Teaching scholars programs: faculty development for educators in the health professions.

OBJECTIVE: This article 1) provides an overview of formal Health Sciences Teaching Scholars Programs as presented in medical education literature and 2) presents information about an innovative multidiscipline Teaching Scholars Program. METHOD: Health Sciences Teaching Scholars Programs and similar programs were reviewed in the medical education literature to identify similar and dissimilar characteristics. The WVU Teaching Scholars Program highlighted in this article is presented with a discussion of goals, objectives, target audiences, course length, session frequency, program topics, learning methods, and assessments of the programs. A summary of the WVU Teaching Scholars Program and two Teaching Scholars Programs at McGill University and the University of Toronto were presented at the Association for American Medical Colleges (AAMC) annual meeting in 2006 for input from the general medical education audience. RESULTS: Comparisons of Health Sciences Teaching Scholars Programs reveal that successful programs are uniquely shaped by their educational environments. Scholars report that they value learning new teaching methods and improving their educational careers. CONCLUSION: Teaching Scholars Programs are valuable for the development of enhancing both teaching and scholarship in Health Sciences Programs and must adapt to the uniqueness of their respective educational environments and must continue to nurture scholars beyond graduation.     

Vigabatrin in adults with poorly-controlled epilepsy and learning disabilities.

Twenty-two adult patients with uncontrolled epilepsy and severe learning difficulties were included in an open study of vigabatrin. Patients were all in residential care and had experienced at least 12 seizures during the previous 12 months despite all attempts to optimize antiepileptic drug (AED) treatment. Following a 4 month baseline period, vigabatrin 500 mg twice daily was added to the current AED treatment and the dose increased according to response, up to a maximum of 4 g/day. Ten patients achieved a reduction in seizure frequency of more than 50% during this 4 month dose titration phase. Two patients had no seizures during the baseline period. For the 30 patients with seizures during the baseline period the median improvement in seizure frequency with the addition of vigabatrin was 49% (P = 0.014). The response rate was higher for patients with partial seizures than for those with generalized seizures. Ten patients continued with vigabatrin while the dose of one of their other AEDs was gradually reduced and successfully withdrawn in three patients. Adverse events were reported in 20 patients during the 64 week study period. The most frequently reported events were sedation (8 patients), aggression (4 patients), agitation (3 patients) and ataxia (3 patients). No patients were withdrawn from the study as a consequence of adverse events. Vigabatrin was therefore an effective add-on therapy in 45% of these difficult-to-treat patients and allowed reduction of other AED treatment in a small number.     

Surgical correction of burn scar contractures of the foot in children

The results of reconstructive procedures for the treatment of burn scar contractures of the feet in 55 children undergoing 90 operations were reviewed. The patients were treated in all but one case by release of the contracture band with placement of a skin graft in the resulting defect. There was an overall recurrence rate of 15 per cent that was not affected by the use of split-thickness versus full-thickness grafts. The time delay from the thermal injury to the reconstructive procedure was also found not to affect the outcome. Postoperative immobilization by the use of either a dynamic or an adynamic splint was found to be important both for preventing graft loss and for decreasing the rate of contracture recurrence.     

Joint custody: historical, legal, and clinical perspectives with emphasis on the situation in Canada

The search for ways to mitigate the effects of family breakdown on parents and children includes legislative and clinical efforts which to some extent influence each other. In the past year much public interest has been aroused in Canada, and particularly in Ontario, in the issue of legislative changes which would make joint custody the usual or "preferred" legal disposition of custody cases. This paper provides a discussion of the legislated preference, or "rebutable presumption" of joint custody from a historical, legal and clinical point of view. Definition and elaboration of what joint custody is from the legal and practical perspectives is provided with an emphasis on Canadian laws and practice. The legal rights of the non-custodial parent are explained, and relevant case law is highlighted. The relationship between joint custody, support orders and relitigation rates are elaborated. Following this is a critical overview of the empirical research on joint custody as it relates to the adjustment of children and parent satisfaction is included. It is concluded that while there is little question that shared parenting can be beneficial to children, the enthusiasm of legislators for joint custody has not been supported by empirical data. It is necessary to examine under what circumstances and for which kinds of parents and children joint custody might be beneficial since it is unlikely that one solution will fit the needs of all families and all stages of family life.     

Expression of interleukin-8 correlates with vascularity in human gastric carcinomas.

Interleukin (IL)-8 is a multifunctional cytokine that can stimulate the division of endothelial cells. We examined the expression of IL-8 mRNA using Northern blot analysis and in situ mRNA hybridization (ISH) and protein production using enzyme-linked immunosorbent assay and immunohistochemistry in 8 human gastric carcinoma cell lines and 39 gastric carcinomas and corresponding normal mucosa (34 surgical specimens and 5 biopsy specimens). Of the 8 human gastric carcinoma cell lines, 6 expressed 1.8-kb IL-8 mRNA and secreted various levels of IL-8 protein. The expression of IL-8 by TMK-1 cells was induced by exposure to IL-1 alpha, epidermal growth factor, and transforming growth factor-alpha, shown previously to be autocrine growth stimulators for human gastric carcinoma cells. In tumor tissues, most of the tumors (28 of 34 surgical specimens and 4 of 5 biopsy specimens) expressed IL-8 at higher levels than the corresponding normal mucosa. ISH and immunohistochemical analyses revealed that IL-8 mRNA and protein were localized in the cytoplasm of tumor cells. The number of blood vessels in the gastric carcinomas was determined by using antibodies against CD34. The level of IL-8 mRNA in the neoplasms strongly correlated with vascularization (Spearman correlation, r = 0.812; P = 0.001). The data suggest that IL-8 produced by tumor cells may regulate neovascularization and, hence, the growth and spread of human gastric carcinoma.     

