Biomedical subjects
B Kimball
Publications and source records attributed to B Kimball.
Pituitary adenylate cyclase-activating peptide stimulates neurite growth in PC12 cells.
The ability of PACAP-38 to stimulate morphological development was studied using rat pheochromocytoma PC12 cells. PACAP-38 produced concentration-dependent increases in percentage of cells exhibiting neurite extension. Similar increases were produced by forskolin (28 +/- 2% at 96 h) and 8-bromo cAMP (30 +/- 2%). Vasoactive intestinal peptide and alpha-calcitonin gene-related peptide were without effect. PACAP-38 produced significant increases in PC12 cell cAMP content and inositol phosphate turnover. Intracellular [Ca2+] increased from 169 +/- 14 nM to 560 +/- 58 nM in response to 1 microM PACAP-38. PACAP-stimulated neurite outgrowth was abolished by RpcAMPS, an inhibitor of cAMP-dependent kinases but was unaffected by the protein kinase C antagonist H7.
Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.
BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined. METHODS AND RESULTS: To address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after 2 years. In 299 patients (90%), 3858 coronary segments containing 2309 stenoses were measured blindly on pairs of films with an automated computerized quantitative system. Total and LDL cholesterol decreased by 21 +/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but changed by < 2% in placebo patients. The primary end point, coronary change score, defined as the per-patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01). Progression (a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm) with no regression at other sites occurred in 48 of 146 lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New coronary lesions developed in 23 lovastatin and 49 placebo patients (P = .001). The beneficial effect of treatment was most pronounced in the more numerous, milder lesions and in patients whose baseline total or LDL cholesterol levels were above the group median. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and inhibits the development of new coronary lesions.
Design features of a controlled clinical trial to assess the effect of an HMG CoA reductase inhibitor on the progression of coronary artery disease. Canadian Coronary Atherosclerosis Intervention Trial Investigators Montreal, Ottawa, and Toronto, Canada.
This report describes the design and methodological features of a double-masked, randomized, placebo-controlled trial to determine whether administration of the HMG CoA reductase inhibitor lovastatin retards the progression or facilitates the regression of coronary atherosclerosis. The study population consists of coronary patients with a recent arteriogram that characterizes them as being at high risk for coronary progression and a baseline fasting total serum cholesterol > or = 5.7 mmol/L and < or = 7.8 mmol/L. Lovastatin, or matching placebo, are up-titrated from 20 mg to 40 mg to 80 mg/day during the first 16 weeks of the study in an attempt to attain a fasting serum LDL cholesterol level of 3.4 mmol/L; patients and study personnel remain masked as to cholesterol levels throughout the trial. Coronary arteriography is repeated at 2 years, or earlier if necessitated by worsening symptoms, and all segments are measured quantitatively using a computer-based system. The primary outcome of the trial is a comparison between the lovastatin and placebo groups for coronary change score, defined as the mean of the minimum lumen diameter changes for all lesions (follow-up minus baseline arteriogram) per patient. The advantages and limitations of coronary arteriographic trials and some of the issues related to outcome measurements are discussed. The question posed by this study is of clinical relevance because the consequences of progression of coronary disease, angina, myocardial infarction, and sudden cardiac death are leading causes of morbidity and mortality.
Planetree nursing: a paradigm of advocacy and humanistic care.
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Disopyramide in hypertrophic cardiomyopathy. I. Hemodynamic assessment after intravenous administration.
The hemodynamic effects of intravenous disopyramide were determined in 43 patients with hypertrophic cardiomyopathy and pressure gradients at rest (resting obstruction). The basal subaortic pressure gradient decreased in all patients by a mean of 61 mm Hg (range 16 to 123); in 35 patients the gradient was abolished (less than 20 mm Hg). The reduction in pressure gradient was achieved through a decrease in left ventricular systolic pressure, from 178 to 135 mm Hg (p less than 0.0001), and a rise in aortic systolic pressure, from 105 to 123 mm Hg (p less than 0.0001). Left ventricular ejection time was reduced from 326 to 273 ms (p less than 0.0001). Left ventricular end-diastolic pressure decreased from 19 to 16 mm Hg (p less than 0.0001). In a subgroup of 13 patients, cardiac output was unchanged after disopyramide, despite a prolongation of the pre-ejection period from 104 to 137 ms (p less than 0.0001) indicating a decrease in contractility. The maintenance of cardiac output, despite a decrease in contractility, may reflect a decrease in mitral regurgitation resulting from the reduction of systolic anterior motion of the mitral valve by disopyramide. These results indicate that disopyramide produces predictably favorable hemodynamic effects in patients with hypertrophic cardiomyopathy and resting obstruction to left ventricular outflow.
