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Biomedical subjects

P Schofield

Publications and source records attributed to P Schofield.

At least 55 records · Page 3Linked to original sources

Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease.

BACKGROUND: Oestrogen use by postmenopausal women has many health benefits, but findings on the effect of oestrogen in Alzheimer's disease are conflicting. Oestrogen promotes the growth and survival of cholinergic neurons and could decrease cerebral amyloid deposition, both of which may delay the onset or prevent Alzheimer's disease. To investigate whether use of oestrogen during the postmenopausal period affects the risk of Alzheimer's disease, we studied 1124 elderly women who were initially free of Alzheimer's disease, Parkinson's disease, and stroke, and who were taking part in a longitudinal study of ageing and health in a New York City community. METHODS: Relative risks and age-at-onset distributions were calculated from simple and adjusted Cox proportional hazards models. Standard annual clinical assessments and criterion-based diagnoses were used in follow-up (range 1-5 years). FINDINGS: Overall, 156 (12.5%) women reported taking oestrogen after onset of menopause. The age at onset of Alzheimer's disease was significantly later in women who had taken oestrogen than in those who did not and the relative risk of the disease was significantly reduced (9/156 [5.8%] oestrogen users vs 158/968 [16.3%] nonusers; 0.40 [95% Cl 0.22-0.85], p < 0.01), even after adjustment for differences in education, ethnic origin, and apolipoprotein-E genotype. Women who had used oestrogen for longer than 1 year had a greater reduction in risk; none of 23 women who were taking oestrogen at study enrolment has developed Alzheimer's disease. INTERPRETATION: Oestrogen use in postmenopausal women may delay the onset and decrease the risk of Alzheimer's disease. Prospective studies are needed to establish the dose and duration of oestrogen required to provide this benefit and to assess its safety in elderly postmenopausal women.

Age of Onset↗

Lipids, lipoprotein (a) and coronary artery disease in patients following cardiac transplantation.

Cardiac allograft vascular disease (CAVD) is the most important cause of late mortality in cardiac transplant recipients. While the pathogenesis of the disease is believed to be immunological, other factors like hyperlipidaemia may contribute. Total cholesterol, LDL cholesterol. HDL cholesterol, triglycerides, apolipoprotein A1 and B and Lp(a) levels were measured in 174 cardiac transplant recipients attending our clinic for routine follow-up. Univariate and multivariate logistic regression analysis was carried out to assess the relationship of the variables studied to the presence of CAVD diagnosed with coronary angiography. CAVD was present in 42 of the 174 patients. The group with CAVD had a higher total cholesterol (6.8 vs 6.3 mmol/l), lower HDL cholesterol (0.8 vs 0.9 mmol/l), higher triglyceride (2.8 vs 2.0 mmol/l) and higher Lp(a) level (317.5 vs 95 mg/l) than the group without CAVD. In multivariate analysis, after adjusting for gender, hypertension, time from transplantation, preoperative diagnosis and lipid-lowering therapy, Lp(a), total cholesterol, HDL cholesterol and triglycerides remained significantly correlated with CAVD. The results indicate a significant association between hyperlipidaemia, Lp(a) levels and allograft vascular disease. Further studies are needed to show whether treatment of hyperlidaemia in this population delays the onset or slows the progression of CAVD.

Adult↗

The management of post-cardiac transplantation coronary artery disease.

OBJECTIVE: Allograft coronary artery disease remains the single greatest limitation to long term survival after cardiac transplantation. It is peculiarly aggressive in its behavior and diffuse in its nature. The role of conventional approaches to coronary artery revascularisation were studied in a selected group of cardiac transplant recipients. METHODS: Of the 557 patients undergoing cardiac transplantation at our unit between January 1979 and December 1993, all were screened for the development of allograft coronary artery disease routinely after 2 years and yearly thereafter or after 4 years. Twenty patients with allograft coronary artery disease were considered suitable for treatment by conventional means 17 of whom had undergone transplantation for ischaemic cardiomyopathy and the others for dilating cardiomyopathy. Percutaneous transluminal coronary angioplasty was performed in 18, 25-103 months after transplantation (mean 60 months) all of whom had severe proximal stenoses and reversible defects on perfusion scans. None suffered chest pain. Coronary artery bypass grafting was performed in 5, 95-105 months after transplantation (mean 101 months) 2 of whom had post-infarction unstable angina and 3 had severe triple vessel disease, dyspnoea, and perfusion abnormalities. RESULTS: The primary success rate for PTCA was 84% (16/19). Two lesions restenosed and 3 patients had progressive disease which necessitated coronary revascularisation. No patient died. Of the 5 patients undergoing coronary artery surgery 2 died perioperatively, one from acute left ventricular failure and one from acute rejection. All 18 survivors have improved perfusion scans. Following surgery, all survivors had improvement in dyspnoea and relief of angina. Five late deaths a mean of 89 months after transplantation were from coronary artery disease (4) and lung malignancy (1). CONCLUSIONS: Revascularisation by PTCA and CABG is feasible and successful in selected cardiac transplant recipients. Further study is required to determine the effect of revascularisation on prognosis.

