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Biomedical subjects

M J Williams

Publications and source records attributed to M J Williams.

At least 19 recordsLinked to original sources
PubMed1999

Impaired endothelial function following a meal rich in used cooking fat.

OBJECTIVES: The purpose of this study was to test the hypothesis that intake of used cooking fat is associated with impaired endothelial function. BACKGROUND: Diets containing high levels of lipid oxidation products may accelerate atherogenesis, but the effect on endothelial function is unknown. METHODS: Flow-mediated endothelium-dependent dilation and glyceryl trinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 10 men. Subjects had arterial studies before and 4 h after three test meals: 1) a meal (fat 64.4 g) rich in cooking fat that had been used for deep frying in a fast food restaurant; 2) the same meal (fat 64.4 g) rich in unused cooking fat, and 3) a corresponding low fat meal (fat 18.4 g) without added fat. RESULTS: Endothelium-dependent dilation decreased between fasting and postprandial studies after the used fat meal (5.9 +/- 2.3% vs. 0.8 +/- 2.2%, p = 0.0003), but there was no significant change after the unused fat meal (5.3 +/- 2.1% vs. 6.0 +/- 2.5%) or low fat meal (5.3 +/- 2.3% vs. 5.4 +/- 3.3%). There was no significant difference in endothelium-independent dilation after any of the meals. Plasma free fatty acid concentration did not change significantly during any of the meals. The level of postprandial hypertriglyceridemia was not associated with change in endothelial function. CONCLUSIONS: Ingestion of a meal rich in fat previously used for deep frying in a commercial fast food restaurant resulted in impaired arterial endothelial function. These findings suggest that intake of degradation products of heated fat contribute to endothelial dysfunction.

Adult↗
PubMed1998

Relative efficacy of medical therapy and revascularization for improving exercise capacity in patients with chronic left ventricular dysfunction.

BACKGROUND: In patients with left ventricular dysfunction one of the aims of therapy may be to improve functional capacity. This study compared the improvement of functional capacity in response to medical therapy with that caused by revascularization. METHODS: Fifty-two patients with severe left ventricular dysfunction were divided into groups with ischemic cardiomyopathy undergoing revascularization (group A, n = 20) or incremental medical treatment (group B, n = 16) and a control group receiving maximal medical therapy at the start of the study (group C, n = 16). All patients underwent a baseline metabolic exercise test with evaluation of peak oxygen consumption and derived exercise capacity in metabolic equivalents (METS) with standard electrocardiographic and hemodynamic monitoring. Therapy was then optimized in the medical treatment group, whereas the revascularization group underwent coronary bypass grafting. All patients subsequently underwent follow-up metabolic exercise testing. RESULTS: In groups A, B, and C resting left ventricular ejection fractions were comparable (26%+/-5%, 25%+/-7%, and 23%+/-8%, respectively), as were results of initial metabolic exercise tests (4.7+/-0.9 METS, 4.7+/-1.4 METS, and 5.2+/-1.4 METS). At follow-up group A improved exercise capacity from 4.7 to 5.6 METS (p = 0.01). Groups B (4.7 to 5.0 METS) and C (5.2 to 5.6 METS) had no significant improvement. The mean respiratory exchange ratio improved significantly in group A (1.14 to 1.20, p = 0.02), as did left ventricular ejection fraction (26% to 31%, p = 0.02). However, neither parameter changed significantly in groups B or C. CONCLUSIONS: In patients with severe left ventricular dysfunction improvements of exercise capacity are more marked after coronary revascularization than may be obtained after maximization of medical therapy.

Adult↗
PubMed1998

Estrogen increases cGMP in selected brain regions and in cerebral microvessels.

