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J D Horowitz

Publications and source records attributed to J D Horowitz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of a home-based intervention among patients with congestive heart failure discharged from acute hospital care.

BACKGROUND: We examined the effect of a home-based intervention (HBI) on readmission and death among "high-risk" patients with congestive heart failure discharged home from acute hospital care. METHODS: Hospitalized patients with congestive heart failure and impaired systolic function, intolerance to exercise, and a history of 1 or more hospital admissions for acute heart failure were randomized to either usual care (n=48) or HBI at 1 week after discharge (n=49). Home-based intervention comprised a single home visit (by a nurse and pharmacist) to optimize medication management, identify early clinical deterioration, and intensify medical follow-up and caregiver vigilance as appropriate. The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge. Secondary end points included duration of hospital stay and overall mortality. RESULTS: During follow-up, patients in the HBI group had fewer unplanned readmissions (36 vs 63; P=.03) and fewer out-of-hospital deaths (1 vs 5; P=.11): 0.8+/-0.9 vs 1.4+/-1.8 (mean +/- SD) events per patient assigned to HBI and usual care, respectively (P=.03). Patients in the HBI group also had fewer days of hospitalization (261 vs 452; P=.05) and fewer total deaths (6 vs 12; P=.11). Patients assigned to usual care were more likely to experience 3 or more readmissions for acute heart failure (P=.02). Predictors of unplanned readmission were (1) 14 days or more of unplanned readmission during the 6 months before study entry (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.8-16.2), (2) previous admission for acute myocardial ischemia (OR, 3.3; 95% CI, 1.2-9.1), and (3) an albumin plasma concentration of 38 g/L or less (OR, 2.4; 95% CI, 1.2-6.0). Home-based intervention was also associated with a trend toward reduced risk of unplanned readmission (OR, 0.4; 95% CI, 0.2-1.1). CONCLUSION: Among a cohort of high-risk patients with congestive heart failure, HBI was associated with reduced frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge from the hospital.

Acute Disease↗
PubMed1998

Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.

PURPOSE: To report clinical features and surgical management of neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. METHODS: Seven consecutive eyes of seven nondiabetic patients who developed neovascular complications associated with rubeosis iridis and peripheral retinal detachment after scleral buckling and vitrectomy procedures were retrospectively reviewed. None of the eyes had clinical evidence of anterior segment ischemia or retinal vascular disease, but each eye developed rubeosis iridis and neovascular complications. RESULTS: Of the seven eyes with rubeosis iridis and peripheral retinal detachment, six developed recurrent or progressive vitreous hemorrhage, and three developed progressive neovascular glaucoma. Four eyes underwent a revision procedure to repair the peripheral retinal detachment, and anterior proliferative vitreoretinopathy was found in each of these cases. Rubeosis iridis regressed in all three eyes in which surgery resulted in complete reattachment of the retina. In one eye with persistent peripheral retinal detachment and in the three remaining eyes that did not undergo revision surgery, rubeosis iridis persisted and was associated with long-term neovascular complications. Final corrected visual acuity was 20/70 to 20/400 in three eyes with total retinal reattachment and no light perception to hand motions in four eyes with persistent peripheral retinal detachment and rubeosis iridis. CONCLUSION: Visually significant neovascular complications may occur in eyes that develop rubeosis iridis associated with peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. Successful repair of the peripheral retinal detachment may induce regression of rubeosis iridis, reduce associated complications, and improve the long-term prognosis of these eyes.

Adult↗
PubMed1998

Peripherally inserted central catheters revisited.

