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Biomedical subjects

M Cohen

Publications and source records attributed to M Cohen.

At least 217 records · Page 12Linked to original sources

Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis.

BACKGROUND: Two phase III trials of enoxaparin for unstable angina/non-Q-wave myocardial infarction have shown it to be superior to unfractionated heparin for preventing a composite of death and cardiac ischemic events. A prospectively planned meta-analysis was performed to provide a more precise estimate of the effects of enoxaparin on multiple end points. METHODS AND RESULTS: Event rates for death, the composite end points of death/nonfatal myocardial infarction and death/nonfatal myocardial infarction/urgent revascularization, and major hemorrhage were extracted from the TIMI 11B and ESSENCE databases. Treatment effects at days 2, 8, 14, and 43 were expressed as the OR (and 95% CI) for enoxaparin versus unfractionated heparin. All heterogeneity tests for efficacy end points were negative, which suggests comparability of the findings in TIMI 11B and ESSENCE. Enoxaparin was associated with a 20% reduction in death and serious cardiac ischemic events that appeared within the first few days of treatment, and this benefit was sustained through 43 days. Enoxaparin's treatment benefit was not associated with an increase in major hemorrhage during the acute phase of therapy, but there was an increase in the rate of minor hemorrhage. CONCLUSIONS: The accumulated evidence, coupled with the simplicity of subcutaneous administration and elimination of the need for anticoagulation monitoring, indicates that enoxaparin should be considered as a replacement for unfractionated heparin as the antithrombin for the acute phase of management of patients with high-risk unstable angina/non-Q-wave myocardial infarction.

Aged↗

The relative value of CD4 cell count and quantitative HIV-1 RNA in predicting survival in HIV-1-infected women: results of the women's interagency HIV study.

OBJECTIVES: To determine factors associated with survival and to assess the relative strength of CD4 cell count and HIV-1 RNA in predicting survival in a cohort of HIV-1-infected women. DESIGN: Prospective cohort, enrolled during 1994-1995, with median follow-up of 29 months RESULTS: Of 1769 HIV-infected women 252 died. In multivariate analyses, lower CD4 cell count, higher quantitative plasma HIV-1 RNA, and the presence of a self-reported AIDS-defining (Class C) condition were significantly associated with shorter survival: the relative hazard (RH) of dying was 1.17, 3.27, and 8.46, respectively for women with baseline CD4 cell count of 200-349, 50-199, and < 50 x 10(6) cells/l, compared with women with CD4 cell count of > or = 350 x 10(6) cells/l. Compared with women with HIV-1 RNA levels of < 4000 copies/ml plasma, the RH of dying for women with baseline quantitative HIV-1 RNA measurements of 4000-20,000, 20,000-100,000, 100,000-500,000 and > 500,000 copies/ml, was 2.19, 2.17, 3.16, and 7.25, respectively. CD4 cell count had as strong a prognostic value as HIV-1 RNA level, particularly among participants with more advanced immunodeficiency. When the analysis was adjusted to eliminate the distortion created by having disproportionately sized strata of the categorized variables, the relative hazard of death associated with CD4 cell count became even larger in comparison with that for HIV-1 RNA. Eliminating from the analysis all follow-up time during which participants could have received highly active antiretroviral therapy did not change these findings. Age was not a predictor of survival after adjustment for covariates. CONCLUSIONS: CD4 cell count and HIV-1 RNA had similar prognostic value in this cohort of HIV-1-infected women. Even in the presence of a low viral burden, a substantially decreased CD4 cell count remained a strong predictor of mortality.

CD4 Lymphocyte Count↗

Telomerase activity in patients with transitional cell carcinoma: a preliminary study.

