Guidance for the implementation of best practice for the care of patients with tuberculosis.

The first two chapters of Best practice for the care of patients with tuberculosis: a guide for low-income countries include an introduction and guidance regarding implementation of best practice. The background to how the guide was developed is significant, as it was developed in collaboration with nurses and other health workers working in the most challenging settings. It therefore provides realistic and practical guidance for best practice where patient loads are large and resources are stretched. Guidance regarding standard setting and clinical audit is an important part of enabling people to recognise the strengths that already exist in their practice and approach those areas that require change in a systematic and practical way. The guide itself consists of a series of standards covering different aspects of patient care, from the moment they seek health care with symptoms to their diagnosis to early stages of treatment, directly observed treatment, the continuation phase and transfer of treatment. There are also standards relating specifically to HIV testing and the care of patients co-infected with tuberculosis and HIV. The standards themselves will appear in full in the subsequent chapters of this series.     

Hb Iowa or alpha 2 beta 2(119)(GH2)Gly----Ala

Hb Iowa with a Gly----Ala mutation at position beta 119(GH2) was observed in a Black infant and her mother. The baby was also heterozygous for Hb S; Hb Iowa was confused with Hb F at birth because its electrophoretic mobility was similar to that of Hb F1. The beta chain of Hb Iowa could be readily separated from the beta A, alpha, and gamma chains by polyacrylamide gel electrophoresis and by reversed phase high performance liquid chromatography. Structural characterization was through amino acid analyses of peptides isolated from a tryptic digest of the aminoethylated beta-Iowa chain. The Gly----Ala replacement in Hb Iowa does not affect its stability and oxygen carrying properties; hematological data for mother and child were within normal ranges.     

The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone

A subset of human T cells has recently been described. These cells express the CD3 complex but they do not carry the classical T-cell receptor (TCR)-alpha/-beta heterodimer on their surface (WT31- CD3+). Instead, they express a TCR-gamma chain associated with another type of polypeptide termed TCR-delta. We report here that a T-cell clone with natural killer (NK)-like activity, WM-14, had a disulfide bridged TCR-gamma homodimer associated with CD3 on its surface. The TCR-gamma chains of WM-14 cells were present in three different glycosylation forms of 43, 40, and 38 kDa, but they appeared to contain the same polypeptide backbone. Since cytotoxicity by WM-14 could be inhibited by anti-CD3 antibodies, we concluded that the TCR-gamma-CD3 complex was involved in the NK-like unrestricted killer activity. Although normal CD3-gamma, CD3-delta, and CD3-epsilon chains were present in this clone, the association with the TCR-gamma homodimer may be the cause of a complete processing of the N-linked oligosaccharides attached to the CD3-delta chain.     

Interaction of malnutrition and difluoromethylornithine-induced intestinal mucosal damage: degree of severity and subsequent recovery

The interaction between malnutrition and exposure to a mucosal damaging agent, difluoromethylornithine (DFMO), was examined by monitoring the small-intestinal changes in weanling rats. Malnutrition as induced by the expanded-litter method resulted in severe reduction in body weights in the expanded litters as compared to normal litters. Subsequent treatment of malnourished and well-nourished pups with DFMO for 7 days resulted in decreases in small-intestinal weights and enzyme contents. A 2 factors (well-nourished and malnourished) by 2 factors (DFMO-treated and nontreated) analysis of variance showed no interaction between malnutrition and DFMO treatment in terms of food intake, total mucosal protein, and contents of enterokinase, leucine aminopeptidase and sucrase. Very slight and insignificant interactions (p less than or equal to 0.2) were found for body weights, intestinal weights and total DNA content. Only one parameter studied, the maltase content, showed significant interaction between malnutrition and DFMO treatment (p less than 0.05). Three weeks after the withdrawal of DFMO, essentially all the changes caused by DFMO recovered. But those changes caused by malnutrition did not, such that the malnourished group, whether treated with DFMO or not, still remained significantly less than the control group in their small-intestinal parameters. Analysis of variance showed no interaction between malnutrition and DFMO treatment in the recovery phase. The results suggest that malnutrition is a more important factor in determining the intestinal damage and that malnutrition in the immediate postnatal period does not increase the sensitivity of the small intestine to the damaging effect of DFMO.     

Rapid HIV type 1 testing of women presenting in late pregnancy with unknown HIV status in Lima, Peru

We studied the feasibility and acceptability of HIV-1 testing using rapid serological assays in pregnant women presenting in late pregnancy without prior HIV-1 testing. Pregnant women presenting to the emergency room at the Instituto Materno-Perinatal in Lima, Peru, were offered on-site rapid HIV-1 testing. Consenting women were provided HIV counseling and had samples taken for rapid detection of antibodies in the blood and oral secretions. Women testing HIV-1 seropositive by one or both assays were offered standard HIV obstetrical care including antiretrovirals. Between October 2000 and August 2001, 3543 women were tested for HIV-1 antibodies through the rapid testing protocol. Twenty-seven women tested positive by one or both assays. Standard EIA results were negative for two of the 27 women and EIA results were not available for an additional three women. Seventeen of the 19 women (89%) for whom delivery information is available received antiretroviral therapy prior to delivery. Eighty percent of the women treated with nevirapine received the drug at least 1 hr prior to delivery. Study personnel reported problems with performing the rapid assays for less than 1% of the samples and the majority of the women did not express a preference for either the oral fluid or blood sample collection. While HIV-1 testing early in pregnancy is preferable, rapid HIV-1 testing in late pregnancy or at delivery is feasible, acceptable to most women, and allows for timely intervention to reduce maternal-child transmission.     

Comparative in vitro analysis of different hematopoietic cell populations from human cord blood: in search of the best option for clinically oriented ex vivo cell expansion

BACKGROUND: Ex vivo expansion of hematopoietic stem and progenitor cells has become a priority in the experimental hematology arena. In this study we have obtained different hematopoietic cell populations from umbilical cord blood and simultaneously assessed their proliferation and expansion kinetics. Our main goal was to determine which one of these cell populations would be more suitable for clinical‐grade ex vivo expansion. STUDY DESIGN AND METHODS: By using immunomagnetic‐negative selection and cell sorting, five cell populations were obtained: unseparated mononuclear cells (MNCs; I); two lineage‐negative cell populations, one enriched for CD34+ CD38+ cells (II) and the other enriched for CD34+ CD38? cells (III); and two CD34+ cell fractions purified by fluorescence‐activated cell sorting, one containing CD34+ CD38+ cells (IV) and the other containing CD34+ CD38? cells (V). The kinetics of such populations were analyzed in both relative and absolute terms. RESULTS: No expansion was observed in Population I; in contrast, significant increments in the numbers of both progenitor and stem cells were observed in cultures of Populations II to V. Population V (reaching 12,800‐fold increase in total cells; 1280‐fold increase in CD34+ cells; 490‐fold increase in colony‐forming cells; and 12‐fold increase in long‐term culture–initiating cells) showed the highest proliferation and expansion potentials. CONCLUSION: Our study suggests that the cell fraction containing greater than 98% CD34+ CD38? cells would be the ideal one for large‐scale ex vivo expansion; however, based on our data, it seems that, except for MNCs, all other cell populations could also be used as input cell fractions.