (P0.05). Serum estradiol was greater in premenopausal AAF than in CF. Serum dehydroepiandrosterone sulfate was inversely related to age (r = 0.42; P = 0.004 in AAF and r = 0.51; P = 0.005 in CF). Serum osteocalcin was related to age in AAF (r = 0.47; P = 0.001), but not in CF. There was also a trend for an increase in urinary dipyridinoline (expressed per 100 mg urinary creatinine) with age (r = 0.31; P = 0.055 in AAF and r = 0.37; P = 0.066 in CF). Both lean and fat mass were major determinants of femoral neck BMD in AAF. Femoral BMD was directly related to body weight and body mass index in both races. Serum 25OHD and dehydroepiandrosterone sulfate approached statistical significance as independent predictors of femoral BMD in AAF. We conclude that in AAF, 1) bone density is higher than in CF, but there is a significant risk of fracture in a substantial number of subjects on the basis of BMD; 2) there is no difference in rates of age-related bone loss compared to those in CF; 3) both lean and fat mass are significant determinants of bone density; 4) serum estradiol and testosterone were higher than those in CF; and 5) aging is associated with increased bone turnover, 25OHD deficiency, and secondary hyperparathyroidism in both races. The absence of a difference in rates of bone loss between AAF and CF despite higher serum levels of PTH is compatible with the concept of a relative skeletal resistance to PTH in AAF.

Objective: To determine normal serum bone-related biochemical variables in older African-Americans. Design: A convenience sample of older African-Americans who had a health screening and blood testing for calciotropic hormones was compared with white Americans who were recruited at the end of the Systolic Hypertension in the Elderly Program (SHEP) study and were not on a thiazide diuretic. Setting: Community-dwelling African-Americans who participated in SHEP or who attended one of two mass health screenings. Participants: Thirty-two African-Americans aged 68–93 years and 43 white Americans aged 70–89 years. Measurements: Twenty-five hydroxyvitamin D (250HD), parathyroid hormone, osteocalcin, and calcitonin. Results: Serum 250HD levels in 38% of the African-American men and 38% of African-American women were less than 8 ng/mL compared with 22% of Caucasian men and 40% of Caucasian women. Serum parathyroid hormone (PTH) was above the normal range in 25% of men and 33% of women of African-American descent and 14% of Caucasian men and 30% of Caucasian women. Serum 25OHD was lower (P < 0.05) in individuals with a previous history of fracture. Serum albumin (P < 0.05), calcitonin (P < 0.05), and osteocalcin (P < 0.05), but not 25OHD, were lower in African-Americans (men and women) when compared with Caucasians (P < 0.05). Serum calcium corrected for albumin was higher in the African-Americans than in the Caucasians (P < 0.05). As previously reported in Caucasians, PTH was inversely related to log 25OHD in African-Americans. Serum osteocalcin was positively correlated to PTH in African-Americans, as previously reported in Caucasians. Log 25OHD correlated inversely with osteocalcin in African-Americans, but this was not seen in Caucasians. Conclusions: In this limited sample, hypovitaminosis D (as assessed by 25OHD level) with secondary hyperparathyroidism occurred frequently in elderly African-Americans. Osteocalcin, a measure of osteoblast activity, correlated with 25OHD and parathyroid hormone. Osteocalcin serum levels were lower in African-Americans than Caucasians, but serum calcium corrected for albumin was higher in the former compared to the latter.

Parathyroid hormone (PTH) induces osteoblastlike cells to secrete factors capable of increasing cellular bone resorption; these factors are extremely labile. We have partially isolated them from supernatants of PTH-stimulated ROS 17.2 cells using affinity chromatography. Products eluted from the matrix, carboxymethyl cellulose covalently linked to Cibacron Blue F3GA, (CM-AB) were used as immunogens in mice. Serum from these mice blocked the effect of PTH-stimulated supernatants in a bioassay for bone resorption (the bone rudiment system). Then, hybridomas were produced from spleen cells of these mice. Screening of these hybridoma cultures revealed a consistent blocking effect of supernatants at a dilution of 1:100 in the bioassay. At higher dilution (1:1000), however, fewer culture supernatants blocked this effect in the bioassay. Mixed hybridoma cultures have been cloned and subcloned. Evaluation of the resulting hybridoma supernatants revealed that supernatants from at least three clones were necessary to neutralize the effect of the PTH-induced, osteoblast-produced resorption factors in organ culture. Similarly, using sucrose density gradient analysis, it is necessary to use three antibodies to bind all the 35S-labeled protein from supernatants of PTH-stimulated ROS cultures (equivalent to the fraction used as immunogen in the mice). The effect of PTH in organ culture is blocked by this same group of hybridoma supernatants. The antibodies appear specific for osteoblast-like cell resorption factors, as they do not block the effect of PTH on cAMP accumulation in ROS cell cultures. On the other hand, they do block the effects of dibutyral cAMP on resorption in organ culture. The effect of antibodies on bone resorption is not nonspecific, as hybridomas have no effect on increased 45Ca release from organ culture induced by thyroxine. We conclude that we have isolated hybridomas that produce antibodies capable of binding to PTH-induced, osteoblast-produced factors. These antibodies are able to inhibit the increase in cellular bone resorption in organ cultures caused to either PTH or these factors.

