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R Davies

Publications and source records attributed to R Davies.

At least 73 records · Page 4Linked to original sources
PubMed2000

Antideuteron yield at the AGS and coalescence implications

We present Experiment 864's measurement of invariant antideuteron yields in 11.5A GeV/c Au+Pt collisions. The analysis includes 250x10(6) triggers representing 14x10(9) 10% central interactions sampled for events with high mass candidates. We find (1/2pip(t))d(2)N/dydp(t) = 3.5+/-1.5(stat)+0.9-0.5(syst)x10(-8) GeV-2 c(2) for 1.8 = 0.35 GeV/c ( y(c.m.) = 1.6) and 3.7+/-2.7(stat)+1.4-1.5(syst)x10(-8) GeV-2 c(2) for 1.4 = 0.26 GeV/c, and a coalescence parameter B2; of 4.1+/-2. 9(stat)+2.3-2.4(syst)x10(-3) GeV2 c(-3). Implications for coalescence and antimatter annihilation are discussed.

Journal Article↗
PubMed2000

Cortical cell death induced by IL-1 is mediated via actions in the hypothalamus of the rat.

The cytokine IL-1 mediates diverse forms of neurodegeneration, but its mechanism of action is unknown. We have demonstrated previously that exogenous and endogenous IL-1 acts specifically in the rat striatum to dramatically enhance ischemic and excitotoxic brain damage and cause extensive cortical injury. Here we tested the hypothesis that this distant effect of IL-1 is mediated through polysynaptic striatal outputs to the cortex via the hypothalamus. We show that IL-1beta injected into the rat striatum with the excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA) caused increased expression of IL-1beta (mRNA and protein) mainly in the cortex where maximum injury occurs. Marked increases in IL-1beta mRNA and protein were also observed in the hypothalamus. S-AMPA, injected alone into the striatum, caused only localized damage, but administration of IL-1beta into either the striatum or the lateral hypothalamus immediately after striatal S-AMPA resulted in widespread cell loss throughout the ipsilateral cortex. Finally we showed that the cortical cell death produced by striatal coinjection of S-AMPA and IL-1beta was significantly reduced by administration of the IL-1 receptor antagonist into the lateral hypothalamus. These data suggest that IL-1beta can act in the hypothalamus to modify cell viability in the cortex. We conclude that IL-1-dependent pathways project from the striatum to the cortex via the hypothalamus and lead to cortical injury, and that these may contribute to a number of human neurological conditions including stroke and head trauma.

Animals↗
PubMed2000

Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.

BACKGROUND: Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure. METHODS: A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper. RESULTS: A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03). CONCLUSIONS: Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

Aged↗
PubMed2000

Partners' expressed emotion and the control and management of type 1 diabetes in adults.

OBJECTIVE: "Expressed emotion" (EE) refers to a set of valid and reliable measures of family emotional attitudes, which are robust predictors of illness course in several psychiatric conditions and which have recently been studied in some medical conditions. We hypothesised that high EE in partners of diabetes patients would be associated with poorer glucose control, management of and adaptation to diabetes. METHODS: Sixty adult Type 1 diabetes patients, who were attending routine clinics at a specialist diabetes centre, and their partners were interviewed separately and completed various questionnaire measures. Partners' EE was rated from a modified Camberwell Family Interview; patients were interviewed to assess self-management practices. Glycated hemoglobin (HbA(1c)) was the measure of glucose control. RESULTS: Only 10/60 (17%) partners were classified as high EE. Patients with high-EE partners had significantly worse self-management scores, more negative appraisal of diabetes, and higher depression scores than those with low-EE partners, but there was no association between EE measures and HbA(1c). CONCLUSIONS: In contrast to findings from previous research on the families of patients with psychiatric illnesses, only a minority of partners of adult patients with Type 1 diabetes are classified as high-EE. We found no evidence that partners' EE was related to patients' blood glucose control.

Adolescent↗
PubMed2000

Highly purified CD34+ cells isolated using magnetically activated cell selection provide rapid engraftment following high-dose chemotherapy in breast cancer patients.

The primary objective of this study was to evaluate the safety of infusion of CD34+ cells, selected using a clinical scale magnetically activated cell sorting device, assessed by time to hematological engraftment and incidence of adverse events. Secondary objectives included evaluation of device performance in terms of purity and recovery of the CD34+ cell product. Breast cancer patients suitable for transplantation received cyclophosphamide and filgrastim for mobilisation, followed by three leukaphereses. The products of the first two leukaphereses underwent CD34+ cell selection. The product of the third leukapheresis was cryopreserved unmanipulated. Following high-dose cyclophosphamide, thiotepa and carboplatin, selected CD34+ cells were infused. In 54 patients who received selected cells only, the median time to platelet recovery and neutrophil recovery was 11 days (range 5-51) and 9 days (range 5-51), respectively. There were no adverse events associated with infusion of selected cells. A total of 126 leukapheresis samples was available before and after selection for central CD34+ analysis. The median purity was 96.1% (27.4-99.4) and the median recovery was 52. 3% (15.2-146.3). These data show that cells selected using magnetically activated cell selection provide safe and rapid engraftment after high-dose therapy. Bone Marrow Transplantation (2000) 25, 243-249.