Adult↗

Snoezelen: its potential for people with chronic pain.

The purpose of this paper is to outline the application of a new form of chronic pain management which is currently under investigation by the writer as a PhD study with the University of Wales, Cardiff, UK. The study was initiated by the writer whilst working as a Senior Nurse Specialist in pain management. It is anticipated that the results of the study will be available by 1996. The concept of the Snoezelen will be discussed. Snoezelen has been used by many centres for the care of individuals with learning disabilities. The paper will also describe the Snoezelen centre based in Chesterfield, UK and some of the experiences that are available. Finally, the rationale behind the application of a strategy for the management of individuals experiencing chronic pain will be discussed relating to some of the appropriate literature. As a result of this study several pain clinics are interested in looking at the use of some of the concepts.

Chronic Disease↗

Effect of maturity on digestion kinetics of water-soluble and water-insoluble fractions of alfalfa and brome hay.

Alfalfa and bromegrass, each harvested at five different stages of maturity, were separated into water-insoluble and -soluble fractions. The NDF concentrations ranged from 19 to 43% for alfalfa and from 42 to 58% for brome. The rates of digestion, by mixed ruminal microflora, of the unfractionated forage and of the water-insoluble and -soluble fractions were measured in vitro using pressure sensors to monitor gas production. Both forages showed the expected decline in fiber digestibility with increasing maturity. A dual-pool logistic model gave pool sizes, specific rates, and a single lag time for both the faster- and slower-digesting fractions. The main difference between alfalfa and brome was in the soluble pool. This pool produced approximately 40% of the total gas in alfalfa, 25% in brome. The specific digestion rates of the brome soluble pool were approximately 50% higher than those for alfalfa. Net VFA production showed a somewhat higher acetate: propionate ratio for brome (3.2) compared with alfalfa (2.2), but there was little change with increasing maturity within a given forage. Gas production curves for the unfractionated forage showed a 0 to 10% positive deviation from curves created by adding data from separate digestion of the insoluble and soluble forage fractions. Gas measurements offer a promising approach to the study of the water-soluble extracts of forages and the interaction of the soluble- and insoluble-fractions during fermentation.

Acetates↗

Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City.

Apolipoprotein-E epsilon 4 (APOE-epsilon 4) has been consistently associated with Alzheimer disease (AD) and may be responsible for an earlier age at onset. We have previously reported a diminished association between APOE-epsilon 4 and AD in African Americans. Using a new method, which allows inclusion of censored information, we compared relative risks by APOE genotypes in an expanded collection of cases and controls from three ethnic groups in a New York community. The relative risk for AD associated with APOE-epsilon 4 homozygosity was increased in all ethnic groups (African American relative risk [RR]=3.0; 95% confidence interval [CI]=1.5-5.9; Caucasian RR=7.3, 95% CI=2.5-21.6; and Hispanic RR=2.5, 95% CI=1.1-5.7), compared with those with APOE-epsilon 3/epsilon 3 genotypes. The risk was also increased for APOE-epsilon 4 heterozygous Caucasians (RR=2.9, 95% CI=1.7-5.1) and Hispanics (RR=1.6, 95% CI=1.1-2.3), but not for African Americans (RR=0.6, 95% Ci=0.4-0.9). The age distribution of the proportion of Caucasians and Hispanics without AD was consistently lower for APOE-epsilon 4 homozygous and APOE-epsilon 4 heterozygous individuals than for those with other APOE genotypes. In African Americans this relationship was observed only in APOE-epsilon 4 homozygotes. These results confirm that APOE genotypes influence the RR of AD in Caucasians and Hispanics. Differences in risk among APOE-epsilon 4 heterozygote African Americans suggest that other genetic or environmental factors may modify the effect of APOE-epsilon 4 in some populations.

Age of Onset↗

Routes of administration and effect of carbidopa pretreatment on 6-[18F]fluoro-L-dopa/PET scans in non-human primates.

