Glomerular filtration rate and N-terminal pro-brain natriuretic peptide as predictors of cardiovascular mortality in vascular patients.

OBJECTIVES: The purpose of this work was to assess the prognostic role of glomerular filtration rate (GFR) and NT-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality end points in the vascular population. BACKGROUND: The GFR and NT-proBNP have been shown to predict mortality end points in free-living and limited vascular populations, independent of traditional risk factors. However, their prognostic power in an unrestricted vascular population is poorly understood. METHODS: A total of 412 subjects from a vascular cohort with a history of either peripheral arterial disease (PAD) and/or other cardiovascular disease (CVD) were included in this prospective cohort analysis and followed for an average of 6.7 years. Outcome variables were all-cause mortality, ischemic heart disease (IHD) mortality, and any cardiovascular mortality. The prognostic roles of GFR and NT-proBNP levels were determined using multivariate survival analysis. RESULTS: Higher GFR (per 10 ml/min/1.73 m2) was significantly protective for all-cause mortality (hazard ratio [HR] 0.81, p < 0.001), IHD mortality (HR 0.82, p = 0.008), and CVD mortality (HR 0.84, p = 0.005). Conversely, NT-proBNP was not a significant predictor of any mortality end point. The GFR showed the strongest association in subjects with a history of other CVD. Although NT-proBNP did not demonstrate a significant prognostic role in any of the subgroups, the data were suggestive for patients with PAD alone. CONCLUSIONS: Glomerular filtration rate was a robust predictor of all-cause, IHD, and cardiovascular mortality in the vascular population, particularly in those with a history of other CVD, while NT-proBNP showed a suggestive association limited to the group with PAD only. These findings suggest that these markers must be selectively applied in the vascular population for greatest clinical utility.     

A light-hearted look at a lion-hearted organ (or, a perspective from three standard deviations beyond the norm) Part 2 (of 2 parts)

Throughout history, the heart has been associated not only with its life-sustaining function but also with its close ties to the human emotions. In this literature and internet review, we attempt to gather and organize information from both of these perspectives as they relate to the heart in the following 11 categories: (1) fun facts, (2) medical photography, (3) history, (4) languages (etymology), (5) nonmedical English expressions, (6) death, (7) the arts, (8) movie titles, (9) song titles, (10) Shakespeare, and (11) the Bible. Part 1 (previously published) covered the first five topics, and Part 2 will cover the last six topics. These data may be useful to those who are engaged in teaching about the cardiovascular system.     

Percutaneous biopsy in evaluation of lung nodules.

Management of an indeterminate pulmonary nodule is a diagnostic challenge that commonly confronts primary care physicians and specialists. Patients often present with this radiographic finding in the course of an unrelated medical evaluation. We examined our institution's experience with percutaneous biopsy of lung nodules to determine the impact of this procedure on overall patient care. Although significant complications are uncommon, the expedience of percutaneous lung biopsy often supplants a surgical opinion prior to initiation of therapy without added diagnostic benefit or cost-savings. Hence, we caution practitioners to use this technique as an adjunct to diagnosis and not a substitute for multidisciplinary care.     

Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities.

The incidence of transient hypogammaglobulinaemia of infancy (THI) detected in a major paediatric centre over a 10 year period was examined. A total of 2468 subjects less than 2 years of age had an IgG measurement taken between July 1979 and March 1990. Subjects with known immunodeficiencies were excluded. Fifteen patients were classified as having THI with an initial IgG level less than the fifth centile followed by a second measurement within the normal range. A further 24 patients were identified as having possible THI with a single low IgG concentration. There were 60,174 live births each year in Victoria in the years 1979-88. This gives an incidence of proved THI of 23 per 10(6) births, and including proved and probable THI an incidence of 61 per 10(6) live births. Of those patients with proved THI 12/15 had symptoms of either atopic disease or food allergy/intolerance and three had gastrointestinal symptoms without any evidence of atopic disease. At presentation 12/15 (80%) were IgA deficient and 9/15 had IgM concentrations less than the 20th centile for age. It is suggested that in view of the preponderance of atopic and food intolerant patients that subclinical protein loss from the bowel due to allergic inflammation may be a contributing factor to the development of THI in some patients.     

Case-control study of the alpha-synuclein interacting protein gene and Parkinson's disease.

We conducted a case-control study of the alpha-synuclein-interacting protein gene (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319 PD cases and 195 controls were genotyped for four SNCAIP variants, including a microsatellite repeat in intron 4 and three restriction fragment length polymorphisms (RFLP) proximal to the 5' terminal of exons 1, 4, and 6. None of the variants were found associated with PD overall. Global score statistics were not significant for four, three, and two loci haplotypes. All four loci were in linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene.     

Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody.

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.     

Concurrent systemic cryptococcosis and haemangiosarcoma in a dog

A young dog with progressive neurological signs was humanely killed by the injection of barbiturate for postmortem examination. Lesions in the nose, lung, pancreas, lymph nodes, kidneys and the meninges were heavily infiltrated with Cryptococcus neoformans. In addition, haemangiosarcoma was detected in the right atrium. The finding of systemic mycosis and neoplasia together in a young dog suggests an immunosuppressed state.