BACKGROUND: This study compares central venous catheters (CVC) and peripherally inserted central catheters (PICC) for indications for insertion, complications, and economic impact. METHODS: A retrospective review of 838 (283 CVC, 555 PICC) consecutively placed venous catheters reflected 49,365 CVC and 11,814 PICC days. RESULTS: There were 57 (20%) complications in the CVC group, 197 (35%) complications in the PICC group. PICC were associated with a statistically significant increase in the incidence of catheter malfunction (P = 0.0005), arm vein phlebitis (P = 0.0004), and overall complications (P = 0.00001). A higher complication rate was noted in PICC inserted for chemotherapy (P = 0.00001) and parenteral hyperalimentation administration (P = 0.04). Charges for inpatient insertion of PICC and CVC were $500 and $2,500, respectively. CONCLUSIONS: PICC have a significantly higher complication rate than CVC. PICC provide cost-effective central access of 2 to 3 weeks' duration, reserving operatively placed CVC for longer access requirements.

Adult↗
PubMed1998

Endothelin B receptor-mediated vasoconstriction induced by endothelin A receptor antagonist.

OBJECTIVE: The vasoconstrictor effect of endothelins (ET) is mediated by endothelin A (ETA) and endothelin B (ETB) receptors. Furthermore, ETB receptor stimulation results in release of vasodilators. Hence, ETA receptor antagonists should attenuate ET-mediated vasoconstriction. The aim of the present study was to evaluate and compare the effects of BQ-123, an ETA receptor antagonist, and bosentan, an ETA and ETB receptor antagonist, on coronary vasomotor tone, left ventricular systolic function and ET-1 efflux in the presence or absence of myocardial ischaemia/reperfusion. METHODS: Isolated rat hearts were perfused using a Langendorff preparation. Global ischaemia was induced on average by 68 +/- 2% (+/- standard error of the mean) reduction of a baseline perfusion flow-rate 10 min after introduction of ET antagonists. Thirty minutes of ischaemia was followed by 30 min reperfusion. ET-1 efflux in coronary perfusate was measured by radioimmunoassay. RESULTS: In non-ischaemic hearts (n = 7), BQ-123 (10(-6) M) perfusion induced a progressive decrease in coronary flow-rate compared with control group. This flow reduction persisted after wash-out of BQ-123. In contrast, bosentan (10(-5) M, n = 7) induced no change in perfusion rate. In the absence of ET antagonists (n = 16), there was a 22 +/- 6% post-ischaemic increase in perfusion flow-rate. BQ-123 (n = 5) but not bosentan (n = 12) abolished this post-ischaemic increase in flow-rate. Neither BQ-123 nor bosentan induced significant variation in force of contraction. In ischaemic hearts, ischaemia per se induced a transient decrease in force of contraction. Bosentan significantly (P < 0.05) accentuated and BQ-123 tended to accentuate (P = 0.06) this decrease in force of contraction during ischaemia. Bosentan but not BQ-123 significantly impaired the recovery of systolic function during reperfusion (P < 0.05). Both BQ-123 and bosentan perfusion increased ET-1 efflux rate to 730 +/- 188% and 315 +/- 81% respectively. This effect was abolished during ischaemia for BQ-123, but not for bosentan. CONCLUSIONS: In isolated perfused rat hearts, both BQ-123 and bosentan increased ET-1 efflux, but only BQ-123 exerted vasoconstrictor effects. These results thus generated the hypothesis that: (1) ET-1 release within the coronary vascular bed may be physiologically subject to negative feedback regulation mediated via ETA receptors; (2) ETA receptor antagonists increase ET-1 efflux, which may lead to net vasoconstriction via unopposed ETB stimulation. Furthermore, the negative inotropic effects observed during ischaemia suggest that ET is critical to the maintenance of systolic function during ischaemia.

Animals↗
PubMed1998

Nitrate therapy is an alternative to furosemide/morphine therapy in the management of acute cardiogenic pulmonary edema.

