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Biomedical subjects

D C Lynch

Publications and source records attributed to D C Lynch.

At least 19 recordsLinked to original sources

Interim evaluation of the Rural Health Scholars Program.

BACKGROUND: The imperative to address physician maldistribution has been directed in part at medical schools. DESCRIPTION: The Rural Health Scholars Program (RHSP) is an enrichment initiative that has been implemented at 2 medical schools to increase the number of students likely to practice primary care in rural, underserved areas. It is a longitudinal program that includes a skill-building workshop; a 5-week summer preceptorship with community-based preceptors in rural, underserved areas; and opportunities to return to preceptorship sites during 3rd- and 4th-year rotations. Students also attend community-based and teleconference seminars and workshops, as well as informal social gatherings. EVALUATION: A static-group comparison design was used to compare program participants with nonparticipants regarding residency program types and locations. CONCLUSIONS: The RHSP is meeting some interim objectives conducive to its long-term goal of developing physicians who will practice primary care medicine in rural, underserved areas of North Carolina.

Career Choice↗

Moving from policy to practice in curriculum change at the University of Virginia School of Medicine, East Carolina University School of Medicine, and SUNY-Buffalo School of Medicine.

A set of formative evaluation studies from the medical schools of the University of Virginia (UVA), East Carolina University (ECU), and the State University of New York at Buffalo (SUNY-Buffalo) portrays, in qualitative and quantitative terms, evidence of achievements and obstacles to the curricular reform supported by The Robert Wood Johnson Foundation's Generalist Physician Initiative (GPI). In this paper, innovations in the under-graduate curriculum, a specific course, and instructional strategies are examined. Individual interviews of faculty and focus groups with students assessed opinions about curricular change at the University of Virginia. Questionnaires and focus groups provided information about the impact of course changes at East Carolina University. Questionnaires completed by students provided information of the effect of modifying the instructional strategies at SUNY-Buffalo. The obstacles to implementing change at the three schools included breakdowns in the faculty's understanding and support of change, lack of skills required to implement change, and weakness in coordinating and assessing planned change. Although the GPI catalyzed changes in the content and conduct of generalist education at the three schools, many lessons were learned that are applicable to other medical schools.

Curriculum↗

Academic models for practice relief, recruitment, and retention at the University of New Mexico Medical Center and East Carolina University School of Medicine.

Locum tenens programs were independently developed by the University of New Mexico Health Sciences Center and East Carolina University School of Medicine to address health care needs within their states. The programs represent distinct models to provide locum tenens services for practices in rural and medically underserved regions through collaboration with stage government representatives and agencies. Differences between programs include years of operation, days of coverage provided, types of learners and providers involved, sources of funding, costs of the programs, and extent of institutional support. Common beneficial outcomes of the programs include coverage for struggling practices, training in rural medicine for locum tenens providers, recruitment of physicians to rural practice sites, and improved relationships with program partners. Adequate funding and institutional support are essential for success of locum tenens programs.

Career Choice↗

Influence of medical school on medical students' opinions about primary care practice.

PURPOSE: To compare first- and fourth-year medical students' opinions about primary care practice. METHOD: A cross-sectional survey was made of medical students at New York Medical College (NYMC) and East Carolina University School of Medicine (ECUSOM) over three years (1993-94, 1994-95, and 1995-96). Three consecutive classes of first-year students from both schools (n = 807), two consecutive classes of fourth-year NYMC students (n = 373), and three consecutive classes of fourth-year ECUSOM students (n = 221) were given a self-administered questionnaire about professional aspects of primary care practice. Responses to ten items about primary care practice were the independent variables in a logistic regression analysis. Career choice, categorized as primary care or non-primary care, was the dependent variable. Independent, two-tailed t-tests were employed to compare the responses of the first-year students interested in primary care careers with those of the fourth-year students interested in primary care careers. RESULTS: In all, 639 (79%) of the first-year students and 396 (67%) of the fourth-year students returned completed questionnaires. The first-year students interested in primary care careers were significantly more likely to believe that primary care practice has more prestige, has more intellectual stimulation, needs a large knowledge base, and involves work that is more important than that of non-primary care physicians, and were significantly more likely to disagree with the assertion that in primary care practice, physicians have more control over their working hours. With one exception (prestige of primary care practice), all these independent variables were significant for the fourth-year students as well. The comparison of the first- and fourth-year students indicated that the fourth-year students were significantly more likely to believe that primary care practice has more intellectual stimulation, needs a large knowledge base, and requires knowledge that non-primary care practice may not; they were also significantly more likely to disagree with the assertions that primary care practice is adequately compensated, has more prestige, and allows more control over working hours. CONCLUSION: It appears that students' positive perceptions about primary care practice may change as realistic perceptions about the professional demands on primary care physicians develop during medical school.