Adolescent↗
PubMed2000

Mutation frequency in the lacI gene of liver DNA from lambda/lacI transgenic mice following the interaction of PCBs with iron causing hepatic cancer and porphyria.

The synergistic interaction of iron overload, AHR: genotype and exposure to a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1254) in mice leads to hepatic porphyria, oxidative DNA damage and cancer. In humans, hepatocellular cancer is associated with iron overload and hepatic porphyria. Neither the mechanism of hepatic carcinogenesis induced by PCBs in rodents nor hepatocellular cancer induced by iron and porphyria in humans are understood. To test the hypothesis that chronic interaction of iron and PCBs may induce mutagenesis in liver DNA, lambda /lacI transgenic C57BL/6 mice were given iron dextran (600 mg iron/kg) and then administered Aroclor 1254 in the diet (0.01%) for 7 weeks. Hepatic iron, CYP1A activity and CYP1A1/1A2 protein were elevated >20-fold as a result of iron or Aroclor treatments, respectively, but porphyria with associated histological changes only developed in the combined iron/Aroclor treatment group. lambda/lacI shuttle vectors were isolated from liver genomic DNA and the mutational frequency (MF) in the lacI gene determined. Both iron and Aroclor treatments alone caused significant small increases in MF (1.5- and 1.4-fold, respectively), however, the MF following the combined iron and Aroclor treatment (1. 6-fold) was not greater than the additive effects. In contrast, the MF was significantly elevated (4.7-fold) in liver DNA of mice 2 weeks following five daily doses of N-nitrosodimethylamine (4 mg/kg). These studies demonstrate that neither PCBs nor iron overload caused marked point mutations even in a combination regime that leads to oxidative damage and cancer. There was also no strong evidence either that porphyrins or chronic CYP1A1 expression induced by the PCBs after this period caused marked point mutagens or simple deletions. Hence, to understand the PCBs-iron synergism more complex scenarios than point mutations or simple deletions must be invoked.

Animals↗
PubMed2000

Assessment of health status at two years of very low birthweight infants--clinical governance.

Aims to establish a mechanism to determine prospectively the health status at two years of babies who weighed less than 1.5 kg at birth, born and receiving neonatal intensive care in North Wales. Maternal and neonatal data on all babies discharged from each of the three units in North Wales meeting this criteria were collated by the study coordinator. A mechanism for review of the health status at two years, corrected for gestational age, was established using the data set recommended by a working group convened by the National Perinatal Epidemiology Unit and Oxford Regional Health Authority. The procedures developed and the outcome data, for a two year cohort of babies born in 1995 and 1996, are reported. Concludes that prevalence of severe disability was similar to that found in other studies, with a considerable number exhibiting impaired growth and delay in speech development.

Child Development↗
PubMed2000

Appropriate insulin regimes for type 2 diabetes: a multicenter randomized crossover study.

OBJECTIVE: To directly compare the rate of hypoglycemia and metabolic control achieved on once-daily ultralente insulin administration with twice-daily NPH insulin administration in patients with type 2 diabetes. Patient treatment satisfaction and quality of life were also examined before and during each treatment. RESEARCH DESIGN AND METHODS: A crossover study was performed involving five centers and 79 patients with type 2 diabetes (fasting blood glucose > 8 mmol/l) with a 2-month run-in followed by two 6-month periods of either NPH or ultralente insulin administration. Patients were managed by a specialist nurse using a dosage adjustment protocol. RESULTS: HbA1c was lower with NPH insulin therapy during each of the 6-month periods (9.7 +/- 0.2 vs. 9.1 +/- 0.3 and 9.8 +/- 0.2 vs. 9.0 +/- 0.3 mmol/l; both P < 0.01). The difference was accounted for by higher evening glucose levels with ultralente insulin (fasting 8.2 +/- 0.3 vs. 8.2 +/- 0.3 mmol/l, 6:00 P.M. 11.5 +/- 0.4 vs. 10.6 +/- 0.4 mmol/l). Despite worse control, the total number of hypoglycemic episodes was greater with ultralente insulin (220 vs. 171), and hypoglycemic episodes requiring third-party assistance occurred almost entirely with ultralente (14 vs. 1). Treatment satisfaction scores increased more with NPH insulin compared with ultralente and rose further upon changing to NPH insulin, but fell upon changing to ultralente insulin. These changes were highly significant (P < 0.001). Diabetes quality of life improved on both regimens. CONCLUSIONS: These data clearly demonstrate the lower hypoglycemia rate, better glucose control, and greater treatment satisfaction accompanying therapy for type 2 diabetes with twice daily NPH compared with once daily ultralente insulin.