T EPTIN is a newly discovered honnone timt is produced by L adipocytes (1). Leptin decreases food intake and increases energymetabolism in rodents. In addition, leptinappears to playa role in the regulation of the hypothalamic-pituitary-gonadal axis (2). In this issue of the Journal 0/ Gerontology: Biological Sciences, Wolden-Hanson and colleagues (3) report on the relationship of leptin to adiposity in aging male BrownNorway rats. Fat mass and leptin increased with age. Testos-terone declined with aging and was associated with a decreased skeletal muscle mass. In another study, Li and colleagues (4) found that in aging male rats there was an increase in leptingene expression timt was greaterthan the increase in adiposity withaging. In micemessenger RNA leptin levels increased with age, but correlated with body mass (5). In thestudy in the Journal, leptinwas associated withsubcutaneous fatand not visceral fat, Barzilai and colleagues (6) haveshownin youngrats thatleptinadministration selectively decreased visceral adiposity. The elevated leptin levels with age givea possible explanation for the decrease in visceral fat in older BrownNorwayrats. Wolden-Hanson and colleagues (3) claimed that the Brown Norway rat is a good model of human aging. In human females, leptin levels increase at middle age and decline in old age in concert with alterations in adipose tissue mass (7). The New Mexico Aging Process Studies of Baumgartner and colleagues (8) found that leptin levels were related to subcutaneous rather than visceral adipose tissue. This is the same as was found in rats. In addition, in older females, but not males, leptin levels correlated with resting metabolie rate (9). Endogenous and exogenous estrogens do not appear to alter leptin levelsin females (10). Leptin levels are lower in males than females even when correctedfor bodyfat.In malesleptinlevels increase withagein both cross-sectional and longitudinal series (11). In these studies besides correlating with fat mass, leptin was also correlated with testosterone. Another cross-sectional study has also implicated testosterone in the alterations of leptin in aging males (12). Both cmss-sectional (13) and longitudinal studies (14) haveshownthat testosterone levels decline withaging. This declinein testosterone has been correlated with the decline of body mass and strength that occur with aging (15-17). Testos-terone replacement in young hypogonadal males and in older males increased strength anddecreased leptinlevels (18-21). Overall thesestudies strangly support the concept that the age-related decline in testosterone is

Context. —Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. Objective. —To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. Design. —Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Participants. —A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). Intervention. —Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. Main Outcome Measures. —Fatal and nonfatal heart failure. Results. —During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71;P Conclusion. —In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

Background: Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities. Methods: A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447 921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed. Results: Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period. Conclusions: The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities. (Arch Intern Med. 1994;154:2154-2160)

Industrial exposure to large amounts of cadmium is known to be toxic to man; however, the low levels of cadmium in water, food, and air to which everyone is continually exposed have no obvious effects. During childhood and adolescence, ingestion and inhalation of cadmium are responsible for the average American accumulating about 30 mg of cadmium in his body, with the highest concentration being in the kidney. It has been suggested on the basis of two observations that elevated renal cadmium might be associated with essential hypertension: (1) Hypertensives have been reported to have higher renal cadmium concentrations than normotensives. (2) Long-term exposure to low levels of cadmium has reproducibly caused mild hypertension in animals. Finally, increased levels of cadmium have been found in lungs and other tissues of emphysematous subjects. Language: en

