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Biomedical subjects

J Newton

Publications and source records attributed to J Newton.

At least 19 recordsLinked to original sources
PubMed2005

Analysis of IL10 haplotypic associations with severe malaria.

We investigated the association between severe malaria and genetic variation of IL10 in Gambian children, as several lines of evidence indicate that IL10 is protective against severe malaria and that IL10 production is genetically determined. We began by identifying five informative SNPs in the Gambian population that were genotyped in a combined case-control and intrafamilial study including 654 cases of severe malaria, 579 sets of parents and 459 ethnically matched controls. No significant associations were identified with individual SNPs. One haplotype of frequency 0.11 was strongly associated with protection against severe malaria in the case-control analysis (odds ratio 0.52, P=0.00002), but the transmission disequilibrium test in families showed no significant effect. These findings raise the question of whether IL10 associations with severe malaria might be confounded by foetal survival rates or other sources of transmission bias.

Case-Control Studies↗
PubMed2004

Explosive hydrogen burning of 17O in classical novae.

We report on the observation of a new resonance at E(lab)(R)=190 keV in the 17O(p,gamma)18F reaction. The measured resonance strength amounts to omegagamma(pgamma)=(1.2+/-0.2)x10(-6) eV. With this new value, the uncertainties in the 17O(p,gamma)18F and 17O(p,alpha)14N thermonuclear reaction rates are reduced by orders of magnitude at nova temperatures. Our significantly improved reaction rates have major implications for the galactic synthesis of 17O, the stellar production of the radioisotope 18F, and the predicted oxygen isotopic ratios in nova ejecta.

Journal Article↗
PubMed2004

Characterization of the dog Agouti gene and a nonagoutimutation in German Shepherd Dogs.

The interaction between two genes, Agouti and Melanocortin-1 receptor ( Mc1r), produces diverse pigment patterns in mammals by regulating the type, amount, and distribution pattern of the two pigment types found in mammalian hair: eumelanin (brown/black) and pheomelanin (yellow/red). In domestic dogs ( Canis familiaris), there is a tremendous variation in coat color patterns between and within breeds; however, previous studies suggest that the molecular genetics of pigment-type switching in dogs may differ from that of other mammals. Here we report the identification and characterization of the Agouti gene from domestic dogs, predicted to encode a 131-amino-acid secreted protein 98% identical to the fox homolog, and which maps to chromosome CFA24 in a region of conserved linkage. Comparative analysis of the Doberman Pinscher Agouti cDNA, the fox cDNA, and 180 kb of Doberman Pinscher genomic DNA suggests that, as with laboratory mice, different pigment-type-switching patterns in the canine family are controlled by alternative usage of different promoters and untranslated first exons. A small survey of Labrador Retrievers, Greyhounds, Australian Shepherds, and German Shepherd Dogs did not uncover any polymorphisms, but we identified a single nucleotide variant in black German Shepherd Dogs predicted to cause an Arg-to-Cys substitution at codon 96, which is likely to account for recessive inheritance of a uniform black coat.

Agouti Signaling Protein↗
PubMed2003

Non-inherited maternal HLA alleles are associated with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids ((70)Q/R K/R R A A(74)) in the DRbeta1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. METHODS: One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data RESULTS: We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). CONCLUSION: A role for HLA NIMA in RA is suggested by these results.

Alleles↗
PubMed2003

Development of rheumatoid arthritis is not associated with two polymorphisms in the Crohn's disease gene CARD15.

INTRODUCTION: It has been proposed that genetic susceptibility loci for rheumatoid arthritis (RA) may be shared with other autoimmune/inflammatory diseases. Recently, common variation in the CARD15 (NOD2) gene on chromosome 16q12 has been associated with Crohn's disease (CD) in several independent populations. CARD15 is an excellent functional and positional candidate gene for RA. METHODS: Genomic DNA was obtained from 392 RA cases and 471 ethnically matched healthy controls. All samples were genotyped for two polymorphisms in CARD15, 1007fs and R702W, using 5' nuclease reporter assays. Allele frequencies were compared between cases and controls using the chi(2) test. Estimated haplotype frequencies across the two mutations were determined using the EH program. RESULTS: The allele frequency of the 1007fs variant in RA cases was 1.8% compared with 1.6% in normal controls (not significant). The frequency of the R702W variant was 4.0% in both cases and controls. Haplotypes carrying either of the two mutations accounted for 5.6% of possible haplotypes. A haplotype carrying both mutations was rare, with estimated frequency <0.01%. This study provided high power to detect an association of similar magnitude to that in Crohn's disease. These data therefore exclude the possibility that the contribution of these mutations to RA is comparable to that seen in CD. CONCLUSION: Within defined statistical parameters, we excluded a role for the CARD15 1007fs and R702W variants in RA susceptibility. These data do not preclude a role for other polymorphisms in the CARD15 gene in RA susceptibility. Results from other autoimmune and inflammatory diseases will reveal whether the CARD15 gene is in fact a common autoimmune susceptibility locus.

