H. Mitchell Perry

Effects of Testosterone Replacement Therapy in Old Hypogonadal Males: A Preliminary Study

To examine the effects of testosterone administration to older hypogonadal males (bioavailable testosterone less than 70 ng/dL).

Early Predictors of 15-Year End-Stage Renal Disease in Hypertensive Patients

There has been a continuing increase in the incidence of end-stage renal disease (ESRD) in the United States, including the fraction that has been attributed to hypertension. This study was done to seek relationships between ESRD and pretreatment clinical data and between ESRD and early treated blood pressure data in a population of hypertensive veterans. We identified a total of 5730 black and 6182 nonblack male veterans as hypertensive from 1974 through 1976 in 32 Veterans Administration Hypertension Screening and Treatment Program clinics. Their mean age was 52.5 +/- 10.2 years, and their mean pretreatment blood pressure was 154.3 +/- 19.0/100.8 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5337 (44.8%) of these patients died and 245 developed ESRD. For 1055 of these subjects, pretreatment systolic blood pressure (SBP) was greater than 180 mm Hg; 901 were diabetic; 1471 had a history of urinary tract problems; and 2358 of the 9644 who were treated had an early fall in SBP of more than 20 mm Hg. We used proportional hazards modeling to fit multivariate survival models to determine the effect of the available pretreatment data and early treated blood pressure levels on ESRD. This model demonstrated the independent increased risk of ESRD associated with being black or diabetic (risk ratio, 2.2 or 1.8), having a history of urinary tract problems (risk ratio, 2.2), or having high pretreatment SBP (for SBP 165 to 180 mm Hg, risk ratio was 2.8; for SBP > 180 mm Hg, risk ratio was 7.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis.

Abstract Of 371 patients with hypertension who were observed for two months to 20 years and who were initially treated with from 100 to 1,600 mg of hydralazine daily, late toxic manifestations to the drug developed in 44. They were serious in 14. The course of such toxicity is presented, with emphasis on factors predisposing to the syndrome and on the long-term course of oncetoxic patients, including the results of readministering hydralazine to them. Among drug-induced diseases, late hydralazine toxicity is of peculiar interest because of its clinical similarity to idiopathic lupus erythematosus and rheumatoid arthritis. The syndrome, however, is a relatively benign one; the toxic manifestations are reversible when the drug is withdrawn, and the arthritis is not deforming. Several interesting observations concerning the toxicity have recently been made: first, only that half of the population with a low level of hepatic acetyl transferase activity is susceptible to clinical hydralazine toxicity; second, both antihydralazine antibodies, suggesting hypersensitivity, and antiDNA antibodies, suggesting lupus erythematosus, are demonstrable in toxic patients; third, significant remissions of serious hypertension, although rare, seem to occur more frequently in once-toxic patients; and fourth, survival time from the onset of therapy is suggestively better in toxic patients than in similarly treated, matched patients with no history of toxicity.

Systolic Hypertension in the Elderly Program (SHEP): Antihypertensive efficacy of chlorthalidone

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.

Studies on the control of hypertension by hyphex. II. Toxic reactions and side effects.

Although effective in maintaining relatively normal levels of blood pressure in hypertensive patients and retarding some of the serious and fatal secondary consequences of the disease, hexamethonium ion and 1-hydrazinophthalazine can cause severe immediate and late reactions. The latter drug has produced collagen diseases of varying degrees of severity, all of which have regressed on cessation of medication, in 14 of 253 patients. The combination has given rise to fatal interstitial pneumonia in 5 of 89 in malignant stages of hypertension. Less serious side effects of each agent are also discussed.

Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Diuretics and &bgr;-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and &agr;-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged ≥55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged ≥70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics?

NORMAL CONCENTRATIONS OF SOME TRACE METALS IN HUMAN URINE: CHANGES PRODUCED BY ETHYLENEDIAMINETETRAACETATE *

Interest in the biologic role of trace elements prompted an investigation of their renal excretion. Preliminary qualitative analysis revealed that except for cobalt the entire first transition series of metals, namely, titanium, vanadium, chromium, manganese, iron, nickel and copper, were detectable in most human urines. In addition the heavier transition metals, molybdenum and silver, as well as the related metals, zinc, cadmium, tin and lead, were ordinarily present. A method was evolved by which the urinary concentrations of such metals could be quantitatively estimated. The procedure included initial chemical concentration followed by spectrographic analysis. Contamination was minimized by careful preparation of equipment and reagents. Since extraneous iron and copper were particularly difficult to avoid and since these two metals had frequently been studied by other techniques, no attempt was made to measure them spectrographically. The exclusion of significant positive contamination, the demonstration that the low renal excretion of cobalt permitted its use as an internal standard, and the determination of standard working curves and recovery data for each metal constituted the control data for the assay procedure. Estimations were less satisfactory for chromium and titanium than for the remaining nine metals. Collection and assay of 24 hour urines were