In 6-[18F]fluoro-L-dopa (Fdopa)/positron emission tomography (PET) studies, carbidopa pretreatment increases the Fdopa bioavailability to the brain and enhances the intensity of striatal PET images. Different PET research teams have used various carbidopa doses and routes of administration in non-human primate studies. The purpose of this study was to examine the plasma profiles of carbidopa and the effect of the route of administration of carbidopa on a Fdopa/PET scan. Cynomolgus monkeys were given carbidopa either orally (5 mg/kg), intraperitoneally (2.5 and 5 mg/kg) or intravenously (5 mg/kg) 60-90 min prior to the Fdopa injection. Carbidopa-treated monkeys were compared to monkeys without carbidopa treatment. No carbidopa was detected in the plasma samples when it was given orally, possibly due to poor absorption in the gastrointestinal tract. In addition, the striatal and cortical activities were not statistically different from those of the untreated monkeys, indicating that little or no inhibition of the peripheral decarboxylation of Fdopa by carbidopa had taken place. When carbidopa was given intraperitoneally at a dose of 2.5 and 5 mg/kg and intravenously at 5 mg/kg, plasma carbidopa concentrations at the time of Fdopa injection were 0.95 +/- 0.26, 2.22 +/- 0.23 and 2.79 +/- 0.26 micrograms/ml, respectively. Because of inhibition of peripheral decarboxylation of Fdopa by carbidopa, more Fdopa was available for transport into the brain and as a result, both the striatal and cortical activities were significantly higher than those of the untreated monkeys. Carbidopa administration had no effect on either the striatal-to-cortical activity ratio or the striatum uptake value.

Administration, Oral↗

The Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) trial. Results of a multicenter randomized trial investigating the effects of high dose unfractionated heparin on angiographic restenosis and clinical outcome.

OBJECTIVES: We sought to determine whether 12,500 IU of unfractionated heparin given subcutaneously twice daily for 4 months after percutaneous transluminal coronary angioplasty beneficially influences the subsequent rate of angiographic restenosis and the incidence of clinical events. BACKGROUND: Heparin has been shown to exhibit powerful antiproliferative effects against smooth muscle cells in several animal models. METHODS: A randomized trial with blinded data analysis was undertaken to assess the effect of unfractionated subcutaneous heparin on angiographic restenosis after coronary angioplasty. After successful angioplasty, patients were randomized to receive no heparin or 12,500 IU of heparin given subcutaneously twice daily for 4 months. Quantitative coronary angiography was performed before angioplasty, immediately after angioplasty and at follow-up ("early" [before 4 months] or electively [at 4 months]). RESULTS: The study group comprised 339 patients, 167 randomly assigned to receive heparin, 172 to receive no heparin. Repeat cardiac catheterization was performed in 90% of randomized patients. At early and elective restudy (mean 4.2 months), the mean +/- SD difference in minimal lumen diameter between the postangioplasty and follow-up measurement was -0.55 +/- 0.58 mm for the no heparin group and -0.43 +/- 0.59 mm for the heparin group (p = NS). Clinical events during the follow-up period did not differ significantly between groups: fatal myocardial infarction (1 patient in each group), coronary bypass grafting (5 patients in each group), repeat angioplasty (12 in the no heparin, 6 in the heparin group), angina at 4-month assessment (33% in the no heparin, 32% in the heparin group). CONCLUSIONS: Long-term treatment with high dose subcutaneous heparin (12,500 IU twice daily) for 4 months did not favorably influence angiographic or clinical outcome after coronary angioplasty.

Angioplasty, Balloon, Coronary↗

Homograft replacement of fungal endocarditic pulmonary valve.

Right-sided infective endocarditis is uncommon but is increasingly seen as a reflection of the prevalence of drug abuse, chronic intravenous catheters and associated congenital malformations. Isolated pulmonary valve endocarditis has rarely been reported and there has been only one previous report of isolated pulmonary valve fungal endocarditis. This resolved with antimicrobials. We describe a case of isolated mycotic pulmonary valve endocarditis resistant to existing anti-fungal chemotherapy, which necessitated pulmonary valve resection and replacement with a homograft.

Adult↗

Isolation and characterization of an anaerobic ruminal bacterium capable of degrading hydrolyzable tannins.

An anaerobic diplococcoid bacterium able to degrade hydrolyzable tannins was isolated from the ruminal fluid of a goat fed desmodium (Desmodium ovalifolium), a tropical legume which contains levels as high as 17% condensed tannins. This strain grew under anaerobic conditions in the presence of up to 30 g of tannic acid per liter and tolerated a range of phenolic monomers, including gallic, ferulic, and p-coumaric acids. The predominant fermentation product from tannic acid breakdown was pyrogallol, as detected by high-performance liquid chromatography and mass spectrometry. Tannic acid degradation was dependent on the presence of a sugar such as glucose, fructose, arabinose, sucrose, galactose, cellobiose, or soluble starch as an added carbon and energy source. The strain also demonstrated resistance to condensed tannins up to a level of 4 g/liter.

