Commitment to change statements: a way of understanding how participants use information and skills taught in an educational session.

BACKGROUND: Commitment to change has gained increasing use in assessing short course effectiveness. This study examined the changes that learners intended to make in practice following an intensive day-long course offered at multiple sites, counted changes relative to the curriculum's focus, and analyzed which changes were implemented in practice. METHODS: Participants at a course on the management of male sexual dysfunction were asked to identify the changes to which they would commit. Six months after the course, they were asked to indicate which changes they implemented fully, partially, or not at all. RESULTS: A total of 352 physicians attended the courses held in 21 centers. A majority of attendees (344 or 97.7%) completed forms at the end of the course, providing 1,635 commitment statements. Six months later, 197 (57.3%) physicians provided follow-up data about 935 (55.4%) of the commitment statements originally submitted. Of these, 602 (66.52%) were completely implemented. Many of the changes related to two specific aspects of the course, namely, sexual history taking and medical intervention, accounting for 45.93% of the intended commitments and 47.67% of the changes completely implemented. Slightly over half (58%) of the course time was devoted to these two areas. There was a significant correlation between the number of changes and the amount of time allocated to that content within the course. FINDINGS: Commitment to change statements offered by course participants can be used to examine the impact of a course relative to its learning focus. Continuing medical education providers must take a critical look at commitment to change statements as an "intervention" in their own right and determine how the tool can best be used as a continuing medical education intervention.

Changing physicians' practices: the effect of individual feedback.

OBJECTIVE: To determine whether physicians who received feedback from six peers, six referring/referral physicians, six co-workers, and 25 patients about 55 aspects of their medical practices (e.g., able to reach doctor by phone after office hours) would make changes to their practices based on that feedback. METHOD: In an earlier study, 308 physicians were given feedback about 106 aspects of their practices in the form of mean Likert-scale ratings that (1) the peers made on 26 aspects; (2) the referring/referral physicians made on 23 aspects; (3) the co-workers made on 17 aspects; and (4) the patients made on 40 aspects. Three months later 255 of these physicians responded when asked to indicate whether they had contemplated or initiated changes, or whether no change had been necessary, regarding 31 practice aspects, each of which was a summary of one or more of 55 of the original 106 aspects on which they had received ratings. These 55 were considered the aspects most amenable to change over a short period. The physicians were also asked about the educational interventions that they felt would help them make changes. Multivariate analysis of variance was used to see whether the types of changes reported for the specific aspects of practice were associated with the feedback ratings received for those aspects. RESULTS: An examination of the responses showed that 83% of the 255 physicians reported having contemplated a change, and 66% reported having initiated a change for at least one aspect of practice. Changes were contemplated most frequently for aspects of practice associated with clinical skills and resource use. Changes were initiated most frequently for aspects of practice associated with communication with patients and support of patients. Physicians who contemplated or initiated changes had lower (i.e., more negative) mean ratings than did physicians who reported that no change was necessary, which suggests that the physicians did use their feedback ratings to decide about changes, although their qualitative comments indicated other sources as well. Printed material was chosen most often as a method of receiving continuing medical education related to making changes in the practice areas examined.

Concordance in communication between surgeon and patient.

OBJECTIVES: To examine (1) the capability of using interactive voice response (IVR) system technology for clinical research studies involving assessment of clinician-patient interactions and (2) the concordance of surgeons and their breast cancer patients about the content of a postbiopsy pre-treatment decision meeting. DESIGN: A descriptive comparison of the perceptions of 2 volunteer groups--surgeons and their patients--using interactive voice technology. SETTING: Surgeons' offices. PARTICIPANTS: Twenty-six dyads of surgeons and their patients with newly diagnosed breast cancer. OUTCOME MEASURES: Concordance as determined through a 15-item patient questionnaire and a parallel 11-item surgeon questionnaire addressing surgical and psychosocial aspects of breast cancer treatment. RESULTS: Fifty-four percent to 100% of the 26 dyads indicated concordance about treatment preference, treatment choice, how treatment was chosen, preference for how treatment was chosen, time for discussion about treatment, and discussion about lymph-node removal. Only 27% to 50% of dyads agreed about patient understanding of lymph-node removal, the thoroughness of discussions about adjuvant treatment, the thoroughness of discussion about emotional coping, and the sufficiency of time for the discussion of patient's concerns. In these areas of disagreement surgeons often underestimated the patient's ability to understand and underestimated the patient's perception of the thoroughness of discussions about the psychosocial aspects of the illness (concerns and coping). CONCLUSION: Surgeons and patients demonstrated concordance on their perceptions of the type of treatment desired and needed but were discordant on their perceptions of the degree of patients' understanding about post-treatment and psychosocial issues.

