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Biomedical subjects

W J Elliott

Publications and source records attributed to W J Elliott.

At least 55 records · Page 3Linked to original sources
PubMed1995

An individualized approach to the hypertensive patient with renal disease: six illustrative case studies.

One of the biggest challenges in medicine is the area of therapeutics, wherein the physician attempts to match the needs of the individual patient with a specific agent from the pharmacopeia, at the dose that might be best suited to treat the individual's problem. A great deal of the art of medicine is involved in this "matching process," in which the scientific aspects of diagnosis and therapy meet with the physician's knowledge of clinical pharmacology. The abbreviated case histories of six patients who came to the author with specific questions regarding therapy of their hypertension and renal impairment illustrate the fact that one of any number of therapies might have reduced blood pressure in these patients, but in each, there was a specific reason to attempt a single approach first. If physicians could better understand and extrapolate the results of clinical research to the treatment of specific patients, choice of therapy might become more successful.

Adrenergic alpha-Antagonists↗
PubMed1995

Glucose and cholesterol elevations during thiazide therapy: intention-to-treat versus actual on-therapy experience.

PURPOSE: This nonrandomized, parallel-group, prospective clinical series in consecutive patients was conducted to determine if the method of analysis of biochemical data collected in long-term treatment trials can explain the controversy regarding the effects of thiazides on plasma glucose or cholesterol. PATIENTS AND METHODS: Fasting serum glucose, potassium, and cholesterol levels were determined before therapy, and yearly thereafter (4.0 +/- 0.1 years) in 634 consecutive patients treated for more than 1 year with antihypertensive monotherapy. RESULTS: When the data were analyzed by the intention-to-treat paradigm (ignoring changes in therapy), glucose and cholesterol levels in the thiazide group were significantly higher (compared to baseline or to the other therapy group) only at year 1. When the data were analyzed by actual on-therapy experience (censoring patients when therapy is altered)--a more traditional way to examine side effects--these differences were significant for all 5 years studied. Even if as few as 8% of patients who changed therapies were included in an intention-to-treat analysis, these differences became nonsignificant. CONCLUSION: These comparisons not only indicate why a dichotomy might exist between clinical practice (analyzed by actual on-therapy experience) and randomized trials (analyzed by intention-to-treat methods), regarding biochemical changes in glucose and cholesterol during thiazide therapy, but also that, for secondary hypotheses, analyzing data by both methods of assignment is important.

Benzothiadiazines↗
PubMed1994

Cardiovascular risk factors. Which ones can and should be remedied?

Coronary artery disease (CAD) is probably the most common example of a multifactorial disease that can be reduced in incidence (if not prevented in some cases) by appropriate attention to and control of risk factors. This conclusion is supported by large epidemiologic studies, confirmed by randomized intervention trials in which a putative risk factor is attacked with specific therapy, and put into context by the results of multiple risk factor intervention trials. The job of the physician is to take the pieces of scientific data regarding CAD and extrapolate them, if appropriate, to individual patients, who presumably will benefit from all the hard work their predecessors in clinical trials went through to prove that the intervention was successful.

Cardiovascular Diseases↗
PubMed1994

Selected factors that influence responses to antihypertensives. Choosing therapy for the uncomplicated patient.

Numerous factors may influence an individual patient's response to antihypertensive therapy. The physician should select therapy that is more likely to effectively control the patient's blood pressure. In addition to age and race, specific properties of the drugs plus the method of administration can influence response. Most antihypertensives can be given once or twice daily without the need for sustained-release dosage forms. The appropriate selection of regular-release products can significantly reduce the cost of therapy and improve adherence to the regimen. Because most antihypertensives exist as isomers of two compounds, response to a given agent can be influenced by the type of product (eg, sustained-release) or the method of administration. When these variables are considered for individual patients, it is more likely that a given drug will be effective.

Adrenergic beta-Antagonists↗
PubMed1994

Compliance strategies.

Results of treatment in clinical practice and in randomized trials are usually improved when patients actually take their medications as prescribed. This is particularly important in chronic diseases such as hypertension and renal impairment, in which specific, recurrent, troubling symptoms are unlikely to be remedied with therapy. Compliance with medication often parallels appointment adherence, which also improves long-term outcomes. Factors that improve compliance include culturally sensitive patient education and attitude about the disease undergoing treatment; patient-specific reminders (eg, computed medication reminders and charts); medical regimens that minimize the frequency, inconvenience, and number of pills taken; and positive physician attitude regarding therapy.

