Treatment of diffuse coronary lesions: a time for randomized trials.
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Biomedical subjects
Publications and source records attributed to D J Cohen.
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Ondansetron, a selective 5-HT3 antagonist, may lower mesolimbic dopaminergic hyperactivity. The present open-label pilot study evaluated the effect of ondansetron in Tourette's syndrome. Six Tourette's syndrome men aged 14-48 years resistant to haloperidol participated in the study. Assessments included the Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and Tourette's syndrome-Clinical Global Impression (TS-CGI) scale. The maximal ondansetron dosage (8-16 mg per day) was given for 3 weeks. Ondansetron treatment was associated with a significant decrease in the severity of tics. Two patients showed a definite response (score improvement of 40% or more), and two showed a probable response (> 25%). Two patients did not improve. Side-effects were transient and included abdominal pain (n = 5) and constipation (n = 2). Ondansetron may possess anti-tic effects in some Tourette's syndrome patients.
This study focuses on early parental preoccupations and behaviors (EPPB) surrounding the birth of a new family member. An interview instrument was developed to assess EPPB at eight months prepartum and two weeks and three months postpartum. Measures with adequate psychometric and conceptual properties were used to assess the overall level of parental preoccupations and associated actions as well as three content domains: caregiving (CARE), relationship building (RELATIONSHIP), and anxious intrusive thoughts associated with harm avoidant behaviors (AITHAB). The hypothesis that preoccupations and behaviors would peak for both parents close to the birth of the child was confirmed. Measures of EPPB were distinguished from symptoms of depression and generalized anxiety. Consistent with our a priori hypothesis the content and character of the AITHAB was found to resemble the symptoms of obsessive-compulsive disorder (OCD). The study findings suggest the potential adaptive significance of EPPB and the possible evolutionary origins of OCD.
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To analyze visual scenes, the visual system decomposes the visual scene into features that are processed in parallel by separate subsystems. Certain theories (Treisman, Wolfe) propose that these subsystems function independently before focal attention integrates their output. We describe a new paradigm-the gestalt detection task--that directly assesses the degree of preattentive dependence between any two subsystems. We present five experiments that test whether the subsystems that process form and color function independently in processing brief (and, therefore, preattentively processed) stimuli. Our data show that these two subsystems interact during the preattentive processing of feature-dependent information. They are synergistic when the information they receive is consistent; they are antagonistic when the information they receive is inconsistent.
BACKGROUND: Admission to a hospital with a capability for cardiac procedures is associated with a higher likelihood of referral for a cardiac procedure but not with a better short-term clinical outcome. Whether there are differences in long-term mortality and resource consumption is not clear. We sought to determine whether elderly Medicare patients with acute myocardial infarction admitted to hospitals with on-site cardiac catheterization facilities have lower long-term hospital costs and better outcomes than patients admitted to hospitals without such facilities. METHODS AND RESULTS: As part of the Cooperative Cardiovascular Project pilot in Connecticut, we conducted a retrospective cohort study using data from medical charts and administrative files. The study sample included 2521 patients with acute myocardial infarction covered by Medicare from 1992 to 1993. The cardiac catheterization rate was higher in the hospitals with facilities (38.6% versus 26.9%; P<0.001), but the revascularization rate was similar (20.5% versus 19.5%) during the initial episode of care and at 3 years (29.7% versus 29.7%). Mortality rates were similar for patients admitted to the 2 types of hospitals at 30 days (OR, 1.08; 95% CI, 0.83 to 1.42) and at 3 years (OR, 1.02; 95% CI, 0.83 to 1.26). The adjusted readmission rates were significantly lower among patients admitted to hospitals with cardiac catheterization facilities (OR, 0.76; 95% CI, 0.61 to 0.94). However, the overall mean days in the hospital for the 3 years after admission was 25.9 for patients admitted to hospitals with facilities and 24.6 for the other patients (P=0.234). Adjusting for baseline patient characteristics, there was no significant difference in the 3-year costs between patients admitted to the 2 types of hospitals. CONCLUSIONS: With higher rates of cardiac catheterization and lower readmission rates, patients admitted to hospitals with on-site cardiac catheterization facilities did not have significantly different hospital costs compared with patients admitted to hospitals without these facilities. There was also no significant difference in short- or long-term mortality rates.
