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Biomedical subjects

C L Sears

Publications and source records attributed to C L Sears.

40 records · Page 3Linked to original sources

AIDS enteropathy.

Chronic diarrhea is one of the hallmarks of advanced human immunodeficiency virus (HIV) disease. The symptoms of this complication are troublesome, have a significant impact on the patient's quality of life, and in severe cases can lead to extreme abnormalities in fluids and electrolytes and can even cause death. The workup for AIDS-associated diarrhea is often frustrating and frequently unrewarding. However, during the last 10 years, much has been learned about the causes of diarrhea; while treatment is still often ineffective, some advances have been made. Dr. John G. Bartlett and his colleagues in the Department of Medicine at Johns Hopkins University School of Medicine have been responsible for many of these advances. In this AIDS Commentary, these experts discuss recent advances that have enhanced our understanding of chronic diarrhea in HIV-infected persons and offer their recommendations for the most efficient and effective approach to managing these patients.

AIDS-Related Opportunistic Infections↗

Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C.

The heat-stable enterotoxin of Escherichia coli (STa) stimulates membrane-bound guanylate cyclase in intestinal epithelium and induces fluid and ion secretion. Using the T84 human colon carcinoma cell line as a model, we observed that phorbol esters markedly enhanced STa-stimulated cyclic GMP accumulation in T84 cells (C. S. Weikel, C. L. Spann, C. P. Chambers, J. K. Crane, J. Linden, and E. L. Hewlett, Infect. Immun. 58:1402-1407, 1990). In this study we document that the phorbol ester treatment increases 125I-STa-binding sites as well as membrane-bound guanylate cyclase activity in T84 cells and provide evidence that both effects are mediated by phosphorylation. Guanylate cyclase activity was increased approximately 50% in membranes prepared from intact T84 cells treated with phorbol-12,13-dibutyrate (beta-PDB) and after treatment of homogenates with beta-PDB in a manner dependent on ATP, MgCl2, and cytosol. Similarly, treatment of membranes with purified bovine brain protein kinase C in the presence of appropriate cofactors and beta-PDB resulted in an increase in STa-stimulated guanylate cyclase activity of about 70%. Likewise, the number of 125I-STa-binding sites was increased by about 25 to 40% in membranes prepared from intact cells or homogenates treated with beta-PDB; no effect on binding affinity (Kd = 0.15 nM) was noted. These experiments suggest that protein kinase C may phosphorylate the STa receptor-guanylate cyclase or a closely related protein and increase guanylate cyclase activity. The stimulatory effects of protein kinase C on STa-sensitive guanylate cyclase are opposite in direction to the profound inhibitory effects of the kinase on atrial natriuretic peptide-stimulated guanylate cyclase, demonstrating differential regulation by protein kinases within the guanylate cyclase-receptor family.

Adenosine Triphosphate↗

The effectiveness of a consultation. Compliance with initial recommendations.

To identify the attributes of an effective consultation, 202 general medicine consultations were analyzed to assess the extent of compliance with the consultant's initial recommendations. The overall compliance rate was 77 percent. Compliance decreased as the number of recommendations increased. The consultant made more recommendations among patients who had more complex and more severe illnesses. Although compliance did increase significantly in severely ill patients (p less than 0.01), with each severity level, compliance was higher when five or fewer recommendations were made. In fact, compliance decreased from 96 percent in severely ill patients with small consultation lists to 79 percent in those with large lists. Compliance was greatest with recommendations involving medications and least with those requiring direct physician and nursing action. Multivariate analysis confirmed that clinical severity of the patients' illnesses and the type and number of recommendations were all predictors of compliance. To promote overall compliance, consultants should limit the total number of recommendations in their initial consultation to five or fewer, focusing on issues central to current patient care. This is especially true in severely ill patients. Since recommendations that must be implemented by physicians or nurses have a lower compliance rate, consultants must carefully follow up those requests.

Age Factors↗

General medicine consultation. Lessons from a clinical service.

The 564 consultations performed by a general medicine consultation service during its first year were analyzed in order to provide a concrete definition of this new academic domain. Of the consultations, 52 percent were for patients on the surgical service. Among these patients, the most common reason for consultation was the preoperative management of chronic illness, specifically, hypertension, diabetes, and angina; 47 percent of such patients had two or more chronic illnesses. The service recommended cancellation of planned surgery in 2 percent and postponement in 9 percent of the 210 patients seen preoperatively. Patients on the psychiatric service accounted for 47 percent of the consultations. In this group, diagnostic issues were the most common reasons for consultation, that is, abdominal pain, dementia, and the suspicion of thyroid disease. Only 12 percent of the patients were seen for prognostic reasons, usually related to the planned use of electroconvulsive therapy or tricyclic antidepressants. The service was evaluated by the referring physicians who rated the service favorably on its "mechanics," as well as on its qualitative performance. However, complaints of triviality were voiced when the average length of the list of recommendations seemed disproportionate to the complexity of the problems. The service was also evaluated by the residents who had provided consultations. From their perspective, the service was more successful in teaching the "art" of consultation than the "science." This experience provides an operational definition of the work facing a general medicine consultation service as well as data useful in focusing future educational programs and research efforts.

Family Practice↗