Antihypertensive Agents↗
PubMed1993

Comparison of two noninvasive screening tests for renovascular hypertension.

OBJECTIVE: To compare and contrast the diagnostic accuracy rates of two newer noninvasive screening tests for renovascular hypertension, the most common curable cause of secondary hypertension. PATIENTS AND METHODS: One hundred fifty patients, thought to have a high probability of renovascular hypertension by established clinical criteria, underwent both the captopril challenge test and the renal scintigram with angiotensin-converting enzyme inhibitor, while on their usual antihypertensive regimen except angiotensin-converting enzyme inhibitors. If the result of either test was abnormal, angiography was undertaken, followed immediately by angioplasty (if a stenosis was found) or by renal vein renin determinations. Patients whose blood pressures were lower 6 to 12 weeks after a revascularization procedure (surgery or angioplasty) were diagnosed as having renovascular hypertension. RESULTS: Of the 150 patients, 100 underwent angiography, and 59 had renal artery stenosis. Of 53 patients who had surgery (n = 21) or angioplasty (n = 32), 51 had lowered blood pressures compared with before the procedure. Sensitivity and specificity of the tests were as follows: renal scintigram with angiotensin-converting enzyme inhibitor: 92% and 91% (all patients) and 92% and 80% (only patients with angiograms); captopril challenge test: 76% and 82% (all patients) and 76% and 58% (only patients with angiograms). Little difference in accuracy rates was observed in subgroup analyses in patients with chronic renal impairment, previous diuretic or beta-blocker therapy, or bilateral renal artery stenosis. CONCLUSIONS: In selected, treated patients with a high probability of renovascular hypertension, the renal scintigram with angiotensin-converting enzyme inhibitor was a more accurate noninvasive screening test than the captopril challenge test. Noninvasive screening tests for renovascular hypertension can help to identify patients who should undergo angiography and often predict success after revascularization.

Aged↗
PubMed1993

Fenoldopam, but not nitroprusside, improves renal function in severely hypertensive patients with impaired renal function.

PURPOSE: Patients with hypertensive crises often experience reduced renal function that may worsen as the elevated blood pressure is treated. Fenoldopam, a novel, peripherally acting dopamine-1 agonist, lowers blood pressure through arteriolar vasodilation, with particularly prominent effects on the renal vascular bed. This study was conducted to examine the effects of fenoldopam on blood pressure and renal function compared to those of sodium nitroprusside in severely hypertensive patients with impaired renal function. PATIENTS AND METHODS: Renal function and systemic hemodynamics were studied in 19 severely hypertensive patients (diastolic blood pressure greater than or equal to 120 mm Hg) with impaired renal function (creatinine clearance less than or equal to 70 mL/min) enrolled in clinical trials of fenoldopam and sodium nitroprusside. For comparison, an additional 22 severely hypertensive patients with nonimpaired renal function were studied under the same conditions. Blood pressure and heart rate were measured at baseline before treatment and periodically during treatment. Renal function was determined before and during drug infusion by collection of timed urine specimens and blood samples. Creatinine clearance, urine flow rate, and sodium and potassium excretions were measured and compared. RESULTS: In patients with impaired renal function, blood pressure (mean +/- SEM) was reduced successfully in both groups (fenoldopam: 214 +/- 8/139 +/- 6 mm Hg to 176 +/- 8/107 +/- 3 mm Hg, p < 0.001 for systolic and diastolic comparisons; nitroprusside: 226 +/- 4/145 +/- 5 mm Hg to 171 +/- 6/108 +/- 2 mm Hg, p < 0.001 for systolic and diastolic comparisons). Results of renal function studies showed significant increases in creatinine clearance (from 39 +/- 7 mL/min to 75 +/- 16 mL/min, p < 0.05), urine flow (from 119 +/- 37 mL/h to 275 +/- 84 mL/h, p < 0.01), and sodium excretion (from 75 +/- 22 microEq/min to 227 +/- 60 microEq/min, p < 0.01) in patients with impaired renal function treated with fenoldopam. No significant changes were seen in patients treated with nitroprusside. In patients with nonimpaired renal function, blood pressure was reduced by both agents, but only patients who received fenoldopam experienced significant increases in creatinine clearance, urine flow rate, and sodium excretion. CONCLUSION: Fenoldopam, but not nitroprusside, improved renal function in severely hypertensive patients at all levels of baseline renal function while lowering blood pressure. Because of these effects, fenoldopam may be particularly useful in treating severely hypertensive patients with impaired renal function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Low predictive value of positive Osler manoeuvre for diagnosing pseudohypertension.