We have previously reported that exogenous and endogenous estrogen can amplify residual cerebral blood flow during experimental cerebral ischemia. Because estrogen has been linked to nitric oxide and cyclic guanosine monophosphate (cGMP) signaling in noncerebral tissue, we tested the hypothesis that long-term 17beta-estradiol treatment increases basal cGMP in brain homogenates and cerebral microvessels in female rabbits. We also determined whether there are important baseline gender-specific differences in regional cGMP. Adult female rabbits were implanted with 17beta-estradiol pellets, 10 mg (F10, n = 10) or 50 mg (F50, n = 13), and compared with untreated females (F, n = 19) and males with negligible estrogen (M, n = 19) (plasma 17beta-estradiol levels of 4+/-4 pg/mL in M, 7+/-5 pg/mL in F, 141+/-74 pg/mL in F10, and 289 +/-10 pg/mL in F50). Cyclic GMP was determined by radioimmunoassay in cerebellum, hypothalamus, caudate nucleus, hippocampus, and cortex. Cerebral microvessels were harvested from additional cohorts of untreated males and females or estradiol-implanted females (n = 6 per group). Basal cGMP was higher in F versus M only in cerebellum. Estrogen-induced increases in regional cGMP were prominent in hippocampus at all doses (M = 43+/-26, F = 43+/-21, F10 = 84+/-24, F50 = 117+/-55 fmol/mg protein) and in cortex at the high dose (M = 78+/-55, F = 88+/-51, F10 = 69+/-34, F50 = 143+/-52 fmol/mg protein). Similarly, microvascular cGMP increased only in females treated with the 50 mg dose (M = 77+/-13, F = 86+/-25, F10O = 106+/-35, F50 = 192+/-88 fmol/mg protein). Therefore, 17beta-estradiol increases cGMP content in parenchymal regions that are known physiologic targets for reproductive steroids but are also areas of selective vulnerability to ischemic insult. Further, high doses of estrogenic steroids could amplify cGMP signaling within the cerebral microvasculature.

Animals↗
PubMed1998

Myocardial infarction in young people with normal coronary arteries.

Myocardial infarction occurring in young people with angiographically normal coronary arteries is well described but the pathophysiology of this condition remains unknown. Coronary artery spasm in association with thrombus formation and minimal atheromatous disease or spontaneous coronary artery dissection are possible causes. Two young men presented with severe chest pain after acute alcohol intoxication and each sustained an extensive anterior myocardial infarction. Investigations including intravascular ultrasound showed no evidence of atherosclerotic coronary artery disease. Coronary artery spasm associated with acute alcohol intoxication as well as prothrombotic state and endothelial damage related to cigarette smoking may be mechanisms leading to acute myocardial infarction in these cases. Acute myocardial infarction occurs in young persons with normal coronary arteries and the diagnosis should be considered in young patients presenting with severe chest pain, particularly those abusing cocaine or alcohol, so that reperfusion therapy can be initiated promptly.

Adult↗
PubMed1998

IDL composition and angiographically determined progression of atherosclerotic lesions during simvastatin therapy.

Some patients with coronary artery disease experience continued progression of one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and markedly lower plasma cholesterol levels. We examined relationships between the progression of coronary artery lesions and plasma lipoproteins, in particular intermediate density lipoprotein (IDL) and its composition, in 38 patients with coronary artery disease who had been treated with simvastatin for 2 years. Patients were given lipid-lowering dietary advice; 3 months later they were started on simvastatin therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target level of plasma cholesterol had not been attained. Progression of lesions was determined by serial quantitative coronary angiography (variability of 5.5%) and was defined as an increase in percent diameter stenosis (%S)> or =10%; regression was defined as a decrease in %S > or =10%. The proportions of cholesteryl esters (CEs) and free cholesterol decreased significantly (P<.001), and proportions of protein and triglycerides increased significantly (P<.001) in IDL during simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in progressors (patients who showed progression of one or more lesions without regression of any lesion). This decrease in IDL CE content in nonprogressors was significantly (P=.01) different compared with the corresponding change in patients classified as progressors. Mean plasma cholesterol concentration tended to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors (-0.39 mmol/L) during the initial 3-month diet period, and these changes were significantly different (P=.02). Furthermore, this change in plasma cholesterol level during the initial diet period was correlated significantly with the change in IDL CE content during the entire study (r=.348, n=38, P=.03). These data suggest that IDL CE content may be a determinant of progression of coronary lesions and may be influenced by compliance with or metabolic response to lipid-lowering dietary advice in patients with coronary artery disease during simvastatin treatment.

Adult↗
PubMed1998

Average daily gain, blood metabolites, and body composition at first conception in Hereford, Senepol, and reciprocal crossbred heifers on two levels of winter nutrition and two summer grazing treatments.

Hereford (n = 48), Senepol (n = 42), and reciprocal crossbred (n = 34) heifers from two consecutive calf crops were stratified by breed, age, and BW to receive bahiagrass (Paspalum notatum) hay offered free choice and 150 mg monensin x heifer(-1) x d(-1) in addition to either 2.27 kg x heifer(-1) x d(-1) of a 75% cracked corn and 25% soybean meal mixture (CS) or .91 kg x heifer(-1) x d(-1) of soybean meal (SBM). Heifers in each treatment were divided into two winter pasture replicates and exposed to fertile bulls. In spring of each year, one-half of the heifers from each winter treatment were allotted to either a continuous (CONT) or rotational (ROTA) grazing system on bahiagrass pastures for the summer phase of the study. Heifers supplemented with CS had higher ADG from the beginning of the study to first conception than heifers fed SBM (.39 vs .31 +/- .02 kg/d; P < .01). Heifers fed CS were younger at first conception than SBM heifers (500 vs 563 +/- 32 d of age; P < .05) but had similar BW (312 vs 317 +/- 7 kg; P > .10). During the 2-yr study, a subset of Hereford (n = 12), Senepol (n = 15), and reciprocal crossbred (n = 14) heifers were subjected to urea space measurements to determine body composition at first conception. Change in body composition over time was analyzed by regression and body composition at first conception was predicted from these regressions. At first conception, percentage of empty body fat was not affected by treatment or year; however, percentage of empty body fat tended to be higher in crossbred than in Hereford and Senepol heifers (16.6 vs 14.3 and 14.4 +/- .94%; P < .10). Stepwise regression of BW, body condition score (BCS), fat thickness (determined by ultrasound), and body composition at first conception on age at first conception revealed that BCS and BW accounted for 55% of the variation in age at first conception (P < .01).

Animal Feed↗
PubMed1998

Transcobalamin II and in vitro proliferation of leukemic cells.

We have recently shown that antibodies to transcobalamin II (TCII) inhibit the in vitro growth of human and murine leukemic cells. This antiproliferative strategy targets the uptake of cobalamin (Cbl), an essential cofactor for two biochemical reactions in humans. To date there has been no appropriate cell culture model available to study antagonism of Cbl as a potential antiproliferative strategy. We have established cell culture conditions which allow reproducible measurements of cell proliferation that is dependent on Cbl and its carrier protein, TCII. This bioassay has allowed us to demonstrate that several monoclonal antibodies, raised against TCII, are potent inhibitors of cell proliferation and that excess Cbl abrogates this inhibitory effect. Thus, supporting our hypothesis that interference with Cbl uptake or metabolism will result in inhibition of cell proliferation. Furthermore, Cbl metabolism appears to provide a useful target for antiproliferative strategies which now involve the use of inactive Cbl analogs. In this review, we update our work on the role of targeting TCII and Cbl as an antiproliferative strategy for leukemic cells. We suggest that this strategy may provide a novel direction for anti cancer reagents.

Animals↗
PubMed1998

Self-efficacy, outcome expectations, and fantasies as predictors of alcoholics' postreatment drinking.

The usefulness of distinguishing between alcoholic patients' expectations and their fantasies about treatment outcome was examined. Results at 6 and 12 months follow-up did not support the results of research with nonalcoholic participants which related better outcomes to a combination of positive expectations and negative fantasies about future drink-related situations. Higher self-efficacy expectancy at intake, however, was associated with better clinical outcome. Findings supported Bandura's (1986) contention that outcome expectations add little information on prediction beyond that explained by self-efficacy expectancy. The clinical implications of these results are discussed.

Adult↗
PubMed1997

The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense.

Mammals and insects employ similar Rel/NF-kappaB signaling cascades in their humoral immune responses. The mammalian interleukin-1 type I receptor (IL-1R) is one way of activating this cascade. The Drosophila Toll protein, whose cytoplasmic domain shows striking similarity to that of the IL-1R, acts in the humoral antimicrobial response. Here we demonstrate that a second IL-1R-related Drosophila protein, 18-Wheeler (18W), is a critical component of the humoral immune response. 18-wheeler is expressed in the larval fat body, the primary organ of antimicrobial peptide synthesis. In the absence of the 18W receptor, larvae are more susceptible to bacterial infection. Nuclear translocation of the Rel protein Dorsal-like immunity factor (Dif) is inhibited, though nuclear translocation of another Rel protein, Dorsal, is unaffected. Induction of several antibacterial genes is reduced following infection, relative to wild-type: attacin is reduced by 95%, cecropin by 65% and diptericin by 12%. Finally, 18-wheeler (18w) expression is induced in response to infection and, in addition to the receptor form, four immune-specific transcripts and proteins are produced.

Animals↗
PubMed1997

The evolution of genomic imprinting: two modifier-locus models.

