The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism.

The minor histocompatibility antigen (mHag) HA-1 is the only known mHag for which mismatching is correlated with the development of severe graft versus host disease (GvHD) after human leukocyte antigen-identical bone marrow transplantation. HA-1 was found to be a nonapeptide derived from an allele of the KIAA0223 gene. The HA-1-negative allelic counterpart encoded by KIAA0223 had one amino acid difference from HA-1. Family analysis with HA-1 allele-specific polymerase chain reaction showed an exact correlation between this allelic polymorphism and the HA-1 phenotype. HA-1 allele typing of donor and recipient should improve donor selection and allow the determination of bone marrow transplantation recipients with high risk for HA-1-induced GvHD development.

alpha-Interferon and 5-fluorouracil: possible mechanisms of antitumor action.

We have treated 17 patients with 5-fluorouracil (5-FU, 300 mg/m2/d by continuous ambulatory infusion for 8 weeks) and interferon alfa-2b (escalating doses to cohorts of three to five patients, given subcutaneously on a daily schedule at 2.0, 3.5, 5.0, and 10.0 x 10(6) IU/m2). The two major toxicities observed were mucositis, which occurred in 10 patients at 2 weeks and required interruption of therapy and 5-FU dose reduction, and chronic fatigue syndrome, which required reduction of the dose of interferon alfa-2b. Other toxicities seen included elevation in BUN/creatinine, elevation in liver function tests, alopecia, diarrhea, confusion, and myelosuppression. No toxic deaths occurred. Five responses were observed: two complete responses, two partial responses, and one minor response, all in patients with gastrointestinal malignancy; three of the responding patients had previously failed 5-FU-containing regimens. When we measured 5-FU plasma levels in nine of our patients, they were at or below 1 ng/mL in most patients; however, within 1 hour of administration of interferon alfa-2b, plasma levels rose 16-fold. This elevation of 5-FU levels persisted for at least 24 hours, and could not be accounted for on the basis of altered interleukin-6 levels. When the regimen was tested in eight patients with metastatic renal cell carcinoma as part of a pilot study, three partial responses were observed, and no patient developed disease progression while on treatment. The combination of 5-FU, given by continuous infusion, and interferon alfa-2b, given daily, appears worthy of advancement to phase II trials.

Testing for predictive validity in health care education research: a critical review.

BACKGROUND: The assessment of predictive validity is the essential core from which a sound model of prediction is built. METHOD: Three methods for assessing predictive validity in health care education research were reviewed: longitudinal profile development, cross-validation, and inspection of the adjusted R2. A total of 47 articles published between 1973 and 1993 in nine health care disciplines were critically reviewed to determine whether the studies tested for predictive validity by using these methods. RESULTS: Very few of the 47 studies used at least one of the three methods for assessing predictive validity. Furthermore, the proportion of variance explained that is reported in the articles is typically small even before assessment of predictive validity. It is sobering to note that these small values may be inflated, since shrinkage is likely to occur when assessing predictive validity on a second, or cross-validation, sample. CONCLUSION: The scarcity of testing of predictive validity in the studies reviewed highlights the necessity of future research to establish the degree of predictive validity, if improvements in predicting success in health care education research are to be realized.

Immigrant women's health.

The immigration process entails many changes in the lives of those who emigrate including establishing oneself in a new country. There is continuing interest in what happens to the health of those who undergo this process. This qualitative study investigated the perceived health and health-related experiences of a sample of mid-life immigrant women and explored relationships between determinants of health and their experiences connected to immigration. Forty-two women participated in the study. While respondents were relatively well educated, their current socioeconomic status was relatively low. While women defined their health in a holistic manner. personal health focused on their physical health and their ability to function. This functionality was closely related to women's roles as resources for their families' well-being. Several health-related themes were identified that related to their change in homelands as adults: immigration and health, adapting to immigration and rebuilding their lives. Women are unlikely to talk about non-physical aspects of health unless asked about the general context of their lives. The family-centredness of immigrant women's well-being is a mediating factor in all aspects of their health; it is the health of the family unit that is the final point of adjudication for women. Spirituality and religious practices were identified as important resources for health. In addition, the process of immigration needs to be recognized as a determinant of health in and of itself. An understanding of these conceptualizations and health beliefs is an important component of the knowledge to be brought to formulating health promotion strategies and health services delivery that are relevant to and appropriate for this population of mid-life women.

Irritable bowel syndrome. An exploration of the patient perspective.

