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.     

Modulation of telomerase activity by telomere DNA-binding proteins in Oxytricha

Telomere proteins protect the chromosomal terminus from nucleolytic degradation and end-to-end fusion, and they may contribute to telomere length control and the regulation of telomerase. The current studies investigate the effect of Oxytricha single-stranded telomere DNA-binding protein subunits α and β on telomerase elongation of telomeric DNA. A native agarose gel system was used to evaluate telomere DNA-binding protein complex composition, and the ability of telomerase to use these complexes as substrates was characterized. Efficient elongation occurred in the presence of the α subunit. Moreover, the α–DNA cross-linked complex was a substrate for telomerase. At higher α concentrations, two α subunits bound to the 16-nucleotide single-stranded DNA substrate and rendered it inaccessible to telomerase. The formation of this α·DNA·α complex may contribute to regulation of telomere length. The α·β·DNA ternary complex was not a substrate for telomerase. Even when telomerase was prebound to telomeric DNA, the addition of α and β inhibited elongation, suggesting that these telomere protein subunits have a greater affinity for the DNA and are able to displace telomerase. In addition, the ternary complex was not a substrate for terminal deoxynucleotidyltransferase. We conclude that the telomere protein inhibits telomerase by rendering the telomeric DNA inaccessible, thereby helping to maintain telomere length.     

Preferential apoptosis of CD56dim natural killer cell subset in patients with cancer

Natural killer (NK) cells (CD56(+)/CD3(-)) in the circulation of cancer patients were reported to have low NK activity and undergo spontaneous apoptosis. A possible relationship between apoptosis and impaired NK activity was studied by Annexin V-binding and NK-cell assays performed with peripheral blood mononuclear cells of patients with head and neck cancer (HNC), breast cancer (BC) and normal controls (NC). Cells stained with Annexin V (Anx) and antibodies to CD56, CD3, CD95, CD25, CD122 or CD132 were examined by flow cytometry. NK activity was tested against K562 targets in 4-h (51)Cr-release assays. The ratio of CD56(dim)/CD56(bright) NK cells was significantly different in patients vs. controls (10 vs. 16; p<0.01). A significantly greater percentage of CD56(dim) NK cells bound Anx in HNC patients (27+/-17%, median +/- SD) or BC (46+/-18%) than in NC (15+/-18%, p<0.04 and p<0.0002, respectively). CD56(dim) NK cells were preferentially targeted for apoptosis. NK activity was significantly lower in patients with HNC and BC than in NC (p<0.009). An inverse correlation between NK activity and the percent of Anx(+)CD56(dim) NK cells was observed in cancer patients (p =0.002) but not in NC. In patients, circulating CD56(dim) NK cells were targeted for apoptosis, leading to low levels of NK activity.     

Association of defensin beta-1 gene polymorphisms with asthma

BACKGROUND: Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness. OBJECTIVE: We characterized the genetic diversity in the defensin beta-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis. METHODS: To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program. RESULTS: Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5' genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma ( P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion ( P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted ( P = .04) and was more prominent in female subjects ( P = .007). CONCLUSION: Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.     

Growth, morbidity, and mortality in a cohort of institutionalized HIV-1-infected African children

OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors.     

Estradiol effects on the growth hormone/insulin-like growth factor-1 axis in amenorrheic athletes.

Disruption of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis has been reported and studied in menopause, hypothalamic amenorrhea, and anorexia nervosa, but not in weight-stable amenorrheic athletes. We investigated the effects of short-term transdermal estradiol on basal and exercise-stimulated serum GH, IGF-1, and associated binding proteins (IGFBP-1 and IGFBP-3) in seven weight-stable female amenorrheic athletes with percentage body fats greater that 12%. Each subject received a 72 h placebo patch followed by 144 h of transdermal estradiol. Serum samples for GH, IGF-1, IGFBP-1, and IGFBP-3 were obtained at baseline (t1), 72 hr (t2), 144 hr (t3), and during three 90-minute trials of aerobic exercise. Basal, and exercise GH, IGF-1, and IGFBP-1 were not different between trials. Baseline IGFBP-3 decreased from t1 to t2 (p = 0.04) and serum free fatty acids increased from t1 to t2, and t1 to t3 (p = 0.04, and 0.02 respectively). These findings differ from postmenopausal women, and women having weightloss-associated amenorrhea, suggesting that estrogen, exercise, and nutritional deficiencies may have independent effects on the GH/IGF-1 axis.     

