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Biomedical subjects

M J Williams

Publications and source records attributed to M J Williams.

At least 55 records · Page 3Linked to original sources
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

The mechanism of blood flow in cardiopulmonary resuscitation--introducing the lung pump.

The mechanism of blood flow in cardiopulmonary resuscitation remains controversial. Inconsistencies in the cardiac pump model necessitated the development of the thoracic pump. Neither hypothesis alone can account for blood flow during external massage. Using the postulates that a cyclical pump has three components, an inlet valve, a compression chamber and an outlet valve, we propose the lung pump hypothesis where these components are represented by the pulmonary valve; the lung vasculature/left atrium/left ventricle; and the aortic valve. We explore the mechanism and effect of this hypothesis and match it to previous observations. The implications to cardiopulmonary resuscitation are addressed.

Animals↗
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↗
PubMed1996

Biopsy-induced flail tricuspid leaflet and tricuspid regurgitation following orthotopic cardiac transplantation.

Damage to the tricuspid valve apparatus has been described after endomyocardial biopsy and may be associated with hemodynamically significant tricuspid regurgitation (TR). This study was performed to determine the prevalence of TR and flail tricuspid leaflet in cardiac transplant recipients and to evaluate the use of a 45 cm sheath placed directly in the right ventricle during endomyocardial biopsy to reduce the incidence of these complications. Echocardiograms and right heart catheterization data of 72 orthotopic cardiac transplant recipients were assessed for the presence of flail tricuspid leaflet, TR, and right-sided cardiac dysfunction 29 +/- 20 months (mean +/- SD) after transplantation. Moderate or severe TR was present in 23 patients (32%). Ten patients (14%) had flail tricuspid leaflet, with 7 of these having severe TR. Right atrial pressure (10 +/- 5 vs 6 +/- 5 mm Hg, p < 0.05) was higher, cardiac index (2.0 +/- 0.2 vs 2.5 +/- 0.7 L/min/m2, p < 0.05) was lower, and right-sided cardiac dimensions were greater in patients with flail leaflets than in those without flail leaflets. Both the prevalence of flail tricuspid leaflet (41% to 6%, p < 0.0001) and mean grade of TR (2 to 1, p < 0.0001) were reduced after the use of a 45 cm sheath. We conclude that TR secondary to biopsy-induced damage to the valve apparatus occurs in cardiac transplant recipients and is associated with signs of early right-sided heart failure. Use of a 45 cm sheath during endomyocardial biopsy reduces the prevalence of flail tricuspid leaflet and the severity of TR.

Biopsy↗
PubMed1996

Intact spatial learning following lesions of basal forebrain cholinergic neurons.

The role of the basal forebrain cholinergic system in learning and memory has held considerable interest since the discovery of cholinergic neurodegeneration in the basal forebrain in Alzheimer's disease. Contrary to expectation, selective removal of basal forebrain cholinergic neurons projecting to either hippocampus or neocortex fails to impair learning in a spatial task widely used to study hippocampal/cortical function. If cholinergic neurons contribute to learning and memory by integrated regulation of hippocampal and cortical processing, combined removal of hippocampal and cortical cholinergic projections might be necessary to produce impairment. However, this combined lesion failed to impair spatial learning. These data argue against the view that basal forebrain cholinergic deficiency plays a prominent role in disorders of learning and memory.

Acetylcholine↗