BACKGROUND: Nitrates are superior to furosemide in the management of acute pulmonary edema associated with myocardial infarction; however, their role in the absence of infarction is unclear. METHODS AND RESULTS: A randomized comparison was undertaken of the relative effectiveness of primary therapy with either intravenous morphine/furosemide (men/women; n = 32) or nitroglycerin/N-acetylcysteine (NTG/NAC; n = 37) in consecutive patients with acute pulmonary edema. The primary end point was change in PaO2/FIO2 over the first 60 minutes of therapy. Secondary end points were needed for mechanical respiratory assistance (ie, continuous positive airway pressure via mask or intubation and ventilation) and changes in other gas exchange parameters. Both treatment groups showed improvement in oxygenation after 60 minutes of therapy; however, this reached statistical significance only with NTG/NAC therapy. There was no significant difference between groups in the assessed parameters (95% CI for differences in Pao2/FIO2: furosemide/morphine -12 to 23 and NTG/NAC 4 to 44), a finding also confirmed in 32 patients presenting with respiratory failure. Only 11% of the study group required mechanical ventilatory assistance (continuous positive airway pressure in 4 patients and intubation and ventilation in 3 patients). CONCLUSIONS: NTG/NAC therapy is as effective as furosemide/morphine in the initial management of acute pulmonary edema, regardless of the presence or absence of respiratory failure. The necessity for mechanical ventilatory assistance is infrequent in these patients, regardless of the initial medical treatment regimen.

Acetylcysteine↗
PubMed1998

Regional differences in the characteristics and treatment of patients participating in an international heart failure trial. The Assessment of Treatment with Lisinopril and Survival (ATLAS) Trial Investigators.

AIMS: This study was designed to determine regional differences in patient characteristics and medication use among patients entered into an international heart failure trial. METHODS AND RESULTS: Data for this analysis were derived from the Assessment of Treatment with Lisinopril and Survival Study (ATLAS), a prospective randomized comparison of high- and low-dose therapy with lisinopril in patients with New York Heart Association class II, III, or IV chronic heart failure, which enrolled 3164 patients in 291 centers in 19 countries on 3 continents. Information was collected at baseline concerning patient demographics, etiology of heart failure, accompanying conditions, prior revascularization procedures, and medication use. The primary findings were a lower incidence of ischemic cardiomyopathy in southern and western Europe, more frequent diabetes in North America, and a greater use of coronary revascularization in the United States and Canada. There was substantial variation in medication use, particularly with regard to digoxin, anticoagulants, and amiodarone. CONCLUSIONS: Although there is considerable overlap in guidelines concerning the treatment of heart failure issued by authorities in Europe and North America, there are significant regional variations in medication use. Some, but not all, of these differences can be explained by differences in patient characteristics.

Aged↗
PubMed1998

Myocardial effect compartment modeling of metoprolol and sotalol: importance of myocardial subsite drug concentration.

We have recently reported the time course of acute myocardial drug uptake and simultaneous pharmacodynamic effects for metoprolol (4 mg; n = 12) and sotalol (20 mg; n = 10) in patients with ischemic heart disease. The acute pharmacodynamic effects of the two drugs included reductions in both spontaneous heart rate and the contractile index peak positive rate of left ventricular pressure rise and prolongation of the electrocardiographic PR interval, all of which exhibited an equilibration delay compared with myocardial drug content. The objective of the current study was to analyze the relationship between myocardial drug content and effect for both metoprolol and sotalol using an effect compartment model, to examine the potential for the two drugs to share a common subsite of action in the myocardium. The time course of myocardial drug content was best described by a one-compartment model for metoprolol and a two-compartment model for sotalol. A linear pharmacodynamic model, relating the amount of drug at the effect-site (Ae) with each of the three effects, was used in the effect compartment modeling. The slope of each of these effects as a function of Ae was considerably flatter for sotalol than for metoprolol, reflecting the relative beta-adrenoceptor antagonistic potencies of the two drugs. The exit rate constant from the effect compartment (K(eo)) did not differ significantly from each other or from the exit rate constant from the "peripheral" compartment (K21) for sotalol. The results suggest that the effect compartment within the myocardium for both drugs may correspond to a "peripheral" compartment, even though a "peripheral" pharmacokinetic compartment for myocardial metoprolol content was not apparent. Thus, the effect compartment for many cardioactive drugs may correspond to a pharmacokinetically "peripheral" compartment, irrespective of localization of effect to a small (e.g. sinoatrial node) or large (e.g. ventricular myocardium) region of the heart.