Blood Glucose↗
PubMed2000

A six-week clinical tooth whitening study of a new calculus-inhibiting dentifrice formulation.

This six-week double-blind clinical study compared the toothwhitening effects of a new calculus-inhibiting dentifrice containing pyrophosphate, tripolyphosphate and copolymer in a 0.243 sodium fluoride/silica base (Test Dentifrice) with two commercially available dentifrices: Aquafresh Whitening Toothpaste with Fluoride and Crest Regular Fluoride Toothpaste. After a baseline examination for extrinsic tooth stain, qualifying adult males and females from Manchester, United Kingdom and from Mississauga, Ontario, Canada were randomly assigned into three test groups. Each group was balanced for gender, tobacco habits and levels of tooth stain. Subjects were to brush their teeth twice daily with a soft-bristled toothbrush using the assigned toothpaste. One-hundred and twenty-eight (128) subjects complied with instructions and completed the trial. Subjects using the Test Dentifrice exhibited statistically less stain area and less stain intensity than did either the Aquafresh or Crest groups. Crest Regular Fluoride toothpaste was statistically less effective than Aquafresh Whitening toothpaste in removing stain. Results in this trial support the conclusion that a new dentifrice formulation containing pyrophosphate, tripolyphosphate and a copolymer, in a 0.243% sodium fluoride/silica base, effectively removes extrinsic tooth stain.

Adolescent↗
PubMed2000

Effectiveness of two fluoride dentifrices to arrest root carious lesions.

PURPOSE: To compare the effectiveness of Prevident 5000 Plus (5,000 ppm F) and Colgate Winterfresh Gel (1100 ppm F) to arrest root carious lesions. MATERIALS AND METHODS: 201 subjects with at least one root carious lesion were recruited from dental school patients. They were randomly assigned to use either Prevident 5000 Plus (5000 ppm F) or Colgate Winterfresh Gel (1100 ppm F) as sodium fluoride in the same silica base. Measurements of lesion hardness, area, distance from the gingival margin, cavitation and plaque were recorded at baseline and after 3 months by a single examiner. RESULTS: After 3 months 38% of subjects using Prevident 5000 Plus and 10% using Winterfresh Gel had one or more lesions that had become hard (P < 0.001). Non-cavitated lesions at baseline were more likely to become hard than cavitated lesions. Compared to the Winterfresh group there was significant increase in the distance from the base of the lesion to the gingival margin and plaque scores were reduced in those using Prevident 5000 Plus.

Adult↗
PubMed1999

Multiple roles for the Wilms' tumor suppressor, WT1.

Wilms' tumor is a childhood kidney tumor that is a striking example of the way that cancer may arise through development gone awry. A proportion of these tumors develop as a result of the loss of function mutations in the Wilms' tumor suppressor gene, WT1. Inherited mutations in the WT1 gene can lead to childhood kidney cancer, severe gonadal dysplasia, and life-threatening hypertension. Knockouts show that the gene is essential for the early stages of kidney and gonad formation. These tissues are completely absent in null mice. The WT1 gene encodes numerous protein isoforms, all of which share four zinc fingers. There is a large body of evidence supporting the notion that WT1 is a transcription factor, particularly a transcriptional repressor. Recently, however, we obtained evidence that WT1 colocalizes and is physically associated with splice factors. What is more, one alternative splice isoform of WT1 containing three amino acids, Lys-Thr-Ser (KTS; inserted between zinc fingers 3 and 4) is preferentially associated with splice factors, whereas the other alternative splice version, lacking these three amino acids, preferentially associates with the transcriptional apparatus. Both genetic and evolutionary considerations suggest that these two different forms of the protein have different functions. We will discuss recent evidence to further implicate WT1 in splicing. Our results raise the possibility that regulation of splicing is a crucial factor in the development of the genitourinary system, and that tumors may arise through aberrant splicing. To pursue the regulation and function of WT1 in whole animals, we have been introducing the human gene and large flanking regions cloned in yeast artificial chromosomes directly into mice. These studies have allowed us to dissect the function of WT1 at late as well as at early stages in organogenesis and to identify new sites and surprising new potential functions for the gene.

Alternative Splicing↗
PubMed1999

Interval or permanent nonoperative management of acute type A aortic dissection.

