Oral versus written feedback in medical clinic.

OBJECTIVE: To determine whether residents perceived oral, face-to-face feedback about their continuity clinic performance as better than a similar, written version. DESIGN: Single-blind, randomized controlled trial. SETTING: Two university-based, internal medicine residency clinics. PARTICIPANTS: All 68 internal medicine and combined program (medicine-pediatrics, medicine-psychiatry, medicine-neurology, and preliminary year) residents and their clinic preceptors. MEASUREMENTS AND MAIN RESULTS: Residents at each program were separately randomized to oral or written feedback sessions with their clinic preceptors. The oral and written sessions followed similar, structured formats. Both groups were later sent questionnaires about aspects of the clinic. Sixty-five (96%) of the residents completed the questionnaire. Eight of the 19 questions dealt with aspects of feedback. A feedback scale was developed from the survey responses to those eight questions (alpha = .86). There were no significant differences in the responses to individual questions or in scale means (p > .20) between the two feedback groups. When each university was analyzed separately, one had a higher scale mean (3.10 vs 3.57, p = .047), but within each university, there were no differences between the oral and written feedback groups (p > .20). CONCLUSIONS: No differences were observed between the oral and written feedback groups. In attempting to provide better feedback to their residents, medical educators may better apply their efforts to other aspects, such as the frequency of their feedback, rather than the form of its delivery.

Dietary vitamin C, beta-carotene and 30-year risk of stroke: results from the Western Electric Study.

The relations of dietary antioxidants vitamin C and beta-carotene to 30-year risk of stroke incidence and mortality were investigated prospectively in the Chicago Western Electric Study among 1,843 middle-aged men who remained free of cardiovascular disease through their second examination. Stroke mortality was ascertained from death certificates, and nonfatal stroke from records of the Health Care Financing Administration. During 46, 102 person-years of follow-up, 222 strokes occurred; 76 of them were fatal. After adjustment for age, systolic blood pressure, cigarette smoking, body mass index, serum cholesterol, total energy intake, alcohol consumption, and diabetes, relative risks (and 95% confidence intervals) for nonfatal and fatal strokes (n = 222) in highest versus lowest quartiles of dietary beta-carotene and vitamin C intake were 0.84 (0.57-1.24) and 0.71 (0.47-1.05), respectively. Generally similar results were observed for fatal strokes (n = 76). Although there was a modest decrease in risk of stroke with higher intake of beta-carotene and vitamin-C intake, these data do not provide definitive evidence that high intake of antioxidant vitamins decreases risk of stroke.

The role of the EST genes in yeast telomere replication.

We have recently completed a large mutant screen designed to identify new mutants of Saccharomyces cerevisiae with a telomerase-like defect. From this screen; 22 mutants were identified that mapped to three genes, called EST1, EST2 and EST3, as well as a novel EST-like mutation in a fourth gene, previously identified as CDC13. Mutations in each of these genes give rise to phenotypes that are indistinguishable from those observed when TLC1, encoding the yeast telomerase RNA, is deleted. In addition, genetic analysis indicates that all four genes function in the same pathway for telomere replication as defined by TLC1, the one known component of telomerase. This indicates that these genes encode factors that are essential in vivo for telomerase function. Genetic and biochemical analyses have shown that EST1 and CDC13 encode single-stranded telomeric DNA-binding proteins, suggesting that these two proteins may function to mediate access of telomerase to the end of the telomere.

Programmed translational frameshifting in a gene required for yeast telomere replication.

BACKGROUND: Telomeres are replicated in most eukaryotes by the enzyme telomerase, a specialized reverse transcriptase. A genetic screen in Saccharomyces cerevisiae designed to detect telomerase components previously led to the identification of four EST ('ever shorter telomeres') genes which are required for telomerase function in vivo. This report describes the cloning and characterization of EST3. RESULTS: We identified a potential site of +1 ribosomal frameshifting in the EST3 coding sequence and demonstrated that translation both upstream and downstream of this site is required for EST3 function. Mutation of EST3 such that it could not frameshift resulted in a strain with the same phenotype as an est3 null mutant, showing that EST3 frameshifting is required for telomere replication. Immunoblot analysis revealed that two proteins were synthesized from EST3: a truncated protein resulting from translation of only the first open reading frame, as well as the full-length 181 amino-acid Est3 protein resulting from translation through the frameshift site. Only the full-length Est3 protein was required for normal EST3 function. CONCLUSIONS: A programmed translational frameshifting mechanism similar to that used by yeast retrotransposons is employed to produce full-length Est3 protein. This is the first example in yeast of a cellular gene that uses frameshifting to make its protein product, and a potential link is suggested between retrotransposition and the telomerase pathway for telomere maintenance.

Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes.

The primary determinant for telomere replication is the enzyme telomerase, responsible for elongating the G-rich strand of the telomere. The only component of this enzyme that has been identified in Saccharomyces cerevisiae is the TLC1 gene, encoding the telomerase RNA subunit. However, a yeast strain defective for the EST1 gene exhibits the same phenotypes (progressively shorter telomeres and a senescence phenotype) as a strain deleted for TLC1, suggesting that EST1 encodes either a component of telomerase or some other factor essential for telomerase function. We designed a multitiered screen that led to the isolation of 22 mutants that display the same phenotypes as est1 and tlc1 mutant strains. These mutations mapped to four complementation groups: the previously identified EST1 gene and three additional genes, called EST2, EST3 and EST4. Cloning of the EST2 gene demonstrated that it encodes a large, extremely basic novel protein with no motifs that provide clues as to function. Epistasis analysis indicated that the four EST genes function in the same pathway for telomere replication as defined by the TLC1 gene, suggesting that the EST genes encode either components of telomerase or factors that positively regulate telomerase activity.

Est1 has the properties of a single-stranded telomere end-binding protein.

In Saccharomyces cerevisiae, deletion of the EST1 gene results in phenotypes identical to those displayed by a deletion of a known component of telomerase (the yeast telomerase RNA), arguing that EST1 is also critical for telomerase function. In this study, we show that the Estl protein binds to yeast G-rich telomeric oligonucleotides in vitro. Binding is specific for single-stranded substrates and requires a free 3' terminus, consistent with the properties expected for a protein bound to the 3' single-stranded G-rich extension present at the telomere. Assessment of the in vivo function of this single-stranded DNA-binding protein has shown that EST1 acts in the same pathway of telomere replication as the TLC1 telomerase RNA, by several different genetic criteria: est1 tlc1 double mutant strains show no enhancement of phenotype relative to either single mutant strain, and EST1 dominant mutations have an effect on telomeric silencing similar to that displayed by TLC1 previously. We propose that Est1 is a telomere end-binding protein that is required to mediate recognition of the end of the chromosome by telomerase.

Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study.

Dietary factors are likely candidates for important determinants of prostatic cancer risk. Among the most investigated nutritional factors have been antioxidants. We evaluated dietary beta-carotene and vitamin C in relation to subsequent risk of prostate cancer in a prospective study of 1,899 middle-aged men. We combined prostate cancer cases diagnosed in the first 24 years of follow-up with incident cases identified from the Health Care Financing Administration hospitalization and outpatient files during an additional 6-year follow-up period. We obtained death certificates for all decedents. During the 30-year follow-up, prostate cancer developed in 132 men. There was no indication that consumption of beta-carotene or vitamin C was related to increased or decreased risk of prostate cancer. Relative risks for highest vs lowest quartiles of beta-carotene and vitamin C intake were 1.27 [95% confidence interval (CI) = 0.75-2.14] and 1.03 (95% CI = 0.59-1.60), respectively, after adjustment for age, number of cigarettes smoked per day, dietary cholesterol and saturated fat, alcohol consumption, total energy intake, and occupation. Associations between intake of these nutrients and risk of prostate cancer differed depending on whether the cancer was diagnosed during the first 19 years of follow-up or the next 11 years of follow-up. Overall survival over the 30 years of follow-up was positively associated with intake of beta-carotene and vitamin C.

Interpretive and procedural skills of the internal medicine clerkship: performance and supervision.