PTH stimulates osteoblast-like cells to produce a product(s) capable of increasing cellular bone resorption. We have investigated this phenomenon using primary cultures of osteoblasts and the clonal osteoblast-like cell line ROS 17/2. Conditioned medium from PTH-stimulated populations of either culture increases bone resorption compared to conditioned medium measured in three independent assay systems; the isolated osteoclast assay system, elicited macrophages, and the fetal bone rudiment system. Characterization of the factor(s) of PTH-stimulated osteoblast-like cell (ROS 17/2) suggests that the compound(s) is not prostaglandin (no inhibition by indomethacin; not extractable in diethylacetate). Rather, it is heat and protease sensitive. In addition, secretion of the product is sensitive to cycloheximide. These findings lead us to the conclusion that the factor(s) is protein. Further work demonstrates the necessity for a divalent cation for retention of factor activity. Finally, we have estimated the molecular radius of the factor as about 110,000 daltons and perhaps a second at about 70,000 daltons using a sizing column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of [35S]methionine-labeled PTH-stimulated ROS culture supernatants reveals relatively increased secretion of proteins with these approximate molecular radii.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Because high barium concentrations (2-10 ppm) in human drinking water have been reported to be associated with elevated cardiovascular mortality, hypertension and other cardiovascular effects were sought in rats chronically exposed for 1-16 mo to drinking water containing 1, 10, or 100 ppm barium. From weaning, female Long-Evans rats were kept in a "low contamination" environment and fed a diet low in trace metals. Their drinking water was deionized, fortified with 5 essential trace metals, and either 0, 1, 10, or 100 ppm barium was added. Indirect systolic pressure of unanesthetized rats was measured in triplicate at 1, 2, 4, 8, 12, and 16 mo. Average systolic pressure increased significantly after exposure to 100 ppm barium for 1 mo or longer and after exposure to 10 ppm barium for 8 mo or longer. After 4 or 16 mo, barium exposure failed to alter organ weights or tissue concentrations of calcium, magnesium, sodium, or potassium; however, both 10 and 100 ppm barium resulted in significant increases in tissue barium. Rats exposed to 100 ppm Ba for 16 mo exhibited depressed rates of cardiac contraction and depressed electrical excitability in the heart. Hearts from these maximally exposed rats also had significantly lower ATP content and phosphorylation potential, as measured by 31P NMR spectroscopy. Although the barium-induced increase in the blood pressure of rats was modest, comparable mild hypertension in humans would have major health implications.

SummaryExposing female Long-Evans rats to 0.1, 0.25, or 0.5 ppm of cadmium in drinking water for 6 to 18 months from the time of weaning induced a statistically significant average increase in systolic pressure of 10 to 24 mm Hg, and there was no evidence of cadmium toxicity. Comparable exposure to 0.01 or 0.03 ppm of cadmium was much less effective in raising pressure and probably had no pressor effect. After 18 months of exposure, the average renal cadmium level for the “0.1 ppm cadmium group” approximated 1 μg/g in contrast to more than 40 μg/g for the standard “5 ppm group” and less than 0.1 μg/g for the control group.

Metabolic and functional (heart only) effects of long-term (15 months), low level (5 parts/10 6 in drinking water) cadmium and/or lead ingestion on myocardial, hepatic and renal tissues were assessed. Myocardial peak active tension was lower and tissue heavy metal levels were elevated significantly in cadmium and/or lead-exposed rats. The ATP ( P P P P P

The presence of bilateral pseudofractures is generally considered a reliable radiologic diagnostic feature of osteomalacia. We report two women with long-standing bilaterally symmetrical femoral pseudofractures that did not demonstrate the histologic features of osteomalacia upon examination of non-decalcified sections of iliac crest bone. One patient treated empirically for osteomalacia developed evidence of early vitamin D intoxication. We conclude that there is no completely reliable non-invasive diagnostic test for osteomalacia.

Groups of 15 to 18 female weanling Long-Evans rats fed a rye-based diet low in lead (0.25 ppm) were exposed to 0.1, 1.0, and 5.0 ppm lead in drinking water. No suggestion of clinical lead toxicity was recognized. Systolic pressures were measured at 3-month intervals after weaning. The groups of lead-exposed animals had consistently and significantly higher average pressures than control animals, the increase approximating 15 mm Hg. With the lowest lead exposure (0.1 ppm), the increase in average pressure was gradual, being half minimal at 3 months and requiring 1 year to become maximal. After 1 year, half of these rats had pressures from 0 to 10 mm Hg above the control average; 40, 20, and 10% had pressures that were 20, 30, and 40 mm Hg, respectively, above the control average. Thus, rats exposed to lead in amounts comparable to the environmental exposure of many Americans had an average elevation in systolic pressure comparable to that of human beings with essential hypertension.

We have developed a monoclonal antibody capable of detecting 1 pg/ml of 1,25-dihydroxycholecalciferol. At a dilution of 1:80,000 of ascitic fluid this antibody has an apparent K D of 3.3 × 10 −11 ML −1 . The immunogen used was a vitamin D analogue, calcitroic acid [1α, 3 β-dihydroxy-9, 10 seco-24-nor 5,7,10 (19) cholatriene-23-oic acid], conjugated to bovine serum albumin. Although this antibody is extremely sensitive, it also recognizes other important vitamin D 3 metabolites.

Serum calcium, ionized calcium, and phosphorus have been obtained at hourly intervals in nine healthy postmenopausal women. The hourly means of ionized calcium and phosphorus demonstrate significant diurnal variation with a similar apogee, nadir, and periodicity (24 hours). These results are distinct from the diurnal variation of ionized calcium and phosphorus previously reported for young men and provide more evidence of an altered mineral hemostasis in postmenopausal women.