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Biomedical subjects

M R Weir

Publications and source records attributed to M R Weir.

At least 145 records · Page 8Linked to original sources
PubMed1991

Hypertension and the kidney.

Pathophysiologic and hereditary mechanisms impacting on the kidneys are crucial for the initiation and maintenance of essential hypertension. An appreciation of these renal mechanisms is important for the institution of appropriate antihypertensive therapy. The clinician must develop a physiologic algorithm to control systemic blood pressure while maintaining adequate blood supply to the kidneys. This approach is particularly important in patients at higher risk for progressive renal insufficiency (i.e., older patients, blacks, diabetics, and those with chronic renal failure). Better perfusion reduces the likelihood of activating the compensatory neurohormonal systems that augment the intrarenal effects of the renin-angiotensin-aldosterone and sympathetic nervous systems, which ultimately may be responsible for renal structural changes leading to nephrosclerosis. In addition, dietary concerns are also important, particularly in the patients with evidence of early renal disease. Controlling blood pressure in a physiologic way by using drugs that can potentially dampen neurohormonal systems may prevent or at least delay the development of nephrosclerosis. Thus, the clinician should use an individualized therapeutic approach to the patient with hypertension. If nonpharmacologic means of blood pressure control are unsuccessful, an attempt should be made to blend the specific physiologic needs of the patient with specified pharmacologic antihypertensive mechanisms, paying particular attention to the preservation of renal function and perfusion.

Clinical Protocols↗
PubMed1991

Impedance tympanometry and acoustic reflectometry at myringotomy.

A total of 220 ears undergoing myringotomy and pressure-equalizing tube placement were studied with impedance tympanometry and acoustic reflectometry in a direct comparison for detection of middle-ear effusion. Impedance tympanometry and acoustic reflectometry were equally accurate, detecting the presence or absence of middle-ear effusion in 73% and 72% of ears, respectively. The presence of effusion in ears with tympanographic patterns other than type A and type B was not consistently and reliably predicted. The higher sensitivity of impedance tympanometry (90%) compared with that for acoustic reflectometry (58%) contrasted with the opposite findings for specificities (54% vs 88%). It is concluded that impedance tympanometry and acoustic reflectometry measure different events at the tympanic membrane and their utility lies in the fact that they complement each other. These instruments can aid the experienced otoscopist in confirming a clinical impression and assist the less experienced clinician in validating or improving otoscopic skills.

Acoustic Impedance Tests↗
PubMed1991

Depression of vitamin B6 levels due to dopamine.

Dopamine is a commonly used pressor agent. Frequently recognized side effects other than occasional reports of pedal gangrene respond to reduction of dose. Because a number of compounds interfere with vitamin B6 and dopamine toxicity in animals is modified by B6, we studied the dopamine-vitamin B6 interaction in rabbits. Six animals received 40 mg dopamine/kg and 10 mg pyridoxine injections; 6 received dopamine and saline. Dopamine administration led to an average fall of 20% (p = 0.04) in plasma pyridoxal 5'-phosphate (PLP) levels, which declined 42% by day 5. Three days later, a 25% decrease persisted (p = 0.03). Dopamine with pyridoxine caused a PLP rise of 65% (p = 0.007), but the post-study level was 28% lower than baseline (p = 0.04). We interpret our data to mean that dopamine reduced PLP levels during and 3 days after the study, and that dopamine appeared to increase the requirements for B6. We worry that dopamine given with other drugs, ie gentamicin, digoxin and theophylline which are frequently used in critical care settings, could aggravate alterations of requirements for or body stores of vitamin B6, creating B6 deficiency.

Animals↗
PubMed1991

Hypertensive renal damage.

The primary focus of both nonpharmacologic and pharmacologic therapy should be to control systemic blood pressure in a simple, affordable, and nontoxic fashion that provides an adequate quality of life. Although newer agents provide hope for greater capability of preventing renal dysfunction, their cost may prevent their broad availability in the black hypertensive population (see Chapter 5). Judicious use of traditional therapies, combined with newer approaches when possible, may offer prescribing physicians the best opportunity to control blood pressure in ways to avoid renal dysfunction. The lessons of the past 20 years have taught us that lowering blood pressure by any means helps in reducing target organ damage. More recent observations in hypertensive blacks illustrate the need for improved therapies to prevent renal dysfunction. A more physiologic approach to blood pressure control in the black patient that conserves perfusion to the kidney may delay the development of nephrosclerosis. Increased awareness, educational support, and encouragement will be necessary to insure compliance with therapy for a disease that is largely asymptomatic.