Adrenergic beta-Antagonists↗
PubMed1998

Effect of trimetazidine on carnitine palmitoyltransferase-1 in the rat heart.

The mechanism of action of the antiischemic effect of the antianginal agent trimetazidine remains uncertain. However, there is evidence that it inhibits long-chain fatty acid oxidation, which may increase the efficiency of myocardial oxygen utilization. We examined the effects of trimetazidine (0.1-5 mmol/L) on the activity of carnitine palmitoyltransferase-1 (CPT-1) in rat myocardium. Trimetazidine inhibited CPT-1 (IC50 1.3 mmol/L); this effect was less potent than that of perhexiline (IC50 77 mumol/L) or amiodarone (IC50 228 mumol/L), but appeared to interact with the enzyme at a similar site as that of both perhexiline and amiodarone. It is concluded that the relatively low potency of trimetazidine as a CPT-1 inhibitor makes this an unlikely mechanism to explain its therapeutic antiischemic effect.

Amiodarone↗
PubMed1998

Short-term myocardial uptake of d- and l-sotalol in humans: relation to hemodynamic and electrophysiologic effects.

The myocardial concentration of many cardioactive drugs has been identified as an important determinant of their short-term effects in previous studies. Although sotalol is frequently administered via short-term intravenous injection, no previous studies had sought to correlate its uptake by the heart with its various effects. We determined the time course of short-term uptake of d,l-sotalol by human myocardium in vivo and investigated the relation between myocardial content of sotalol and the short-term hemodynamic, electrocardiographic, and electrophysiologic effects of the drug. Sixteen patients received a 20-mg intravenous bolus of sotalol at the time of diagnostic cardiac catheterization. Myocardial content of d- and l-sotalol (by using a paired transcoronary sampling technique) and the short-term hemodynamic and electrophysiologic effects of the drug were determined < or = 20 min after injection. Myocardial accumulation of sotalol was not enantioselective, proceeded very rapidly (maximal at 0.74 +/- 0.10 min, representing 2.05 +/- 0.45% of the total injected dose), and was not significantly influenced by left ventricular systolic function or the extent of coronary artery disease. Approximately one third of peak myocardial content was still present 17.5 min after sotalol administration. Maximal effects of the drug (reduction in spontaneous heart rate, p < 0.005; reduction in maximal rate of LV pressure increase (LV+dP/dtmax, p < 0.005); and prolongation of PR intervals, p < 0.02) were delayed by approximately 10 min relative to maximal myocardial sotalol content. The significant prolongation of AH intervals (p < 0.01) and atrioventricular nodal effective refractory periods (p < 0.0002) that was observed was also maximal 10 min after administration of sotalol. Thus a consistent delay between myocardial sotalol content and the short-term effects of the drug was observed. In conclusion, the accumulation of both d- and l-sotalol by the human myocardium is more rapid than that of any other agent studied to date, with considerable hysteresis between myocardial drug uptake and subsequent cardiac effects.

Adrenergic beta-Antagonists↗
PubMed1998

Relationship between myocardial milrinone content and its acute hemodynamic and electrophysiologic effects.

One of the major determinants of the short-term effects of many cardioactive drugs is the concentration of the drug specifically within the myocardium. However, no information regarding the disposition of the phosphodiesterase inhibitor milrinone in the heart is available. We therefore determined the time course of short-term myocardial milrinone uptake from paired transcoronary sampling and simultaneous coronary sinus blood flow after a 1-mg intravenous bolus in patients undergoing diagnostic cardiac catheterization. In accordance with this intention, a sensitive, reproducible method for the determination of milrinone in human whole-blood samples was developed. The reverse-phase high-performance liquid chromatographic method described used a C18 column with UV-absorbance detection at 326 nm, with a limit of detection of 0.6 ng/ml, and was highly reproducible. The short-term hemodynamic and electrophysiologic effects of the drug also were determined. Significant increases in spontaneous heart rate and LV+dP/dtmax (at constant heart rate) were observed, accompanied by reductions in mean arterial pressure, systemic vascular resistance, and PR interval, without significant changes in atrioventricular nodal or ventricular effective refractory periods. Peak content (1.89 +/- 0.30% of injected dose) was rapidly attained, 0.56 +/- 0.06 min after milrinone injection. Time of peak effects was significantly delayed (7-10 min after injection) relative to time of peak myocardial milrinone content. Residual myocardial milrinone content was 69.1 +/- 5.7% of maximum 12.5 min after injection. It is concluded that both myocardial uptake and the onset of positive inotropic effects after intravenous injection of milrinone were very rapid. However, there was significant hysteresis between peak myocardial content and subsequent hemodynamic effects.

Adult↗
PubMed1998

Effects of home-based intervention on unplanned readmissions and out-of-hospital deaths.

OBJECTIVE: To determine the effect of a home-based intervention (HBI) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care. DESIGN: A randomized controlled trial comparing HBI with usual care (UC). SETTING: A tertiary referral hospital servicing the northwestern region of Adelaide, South Australia. PARTICIPANTS: Medical and surgical patients (n = 762) discharged home after hospitalization. INTERVENTION: Home-based intervention (n = 381) consisted of counseling of all patients before discharge followed by a single home visit (by a nurse and pharmacist) to those patients considered to be at high risk of readmission (n = 314) in order to optimize compliance with and knowledge of the treatment regimen, identify early clinical deterioration, and intensify follow-up of such patients where appropriate. MEASUREMENTS: The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period. RESULTS: During the study follow-up, the major endpoint occurred most commonly in the UC group (217 vs 155 episodes: P < .001). Overall, the HBI group demonstrated fewer unplanned readmissions (154 vs 197: P = .022), out-of-hospital deaths (1 vs. 20: P < .001), total deaths (12 vs. 29: P = .006), emergency department attendances (236 vs 314: P < .001), and total days of hospitalization (1452 vs 1766: P < .001). There was a disproportionate reduction in multiple events among HBI patients (P = .035). Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ($A2190 vs $A2680 per patient: P = .102). Mean cost of HBI was $A190 per patient visited, whereas other community-based health care costs were similar for both groups. CONCLUSIONS: Among high-risk patients discharged from acute hospital care, HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death. It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission.

Aged↗
PubMed1997

Nitroglycerin tolerance at the platelet level in patients with angina pectoris.

Suppression of platelet aggregation may be an important component of the therapeutic effect of nitroglycerin (NTG). Because of the phenomenon of hemodynamic tolerance to NTG, we tested the hypothesis that the anti-platelet effects of NTG in humans are also subject to tolerance induction. In patients with stable angina who had not received nitrates for at least 24 hours before study, sublingual administration of NTG (300 microg; n = 17) attenuated the reversal of adenosine diphosphate-induced platelet aggregation by NTG applied in vitro. Three minutes after in vivo NTG administration, concentration of NTG producing 50% reversal of aggregation (C50) increased from 7.9 +/- 1.9 x 10(-5) to 5.5 +/- 0.3 x 10(-4) M (p <0.01); this change persisted for at least 60 minutes. There was no concomitant change in C50 values for sodium nitroprusside applied in vitro. Basal activity of platelet guanylate cyclase and its response to sodium nitroprusside were not affected after administration of NTG. Brief intravenous infusion of NTG (10 microg/min for 10 minutes) produced no significant changes in platelet responses to NTG in vitro. However, prolonged infusion of NTG (5 microg/min for 24 hours, patients with unstable angina pectoris, n = 11) caused suppression of in vitro platelet response to NTG. Platelets from patients receiving prophylactic nitrates (n = 19) were less responsive to the antiaggregatory effects of NTG in vitro than those from patients who had not received nitrates in the previous 24 hours (n = 21). Thus, clinical exposure to NTG, even in very low doses, induces tolerance to antiaggregatory effects of NTG. This phenomenon is not associated either with cross tolerance to sodium nitroprusside or with down-regulation of platelet guanylate cyclase.