Animals↗

Haemochromatosis presenting as congestive cardiac failure.

A 24 year old man with congestive cardiac failure was found to have grossly increased transferrin saturations, raised serum ferritin, and an iron-laden myocardium on biopsy. Initial treatment with the iron chelator desferrioxamine was replaced by weekly venesection. He was placed on the cardiac transplant list because of severe left ventricular dysfunction but was later removed because his symptoms and function improved. He remains well with few symptoms and is maintained on regular venesection and testosterone injections.

Adult↗

Neurologic signs and symptoms in a cohort of homosexual men followed for 4.5 years.

We traced the development of neurologic impairment in 207 homosexual men (123 human immunodeficiency virus [HIV]-positive and 84 HIV-negative controls) over 4.5 years of follow-up. We applied generalized estimating equations to logistic regression analyses with repeated measures to examine the differences between HIV-positive and HIV-negative subjects with respect to the likelihood of developing six neurologic outcomes derived from a factor analysis, significant neurologic impairment (modified Kurtzke disability score of > or = 3), or significant neuropsychological impairment. We found that, over time, HIV-positive subjects were more likely to develop clinically significant extrapyramidal signs and frontal release signs than HIV-negative subjects. Controlling for age or education, as CD4 count declined, the odds of developing significant extrapyramidal signs, abnormalities in alternating movements, frontal release signs, and a Kurtzke score > or = 3 increased. HIV-positive subjects were almost five times as likely (odds ratio [OR], 4.6; 95% CI, 1.6 to 13.4) as HIV-negative subjects to stay the same or worsen neurologically on the next visit, and those with CD4 < or = 200 were 4.8 times as likely (OR, 4.8; 95% CI, 2.2 to 10.7) to maintain or worsen neurologically relative to those with higher CD4 counts. We conclude that neurologic impairment becomes increasingly apparent over time in HIV-infected men, especially in those with low CD4 counts.

Adult↗

Measurement and kinetic analysis of the neutral detergent-soluble carbohydrate fraction of legumes and grasses.

The fermentation of the neutral detergent-soluble (NDS) fraction of two legumes (clover, alfalfa) and two grasses (timothy, guinea grass) was measured using a curve subtraction technique with in vitro gas production data from the whole forage and the isolated neutral detergent-extracted fiber. The NDF disappearance and VFA production also were measured. There were no significant differences between the VFA patterns from whole forage and NDF. There was a good linear correlation between the volume of gas produced and the mass of fiber digested in the NDF samples. Analysis of the gas curves with a dual-pool logistic model gave a lag value, digestion rates and pool sizes for the whole forage, the fiber component, and the NDS fraction. Rates for the NDS fraction ranged from .152 h-1 for clover to .191 h-1 for timothy. These rates are appreciably lower than values assumed in some models. Application of a triple-pool logistic model revealed the presence of faster-digesting material in the legumes. We discuss several different ways to measure the NDS pool size. The simplest method requires only a single gas measurement at the end of in vitro digestion of the whole forage coupled with an NDF disappearance measurement. The curve subtraction technique can provide information on the size and digestion kinetics of the NDS pool. This information is useful both for model studies and for agronomic research and may help us to understand the nutritional significance of this fast-digesting carbohydrate fraction.

Carbohydrate Metabolism↗

Validity of using accumulated gas pressure readings to measure forage digestion in vitro: a comparison involving three forages.

Gas output from in vitro digestion of forage can be used to measure both forage digestibility and the kinetics of microbial digestion. Two different approaches are used to measure gas volumes: 1) either the gas is collected at atmospheric pressure and its volume determined directly, or 2) the gas accumulates in a fixed volume container, and the volume is calculated from pressure changes. We have used the latter technique to study the in vitro digestion of alfalfa, timothy, and corn silage by ruminal microorganisms in bottles of different sizes. We measured pH changes, NDF disappearance, and VFA concentrations and characterized the digestion profiles using a single- or dual-pool logistic model. Bottle size had a slight effect on pH but was not associated with changes in any of the other characteristics measured including the kinetic parameters. Gas measurements based on pressure increases in a fixed volume container appear to offer a valid alternative to methods based on gas collection at atmospheric pressure. We present an equation to adjust pressure sensor calibration values for use in different sized containers.

Animal Feed↗

Using assessment tools to help patients in pain.

Pain is a subjective experience; assessment tools allow some objective indication of the effectiveness of care. Assessment tools can be time-consuming to complete and are not a substitute for one-to-one communication and a thorough nursing assessment. Assessment tools increase the options available when pain is a serious problem.

Humans↗