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Biomedical subjects

J M King

Publications and source records attributed to J M King.

At least 19 recordsLinked to original sources

Protease activated receptors modulate aortic vascular tone.

The effect of agonists of the known protease activated receptors (PAR), the thrombin and the PAR-2 receptors, on vasoactive mediator release and vascular tone were studied using rings of rat aorta. Stimulation of aortic rings with the thrombin receptor agonist, Trap-14, or the PAR-2 agonist, SLIGRL, resulted in a rapid release of nitric oxide. Trap-14 and SLIGRL-induced nitric oxide release was reduced by pre-treatment with BQ-788, an ETB endothelin receptor-specific antagonist. Consistent with a role for endothelin-1 receptor activation in Trap-14 and SLIGRL-induced nitric oxide release, endothelin-1 levels were increased significantly following 5 min treatment of aortic rings with Trap-14 or SLIGRL. Cumulative addition of Trap-14 to aortic rings denuded of endothelium resulted in dose-dependent contraction with an EC50 value of 23 +/- 5 microM, whereas SLIGRL addition failed to induce aortic contraction. These data suggest that the known protease activated receptors are functionally coupled to nitric oxide release. In addition, the thrombin receptor appears to modulate both vasodilator and contractile responses, whereas the PAR-2 receptor is linked only to vasodilation.

Animals

The South Australian Breast X-Ray Service: results from a statewide mammographic screening programme.

The South Australian Breast X-Ray Service is a centralised breast cancer screening programme in the State of South Australia. In its first 5 years of operation nearly 100 000 screens were performed. This study reports the clinical performance of the programme and compares it with other published series. Women aged 40 years and over were screened with two-view mammography every 2 years. Radiologists double-read the screening films and multidisciplinary teams assessed the recalled women at a single centre. In the prevalent round 76 106 women were screened, and subsequently 21 506 of them were rescreened. The recall rate for further investigation was 4.9% in the prevalent round and 2.4% in the incident rounds. The cancer detection rate per 1000 women was 7.0 in the prevalent screening round and 3.4 in the incident rounds. Forty-two per cent of invasive carcinomas measured < or = 10 mm in the prevalent screening round and the median tumour size was 12 mm. The benign to malignant biopsy ratio was 1:1.4 in the prevalent round and 1:2.8 in the incident rounds. In the prevalent round 77% of invasive tumours were lymph node negative and this proportion increased to 86% in the incident rounds.

Adult

Does the colon adopt small bowel features in a small bowel environment?

BACKGROUND: Isoperistaltic colon interposition is one of several surgical options available in the treatment of short bowel syndrome. It functions primarily by slowing the rapid intestinal transit that follows small bowel resection (SBR). Previous studies have interposed distal colonic segments and although there is evidence of adaptation by the interposed colon it is not known whether these segments develop histologic or functional small bowel characteristics. METHODS: In this study evidence was sought of metaplasia in the interposed segments after 80% SBR and, because proximal colon is a midgut derivative, the differences between proximal and distal colonic segments were examined. RESULTS: There was no qualitative histological evidence of metaplasia by the interposed segments. There was a significant increase in crypt depth, mucosal thickness and maltase concentration of the interposed segments compared with the nontransposed colon of the controls. The maltase concentations were increased to the extent that they were not significantly different from the concentration present in normal ileum. CONCLUSIONS: Although there was no gross evidence of small bowel intestinalization by the interposed segments, there was evidence of adaptation which was not merely an extension of the adaptive process seen after SBR alone. These changes resulted in the colon taking on some small bowel features. There was no significant difference between proximal vs distal interposed segments.

Adaptation, Physiological

Effects of intravenous infusion of lipid-free apo A-I in humans.

