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Biomedical subjects

R Greenhalgh

Publications and source records attributed to R Greenhalgh.

At least 19 recordsLinked to original sources

Advances in prostate cancer immunotherapy.

Metastatic prostate cancer remains incurable. Harnessing the body's own immune system to control or eradicate tumours has long been an attractive concept. Only recently has the field of tumour immunology provided the basic science behind the mechanisms of tumour genesis, molecular basis of the recognition of tumour associated antigens and the interactions of the antigen-presenting cells with effector cells. This research has been translated into numerous clinical immunotherapy strategies, which have reached the oncology clinic and which should provide options for our patients.

Animals↗

The influence of 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene promoter on the incidence, growth and operative risk of abdominal aortic aneurysm.

BACKGROUND: a single base pair deletion/insertion (4G/5G) polymorphism in the plasminogen activator inhibitor (PAI-1) promoter appears to influence PAI-1 synthesis (increased PAI-1 and inhibition of fibrinolysis with the 4G allele) and survival after severe trauma. OBJECTIVE: to identify whether the 4G/5G polymorphism influences the natural history of abdominal aortic aneurysm (AAA). METHODS: Four hundred and sixty patients with small AAA were genotyped for the 4G/5G polymorphism. AAA growth was assessed from serial ultrasonographic measurements, subject to linear regression analysis. Mortality following eventual elective surgery was recorded. RESULTS: the frequency of the 3 genotypes (4G4G, 4G5G and 5G5G) was in Hardy-Weinberg equilibrium and similar to that in a healthy population. The mean aneurysm growth rate was 0.37, 0.35 and 0.44 cm/year respectively for patients of 4G4G, 4G5G and 5G5G genotype respectively, p = 0.07. The 30d mortality following open elective aneurysm repair was 8% (7/87), 8% (11/145) and 0% (0/56) for patients of 4G4G, 4G5G and 5G5G genotype respectively, giving a higher mortality for those carrying a 4G allele p = 0.03. CONCLUSIONS: polymorphism of the PAI-1 gene promoter does not influence the development of AAA, although AAA growth is faster for patients of 5G5G genotype. However, this genotype (5G5G), which is associated with enhanced fibrinolysis, appears protective following open aneurysm repair. This effect of PAI-1 genotype on survival following surgery is likely to have widespread significance in vascular and general surgery.

Aged↗

Fathers' coping style, antenatal preparation, and experiences of labor and the postpartum.

BACKGROUND: In recent years the trend for fathers in Western postindustrial countries to attend childbirth has increased. This study examined the interaction between fathers' information-seeking coping predispositions and their level of attendance at antenatal classes with respect to their experiences of attending childbirth. Associations between fathers' childbirth experiences, their relationship with their baby, and level of depressive symptomatology at 6 weeks postpartum were also examined. METHODS: A quantitative methodology was employed in which 78 fathers completed several questionnaires, some within 6 days of childbirth and others at 6 weeks postpartum. RESULTS: Fathers who were characterized as high blunters (avoiders) of threat information, from antenatal classes reported that experiencing childbirth was less fulfilling than fathers with similar coping styles who did not attend classes. Fathers' reports of fulfillment and delight while attending childbirth were negatively related to their level of depressive symptomatology at 6 weeks postpartum. Levels of distress were associated with subsequent depressive symptoms, but their effect was removed when preexisting depressive symptoms were partialled out. Fathers whose children were born by cesarean delivery used significantly more negative adjectives to describe their baby at 6 weeks postpartum compared with those born by vaginal delivery. More married fathers attended antenatal classes and reported lower levels of depressive symptomatology than unmarried fathers. CONCLUSIONS: Although fathers' attendance at antenatal classes may have positive consequences for them and their partner, for some fathers, attendance at classes may be associated with less positive reports of experiencing childbirth. The way in which men experience childbirth may have some influence on their subsequent emotional well-being.

Adaptation, Psychological↗

Mixed leg ulcers.

Explore the source record for details and available documents.

Angiography↗

The European Board of Surgery Qualification (EBSQ) was born in 1996.

The EU has sent delegates to the Section of Surgery, UEMS and the EBS for some years. The EBSQ is the only way to harmonise surgical standards across the EU. It is recognised that standards very across Europe and although CCST must be recognised across Europe, in practice there are 15 CCSTs of different standards. UK and Ireland have surgical training programmes and standards which are admired and the EBSQ has been centred in London and the sterling area. There is therefore a unique opportunity to influence European surgery. What is far from certain is whether UK trainee surgeons will feel the need to take EBSQ, for them it is very much an optional extra.

Education, Medical↗

The impact of genetic counselling on risk perception in women with a family history of breast cancer.

Women with a family history of breast cancer generally self-refer because they have a feeling that their risk is high. However, they have, in general, only a hazy notion of the population risk of breast cancer and their own risk in relation to this. It is probable that they are helped by genetic counselling and, if at substantial risk, by annual mammography. However, the psychological impact of assigning true risk and the value of mammography need to be evaluated. We have assessed risk perception by questionnaire in 517 new referrals to a family history clinic and 200 women returning to the clinic at least 1 year after counselling. Correct assignment of population lifetime risk of breast cancer was 16% in the uninformed precounsel group and 33% in the post-counsel group, likewise personal risk was correct in 11% and 41% respectively. Post-counsel women were significantly more likely to retain information if they were sent a post-clinic letter or if they assessed their personal risk as too high initially.

Adult↗

Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.

To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.

Aspirin↗

The influence of smoking and plasma factors on prosthetic graft patency.

The effects of smoking and plasma risk factors on the patency of prosthetic femoro-popliteal bypass grafts were investigated in 93 patients entered into a multicentre trial of prosthetic graft materials (70 patients had patent grafts and 23 patients had occluded grafts 2 years after surgery). The smoking markers thiocyanate and fibrinogen were significantly higher in patients with occluded grafts, whereas LDL-cholesterol was significantly higher in patients with patent grafts 2 years after bypass. Based on smoking markers, graft patency in smokers was 57% at 2 years by life table, compared to 78% in non-smokers. P less than 0.05. Fibrinogen was an important variable, predicting graft occlusion with graft patency in patients with below median fibrinogen levels, being 84% at 2 years by life table compared to 51% in those with above median fibrinogen levels, P less than 0.025. Although increased levels of LDL-cholesterol have been associated with accelerated atherosclerosis, patients with above median levels of LDL-cholesterol had improved graft patency (83%) at 2 years compared to patency in patients with below median LDL-cholesterol (60%), P less than 0.05. The plasma risk factors associated with the failure of prosthetic grafts are similar to those associated with the failure of saphenous vein grafts, indicating that higher fibrinogen levels and smoking may contribute to an hypercoagulable state. Greater efforts are needed to stop patients smoking after vascular reconstruction.

Aged↗

Lipids and apolipoprotein profiles in men with aneurysmal and stenosing aorto-iliac atherosclerosis.

The plasma lipids, lipoproteins and apolipoproteins have been compared in two groups of men with aorto-iliac atherosclerosis: Aneurysmal disease (n = 42) and stenosing disease (n = 86). The mean age of the men aneurysmal disease was 67.5 +/- 5.8 years and the mean age of the men with stenosing disease was 65.0 +/- 6.1 years: There was no significant different in body mass indices or smoking habits between the groups. The patients with aneurysmal disease had lower levels of plasma cholesterol than patients with stenosing disease (5.53 +/- 1.17 versus 6.11 +/- 1.20 mmol/L, P less than 0.05), but carried more cholesterol in VLDL compared to patients with stenosing disease (1.00 +/- 0.90 versus 0.60 +/- 65 mmol/L, P less than 0.05). Significantly lower concentration of apolipoprotein AI and HDL-cholesterol in patients with aneurysmal disease (ApoAI 1.01 +/- 0.31 versus 1.18 +/- 0.31 mmol/L, P less than 0.02, HDL 0.93 +/- 0.53 versus 1.13 +/- 0.34, P less than 0.05) was another characteristic difference between these two groups of patients with peripheral arterial disease. Otherwise, there were no obvious differences in the levels of plasma triglyceride, VLDL-triglyceride, LDL-cholesterol, and apolipoproteins B, C-III and E between the two groups. Although lipid and apolipoprotein profiles may not discriminate between aneurysmal and stenosing disease, different types of lipoprotein particles may contribute to the atherosclerotic process characterising both diseases.