Pseudohypertension is a condition where indirectly determined BP (e.g. via sphygmomanometry) significantly overestimates actual intraarterial pressure. A patient who has a palpable, although pulseless, radial artery while the blood pressure cuff is inflated above systolic pressure, has a positive 'Osler sign'. This 'Osler manoeuvre' has been reported to predict the presence of pseudohypertension. To evaluate its importance in diagnosing pseudohypertension, 19 hypertensive patients deemed Osler-positive by at least two observers were studied. BP was determined indirectly using a stethoscope and mercury sphygmomanometer. Intraarterial pressure was determined by a brachial artery catheter-transducer-monitoring system. For both pressure-measurement techniques and each patient, six readings were averaged to give a single systolic and diastolic value. Mean arterial pressure was calculated as diastolic pressure plus one-third the pulse pressure. Pseudohypertension was defined as a sphygmomanometric mean pressure that exceeded intraarterial mean pressure by > or = 10 mmHg. In this group of 19 Osler-positive patients, stethoscope-sphygmomanometry underestimated systolic and overestimated diastolic intraarterial pressure. For mean pressure, sphygmomanometry was > or = 10 mmHg higher than intraarterial in two patients and > or = 10 mmHg lower than intraarterial in three patients. Thus, while two patients had pseudohypertension, three could be considered to have pseudohypotension, defined as a condition where indirect blood pressure significantly underestimates intraarterial pressure. Accordingly, a positive Osler manoeuvre did not reliably predict the presence of pseudohypertension in this population.

Aged↗
PubMed1992

Electrocardiographic changes during acute treatment of hypertensive emergencies with sodium nitroprusside or fenoldopam.

BACKGROUND: Electrocardiograms are routinely obtained before and during the acute treatment of hypertensive emergencies, usually to rule out "ischemic changes." Despite a few anecdotal reports of electrocardiographic changes, little is known about the incidence and significance of such changes, or their relationship to the treatment used. METHODS: We prospectively analyzed 12-lead electrocardiograms from 21 patients admitted for hypertensive emergencies (average blood pressure, 222 +/- 4/140 +/- 3 mm Hg). Patients were randomly assigned to treatment with sodium nitroprusside (n = 11) or the dopamine receptor agonist fenoldopam mesylate (n = 10). Electrocardiograms were obtained at baseline and within 30 minutes of reaching goal blood pressure (diastolic blood pressure, 100 to 110 mm Hg). RESULTS: There was no significant effect of either drug treatment on PR interval, QRS duration, QT interval, or R-wave amplitude, and no major ST-segment changes were noted. During treatment with either drug, the average T-wave amplitude decreased in all leads except aVR. New T-wave inversions in lead V4 occurred in two and four patients after fenoldopam and nitroprusside treatment, respectively. There were no clinically apparent episodes of myocardial ischemia in any patient. CONCLUSIONS: Even in the absence of obvious myocardial ischemia, a decrease in T-wave amplitude, including T-wave inversion, occurs commonly during acute blood pressure reduction in hypertensive emergencies, an observation that may be explained by the accompanying acute changes in cardiac chamber volumes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Influence of diuretic therapy on the clonidine suppression test.

