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Biomedical subjects

R A Stone

Publications and source records attributed to R A Stone.

208 records · Page 12Linked to original sources

Accounting for covariate measurement error in a Cox model analysis of recurrence of depression.

When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.

Aged↗

Some visual and neurochemical correlates of refractive development.

Increasing evidence indicates that the retina takes part in the postnatal regulation of eye growth, functioning in this respect to minimize refractive error. The evidence derives both from clinical observations in man and from experiments in animals. The discovery that visual form deprivation leads to an axial overgrowth of the eye and to myopia has opened the way to many current research initiatives. Neurochemical and immunocytochemical experiments in chick and monkey suggest that definable retinal neurons participate in the regulatory pathway controlling eye growth. The most comprehensive data presently implicate dopaminergic amacrine cells. Other important issues to be addressed include the relevance of an intact connection to the central nervous system and the precise retinal mechanism by which eye growth is regulated.

Animals↗

An investigation of secondary exposure misclassification effects of lifelong occupational history in exposure estimation.

The effects of exposure misclassification on the interpretation of results of occupational epidemiological studies has been widely investigated and reported. Usually, only the direct effects of misclassification have been considered or simple estimates of misclassification rates have been assigned to various types of exposure estimation processes. Lifelong job profile data obtained from a previously published case-control study provided complete or nearly complete job histories of 511 decedents. An analysis of these work histories and the comparison of exposures related to longest-held job to estimated total lifetime exposures suggest that single job-based exposure estimates may lead to significant exposure misclassification rates. In addition, the appearance of shorter duration jobs in a study population occurring predominantly early in the work history may exacerbate problems associated with exposure misclassification. While few specific suggestions emerge from this analysis, the inclusion of extensive recording of the work history of study subjects emerges as a reasonable basis for the investigation and potential reduction of secondary misclassification of exposures in occupational epidemiological studies.

Aged↗

A case-control study of lung cancer mortality in four rural Arizona smelter towns.

To investigate factors related to lung cancer mortality in four Arizona copper-smelter towns, the authors identified 142 lung cancer cases and 2 matched controls per case from decedent residents during 1979-1990. The authors obtained detailed information on lifetime residential, occupational, and smoking histories via structured telephone interviews with knowledgeable informants. The authors linked estimated historical environmental exposures to smelter emissions (based on atmospheric diffusion modeling of measured sulfur dioxide concentrations) with residential histories to derive individual profiles of residential exposure. The results of this study provided little evidence of a positive association between lung cancer and residential exposure to smelter emissions. Conditional logistic regression analysis revealed a statistically significant positive association between lung cancer and reported employment in copper mines and/or smelters, although specific factors associated with the apparently increased risk among these workers could not be identified in this community-based study.

Adult↗

Baroreflex function in uremic and hypertensive man.

Human hypertension has been related to abnormalities of autonomic blood pressure regulation. In order to characterize a possible defect, we have studied several aspects of reflex autonomic circulatory control in normal subjects, patients with primary hypertension, and two types of subjects with uremia and elevated blood pressure. Phenylephrine infusion (a measurement of baroreceptor response to high pressure stimulus) resulted in similar hemodynamic changes in all types of subjects. However, all groups of patients exhibited significantly different hemodynamic responses to amyl nitrite inhalation (an index of baroreceptor response to low pressure stimulus). These results suggest that patients with uremia and those with primary hypertension differ from each other and normal subjects regarding baroreceptor reflex function. Furthermore, one type of uremic patient may have a neurogenic component to their hypertension similar to experimental animals following surgical section of afferent baroreceptor nerves.

Adult↗

Renal vein renin activity in primary hypertension: variability and influence of contrast material.

Despite recognized limitations, the renal vein renin ratio (RVRR) remains the most commonly used index of surgical curability in hypertensive patients with renal artery stenosis. It is generally held that a ratio exceeding 1.5 forecasts a favorable response to surgery. Measurement of this ratio in 40 patients with essential hypertension (no arteriographically demonstrated stenosis) showed 8 (20%) with RVRR over 1.5, confirming an overlap of this ratio between patients with essential and renovascular hypertension. Intra-arterial injection of contrast material influenced renal vein renin activity (RVRA) in some individuals, but we were unable to demonstrate significant alterations in the group as a whole. Since the influence of intra-arterial contrast material on RVRA is variable and unpredictable, it appears unwise to collect renal venous blood for renin measurements soon after angiography.

Adult↗

Involvement of kallikrein in the antihypertensive response to furosemide in essential hypertension.

Twelve white men with essential hypertension were treated for 1 month in randomized order with either placebo or low-dose furosemide (40 mg/day) and compared to 22 race-, age-, and diet-matched normal controls. Furosemide therapy significantly reduced mean arterial pressure (108.6 +/- 2.4 vs. 101.0 +/- 2.7 mm Hg, p < 0.02) in association with a significant increase in 24 hr urinary kallikrein activity (7.9 +/- 1.8 vs. 13.4 +/- 2.8 esterase units/24 hr, p < 0.02). Normal controls on no therapy excreted 19.4 +/- 2.6 esterase units/24 hr of urinary kallikrein activity, significantly greater than hypertensives on placebo (p < 0.01) but not hypertensives on furosemide (p > 0.1). A significant (p < 0.05) inverse correlation between mean arterial pressure and urinary kallikrein activity suggests a possible role for the kallikrein-kinin system in the antihypertensive mechanism of furosemide.

Aldosterone↗

Urinary kallikrein activity and renal vascular resistance in the antihypertensive response to thiazide diuretics.

To evaluate the mechanism of chronic thiazide diuretic action in hypertension, we treated 19 essential hypertensive white men for 1-month periods on placebo alone and hydrochlorothiazide alone. During therapy, mean arterial pressure (MAP) fell, but radioisotopically determined intravascular volume remained unchanged, suggesting other mechanisms of thiazide action upon blood pressure. In the renal circulation, thiazides did not change renal plasma flow or glomerular filtration rate, but renovascular resistance was diminished, probably at the afferent arteriole. Concomitant with the decline in blood pressure and renovascular resistance, urinary kallikrein excretion increased, from subnormal (hypertensive) levels back into the normal range. The kallikrein increase did not correlate with changes in plasma aldosterone. In addition, patients with blood pressure responses (reduction greater than or equal to 10%) to thiazides (n = 12) had greater increases in kallikrein excretion than those without such a blood pressure decrement (n = 7), suggesting a role for renal kallikrein in the hypotensive response to thiazide diuretics.

Aldosterone↗

Prazosin and renal hemodynamics: arteriolar vasodilation during therapy of essential hypertension in man.

Renal hemodynamic effects of chronic prazosin therapy were studied in 10 men and with essential hypertension. Successful antihypertensive therapy was accompanied by diminution in total renovascular resistance, probably at the level of the afferent arteriole. The resistance change was unexplained by alterations in intravascular volume, the vasodilatory renal kallikrein-kinin system, or sympathetic nervous system activity, but was associated with a diminution in plasma renin activity. Potential mechanisms for the resistance decrement are discussed, including renal perfusion autoregulation, diminished activity of the vasoconstrictive renin-angiotensin system, and direct intrarenal afferent arteriolar alpha adrenergic blockade.

Adult↗