The human T-cell V gamma gene locus: cloning of new segments and study of V gamma rearrangements in neoplastic T and B cells

The authors have analyzed the involvement of V gamma and J gamma segments in TRG gamma rearrangement from a series of 40 acute lymphoblastic leukemia (ALL), including 25 T- and 15 B-lineage cases, in which TRG gamma are rearranged. Sixty-five rearranged alleles were studied. The authors first describe the cloning and sequencing of two variable segments, V gamma 11 and psi V gamma 12, which rearrange in T- and B-neoplastic cells. To date three subgroups of translatable V gamma segments have been described. The authors show that V gamma 11 is the unique member of a new fourth V gamma subgroup that also rearranges in normal polyclonal T cells and that psi V gamma 12 is located at 5- kilobase (kb) downstream to V gamma 11. As shown by DNA sequence analysis, V gamma 11 shares a 60% homology with V gamma 10 (third subgroup) and a 50% homology with V gamma 9 (second subgroup) but no appreciable homology with the V gamma segments from the first family. In contrast to psi V gamma 12, V gamma 11 is translatable. In this paper the authors have also attempted to determine which V gamma segments were rearranged in the ALL cases by hybridization with a J gamma probe and genomic probes specific of the four subgroups. In the 54 instances in which the rearrangement was consistent with J gamma 1 or J gamma 2 involvement, the authors have identified the corresponding V gamma segments and have not found any other rearrangements suggestive of the existence of further V regions. The V gamma segments, belonging to the first subgroup, were the most frequently used (41 alleles). V gamma 9, V gamma 10, V gamma 11, and psi V gamma 12 were found rearranged in cases 3, 4, 5, and 1, respectively. No cases using the pseudo psi V gamma 1, psi V gamma 5, and psi V gamma 6 segments were found. Pseudo V gamma segments were not found rearranged in T cells, while V gamma 2 and V gamma 4, segments are frequently used. In contrast to the V gamma I gene rearrangement, the involvement of the V gamma II, V gamma III, and V gamma IV subgroups was most frequently observed in T-ALL with stage II differentiation (CD7+, CD4+, and/or CD8+, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-), than in those with stage I (CD7+, CD4-, CD8-, CD3-) and stage III (CD7+, CD4+/-CD8+/-CD3+).(ABSTRACT TRUNCATED AT 400 WORDS)     

Parasitic culture of buffy coat for diagnosis of visceral leishmaniasis in human immunodeficiency virus-infected patients.

Two samples of buffy coat from the peripheral blood of 25 human immunodeficiency virus-positive patients with proven visceral leishmaniasis, as determined with a bone marrow aspirate (stain and culture), were cultured onto Schneider's and Novy-McNeal-Nicolle media. Hemoculture positivity was 67%. The average growing time was 10 days. This is an easy, noninvasive, and sensitive technique.     

Evaluation of antiretroviral therapy results in Blantyre,Malawi

We performed a cross sectional study to evaluate treatment results of the paying antiretroviral therapy clinic of Queen Elizabeth Central Hospital, Blantyre. The only antiretroviral therapy was a fixed drug combination of stavudine, lamivudine and nevirapine.

Methods

Interviews, laboratory tests (CD4 count, viral load, nevirapine plasma levels, transaminases) and data extraction from files. 422 (59 %) of the patients who started antiretroviral therapy since 2000 were lost to follow up. The 176 patients enrolled in the study had good virological and excellent clinical treatment results. The most common side effect was peripheral neuropathy. Nevirapine plasma levels were remarkably high and associated with successful virological treatment results. Two simple adherence questions pertaining to the use of medication in the previous 8 days corresponded well with nevirapine levels. The most important reasons for non-adherence were shortage of drugs in the hospital pharmacy and personal financial constraints.

Conclusions

1. Many patients were lost to follow up.
2. High nevirapine levels contributed to good therapy results in those studied.
3. Simple adherence questions predicted sub-therapeutic nevirapine levels.
4. Antiretroviral drug supply needs to be uninterrupted and free of charge, to prevent avoidable non-adherence.

     

Differing mental health practice among general practitioners,private psychiatrists and public psychiatrists

Background

Tuberculosis is still a great challenge to public health in Brazil and worldwide. Early detection followed by effective therapy is extremely important in controlling the disease. Recent studies have investigated reasons for delays in treatment, but there is no agreed definition of what constitutes an "acceptable" delay. This study investigates factors associated with total delay in treatment of tuberculosis.