Inhibition of nuclear factor-kappaB-mediated adhesion molecule expression in human endothelial cells.

The transcriptional regulatory protein nuclear factor-kappaB (NF-kappaB) participates in the control of gene expression of many modulators of the inflammatory and immune responses, including the adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1). NF-kappaB is found in the cytoplasm complexed with its inhibitory protein IkappaB. On activation, IkappaB is phosphorylated and degraded, thereby freeing NF-kappaB for translocation to the nucleus. We have generated populations of endothelial cells expressing wild-type and a proteolysis-resistant mutation of IkappaB that is lacking the 36 N-terminal amino acids (IkappaBdeltaN) in order to examine the effects of expression of the mutated IkappaB on tumor necrosis factor-alpha (TNF-alpha)-induced E-selectin and ICAM-1 expression. Wild-type and IkappaBdeltaN were introduced into primary endothelial cells using retrovirus infection followed by selection with G418. The IkappaBdeltaN protein remained at untreated control levels in endothelial cells treated with TNF-alpha and also remained complexed with the NF-kappaB family member p65. Furthermore, TNF-alpha-induced NF-kappaB DNA binding activity was inhibited in the population of endothelial cells expressing IkappaBdeltaN. That population of cells was also refractory to upregulation of E-selectin and ICAM-1 after treatment with TNF-alpha. The use of a truncated IkappaBalpha protein to prevent NF-kappaB-mediated gene expression provides a novel and specific approach for investigating the role of NF-kappaB in processes associated with adhesion molecule expression during inflammation.

Analysis of stress levels among medical students, residents, and graduate students at four Canadian schools of medicine.

PURPOSE: To assess stress in medical students, residents, and graduate science students at four Canadian schools of medicine. METHOD: Four schools with different curricula in three different parts of Canada participated in the study: the University of Calgary Faculty of Medicine, the University of Alberta Faculty of Medicine, the Dalhousie University Faculty of Medicine, and the McMaster University Faculty of Health Sciences. All the medical students, residents, and graduate science students at each school were surveyed in 1994-95. The three instruments used were the University of Calgary Stress Questionnaire, the Social Readjustment Rating Scale (SRRS), and the Symptom Checklist-90. Demographic data were compared across all four schools. Analysis of variance was calculated for all test-item scores, utilizing a four (school) by three (program) by two (gender) design, which were all between subject factors. Significant main effects were followed up by using planned comparisons (Newman-Keuls, with a probability level of p < .05). Significant interaction effects were followed up by using an analysis of simple effects. RESULTS: A total of 1,681 questionnaires were returned as follows: 621 of 1,304 (48%) from the medical students, 645 of 1,495 (43%) from the residents, and 415 of 829 (50%) from the graduate science students. There were significant differences between the three groups in the natures and degrees of stress, with the graduate students reporting higher levels of stress. There were significant gender differences as well, with the women reporting higher levels of stress. Overall, stress levels were found to be mild, based on the University of Calgary Stress Questionnaire and the SRRS. CONCLUSION: This study suggests that medical students and residents experience stress at levels that appear acceptable, but ongoing monitoring and the provision of appropriate support systems will continue to be important.

Distinct transcriptional pathways of TAR-dependent and TAR-independent human immunodeficiency virus type-1 transactivation by Tat.

Tat stimulates HIV-1 gene expression during transcription initiation and elongation. Tat functions primarily through specific interactions with TAR RNA and several putative cellular cofactors to increase the processivity of RNA polymerase II complexes during HIV-1 transcription elongation. Although HIV-1 transactivation by Tat in most cell types requires intact TAR sequences, previous reports demonstrate that Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression in several central nervous system-derived astrocytic/glial cell lines in the absence of TAR. Within this study, transient expression assays performed in the astrocytic/glial cell line, U87-MG, confirm that kappa B elements within the HIV-1 LTR mediate TAR-independent transactivation by Tat and demonstrate additionally that distinct amino acid residues within the cysteine-rich activation domain of Tat are required for TAR-independent versus TAR-dependent transactivation. Established U87-MG cell lines expressing a transdominant negative mutant of I kappa B alpha, I kappa B alpha delta N, fail to support TAR-independent transactivation by Tat, suggesting that binding of NF-kappa B to kappa B enhancer elements within the HIV-1 LTR is necessary for Tat-mediated transactivation in the absence of TAR. Ribonucleic acid protection analyses of promoter-proximal and -distal transcripts derived from TAR-deleted and TAR-containing HIV-1 LTR reporter constructs in U87-MG cells indicate that the predominant effect of Tat during TAR-independent transactivation occurs at the lavel of transcription initiation, whereas a prominent elongation effect of Tat is observed in the presence of TAR. These data suggest an alternative regulatory pathway for Tat transactivation in specific cells derived from the central nervous system that is independent of TAR and that requires direct or indirect interaction of Tat with NF-kappa B-binding sites in the HIV-1 LTR.