Moduretic has been reported to inhibit the suppression of plasma norepinephrine (NE) levels by the alpha 2 adrenoceptor agonist, clonidine. To determine whether plasma volume reduction by hydrochlorothiazide (HCTZ) or antagonism of Na+/H+ exchange by amiloride (the constituents of Moduretic) is responsible, the authors performed a modified clonidine suppression test (CST) in nine normal volunteers (aged 25 +/- 2 years), pretreated for 1 week with HCTZ 50 mg daily, amiloride 10 mg daily, or placebo, in a randomized, double-blind, crossover study. Baseline characteristics were identical on all study days, except serum [K+] and weight, which were lowest on HCTZ (3.6 +/- 0.2 mEq/L and 78.7 +/- 2.5 kg), compared with amiloride (4.2 +/- 0.1 mEq/L and 79.9 +/- 2.4 kg) and placebo (4.0 +/- 0.1 mEq/L and 80.2 +/- 2.7 kg, P less than .05). Oral clonidine (0.3 mg) produced a reduction in mean blood pressure by about 20%. Plasma norepinephrine levels were similar in patients receiving placebo, HCTZ, and amiloride (205 +/- 18, 272 +/- 40 and 277 +/- 44 pg/mL, P greater than .20), and decreased significantly during CST. The maximal reduction for each subject averaged 72.7 +/- 12.4%, 87.9 +/- 3.8%, and 82.9 +/- 5.7% for placebo, HCTZ, and amiloride. Clonidine also produced a four to seven-fold increase in plasma growth hormone levels, reduced salivary flow by about 75%, and increased the level of sedation. There were no differences among the three pretreatment regimens in the effects of clonidine, indicating that diuretic therapy does not need to be systematically discontinued in patients undergoing CST.

Adult↗
PubMed1991

A double-blind, randomized, placebo-controlled comparison of the metabolic effects of low-dose hydrochlorothiazide and indapamide.

To compare the metabolic effects of indapamide (I) and hydrochlorothiazide (HCTZ) at equivalent hypotensive doses, 11 hypertensive patients (5 male, 8 black, aged 56 +/- 8 yr--mean +/- SEM) having serum uric acid concentrations greater than 8.0 mg/dL while receiving previous therapy with thiazides, received 28-day courses of placebo, indapamide (2.5 mg/d), and HCTZ (25 mg/d) in randomized, double-blind, double-crossover design. Supine and standing blood pressures, weight, pulse rates and sera were obtained after each 28 day period. Blood pressures and weights were lowered (P less than .001 and 0.01, respectively) equally by the diuretics: supine blood pressures fell from 168 +/- 4/104 +/- 2 (placebo) to 153 +/- 4/93 +/- 2 (HCTZ) and 155 +/- 4/94 +/- 2 mm Hg (I); standing blood pressures (after 2 minutes upright) also decreased: 171 +/- 5/104 +/- 2 (placebo) to 156 +/- 5/93 +/- 2 (HCTZ) and 157 +/- 4/94 +/- 2 mm Hg (I). There was a statistically significant difference (P less than .05) across treatments by analysis of variance in both uric acid and potassium concentrations: serum urate (in mg/dL) was lowest with placebo (7.1 +/- 0.3), and rose to 8.3 +/- 0.2 with HCTZ (P less than .001 compared with placebo by paired t test), and 8.1 +/- 0.2 with I (P less than .005 vs. placebo). The urate concentration with I was significantly lower than that with HCTZ (P less than .02), but the magnitude of the difference was small (0.2 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Increased all-cause and cardiac morbidity and mortality associated with the diagonal earlobe crease: a prospective cohort study.

PURPOSE: To ascertain whether the diagonal earlobe crease (ELC) is associated prospectively with future death or cardiac events over 8 years of follow-up in two sets of patients: those with known coronary artery disease (CAD) and those without evidence for CAD. PATIENTS AND METHODS: We performed a prospective, observational study of 108 patients in four cohorts (each matched for age, sex, and race, but differing in the presence or absence of both a diagonal ELC and CAD in 1979 to 1982). Follow-up information was gathered by telephone interviews, and dates and causes of death were determined by reference to death certificates (n = 48), hospital records (n = 9), or attending physician statements (n = 1). RESULTS: During 8 to 10 years of follow-up, 58 of the patients had died. Patients with ELCs had poorer survival rates than those without creases, by stratified log-rank test (p = 0.006 for the cohorts thought not to have CAD, and p = 0.058 for those with CAD). Cardiac death rates (due to acute myocardial infarction, "sudden cardiac death," or heart failure) were also higher for patients with ELCs: 8.0 versus 0.9 cardiac deaths per 100 patient-years (p less than 0.001) in patients without CAD at entry, and 11.7 versus 3.7 cardiac deaths per 100 patient-years (p = 0.008) in patients with CAD in 1979 to 1982. Cardiac event rates (cardiac death, nonfatal myocardial infarction, or coronary artery bypass surgery) were also higher in those with ELCs: 10.4 versus 1.4 events per 100 patient-years (p less than 0.001) for those without known CAD, and 15.8 versus 5.7 events per 100 patient-years (p = 0.009) for those with CAD. CONCLUSION: These results suggest that a diagonal ELC is associated with increased all-cause and cardiac morbidity and mortality. Patients with ELCs may be at higher risk for coronary events, and might be especially cautioned to control or reduce other cardiac risk factors, even if currently without diagnostic evidence of CAD.

