Effect of lung-volume-reduction surgery in patients with severe emphysema

BACKGROUND: Although many patients with severe emphysema have undergone lung-volume-reduction surgery, the benefits are uncertain. We conducted a randomized, controlled trial of the surgery in patients with emphysema. Patients with isolated bullae were excluded because such patients are known to improve after bullectomy. METHODS: Potentially eligible patients were given intensive medical treatment and completed a smoking-cessation program and a six-week outpatient rehabilitation program before random assignment to surgery or continued medical treatment. After 15 patients had been randomized, the entry criteria were modified to exclude patients with a carbon monoxide gas-transfer value less than 30 percent of the predicted value or a shuttle-walking distance of less than 150 m, because of the deaths of 5 such patients (3 treated surgically and 2 treated medically). RESULTS: Of the 174 subjects who were initially assessed, 24 were randomly assigned to continued medical treatment and 24 to surgery. At base line in both groups, the median forced expiratory volume in one second (FEV1) was 0.75 liter, and the median shuttle-walking distance was 215 m. Five patients in the surgical group (21 percent) and three patients in the medical group (12 percent) died (P=0.43). After six months, the median FEV1 had increased by 70 ml in the surgical group and decreased by 80 ml in the medical group (P=0.02). The median shuttle-walking distance increased by 50 m in the surgical group and decreased by 20 m in the medical group (P=0.02). There were similar changes on a quality-of-life scale and similar changes at 12 months of follow-up. Five of the 19 surviving patients in the surgical group had no benefit from the treatment. CONCLUSIONS: In selected patients with severe emphysema, lung-volume-reduction surgery can improve FEV1, walking distance, and quality of life. Whether it reduces mortality is uncertain.     

Phase II study of bisantrene administered by continuous 72-hour infusion for advanced pancreatic adenocarcinoma

Eighteen ambulatory patients who had proven metastatic adenocarcinoma of the pancreas and measurable disease but no previous chemotherapy were treated with bisantrene given by constant central intravenous infusion over 72 hours at a total dose of 300 mg/m2 repeated every 3 to 4 weeks. No objective regression was seen. The median interval to progression was 6 weeks; the median survival was 14 weeks. Primary toxic reactions were nausea, vomiting, and leukopenia. In no instance were these life-threatening. When administered by the method we used, bisantrene cannot be recommended for treatment of advanced pancreatic adenocarcinoma.     

Antenatal and perinatal predictors of infant mortality in rural Malawi

BACKGROUND: The slow pace in the reduction of infant mortality in sub-Saharan Africa has partially been attributed to the epidemic of human immunodeficiency virus (HIV) infection. To facilitate early interventions, antenatal and perinatal predictors of 1st year mortality were identified in a rural community in southern Malawi. METHODS: A cohort of 733 live born infants was studied prospectively from approximately 24 gestation weeks onwards. Univariate analysis was used to determine relative risks for infant mortality after selected antenatal and perinatal exposures. Multivariate modelling was used to control for potential confounders. FINDINGS: The infant mortality rate was 136 deaths/1000 live births. Among singleton newborns, the strongest antenatal and perinatal predictors of mortality were birth between May and July, maternal primiparity, birth before 38th gestation week, and maternal HIV infection. Theoretically, exposure to these variables accounted for 22%, 22%, 17%, and 15% of the population attributable risk for infant mortality, respectively. INTERPRETATION: The HIV epidemic was an important but not the main determinant of infant mortality. Interventions targetting the offspring of primiparous women or infants born between May and July or prevention of prematurity would all have considerable impact on infant survival.     

Characterization of heat shock protein-specific T cells in atherosclerosis

A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) Vbeta expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR Vbeta5.2 family in all lines. These cytokine, chemokine, and Vbeta profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients. These results support the hypothesis that in some patients cross-reactivity of the immune response to bacterial HSPs, including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may explain the apparent association between atherosclerosis and periodontal infection.