Previous studies have shown a high rate of repeat intervention after treating diffuse in-stent restenosis with percutaneous transluminal coronary angioplasty (PTCA) alone. It is not clear whether debulking with atherectomy is more effective in this condition. Between January 1994 and February 1997, we treated 60 consecutive patients with diffuse in-stent restenosis of a native coronary artery using conventional PTCA (n=30) or debulking (with rotational or directional atherectomy) plus adjunctive PTCA (n=30). Paired angiograms were analyzed by quantitative angiography, and clinical follow-up was obtained in all patients at 1 month, 6 months, and 1 year after revascularization. The mean lesion lengths were 13.5+/-8.3 and 18.4+/-13.2 mm in the debulking and PTCA groups, respectively (p=0.09). Acute procedural success was 100% in both cohorts, with no major complications in either group. Treatment with atherectomy plus adjunctive PTCA resulted in lower postprocedure stenoses (18+/-10 vs 26+/-13%, p=0.01) than treatment with balloon angioplasty alone. At 1-year follow-up, repeat target vessel revascularization was required in 28% of patients in the debulking group compared with 46% in the PTCA group (p=0.18). Independent predictors of the need for repeat target vessel revascularization were longer lesion lengths, diabetes mellitus, and smaller postprocedure lumen diameter. Thus, the strategy of atherectomy and adjunctive PTCA for diffuse in-stent restenosis is safe, improves acute angiographic results compared with PTCA alone, and may decrease the need for target vessel revascularization.
BACKGROUND: Continuous-loop event recorders are widely used for the evaluation of palpitations, but the optimal duration of monitoring is unknown. OBJECTIVE: To determine the yield, timing, and incremental cost-effectiveness of each week of event monitoring for palpitations. DESIGN: Prospective cohort study. PATIENTS: 105 consecutive outpatients referred for the placement of a continuous-loop event recorder for the evaluation of palpitations. MEASUREMENTS: Diagnostic yield, incremental cost, and cost-effectiveness for each week of monitoring. RESULTS: The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per patient in week 3 and beyond. Over time, the cost-effectiveness ratio increased from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and $5832 per new diagnosis in week 3. CONCLUSIONS: In patients referred for evaluation of palpitations, the diagnostic yield of continuous-loop event recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring period is reasonably cost-effective for most patients and should be the standard period for continuous-loop event recording for the evaluation of palpitations.
BACKGROUND: Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. METHODS: Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. RESULTS: For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. CONCLUSION: Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.
This report describes the treatment by rotational atherectomy of three restenotic ostial diagonal lesions that originated within stented segments of the left anterior descending artery. Excellent results were obtained without complications to stent architecture.
Although cost estimates for acute myocardial infarction are necessary for decisions about allocating scarce resources, there is a relative paucity of studies that estimate these costs across the entire spectrum of hospitals in actual clinical practice. This study sought to determine the correlates of in-hospital costs for acute myocardial infarction in patients 65 years of age and older. In the Cooperative Cardiovascular Project pilot, medical records were abstracted for acute myocardial infarction hospitalizations in Connecticut from June 1, 1992, through May 20, 1993. In-hospital costs were calculated by multiplying charges from cost centers by the Medicare ratio of cost-to-charge. Among the 2628 patients in the study sample, the total mean in-hospital cost was $14,772, and the median in-hospital cost was $10,409 (twenty-fifth to seventy-fifth percentile, $6960 to $17,225). The largest proportion of the costs were concentrated in room costs (43% of the total). Although several demographic and clinical characteristics were significantly associated with cost, they accounted for only 7% of the variation. In-hospital procedures and adverse outcomes accounted for 53% of the variation.
