SPECIFICITY OF HEMATOPOIETIC STEM CELL HOMING

Homing of hematopoietic stem cells (HSC) may be defined as the cells’ ability to seek marrow stroma selectively, to interact with it and subsequently to lodge within it to initiate hematopoiesis. This complex process is no doubt mediated through multiple recognition/adhesion events. Homing may proceed through one of several alternative mechanisms, however, such as through physical trapping of stem cells by marrow ultrastructural elements or through the providing of a selective survival and/or proliferative advantage by marrow. A third alternative that provides for the central element of stem cell homing—its high degree of specificity—is through the action of a specific homing protein in HSC. There are data to support this latter mechanism of stem cell homing as the correct one, and the nature of this protein may be similar to that of the lymphocyte homing receptors that are lectin-like molecules. Lectin–carbohydrate interactions are known to provide enormous specificity to cell recognition processes and to participate in cellular targeting. Leukemic cells have recently been demonstrated to home to marrow stroma and proliferate in the same way as normal stem cells. Thus, identification of proteins or other adhesion molecules that participate in normal and malignant cell homing could lead to more specific recruitment regimens for tumour-free collections.     

SIMULTANEOUSLY MODELLING CENSORED SURVIVAL DATA AND REPEATEDLY MEASURED COVARIATES: A GIBBS SAMPLING APPROACH

Recent methodologic developments in the analysis of longitudinal data have typically addressed one of two aspects: (i) the modelling of repeated measurements of a covariate as a function of time or other covariates, or (ii) the modelling of the effect of a covariate on disease risk. In this paper, we address both of these issues in a single analysis by modelling a continuous covariate over time and simultaneously relating the covariate to disease risk. We use the Markov chain Monte Carlo technique of Gibbs sampling to estimate the joint posterior distribution of the unknown parameters of the model. Simulation studies showed that jointly modelling survival and covariate data reduced bias in parameter estimates due to covariate measurement error and informative censoring. We illustrate the methodology by application to a data set that consists of repeated measurements of the immunologic marker CD4 and times of diagnosis of AIDS for a cohort of anti-HIV-1 positive recipients of anti-HIV-1 positive blood transfusions. We assume a linear random effects model with subject-specific intercepts and slopes and normal errors for the true log and square root CD4 counts, and a proportional hazards model for AIDS-free survival time expressed as a function of current true CD4 value. On the square root scale, the joint approach yielded a mean slope for CD4 that was 7 per cent steeper and a log relative risk of AIDS that was 35 per cent larger than those obtained by analysis of the component sub-models separately.     

Fundamentals of Obstetric, Gynecologic, and Neonatal Nursing Research: Part I

The basics of obstetric, gynecologic, and neonatal nursing research are discussed in a three-part article series. In Part I, the first six steps of the research process, including the research problem, literature review, theoretical framework, variables, hypotheses, and sampling, are explained. Parts II and III will appear in the July/August and September/October 1989 issues respectively. Highlighting each step of the research process are examples from published nursing research in the areas of obstetric, gynecologic, and neonatal nursing.     

The rationale behind early prevention of cardiovascular disease in young people

The rationale for primary prevention of cardiovascular disease(CVD) in young people is based on the applicability to youthof the causal aetiologic model of CVD among adults. Young peoplein developed countries exhibit early atherosclerotic lesions,as well as elevated physiological risk factors. Young peoplein the United States consume a higher fat diet than recommended,approximately half are physically active and nearly 1 in 5 graduatefrom high school as regular cigarette smokers. Not only arerisk factors and risk behaviours evident in youth, but theyappear to track through adolescence and into adulthood. Thisreview suggests that early prevention efforts are prudent andmay be critical.     

Erythropoiesis: Erythrocyte Deformability is Reduced and Fragility increased by Iron Deficiency

Hypochromic and microcytic erythrocytes, resulting from absolute iron deficiency, have a shortened survival due to ineffective production coupled with accelerated reticuloendothelial cell sequestration once released into the circulation. To explore the contribution of diminished deformability and increased fragility to these in vivo phenomena, iron status was correlated with the corresponding in vitro measurements using ektacytometry on whole erythrocytes or resealed ghost membranes. Compared to normal controls (Group 1: n = 15), those with iron deficiency of unknown origin (Group 2: n = 15), or when associated with primary proliferative polycythemia (Group 3: n = 20), were significantly less deformable and more fragile, whereas the latter category of patients, who were not anaemic (Group 4: n = 33), occupied an intermediate position. These observations support the contention that shortened intramedullary and extramedullary lifespan is contributed to by the altered physical characteristics of the red cell membrane. This observation is therapeutically important since the lesion can be readily corrected by oral iron supplementation which, at the same time, reverses the symptoms of the anaemia and prevents the development of paradoxical hyperviscosity. Additionally, it is speculated that the risk of thrombotic events in the polycythemic group may be reduced, since these appear to occur more frequently in the face of depleted body iron stores.     

Trisomy 11: an association with stem/progenitor cell immunophenotype

Summary. The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patient ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n=7). Ml (n=5), M4/5 (n=2), M3 (n=l)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for >34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemo-therapeutic regimens and an unfavourable prognosis.     

Selection of medical students and the maldistribution of the medical workforce in Queensland, Australia

ABSTRACT: The relative shortage of both general practitioners and specialists providing medical services to rural areas disadvantages people living in the country. This maldistribution of the medical workforce is due in part to the medical education system. The selection and socialisation of medical students, the adequacy of training for rural practice and the continuing support of rural doctors must all be addressed. While progress is being made in vocational training and continuing support of rural practice, aspects of undergraduate education continue to contribute to the shortage of rural practitioners.
The school and home addresses of 1991 school leavers in the 1992 intake into first year medicine at the University of Queensland were analysed and compared with those previously reported. Results indicated that students from rural backgrounds remain underrepresented despite previous recommendations to redress the disproportionately low number of rural students entering medical school. Changes to the selection of medical students aimed at increasing the number of rural students entering the course are discussed. This issue needs to be addressed in conjunction with many other factors contributing to the maldistribution of general practitioners if the shortage of rural medical practitioners is to be ultimately corrected.     

Community-wide cardiovascular disease prevention in young people: Long-term outcomes of the Class of 1989 Study

The Class of 1989 Study, as part of the Minnesota Heart HealthProgram, examines 2 cohorts of adolescents in 2 communitiesin northcentral US. The goal of the study was to reduce therisk of cardiovascular disease among young people in one ofthe cohorts through changes in smoking, eating patterns andphysical activity levels. Because of its importance as a healthbehaviour, alcohol use was also addressed, even though it wasnot a specific target of the Minnesota Heart Health Program.The behaviour patterns of both cohorts were surveyed annuallyin schools from 1983 to 1989. One cohort additionally was exposedto 5 years of behavioural health education in their schools,peer leadership and a community-wide programme for adults. Thebehaviour health education curricula focused on skills, competencies,role models and norms for healthier behaviour. Students in theeducated cohort demonstrated significant reductions in smokingfrom 1984 to 1989. Females in the educated cohort also consistentlyreported significantly healthier eating habits and physicalactivity patterns than the reference cohort. Short-term changesin alcohol use were also noted among both males and females,consistent with the results of other research studies of school-basedprogrammes. Results for eating patterns and physical activitypatterns with males were not as robust as with females. Nevertheless,behavioural health programmes in schools coordinated with community-wideeducation and campaigns with adults appears promising.