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Biomedical subjects

A C Wilson

Publications and source records attributed to A C Wilson.

At least 55 records · Page 3Linked to original sources

Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP).

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.

Aged↗

Coronary heart disease risk factors in men and women aged 60 years and older: findings from the Systolic Hypertension in the Elderly Program.

BACKGROUND: Coronary heart disease (CHD) is the most common cause of death in men and women aged 60 years and older. Although a number of studies support the concept that CHD risk factors that have been defined in younger adults are significantly associated with CHD events in older adults, others do not support this thesis, and further definition of the risk-factor concept in older adults is required. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years); 14% were black, and 43% were men. Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. About 13% of participants were current smokers; 10% had a history of diabetes; 5%, a prior myocardial infarction; 5% angina pectoris; 2.3%, intermittent claudication; and 7%, a carotid bruit. Mean total cholesterol value was 6.11 mmol/L. Mean follow-up was 4.5 years. In multivariate Cox regression analyses for CHD, variables that were significant were baseline total cholesterol value, smoking, history of diabetes, presence of carotid bruit, and treatment group in the trial. Active treatment yielded a 27% reduction in CHD risk. For each 1.03 mmol/L increase in total cholesterol value, there was an increase in risk of about 20%. Current smokers had a 73% increase, diabetics a 121% increase, and those with carotid bruit a 113% increase in CHD risk. CONCLUSIONS: The results of this study support the concept that CHD risk factors are important in older men and women with isolated systolic hypertension.

Aging↗

Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry.

Diabetes is an independent predictor of morbidity and mortality in patients with symptomatic heart failure, patients with asymptomatic left ventricular dysfunction (defined as an ejection fraction of 35% or less), and in a broader registry population with less stringent entry criteria. Although the SOLVD Trials made a major clinical contribution by proving the value of enalapril, diabetes remains a significant predictor of outcome even after adjusting for treatment with enalapril.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of prolonged blood contact time on deposition of cellular and amorphous material on teflon-coated guidewires: a scanning electron microscopy study.

Prolonged contact of blood with guidewires and catheters has been implicated in leading to thromboembolic complications during cardiac catheterization. To study the effect of exposure time on blood product deposition on Teflon-coated guidewires, 35 patients undergoing routine coronary arteriography were randomly assigned to three time groups with exposure of the guidewire to blood of 3, 5, and 10 min, respectively. The exposed wires were examined by scanning electron microscopy, and the micrographs were graded by a pathologist "blinded" as to the exposure time. Deposition of cellular and amorphous material on the guidewire surface and interstices was graded using an arbitrary scale of 1-10 (1, least amount; 10, abundant amount of material). All patients received low-dose systemic administration of heparin (2,500 units) at the beginning of the procedure. The overall activated clotting time (ACT) was 147 +/- 39 sec (mean +/- SD) prior to heparin dose. The mean ACT after low-dose systemic heparin, measured at sheath removal immediately after exposure of the wire to blood had been completed, rose to 241 +/- 79 sec (P < 0.0001). The deposition of cellular and amorphous material on the surface and grooves of the wire was not significantly different at 3, 5, and 10 min. Thus, in this study, Teflon-coated guidewires showed no increase in cellular or amorphous deposits from 3 min to 10 min of blood-wire contact time in the presence of low-dose heparinization.

Aged↗

Attenuation of myocardial stunning in isolated rat hearts by a 21-aminosteroid lazaroid (U74389G).

The purpose of this study was to evaluate the effects of reperfusion or in vivo pretreatment with a lipid peroxidation inhibitor, lazaroid (U74389G), on attenuating systolic and diastolic alterations occurring during myocardial stunning in isolated rat hearts. Male Sprague-Dawley rats (350-400 g) were randomized into three groups: control animals (n = 13) received no drugs; hearts from reperfused animals (n = 11) received 5 microM U74389G in the reperfusion solution; pretreated animals (n = 11) received 6 mg/kg U74389G by i.v. infusion 30 min before killing. Isolated, isovolumic rat hearts were subjected to 20 min of ischemia at 37 degrees C and subsequent reperfusion for 30 min. Left ventricular isovolumic developed pressure (LVDP), its first derivative (LVDPdP/dt), end-diastolic pressure (LVEDP), and the time constant of diastolic relaxation (tau) were measured. At baseline, no statistically significant differences were detected in systolic or diastolic function in hearts of rats with or without U74389G treatment. After reperfusion, LVDP stabilized at 87 and 92% in both drug-treated groups compared with 52% in the control group (p < 0.01) and dP/dtmax recovered to 101 and 110% of baseline compared with 58% in the control group (p < 0.01). Diastolic dysfunction showed significant improvement in both U74389G pretreatment groups. The increases in LVEDP and tau were 2.0- and 1.2-fold in pretreated hearts and 2,8-fold and 1.5-fold in drug-reperfused hearts, respectively (compared with 6-fold increases in LVEDP and a 2.5-fold increase in tau in controls; p < 0.05). In conclusion, whether administered before ischemia or during reperfusion, U74389G effectively attenuated the systolic and diastolic dysfunction in this model of myocardial stunning, probably protecting cell membranes from peroxidation by oxygen-derived metabolites.