OBJECTIVES: This study sought to investigate the effects of tirofiban versus placebo on the incidence of adverse cardiac outcomes and coronary artery restenosis at 6 months. BACKGROUND: Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein IIb/IIIa. In a recent clinical study, tirofiban reduced the incidence of adverse cardiovascular events at both 2 and 7 days after coronary angioplasty or directional coronary atherectomy. This reduction persisted but was no longer statistically significant at 30 days. METHODS: The Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 h of presentation with either unstable angina pectoris or acute myocardial infarction. All patients received an initial bolus (10 microg/kg body weight over 3 min), followed by a 36-h infusion (0.15 microg/kg per min) of either tirofiban or placebo. RESULTS: At 6 months the composite end point (either death from any cause, new myocardial infarction, bypass surgery for angioplasty failure or recurrent ischemia, repeat target vessel angioplasty or stent insertion for actual or threatened abrupt closure) occurred in 1,070 placebo group patients (27.1%) and 1,071 tirofiban group patients (24.1%, p = 0.11). Analysis of 6-month coronary arteriograms by means of quantitative coronary arteriography showed no significant difference between placebo- and tirofiban-treated patients in either the incidence of a > or =50% diameter stenosis (57% vs. 51%, p = NS), a loss of > or =50% of lumen diameter gained (50% vs. 50%, p = NS) or a loss of > or =0.72 mm of lumen diameter (44% vs. 42%, p = NS). CONCLUSIONS: The 3% absolute reduction in the incidence of the composite end point at 6 months (27.1% placebo vs. 24.1% tirofiban) was similar to that previously reported at 2 days (8.7% vs. 5.4%, p < 0.005), and there does not appear to be any late effect of tirofiban on clinical end points between day 2 and 6 months. Tirofiban did not reduce the incidence of restenosis at 6 months when defined in a number of ways.
OBJECTIVES: The purpose of this study was to compare the immediate angiographic and long-term results of debulking versus balloon angioplasty for treatment of true bifurcation lesions. BACKGROUND: Previous studies have shown true bifurcation lesions to be a high risk morphological subset for percutaneous transluminal coronary angioplasty (PTCA). Although atherectomy devices have been used to treat bifurcation lesions, no studies have compared the outcomes of these alternative treatment modalities. METHODS: Between January 1992 and May 1997, we treated 70 consecutive patients with true bifurcation lesions (defined as a greater than 50% stenosis in both the parent vessel and contiguous side branch) with conventional PTCA (n = 30) or debulking (with rotational or directional atherectomy) plus adjunctive PTCA (n = 40). Paired angiograms were analyzed by quantitative angiography, and clinical follow-up was obtained in all patients. RESULTS: Acute procedural success was 73% in the PTCA group and 97% in the debulking group (p = 0.01). Major in-hospital complications occurred in two patients in the PTCA group and one in the debulking group. Treatment with atherectomy plus PTCA resulted in lower postprocedure residual stenoses than PTCA alone (16+/-15% vs. 33+/-17% in the parent vessel, and 6+/-15% vs. 39+/-22% in the side branch; p < 0.001 for both comparisons). At 1 year follow-up, the incidence of target vessel revascularization (TVR) was 53% in the PTCA group as compared with 28% in the debulking group (p = 0.05). Independent predictors of the need for repeat TVR were side branch diameter >2.3 mm, longer lesion lengths, and treatment with PTCA alone. CONCLUSIONS: For the treatment of true bifurcation lesions, atherectomy with adjunctive PTCA is safe, improves acute angiographic results, and decreases target vessel revascularization compared to PTCA alone. The benefits of debulking for bifurcation lesions were especially seen in lesions involving large side branches.
The endothelial cell regulates vessel tone by elaborating a number of vasoactive substances such as thromboxane and endothelin, both of which are highly vaosconstrictive, and prostacyclin and nitric oxide, both of which are vasodilatory. The current study examines the postulate that one of the mechanisms responsible for the increased vessel tone found in hypertension is the presence of substances in the sera of patients with this disorder that stimulates selectively the endothelial cell production of thromboxane and endothelin. Sera from ten patients with mild hypertension and from 11 age-matched controls were incubated with human umbilical arterial endothelial cells and the concentrations of endothelin, thromboxane, prostacyclin, and nitric oxide produced by the cells was measured in the supernatant. The results of the assays showed that the amounts of thromboxane and endothelin produced by endothelial cells in response to stimulation by hypertensive sera were significantly higher than the amounts produced in response to control sera; in comparison, the amounts of prostacyclin and nitric oxide produced by the cells in response to either hypertensive sera or control sera were not significantly different. The findings suggest that a mechanism that may be responsible for the increased vascular tone found in hypertension is the presence of substances in hypertensive sera that stimulate endothelial cells selectively to produce increased amounts of the vasoconstrictive hormones, endothelin and thromboxane.
Although heparin is widely used as the injectable anticoagulant of choice, it has several potential shortcomings. These include heparin resistance, excessive bleeding, allergic reactions, and, with longterm use, occasional osteoporosis or alopecia. Perhaps the most notorious complication is heparin-induced thrombocytopenia and thrombosis (HITT); although unusual, it often results in major morbidity or death. Until recently, reliable diagnostic tests and anticoagulation alternatives have not been widely available. After a review of the pharmacology of heparin and related drugs, advances in the prevention, diagnosis, and treatment of this problem are discussed.