Adult↗

Standardized examination performance and specialty choice.

BACKGROUND AND OBJECTIVES: It has been suggested that medical students who attend schools known for graduating prospective primary care physicians may enter primary care residencies, rather than non-primary care residencies, because they are unable to compete for subspecialty residencies due to poorer academic performance. This study determined if performance on standardized examinations conducted by the National Board of Medical Examiners (NBME) could differentiate between students who selected primary care and those who selected non-primary care specialties at a medical school in the southeastern United States committed to graduating primary care physicians. METHODS: We examined initial scores on NBME examinations and subsequent residency selections by 780 students over a 14-year period to determine if there were differences in the kind of residency placements of students who passed and those who failed the examinations. RESULTS: Data analysis indicated that medical students who entered primary care and non-primary care residencies were not distinguishable on the basis of standardized examination performance. CONCLUSIONS: These results may help to refute negative stereotypes about students who enter primary care residencies and about medical schools known for promoting careers in primary care.

Career Choice↗

Clearance of normal and type 2A von Willebrand factor in the rat.

A model for the in vivo clearance of normal and mutant forms of human von Willebrand factor (vWF) has been established using catheterized rats. vWF clearance rates in rat plasma were determined by quantitation of reduced vWF subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and multimeric vWF was analyzed using nondenaturing SDS-agarose gels. Normal vWF derived from human umbilical vein endothelial cells displayed a biphasic pattern of clearance, with half times of 35 minutes (T 1/2 a; SD 15. min.) and 245 minutes (T 1/2 b; SD 76. min.); metabolic clearance rate = 0.65%/minute. High molecular weight multimers of vWF were cleared more rapidly than dimeric vWF. vWF containing the S1613P mutation found in some type 2A von Willebrand disease (vWD) patients was observed to undergo proteolysis in vivo resulting in a reduction of high molecular weight vWF and concomitant appearance of rapidly-migrating satellite species, although the overall clearance rate of vWF antigen was similar to wild type vWF. These results provide direct in vivo evidence that the S1613P mutation causes the characteristic type 2A vWD phenotype. Full-length recombinant vWF produced from transfected Chinese hamster ovary cells was cleared at a similar rate to endothelial cell-derived vWF, and recombinant vWF devoid of O-linked carbohydrates was cleared significantly faster. vWF devoid of sulfate was cleared at a similar rate as wild type vWF, indicating the sulfate moiety of vWF does not regulate in vivo clearance. This animal model should prove useful in subsequent in vivo analysis of additional forms of vWD and in the development of protease inhibitor therapy for 2A vWD.

Animals↗

Tuberculosis control through contact investigation.

With the resurgence of tuberculosis (TB) in the United States since 1984, much has been said of insuring proper treatment with modern therapy regimens and of patient compliance with medications. Yet, little has been said of the role of contact investigations associated with each case. TB control programs are uniquely prepared to perform these contact investigations. This article describes the contact investigations performed by a county TB program in one year to illustrate the effort involved.

Communicable Disease Control↗

Endothelial-cell-specific regulation of von Willebrand factor gene expression.

In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothelial-cell-specific gene expression. In this study, deletion analyses were carried out to identify the region of the vWf gene which regulates its endothelial-cell-specific expression. A 734-bp fragment which spans the sequence from -487 to +247 relative to the transcription start site was identified as the cell-type-specific promoter. It consists of a minimal core promoter located between -90 and +22, a strong negative regulatory element located upstream of the core promoter (ca. -500 to -300), and a positive regulatory region located downstream of the core promoter in the first exon. The activity of the core promoter is not cell type specific, and the negative regulatory region is required to inhibit its activity in all cell types. The positive regulatory region relieves this inhibition only in endothelial cells and results in endothelial-cell-specific gene expression. The positive regulatory region contains sequences predicting possible SP1, GATA, and octamer binding sites. Mutations in either the SP1 or octamer sequence have no effect on transcriptional activity, while mutation in the GATA binding element totally abolishes the promoter activity. Evidence that a GATA factor is involved in this interaction is presented. Thus, the positive regulatory region with an intact GATA binding site is required to overcome the inhibitory effect of the negative regulatory element and activate vWf gene expression in an endothelial-cell-specific manner.

Animals↗

O-linked carbohydrate of recombinant von Willebrand factor influences ristocetin-induced binding to platelet glycoprotein 1b.