Aged↗

Pilot study of a screening test for peripheral arterial disease in middle aged men: fibrinogen as a possible risk factor.

A simple one minute exercise test was used as a screening test for asymptomatic peripheral arterial disease in a sample of 100 men in their sixth decade with no previous referrals for cardiovascular disease. Other investigations included resting ECG, non-invasive carotid artery assessment, and plasma biochemical analysis. Of these 100 men (mean age 56), 10 had evidence of peripheral disease on exercise testing, four had ischaemic changes on resting ECG, and one showed evidence of carotid artery stenosis. A total therefore of 15 out of 100 (15%) had asymptomatic arterial disease. These 15 men had increased concentrations of plasma fibrinogen (4.3(0.7) g.litre-1) compared with men with no evidence of arterial disease (3.5(0.7) g.litre-1; p less than 0.01). The one minute exercise test is a useful screening test for peripheral arterial disease, and this pilot study suggests that raised plasma fibrinogen concentrations may be an important risk factor.

Arterial Occlusive Diseases↗

13C NMR study of the biosynthesis of toxins by Fusarium graminearum.

13C NMR spectroscopic investigations on the biosynthesis of mycotoxins produced by Fusarium graminearum (M69) were carried out through the incorporation of [1-13C]- and [2-13C]acetate precursors. The major secondary metabolites produced by this species in still culture were deoxynivalenol (3,7,15-trihydroxy-12,13-epoxytrichothec-9-en-one), 15-acetyldeoxynivalenol, zearalenone, and butenolide. [1-13C]- and [2-13C]acetate were incorporated in alternate carbon atoms in zearalenone, consistent with the head to tail condensation of nine acetate units. The trichothecenes were enriched in a manner consistent with the condensation of three mevalonate units. 13C/13C couplings, observed between C-5 and C-12, as well as between C-6 and C-15 of 15-acetyldeoxynivalenol, confirms the current hypothesis of formation of the trichothecene ring system by cyclization of farnesyl pyrophosphate. The incorporation pattern in ergosterol is also consistent with a mevalonate origin, while the adjacent incorporation of acetate methyl groups in butenolide suggests a glutamate precursor. The degree of enrichment in the secondary metabolites, which ranged from 3 to 10% at each carbon site, was observed in the 13C NMR spectra of the crude fungal extracts to be dependent on the timing of acetate addition to the culture. The specific toxins produced together with the quantity of each, were also found to be dependent on the timing of acetate addition. Competition between the three biosynthetic pathways of secondary metabolism, i.e. polyketide, mevalonate, and amino acid for the labeled acetate in this organism is a complex function of culture conditions.

Acetates↗

The sorptive capacity of an aquatic macrophyte for the pesticide aminocarb.

Ceratophyllum demersum exposed to a constant 1 microgram/ml aminocarb exhibited a large capacity for the sorption of the pesticide, up to 400 micrograms/g fresh weight in the dark and 1000 micrograms/g fresh weight in the light. Smaller, actively growing sprigs sorbed 5 times more pesticide per gm fresh weight than larger, older sprigs, although total uptake per plant was greater in the larger plants. Membrane conformation and integrity appear to be important factors in determining the capacity of this aquatic plant for pesticide sorption.

