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Biomedical subjects

B Lewis

Publications and source records attributed to B Lewis.

374 records · Page 21Linked to original sources
PubMedDate not supplied

Hereditary hyperlipidemia in the rabbit due to overproduction of lipoproteins. I. Biochemical studies.

An inherited metabolic disorder in a strain of New Zealand White rabbits, characterized by marked hypercholesterolemia (394 +/- 100 mg/dl), with moderately elevated or normal triglyceride levels is described. Low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and very low density lipoprotein (VLDL) cholesterol levels were increased. VLDL and IDL, and to a lesser extent LDL, had increased free cholesterol and esterified cholesterol content, and triglyceride content was reduced. Kinetic studies with 131I and 125I-labelled rabbit lipoproteins showed a marked increase in production rates of VLDL apo B and LDL apo B. LDL cholesterol levels were directly related to LDL apo B production rate (r = 0.938, p less than 0.001). Both in hypercholesterolemic and normal rabbits injected with labelled VLDL, the specific activity-time curves of VLDL apo B and LDL apo B did not intersect, indicating that LDL apo B was in part derived from sources other than VLDL. No defect was demonstrated in receptor-mediated catabolism of LDL by cultured skin fibroblasts from hyperlipidemic animals. The fractional catabolic rate of LDL apo B was subnormal, but increased when the expanded LDL apo B pool size was reduced by exchange transfusion; the low fractional catabolism may therefore be attributable, at least in part, to saturation of LDL receptors consequent upon the increased pool size of LDL. The hyperlipidemia in this strain of rabbits may be unique in that the underlying mechanism appears to be overproduction of VLDL and LDL.

Animals↗
PubMedDate not supplied

Hereditary hyperlipidemia and atherosclerosis in the rabbit due to overproduction of lipoproteins. II. Preliminary report of arterial pathology.

A genetically determined hyperlipidemic strain of New Zealand White rabbit that has features in common with combined familial hyperlipidemia in humans has been identified. The morphologic findings in a few animals fed a normal chow diet are reported. These consisted of macroscopically visible aortic intimal elevations found in the greatest number in the descending thoracic aorta. The plaques showed the presence of a cell population consisting of modified smooth muscle cells and lipid-laden macrophages. The lesion bases were necrotic and acellular, and some showed the presence of dystrophic calcification. Scanning electron microscopy revealed numerous monocytes attached to the endothelium. Endothelial defects were common, and these were filled with swollen and "ruffled" macrophages. Transmission electron microscopy confirmed the presence of lipid-laden cells penetrating between adjacent endothelial cells. These findings resemble those reported in a number of different animal species after dietary induction of hyperlipidemia. This strain is a useful new model for the study of atherogenesis.

Age Factors↗
PubMedDate not supplied

Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers.

BACKGROUND: Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers. METHODS: Residents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function. RESULTS: Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups. CONCLUSIONS: Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.

Administration, Oral↗
PubMedDate not supplied

Correlation of tumor suppressor P53 RNA expression with human immunodeficiency virus disease in rapid and slow progressors.

OBJECTIVE: To determine the relation between P53 tumor suppressor RNA expression and human immunodeficiency virus (HIV) disease progression. STUDY DESIGN/METHODS: A quantitative assay of P53 RNA expression was used to analyze a cohort of HIV-negative persons. The assay was then used in longitudinal and cross-sectional studies of HIV slow and rapid progressors. RESULTS: We demonstrate first that P53 expression in peripheral blood mononuclear cells from HIV-1-seronegative persons is minimal. Longitudinal studies in a small cohort of HIV-1-infected slow and rapid progressors reveal that rapid progressors seem to have greater P53 RNA expression over time. This was validated in a cohort of 26 HIV-1-infected persons in whom the expression of P53 RNA was significantly greater in persons with rapid progression of HIV-1 disease. CONCLUSION: These data suggest that P53 RNA expression may play a role in the pathogenesis of HIV-1 disease, though the mechanism of this interaction remains unknown.

Animals↗
PubMedDate not supplied

A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa.

Rat spermatozoa from both the caput and cauda epididymidis were shown to generate superoxide anion (O2-.) both spontaneously and following stimulation with NAD(P)H. Caput spermatozoa gave a significantly greater O2- response to NADPH stimulation than caudal cells, whereas in both cell types the responses to exogenous NADPH and NADH were approximately equivalent. Analysis of H2O2 production revealed that this oxidant was generated only by caudal epididymal cells and only in these cells did the stimulation of reactive oxygen species (ROS) production with NADPH lead to an increase in tyrosine phosphorylation. Stimulation of ROS production with NADPH increased intracellular cyclic adenosine monophosphate (cAMP) levels in both caput and caudal epididymal cells, but only in caudal cells did cAMP stimulate tyrosine phosphorylation, in keeping with the NADPH results. On the basis of these findings we propose that tyrosine phosphorylation in rat spermatozoa is driven by ROS acting via 2 different but complementary mechanisms; O2-. stimulates tyrosine kinase activity indirectly through the elevation of intracellular cAMP while H2O2 acts directly on the kinase/phosphatase system, stimulating the former and inhibiting the latter. Zinc was examined as a potential regulator of this signal transduction cascade and was shown to suppress tyrosine phosphorylation in caput cells but to promote this activity in caudal spermatozoa, possibly through an inhibitory effect on tyrosine phosphatase activity. These results reveal the maturation of a redox-regulated, cAMP-mediated, signal transduction cascade during epididymal transit in the rat that is sensitive to zinc and plays a key role in the control of tyrosine phosphorylation events associated with capacitation.