Methods

A cohort of adult cases of pulmonary tuberculosis diagnosed over a two-year period was studied. Patients were interviewed on entry, reporting the duration of symptoms before the start of treatment, and sputum and blood samples were collected. It was decided that sixty days was an acceptable total delay. Associations were investigated using univariable and multivariable analysis and the population attributable fraction was estimated.

Results

Of 1105 patients, 62% had a delay of longer than 60 days. Age, sex, alcoholism and difficulty of access were not associated with delays, but associations were found in the case of unemployment, having given up smoking, having lost weight and being treated in two of the six health districts. The proportion attributable to: not being an ex-smoker was 31%; unemployment, 18%; weight loss, 12%, and going to the two worst health districts, 25%.

Conclusion

In this urban area, delays seem to be related to unemployment and general attitudes towards health. Although they reflect the way health services are organized, delays are not associated with access to care.     

Amphotericin B lipid complex versus no treatment in the secondary prophylaxis of visceral leishmaniasis in HIV-infected patients

OBJECTIVES: Visceral leishmaniasis (VL) in HIV-positive patients is characterized by a chronic course with frequent relapse. The aim of this study was to evaluate the efficacy and safety of amphotericin B lipid complex (ABLC) in preventing VL relapses in HIV-infected patients. METHODS: This was a multicentre, open-label (with blinded centralized randomization), parallel, no-treatment, controlled clinical trial. HIV-infected patients, with at least one previous treated episode of VL and with negative bone marrow aspirate for Leishmania parasites prior to the study, were randomized to receive either ABLC 3 mg/kg/day every 21 days (ABLC) or no treatment (NT). Patients were followed-up every 9 weeks for up to 12 months, and the efficacy was measured as the proportion of patients remaining free (non-relapse) of VL at 1 year of follow-up. The primary analysis was performed on an intention-to-treat basis. RESULTS: One hundred and fifteen patients were screened, but only 17 were randomized: eight in the ABLC group and nine in the NT group. The intention-to-treat analysis of data showed 50% of patients remaining free of VL at 12 months of follow-up (95% CI = 15.7%, 84.3%) in the ABLC group, and 22.2% (95% CI = 2.8%, 60.0%) in the NT group. The non-relapse odds ratio was 3.5 (95% CI = 0.30%, 52.0%) favouring ABLC. ABLC was well tolerated: patients only presented infusion-related mild adverse events. No patients from either group discontinued treatment or died during follow-up. CONCLUSIONS: ABLC, administered every 21 days for 12 months, is useful as secondary prophylaxis in preventing VL relapse in HIV-infected patients, and is well tolerated.     

Epidemiological Differentials of Hepatitis B Carrier State in the Army : A Community Based Sero-epidemiological Study

Background

Most available studies on seroprevalence of Hepatitis B in the Armed Forces and also at the national level are based on hospital patients and blood donors. Hence, there was a perceived need to undertake a seroepidemiological study on an adequately large and representative random sample of the general cross section of Army personnel, with a view to obtain the exact picture of the frequency and distribution of HBV in the Army.

Methods

A community based cross sectional study with random samples from four groups were drawn, viz recruits from the Army Medical Corps (AMC) and other Arms and Services; AMC personnel and personnel from other Arms and Services who had served for more than 10 years. A structured pretested questionnaire was administered to all participants and blood samples were drawn aseptically subsequently, with separation of serum and testing by ELISA technique for HBsAg. Multivariate analysis using multiple logistic regression procedure was done after appropriate data entry.

Results

The overall seroprevalence was 7.9% (95%CI = 6.5% to 9.26%). The differential seroprevalence in the four groups being 7.72%, 7.92%, 8.28% and 7.75% respectively. There was statistically no significant difference as regards the seroprevalence levels [p > 0.05]. As regards serving medical personnel, the seroprevalence was observed to be higher among personnel involved in direct nursing care. On multiple logistic regression analysis, two risk factors emerged as independent and significant predictors of hepatitis B positivity. These were history of sexual exposure with commercial sex workers (CSWs) (OR = 3.06, p < 0.01) and history of having taken injections from civil sources (OR = 1.92, p < 0.001).

Conclusion

The relatively high level of seroprevalence among recruits has led to certain recommendations on testing and further studies in specific groups, based on the findings of the study.Key Words: Health care workers, Hepatitis B - seroprevalence, Military personnel, Multivariate analysis, Risk factors