By transfecting the full-length cDNA for human von Willebrand factor (vWf) into a line of Chinese hamster ovary cells with a defect in carbohydrate metabolism, we have prepared recombinant vWf specifically lacking O-linked carbohydrates. We have compared this under-glycosylated protein to fully glycosylated recombinant vWf with respect to several structural and binding properties. vWf deficient in O-linked glycans was synthesized, assembled into multimers, and secreted in an apparently normal manner and was not prone to degradation in the extracellular milieu. It did not differ from fully glycosylated vWf in ability to bind to heparin or to collagen type I but did interact less well with glycoprotein 1b on formalin-fixed platelets. This decreased interaction was evidenced in both a lessened overall binding to platelets and in diminished capacity to promote platelet agglutination, in the presence of ristocetin. In contrast, no difference was seen in platelet binding in the presence of botrocetin. These data indicate a possible role for O-linked carbohydrates in the vWf-glycoprotein 1b interaction promoted by ristocetin and suggest that abnormalities in carbohydrate modification might contribute to the altered ristocetin-dependent reactivity between vWf and platelets described for some variant forms of von Willebrand disease.

Amino Acid Sequence↗

Development and crossmodal transfer of contextual control of emergent stimulus relations.

Six normally capable adults first learned three conditional relations in each of two prospective equivalence classes via match-to-sample training with figures as conditional (sample) and discriminative (comparison) stimuli. Then one trained conditional relation in each prospective class was brought under the control of contextual stimuli, two dictated nonsense syllables. Test performances indicated the emergence of untrained conditional relations, and therefore two equivalence classes, that were conditional on the contextual stimuli. These tests involved untrained combinations of contextual stimuli and stimuli in conditional relations, suggesting that the contextual stimuli functioned independently to control conditional relations rather than forming compound stimuli with samples and comparisons in training. Next, two novel figures were made equivalent to each of the original dictated contextual stimuli by match-to-sample training and testing. On subsequent tests, all subjects demonstrated transfer of conditional control of untrained conditional relations from the original auditory contextual stimuli to equivalent visual stimuli. These outcomes further supported the conclusion that the contextual stimuli exerted true conditional control over conditional relations in the equivalence classes and were not merely elements of compound stimuli.

Adult↗

Sulfation of von Willebrand factor.

von Willebrand factor (vWF) is a multimeric adhesive glycoprotein essential for normal hemostasis. We have discovered that cultured human umbilical vein endothelial cells incorporate inorganic sulfate into vWF. Following immunoisolation and analysis by polyacrylamide or agarose gel electrophoresis, metabolically labeled vWF was found to have incorporated [35S]-sulfate into all secreted multimer species. The time course of incorporation shows that sulfation occurs late in the biosynthesis of vWF, near the point at which multimerization occurs. Quantitative analysis suggests the presence, on average, of one molecule of sulfate per mature vWF subunit. Virtually all the detectable sulfate is released from the mature vWF subunit by treatment with endoglycosidases that remove asparagine-linked carbohydrates. Sulfated carbohydrate was localized first to the N-terminal half of the mature subunit (amino acids 1 through 1,365) by partial proteolytic digestion with protease V8; and subsequently to a smaller fragment within this region (amino acids 273 through 511) by sequential digestions with protease V8 and trypsin. Thus, the carbohydrate at asparagine 384 and/or 468 appears to be the site of sulfate modification. Sodium chlorate, an inhibitor of adenosine triphosphate-sulfurylase, blocks sulfation of vWF without affecting either the ability of vWF to assemble into high molecular weight multimers or the ability of vWF multimers to enter Weible-Palade bodies. The stability of vWF multimers in the presence of an endothelial cell monolayer also was unaffected by the sulfation state. Additionally, we have found that the cleaved propeptide of vWF is sulfated on asparagine-linked carbohydrate.

Chlorates↗

Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease.

Severe von Willebrand disease is characterized by undetectable or trace quantities of von Willebrand factor in plasma and tissue stores. We have studied the genomic DNA of 10 affected individuals from six families with this disorder using probes from the 5' and 3' ends of the vWF cDNA and with a probe extending from the 5' end into the central region. Southern blots of restriction endonuclease digests and gene dosage analysis measurements carried out with quantitative slot blots of undigested genomic DNA separated these patients into three groups. The first group consisted of a family with complete homozygous deletions of the vWF gene in the four probands. Gene dosage analysis was consistent with heterozygous deletions in both of the asymptomatic parents and four asymptomatic siblings of this kindred (P less than 0.01). The second group was comprised of a family in which there was a complete heterozygous deletion of the vWF gene in the proband and one asymptomatic parent, suggesting that a different type of genetic abnormality was inherited from the other parent. Thus, the patient appeared to be doubly heterozygous for interacting genetic abnormalities affecting vWF expression. In the third group, no gene deletions could be detected. Alloantibodies developed only in the kindred with homozygous deletions. These techniques should prove useful in identifying carriers of severe von Willebrand disease and also in defining patients predictably at risk of developing alloantibodies to vWF.

Chromosome Deletion↗