BACKGROUND: Telomerase activity is not detectable in normal cells, and their telomers shorten until the chromosome is unable to replicate. Immortal cells have short but stable chromosomes and increased telomerase activity. Transitional cell carcinoma (TCC) has only a few useful markers of diagnostic or prognostic importance. The objective of this study was to determine whether there was a correlation between telomerase activity and the grade or stage of TCC, and whether the enzyme's activity could serve as a biochemical marker of this tumor. METHODS: The study included 29 patients with TCC. From each patient, samples of urine cells were obtained, and a cup biopsy was taken from an apparently normal area as well as from a part of the bladder tumor resected transurethrally. Control uroepithelial biopsies were taken from normal transitional cell sites from non-TCC patients. Biopsies or cells were subjected to either histologic examination or telomerase activity determination. RESULTS: Twenty-six of 29 (90%) of the tumor biopsies exhibited telomerase activity. Most of the cup biopsies were categorized as metaplastic or dysplastic, and 20 of 29 (69%) of these exhibited telomerase activity. Telomerase activity was found in 17 of 21 (81%) of the urine cells but in only 3 of 14 (21%) of control urine cells. All (10 of 10) of the uroepithelial biopsies taken from non-TCC patients did not show any telomerase activity. CONCLUSIONS: In this study, almost all tumor biopsies exhibited telomerase activity. The high incidence of telomerase activity found in cup biopsies of the malignant field uroepithelial cells from cup biopsies of TCC patients may suggest that telomerase could be activated early in carcinogenesis. A high incidence of telomerase activity was found in voided uroepithelial cells of TCC patients; however, no correlation between this activity and the histologic determination of grading and staging of the tumor was found.

Aged↗

Human herpesvirus-8 (HHV-8) associated with small non-cleaved cell lymphoma in a child with AIDS.

The association of human herpesvirus-8 (HHV-8) with a small non-cleaved cell lymphoma is described in a child with the acquired immunodeficiency syndrome (AIDS) who developed a malignant pleural effusion and radiologic evidence of multiple solid tumors. HHV-8 DNA and Epstein-Barr virus DNA were identified in pleural fluid cells by polymerase chain reaction (PCR) amplification. The serum antibody titer against lytic HHV-8 proteins was 1:640; antibodies to latent HHV-8 proteins were not detected. Cytogenetic analysis of malignant cells revealed three abnormal karyotypes sharing the common finding of a t(8;14) translocation. Rearrangement of c-myc was demonstrated by PCR analysis. Oligoclonal JH immunoglobulin bands were found. Insufficient pleural fluid cells were available to permit localization of HHV-8 to malignant cells by in situ hybridization. This malignancy contrasts with HHV-8-associated lymphomas reported in adult patients with AIDS with respect to cell morphology, c-myc translocation, and oligoclonal immunoglobulin gene rearrangement. HHV-8 is associated with a wider spectrum of malignancies than recognized previously.

Adult↗

Comparison of flash lamp pulsed-dye laser (585 nm) and conventional surgery in the delay of random dorsal rat flaps.

BACKGROUND AND OBJECTIVE: Delay is a basic surgical technique used by flap surgeons to improve the blood supply to the distal parts of a random skin flap. The aim of this study was to determine whether a scarless delay can be done by the use of the flash lamp pulsed-dye laser operating at a wavelength of 585 nm. STUDY DESIGN/MATERIALS AND METHODS: The pilot study showed that 6 J/cm(2) had a selective photothermolysis effect and therefore was chosen for testing the delay procedure on 15 rats. The percentage of flap necrosis of this group was compared to the results of 15 rats that underwent delay by surgery and 15 rats that were not treated prior to flap surgery (control group). RESULTS: Laser delay of McFarlane flaps resulted in an average of 15.5% smaller necrotic area compared to the control group (52.7% +/- 14.4% and 68.2% +/- 9.6%, respectively, P < 0.01) and was as effective as surgical delay (53.3% +/- 13.6%). CONCLUSIONS: The results indicate that the flash lamp pulsed-dye laser operating at 585 nm is effective for delaying cutaneous flaps in the rat model.

Analysis of Variance↗

Reduction in ischemic vascular complications with a hydrophilic-coated intra-aortic balloon catheter.

Hydrophilic coatings improve the handling characteristics of angioplasty equipment, but until recently this technology has not been available for intra-aortic balloon (IAB) catheters. To determine whether a new hydrophilic coating is associated with a reduction in IAB-related complications, we prospectively evaluated 188 patients undergoing insertion of this new IAB catheter. Complications related to IAB insertion were recorded and compared to data from 682 patients previously treated with an uncoated IAB catheter of the same shaft diameter and balloon size. By multivariate analysis the hydrophilic-coated IAB catheter was associated with a 72% reduction in ischemic vascular complications (relative risk 0.28, 95% CI 0.08-0.96, P= 0.04). There were also trends toward reductions in IAB rupture and the need for vascular surgical repair for bleeding or ischemia. While further investigation is warranted, hydrophilic coatings that reduce the coefficient of friction during IAB catheter insertion may also reduce subsequent ischemic vascular complications.

Aged↗

Trials of glycoprotein IIb-IIIa inhibitors in non-ST-segment elevation acute coronary syndromes: applicability to the practice of medicine in the United States.