Aging↗
PubMed1991

Maximizing the informational content of vectorial data in the electrocardiogram.

Scalar electrocardiograms contain a great deal of vectorial data. The informational content of these data can be maximized by treating each angle as a point on a plane whose distance from the origin is equal to the magnitude of its vector. These points can be resolved into their horizontal and vertical coordinates. The coordinates are linear values and can therefore be subjected to standard statistical methodology.

Adolescent↗
PubMed1990

Renal effects of angiotensin-converting enzyme inhibition in congestive heart failure.

Some studies report that inhibition of angiotensin-converting enzyme (ACE) improves renal function in patients with congestive heart failure, whereas others report that renal deterioration is a frequent complication of treatment with ACE inhibitors. This article explores the mechanisms by which antagonism of the renin-angiotensin system improves kidney function in some patients while causing harm in others. ACE inhibition may alter renal blood flow, glomerular perfusion pressure, basement membrane activity and renal tubular function both directly and indirectly. In most patients, renal function is maintained as other neurohormonal mechanisms compensate for the negative effects and permit the positive effects (such as improved renal flow) to predominate. However, when physiologic characteristics or iatrogenic interventions (such as volume reduction or prostaglandin inhibition) limit the effectiveness of neurohormonal compensation to maintain renal autoregulation, clinically important deterioration in renal function may occur. An understanding of the renal effects of ACE inhibitors permits their safe and effective use in most patients with congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

An assessment of diltiazem and hydrochlorothiazide in hypertension. Application of factorial trial design to a multicenter clinical trial of combination therapy.

This multicenter, factorial-design trial assessed the safety and additive antihypertensive efficacy of a slow-release (SR) formulation of diltiazem hydrochloride given alone or in combination with hydrochlorothiazide for treatment of mild to moderate hypertension. After a 4- to 6-week placebo run-in period, 297 qualifying patients were randomized to receive placebo, 1 of 4 doses of diltiazem SR monotherapy, 1 of 3 doses of hydrochlorothiazide monotherapy, or 1 of 12 possible combinations of diltiazem SR and hydrochlorothiazide for 6 weeks. A dose-related reduction in blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Absolute blood pressures of patients who received combination therapy were lower by an overall mean of 3.0 mm Hg diastolic and 8.0 mm Hg systolic vs diltiazem SR used alone and 3.5 mm Hg diastolic and 4.0 mm Hg systolic vs hydrochlorothiazide used alone. At the largest doses used, 50% of patients achieved goal blood pressure while taking hydrochlorothiazide, 57% while taking diltiazem SR, and 75% while taking combination therapy. Combination therapy was well tolerated. This trial clearly demonstrates that diltiazem SR and hydrochlorothiazide have additive antihypertensive effects.

Adult↗
PubMed1990

Hypertensive black men and women. Quality of life and effects of antihypertensive medications. Black Hypertension Quality of Life Multicenter Trial Group.