Although research into the etiology of irritable bowel syndrome (IBS) is extensive, this is not true for the patient experience of IBS. International population studies indicate that 15-20% of persons suffer from IBS. IBS is one of the eight most common somatic symptom complexes that account for 23% of visits to primary care physicians. This article details the journey of IBS sufferers in their attempt to understand and manage their illness through documenting patient perceptions of the origin of the illness, their search for treatment, their present management strategies, and their need for information and control. A grounded theory approach is used. Clinical practice protocols reflect the state of knowledge surrounding IBS: The variables are many and diagnosis and outcomes are uncertain. Further, our data suggest there is a desperate need for support groups and opportunities for patients, physicians, and supportive others to share experiences and concerns.

Health promotion and preventive measures: interpreting messages at midlife.

In this article, the authors provide important insight into the cultural messages that midlife women receive about preventive health care. Data were collected from 24 rural women as part of an ongoing project on midlife women's health. Kleinman's model of the popular and professional health care sectors was used to examine the data. There is clear evidence of clashes between the orientations and expectations of these sectors. Women's experiences reveal some consistent themes that contextualize their preventive health pursuits: time constraints, claims for expert knowledge, salience of family history, and the inclusion of nonallopathic resources as part of the professional realm. At the macrolevel, messages regarding women's responsibility for their health are ubiquitous. At the microlevel, women must negotiate among competing messages and resources and a health care system that often confounds their efforts. These contradictions must be addressed before there are long-term effects on the health of midlife women.

Rurality and health: perspectives of mid-life women.

INTRODUCTION: Health researchers have paid scant attention to the role of place in health except as settings where interventions take place, and even less attention has been given to the influence of rural context on health. Explanations of the impact of environment on health status have traditionally been limited to a narrow picture of rural life. Much of the relevant research in health focuses on farming as central to rural living and as such, suggests that rural living is not conducive to optimum health. Using the term 'rural health' in a limited sense (only to mean the health of farmers) is also implicit in rural health research that emphasizes occupational health rather than general health. In this paper we explore the influence of living in a rural area as described by mid-life rural women from different parts of the province of Alberta in Canada. Our analysis focuses on ways in which these rural women understand, talk about, and experience health. Their insights add to our understanding of rural environments not just as a setting for research but also as a social construct (i.e. a range of social relationships and social processes associated with rural environments) that informs the results of research. METHODS: This qualitative research used approaches from ethnography and grounded theory. 'Statistics Canada' criteria were used to define 'rural' as an area with a population of less than 10,000; therefore, small towns were included. Four female rural community interviewers from three geographic regions in the province were hired and trained for the purposes of the study. Participants were recruited through convenience and snowball sampling. Data collection using an interview guide continued until theoretical saturation was reached. All interviews were transcribed verbatim and imported into a software program for summary analysis and to aid in interpretation. Thematic analysis was conducted using memoing and coding as well as immersion and crystallization in conjunction with revisiting relevant literature. RESULTS: Twenty-four women ranging in age from 40 to 65 years were interviewed. The majority was married and the minority had children still living at home. Women held a holistic view of health. They described rural living as very important to their health. Through analysis and interpretation, four important aspects of rurality were revealed: the meaning and symbols of rurality; change and the understanding of rurality; getting away and getting around; and, diversity in rurality. Heterogeneity or difference in rural places was evident in the women's discussions, including their descriptions of what it was like to inhabit a rural place. CONCLUSIONS: The finding of differences in rurality reinforces the work of others and has important implications for researchers and program planners. To ignore this may perpetuate generalizations about rurality that are too simple to be useful and that have the potential to obscure important features of place. The data also challenge assumptions about the detrimental relationship between rurality and health. Myths of rural living should be set aside, and researchers and policy makers would be wise to listen to inhabitants to develop contextually relevant research and policy.

The importance of communication in secondary fragility fracture treatment and prevention.

INTRODUCTION: We report on a Canadian longitudinal qualitative case study of midlife women with fragility fractures, their treating orthopaedic surgeons and family physicians. METHODS: Women and their treating physicians were followed for an average of one year post fracture to investigate the health outcomes and what, if any, follow-up occurred aimed at secondary fracture prevention. The final dataset includes 223 interviews gathered from women aged 40 to 65 with fragility fractures, orthopaedic surgeons and family physicians. RESULTS: The circle of care for those with fragility fractures is disrupted at vital communication junctures: (1) the inconsistent flow of information between acute care institutions and family physicians; (2) unidirectional and inconsistent communication from orthopaedic surgeons to family physicians; and (3) competing demands of the cast clinic environment and patient expectations. It is not the lack of will that is undermining the consistent and detailed communication among patients, physicians and institutions. It is the episodic nature of fracture care that makes communication among involved parties difficult, if not impossible. CONCLUSIONS: Communication about events, acuity and clear expectations around roles and follow-up is urgently needed to improve communication throughout the circle of care to support secondary fracture prevention. Fractures from a standing height or similar trauma in women aged 40 to 65 should be treated as suspicious fractures and followed-up to investigate the underlying bone condition. This article reports on challenges and barriers to clear communication among women, their orthopaedic surgeons and family physicians that is necessary for follow-up and prevention of future fractures.