Administration, Sublingual↗
PubMed1997

Indinavir nephropathy.

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Acquired Immunodeficiency Syndrome↗
PubMed1997

Perhexiline improves symptomatic status in elderly patients with severe aortic stenosis.

BACKGROUND: The prognosis of severe symptomatic aortic stenosis is poor without aortic valve replacement, with no previous reports of beneficial effects of any medical treatment on either symptoms or outcome. However, this condition is increasingly a disease of the elderly and cardiothoracic surgery is associated with significant mortality and morbidity in this group. AIMS: We postulated that perhexiline, a novel anti-ischaemic agent with an oxygen-sparing metabolic effect in the myocardium (via inhibition of carnitine palmitoyltransferase-1) and no adverse haemodynamic effects, may improve symptomatic status in elderly patients with severe aortic stenosis. We report here our initial experience with perhexiline treatment in such patients. METHODS: Elderly patients with symptomatic severe aortic stenosis, who were deemed unsuitable for aortic valve replacement, were treated with perhexiline, the drug dosage titrated according to steady state plasma perhexiline concentrations. NYHA functional class was determined prior to and three months following commencement of perhexiline, and changes were analysed using McNemar's test. RESULTS: Fifteen patients, age range 73-87, were followed for up to 30 months (median 18 months). Symptomatic status improved in 13 of the 15 patients over the first three months of perhexiline therapy (p < 0.01), five patients becoming asymptomatic. Twelve month actuarial survival was 80% (95% CI = 57, 100). Perhexiline was well tolerated, with no withdrawals due to toxicity or deteriorating clinical status. CONCLUSION: Therapy with perhexiline was associated with a marked improvement in clinical status in this group of elderly patients with severe aortic stenosis.

Aged↗
PubMed1996

Heterogeneity of glyceryl trinitrate response in isolated bovine coronary arteries.

Factors determining heterogeneity of response to glyceryl trinitrate in coronary microvessels have been extensively documented in recent years, but determinants of heterogeneity between conduit and large resistance vessels are poorly understood. The current study has characterised heterogeneity to glyceryl trinitrate and other vasodilators in bovine isolated proximal (4.5 mm i.d.) and distal (0.5 mm i.d.) segments of left anterior descending artery. Compared with proximal segments, distal segments were less responsive to glyceryl trinitrate and sodium nitroprusside, equi-responsive to S-nitroso-N-acetylpenicillamine, and more responsive to isoprenaline. Heterogeneity to glyceryl trinitrate was unaffected by the presence of the thiols (cysteine or N-acetylcysteine, 100 microM). The results are interpreted as evidence that heterogeneity of vascular responsiveness to glyceryl trinitrate reflects impairment in the small artery of the cellular events which precede activation of the cyclic GMP pathway. An implication is that the impairment is not a consequence of limited thiol availability, and in this respect the cellular mechanism of heterogeneity differs from those proposed for the coronary microvasculature.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Lack of inhibition of glyceryl trinitrate by diphenyleneiodonium in bovine coronary artery.

Recent studies indicate that diphenyleneiodonium is a potent inhibitor of glyceryl trinitrate-induced relaxation in rat aorta precontracted with phenylephrine. We have explored the generality of this action in bovine coronary artery precontracted with the thromboxane A2 mimetic, 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F2 alpha (U46619). Diphenyleneiodonium 0.3 microM was without effect (endothelium absent) or caused mild potentiation (0.3 microM or 10 microM; endothelium present) of the relaxant response to gylceryl trinitrate. Lack of inhibition was not due to U46619, since inhibition was still prominent in rat aorta precontracted with this agent. It is concluded that diphenyleneiodonium distinguishes between cellular mechanisms mediating vasodilator responses to glyceryl trinitrate in rat aorta and bovine coronary artery.

Animals↗