Removal Tools are Faster and Produce Less Force and Torque on the Helmet Than Cutting Tools During Face-Mask Retraction

OBJECTIVE: To investigate the retraction time, forces, and torques applied to the football helmet during removal of the face mask with different face-mask removal tools. DESIGN AND SETTING: Subjects retracted the face mask of a football helmet mounted to a force platform in a laboratory setting. They removed a standard face mask by cutting or removing (or both) the lateral plastic loop straps using 4 different tools: the Trainer's Angel (TA), FM Extractor (FM), power screwdriver (SD), and Quick Release System (QR) in a counterbalanced fashion. SUBJECTS: Eighteen certified athletic trainers participated in this study. MEASUREMENTS: We started measuring time when the subject picked up the tool and ended when the face mask was in a fully retracted position. Maximum forces and torques were measured from the force platform during the retraction process. RESULTS: The SD and QR retracted the face mask significantly faster than the TA and FM. Forces producing superior-inferior translation were least with the SD. The SD and QR produced less lateral translation and rotation and lateral flexion moment than the TA and FM. The FM produced less torque in the lateral flexion moment than the TA. CONCLUSIONS: Tools that removed the loop straps (SD, QR) were faster and produced less force and torque on the helmet than the tools that cut through the loop straps (TA, FM).     

FAS and FAS-L expression by tumor cells and lymphocytes in breast carcinomas and their lymph node metastases

FAS receptor (FAS, CD95) and FAS ligand (FAS-L, CD95-L) are complementary members of a particular apoptotic pathway that plays a major role in immune regulation. The activation of FAS-L may trigger cytotoxic mechanisms leading to the death of FAS-expressing cells. Tumor cells and tumor-infiltrating lymphocytes (TIL) may express FAS and FAS-L in various proportions, and their interplay may affect tumor behavior. In the present study, we explored the expression of FAS and FAS-L in 28 mammary carcinomas (19 ductal and 9 lobular) and in their lymph node metastases. The expression of these mediators in immunostained sections was graded and evaluated comparatively between normal and neoplastic mammary epithelium, between tumor cells and TILs, and between mammary carcinoma cells and their lymph node metastases. We demonstrated the coexpression of FAS and FAS-L by breast carcinoma cells and TIL, with FAS expressed more strongly by normal epithelial cells and TIL than tumor cells. FAS-L was better stained on tumor cells than on TIL. There was equal or greater expression of FAS and FAS-L in the primary tumors and their TIL than in the metastatic counterparts. Comparing the expression of FAS with that of FAS-L, we recorded FAS equal or stronger than FAS-L in the primary mammary tumors and the reversal of their expression, FAS-L greater than FAS in the lymph node metastases. These results are consistent with reports of studies with other tumors, suggesting that the upregulated FAS-L indicates an increased ability of tumor cells to induce apoptosis in TIL and in the normal tissues invaded. However, it is understood that the FAS/FAS-L system, although essential for apoptosis, is only a contributing factor to the complex process of tumor invasion and antitumor defense.     

Lymphocyte proliferative responses to chlamydial antigens in human chlamydial eye infections.

In order to study the relationship between cell-mediated immune responses to Chlamydia trachomatis and the pathogenesis of human chlamydial eye disease, we have measured the peripheral blood lymphocyte proliferative responses to whole chlamydial elementary bodies in 40 subjects with oculogenital chlamydial infection of varying severity, 13 subjects with genital chlamydial infections and 12 healthy seronegative controls. The mean stimulation index was significantly higher in those with oculogenital infections than in controls. There was a strong correlation between the response to C. trachomatis serotypes B and L1. We studied the relationship between proliferative responses and four clinical parameters: follicular conjunctivitis, papillary hypertrophy, corneal pannus and epithelial punctate keratitis, but were unable to show a significant association with any of these. Nor was there any association between proliferative response and serum antibody titre to C. trachomatis (pooled serotypes D-K), duration of disease or quantitative isolation of chlamydia from the conjunctiva. The depletion of CD8+ cells had no consistent effect on proliferative responses to serotype L1 in 13 subjects.