Platelet-mediated thrombosis has been recognized as the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute complications of percutaneous coronary intervention (PCI). Despite the clinical efficacy of the two most widely used antithrombotic agents, aspirin and heparin, each of them has significant therapeutic limitations. As a result, thrombosis and clinical events may occur despite the use of aspirin and heparin. The discovery that the platelet glycoprotein (GP) IIb-IIIa represents the final common pathway to platelet aggregation and the growing recognition of the key role of platelets in the progression of thrombosis prompted the development of several GP IIb-IIIa inhibitors as a potentially more effective form of antithrombotic therapy. Numerous trials of various GP IIb-IIIa inhibitors as adjuncts to PCI have strongly supported this hypothesis. The subject of this supplement is the review of more recent evaluations of GP IIb-IIIa inhibitors in the context of various treatment strategies for the management of patients with unstable angina or non-ST-segment elevation myocardial infarction, collectively known as non-ST-segment elevation ACS. Appropriate translation of these trials into clinical practice requires not only the knowledge of the trials' results but also the understanding of the design of individual studies, most notably the entry criteria and patient management strategies.

Acute Disease↗

Clinical applications of gamma-detection probes - radioguided surgery.

Radioguided surgery (RGS) is a surgical technique that enables the surgeon to identify tissue "marked" by a radionuclide before surgery, based on the tissue characteristics, the radioactive tracer and its carrying molecule, or the affinity of both. Thus, yet another tool has been added to the inspection and palpation traditionally used by the surgeon. Current clinical applications of radioguided surgery are: radioimmunoguided surgery (RIGS) for colon cancer, sentinel-node mapping for malignant melanoma (which has become state-of-the-art), sentinel-node mapping for breast, vulvar and penile cancer, and detection of parathyroid adenoma and bone tumour (such as osteid osteoma). Although the same gamma-detecting probe (GDP) may be used for all these applications, the carrier substance and the radionuclide differ. MoAb and peptides are used for RIGS, sulphur colloid for sentinel-node mapping, iodine-125 for RIGS, technetium-99m for sentinel node, parathyroid and bone. The mode of injection also differs, but there are some common principles of gamma-guided surgery. RIGS enables the surgeon to corroborate tumour existence, find occult metastases, and assess the margins of resection; this may result in a change on the surgical plan. Sentinel lymph-node (SLN) scintigraphy for melanoma guides the surgeon to find the involved lymph nodes for lymph-node dissection. SLN for breast cancer is being investigated with promising results. This procedure has also changed the outlook of lymph-node pathology by giving the pathologist designated tissue samples for more comprehensive examination. Gamma-guided surgery will result in more accurate and less unnecessary surgery, better pathology and, hopefully, in better patient survival.

Humans↗

Neuroblastoma arising from the organ of Zuckerkandl: an unusual site with a favorable biologic outcome.

BACKGROUND: Prognosis in neuroblastoma has been shown to correlate with age and stage at diagnosis and site of origin. Extra-abdominal tumors (chest, neck, pelvis) do better in terms of survival than tumors arising from the upper abdomen. OBJECTIVE: We evaluated a subgroup of abdominal neuroblastomas arising near to the aortic bifurcation (commonly called organ of Zuckerkandl, O. Z.) to assess their biologic outcome and problems in diagnosis and therapy. MATERIALS AND METHODS: Sixteen O. Z. primary tumors were seen at three children's hospitals. Their clinical records and imaging studies were reviewed, including the sonographic, CT, and MRI findings. When available, MYCN amplification was noted (MYCN is the current term previously called N-MYC). RESULTS: Despite more than half of the tumors being very large, survival was the rule, with only one fatality (following multiple local recurrences). Only one patient (who survived) had bone metastases. The larger masses were usually palpated in otherwise well children, while the smaller ones were found in the course of evaluation for unrelated problems such as urinary tract infection. Intraspinal extension was common, though usually asymptomatic. MYCN amplification was absent in the four patients studied. CONCLUSIONS: Lower abdominal (O. Z.) neuroblastomas present technical problems of surgical removal, but form a group with a favorable outcome similar to cervical and thoracic primary sites. MRI was useful in delineating intraspinal extension.

Abdominal Neoplasms↗

Emergent management of multisystem injuries by a general trauma surgeon.