Aged↗
PubMed1991

Intraocular pressure increases with fenoldopam, but not nitroprusside, in hypertensive humans.

Fenoldopam mesylate stimulates adenyl cyclase in porcine ocular trabecular meshwork and raises intraocular pressure in humans. To clarify whether this results from direct activation of the dopamine-1 receptor or indirectly from baroreflex sympathetic stimulation after blood pressure reduction, intraocular pressure was measured in 14 patients with accelerated/malignant hypertension, randomized between intravenous fenoldopam or sodium nitroprusside. Intraocular pressure was measured with a Perkins tonometer, before and at the twentieth minute of each dose increment. In seven patients with a mean blood pressure of 232/131 mm Hg treated with fenoldopam, intraocular pressure increased in a dose-dependent fashion, from 16 +/- 1 to 20 +/- 2 mm Hg (p less than 0.005). In contrast, seven patients with a mean blood pressure of 225/134 mm Hg treated with sodium nitroprusside exhibited no change in intraocular pressure (15 +/- 1 versus 14 +/- 1 mm Hg) despite similar blood pressure reduction. Increases in heart rate were not significantly different. Rates of urinary excretion of norepinephrine plus epinephrine increased significantly relative to baseline (p less than 0.05) but were not different between groups. These data suggest that the increase in intraocular pressure with fenoldopam results from specific activation of the dopamine-1 receptor and is not caused by baroreflex sympathetic stimulation. Because dopamine-1 receptors may modulate intraocular pressure, dopamine-1 receptor blockers might be useful therapy for glaucoma.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.

The renal and hemodynamic effects of intravenously administered fenoldopam mesylate, a novel dopamine-1 receptor agonist, were compared with those of sodium nitroprusside in 28 patients (18 male; 26 black, two white; average age, 49 +/- 3 years) with an average blood pressure of 219/137 mm Hg, most of whom presented with acute target organ damage. Fenoldopam and nitroprusside lowered blood pressure safely to an average pressure of 176/105 mm Hg; highly significant dose-response relations were found for the 13 patients receiving fenoldopam and the 15 receiving nitroprusside. Volume and sodium, potassium, and creatinine concentrations were measured in freely voided urine specimens both before and during intravenous therapy. In the fenoldopam-treated patients, there were significant increases in urinary flow (92 +/- 21 to 168 +/- 37 ml/hr, p less than 0.003), sodium excretion (227 +/- 73 to 335 +/- 90 mu eq/min, p less than 0.001), and creatinine clearance (70 +/- 11 to 93 +/- 13 ml/hr, p less than 0.003). In the nitroprusside-treated group, however, all these parameters decreased, but not significantly. For direct comparison of the two agents, the increments in urinary flow rate (+76 +/- 20 vs. -16 +/- 15 ml/hr, fenoldopam vs. nitroprusside), sodium excretion (+109 +/- 28 vs. -39 +/- 28 mu eq/min), and creatinine clearance (+23 +/- 6 vs. -11 +/- 7 ml/min) were significantly greater (p less than 0.001 for each) in the fenoldopam-treated group. Significant differences were also obtained when these parameters were calculated as percentage increase over baseline. Fenoldopam and nitroprusside are effective therapies for severe, accelerated, or malignant hypertension, but fenoldopam had additional salutary renal effects in these patients.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Dopamine and dopamine receptor agonists in cardiovascular therapy.

Dopamine (DA)--previously regarded simply as the precursor of norepinephrine--is now known to have its own unique effects on cardiovascular regulation which are mediated, in part, by activating specific DA receptors. DA has long been used in the treatment of shock and heart failure. In recent years it has been used at low infusion rates for its renal effects, in combination with other more specific inotropic or pressor agents. Lack of oral bioavailability has limited its use in long-term therapy, however; levodopa and dopa conjugates which are orally absorbed and metabolized to the active form are under investigation. The novel DA1 receptor agonist fenoldopam is claiming a role in the management of hypertension, heart failure, and the preservation of renal function. DA2 receptor agonists are also being evaluated as potential antihypertensive agents.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