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Biomedical subjects

R Gottlieb

Publications and source records attributed to R Gottlieb.

At least 19 recordsLinked to original sources
PubMed1999

Ovarian cancer: comparison of observer performance for four methods of interpreting CT scans.

PURPOSE: To assess the effects of four interpretative methods on observers' mean sensitivity and specificity by using computed tomography (CT) of ovarian carcinoma as a model. MATERIALS AND METHODS: CT scans in 98 patients with ovarian carcinoma and 49 women who were disease free were retrospectively reviewed by four experienced blinded radiologists to compare single-observer reading, single-observer reading with an anatomic checklist, paired-observer reading (simultaneous double reading), and replicated reading (combination of two independent readings). Confidence level scoring was used to identify three possible disease forms in each patient: extranodal tumor, lymphadenopathy, and ascites. Patient conditions were then categorized as abnormal or normal. RESULTS: There were no significant improvements in sensitivity or specificity for classification of patient conditions as abnormal or normal when comparing single-observer interpretation with single-observer interpretation with a checklist or paired-observer interpretation. Although there was no significant improvement in the mean sensitivity (93% vs 94%) by using the replicated reading method, there was a statistically significant improvement in mean specificity (85% vs 79%) for the replicated readings compared with single-observer interpretations (P < .05). CONCLUSION: Diagnostic aids such as checklists and paired simultaneous readings did not lead to an improved mean observer performance for experienced readers. However, an increase in the mean specificity occurred with replicated readings.

Female↗
PubMed1996

New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis.

Lymphocyte granule-mediated apoptosis is postulated to entail the formation of membrane pores by perforin. Then soluble granzyme reaches the cytosol either through these pores or by reparative pinocytosis. We demonstrate here that Jurkat cells bind and internalize granzyme B via high affinity binding sites without toxic consequence. Apoptosis occurs, however, if sublytic perforin is added to targets washed free of soluble granzyme B. We suggest that granule-mediated apoptosis mimics viral strategies for cellular entry. Accordingly, co-internalization of granzyme B with adenovirus, a virus that escapes endosomes to reach the cytosol, also induced apoptosis. Poly(ADP-ribose) polymerase cleavage and processing of CPP32, ICE-LAP3, and Mch2 were detected at 30 min, while cytosolic acidification and DNA fragmentation occurred at 60 min. Annexin V binding and membrane permeabilization arose at 4 h. The concurrent activation of the Ced-3 proteases differed from the rate at which each cysteine protease is cleaved in vitro by granzyme B. Thus, granzyme B may not directly process these proteases in whole cells but rather may function by activating a more proximal enzyme. These results indicate that adenovirus-mediated delivery of granzyme B is suitable for elucidating biochemical events that accompany granule-mediated apoptosis.

Apoptosis↗
PubMed1996

Commentary.

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Journal Article↗
PubMed1995

Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention. EPIC Investigators.

BACKGROUND: The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial. METHODS AND RESULTS: Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively). CONCLUSIONS: Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.

Aged↗
PubMed1994

Low molecular weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial.

BACKGROUND: Heparin, an anticoagulant, possesses antiproliferative effects and has been shown to reduce neointimal proliferation and restenosis following vascular injury in experimental studies. METHODS AND RESULTS: The primary aim of this double-blind multicenter study was to determine if 40 mg Enoxaparin, a low molecular weight heparin, administered subcutaneously once daily for 1 month after successful angioplasty would reduce the incidence of restenosis. Four hundred fifty-eight patients were randomized at nine clinical centers (231 to placebo and 227 to Enoxaparin). The primary end point was angiographic or clinical restenosis. Angiographic restenosis was defined as a loss of 50% of the initial gain as measured by quantitative coronary angiography (QCA) at a core laboratory. In the absence of QCA, clinical evidence of restenosis was defined as death, myocardial infarction, repeat revascularization, or worsening angina. Using the intention-to-treat analysis for all patients, restenosis occurred in 51% of the placebo group and 52% of the Enoxaparin group (relative risk, 1.07, P = .625). Likewise, no difference in restenosis was evident when the change in minimal lumen diameter or other angiographic definitions of restenosis were used. Adverse clinical events were infrequent and did not differ between the groups with the exception of minor bleeding complications, which were more common in the Enoxaparin group. CONCLUSIONS: Enoxaparin (40 mg/d SC for 1 month) following successful angioplasty did not reduce the incidence of angiographic restenosis or the occurrence of clinical events over 6 months. The treatment was well tolerated, although in-hospital minor bleeding was more common with active treatment.

Angioplasty, Balloon, Coronary↗
PubMed1992

Myelographic and enhanced computed tomographic appearance of acute traumatic spinal cord avulsion.

The neuroradiological findings that revealed spinal cord transection/laceration in 6 patients with acute, blunt spinal trauma are described. Four patients suffered cervical spine injuries, and two had thoracic injuries. Initially, all patients had complete neurological deficit at the level of injury. The deficit improved in only 1 patient. On the basis of clinical history and spinal radiographs, spinal hyperflexion with distraction was the predominant mechanism of injury in our patients. Computed tomography with intrathecal contrast was performed on all patients and was always diagnostic. Visualization of intrathecal contrast material accumulating within the cord or the absence of cord shadow within the contrast column established the diagnosis in all cases. A dural tear was noted in 3 patients. Thoracic myelography was performed in 2 patients and, in both, demonstrated contrast pooling within the spinal cord at the level of the laceration. Magnetic resonance imaging was obtained in 1 patient and revealed an irregular, low-signal-intensity, intramedullary region extending to the cord surface on T1-weighted axial images. The myelographic and enhanced computed tomographic appearances of acute, traumatic spinal cord avulsion/laceration, which have been infrequently reported in the literature, are described.

Acute Disease↗
PubMed1983

Corynebacterium parvum versus BCG adjuvant immunotherapy in human malignant melanoma.

One-hundred and sixteen patients with Stage I and Stage II malignant melanoma were randomized to treatment with either Bacillus Calmette-Guerin (BCG) (Tice) or subcutaneous Corynebacterium parvum (Burroughs-Wellcome). Life table analysis failed to reveal a difference between these two forms of treatment in 68 Stage I patients. The relapse rate was significantly reduced in Stage II patients treated with C. parvum.

BCG Vaccine↗
PubMed1983

Coronary angiographic assessment of left posterior hemiblock.

The ECGs of 1,095 patients with coronary angiographic evidence of significant coronary artery disease (greater than or equal to 50% obstructive lesion in at least one major coronary artery) were reviewed. Five patients had left posterior hemiblock (LPHB), an incidence of 0.5%. Three of five patients also had a right bundle branch block (RBBB). Of the five patients with LPHB, all had significant right coronary artery (RCA) disease (four complete occlusions, one 90% obstructive lesion). All five patients having LPHB also had evidence of critical disease (greater than or equal to 75% obstruction) of at least one of the major branches of the left coronary artery; four of the five had complete occlusion of the left anterior descending coronary artery (LAD). The left circumflex coronary artery (CFx) was critically diseased in three patients. The ECGs of four patients showed evidence of only one myocardial infarction while one patient had evidence of an anterior and an inferior infarction. It is concluded that the presence of LPHB in patients with coronary artery disease is an ominous electrocardiographic finding, and is associated with extensive coronary artery disease.

Adult↗
PubMed1979

Phase II trial of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) combination chemotherapy in advanced ovarian carcinoma.

A monthly four-drug regimen of cyclophosphamide, adriamycin, and cis-dichlorodiammineplatinum(II), each given iv of Day 1, and hexamethylmelamine, given orally on Days 1--14 (CHAP), was administered to 39 women with advanced epithelial ovarian carcinoma who had previously failed alkylating agent therapy. Of 35 evaluable patients with a measurable disease parameter, seven (20%) achieved a clinical complete response and ten (29%) achieved a clinical partial response. The median duration of complete response is greater than 9 months and the median duration of partial response is 4 months. Ninety percent of the patients required dose adjustments because of profound leukopenia, thrombocytopenia, or gastrointestinal intolerance. CHAP is an active but toxic regimen in the management of advanced ovarian cancer. The toxicity encountered reflected the intensity of the drug schedule as well as the combined influences of advanced stage of disease, poor nutritional and performance status, and prior therapy. The efficacy of this CHAP regimen warrants a controlled trial compared to other active drug programs.

Alkylating Agents↗
PubMed1977

Improved survival after coronary bypass surgery in patients with poor left ventricular function: role of intraaortic balloon counterpulsation.

The operative mortality rate of aortocoronary bypass surgery in 23 patients with poor left ventricular function (ejection fraction 0.30 or less) operated on in 1973-74 was 34.7 percent. The incidence rate of operative myocardial infarction was 30.4 percent. In an attempt to improve survival, intraaortic balloon counterpulsation was used therafter in 25 similar patients. Counterpulsation was instituted preoperatively and continued intra- and postoperatively for 2 to 5 days. Preoperative studies revealed an "unloading" effect of the left ventricle, with significant reductions of systolic arterial blood pressure, end-diastolic pulmonary arterial pressure and end-diastolic left ventricular volume and pressure. Metabolic improvement was demonstrated by the lesser production of myocardial lactate after pacing-induced tachycardia when the ventricle was balloon-assisted. Intraoperatively, blood flow through the vein graft was found to increase with counterpulsation. The rate of operative myocardial infarction was reduced to 4 percent and the mortality rate to 8 percent. In patients who have sustained a significant loss of functioning myocardium, the beneficial hemodynamic and metabolic effects of intraaortic balloon counterpulsation appear to prevent furhter, possibly critical, myocardial damage in the perioperative period.

Assisted Circulation↗