Apolipoprotein (apo) A-I is the principal protein component of the plasma high density lipoproteins (HDLs). Tissue culture studies have suggested that lipid-free apo A-I may, by recruiting phospholipids (PLs) and unesterified cholesterol from cell membranes, initiate reverse cholesterol transport and provide a nidus for the formation, via lipid-poor, pre-beta-migrating HDLs, of spheroidal alpha-migrating HDLs. Apo A-I has also been shown to inhibit hepatic lipase (HL) and lipoprotein lipase (LPL) in vitro. To further study its functions and fate in vivo, we gave lipid-free apo A-I intravenously on a total of 32 occasions to six men with low HDL cholesterol (30 to 38 mg/dL) by bolus injection (25 mg/kg) and/or by infusion over 5 hours (1.25, 2.5, 5.0, and 10.0 mg.kg-1.h-1). The procedure was well tolerated: there were no clinical, biochemical, or hematologic changes, and there was no evidence of allergic, immunologic, or acute-phase responses. The 5-hour infusions increased plasma total apo A-I concentration in a dose-related manner by 10 to 50 mg/dL after which it decreased, with a half-life of 15 to 54 hours. Coinfusion of Intralipid reduced the clearance rate. The apparent volume of distribution exceeded the known extracellular space in humans, suggesting extensive first-pass clearance by one or more organs. No apo A-I appeared in the urine. Increases in apo A-I mass were confined to the pre-beta region on crossed immunoelectrophoresis of plasma and to HDL-size particles on size exclusion chromatography. Increases were recorded in HDL PL, but not in HDL unesterified or esterified cholesterol. Increases also occurred in LDL PL and in very low density lipoprotein cholesterol, triglycerides, and PL but not in plasma total apo B concentration. These results can all be explained by combined inhibition of HL and LPL activities. Owing to the effects that this would have had on HDL metabolism, no conclusions can be drawn from these data about the role of lipid-free apo A-I in the removal of PL and cholesterol from peripheral tissues in humans. The kinetic data suggest that the fractional catabolic rate of lipid-free apo A-I exceeds that of spheroidal HDLs and is reduced in the presence of surplus PL.

Aged

Factors associated with participation in a preventive cardiology service by patients with coronary heart disease.

A free preventive cardiology service for patients and their asymptomatic family members was established at a large teaching hospital in the southeastern United States to provide medical triage and risk reduction counseling for prevention of coronary heart disease. Patients and families were informed about the service and invited to attend during a personal visit from members of the preventive cardiology consultation service. Our study was designed to explore determinants of decisions to attend the clinic. We conducted telephone interviews with 62 consecutive patients to collect data on individual perceptions of health risks, factors that modify perceptions of health risks and ability to make behavior changes, and actions taken to reduce risk of disease. Of the 62 patients interviewed, 39% had attended the clinic. Patients hospitalized for myocardial infarction or bypass surgery were more likely to attend the clinic than those who had angioplasty or catheterization without bypass surgery.

Adult

Effect of ambient temperature and humidity on performance of blood glucose meters.

The accuracy of four blood glucose meters (Accutrend, ExacTech Companion, Medisense Companion 2, and Glucometer III) was tested at temperatures ranging from 4 to 44 degrees C (control solutions) and 8 degrees C, 24 degrees C, and 36 degrees C (venous blood) and at humidities of 60% and 80%. Low and high temperatures resulted in a number of statistically significant changes in glucose readings with all meters. However, Accutrend, Medisense Companion 2, and Glucometer III were 100% clinically accurate at all temperatures. With the ExacTech Companion, only 70.8% of control solution and 55.6% of venous blood results were clinically accurate. The main errors were: (1) cold temperatures lowered the result so that euglycaemic levels erroneously read in the hypoglycaemic range and hyperglycaemic levels gave a better than actual result and (2) hot temperatures increased the result whereby hypoglycaemic levels falsely gave a euglycaemic result. Weather conditions at which blood glucose meters may be operated can affect results and potentially lead to errors in clinical decisions.

Blood Glucose

Evaluation of effects of unmodified niacin on fasting and postprandial plasma lipids in normolipidemic men with hypoalphalipoproteinemia.