Immunihistochemical detection of Bcl-2 in AIDS-associated and classical Kaposi's sarcoma.

Kaposi's Sarcoma (KS) is an angioproliferative disease that is characterized by proliferation of spindle-shaped cells predominantly of vascular endothelial cell origin, neoangiogenesis, inflammatory cell infiltration, and edema. Although the lesions of classical KS and AIDS-associated KS (AIDS-KS) share common histological features, AIDS-KS occurs at a markedly higher frequency with a more aggressive clinical course. Immunohistochemical analyses of 26 evolutionarily staged AIDS-KS lesions derived from HIV-infected patients demonstrate significant cytoplasmic levels of Bcl-2, a protooncogene known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression increases as the pathological stage of KS advances. Immunohistochemical analyses of classical KS lesions demonstrate prevalent expression of Bcl-2 as well, indicating that upregulation of Bcl-2 may be important in the pathogenesis of both classical and AIDS-associated KS. Coexpression of Bcl-2 and factor VIII-related antigen in spindle-shaped cells present within KS lesions suggests that Bcl-2 is upregulated within the vascular endothelial spindle-shaped cells of KS. The consequences of upregulated Bcl-2 expression within KS lesions may be prolonged spindle cell viability which, when coupled with dysregulated cellular proliferation due in part to synergistic activities of inflammatory and angiogenic cytokines and HIV-1 Tat protein, may result in the maintenance, growth, and progression of KS.

Determining priorities for family physician education in substance abuse by the use of a survey.

As the initial stage in developing a curriculum to assist family physicians to diagnose and manage alcohol abuse in their practices, questionnaires were mailed to a selected group of family physicians. A total of 117 physicians (34%) completed the questionnaire. The majority of physicians (70.1%) reported that fewer than 10% of their caseload experienced alcohol-related problems. Most physicians (59.3%) did not use any of the standard diagnostic instruments but reported that screening and detection was the most challenging alcohol-related problem along with patient management. The questionnaire identified a number of areas that could be used in the development of educational strategies to increase the expertise of primary care physicians in the diagnosis and management of alcohol-related problems.

Expression and specificity of human GM2 activator protein.

The cDNA encoding GM2 activator was expressed in the Escherichia coli/pT7-7 system. The yield of the GM2 activator with greater than 99% purity was about 3 mg per liter culture. The recombinant GM2 activator was found to be as active as that isolated from human kidney. The availability of the recombinant GM2 activator enabled us to critically examine the specificity of this activator protein. Our results show that the specificity of GM2 activator is not as strict as that reported previously. Although GM2 activator stimulates most efficiently the degradation of GM2 carried out by beta-N-acetylhexosaminidase A (Hex A), this activator also stimulates the following reactions: (a) conversion of GM2 to GA2 by clostridial sialidase; (b) hydrolysis of GalNAc from dipalmitoylphosphatidylethanolamine-II3NeuAcGgOse3 by Hex A; and (c) liberation of Gal from GM1 by beta-galactosidase at a high activator concentration. Thus, this activator does not differentiate between GM2 and dipalmitoylphosphatidylethanolamine-II3NeuAcGgOse3 or between Hex A and clostridial sialidase. The micellar forms of GD2 and GalNAc-GD1a were found to be more readily hydrolyzed by Hex A than GM2 in the absence of GM2 activator. Our results also show that saposin B can enhance the stimulatory activity of GM2 activator, but it cannot promote the stimulatory activity of sodium taurodeoxycholate. Taken together, our results suggest that the mechanism of action of GM2 activator is different from saposin B, and the action of GM2 activator is more than to solubilize lipid substrates. The effectiveness of GM2 activator in stimulating the hydrolysis of GM2 may be due to its ability to recognize the specific trisaccharide structure of the GM2 epitope, GalNAc beta 1-->4(NeuAc alpha 2-->3)Gal-, and to modify the GalNAc-NeuAc interaction in this structure.

Human serum biotinidase. cDNA cloning, sequence, and characterization.

