Benchmarks of support in internal medicine residency training programs.

PURPOSE: To identify benchmarks of financial and staff support in internal medicine residency training programs and their correlation with indicators of quality. METHOD: A survey instrument to determine characteristics of support of residency training programs was mailed to each member program of the Association of Program Directors of Internal Medicine. Results were correlated with the three-year running average of the pass rates on the American Board of Internal Medicine certifying examination using bivariate and multivariate analyses. RESULTS: Of 394 surveys, 287 (73%) were completed: 74% of respondents were program directors and 20% were both chair and program director. The mean duration as program director was 7.5 years (median = 5), but it was significantly lower for women than for men (4.9 versus 8.1; p =.001). Respondents spent 62% of their time in educational and administrative duties, 30% in clinical activities, 5% in research, and 2% in other activities. Most chief residents were PGY4s, with 72% receiving compensation additional to base salary. On average, there was one associate program director for every 33 residents, one chief resident for every 27 residents, and one staff person for every 21 residents. Most programs provided trainees with incremental educational stipends, meals while oncall, travel and meeting expenses, and parking. Support from pharmaceutical companies was used for meals, books, and meeting expenses. Almost all programs provided meals for applicants, with 15% providing travel allowances and 37% providing lodging. The programs' board pass rates significantly correlated with the numbers of faculty fulltime equivalents (FTEs), the numbers of resident FTEs per office staff FTEs, and the numbers of categorical and preliminary applications received and ranked by the programs in 1998 and 1999. Regression analyses demonstrated three independent predictors of the programs' board pass rates: number of faculty (a positive predictor), percentage of clinical work performed by the program director (a negative predictor), and financial support from pharmaceutical companies (also a negative predictor). CONCLUSIONS: These results identify benchmarks of financial and staff support provided to internal medicine residency programs. Some of these benchmarks are correlated with board pass rate, an accepted indicator of quality in residency training. Program directors and chairs can use this information to identify areas that may benefit from enhanced financial and administrative support.     

B cell chronic lymphocytic leukaemia cells have reduced capacity to upregulate expression of MHC class I in response to interferon-gamma

AIMS: An important consideration in the design of a tumour vaccine is the ability of tumour-specific cytotoxic T lymphocytes (CTL) to recognise unmanipulated tumour cells in vivo. To determine whether B-CLL might use an escape strategy, the current studies compared B-CLL and normal B cell MHC class I expression. METHODS: Flow cytometry, TAP allele PCR and MHC class I PCR were used. RESULTS: While baseline expression of MHC class I did not differ, upregulation of MHC class I expression by B-CLL cells in response to IFN-gamma was reduced. No deletions or mutations of TAP 1 or 2 genes were detected. B-CLL cells upregulated TAP protein expression in response to IFN-gamma. Responsiveness of B-CLL MHC class I mRNA to IFN-gamma was not impaired. CONCLUSIONS: The data suggest that MHC class I molecules might be less stable at the cell surface in B-CLL than normal B cells, as a result of the described release of beta(2)m and beta(2)m-free class I heavy chains from the membrane. This relative MHC class I expression defect of B-CLL cells may reduce their susceptibility to CTL lysis in response to immunotherapeutic approaches.     

Analysis of two IL-4 promoter polymorphisms in a cohort of atopic and asthmatic subjects

The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central role in driving the inflammatory immune responses which are present in atopic airway disease. This study examined the distribution of two putative IL-4 promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe and moderate asthma, non-asthmatic atopy and control subjects. Neither polymorphism was identified in any of the samples tested. The data suggest that either the polymorphisms are present at very low frequencies or are artefacts of the B cell lines from which they were identified.     

1141610241Altered expression of HuR, an mRNA stabilizing protein, mediates aberrant Placenta Growth Factor (PlGF) expression in preeclampsia

Background:  Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3'UTR mRNA binding protein, can protect AU-rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU-rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro . We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.
Methods:  Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results:  Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions:  HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects.