A novel T cell receptor transgenic animal model of seborrheic dermatitis-like skin disease

We have characterized a novel animal model of the common inflammatory skin disease seborrheic dermatitis (SD) that involves the expression of the self-specific 2C transgenic T cell receptor on the DBA/2 genetic background. Opportunistic fungal pathogens are present in the primary histological lesions and severe disease can be mitigated by the administration of fluconazole, demonstrating a role for infection in disease pathogenesis. Spontaneous disease convalescence occurs at 70-90 d of age and is preceded by an expansion of CD4+ T cells that partially restores the T cell lymphopenia that occurs in these animals. The adoptive transfer of syngeneic CD4+ T cells into pre-diseased DBA/2 2C mice completely abrogates the development of cutaneous disease. The pattern of disease inheritance in DBA/2 backcrosses suggests that one, or a closely linked group of genes, may control disease penetrance. Bone marrow reconstitution experiments demonstrated that the DBA/2 susceptibility factor(s) governing disease penetrance is likely non-hematopoietic since bone marrow from disease-resistant 2C mice can adoptively transfer the full disease phenotype to non-transgenic DBA/2 animals. This model implicates fungal organisms and CD4+ T cell lymphopenia in the development of a SD-like condition and, as such, may mimic the development of SD in acquired immunodeficiency syndrome.     

Pain and the use of outpatient services among persons with HIV: results from a nationally representative survey

BACKGROUND: The negative impact of pain on health-related quality of life has been documented for persons with human immunodeficiency virus (HIV). Furthermore, pain could be an important factor in seeking medical care. However, the relationship between pain and health service utilization is poorly understood. OBJECTIVES: The objective of this study was to investigate the effect of pain on use of outpatient services among a nationally representative sample of adults receiving medical care for HIV using Andersen's Behavioral Model of Health Services Use. METHODS: We used Poisson regression to assess outpatient use over 6 months among 2267 respondents in the HIV Cost and Services Utilization Study. Key predisposing variables include gender and race/ethnicity. Enabling factors include income and insurance. Need factors include pain, CD4 count, and diagnosis of acquired immunodeficiency syndrome (AIDS). RESULTS: Sixty-seven percent of respondents reported experiencing pain during the previous 4 weeks. Self-reported pain was higher among those with AIDS, intravenous drug-using females, the unemployed, and those without a baccalaureate degree, but lower among blacks. Patients reporting more pain and those developing more pain used more outpatient services. Poorer health (CD4 count <50 cells/mm3, less energy) was also associated with higher use. Persons with Medicare, Medicaid, or private insurance were more likely to have used outpatient services than the uninsured. Persons with a private HMO were no more likely to use services than those without insurance. CONCLUSIONS: Improved pain management could reduce outpatient use for persons experiencing pain and lead to substantial cost savings. Inequalities in outpatient use related to insurance are evident.     

Geospatial information technology: an adjunct to service-based outreach and education

This exemplar highlights how geospatial information technology was effective in supporting academic practice, faculty outreach, and education initiatives at the University of Mississippi School of Nursing. Using this cutting-edge technology created a community-based prototype for fully integrating point-of-service research, practice, and academics into a cohesive strategy to influence change within the health care delivery system. This exemplar discusses ways this knowledge benefits practice and curriculum development; informs critical decision making affecting the people we serve; underscores the vital role nurses play in linking this technology to practice; and develops community residents as partners in their own health and that of the community.     

Professional liability issues in graduate medical education

Resident physicians, attending physicians, and graduate medical education (GME) institutions share a collective responsibility to deliver safe and appropriate care to patients. The law does not offer concessions in quality of care to accommodate GME. Resident physicians are generally held to the same standard of care as attending physicians in their respective specialties. This principle encourages resident physicians to seek supervision and attending physicians to provide the same. Attending physicians face malpractice exposure not only for the care they provide but also for the care they direct. In addition, they may be held vicariously liable for the negligence of resident physicians working with them, or directly liable for inadequate supervision. What constitutes adequate supervision is unsettled in the law. As the standards in this area evolve, it is reasonable to expect that the profession's and the public's heightened attention to patient safety will continue to move the courts toward higher standards of supervision. GME institutions and programs bear legal responsibility for both the care they deliver and the negligence of their employees. They also face liability for failing to administer safe systems of care. Work hour restrictions and a growing understanding of the role of organizational factors in contributing to and preventing medical injury may increase the legal expectations imposed on GME programs.      

Mapping the determinants of health inequalities in social space: can Bourdieu help us?

Considerable research effort has been devoted to describing and explaining, at a variety of spatial scales, geographical inequalities in health outcomes within the developed world. Following Bourdieu, we argue that structures of the social world may be revealed in different kinds of 'social' space. We outline the relational thinking that underlies these ideas. We then 'map', using correspondence analysis (on which Bourdieu himself drew), the structure of social space according to the differential availability of some forms of capital, across four study areas in north-west England. We use logistic regression analysis to explain variation in psychological morbidity (GHQ-score) and then portray the significant predictors of morbidity using multiple correspondence analysis. The area of residence of the survey respondents is used to associate them with particular locations in these social spaces.     

17q-linked frontotemporal dementia-amyotrophic lateral sclerosis without tau mutations with tau and alpha-synuclein inclusions

BACKGROUND: Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutations in the microtubule-associated protein tau gene (MAP tau) and is associated with neuronal or glial tau inclusions. OBJECTIVES: To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family. DESIGN: A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made. SETTING: Family study. PATIENTS: San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members do not have a MAP tau coding or splice regulatory sequence mutation, and the MAP tau is genetically excluded. MAIN OUTCOME MEASURES: Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS). RESULTS: The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAP tau. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and alpha-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform. CONCLUSION: The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS.     

ADAM12: a novel first-trimester maternal serum marker for Down syndrome

OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration. RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers. CONCLUSION: ADAM12 is a promising marker for Down syndrome.