Female heterozygotes of the fra(X) form of mental retardation show variable degrees of mental impairment and phenotype expression of the disorder. This might be an effect of inactivation of the X-chromosome which carries the fra(X)(q). Prior replication studies in heterozygous carriers gave contradictory results with respect to possible genotype-phenotype correlation. In the interpretation of these studies it is important to understand the effect of BrdU on the fra(X)(q) expression. In a group of 13 hemizygous patients with fra(X)(q) and 7 heterozygous carriers we studied the effect of BrdU on fra(X) expression. In the heterozygous carriers the use of BrdU resulted in a significant suppression of the fra(X)(q), while in hemizygous patients no difference in fra(X)(q) frequency with or without BrdU could be observed. It can be concluded that BrdU suppresses the fra(X)(q) preferentially on the inactive X-chromosome. Thus the fra(X)(q) frequency on the active X-chromosome is of primary importance in phenotype correlation studies among heterozygous carriers. In our group of heterozygous carriers we observed a negative correlation between (IQ) phenotype and fra(X)(q) expression on the active X-chromosome. This suggests that the gene for the fra(X)(q) form of mental retardation is on the X-chromosome and undergoes inactivation.

Bromodeoxyuridine↗

PubMedDate not supplied

An alternating chemotherapy combination (MACOBLE) for intermediate and high-grade non-Hodgkin's lymphoma.

From June 1983 to February 1986, 48 patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL) received a CHOP based combination with the addition of etoposide on days 1 and 2, bleomycin days 1 and 10 and methotrexate 1.5 g/m2 on day 10 (MACOBLE). Their median age was 59 years, 20 (42 per cent) had an ECOG performance status (PS) of 2 or 3, 24 (50 per cent) had stage IV disease, 25 (52 per cent) B symptoms and 21 (44 per cent) bulk (greater than 10 cm) disease. With a median follow-up of 62 months, 12 patients are alive, 10 of whom are disease-free. Median overall survival was 13 months (95 per cent confidence interval 6-23 months) with actuarial 5-year survival of 25 per cent (95 per cent confidence interval 13-37 per cent). Factors associated with inferior survival were ECOG PS 2 or 3 (P = 0.004), B symptoms (P = 0.013) and bulk disease (P = 0.017). These data suggest that, when treating an unselected patient population, attempts to increase the intensity of first-line chemotherapy may not improve the outcome.

Adult↗

PubMedDate not supplied

Melioidosis survey in Kenya.

Explore the source record for details and available documents.

Burkholderia pseudomallei↗

PubMedDate not supplied

Serological responses to brucellosis in HIV-seropositive patients.

Serial sera from 2 patients infected with the human immunodeficiency virus (HIV) type 1 attending a clinic in Nairobi, Kenya, and with blood cultures yielding Brucella melitensis, were tested by enzyme-linked immunosorbent assay for their serological response (Brucella-specific immunoglobulin (Ig) M and IgG) to Brucella infection. Antibody responses were comparable to those of immunocompetent individuals, one patient showing serology typical of acute brucellosis, the other of chronic brucellosis. Sera from 100 other patients, 65 of whom were HIV-positive, attending the same clinic but whose routine microbiological cultures were negative for Brucella, were tested retrospectively for Brucella-specific antibody. Eight had Brucella-specific IgM and IgG, 6 had IgM only and 21 had IgG only, suggesting relatively high levels of exposure to Brucella in the study cohort. There was no association between Brucella antibody status and HIV status. Brucellosis is probably underdiagnosed in Kenya. Brucella serology may be helpful in the diagnosis of patients with non-specific symptoms in East Africa, regardless of HIV status.

Antibodies, Bacterial↗

PubMedDate not supplied

Royal Society of Tropical Medicine and Hygiene Meeting at Manson House, London, 12 December 1996. HIV and pneumococcal infection in Africa. Microbiological aspects.

By the 1930s several studies had shown that Streptococcus pneumoniae was an important pathogen in Nairobi (Kenya) and various risk factors for infection were recognized, including seasonally cold conditions, overcrowding and recent arrival in the city. Research into pneumococcal disease declined with the arrival of penicillin but recently interest has been rekindled by recognition of the pneumococcus as a human immunodeficiency virus (HIV)-associated pathogen and by the emergence of antibiotic resistance. The pneumococcus and its association with HIV were studied during the course of the Wellcome Trust/Kenya Medical Research Institute HIV Programme in Nairobi (1988-1993). There were generally high rates of pneumococcal disease. The pneumococcus (with tuberculosis and salmonellosis) was a major HIV-related pathogen. One study showed HIV seropositivity to confer a relative risk of 17.8 for pneumococcal infection. Recurrent infection accounted for a large proportion (25%) of disease episodes in a longitudinally studied cohort of HIV patients. There were higher pneumococcal carriage rates in HIV-positive than in HIV-negative patients (28% vs. 16%, P = 0.003). High rates of resistance were found to penicillin (25%). Molecular characterization of penicillin-resistant strains identified 11 separate clones, showing great genetic diversity in a small sample of isolates, and there was evidence of horizontal spread of penicillin-binding protein genes between separate lineages. Molecular characterization of isolates from patients with recurrent disease suggested that both relapse and reinfection might occur. There was molecular evidence of transfer of capsular genes between clones (serotype switching). The overall spectrum of serotypes resembled those reported elsewhere, most serotypes being included in the 23-valent vaccine. Higher numbered serotypes were associated with respiratory tract source and antibiotic resistance. Various methods were used to show 82% concordance between pernasal and blood isolates in pneumonia cases. HIV-seropositive patients were more prone to infection with penicillin- and tetracycline-resistant organisms than seronegative patients (penicillin, 27% vs. 7%; tetracycline, 40% vs. 17%), a difference reflected by different serotype profiles in the 2 groups. These studies highlight the importance of the pneumococcus as an HIV-related pathogen in one part of Africa. The high rates of antibiotic resistance are a cause of concern. There should be continued monitoring of resistance patterns, and assessments of the significance of pneumococcal disease made elsewhere in Africa are to be encouraged.

Cohort Studies↗

PubMedDate not supplied

Body temperature and the specific heat of water.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer.

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European-Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin-paclitaxel regimen over cisplatin-cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