PURPOSE: The aim of this study was to define the effects of unmodified niacin on basal lipids and lipoproteins and on the plasma triglyceride response to a fatty meal--postprandial or alimentary lipemia--in individuals with low levels of high-density lipoprotein cholesterol (HDL-C) and normal fasting cholesterol and triglyceride concentrations (normolipidemic hypoalphalipoproteinemia, isolated low HDL-C). PATIENTS AND METHODS: Twenty-eight normolipidemic men (total plasma cholesterol concentration [TC] < 230 mg/dL [< 6 mmol/L], plasma triglyceride [Tg] < 250 mg/dL [2.75 mmol/L]) with low plasma concentrations of HDL-C were randomly assigned to increasing doses of crystalline niacin (up to 3,000 mg/d) or no drug for 12 weeks, then crossed over to the alternate regimen. Outcome measures included changes in plasma lipoproteins and alimentary lipemia. RESULTS: Fifteen participants completed the study. Mean baseline HDL-C +/- SD was 31.7 +/- 6.2 mg/dL (0.82 +/- 0.16 mmol/L). Mean baseline TC, plasma concentration of low-density lipoprotein cholesterol (LDL-C), and Tg were 192 +/- 29.4 mg/dL (4.97 +/- 0.76 mmol/L), 123 +/- 27 mg/dL (3.17 +/- 0.69 mmol/L), and 197 +/- 75 mg/dL (2.17 +/- 0.83 mmol/L), respectively. Unmodified niacin treatment resulted in significant (P < 0.001) reductions of 14% in TC (to 165 mg/dL, 4.26 mmol/L), 40% in Tg (to 119 mg/dL, 1.31 mmol/L), and 18% in LDL-C (to 101 mg/dL, 2.60 mmol/L) and significant increases of 30% in HDL-C (to 42 mg/dL, 1.07 mmol/L), 100% in HDL2 cholesterol (from 5 mg/dL to 9 mg/dL, 0.12 mmol/L to 0.24 mmol/L), and 21% in HDL3 cholesterol (from 27 mg/dL to 33 mg/dL, 0.70 mmol/L to 0.85 mmol/L). Unmodified niacin treatment reduced alimentary lipemia by 45% (P < 0.02). CONCLUSIONS: Crystalline niacin effectively raises HDL-C, lowers LDL-C, and reduces alimentary lipemia in patients with isolated low HDL-C. However, many patients have difficulty tolerating the drug, and supervision may be required to sustain patient compliance and avoid toxicity.

Dietary Fats

A practical approach to breast ductal carcinoma in situ and tumors with an extensive intraductal component.

Current problems in the pathological assessment and subclassification of ductal carcinoma in situ of the breast are reviewed, both in its pure form and in association with invasive disease. The different clinical significance of these 2 types of presentations is emphasized, with particular reference to breast-conserving surgery. Adherence to the variably defined concept of extensive intraductal component may not be necessary if completeness of excision of intraductal disease can be demonstrated. A uniform approach is presented for the examination of surgical margins around intraductal carcinoma, regardless of the presence of invasion, using radiological-pathological correlation of sliced specimens.

Breast Neoplasms

Preclinical toxicologic evaluation of DENSPM (N1,N11-diethylnorspermine) in rats and dogs.

A toxicology study of DENSPM was carried out in rats by multiple (once daily for 5 days) intravenous injection. Doses of 12.5, 25 and 50 mg DENSPM/kg were well tolerated. Infusion of 100 mg DENSPM resulted in distressing physical signs, including labored breathing, convulsive movements and acute death. There were no end-organ toxicities induced by this regimen as evaluated by serum chemistry and hematology examinations, and histopathologic exam of all major body organs. Transient hypotension was induced in rats and dogs by rapid infusion of DENSPM; the magnitude of this hypotension was decreased by slow infusion of DENSPM into dogs. Hypotension appears to be the dose-limiting toxicity of this agent when infused rapidly.

Animals

Liposome encapsulated vincristine: preclinical toxicologic and pharmacologic comparison with free vincristine and empty liposomes in mice, rats and dogs.