HYPOTHESIS: Selected patients with acute type A (ascending) aortic dissection who are treated with delayed operation or nonoperative therapy may have better early and short-term outcomes than was previously expected. DESIGN AND SETTING: Retrospective cohort at a university hospital. SUBJECTS: Data on 75 patients with acute or chronic type A aortic dissection treated at one institution from January 1, 1985, to November 30, 1997, were analyzed. Of these 75 patients, 34 (21 male and 13 female, with a mean age of 65.5 years) did not undergo initial operative treatment, and 15 (10 male and 5 female, with a mean age of 72.6 years) never underwent surgery. For the 19 patients who underwent delayed surgery, the mean period between aortic dissection and intervention was 11.4+/-4.83 days. The follow-up period ranged from 0.27 to 149 months, with a mean of 20.2 months. MAIN OUTCOME MEASURES: Vascular complications, hospital mortality, and early survival. RESULTS: Reasons for interval delay in surgical treatment included initial misdiagnosis or delay in diagnosis (13 [68%] of 19), need to address significant comorbidity (4 [21%] of 19), and initial refusal of operative intervention (2 [11%] of 19). For the 15 patients treated entirely by medical therapy, reasons for electing nonoperative management included extensive comorbidity (5 [33%] of 15), refusal of surgical intervention (6 [40%] of 15), and misdiagnosis or long delay in diagnosis (4 [27%] of 15). Of the 34 patients, 15 (44%) presented with moderate or severe aortic insufficiency, 5 (14%) had evidence of pericardial effusion, 6 (21%) had evidence of concomitant coronary ischemia on electrocardiogram, and 8 (24%) had extension of the dissection into the descending aorta. Four patients (11.8%) died while in the hospital. Of the 34 patients, 30 (88%) who underwent either delayed or no surgery received aggressive medical treatment (beta-adrenergic blocking agents and afterload-reducing agents) and were discharged from the hospital. All patients who were operative candidates in the interval treatment group survived to reach definitive operation. There was no statistically significant difference in short-term survival between the group of patients undergoing delayed surgery or medical treatment only and the group of 41 patients undergoing early operation (P = .42). CONCLUSIONS: Immediate surgical therapy is still recommended for acceptable operative candidates with acute type A aortic dissection who seek immediate treatment. However, this study permits the following 2 conclusions: (1) patients with type A aortic dissection who are referred or whose conditions are diagnosed several days after presentation have survived the early dangerous period and can safely undergo surgery semielectively (rather than emergently); and (2) selected patients who are not considered operative candidates and who survive the initial type A aortic dissection without complication may be treated with aggressive medical therapy and achieve acceptable early and short-term outcomes, which is better than previously expected.

Acute Disease↗
PubMed1999

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

Aggressive Periodontitis↗
PubMed1999

Determination of the optimal conditions for dental subtraction radiography using a storage phosphor system.

OBJECTIVES: To determine the optimal kVp and exposure conditions for digital subtraction radiography system using a storage phosphor system. METHOD: Signal-to-noise (SNR) measurements were acquired using a Digora system (Soredex, Helsinki, Finland) of large area, low contrast, clinically realistic details against varying degrees of background attenuation for both single exposure unsubtracted and subtracted images. These results were combined with a measure of estimated thyroid dose to derive a figure of merit (FOM) for the unsubtracted and subtracted images. RESULTS: For both unsubtracted and subtraction radiography, an exposure at 50 kVp and 250 muGy produce the best overall FOM. However, using the system at the 60 kVp maximum a FOM at 1000 muGy for unsubtracted radiography and 500 muGy for subtraction radiography gave the best SNR performance. CONCLUSION: Operating parameters have been derived which allow the user to choose between optimising SNR and dose (50 kVp, 250 muGy for unsubtracted and subtracted radiography) or SNR alone (60 kVp, 1000 muGy for unsubtracted and 60 kVp, 500 muGy for subtracted), for the visualisation of clinically representative details using the Digora system.

Aluminum↗
PubMed1999

Antimicrobial susceptibility of enterococci recovered from commercial swine carcasses: effect of feed additives.

Enterococcus faecium is an important nosocomial pathogen often displaying multiple antibiotic resistance. The increase in clinical isolates can be attributed in part to hospital practices in antibiotic usage, but there is concern that antibiotic-resistant strains might also originate in animals fed rations containing antibiotic growth promoters. Ingestion of meat from carcasses contaminated with faecal enterococci might then result in human colonization or resistance gene transfer to human enterococci. Because there are few comparisons of bacteria isolated from matched animals that have, or have not, been fed a diet containing antibiotic, two such groups of pig carcasses were sampled at a commercial abattoir. Forty isolates from each group of pigs were tested for their resistance to avilamycin and tylosin. Although a modest number of pigs was examined, and the number of strains of E. faecium tested was small, there was no evidence that the feeding of a growth promoter caused selection of enterococci resistant to tylosin or avilamycin.

Abattoirs↗