Animals↗

The HCF repeat is an unusual proteolytic cleavage signal.

The herpes simplex virus VP16-associated protein HCF is a nuclear host-cell factor that exists as a family of polypeptides encoded by a single gene. The mature HCF polypeptides are amino- and carboxy-terminal fragments of a large approximately 300-kD precursor protein that arise through cleavage at one or more centrally located sites. The sites of cleavage are the HCF repeats, highly conserved 26-amino-acid sequences repeated six times in the HCF precursor protein. The HCF repeat alone is sufficient to induce cleavage of a heterologous protein, and cleavage occurs at a defined site--PPCE/THET--within the HCF repeat. Alanine-scan mutagenesis was used to identify a large 18-amino-acid segment of the HCF repeat that is important to induce cleavage of a heterologous protein. Even though HCF is cleaved, the majority of amino- and carboxy-terminal cleavage products remain tightly, albeit noncovalently, associated. Modulation of this noncovalent association may provide a mechanism for regulating HCF activity. For example, the cleaved products of an alternative mRNA splicing variant of HCF do not remain associated.

Alternative Splicing↗

The gene encoding the VP16-accessory protein HCF (HCFC1) resides in human Xq28 and is highly expressed in fetal tissues and the adult kidney.

After herpes simplex virus (HSV) infection, the viral regulatory protein VP16 activates transcription of the HSV immediate-early promoters by directing complex formation with two cellular proteins, the POU-homeodomain transcription factor Oct-1 and the host cell factor HCF. The function of HCF in uninfected cells is unknown. Here we show by fluorescence in situ hybridization and somatic cell hybrid analysis that the gene encoding human HCF, HCFC1, maps to the q28 region of the X chromosome. Yeast artificial chromosome and cosmid mapping localizes the HCFC1 gene within 100 kb distal of the renal vasopressin type-2 receptor (V2R) gene and adjacent to the renin-binding protein gene (RENBP). The HCFC1 gene is apparently unique. HCF transcripts and protein are most abundant in fetal and placental tissues and cell lines, suggesting a role in cell proliferation. In adults, HCF protein is abundant in the kidney, but not in the brain, a site of latent HSV infection and where HCF levels may influence progression of HSV infection.

Animals↗

Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: a statewide study. Myocardial Infarction Data Acquisition System Study Group.

We studied the effect of diabetes mellitus (DM) on mortality rate in 42,595 patients in the statewide Myocardial Infarction Data Acquisition System (MIDAS), which included patients with myocardial infarction from 90 nonfederal hospitals in New Jersey during the years 1986 and 1987. Of these patients 9695 (22.8%) had DM. DM was more prevalent among female, black, and older patients. DM was associated with higher mortality rates, both in-hospital (21.5% vs 19.2%, p < 0.001) and during 3-year follow-up (46.7% vs 37.8%, p < 0.001). This relation persisted in both men and women, blacks and whites, and all age groups. DM was an independent predictor of mortality by multivariate Cox proportional hazards regression analysis after adjustments were made for gender, race, age, hypertension, left ventricular dysfunction, chronic pulmonary disease, chronic liver disease, and anemia. This effect of DM was most pronounced in the younger age groups. Relative risk was 1.87 for age group 30 to 49, 1.36 for 50 to 69, and 1.17 for 70 to 89 years (p < 0.0001).

Adult↗

Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial.

National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.

Aged↗

Current status of coronary artery bypass grafting in patients 70 years of age and older.