Aggregation of complement receptors on human neutrophils in the absence of ligand.
C3bi receptors (CR3) on human polymorphonuclear leukocytes (PMN) bind ligand-coated particles and promote their ingestion. The binding activity of CR3 is not constitutive but is transiently enabled by phorbol esters (Wright, S. D., and B. D. Meyer, 1986, J. Immunol. 136:1759-1764). Our observations indicate that the capacity of CR3 to bind ligand is tightly correlated with the degree of ligand-independent aggregation of the receptor in the plane of the membrane. Fixed PMN were labeled with anti-CR3 monoclonal antibodies and streptavidin colloidal gold before viewing in the electron microscope either en face or in thin section. On unstimulated PMN, gold particles marking CR3 were dispersed randomly. Stimulation of PMN for 25 min with phorbol myristate acetate (PMA) dramatically enhances binding of C3bi-coated particles, and the CR3 on such stimulated cells was observed in clusters containing more than six gold particles. CR3 was not aggregated over coated pits. After 50 min in PMA, the binding activity of CR3 falls, and the distribution of CR3 was again observed to be disperse. If a hydrophilic phorbol ester was washed away after a 20-min stimulation, binding activity remains elevated for at least 50 min, and CR3 remained aggregated. Thus, clustering of CR3 was temporally correlated with its ability to bind ligand and initiate phagocytosis. Unlike CR3, Fc receptors and HLA did not exhibit changes in their aggregation state in response to PMA. Treating PMN with formyl-methionyl-leucyl-phenylalanine, which enhances expression of CR3 but not its function, did not lead to aggregation of CR3. These observations suggest that a clustered configuration is a precondition necessary for binding ligand and signaling phagocytosis.
An innovative approach to geriatric acute care delivery: the Choate-Symmes experience.
Hospitals, like those described in this study, must develop alternative models of health care delivery that allow them to respond to many challenges while providing high-quality health care to geriatric patients. In this program, 10-bed geriatric units were established in two hospitals, and patients age 65 and older were selected at random for admission to the units. Following comprehensive assessment, self-reliance was fostered using individualized interventions. Discharge planning began at admission. A multidisciplinary approach with regular team conferences including families was also used. Results of this approach suggest that such intervention can reduce length of stay without affecting quality of care. This paper describes the delivery model in detail, focuses on issues related to the implementation of the intervention, and highlights the lessons learned by Choate-Symmes personnel through their demonstration of the model.
Effect of intracoronary nitroglycerin on myocardial blood flow and distribution in pacing-induced angina pectoris. Quantitative assessment by single-photon emission tomography.
Changes in regional coronary flow after administration of intracoronary nitroglycerin were assessed by measuring total coronary blood flow (using coronary sinus flow catheters) and its regional distribution (by quantitative single-photon emission tomography of injected radioactive microspheres). After pacing to angina, 10 patients with coronary artery disease received serial selective left coronary injections of technetium-99m microspheres, 40 micrograms of nitroglycerin, and indium-111 microspheres. Significant changes in coronary flow distribution were determined by subtracting prenitroglycerin from postnitroglycerin tomographic profiles. Perfusion of each myocardial segment was classified as normal mildly, moderately or severely compromised, based on upstream coronary anatomy. The overall increase in coronary flow was 23% in the normal territories and 33%, 44% and 15% (p less than 0.05), in the mildly, moderately and severely compromised territories, respectively, compared with control values. Thus, intracoronary nitroglycerin increased coronary blood flow to all perfusion territories. The increase in distribution of coronary flow was greatest in the mildly and moderately compromised regions and the least in the most severely compromised regions; this is probably a reflection of the underlying coronary reserve.