OBJECTIVE: To determine the requisite education and scope of practice for a general surgeon trained to deliver emergent trauma care without the need for specialty consultation. DESIGN: Retrospective case review. SETTING: Private Level I trauma center. PATIENTS: 4097 trauma patients admitted between 1/1/92 and 30/6/97. MAIN OUTCOME MEASURES: Mechanisms of injury; operations (total within the first 24 h) by mechanism and by surgical specialty. RESULTS: Of 4097 trauma patients, 1086 (27%) underwent 1772 operative procedures within 24 h of admission, and 246 (6%) underwent 484 later operations. Orthopaedic and general surgical procedures were most common (51% of early operations). Early operations were most commonly orthopaedic for blunt trauma and general surgical for penetrating trauma. Although 685 patients (16.7%) received neurosurgical evaluation, only 150 early operations were performed (8% of the total early operations). At least 1244 procedures (55%) fell within the scope of current trauma general surgical practice advocated by some authorities. CONCLUSIONS: The contribution of the various specialties to early operative trauma management is a function of the injury mechanism. As orthopaedics and neurosurgery together comprise 34% of emergency practice, a fully credentialed general surgeon with additional training in these disciplines could perform up to 90% of early operations.

Adolescent↗

Painful conditions around the elbow.

This article discusses the origin and histology of conditions causing pain around the elbow as well as possible treatments. Specific conditions examined include epicondylitis and medial, posterior, and anterior musculotendinous injuries.

Algorithms↗

Inadvertent ketamine overdose in children: clinical manifestations and outcome.

STUDY OBJECTIVE: We sought to characterize the clinical manifestations, outcome, and etiology of inadvertent ketamine overdose in the emergency department. METHODS: We investigated cases of inadvertent ketamine overdose in children seen in the ED solicited through electronic mail subscription lists or reported to the Institute for Safe Medication Practices. The clinical manifestations, outcome, and reported cause for each case are described. RESULTS: We identified 9 cases of inadvertent ketamine overdose in children treated in the ED. Patients received either 5(n=3), 10(n=5), or 100(n=1) times the intended dose, either by the intramuscular (n=5) or intravenous (n=4) route. All 9 experienced prolonged sedation (3 to 24 hours). Four experienced brief respiratory depression shortly after administration, and assisted ventilation was performed in 2. Two children without respiratory difficulty or hypoxemia were intubated by their physicians as a precaution. In 5 children, the dosing error was not discovered until late in the sedation, often when the child was not waking at the expected time. No adverse outcomes were noted, and all children were normal neurologically on discharge and longer-term follow-up if available. CONCLUSION: No adverse outcomes were noted in 9 healthy children treated in the ED who inadvertently received 5 to 100 times the intended dose of ketamine. Toxicity manifested as prolonged sedation in all 9 and brief respiratory depression in 4. The margin of safety in ketamine overdose may be wide, although less common and more serious outcomes cannot be excluded by this small, self-reported sample.

Anesthetics, Dissociative↗

Long-term (three-year) prognosis of patients treated with reperfusion or conservatively after acute myocardial infarction. Israeli Thrombolytic Survey Group.

OBJECTIVES: This survey sought to assess the frequency of the use of thrombolytic therapy, invasive coronary procedures (ICP) (angiography, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting [CABG]), variables associated with their use, and their impact on early (30-day) and long-term (3-year) mortality after acute myocardial infarction (AMI). BACKGROUND: Few data are available regarding the implementation in daily practice of the results of clinical trials of treatments for AMI and their impact on early and long-term prognosis in unselected patients after AMI. METHODS: A prospective community-based national survey was conducted during January-February 1994 in all 25 coronary care units operating in Israel. RESULTS: Among 999 consecutive patients with an AMI (72% men; mean age 63+/-12 years) acute reperfusion therapy (ART) was used in 455 patients (46%; thrombolysis in 435 patients [44%] and primary angioplasty in 20 [2%]). Its use was independently associated with anterior AMI location and hospitals with on-site angioplasty facilities, whereas advancing age, prior myocardial infarction (MI) and prior angioplasty or CABG were independently associated with its lower use. The three-year mortality of patients treated with ART was lower than in counterpart patients (22.0% vs. 31.4%, p = 0.0008), mainly as the result of 30-day to 3-year outcome (12.4% vs. 21.1%; hazard ratio = 0.73, 95% confidence interval [CI] 0.52 to 1.03). Independent predictors of long-term mortality were: age, heart failure on admission or during the hospitalization, ventricular tachycardia or fibrillation and diabetes. The outcome of patients not treated with ART differed according to the reason for the exclusion, where patients with contraindications experienced the highest three-year (50%) mortality rate. After ART, coronary angiography, angioplasty and CABG were performed in-hospital in 28%, 12% and 5% of patients, respectively. Their use was independently associated with recurrent infarction or ischemia, on-site catheterization or CABG facilities, non-Q-wave AMI and anterior infarct location. In the entire study population, and in patients with a non-Q-wave AMI, performance of ICP was associated with lower 30-day mortality (odds ratio [OR] = 0.53, 95% CI 0.25 to 0.98, and OR = 0.21, 0.03 to 0.84, respectively), but not thereafter. CONCLUSIONS: This survey demonstrates the extent of implementation in daily practice of ART and ICP and their impact on early and long-term prognosis in an unselected population after AMI.

