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Biomedical subjects

R J Katz

Publications and source records attributed to R J Katz.

At least 37 records · Page 2Linked to original sources
PubMed1990

Mechanisms of nitrate tolerance: a review.

With the increased use of long-acting nitroglycerin preparations, there has been greater recognition of the problem of nitrate tolerance. In recent years extensive research has broadened our understanding of the mechanisms of nitroglycerin action and the mechanisms of drug attenuation. This paper reviews the current state of knowledge regarding nitroglycerin tolerance, with an emphasis on the concepts of cellular and neurohumoral mechanisms of drug attenuation. The discussion includes potential approaches to prevent nitrate tolerance, including the introduction of a nitrate-free interval, or concomitant administration of sulfhydryl donors or neurohumoral blocking agents.

Drug Tolerance↗
PubMed1990

The antiobsessional effects of clomipramine do not require concomitant affective disorder.

Two multicenter double-blind trials of clomipramine (CMI) vs. placebo were carried out in patients with DSM-III defined obsessive-compulsive disorder (OCD). Study entry criteria were similar, but the trials differed in their permitted initial degree of affective disturbance. Subgroups of patients with primary OCD and no mood disturbance were identified in both trials. Analyses of findings from both trials were essentially equivalent and were consistent with significant antiobsessional effects of CMI but not placebo in nondepressed patients with primary OCD. Further comparisons with subgroups with concomitant affective disturbance did not demonstrate marked differences in outcome.

Adult↗
PubMed1989

Clinical and hemodynamic significance of left ventricular diastolic volume changes by exercise radionuclide ventriculography in coronary artery disease.

Recent studies have suggested that left ventricular (LV) dilatation during exercise radionuclide ventriculography may identify coronary artery disease (CAD). Coronary anatomy and LV end-diastolic pressure at catheterization were compared with results of supine exercise radionuclide ventriculography in 66 patients evaluated for chest pain. Forty-six patients had significant CAD (greater than 75% diameter stenosis) and 20 patients were normal. Radionuclide ventriculography was performed within 18 hours of catheterization, at rest and at peak exercise. Relative LV end-diastolic volumes were extrapolated from end-diastolic counts. LV end-diastolic counts increased during exercise in 19 of 20 normal subjects. In patients with CAD, LV end-diastolic counts increased in 35 (group A) and decreased in 11 (group B). The percent change in LV end-diastolic counts from rest to exercise, rest ejection fraction, exercise ejection fraction and rest LV end-diastolic pressure for each group were 20 +/- 23%, 60 +/- 13%, 67 +/- 13% and 8 +/- 3 mm Hg in normal subjects; 20 +/- 20%, 50 +/- 12%, 47 +/- 13% and 12 +/- 4 mm Hg in group A; and -9 +/- 8%, 54 +/- 21%, 49 +/- 18% and 21 +/- 7 mm Hg in group B (mean +/- standard deviation). An increase in LV end-diastolic counts was unrelated to ejection fraction response or presence of underlying CAD but only correlated to rest LV end-diastolic pressure (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1989

Long term treatment with oxaprotiline in patients with major depression.

1) Four hundred thirty-seven patients with depressive illness were treated for up to 11 months with oxaprotiline (Ba-49802B) in a continuation study. 2) Results of this study suggest that oxaprotiline continued to be effective in alleviating depressive symptoms. 3) Additionally, evaluation of safety parameters failed to reveal any significant risk to patients who were treated with oxaprotiline over this extended period of time.

Adult↗
PubMed1989

Oxiracetam in the treatment of multi-infarct dementia.

1. Initial clinical trials in approximately 200 patients with dementias of diverse etiology suggested that oxiracetam, a structural analogue of the nootropic piracetam, was of some benefit in the treatment of cognitive dysfunction. 2. Because previous studies had not specifically examined the effects of oxiracetam upon dementias of vascular origin, the present study evaluated the therapeutic efficacy and safety of oxiracetam in the treatment of symptoms of multi-infarct dementia (MID) of mild to moderate severity. 3. Incremental doses of up to 1200 mg oxiracetam daily were tested in a dose-range finding design in a group of patients with clinically and neuropsychologically confirmed MID. 4. Based on improvement in global evaluations of clinical change, our analysis suggests that the drug may be of some benefit in MID.

Aged↗
PubMed1988

Sustained antianginal efficacy of transdermal nitroglycerin patches using an overnight 10-hour nitrate-free interval.