Biotinidase (EC 3.5.1.12) catalyzes the hydrolysis of biocytin, the product of biotin-dependent carboxylase degradation, to biotin and lysine. Biotinidase deficiency is an inherited metabolic disorder of biotin recycling that is characterized by neurological and cutaneous abnormalities, and can be successfully treated with biotin supplementation. Sequences of tryptic peptides of the purified human serum enzyme were used to design oligonucleotide primers for polymerase chain reaction amplification from human hepatic total RNA to generate putative biotinidase cDNA fragments. Sequence analysis of a cDNA isolated from a human liver library by plaque hybridization with the largest cDNA probe revealed an open reading frame of 1629 bases encoding a protein of 543 amino acid residues, including 41 amino acids of a potential signal peptide. Comparison of the open reading frame with the known biotinidase tryptic peptides and recognition of the expressed protein encoded by this cDNA by monoclonal antibodies prepared against purified biotinidase demonstrated the identity of this cDNA. Southern analyses suggested that biotinidase is a single copy gene and revealed that human cDNA probes hybridized to genomic DNA from mammals, but not from chicken or yeast. Northern analysis indicated the presence of biotinidase mRNA in human heart, brain, placenta, liver, lung, skeletal muscle, kidney, and pancreas.

Sports medicine electives. Are they available in Canadian family medicine programs?

Sports medicine is becoming a larger part of a family physicians' practice. We surveyed all family medicine teaching programs in Canada to determine how many offer sports medicine experiences and who teaches them. The study found that few residents have clinical training in sports medicine, though most have attended seminars. Primary care physicians, orthopedic surgeons, physiotherapists, and rheumatologists teach sports medicine.

Evidence for two cDNA clones encoding human GM2-activator protein.

Two cDNAs encoding GM2 activator, pGM2A (648 bp) and GAP (1093 bp), were isolated from human placenta lambda gt11 libraries. The DNA sequence of pGM2A from 1 to 302 was almost identical with GAP, but diverged from 303-648. PCR was used to demonstrate the presence of both species of GM2 activator in placental RNA. Both cDNAs hybridized to mRNAs of approximately 2.3 kb and to identical single bands on genomic Southern blots.

Sports Medicine: What family physicians see and what they need to learn.

The relative frequency with which family physicians managed several sports-related problems was studied, as well as their level of comfort with each of the conditions and the sources of information they planned to use to improve their knowledge or skills. Physicians reported greater comfort with conditions they managed more often. Most intended to seek information.

Identification of a tissue-specific regulatory element within the human muscle glycogen phosphorylase gene.

Northern blot analysis showed that human muscle glycogen phosphorylase is developmentally regulated in human adult and fetal skeletal muscle. Furthermore, muscle phosphorylase mRNA expression is temporally regulated in the C2C12 mouse muscle cell line. To define regulatory elements that control expression of the human muscle glycogen phosphorylase gene, the structure of the 5' end of the gene was determined, and 1,129 base pairs of the 5'-flanking region were subcloned and sequenced. Primer extension, RNase protection, and S1 nuclease protection experiments mapped the transcription start site to 76 base pairs upstream from the starting methionine. Sequential deletions of the 5'-flanking region were tested for the ability to activate chloramphenicol acetyltransferase (CAT) expression in fused or proliferating C2C12 cells. Inclusion of the 43 base pairs between -612 and -570 led to a 9-fold increase in CAT activity in fused myotubes. No increase was observed in proliferating myoblasts. This region contains a 10-base pair sequence, CTCCAAAAGG, at -592, which is also repeated at -252. Mutation of the sequence at -592 results in a 50% decrease in CAT activity compared with the amount of CAT activity observed with the normal or a control mutation. These results indicate that a regulatory element is found within -612 to -570 of the 5'-flanking DNA of the human muscle glycogen phosphorylase gene which activates transcription only in differentiated muscle cells.

Responses to non-emergency questions in rural medicine: their usefulness to practice decisions.

This study reports the nature of non-emergency, day-to-day practice-related questions which arose in rural practice and were phoned in to a medical information system (MIS). The usefulness of these questions, and their responses, to clinical decision-making is outlined. Sixty-seven practitioners from 10 rural communities enrolled in the project. In response to each inquiry two or three articles were sent to the practitioner and to a consultant for validation. At the conclusion of the study the questions posed, and their responses, were examined. Forty-six per cent of the questions received were categorized as diagnostic; 30% as management; and 24% as therapeutic. Questions were classified using the ICD.9.CM. Those most frequently posed were in the nervous system/sense organs (13%), injury/poisoning (9%), and genito-urinary (9%) categories. Interviews with doctors and consultants were conducted to assess the usefulness of the service. Study findings suggest that an MIS can provide helpful information for improving daily aspects of clinical care, doctor-patient communication, administrative decision-making, and physician education. Practitioners, consultants, and medical librarians reported benefits from this service.