This descriptive study prospectively examined the performance and supervision of interpretive and procedural skills during an internal medicine clerkship. Students (N = 150) documented having done 7 required and 12 elective skills. Preceptors of required skills were interns (44%), residents (29%), attending physicians (12%), and others (16%). The elective procedures and the percentage of students doing them were as follows: skin tests, 78%; nasogastric tube insertion, 57%; paracentesis, 44%; bone marrow sampling, 35%; lumbar puncture, 34%; thoracentesis, 34%; Papanicolaou smear, 29%; central line placement, 27%; cardioversion, 13%; bladder catheter insertion, 11%; arthrocentesis, 9%; and skin biopsy, 7%. Elective procedures per student ranged from 0 to 9 (mean = 4) and were done less often in the first clerkship group than later in the academic year. Preceptors of electives were interns (46%), residents (39%), and attending physicians (9%). House staff were more likely and faculty less likely to precept electives than required procedures. Students' exposures to these skills are unequal. Their preceptor are generally house staff. To prepare medical students for postgraduate training, technical skills should be specifically addressed in the curriculum.

Patient-perceived barriers to preventive health care among indigent, rural Appalachian patients.

OBJECTIVE: To examine perceptions of a cohort of rural Appalachian patients regarding barriers to the use of preventive health measures. METHODS: Consecutive new patients (N = 188) at a clinic for the indigent were confidentially surveyed about their use of six preventive health measures: blood pressure screening, cholesterol level, diphtheria-tetanus immunization, mammography, cervical Papanicolaou smear, and physical examination. When any of these measures was lacking, patients were asked why, and whether they would have the measure performed if the relevant barriers were removed. RESULTS: Applicable screening measures lacking were as follows: blood pressure screening, 16%; cholesterol level, 60%; diphtheria-tetanus immunization, 67%; mammography, 69%; Papanicolaou smear, 22%; and physical examination, 32%. Of the patients, 85% were lacking at least one measure. Patients most often identified the following reasons for having omitted these measures: lack of knowledge about prevention (51%) and cost (36%). Older and less educated patients more often identified cost (P < .01 and P = .06, respectively), and men were more likely to list lack of knowledge (P = .04). If the identified barriers could be removed, 72% of those lacking a screen indicated they would obtain the screening measures. DISCUSSION: This indigent population expressed a desire for preventive care. Our patients identified cost and lack of knowledge as the major reasons for omitting these health screening measures. Data obtained from health care providers, rather than patients, may fail to disclose the barriers these patients face. Adequate education about disease prevention may be as crucial as sufficient funding in improving compliance with preventive guidelines.

Can you hold please? How internal medicine residents deal with patient telephone calls. Telephone Encounters Learning Initiative Group.

Little is known about the mechanisms used in internal medicine residency programs to handle patient telephone calls. To address this, a survey of internal medicine residents was conducted at 10 different internal medicine residency programs. The response rate was 76% (N = 388). Approximately 90% of the residents handled patient telephone calls. The residents saw a mean of 7 patients per week in clinic (standard deviation +/- 2) and received an average of 2 patient calls daily (standard deviation +/- 2). The mean number of patient calls received each night on-call was 3 (standard deviation +/- 6) and on weekend call days, an average of 4 patient calls were received (standard deviation +/- 8). Internal medicine residents reported spending an average of 7 minutes per call talking to the patient (standard deviation +/- 5) and 8 minutes in follow-up activities (standard deviation +/- 6). Residents reported documenting calls less than 35% of the time. Residents disagreed with the statements "I am very satisfied with my patient telephone call system" and "My patients are very satisfied with my telephone call system." Most internal medicine residents handle a significant amount of patient telephone calls, and the systems for handling these calls are less than satisfactory. The procedures used to manage patient calls and the training for this component of practice should be improved.

Retroviral-mediated transduction of p53 gene increases TGF-beta expression in a human glioblastoma cell line.

Transforming growth factor-beta (TGF-beta) has been implicated as a potent growth regulator; the degree of responses to it, whether positive or negative, generally correlates with the stage of cell differentiation in various cell types. We examined the effect of the p53 gene, which participates in the control of cell-cycle progression, on the expression of human TGF-beta. The human glioblastoma cell line SNB-19, which expresses the latent form of TGF-beta, was transfected with a retroviral vector containing wild-type p53 (wt-p53) or p53 with a mutation (mut-p53) at codon 273. Stable G418-resistant SNB-19 clones were isolated. The growth kinetics of wt-p53 transfectants were suppressed compared with those of parental cells, vector transfectants, or mut-p53 transfectants, as assayed by growth-curve measurements and 3H-thymidine incorporation; however, RNA dot blot and Western blot analyses demonstrated that wt-p53 and mut-p53 transfectants expressed higher amounts of TGF-beta 1 and TGF-beta 2 mRNA and intracellular TGF-beta isoform proteins, respectively, than parental cells. By means of the biological assay for active TGF-beta (Mv1Lu cell-growth-inhibition assay), we observed that both transfectants produced active TGF-beta, whereas the parental cells produced only the latent form. These results suggest that, while only the wt-p53 gene inhibits tumor-cell progression, both wt-p53 and codon 273-mutated p53 can cause increased TGF-beta expression.