A multicenter, randomized double-blind clinical trial was conducted among 306 black men and women with mild to moderate hypertension to determine effects of atenolol, captopril, and verapamil SR on measures of quality of life. Patients were randomly assigned to a stable or forced-dose titration sequence. After an 8-week treatment period, the rate of withdrawal from treatment because of adverse effects was low and did not differ by drug treatment group or titration level. Patients taking verapamil SR showed a significantly greater reduction in mean blood pressures than patients treated with atenolol or captopril. Along with absence of worsening on any quality of life total scale scores examined over the treatment period, we found either improvement or no change in the total scale scores for all three treatment groups. Among both male and female patients, comparisons between drug treatment groups showed no differences in degree of change on the total scale scores. In comparisons within each treatment group, improvement in scores of male patients after 8 weeks appeared among those taking atenolol in general well-being and physical symptoms reduction; among male patients taking captopril in general well-being, physical symptoms, and sexual performance; and among male patients receiving verapamil SR in scores in irritability, sleep, and the Digit Span test. Improvement in scores among female patients taking atenolol was found in scores on general well-being, physical symptoms, and sleep; among women taking captopril on general well-being, physical symptoms, and irritability; and among women taking verapamil SR on general well-being. Patients in all treatment groups improved on measures of visuomotor functioning. The research shows that with the three newer generation antihypertensive medications studied, blood pressure control was achieved during the treatment period without negative effects on quality of life scales, along with findings of improvement on some measures. Given the special clinical features of hypertension in black patients, the study underlines as well the potential and utility of systematic tracking of measures of quality of life, while monitoring blood pressures in this patient population.

Black or African American↗
PubMed1990

Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension.

Eighty-four patients with diastolic blood pressure ranging from 100-115 mm Hg were randomized into a multicenter, parallel, double-blind, placebo-controlled, dose response study with nilvadipine (6 mg, 8 mg, 10 mg tid for 28 days). The hypotensive response pattern to nilvadipine was similar with all three doses although duration of response was dose dependent. Maximal decreases in diastolic blood pressure occurred at 1 hour when assessed on days 1 and 15 (16.0, 17.4, and 15.8 mm Hg, vs 17.2, 18.7, and 17.5 mm Hg, respectively). The hypotensive effect remained significant compared to placebo for at least 4 hours after dosing. The increase in heart rate associated with the maximal hypotensive response was minimal and not clinically significant (day 1: 7.6, 5.2, and 4.0 beats/min with 6, 8, and 10 mg; day 15: 4.0, 5.1, 2.6 beats/min with 6, 8, 9, and 10 mg, respectively). Finally, a correlation between plasma drug concentrations and nilvadipine-induced hypotensive response was observed (r = 0.48). Black and white hypertensive patients had similar hypotensive responses. Plasma nilvadipine concentrations on day 15 were similar to those on day 1 suggesting no accumulation of drug with a tid regimen. The most common drug related side effect was headache; less frequently seen were dizziness, edema, palpitations, and abdominal pain. Nilvadipine was well tolerated (only three patients were discontinued due to side effects). The efficacy, lack of tachycardia, and side effect profile observed in this study suggest that nilvadipine may be an important addition to the treatment of hypertension.

Blood Pressure↗
PubMed1990

Acute effects of intravenous cyclosporine on blood pressure, renal hemodynamics, and urine prostaglandin production of healthy humans.

The acute renal failure associated with cyclosporine may result from vasoconstriction of intrarenal arterioles. To evaluate the mechanism of cyclosporine-induced nephrotoxicity, we acutely administered cyclosporine to eight healthy female volunteers with normal blood pressure and renal function. Cyclosporine (4 mg/kg) in 250 ml of 5% dextrose in water (D5W) was administered as a steady intravenous infusion over 6 hr. Glomerular filtration rate and renal plasma flow were measured by serum disappearance of 99m TcDTPA and 131I hippuran, respectively, during the last 3 hr of the infusion. D5W was given to the patients on separate days before the cyclosporine infusion to obtain control data. Systolic and diastolic blood pressure measured every hour during the infusions and renal vascular resistance were slightly higher during cyclosporine administration, but the increases were not statistically significant. Renal plasma flow was not affected by cyclosporine, being 479.6 +/- 24.9 ml/min during the control infusion and 463.3 +/- 12.7 ml/min during the cyclosporine infusion. However, glomerular filtration rate was reduced by cyclosporine in all patients (control, 108.8 +/- 2.5 ml/min, vs. cyclosporine, 91.1 +/- 2.2 ml/min, P less than .01), except one who demonstrated no significant change. Urinary excretion of thromboxane B2 during cyclosporine administration was markedly increased in all patients, being 39.9 +/- 8.2 ng/hr in the control period and 85.8 +/- 22.3 ng/hr during cyclosporine infusion (P less than .05), except for the one patient in whom no decrease in GFR was noted. There was no significant change in the urinary excretion rate for 6-keto-prostaglandin F1a or prostaglandin E during cyclosporine infusion. Serum averaged levels of peripheral renin activity, angiotensin II, and aldosterone did not change during with the cyclosporine administration compared with the control. All patients demonstrated a decrease in 24-h urinary excretion of sodium and potassium on the day of the cyclosporine infusion. Verapamil SR (240 mg daily for 7 days prior to cyclosporine infusion) did not reverse the reduction in glomerular filtration rate induced by cyclosporine; however, a significant reduction in renal vascular resistance and an increase in renal plasma flow (P less than .05) were noted when the volunteers were treated with both verapamil and cyclosporine compared with cyclosporine alone. Intravenous infusion of Cremophor EL, the vehicle to dissolve cyclosporine, demonstrated no significant effects on blood pressure, renal hemodynamics or urinary prostaglandin excretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Radix Tripterygium wilfordii--a Chinese herbal medicine with potent immunosuppressive properties.

