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Biomedical subjects

K Wright

Publications and source records attributed to K Wright.

At least 127 records · Page 7Linked to original sources
PubMed1990

Adjuvant therapy for intracoronary stents. Investigations in atherosclerotic swine.

Early thrombosis has complicated human stent implantation in several trials. To determine the best anticoagulation/antiplatelet therapy to maintain stent patency after percutaneous transluminal coronary angioplasty, we implanted the flexible balloon-expandable coil stent into the left anterior descending coronary artery of 28 atherosclerotic 8-month-old Hanford miniature swine. Animals were randomly assigned to one of three treatment groups: group A, aspirin (1 mg/kg/day) and dipyridamole (1 mg/kg three times a day); group B, aspirin and dipyridamole (same doses) plus Coumadin (dose required to prolong prothrombin time 1.3-1.5-fold that of normal); and group C, control. Adjuvant therapy was begun 3 days before stenting. Two pigs (one from group A and one from group B) died during implantation, both without thrombosis. Twenty-six animals survived until follow-up angiography and sacrifice at 1 month. No occlusive thrombosis of the stent occurred in survivors. Reduction of the stent lumen diameter was observed in every case at follow-up. Percent lumen reduction was 19% in group A, 26% in group B, and 24% in group C. Marked smooth muscle cell hyperplasia was seen by light and transmission electron microscopy at stent struts. Scanning electron microscopy of the luminal surface showed a variable morphology consisting of normal endothelium, adherent leukocytes, stellate periluminal cells, and occasional fibrin strands and red blood cells. Luminal narrowing was not affected by anticoagulation therapy, antiplatelet drugs, cholesterol level, or stent sizing. We conclude that occlusive thrombosis does not complicate stent implantation in this model but that substantial luminal narrowing due in part to smooth muscle hyperplasia does occur. The significance of luminal narrowing at the stent site requires further study.

Angiography↗
PubMed1990

Organic diseases mimicking atypical eating disorders.

The authors present three case studies of patients referred to Children's Hospital and Medical Center, Seattle, Washington, for evaluation of possible eating disorders. The atypical manifestations of the cases warranted further investigation, which revealed an organic basis for their weight loss. The authors summarize the typical findings of bulimia and anorexia nervosa and discuss the clues from the case studies that mandated further evaluation.

Adolescent↗
PubMed1989

Preclinical toxicity and pharmacology of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II).

Liposome-entrapped cis-bis-neodecanoate-trans-R,R-1,2-diaminocylohexane platinum(II) (L-NDDP) is a new lipophilic cisplatin derivative formulated in a liposomal carrier currently in phase I clinical trials. The preclinical toxicity and pharmacology of L-NDDP were studied in mice and dogs. At the LD50 dose (i.v. bolus) in mice (60.5 mg/kg or 181.5 mg/m2), a tenfold decrease in the granulocyte and platelet counts was observed in the absence of renal toxic effects. In dogs, the maximum tolerated dose (MTD) of L-NDDP given i.v. over a period of 45-60 min was 150 mg/m2. This dose produced significant vomiting (6-18 episodes), minimal renal dysfunction, a maximal decrease in granulocyte and platelet counts of from 30% to 70%, and acute and transient elevation of liver enzymes. Higher doses (225 and 300 mg/m2) resulted in severe gastrointestinal (GI) toxicity in one animal and the death of two others within 48 h. Autopsy results showed multifocal hemorrhages in the lungs, GI tract, kidney, and liver. Three dogs were treated monthly with the MTD up to a cumulative dose of 637.5-712.5 mg/m2 with excellent tolerance. No cumulative myelosuppression or liver dysfunction was observed, whereas a slight increase in the creatinine baseline level was detected in all three animals. Autopsy results at the end of the study showed mild changes limited to the liver, kidney, and GI tract. Pharmacologic studies showed that the drug was cleared, fitting a two-compartment model with a mean t1/2 alpha of 7.1 min and a t1/2 beta of 87.8 h. These studies show that L-NDDP can safely be given at therapeutic doses to animals and that the dose-limiting toxic effects consists of myelosuppression in mice and a multiorgan hemorrhagic syndrome related to vascular injury in dogs.

Animals↗
PubMed1989

Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells.

Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter-binding factors. In this report we demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. Our results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level.

Base Sequence↗
PubMed1989

Comparison of in situ hybridization and monoclonal antibodies for early detection of cytomegalovirus in cell culture.

The abilities of each of four diagnostic tests--direct fluorescent monoclonal antibody (direct FA) staining, indirect fluorescent monoclonal antibody (indirect FA) staining, in situ hybridization with biotinylated DNA probes, and in situ hybridization with DNA probes directly linked to enzymatically active horseradish peroxidase-to detect cytomegalovirus soon after culture were compared. Only the indirect FA test and the in situ hybridization method with directly linked HRP-DNA probes provided consistent and reliable cytomegalovirus detection as early as 15 h postinfection.

Antibodies, Monoclonal↗
PubMed1988

Organ distribution and tumor uptake of liposome entrapped cis-bis-neodecanoato trans-R, R-1,2 diaminocyclohexane platinum (II) administered intravenously and into the proper hepatic artery.

Blood and tissue levels of elemental platinum (Pt) were measured after the administration of a liposomally entrapped cisplatin analogue, cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP). In mice bearing subcutaneous B16 melanoma tumors, Pt tumor levels were not significantly different in animals treated i.v. with an equimolar dose of L-NDDP or cisplatin. In rabbits bearing liver tumors of VX2 carcinoma, i.v. administration of L-NDDP resulted in 2- to 20-fold higher Pt levels in all tissues (including VX2 tumors) except the brain and peripheral nerve than in animals treated with an equimolar dose of cisplatin. Compared with i.v. administration, inoculation of either drug into the proper hepatic artery resulted in a severalfold increase of Pt levels in the VX2 tumors. Blood and other tissue levels were not substantially changed by intraarterial (i.a.) administration. These studies show that (1) multilamellar lipid vesicles can adequately deliver a lipophilic cisplatin analogue (NDDP) to nonphagocytic tumors when administered i.v. and (2) the inoculation of L-NDDP into the proper hepatic artery results in higher Pt tumor levels than with i.v. administration but does not decrease the systemic distribution of the drug.

Animals↗
PubMed1988

Should QALYs be programme-specific?

One reason for the development of quality adjusted life years (QALYs) is to facilitate comparison across health care programmes in terms of productivity per unit of expenditure. However, some approaches to QALY measurement have also been developed using 'programme-specific' dimensions of quality of life. Using data, from a longitudinal trial of long-term care for elderly people, it is shown in this paper that an 'across-programme' method of quality of life measurement is less sensitive to changes in elderly people's health states than programme-specific methods more commonly used in the field of evaluating long-term care. It is argued that the same problem is likely to arise in evaluating care for other common chronic conditions like mental handicap, chronic conditions of childhood and terminal cancer. It is concluded that more work should be carried out comparing across-programme and programme-specific measures of quality of life, otherwise it will be difficult to determine whether certain groups in society are being discriminated against in health service resource allocation due to an insensitive across-programme measure of outcome.

Activities of Daily Living↗
PubMed1988

Flying blind.

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Fertility rites.

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Abortifacient Agents↗