The antianginal efficacy of the transdermal nitroglycerin patch may be limited by the rapid development of tolerance during uninterrupted exposure. To address this problem, we investigated the role of intermittent therapy was investigated, using a daily nitroglycerin patch-free interval in 13 patients with chronic stable angina. Concomitant antianginal medications were permitted. Entry criteria required reproducible exercise times to both onset of angina and 1 mm of ST-segment depression. In each patient the highest tolerated nitroglycerin patch dose was determined by a dose-titration phase, which was then used in a double-blind crossover trial comprising 2 randomized treatment arms: 1 week of active nitroglycerin patch and 1 week of matching placebo. All patches were worn only from 8 A.M. to 10 P.M. daily. Exercise testing was repeated before patch application and then 4 and 8 hours after application on both the first and the last day of each treatment arm. Eleven patients completed the randomized crossover phase. Exercise time to the onset of angina and to the onset of 1 mm of ST-segment depression was significantly prolonged during the first day of therapy at both 4 and 8 hours after active nitroglycerin patch application compared with placebo (p less than 0.01). During sustained use, the benefit at 4 and 8 hours after nitroglycerin patch application was still evident (p less than 0.001 and p less than 0.05, respectively). No evidence of a overnight rebound or withdrawal phenomenon was observed by history or by ambulatory Holter monitoring calibrated for ST-segment analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1988

Keratan sulfate content in the superficial and deep layers of osteophytic and nonfibrillated human articular cartilage in osteoarthritis.

Very thin slices of the superficial and deep layers of osteophytic and apparently normal articular cartilage from six human osteoarthritic femoral heads were digested with papain. The digests were analyzed for keratin sulfate content using an enzyme-linked immunosorbent assay (ELISA) with inhibition step, and for chondroitin sulfate and collagen contents using biochemical assays. Although there were marked differences in Safranin-O staining of the superficial and deep layers of osteophytic cartilage, these two layers had identical high ratios of chondroitin sulfate/collagen. Keratan sulfate was present only in small amounts in osteophytic cartilage. However, the deeper layer contained significantly more of this glycosaminoglycan. The deeper layer of articular cartilage contained approximately twice as much chondroitin sulfate and six times more keratan sulfate relative to collagen than the superficial layer. The results of this study showed that this new sensitive approach, which requires as little as 200 micrograms wet cartilage as starting material, provides important qualitative and quantitative information about the major constituents of the matrix.

Cartilage, Articular↗
PubMed1988

Potentiation of the hemodynamic effects of acutely administered nitroglycerin by methionine.

It is believed that nitroglycerin causes vasodilatation by interacting with sulfhydryl groups present in vascular smooth muscle. This study was performed to assess whether methionine, an amino acid capable of increasing sulfhydryl availability, would potentiate the hemodynamic effects of nitroglycerin. Nitroglycerin was initially infused in incremental doses from 1 to 50 micrograms/min in all patients to determine the dose required to reduce mean arterial pressure by 10% and pulmonary capillary wedge pressure by 30%. After a washout period, 10 patients received 5 g methionine i.v. and five patients received an equal volume of 5% dextrose in water (control). Nitroglycerin dose titration was then repeated. Methionine alone induced no hemodynamic effects, but after methionine infusion, there was a significant reduction in the nitroglycerin infusion rate required to reach each hemodynamic endpoint (p less than 0.01). In the control group, there was no significant change in responsiveness to nitroglycerin between infusions. Thus, methionine potentiates the hemodynamic effects of acutely administered intravenous nitroglycerin.

Analysis of Variance↗
PubMed1987

Recurrent early ischemic events after thrombolysis for acute myocardial infarction.

Myocardium salvaged by early thrombolysis and then perfused through a residual stenosis may be at risk for ischemic events. To investigate this possibility, the short-term (2-week) clinical course of 81 consecutive patients managed within a randomized intracoronary thrombolysis trial was reviewed. All patients underwent coronary angiography within 5 hours of symptoms of acute myocardial infarction and were stratified into the following 3 outcome groups: patients with initially subtotal occlusion (subtotal group, n = 17), those with initial total occlusion and infarct artery reperfusion (reperfused group, n = 24) and those with continued infarct artery occlusion (occluded group, n = 40). Recurrent ischemic events were defined as spontaneous typical angina, provokable angina on predischarge exercise testing, and reinfarction. Eleven of 17 patients (65%) in the subtotal and 11 of 23 patients (48%) in the reperfused groups had an ischemic event (difference not significant). In contrast, 4 of 37 patients (11%) with occlusion had an ischemic event (p less than 0.01 compared with patients in the subtotal or reperfused groups). Four patients were excluded because of early (within 72 hours) elective coronary bypass surgery or death from pump failure. To eliminate the impact of multivessel coronary artery disease (CAD), 39 patients with 1-vessel CAD were analyzed separately. Five of 9 patients (56%) in the subtotal group, 3 of 10 (30%) in the reperfused group and only 2 of 20 (10%) in the occluded group had an ischemic event. These observations suggest the need for a more definitive revascularization strategy for acute myocardial infarction.

