Plasma exchange in systemic lupus erythematosus.

Eight out of 10 patients studied longitudinally received benefit from plasmapheresis. The patients were used as their own controls, being treated in a steady state as far as was possible. Levels of circulating complexes did not bear a close relationship with clinical results. On the evidence plasma exchange alone does not appear to represent an important part of the long-term management of patients with systemic lupus erythematosus but may well be of value in combination with other therapy.     

Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease.

In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p < 0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF <30% were similar (area under the curves = 0.83 and 0.80, both p < 0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves; BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD. OBJECTIVES: The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance. BACKGROUND: Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain. METHODS: In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded; BNP and NTproBNP were measured by radioimmunoassay. RESULTS: Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p < 0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p < 0.001), age (0.44 and 0.47, both p < 0.001), and creatinine clearance (-0.51 and -0.51, both p < 0.001). Areas under receiver-operating characteristic curves for detection of LVEF <30% were similar (0.83 and 0.80, both p < 0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves. CONCLUSIONS: In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.     

Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study

PURPOSE: To determine if hormone therapy results in better cognitive function in older postmenopausal women. SUBJECTS AND METHODS: The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized, placebo-controlled trial involving 2763 women with coronary disease. Women were assigned randomly to conjugated estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) in one tablet daily or identical placebo; they were followed for a mean (+/- SD) of 4.2 +/- 0.4 years. Participants at 10 of the 20 HERS centers were invited to enroll in the cognitive function substudy. At the end of the trial, we measured cognitive function in 517 women in the hormone group and 546 in the placebo group using six standard tests: the modified Mini-Mental Status Examination, Verbal Fluency, Boston Naming, Word List Memory, Word List Recall, and Trails B. Cognitive function was not measured at baseline. RESULTS: The mean age of participants at the time of cognitive function testing was 71 +/- 6 years. There were no differences in age-adjusted cognitive function test scores between the two treatment groups, except that women assigned to hormones scored worse on the Verbal Fluency test than women assigned to placebo (15.9 +/- 4.8 vs. 16.6 +/- 4.8, P = 0.02). Adjustment for other potential confounders and restriction of the analyses to women who had been adherent to study medication did not change the results. CONCLUSION: Among older postmenopausal women with coronary disease, 4 years of treatment with postmenopausal hormone therapy did not result in better cognitive function as measured on six standardized tests. Whether these results also apply to elderly women without coronary disease cannot be determined from this study.     

Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.     

Comparison of phenytoin and gold as second line drugs in rheumatoid arthritis.

Phenytoin has known immunosuppressive properties, and a recent pilot study has indicated that it may have a second line effect in rheumatoid arthritis (RA). To evaluate this role 60 patients with active RA were randomly allocated to receive either oral phenytoin or intramuscular gold. The two treatment groups were comparable at the outset (Mann-Whitney U test). Twenty four patients completed 24 weeks of therapy in each group and no unexpected side effects were encountered. All variables except haemoglobin (Hb) improved significantly in the gold group while in the phenytoin group significant improvement was limited to articular index, erythrocyte sedimentation rate (ESR), and Hb. Between group comparison (Mann-Whitney) at week 24 showed a significant advantage of gold over phenytoin for pain score and morning stiffness. Thus phenytoin appears to exert a less potent second line effect than gold and is unusual in influencing laboratory indicators of disease activity more than clinical variables. This is likely to limit its usefulness as a second line drug in RA.     

Preliminary results from the third flight of the Millimeter Anisotropy Experiment (MAX)

Preliminary results from the June 1991 flight of MAX are presented. Simultaneous observations were made in bands centered at 6, 9, and 12 cm-1 with a bolometric receiver operating at 300 mK. The experimental sensitivities are the highest reported at angular scales of 0.3 degrees to 1.0 degrees. Interstellar dust is observed to have an emissivity [symbol, see text] nu 1.4+/-0.3 and to correlate with the Infrared Astronomical Satellite (IRAS) 100- map. After removal of emission from interstellar dust, 1.3 hr of integration on a 6 degrees scan yields an upper limit of temperature difference Delta T/T < 2.6 x 10(-5) at a Gaussian autocorrelation function centered at 0.5 degrees. The experiment and data analysis are described.     

Diagnosis, management, and treatment of Alzheimer disease: a guide for the internist

Alzheimer disease (AD) is a diagnosis of inclusion based on patient history, physical examination, neuropsychological testing, and laboratory studies; however, there is no definitive diagnostic test for AD. Early recognition of AD allows time to plan for the future and to treat patients before marked deterioration occurs. Effective treatment requires monitoring of symptoms, functional impairment, and safety, and the use of multiple treatment modalities including pharmacotherapy, behavioral management, psychotherapies, psychosocial treatments, and support and education for families. Pharmacotherapeutic agents available for AD only provide symptomatic relief. The cholinesterase inhibitors, tacrine and donepezil, are effective in improving cognition, delaying nursing home placement, and improving behavioral complications in some patients. Other cholinesterase inhibitors are in development, as are other cholinomimetic agents such as muscarinic and nicotinic receptor agonists. Symptomatic treatments are available for the psychiatric manifestations of AD. Anti-inflammatories, antioxidants, neurotrophic factors, and other agents are promising new treatments for the future.