Ronald Brookmeyer

The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.

Fifty-one patients with acute nonlymphocytic leukemia (16 with end-stage disease, 17 in second or third remission or in early relapse, and 18 in first remission) were given infusions of HLA-identical sibling marrow after cytoreduction with high doses of busulfan and cyclophosphamide. Actuarial two-year survival rates were 0 per cent, 29 per cent, and 44 per cent, respectively. Twelve patients are still alive and in remission after 327 to 1488 days, with 10 surviving beyond two years. Acute graft-versus-host disease and viral pneumonia were the major causes of death. Leukemic cells failed to clear in one patient with end-stage disease, and a relapse with meningeal leukemia occurred in another. Only one other relapse was seen--in a patient given a transplant during a third remission. Survival was favorably affected by younger age and transplantation during first remission. We conclude that high-dose chemotherapy with busulfan and cyclophosphamide, followed by allogeneic-marrow transplantation, can produce long-term remission of acute leukemia. Chemotherapy with high-dose busulfan and cyclophosphamide before transplantation provides an effective alternative to cyclophosphamide and total-body irradiation before transplantation for the treatment of acute nonlymphocytic leukemia.

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

BACKGROUND: Care for chronic renal failure involves management of complications and preparation for possible dialysis. Patients often are not evaluated by nephrologists in a timely manner. OBJECTIVE: To identify factors associated with late evaluation by a nephrologist and to assess whether late evaluation is associated with worse survival once patients develop end-stage renal disease (ESRD). DESIGN: National prospective cohort study. SETTING: 81 dialysis facilities throughout the United States. PATIENTS: 828 patients with new-onset ESRD. MEASUREMENTS: Time from first evaluation by a nephrologist to initiation of dialysis, classified as late (<4 months), intermediate (4 to 12 months), or early (>12 months); rate of death, from initiation of dialysis to an average of 2.2 years of follow-up; and demographic, clinical, and laboratory characteristics. RESULTS: After adjustment for potential confounders, late evaluation was more common among black men than white men (44.8% vs. 24.5%; P < 0.05), uninsured patients than insured patients (56.7% vs. 29.0%; P < 0.05) and patients with severe comorbid disease than those with mild comorbid disease (35.0% vs. 23.0%; P < 0.05). Compared with patients who had early evaluation, the risk for death was greater among patients evaluated late and was graded (hazard ratio, 1.3 [95% CI, 0.87 to 2.06] for patients with intermediate evaluation and 1.8 [CI, 1.21 to 2.61] for those with late evaluation) after adjustment for dialysis method, demographic characteristics, and socioeconomic status in Cox proportional hazards regression analysis. After additional adjustment for such factors as the presence and severity of comorbid conditions, the association remained graded (hazard ratio, 1.2 [CI, 0.73 to 1.82] for patients evaluated at an intermediate point and 1.6 [CI, 1.04 to 2.39] for those evaluated late). CONCLUSIONS: Late evaluation of patients with chronic renal failure by a nephrologist is associated with greater burden and severity of comorbid disease, black ethnicity, lack of health insurance, and shorter duration of survival.