We present two autosomal two-locus models in which the primary locus, A, may be imprinted according to the alleles present at the second, modifier locus, M. In the first model, the modifier is cis-acting, which assumes that imprinting occurs late in gametogenesis: whether or not A is imprinted depends only on the M allele in the (unfertilized) egg. We examine three cases in which polymorphism at A is maintained by a mutation-selection balance or heterozygote advantage. We show that a newly arising modifier allele without direct fitness effects can increase at a rate only of the order of the mutation rate at the A locus. This result mirrors that found in two-locus models of the evolution of dominance modifiers. Modifiers that also alter fitnesses, however, may spread quickly. In the second model, a monomorphic primary locus, A, is imprinted according to the mother's genotype at the second, diallelic modifier locus, M. The model is therefore trans-acting, which assumes imprinting occurs early in gametogenesis: whether or not A is imprinted depends on both of the mother's M genes. We show that a newly arising modifier will increase in frequency via selection if either imprinting is advantageous and the modifier increases the proportion of imprinted gametes or imprinting is disadvantageous and the proportion is decreased. Both of these factors-the selective effect of imprinting and the proportion of gametes imprinted-affect the rate of modifier evolution. Selectively maintained polymorphism at the modifier locus is unlikely unless the alleles interact in a nonadditive fashion.

Biological Evolution↗
PubMed1997

Increased left ventricular cavity size, not wall thickness, potentiates myocardial ischemia.

Left ventricular (LV) hypertrophy increases the vulnerability of the myocardium to ischemia. The purpose of this study was to determine whether LV diameter or wall thickness was the principal determinant of the effect of LV mass on the development of ischemia, measured by exercise thallium perfusion imaging, in a population with coronary artery disease (CAD). We studied 109 patients with CAD but no prior myocardial infarction who underwent exercise thallium imaging within 1 year of coronary angiography. Thallium perfusion defects were present in 76% of patients. LV mass index was associated with thallium perfusion abnormalities (odds ratio 2.09 for 50 gm increments), an association that persisted after adjusting for extent of CAD. LV end-diastolic diameter had a strong correlation with a thallium defect (odds ratio 3.7 for 10 mm increments), but LV wall thickness had no correlation (odds ratio 1.0 for 5 mm increments). In a stepwise regression model that included extent of CAD and other potential clinical variables, LV end-diastolic diameter was the strongest predictor of thallium defects (adjusted odds ratio 4.5). This study confirms the association of LV hypertrophy with ischemia in patients with CAD, specifically in patients with eccentric hypertrophy.

Coronary Angiography↗
PubMed1997

Progression of the culprit lesion in unstable coronary artery disease with warfarin and aspirin versus aspirin alone: preliminary study.

OBJECTIVES: This study assessed whether combination therapy with aspirin and warfarin for 10 weeks reduces the risk of progression or reocclusion of the unstable coronary artery lesion. BACKGROUND: Reocclusion of the culprit coronary artery occurs in up to one third of patients during the 3 months after myocardial infarction (MI) or unstable angina and is associated with increased morbidity and mortality. METHODS: Fifty-seven patients presenting with unstable angina or MI who had an identifiable culprit lesion at coronary angiography were randomized in double-blind manner to receive warfarin (target international normalized ratio [INR] 2.0 to 2.5) or placebo in addition to aspirin (150 mg daily). Changes in the culprit lesion were assessed by quantitative angiography in 50 patients after 10 weeks of therapy or after a clinical event. Progression of the culprit lesion was defined as a decrease in minimal lumen diameter > 0.4 mm or a new total occlusion. Regression was defined as an increase in minimal lumen diameter > 0.4 mm. RESULTS: In subjects randomized to receive warfarin, the culprit lesion was less likely to progress (1 [4%] vs. 8 [33%]) and more likely to regress (5[19%] vs. 2[9%]) than in subjects receiving placebo (p = 0.02). Recurrent MI or a new occlusion at angiography occurred in 2 (7%) of 29 patients receiving warfarin versus 11 (39%) of 28 patients receiving placebo (p = 0.005). CONCLUSIONS: In patients with an acute coronary syndrome, combined therapy with aspirin and warfarin with a target INR of 2.0 to 2.5 for 10 weeks reduces the risk of progression or reocclusion of the culprit coronary lesion.

Angina, Unstable↗
PubMed1997

Regional fat distribution in women and risk of cardiovascular disease.