Aged↗

Signals controlling the expression of cytosolic ascorbate peroxidase during pathogen-induced programmed cell death in tobacco.

In plants ascorbate peroxidase (APX) is an important H2O2-detoxifying enzyme. The expression of APX is rapidly induced in response to stresses that result in the accumulation of reactive oxygen species (ROS). We have recently reported that the steady-state level of transcripts encoding cytosolic APX (cAPX) is dramatically induced during the hypersensitive response (HR) of tobacco plants infected with tobacco mosaic virus (TMV). Because cAPX expression is closely linked to the production of ROS in plant cells, studying the regulation cAPX mRNA can reveal some of the signal transduction events associated with ROS metabolism during the HR. Analysis of cAPX mRNA induction during the HR suggested that the expression of cAPX is under the control of the HR signal transduction pathway. The activation of cAPX expression followed signaling events such as changes in protein phosphorylation and induction of ion fluxes. Expression of cAPX was suppressed under conditions of low oxygen pressure, and could only be mimicked by enhancing the intracellular generation of ROS. Interestingly, salicylic acid (SA), which is thought to be involved in ROS metabolism during the HR, did not affect the induction of cAPX mRNA during TMV-induced HR. Using cAPX expression as a marker for the production of ROS, it is suggested that SA may not be involved in the formation of ROS during the HR of tobacco to TMV, and that ROS may not be involved in the induction of the pathogenesis-related protein, PR-1, during this process.

Anti-Infective Agents↗

Thrombotic reactant markers in non-ST segment elevation acute coronary syndromes treated with either enoxaparin (low molecular weight heparin) or unfractionated heparin.

BACKGROUND: This study was designed to analyze the impact of treatment with either unfractionated heparin or enoxaparin (low molecular weight heparin) on plasma markers of thrombotic and endogenous thrombolytic activity in patients with non-ST segment elevation acute coronary syndromes. METHODS: A subset of 174 patients derived from the 3,171 patients of the ESSENCE study was evaluated. Eighty-seven patients were assigned to intravenous unfractionated heparin (target aPTT: 55-85 sec) (group UH), and 87 assigned to subcutaneous enoxaparin (1 mg/kg/q12hr) (group ENOX) for a minimum of 48 hours of treatment (average duration of treatment 88+/-45 hours). The thrombin time, and plasma levels of anti-factor Xa activity, prothrombin fragment F 1+2, thrombin-antithrombin complex (TAT), and D-dimer, were assayed at baseline, and at or close to peak activity 24-36 hrs, and at 72-90 hrs for those remaining on treatment with antithrombotic therapy. Major ischemic and hemorrhagic events were assessed throughout hospitalization. The levels of the thrombotic markers measured at or close to peak activity at 36 hours are presented below, and compared to clinical outcome at 30 days. RESULTS: In UH patients, the thrombin time increased 7 fold while the mean value for anti-Xa activity was 0.27 IU/ml; in ENOX patients the thrombin time increased 2.3 fold, and the mean value for anti-Xa activity was 0.83 IU/ml. In UH pts, basal levels of F 1+2, TAT, and D-dimer declined by (deltapaired) -0.8, -3. 3, and -66, respectively. In ENOX pts, basal levels of F 1+2, TAT, and D-dimer declined by (deltapaired) -0.3, -4.7, and -23, respectively. No significant differences were observed between the paired differences in thrombotic markers (UH vs ENOX), nor in the rate of recurrent ischemic events or major hemorrhage. CONCLUSIONS: In this subset of patients enrolled in the ESSENCE study, enoxaparin 1 mg/kg ql2hr significantly increased anti-Xa activity above that seen with unfractionated heparin, and reduced thrombin production without prolonging the thrombin time. The high anti-Xa activity achieved with enoxaparin was not associated with a loss of safety.

Biomarkers↗