Angina Pectoris↗
PubMed1987

Multiple cardiac myxomas with multiple recurrences: unusual presentation of a "benign" tumor.

A 20-year-old woman with a two-week history of palpitations and constitutional symptoms was found to have right atrial and left ventricular myxomas. The myxomas were excised, but the patient had two recurrences of the tumor in the left atrium four and a half years after the initial presentation. The recurrent myxoma was locally aggressive, and removal required excision of the aortic valve. This patient demonstrates the need for careful follow-up for recurrences of myxoma.

Adult↗
PubMed1987

Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise.

Although digoxin is often the first choice for control of ventricular response in chronic atrial fibrillation, it fails to slow exercise rates. Diltiazem, a calcium channel antagonist that slows atrioventricular conduction, was administered to 16 patients who failed to achieve adequate rate control on low level exercise testing despite digoxin therapy. Therapeutic response to diltiazem was assessed with submaximal and maximal exercise tests and 24 hour ambulatory electrocardiographic monitoring. During the diltiazem treatment phase, ventricular response at rest diminished (96 +/- 17 versus 69 +/- 10 beats/min, p less than 0.001) as did rate during submaximal exercise (155 +/- 28 versus 116 +/- 26, p less than 0.001), maximal exercise (163 +/- 14 versus 133 +/- 26, p less than 0.001) and average ventricular response during 24 hour monitoring (87 +/- 13 versus 69 +/- 10, p less than 0.001). Rate at rest decreased 26 +/- 15% and submaximal exercise rate diminished 24 +/- 12%. Thirteen (81%) of the 16 patients exhibited at least 15% slowing of rate at rest and during submaximal exercise. Eleven patients (69%) reported alleviation of symptoms. There was no change in serum digoxin levels during diltiazem treatment (1.3 +/- 0.5 versus 1.3 +/- 0.6 ng/ml, p = NS). On withdrawal of diltiazem, ventricular response returned to baseline values. Diltiazem is an effective agent for control of ventricular response, both at rest and during exercise, in digoxin-treated patients with chronic atrial fibrillation.

Adult↗
PubMed1986

Safety and efficacy of flestolol, a new ultrashort-acting beta-adrenergic blocking agent, for supraventricular tachyarrhythmias.

Flestolol, a new ultrashort-acting (half-life 6.9 minutes) beta-blocking drug, was administered by intravenous infusion to 18 patients with new-onset atrial fibrillation or flutter and rapid ventricular response (120 beats/min or more for at least 30 minutes). Drug dose of flestolol was progressively increased until at least 1 of 3 endpoints was achieved: at least a 20% reduction in heart rate from baseline, heart rate 100 beats/min or less, or conversion to normal sinus rhythm. Flestolol was then administered as a maintenance infusion up to 24 hours. When flestolol was discontinued, patients were monitored for 1 additional hour. The mean ventricular response at baseline of 133 +/- 12 beats/min decreased to 103 +/- 20 beats/min at the end of flestolol titration (p less than 0.0001). Fourteen patients (78%) achieved defined endpoints. All 14 patients who continued to receive maintenance infusion had a sustained response. When flestolol was discontinued, ventricular response increased 33 +/- 23% within 60 minutes. The only adverse effect seen was hypotension in 2 patients. Flestolol is effective in slowing ventricular response in new-onset atrial fibrillation and flutter, maintains a therapeutic effect during continuous infusion and rapidly loses therapeutic effect when discontinued.

Adrenergic beta-Antagonists↗
PubMed1985

Long-term efficacy of bepridil in patients with chronic stable angina pectoris: results of a multicenter, placebo-controlled study of extended bepridil use.

To evaluate whether bepridil once a day provides effective antianginal therapy during extended use, a placebo-controlled withdrawal study was conducted in 33 patients with chronic stable angina. Each patient studied had previously had a favorable response to short-term administration of bepridil and had been taking the drug once daily for greater than or equal to 9 months of continuous use. Patients were then randomly assigned to receive either continued bepridil or a placebo substitution once daily during a 4-week, double-blind, parallel-group comparison. Dosage for the bepridil group was constantly maintained for each patient at a level observed to be clinically effective. The study consisted of a comparison of angina frequency and nitroglycerin tablet consumption obtained from patient diaries and results from maximal-graded multistage treadmill tests. Patients randomized to continue receiving bepridil remained stable in terms of angina frequency and exercise performance. Discontinuation of long-term bepridil significantly increased angina frequency and nitroglycerin tablet consumption and reduced exercise capacity. Four patients (24%), all receiving placebo treatment, had increases in angina frequency and had the study terminated. Bepridil was reinstituted in these patients with resolution of symptoms and no untoward effects. The results of this placebo-controlled, double-blind, randomized study confirm that bepridil continues to provide antianginal benefit during long-term administration.

Adult↗