One hundred and seventy patients 70 years of age and older underwent isolated coronary artery bypass grafting (CABG) from January 1990 to December 1991 at St. Vincent's Hospital, Melbourne, Australia. The clinical records of these patients were analysed to investigate whether elderly patients could undergo safe coronary artery surgery and to determine the factors affecting the outcome. The 30 day or in-hospital mortality was 2.9% (5/170), with 80% (4/5) of the deaths due to cardiac causes. Major postoperative complications occurred in 22.3% (38/170) patients. The median postoperative hospital stay for the patients was 8 days (range 3-103 days). Univariate analysis identified hypertension and female gender as pre-operative risk factors and intraaortic balloon pump, prolonged ventilation, infarct, tamponade, need for inotropes, renal failure and a high APACHE II scores in the intensive care unit as postoperative significant risk factors for operative mortality. There was a trend towards increased mortality with emergency operations; the operative mortality was 2.1% (2/97) for elective operations, 3.1% (2/64) in urgent cases and 11.1% (1/9) for emergencies. Multivariate logistic regression analysis identified prolonged mechanical ventilation, perioperative infarct and APACHE II score as significant independent predictors of mortality. The low operative mortality indicates that elderly patients can undergo safe revascularization. A high incidence of complications necessitates careful monitoring but age per se should not be considered a contraindication to isolated CABG.

Age Factors↗

Body mass index centile charts to assess fatness of British children.

Body mass index (BMI) relates weight to height and reflects the shape of a child, but because of age dependency it has not been used conventionally for the estimation of fatness in children. From measurements of Tayside children (n = 34,533) centile charts were constructed for BMI (wt/ht2) from the raw data of height and weight, using Cole's LMS method for normalised growth standards. These data were compared with the only available European BMI charts published from data of French children obtained over a period of 24 years from 1956-79. British children appear to be 'fatter'. Within a subgroup (n = 445) the BMI values were correlated with estimations of body fat, for boys and girls, from skinfold thickness (r = 0.8 and 0.81) and bioelectrical impedance (r = 0.65 and 0.7). The limits of acceptable BMI have yet to be defined.

Adipose Tissue↗

Coronary angioplasty in unstable angina: contemporary experience.

OBJECTIVE: To evaluate the role of percutaneous transluminal coronary angioplasty (PTCA) in the treatment of patients with unstable angina. DESIGN: Retrospective analysis of administrative records of all acute care hospital discharges at Robert Wood Johnson University Hospital from 1987 to 1993 with International Classification of Diseases, 9th revision, codes for coronary angioplasty and corresponding catheterization laboratory reports. SETTING: Tertiary care teaching hospital. RESULTS: Of 4826 PTCA cases, unstable angina was identified in 780 as the main indication for the procedure. Baseline clinical features of patients with unstable angina were not different from those in patients with stable angina. The overall success rate for PTCA in patients with unstable angina was significantly higher (707 of 780, 91%) than the success rate in patients with stable angina (3466 of 4046, 86%). The major complication rate in unstable angina patients was low (29 of 780, 3.7%) and did not differ from that in stable angina patients (136 of 4046, 3.4%). The success and complication rates in patients with unstable angina were analyzed in terms of time of PTCA, ie, early (less than 48 h from admission) versus late (48 h or more from admission). The procedure was successful in 343 of 380 (90%) patients treated early and 364 of 400 (91%) patients treated late (not significant), and the complication rates were low (12 of 380, 3.2% versus 17 of 400, 4.3%; not significant in both groups). However, length of hospital stay was considerably shorter for patients treated early than for patients treated late (4.5 +/- 3.3 days versus 10.4 +/- 6.6 days, respectively, P < 0.0001). CONCLUSION: Contemporary results of PTCA in patients with unstable angina parallel those reported for stable angina. Thus, PTCA appears to be an effective and safe treatment for unstable angina patients, and treating these patients soon after admission does not appear to affect the success or complication rates.

Angina, Unstable↗

The effect of chlorthalidone on ventricular ectopic activity in patients with isolated systolic hypertension. The SHEP Study Group.