Renal venous renin in hypertension

Abstract Renin activity was measured in the peripheral and renal venous blood of fifty hypertensive patients with varyingly compromised renal arteries. In ten patients with normal and equal renal masses and no renal arterial stenosis, renin activity in peripheral blood and in blood from the two renal veins was essentially the same. Results were similar in six of seven patients with decreased renal mass but no renal arterial stenosis, in seven patients with insignificant but definite unilateral renal arterial stenosis and in four patients with insignificant but bilateral renal arterial stenosis. By contrast, prior to surgery, in eleven of seventeen patients with significant unilateral renal arterial stenosis and in four of five patients with bilateral stenosis, significant on one side at least, the differences in renin activity between blood from the affected or most affected kidney and blood from the other kidney or from the periphery were marked. Renin activity in blood from the affected kidney was normal in four patients with significant unilateral renal arterial stenosis. In nine of fourteen patients, the results of renal venous renin determination correlated well with studies of split renal function. From the data presented and from that reviewed in the literature, an analysis is made of the reportedly high predictive value of renin activity as an index to the ultimate effect of surgery in hypertensive patients with renal arterial stenosis.

Studies on the Control of Hypertension: VIII. Mortality, Morbidity, and Remissions During Twelve Years of Intensive Therapy

EFFECTIVE pharmacological control of severe arterial hypertension has been available for more than a decade. A combination of an orally administered ganglioplegic agent and hydralazine was first found to induce sustained reduction of blood pressure to normal or nearly normal levels in the summer of 1951,1 and a practical therapeutic regimen was quickly developed.2 A large series of patients, selected only for severity of the hypertensive process, was treated with this regimen in order to evaluate its long-term effects on mortality and morbidity. Interim reports on various aspects of the study have been published.3-6 The present report concerns 316 patients suffering from moderately severe and severe hypertension who began to ingest ganglioplegic agents and hydralazine more than 7 years ago; almost half of them began more than 12 years ago. Therapy was intensive, as doses of drugs large enough to produce the desired antihypertensive effect were employed in every case. This report cites the mortality associated with differing severities of hypertensive disease. It examines the significance of advanced hypertensive retinopathy by comparing patients exhibiting this finding with those having other hypertensive complications. The time and cause of death are considered as

THE WASHINGTON UNIVERSITY- EPRI VETERANS' COHORT MORTALITY STUDY: Preliminary Results

This article presents the design of and some results from a new prospective mortality study of a national cohort of about 50,000 U.S. veterans who were diagnosed as hypertensive in the mid 1970s, based on approximately 21 yr of follow-up. This national cohort is male with an average age at recruitment of 51 ± 12 yr; 35% were black and 81% had been smokers at one time. Because the subjects have been receiving care at various U.S. Veterans Administration (VA) hospitals, access to and quality of medical care are relatively homogeneous. The health endpoints available for analysis include all-cause mortality and specific diagnoses for morbidity during VA hospitalizations; only the mortality results are discussed here. Nonpollution predictor variables in the baseline model include race, smoking (ever or at recruitment), age, systolic and diastolic blood pressure (BP), and body mass index (BMI). Interactions of BP and BMI with age were also considered. Although this study essentially controls for socioeconomic status by design because of the homogeneity of the cohort, selected ecological variables were also considered at the ZIP code and county levels, some of which were found to be significant predictors. Pollutants were averaged by year and county for TSP, PM10, CO, O3, and NO2; SO2 and Pb were considered less thoroughly. Both mean and peak levels were considered for gases. SO42 data from the AIRS database and PM2.5, coarse particles, PM15, and SO42 from the U.S. EPA Inhalable Particulate (IP) Network were also considered. Four relevant exposure periods were defined: 1974 and earlier (back to 1953 for TSP), 1975–1981, 1982–1988, and 1989–1996. Deaths during each of the three most recent exposure periods were considered separately, yielding up to 12 combinations of exposure and mortality periods for each pollutant. Associations between concurrent air quality and mortality periods were considered to relate to acute responses; delayed associations with prior exposures were considered to be emblematic of initiation of chronic disease. Preexposure mortality associations were considered to be indirect (noncausal). The implied mortality risks of long-term exposure to air pollution were found to be sensitive to the details of the regression model, the time period of exposure, the locations included, and the inclusion of ecological as well as personal variables. Both positive and negative statistically significant mortality responses were found. Fine particles as measured in the 1979–1984 U.S. EPA Inhalable Particulate Network indicated no significant (positive) excess mortality risk for this cohort in any of the models considered. Among the positive responses, indications of concurrent mortality risks were seen for NO2 and peak O3, with a similar indication of delayed risks only for NO2. The mean levels of these excess risks were in the range of 5–9%;. Peak O3 was dominant in two-pollutant models and there was some indication of a threshold in response. However, it is likely that standard errors of the regression coefficients may have been underestimated because of spatial autocorrelation among the model residuals. The significant variability of responses by period of death cohort suggests that aggregation over the entire period of follow-up obscures important aspects of the implied pollution–mortality relationships, such as early depletion of the available pool of those subjects who may be most susceptible to air pollution effects.