A preclinical toxicology study of liposome encapsulated vincristine, free vincristine and empty liposomes was carried out in mice and dogs by single and multiple (daily for 5 days) intravenous injection. Single and multiple dose intravenous injection studies in mice showed the encapsulated form of vincristine to be less toxic than free vincristine. Empty liposomes injected intravenously into dogs were without significant toxicity. In dogs, the toxicities seen with liposomal vincristine were qualitatively similar to those of free vincristine with only minor quantitative differences. The principal toxicities of free and liposomal vincristine in dogs were anorexia, weight loss, pyrexia, myelosuppression and gastrointestinal toxicity. After single high doses of either formulation gastrointestinal toxicity was the dose-limiting toxicity, while either hematologic or gastrointestinal toxicity was dose limiting after multiple dose administration of either drug. Histopathologic lesions of importance were bone marrow atrophy, necrosis and atrophy of the lymphoproliferative tissues, necrosis of gastrointestinal tract mucosa, liver and pancreas, and hemorrhage. Distribution studies in rats showed significantly higher vincristine levels in serum, spleen, liver, trachea, jejunum, cerebrum, lung, ischiatic nerve and heart, and significantly lower levels in colon, stomach, salivary gland, thymus esophagus and pancreas after injection of the liposome-associated agent. No toxicities were seen that should preclude safe clinical trial of liposomal vincristine in man.

Animals

A review of revision functional endoscopic sinus surgery.

For some patients, traditional or functional endoscopic sinus surgery (FESS) fails to relieve persistent or recurrent sinus disease. This subset of patients may require revision surgery. The objective of this study was to define and evaluate which features of sinus disease and prior treatment were characteristic of patients requiring revision FESS. Within a series of 295 consecutive FESS procedures, 43 patients who had prior sinus surgery and required revision FESS were studied and followed for a mean 14.1-month period. The characteristics of 13 patients with persistent disease following revision FESS and the potential technical risks and complications encountered were also evaluated. This study concludes that revision FESS is a safe technique that was effective in 69.8% of the patients, and that certain factors may predict a poor surgical outcome.

Adolescent

Subclinical lumbar polyradiculopathy, polyneuritis and ganglionitis in aged wild and exotic mammalians.

Subclinical lumbar polyradiculopathy was present in the intradural dorsal and ventral nerve rootlets of 19 aged individuals of the following wild and exotic mammalian species: woodrat, raccoon, mink, lynx, reindeer, red deer, musk ox, scimitar-horned oryx, Arabian oryx, hybrid waterbuck, Persian onager, Przewalski's wild horse, Malayan sun bear, Asian elephant, East African river hippopotamus, vervet monkey and rhesus monkey. It was characterized by mild to severe multifocal ballooning of myelin sheaths. Occasionally, ballooned myelin sheaths contained thin strands of myelin and macrophages surrounding distorted axons. Additionally, a mild incidental lymphocytic polyneuritis was present in intradural nerve rootlets of the Malayan sun bear, and a moderate lymphocytic spinal ganglionitis in the East African river hippopotamus.

Age Factors

Coalition building between public health nurses and parish nurses.

Community-based healthcare, particularly preventive healthcare services, requires mutual understanding and close cooperation between community healthcare providers. The authors describe the emergence of parish nursing, a new area of practice that emphasizes holistic healthcare, health promotion, and disease prevention activities. Similarities between public health and parish nursing practice, and the development of collaborative working relationships between these two groups of nurses are discussed.

Aged

Plasmid-mediated mineralization of naphthalene, phenanthrene, and anthracene.

The well-characterized plasmid-encoded naphthalene degradation pathway in Pseudomonas putida PpG7(NAH7) was used to investigate the role of the NAH plasmid-encoded pathway in mineralizing phenanthrene and anthracene. Three Pseudomonas strains, designated 5R, DFC49, and DFC50, were recovered from a polynuclear aromatic hydrocarbon-degrading inoculum developed from a manufactured gas plant soil slurry reactor. Plasmids pKA1, pKA2, and pKA3, approximately 100 kb in size, were isolated from these strains and characterized. These plasmids have homologous regions of upper and lower NAH7 plasmid catabolic genes. By conjugation experiments, these plasmids, including NAH7, have been shown to encode the genotype for mineralization of [9-14C]phenanthrene and [U-14C]anthracene, as well as [1-14C]naphthalene. One strain, Pseudomonas fluorescens 5RL, which has the complete lower pathway inactivated by transposon insertion in nahG, accumulated a metabolite from phenanthrene and anthracene degradation. This is the first direct evidence to indicate that the NAH plasmid-encoded catabolic genes are involved in degradation of polynuclear aromatic hydrocarbons other than naphthalene.

Anthracenes