Animals↗
PubMedDate not supplied

Polymorphisms of the apolipoprotein B and E genes and their possible roles in familial and non-familial combined hyperlipidaemia.

The frequency of polymorphisms of the apolipoprotein (apo) B and E gene loci were studied in 59 patients with primary combined hyperlipidaemia, including 26 with familial combined hyperlipidaemia. Variation at the apo B gene locus was examined using restriction enzymes XbaI, EcoRI, and PvuII. At the apo E gene locus, variation causing the E2, E3, and E4 phenotypes was detected using the polymerase chain reaction in conjunction with allele-specific oligonucleotide probes. The frequency of apo B RFLPs in patients were not significantly different from healthy controls, however, the apo E4 allele was over-represented. This suggests that possession of the apo E4 allele may contribute to the development of the combined hyperlipidaemic phenotype and to familial combined hyperlipidaemia.

Adult↗
PubMedDate not supplied

The response to papaverine in coronary artery bypass graft flows.

During coronary artery bypass surgery graft flows were measured. The measurements were made after cardiopulmonary bypass had been discontinued. The recordings were made over a ten year period and a total of 1,151 grafts in 720 patients are included. Except where the flow down a graft was large, 20 mg of Papaverine were injected into the graft and this usually resulted in the flow increasing by at least 100%. A satisfactory response was not achieved in 32 of the 538 grafts in which Papaverine was injected but subsequent probing of the distal anastomosis achieved a markedly improved flow in 80%.

Coronary Artery Bypass↗
PubMedDate not supplied

Clinical comparison of elastic supports for venous diseases of the lower limb and thrombosis prevention.

There is little objective evidence available when prescribing aids and appliances such as elastic supports for the leg. Doctors are generally ill-informed about effectiveness, fitting and costs of these garments. The claims of competing suppliers cannot be applied to clinical situations because the garments are tested in vitro on rigid forms. Elastic support for the lower limb is required in the treatment of varicose veins and gravitational disease and has been found effective in prevention of deep venous thrombosis. This study examined the in vivo effectiveness of four commercially purchased garments for these two purposes. The legs of 40 patients with varicose veins, 12 with gravitational disease and 20 patients admitted for elective operations were studied. Pressure exerted by the garment was detected by partly fluid filled bags between garment and limb. The results in patients with varicose veins and gravitational disease were similar. Only two garments exerted effective pressure and of these two the combination of a roller bandage and tapered tubigrip is recommended on grounds of least expense and ease of application. Of the four anti-embolism supports only the roller bandage plus tapered tubigrip produced effective compression: two garments produced reversed flow gradients in the majority of tests. Elastic supports should be double tested, firstly by the manufacturer for basic stretch and regain characteristics and secondly in vivo by clinicians to provide objective evidence of cost effectiveness.

Clothing↗
PubMedDate not supplied

A performance-based incentive program for influenza immunization in the elderly.

Our objective was to implement and evaluate performance-based reimbursement for influenza immunization of the elderly in physician offices. We performed a community-based quasi-experiment with historic and concurrent comparisons, using primary care physician offices in Monroe County, New York. Participants in the intervention group included 53 primary care physicians admitting to one hospital, and the comparison group included 82 primary care physicians admitting to other hospitals. All physicians participated in a Medicare-sponsored demonstration to increase influenza immunization rates, and, during the 1990-1991 immunization season, used a target-based poster to track immunization rates. Physicians in the intervention group were enrolled in a performance-based financial incentive program that rewarded immunization rates above 70%. A survey concerning influenza immunization practices and opinions was sent to all physicians. The average physician-specific immunization rate in the incentive group was 73.1% versus 55.7% in the comparison practices (P < .001). Eligibility for incentives, practice size, sex of physician, medical specialty, reminder postcards, and practice populations including medically indigent patients were associated with immunization level. Controlling for the above variables, we completed a regression analysis showing that eligibility for the incentive was still significant (P = .003). The survey responses were not predictive of performance or significantly different between the two groups, except for the negative influence of sending postcards. This study in a community setting suggests that linking reimbursement to performance may be a successful strategy to increase influenza immunization levels for the elderly.

Aged↗
PubMedDate not supplied

Paradise regained: insights into coronary heart disease prevention from recent clinical trials and basic research.

Many of the uncertainties regarding the place of lipid lowering in the prevention of coronary heart disease have recently been resolved. Some of the newer findings are reviewed, and the scope for a revised clinical approach examined. The results of trials of lipid lowering, based on clinical end-points and particularly on angiographic end-points, and their meta-analyses are discussed. The close relation between coronary-angiographic and clinical outcomes is reviewed in relation to recent advances in understanding of the underlying arterial pathology, and possible underlying mechanisms are proposed. The variables predictive of progression of coronary artery disease, including nutrient intake, are examined. The management of hyperlipidaemia requires that treatment and therapeutic goals are consonant with the patient's cardiovascular risk; for this purpose, clinical and biochemical assessment of risk may be enhanced by angiographic and non-invasive methods to detect potentially-infarctogenic atherosclerotic lesions.

Anticholesteremic Agents↗