In an ancillary study of the Systolic Hypertension in the Elderly Program (SHEP), the effects of diuretics on ventricular ectopic activity were investigated in 186 patients with isolated systolic hypertension. Ventricular premature complexes (VPCs) were examined as the number of VPCs/24 hours, presence of > or = 1 VPC, presence of > or = 10 VPCs/24 hours, and presence of VPC pairs or ventricular tachycardia. Significant changes in VPCs were not observed either in the 92 patients randomized to chlorthalidone stepped-care (12.5 and 25 mg/day) or in the 94 placebo-treated patients (p > 0.1 for all VPC definitions and both groups). Serum potassium decreased from 4.4 +/- 0.5 to 4.1 +/- 0.5 mEq/liter (p = 0.002) in the chlorthalidone group and did not change (4.4 +/- 0.5 to 4.5 +/- 0.4 mEq/liter) in the placebo group. Potassium was prescribed routinely for confirmed hypokalemia < 3.5 mEq/liter. A relation between serum potassium and VPC or change in serum potassium and change in VPC was not observed in the chlorthalidone group. In summary, in patients with isolated systolic hypertension, chlorthalidone in doses that are effective in decreasing stroke and cardiovascular event rates (12.5 or 25 mg/day), did not increase VPCs.

Aged↗

Selenite induction of DNA strand breaks and apoptosis in mouse leukemic L1210 cells.

The effects of selenite on DNA integrity, cell viability, and long-term proliferative potential of mouse leukemic L1210 cells were examined in this study. Selenite treatment resulted in concentration-dependent increases in DNA single-strand breaks and double-strand breaks, as detected by a modified filter elution assay. A time-course experiment showed that DNA single-strand breaks preceded DNA double-strand breaks. Agarose gel electrophoresis of DNA extracted from selenite-treated cells displayed a nucleosomal fragmentation pattern that is characteristic of apoptotic cell death. The involvement of a Ca2+,Mg(2+)-dependent endonuclease responsible for DNA double-strand fragmentation was implied by the observation that two inhibitors of endonuclease activity, i.e. aurintricarboxylic acid and zinc, blocked selenite-induced DNA double-strand breaks. These inhibitors also prevented selenite-induced cell death as defined by loss of ability to exclude trypan blue dye. Selenite treatment severely impaired the colony-forming ability of cells capable of trypan blue exclusion. The induction of DNA strand breaks and commitment to apoptosis may explain the selenite-mediated growth inhibition and loss of long-term proliferative potential.

Animals↗

Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia.

Sleep disturbances and decrements of daytime performance have been attributed to HMG-CoA reductase inhibitors. As a rule, lipophilic compounds more readily cross the blood-brain barrier and are more likely to affect central nervous system function. The authors compared the effects of lovastatin (40 mg), a lipophilic compound, to pravastatin (40 mg), a hydrophilic compound, in a 6-week, double-blind, randomized, placebo-controlled, three-way Latin square design, cross-over study on 22 men with hypercholesterolemia. Patients had LDL cholesterol of more than 165 mg/dL and triglyceride of less than 350 mg/dL after 6 weeks of a low-fat (< 30%), low-cholesterol (< 300 mg/day) diet. Compared with placebo, there were no significant effects of lovastatin or pravastatin on the following subjective and polysomnographic sleep measures: changes in total sleep time, time in each sleep stage, sleep efficiency, sleep latency, REM density, REM activity, and number of arousals. Similarly, there were no effects of the two drugs on measures of cognitive performance. A significant increase in the duration of nocturnal tumescence (NPT) was observed after 2 weeks of treatment with both study drugs. This effect was not significant after 6 weeks of treatment. Both lovastatin and pravastatin caused significant (P < .05 compared with placebo) decreases in total cholesterol (by 20.9 and 20.6%, respectively), LDL cholesterol (by 27.8 and 29.9%), and triglycerides (by 13.6 and 3.7%). Subjects' HDL increased by 2.3% with lovastatin (NS) and by 3.1% with pravastatin (P < .05). Lipoprotein(a) increased by 20.5% with lovastatin and by 1.1% with pravastatin; these changes were not significantly different from placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular adaptation of a leaf-eating bird: stomach lysozyme of the hoatzin.

This report describes a lysozyme expressed at high levels in the stomach of the hoatzin, the only known foregut-fermenting bird. Evolutionary comparison places it among the calcium-binding lysozymes rather than among the conventional types. Conventional lysozymes were recruited as digestive enzymes twice in the evolution of mammalian foregut fermenters, and these independently recruited lysozymes share convergent structural changes attributed to selective pressures in the stomach. Biochemical convergence and parallel amino acid replacements are observed in the hoatzin stomach lysozyme even though it has a different genetic origin from the mammalian examples and has undergone more than 300 million years of independent evolution.

Adaptation, Physiological↗