OBJECTIVE: To determine the value of routine transthoracic echocardiography in patients with cerebral ischemia without known cardiac disease. DESIGN: The literature from 1990 to 1995 was searched and relevant bibliographies from these papers reviewed. Articles reporting the prevalence and/or risk of stroke for myxoma, vegetation, mitral stenosis, left atrial thrombus, left ventricular thrombus or cardiomyopathy, patent foramen ovale, and atrial septal aneurysm were used. Prevalences and recurrent stroke risk were examined for adult patients less than and greater than 45 years. RESULTS: Both the prevalence of transthoracic echocardiographic findings and recurrent risk of stroke differ by age. The finding of a patent foramen ovale can be expected in nearly half of younger patients with stroke, whilst transthoracic echo can be expected to yield no relevant lesion in three quarters of patients > 45 years. Warfarin anticoagulation appears beneficial in patients with mitral stenosis, left atrial thrombus, left ventricular thrombus, and left ventricular dysfunction, but is of unproven benefit for patent foramen ovale, atrial septal aneurysm, or in the absence of a risk-associated abnormality. CONCLUSION: For most transthoracic echo findings in stroke, optimal management strategies have not been well defined. Future research is needed to evaluate the appropriate therapeutic approaches.
Rat epididymal protein DE associates with the sperm surface during maturation and participates in sperm-egg fusion. Immunization of male rats with DE raised specific antibodies and produced a significant reduction in the animals' fertility. The present study focused on determining the in vivo mechanism involved in fertility inhibition. Wistar males were injected with DE, and antibody levels and animal fertility were evaluated. Results revealed an association between the two parameters, since animals with absorbance values lower than 0.5 in ELISA presented high fertility rates (66%, 100%) while those with absorbance values higher than 0.5 exhibited the lowest fertility rates (0%, 33%). Histological studies showed no evidence of orchitis, epididymitis, or vasitis in DE-immunized animals. ELISA results revealed the presence of anti-DE antibodies in epididymal and vas deferential fluids. Indirect immunofluorescence and ELISA experiments indicated that these antibodies would not interfere with the synthesis or secretion of DE or with its association with the sperm surface. Finally, while epididymal sperm recovered from DE-immunized animals presented no changes in motility, viability, or ability to undergo capacitation and acrosome reaction, they exhibited a significant decrease in their ability to fuse with zona-free eggs, with no effect on their ability to bind to the oolemma. Together these results indicate that immunization of male rats with epididymal protein DE specifically interferes with the sperm fertilizing ability, supporting the use of epididymal proteins for contraceptive vaccine development.
OBJECTIVE: To reevaluate platelet serotonin (5-HT) levels in autism, measuring and controlling for effects of race and puberty. The specificity of hyperserotonemia for autism versus cognitive impairment is also assessed. METHOD: Platelet 5-HT levels were measured in 77 individuals, aged 2 through 37 years, with autistic disorder; 65 normal controls; and 22 mentally retarded or otherwise cognitively impaired (MR/CI) prepubertal children. Effects of diagnosis, race, and pubertal status were evaluated by analysis of variance in separate pre- and postpubertal groups. 5-HT levels were expressed as ng/mL blood and ng/microL platelet volume. RESULTS: Among prepubertal children, significant effects of diagnosis (ng/mL; F2,109 = 5.9, p = .004) and race (F2,109 = 14.7, p < .0005) were found. Autistic youngsters had significantly higher 5-HT concentrations than controls, although the elevation (25%) was less than typically reported; MR/CI children had levels very similar to those of controls. White children had significantly lower 5-HT levels than black or Latino youngsters, regardless of diagnosis. Diagnosis and race effects were nonsignificant in the postpubertal group. Postpubertal subjects had lower 5-HT concentrations than prepubertal subjects (ng/mL; F1,114 = 28.5, p < .0005). CONCLUSIONS: The data underscore the importance of matching for race and pubertal status in neuropsychiatric research and suggest that the prevalence of hyperserotonemia in autistic individuals may have been overestimated because of a failure to control for both variables. Hyperserotonemia was not found in MR/CI youngsters without autistic features.