Angioscopic predictors of early adverse outcome after coronary angioplasty in patients with unstable angina and non-Q-wave myocardial infarction

BACKGROUND: Clinical and angiographic criteria have a limited ability to predict adverse outcome in patients with unstable angina who are undergoing percutaneous transluminal coronary angioplasty (PTCA). We investigated whether the use of angioscopy can improve prediction of early adverse outcome after PTCA. METHODS AND RESULTS: Angioscopic characterization of the culprit lesion was performed before PTCA in 32 patients with unstable angina and 10 with non-Q-wave infarction. Seven patients (17%) had an adverse outcome (myocardial infarction, repeat PTCA, or need for coronary artery bypass graft surgery) within 24 hours after PTCA. Six of 18 patients with a yellow culprit lesion had an adverse outcome compared with 1 of 24 in whom the culprit lesion was white (P = .03). Six of 20 patients with plaque disruption suffered an adverse outcome compared with 1 of 22 with nondisrupted plaques (P = .04). Six of 17 patients with intraluminal thrombus had an adverse outcome, whereas only 1 of 25 patients without thrombus suffered an adverse outcome (P = .01). Yellow color, disruption, and thrombus at the culprit lesion site were associated with an eightfold increase in risk of adverse outcome after PTCA. The prediction of PTCA outcome based on characteristics of the plaque that were identifiable by angioscopy was superior to that estimated by the use of angiographic variables. CONCLUSIONS: In patients with unstable angina and non-Q-wave infarction, angioscopic features of disruption, yellow color, or thrombus at the culprit lesion site can identify patients at high risk of early adverse outcome after PTCA. Angioscopy was superior to angiography for prediction of PTCA outcome.     

Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: analysis of 427 cases

The bcl-2 gene product inhibits apoptosis and is thought to participate in oncogenesis. Association of bcl-2 immunopositivity with improved prognosis of non-small cell lung cancers (NSCLC) is controversial. Although two studies have reported better survival in bcl-2-immunopositive NSCLCs, a third series has contradicted this finding. The authors studied a relatively larger case series involving 427 patients for whom detailed information on long-term follow-up was available to determine the prognostic significance of bcl-2 expression. The study included 252 adenocarcinomas (AC), 111 squamous cell carcinomas (SCC), and 64 large cell carcinomas (LC). After antigen retrieval, sections were immunostained using a monoclonal anti-bcl-2 antibody (1:60, Clone 124, Dako) and the avidin-biotin complex technique. Staining was scored as positive or negative and also on a semiquantitative scale as 0, low (<10%), moderate (10% to 75%), or extensive (>75%). Bcl-2 immunoreactivity was correlated with survival using the actuarial survival method, Kaplan-Meier method, and log-rank test and was not associated with statistically significant differences in survival for NSCLCs (P = .5537). Differences in survival remained insignificant even after NSCLCs were stratified for cell type, stage, or grade, singly or in combination. Therefore, using this method, bcl-2 immunopositivity does not appear to act as an independent prognostic indicator in NSCLCs.     

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.     

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.     

Prevalence of central autonomic neuropathy in elderly dialysis patients

BACKGROUND: Autonomic neuropathy is frequently present in dialysis patients. In addition, deterioration of autonomic function occurs with ageing. This study examines the true prevalence of autonomic neuropathy in elderly dialysis patients and questions whether the combination of age and uraemia further increases the chance of dysautonomia being present. METHODS: We compared the results of five different tests (30:15 ratio; Valsalva ratio; heart rate response to deep breathing and the blood pressure responses to sustained hand grip and standing) of parasympathetic and combined parasympathetic and sympathetic dysfunction in older haemodialysis patients (mean age 70.2 years), younger haemodialysis patients (mean age 48.1 years) and two groups of subjects with normal renal function (mean age 73.0 years and 42.5 years respectively). RESULTS: Parasympathetic dysfunction was most prevalent in older patients on dialysis (65.9% (95% confidence intervals 51.4-80.4%), compared with 33.3% (95% confidence intervals 19.0-47.5% in younger dialysis patients), and 11.8 and 0% in the old and young control groups respectively). Combined parasympathetic and sympathetic dysfunction was seen in 41.5% (95% confidence intervals 26.5-56.5%) and 11.9% (95% confidence intervals 2.1-56.5%) of the old and young dialysis patients respectively but not in any of the control subjects. No interaction was seen between age and subject type. CONCLUSIONS: We conclude that although older dialysis patients have severe impairment of cardiovascular autonomic innervation, the prevalence of dysfunction is not higher than would be expected in an ageing population with uraemia.