Creating an objective structured clinical examination for the internal medicine clerkship: pitfalls and benefits.

The objective-structured clinical examination (OSCE) is a useful tool in evaluating clinical competence. Traditional clinical-evaluation measures have been criticized as arbitrary and lacking reliability, whereas written exams test primarily cognitive aspects. The OSCE focuses on learner actions rather than abstract knowledge and evaluates in a uniform fashion. A 15-station OSCE was created for an internal medicine junior clerkship, based on predetermined skill and content goals. The exams then were scored by a single, blinded reviewer, again in a predetermined fashion. The OSCE has been studied in terms of reliability, content validity, and construct validity. The exam has become accepted by the department and has guided the continuing curricular development. The OSCE is not designed to measure all the domains of a learner's educational process. However, when used in conjunction with other evaluating mechanisms, it provides an objective outcome measure of the medical education process.

Characterization of lymphokine-activated killing by human peripheral blood mononuclear cells stimulated with interleukin 2 (IL-2) analogs specific for the intermediate affinity IL-2 receptor.

Interleukin 2-stimulated human peripheral blood mononuclear cells (PBMC) generate lymphokine-activated killing (LAK). Using the IL-2 analogs R38A and F42K, which interact primarily with the beta and gamma subunits of the IL-2 receptor, we assessed the roles of IL-2R beta gamma and the high-affinity IL-2 receptor complex in LAK activation. Although the kinetics of LAK activation were identical, lytic activity was approximately 30% lower and proliferation was up to 55% lower in those PBMC stimulated by R38A or F42K than in those exposed to wild-type IL-2. The percentage of cells expressing cell-surface markers such as CD3, CD4, CD8, and CD16 was not significantly different after treatment with wild-type IL-2, R38A, or F42K; however, the proportion of cells expressing IL-2R alpha increased dramatically in response to stimulation by F42K (30%) compared to stimulation by either rIL-2 or R38A (15%). In addition, by Day 7 the concentration of soluble IL-2R alpha in analog-stimulated LAK culture supernatants was 50-75% less than that from wild-type IL-2-cultured cells. These findings suggest that interaction of IL-2 with IL-2R beta gamma alone is sufficient for both proliferation and the generation of LAK, and that stimulation with subunit-specific IL-2 analogs results in differential regulation of the IL-2R alpha on human LAK cells.

Comparison of two immunochemical methods with thin-layer chromatographic methods for determination of aflatoxins.

Three different methods were compared for the determination of total flatoxins in corn and peanuts naturally contaminated with aflatoxins and in corn, peanuts, cottonseed, peanut butter, and poultry feed spiked with aflatoxins B1, B2, and G1. The 3 methods were an enzyme-linked immunosorbent assay (ELISA) screening test; a monoclonal antibody-affinity column-solid-phase separation method; and the AOAC official thin-layer chromatography (TLC) methods for all except poultry feed, for which Shannon's TLC method for mixed feed was used. The ELISA test is designed to provide only positive results for total aflatoxins at greater than or equal to 20 ng/g or negative results at less than 20 ng/g. The affinity column separation is coupled with either bromination solution fluorometry to estimate total aflatoxins or liquid chromatography (LC) to quantitate individual aflatoxins. Fluorodensitometry was used to determine aflatoxins in commodities analyzed by the TLC methods. The LC and TLC results were in good agreement for all the analyses. The results for the affinity column using bromination solution fluorometry were similar except those for cottonseed, which were about 60% higher. The ELISA screening method correctly identified naturally contaminated corn and peanut positive samples. No false positives were found for controls. The correct response for spiked corn, raw peanuts, peanut butter, and cottonseed at greater than or equal to 20 ng aflatoxins/g was about 90%. The correct response for spiked poultry feed at greater than or equal to 20 ng aflatoxins/g was about 50%.