Tuberculosis-associated severe CD4+ T-lymphocytopenia in HIV-seronegative patients from Dakar. SIDAK Research Group.

OBJECTIVES: To determine the frequency and associated features of severe CD4+ T-lymphocytopenia (<300 cells/mm(3)) in HIV-seronegative patients with tuberculosis. METHODS: Statistical analysis of 430 consecutively enrolled HIV-seronegative inpatients with tuberculosis in two teaching hospitals in Dakar, Senegal. RESULTS: The mean CD4 + cell count was 602+/-318.3 cells/mm(3). CD4 + cell counts were below 300 cells/mm(3)in 62 patients (14.4%). Patients with fewer than 300 CD4+ cells/mm(3)differed from those with higher counts in being less likely to have a positive smear for acid-fast bacilli; in having a higher frequency of extrapulmonary involvement (pleural effusion, adenopathy and miliary disease) and oral candidiasis; and in having smaller tuberculin reactions, lower haemoglobin levels, less cavitation and less patchy infiltration. After adjustment for gender and age, all differences remained except miliary disease. CONCLUSIONS: A substantial percentage (14.4%) of HIV-seronegative hospitalized patients for tuberculosis in a West African country presented with severe CD4 + T-lymphocyte depletion and had clinical and radiographic features indicative of more advanced disease and accompanying immunodepression. These results and those already published suggest that tuberculosis should be regarded as one of the diseases associated with a subgroup of patients with "idiopathic CD4 + T-lymphocytopenia".

Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood.

BACKGROUND: Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment. METHODS: We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child. FINDINGS: Among family members of the 25 SMN cases, there were ten with early-onset (< or = 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4.7 (95% CI 1.3-17.1; p = 0.02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially. INTERPRETATION: Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.