Treatment of gastrointestinal and renal adenocarcinomas with interferon-alpha.

Treatment of adenocarcinomas with interferon-alpha as a single agent has been disappointing. Recent efforts have focused on the combination of interferon with cytotoxic drugs such as 5-fluorouracil. A number of postulated mechanisms can explain synergistic interactions between 5-fluorouracil and interferon-alpha, including interaction with pyrimidine pathways, and alteration of drug metabolism. Previous studies in colorectal cancer, using 5-fluorouracil and interferon-alpha are reviewed, suggesting that the combination is more active than 5-fluorouracil alone. In renal cell carcinoma, the literature is reviewed, suggesting that daily interferon is the most efficacious schedule; preliminary data suggest that addition of 5-fluorouracil to interferon-alpha can double the expected response rate of 16% achieved by interferon-alpha alone.

Structured approach to pharmaceutical representatives. Family medicine residency program.

PROBLEM BEING ADDRESSED: Family medicine residents frequently interact with pharmaceutical sales representatives (PSRs) during their medical training; the literature indicates that these meetings affect future prescribing habits. We needed to develop a structured approach to PSR visits because our program did not provide residents with a consistent experience in dealing with PSRs. OBJECTIVE OF PROGRAM: To develop a structured approach to PSR visits that would permit residents to better understand the role of PSRs and to gain more from their interactions with PSRs in the future. MAIN COMPONENTS OF PROGRAM: First-year family medicine residents at an academic teaching unit in Edmonton were surveyed on their knowledge and attitude to PSRs and then given a 1-hour educational seminar and five structured visits from PSRs. Following each PSR presentation, residents completed an evaluation form and discussed the interaction with their preceptors. CONCLUSIONS: We believe that a structured educational program is better than a written policy restricting interactions between PSRs and residents for providing residents with an understanding of the role of PSRs and making them better prepared for future contact.

Dissociation of thymidine incorporation and transferrin receptor expression from cell growth and c-myc accumulation in alpha-interferon-treated cells.

Alpha-interferon is capable of altering the pattern of growth of both normal and neoplastic cells, but the pathways essential to sensitivity and resistance to alpha-interferon are unknown. To explore the growth inhibition induced by alpha-interferon, we examined the interferon-sensitive cell line Daudi and the resistant cell line HL-60. In Daudi, alpha-interferon induced a fall in c-myc mRNA accumulation at 24 h, inhibited tritiated thymidine ([3H]Thd) uptake at 48-72 h, and inhibited proliferation at 72-96 h. The half-life of c-myc mRNA was shortened from 31 to 13 min by alpha-interferon treatment. In HL-60, no alteration in c-myc accumulation or cell growth was observed, but [3H]Thd uptake was inhibited by 49%. Exogenous thymidine partially reversed the effects of alpha-interferon on [3H]Thd incorporation. The number of transferrin receptors, as measured by immunofluorescence, was unaffected by alpha-interferon in both cell lines. We conclude that the growth inhibitory effects of alpha-interferon are neither dependent upon inhibition of thymidine metabolism nor on expression of the transferrin receptor, but may be linked to control of c-myc.

Whealth study: women's reports of childhood abuse.

Most samples of adult women will contain a significant proportion who have been or are currently in abusive relationships. While past research has linked childhood abuse of girls to adult health concerns, little is known about the process through which women retrospectively reconcile these experiences. This article reports on data collected in an ongoing project on midlife women's health. Twenty-seven of 50 urban, middle-class participants in this phase of the project reported childhood abuse experiences. In the analysis, several aspects of these experiences were identified: definitions of abuse; recontextualizing abuse; responsibility for abuse; abuse avoidance; and experiences of multiple abuse. The women's discourse reflected a number of ideologies that provide a context in which women negotiate their understandings of these childhood experiences. This article provides insight into our understanding of abuse. It addresses the fundamental issue of promoting a worldview that precludes child abuse while leaving adult survivors with options for "moving on."

Hodgkin's disease presenting as myelofibrosis.

Four patients with Hodgkin's disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkin's disease is reviewed. Hodgkin's disease should be considered in the differential diagnosis of idiopathic myelofibrosis.