Radix Tripterygium wilfordii Hook-F (TW) is a Chinese herbal medicine that has been reported to be effective in the treatment of various autoimmune disorders in experimental animals and man. Little is known about the immunosuppressive mechanism of action of this medicine. We demonstrate herein that TW is capable of inhibiting several afferent immune functions including the in vitro response of human peripheral blood mononuclear cells to both mitogen and alloantigen, and the generation of cytotoxic T cells. This inhibition is likely mediated through a reduction in both IL-2 production and IL-2 responsiveness. TW evidenced little capability of impairing IL-2 receptor expression, or efferent immune mechanisms such as cell-mediated cytotoxicity or natural killer cell-mediated cytotoxicity. The immunosuppressive effects of TW were reversible except at the highest concentration tested, 2.4 micrograms/ml, and there was no evidence of TW-mediated cell-well damage as evidenced by trypan-blue exclusion. TW, or some of its constituents, may be important new agents to be studied for immunosuppression in organ transplantation.

Adult↗
PubMed1990

Effect of renal function on the bioavailability of ciprofloxacin.

The effect of renal function on the bioavailability of ciprofloxacin was studied in 21 subjects with measured creatinine clearances ranging from 0 to 8.99 liters/h per 1.73 m2. Each subject received ciprofloxacin, 200 mg intravenously and 750 mg orally, separated by at least 1 week. Serial (12 to 15) blood samples were obtained over 24 to 48 h. Concentrations in serum were assayed by high-pressure liquid chromatography. Area under the curve was calculated by the trapezoidal rule with extrapolation to infinity. Bioavailability was calculated as the ratio between the dose-normalized area under the curve of oral and intravenous administrations. The overall mean (standard deviation) bioavailability observed was 63.4% (14.6%), similar to that observed in those with normal renal function (69.0% [15.7%]). The mean bioavailability in the subgroup of subjects with renal insufficiency was 59.9% (13.3%). The observed range in bioavailability was 33.9 to 91.4%. Linear regression did not reveal a correlation between creatinine clearance and bioavailability. Renal insufficiency does not appear to affect ciprofloxacin bioavailability.

Administration, Oral↗
PubMed1990

Optimal dosing interval for penicillin treatment of streptococcal pharyngitis.

One-hundred-forty-two children with symptomatic pharyngitis had throat cultures positive for group A beta-hemolytic streptococci (GABHA). All were treated orally with penicillin V for ten days. Patients were randomly assigned to receive daily doses of 250 mg four times daily, 500 mg twice daily, or 1000 mg once daily. They were followed four weeks for either recurrent symptomatic pharyngitis or asymptomatic repeat positive throat culture. Patients treated two or four times daily had comparable outcomes. Children given penicillin once daily were more likely to have persistent positive culture after 48 hours treatment (5 of 48 or 10.4% vs. none of 94, p = .004) and more likely to have recurrent positive cultures after end of treatment (10 of 43 or 23% vs. 8 of 94 or 8%, p = .04). The treatment regime of penicillin V 500 mg twice daily is recommended for treatment of pharyngitis due to GABHS.

Adolescent↗
PubMed1990

Calcium channel blockers in organ transplantation: important new therapeutic modalities.