Improvements in technology have allowed more precise measurements of regional fat distribution and also present the opportunity to make a systematic evaluation of the various fat depots, including intraabdominal adipose tissue (IAF), subcutaneous adipose tissue (SAF), trunk fat, arm fat, and leg fat. The purpose of this study was to determine which of the fat distribution variables (arm fat, leg fat, trunk fat, IAF, or SAF) may have independent relations with cardiovascular (CVD) risk factors [serum triacylglycerol, serum cholesterol, high-density-lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, low-density-lipoprotein (LDL) cholesterol, very-low-density-lipoprotein (VLDL) cholesterol, VLDL3 cholesterol, lipoprotein(a), and systolic and diastolic blood pressure] in women after adjusting for age, menopause status, and other fat-distribution variables. Two hundred twenty-four (138 premenopausal and 86 postmenopausal) white females ranging in age from 17 to 77 y were sampled. Percentage body fat ranged from 8.8% to 48.1% and IAF cross sections ranged from 9.2 to 335 cm2. Simple zero-linear correlations and partial correlations were calculated. IAF and trunk fat were consistently positively related to CVD risk factors, whereas leg fat was consistently negatively related to CVD risk, indicating that IAF and trunk fat may put women at increased risk of developing CVD.

Absorptiometry, Photon↗
PubMed1997

Improved trauma management with advanced trauma life support (ATLS) training.

OBJECTIVE: To determine the value of advanced trauma life support (ATLS) training for medical staff in a major incident situation, based upon performance in a simulated exercise. METHODS: A major incident exercise was used to assess the management of trauma victims arriving in hospital suffering from multiple or life threatening injuries. The effect of ATLS training, or exposure to an abbreviated form of ATLS training, on the management of patients with simulated life threatening traumatic injuries was examined. The treatment offered by medical staff of different grades and varying exposure to ATLS training was compared. RESULTS: Medical staff who had undertaken ATLS training attained a higher number of ATLS key treatment objectives when treating the simulated trauma victims. CONCLUSION: Medical staff who have either undertaken the full ATLS course or an abbreviated form of the course were more effective in their management of the simulated trauma cases.

Education, Medical, Continuing↗
PubMed1997

Scotland's first iron lung.

The history of artificial ventilation and the development of the iron lung in the USA by Drinker and his colleagues is discussed. The building and use of an iron lung by Dr R G Henderson in Aberdeen in 1933 is described. The development of other types of ventilator in the UK is recorded and the circumstances whereby positive pressure ventilation was introduced in Denmark in 1952 is outlined.

History, 19th Century↗
PubMed1997

Serial angiography in cocaine-induced myocardial infarction.

A young man suffered an acute inferior myocardial infarction following clinical use of cocaine as topical anesthesia. Coronary angiography showed occlusion of both the posterior descending and posterolateral arteries which was resistant to intracoronary administration of nitroglycerin and verapamil, a finding consistent with thrombotic occlusion. A subsequent angiogram 3 months later showed no residual lesions.

Adult↗
PubMed1997

Effect of rotational vs continuous intensive stocking of bahiagrass on performance of Angus cows and calves and interaction with sire type on gastrointestinal nematode burden.

Performance of Angus cows and calves was compared between two methods of bahiagrass (Paspalum notatum Flügge) grazing management, rotational stocking (ROT) and continuous intensive stocking (CIS), where stocking rate was varied by adjusting available pasture area as forage growth rate changed during the growing season. Effects of sire type (low [LO] vs high [HI] EPD for nematode egg shedding rate [EPG]) also were studied. Data were analyzed for two complete cycles of calf production from breeding through weaning. There was no effect of pasture grazing management method on cow BW, cow body condition score, adjusted 205-d calf weaning weight, and preweaning calf ADG. Five genera of nematodes (Ostertagia, Haemonchus, Trichostrongylus, Cooperia, and Oesophagostomum) were recovered from calves removed and killed at times throughout the grazing season. Mean nematode numbers recovered increased (P < .05) for all species as the grazing season progressed from spring to fall, consistent with results on EPG (P < .001). Effect of sire type on EPG was not significant; however, sire type did affect mean EPG (P < .05) from a subset of calves placed in drylot after weaning and sampled for three consecutive days. Sire type affected IgG1 titer to H. placei (LO = .50 +/- .012, HI = .45 +/- .011) and IgA titer to O. radiatum (LO = .28 +/- .006, HI = .26 +/- .005), and there was a sire type x pasture grazing method interaction on IgG1 titer to H. placei (LO-ROT = .49 +/- .016, HI-ROT = .49 +/- .017, LO-CIS = .50 +/- .017, HI-CIS = .41 +/- .014). Increased anti-parasite antibody titers in progeny of sires with EPD for low nematode egg shedding rates may reflect increased host resistance to these parasites.

Analysis of Variance↗