Absorption↗

Toxigenic potential of some fusarium isolates from southeast Asia.

The isolation and characterization of 10 isolates of six Fusarium spp. from plant and soil samples collected in Southeast Asia is reported. The ability of these isolates to produce trichothecenes both in liquid cultures (CZ, GYEP, and MYRO) and on rice was assessed, and their toxigenic potential was examined by skin assay and gavage studies with culture filtrates. Although culture filtrates of all the isolates caused minor damage to test animals, only that of F. equiseti DAOM 189762 produced trichothecenes.

Journal Article↗

Ingestion of vomitoxin (deoxynivalenol)-contaminated wheat by nonlactating dairy cows.

Our objective was to determine if there were serious deleterious effects of wheat naturally contaminated with vomitoxin (deoxynivalenol) on nonlactating dairy cows. Comparisons were between two Quebec spring wheat sources contaminated with Fusarium graminearum in a feeding trial involving 10 nonlactating Holstein dairy cattle offered good quality hay for ad libitum intake supplemented with wheat-oats concentrate (1 kg concentrate/100 kg body weight). Initially, for 3 wk all cows were fed hay plus wheat-oats containing 1.5 mg vomitoxin/kg. Each week thereafter two more cows, chosen at random, were switched to a second wheat-oats concentrate containing higher mycotoxin concentration (6.4 mg vomitoxin/kg). After the last two cows had been on the latter diet for 6 wk, all cows were returned to the previous wheat-oats concentrate containing the lower mycotoxin concentration (1.5 mg vomitoxin/kg). No unusual symptoms of illness that might be attributed to the mycotoxin-contaminated wheat were observed. In body weight gains, the data reflected a linear growth pattern with no apparent effect of changing from low to high vomitoxin content in the concentrate. Generally, consumption of the wheat-oats ration containing 6.4 mg vomitoxin/kg was lower than the 1.5 mg vomitoxin/kg concentrate. The progressive, linear decrease of hay consumption was not affected by source of contaminated wheat-oats diet.

Animal Feed↗

The tolerance of White Leghorn and broiler chicks, and turkey poults to diets that contained deoxynivalenol (vomitoxin)-contaminated wheat.

Three experiments were done to determine the effects of giving White Leghorn chickens, broiler chickens, and turkey poults diets that contained white winter or spring wheat contaminated with 4-deoxynivalenol (DON). Diets that contained .35 and .7 mg DON/kg from winter wheat did not (P greater than .05) influence feed intake, body weight gain, feed/gain ratio, and organ weight/body weight ratios of Leghorn and broiler chickens, and poults when fed between 7 and 21 days in Experiment 1. Dietary DON levels up to 4.6 mg/kg increased the feed intakes (P less than .01) and daily body weight gains (P less than .05) of Leghorn chickens between 7 and 35 days of age in Experiment 2 but had little effect (P greater than .05) on these variables for broiler chickens between 7 and 52 days of age in Experiment 3. Within Experiments 2 and 3, feed/gain ratios and organ weight/body weight ratios were similar among the Leghorn and broiler chickens, respectively. The dressing percent and chilled carcass weights of eviscerated broiler chickens were not affected (P greater than .05) by DON in the diets of Experiment 3. Mortality was low (less than 3.3%) for the three experiments and necropsy examination indicated that the birds died from several causes unrelated to the dietary treatment. There was no evidence of emesis during the experiments or of overt changes in the appearance of the oral cavity, heart, liver, spleen, kidney, proventriculus, gizzard, and intestines of a random sample of birds killed by carbon dioxide asphyxiation and necropsied. Differences occurred between the analyzed and calculated DON contents of the experimental diets; possible reasons for these differences are discussed. The results of these experiments indicate that young chickens and turkey poults can tolerate diets that contain DON up to at least 5 mg/kg from white winter or spring wheat.

Animal Feed↗