Evidence for the causal role of endogenous interferon-alpha/beta in the regulation of angiogenesis,tumorigenicity, and metastasis of cutaneous neoplasms

Primary tumor growth and metastasis depend on angiogenesis, which is determined by the balance between proangiogenic and antiangiogenic molecules. Interferon (IFN)-α and -β inhibit angiogenesis through downregulation of interleukin-8, matrix metalloproteinase-9, and basic fibroblast growth factor. To provide evidence for the causal role of IFN-α/β in the induction of neoplasms, their angiogenesis, and hence, progressive growth, we carried out experiments using 129S6 IFN-α/β receptor −/− mice back-crossed to BALB/c nude mice. Subcutaneous angiogenesis was determined following implantation of gelfoam sponges containing 0.4% agarose and several proangiogenic molecules. Tumorigenicity and production of lung metastasis were determined subsequent to subcutaneous and intravenous injections, respectively, of highly metastatic A375SM human melanoma cells. Carcinogenesis was induced by chronic exposure of mice to UVB radiation (5 kJ/m², 3 times/week). Angiogenesis, tumorigenicity, and production of metastasis, as well as development of autochthonous skin tumors, were all accelerated in IFN-α/β receptor −/− mice as compared to control mice. Collectively, the data show that inability to respond to endogenous IFN-α/β (through a mutation in the IFN-α/β receptor) leads to increased susceptibility to carcinogenesis, enhanced angiogenesis, tumorigenicity, and metastasis. This revised version was published online in July 2006 with corrections to the Cover Date.     

How important is the 'quality' of the cytotoxic T lymphocyte (CTL) response in protection against HIV infection?

Cytotoxic T lymphocyte (CTL) responses have been associated with protection from HIV-1 infection in people with a high degree of exposure to HIV and who show no serological evidence of HIV infection (HEPS, highly exposed persistently seronegative). However, it remains unclear how protective CTL responses could apparently develop in a minority of people, whilst the great majority of HIV-infected people make strong CTL responses yet progress to AIDS and death. In this paper we review the data which supports the hypothesis that the quality of the T-cell response, rather than its magnitude, may be an important factor that merits further investigation.     

Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load

Therapeutic intervention with antiretroviral therapy (ART) enables the modulation of HIV virus load and hence provides a unique opportunity to study the consequences of varying antigen load on the phenotype of virus-specific CD8(+) T lymphocytes in a persistent human viral infection. The recent advent of tetrameric peptide / HLA class I complexes has enabled the direct phenotypic characterization of antigen-specific T cell populations ex vivo. Here, we use this technology to examine directly ex vivo the consequences of therapeutic manipulation of HIV virus load on the phenotype of HIV-specific CTL. Our observations show that: (1) distinct sequential activation patterns of CD8(+) T cells are associated with increasing virus load; (2) T cell receptor (TCR) down-regulation without apoptosis represents an early event during the generation of a T cell response in a natural infection and precedes the emergence of two distinct antigen-specific CD8(+) T cell populations which differ in TCR and CD8 expression levels. Clear differences in surface Annexin V staining were observed between these populations. The observation that CTL activation, demonstrated by TCR and CD8 down-regulation, in response to rising levels of virus load, co-segregates with apoptosis only during later stages of the response indicates that antigen-associated cell death is restricted to distinct subpopulations of CTL.     

Effect of the 21-aminosteroid,U-74389F,on hyperoxic lung injury in rats

Hyperoxia (>95% oxygen) in rats caused an increase in lung weight and an accumulation of fluid in the thorax. The mean lung wet weight of air-breathing controls at 60 h was 1.2±0.01 g, and that of vehicle-treated, oxygen-exposed animals was 2.45±0.05 g. Treatment with the 21-aminosteroid U-74389F, 3, 10, and 30 mg/kg twice daily throughout oxygen exposure, produced 8, 42, and 18% inhibition of the oxygen-induced increase in lung weight, respectively. However, U-74389F did not inhibit the hyperoxia-induced accumulation of neutrophils in bronchoalveolar lavage fluid.

No pleural fluid could be aspirated from the thorax of air-breathing controls. The volume of pleural fluid in oxygen-exposed, vehicle-treated animals and animals treated with 3, 10, and 30 mg/kg U-74389F b.i.d. was 6.5±0.9, 2.6±0.6, 0.8±0.3, and 1.3±0.5 ml, respectively.

U-74389F or its biologs are of potential value for the treatment of lung diseases in which oxidant damage has been implicated.