The calcium channel blockers have emerged as important therapeutic modalities in the treatment of hypertension, ischemic heart disease, and other cardiovascular diseases. More recently, their potential benefit in recipients of organ transplants has come under closer scrutiny. Calcium channel blockers depress in vitro cellular immunity in an additive fashion with cyclosporine and have been demonstrated to reduce the incidence of rejection posttransplantation in early clinical trials. This class of drugs may also diminish ischemic damage to transplanted organs and reduce the destructive aspects of reperfusion injury. Because of their ability to depress cellular immune responses to mitogens, calcium channel blockers may also prove useful in decreasing the incidence of first-dose side effects (related to lymphocyte stimulation) in response to treatment with the OKT3 monoclonal antibody, a commonly used antirejection medication. Recent investigative efforts also suggest that calcium channel blockers may minimize cyclosporine nephrotoxicity by antagonizing either the direct or indirect vasoconstrictive actions of the drug. Some of the calcium channel blockers also reduce cyclosporine metabolism and excretion, thus allowing adequate levels of cyclosporine in blood with reduced doses of this valuable immunosuppressive agent. Cyclosporine-treated renal transplant recipients are frequently hypertensive, which is likely related to a salt-sensitive physiology. Calcium channel blockers have demonstrated important efficacy in reducing blood pressure in low-renin, salt-sensitive patients and similarly have been efficacious in controlling blood pressure in cyclosporine-treated transplant recipients. The numerous potential applications of calcium channel blockers in the field of organ transplantation illustrates the need for expanded clinical trials evaluating their use in this area.

Animals↗
PubMed1990

A comparison of the efficacy and safety of a beta-blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks.

A double-blind, positively controlled, forced dose titration study comparing the efficacy and safety of atenolol, captopril, and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension (diastolic blood pressure, 95 to 114 mm Hg) was conducted. A total of 394 patients were randomized to one of the three therapies. Mean blood pressures during a 2- to 4-week placebo treatment period (baseline) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups. Of the patients, 355 (of whom 345 had assessable data) completed the first treatment period, which consisted of therapy with either 50 mg/d of atenolol, 25 mg every 12 hours of captopril, or 240 mg/d of verapamil sustained release. During the second 4-week treatment period, which 319 patients completed (307 assessable), half of the patients had their antihypertensive medication increased and the other half continued the same dose. Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10-mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels. Atenolol, captopril, and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1%, 43.8%, and 65.2% of the time, respectively, and during the second treatment period 59.6%, 57.1%, and 73.0% of the time. Side effects were minimal and comparable for all three drugs.

Adult↗
PubMed1990

Depression of vitamin B6 levels due to gentamicin.

The renal toxicity of gentamicin is altered by dietary protein modifications, bicarbonate and acetazolamide administration, magnesium supplementation, polyaspartic acid, piperacillin, hypercalcemia and calcium channel blockers. Renal tissue gentamicin levels have an undetermined role. Reduction of renal pyridoxal 5'-phosphate (PLP- by gentamicin has been shown, as has protection from nephrotoxicity by administration of vitamin B6. To explore an interaction between gentamicin and vitamin B6, gentamicin (5 mg/kg) was given to rabbits by ip injection, with either pyridoxine (10 mg) or isovolemic saline for 3 weeks. There was not a difference between gentamicin levels for animals given gentamicin and pyridoxine versus those given gentamicin and saline. Gentamicin administration led to a 47% fall (p = .0001) in plasma PLP levels. Three days after the last gentamicin administration, the animals maintained a 32% decrease from the pre-gentamicin baseline values (p = 0.02). When pyridoxine was administered concurrently with gentamicin, the PLP rise of 49% was significant (p = 0.001). The mean level after the study (6%) was not significantly lower than baseline (p = .6). We believe that gentamicin interfers with vitamin B6 metabolism, but that vitamin B6 status does not affect levels of gentamicin. A number of drugs affect B6 levels, creating the potential for hypovitaminosis B6 to be an important mechanism of drug-drug interaction in seriously ill patients, particularly in sick newborns or the elderly with lower average PLP levels.

Animals↗