Arthritis, Rheumatoid↗
PubMed2003

Mapping the range and scope of emergency nurse practitioner services in the Northern and Yorkshire Region: a telephone survey.

OBJECTIVE: To map the range and scope of emergency nurse practitioner (ENP) services in the Northern and Yorkshire Region as part one of a three phased study investigating the developing role of the ENP on a multi-professional context. METHODS: A telephone survey was conducted in the 48 hospital trusts within the region. Semi-structured interviews were arranged with the senior nurses responsible for accident and emergency services in responding departments. Data collection entailed completion of a form comprising 14 open-ended questions designed to elicit information about the range and scope of ENP services (as defined by the Royal College of Nursing). Data were analysed using descriptive statistics. RESULTS: Interviews were conducted at 35 (73%) of the sites, 22 (63%) of which had an ENP service as defined above. Wide variation was found in the range of services in relation to: hours/days of availability; age range and sources of referrals of patients accessing the service; clinical caseloads of ENPs and the referral pathways to other services. CONCLUSION: The findings from the survey highlight the organic, context specific nature of ENP role developments in response to national government initiatives, professional agendas, and local service needs.

Age Factors↗
PubMed2002

A pilot study of event-related functional magnetic resonance imaging of monitored wrist movements in patients with partial recovery.

BACKGROUND AND PURPOSE: Previous functional imaging studies of motor recovery after stroke have investigated cerebral activation during periods of repetitive, often complex, movement. This article reports the use of an event-related approach to study activation associated with isolated simple movements (wrist extension). This allows investigation of the pattern of the motor response and corresponding brain activation on a trial-by-trial basis. Patients with partial recovery can be assessed, and allowance can be made for abnormalities in the shape of hemodynamic responses. METHODS: Functional MRI at 3 T was performed during a series of isolated, near-isometric wrist extension movements. A visual tracking procedure was used to elicit forces of 10% and 20% of maximum voluntary contraction. Force output from both wrists was monitored continuously. A voxel-wise procedure was used to fit the optimum hemodynamic response functions in each case. RESULTS: Three chronic stage patients with partial recovery were successfully scanned and compared with 8 healthy controls. The patients showed well-lateralized motor responses but inaccurate control of force. During movement of the paretic wrist, we observed excessive activation of the ipsilateral primary motor cortex and increased relative activation of the supplementary motor area compared with movement of the nonparetic side. In the primary motor area, hemodynamic responses peaked more quickly on the ipsilateral side in 2 patients for movements of the paretic hand, whereas controls showed the opposite trend. CONCLUSIONS: An event-related approach can be used to study the relationship between motor responses and cerebral activation in patients with partial recovery. These preliminary findings suggest that excessive activation in ipsilateral motor cortex and secondary motor areas remains evident under these tightly controlled conditions and cannot be ascribed to mirror movements or abnormalities in the timing of the blood oxygen level-dependent (BOLD) response. However, close monitoring of motor responses also makes evident continuing impairment in motor skill, which makes comparison with activation in normal controls difficult.

Adult↗
PubMed2002

Osteoporosis in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease that is typically progressive, with a significant proportion of patients going on to develop cirrhosis. It predominately affects women and typically develops in the middle years of life. In most centres the median age for presentation is in the range 55 to 60 years, with a significant proportion of patients first presenting over the age of 65. Due to earlier diagnosis, PBC has gone from being a rare disease, characterised by the complications of end-stage liver disease, to a significantly commoner disease (affecting up to 1 in 700 women over the age of 40) diagnosed often in an asymptomatic stage. Osteoporosis increases with advancing age and hence there is an increased prevalence of osteoporosis in older people. The question of whether osteoporosis occurs as a specific complication of PBC has latterly proved to be controversial. This article reviews the current literature and examines why differences occur in osteoporosis prevalence in the available studies. It becomes clear that when determining the true extent of the association between osteoporosis and PBC, conclusions must be drawn from large populations, and that when considering a disease such as osteoporosis that is common in older people, age matched values be used in order to draw these conclusions. As PBC is a disease that often presents for the first time over the age of 65, it is not surprising that osteoporosis is a common problem in a disease predominately affecting peri- or postmenopausal women.

Bone Diseases↗
PubMed2001

Effect of digital image compression on screening for diabetic retinopathy.

BACKGROUND/AIMS: Digital imaging is widely used for diabetic retinopathy screening. The storage and transmission of digital images can be facilitated by image compression. The authors aimed to assess the effect of image compression on the accuracy of grading diabetic retinopathy. METHODS: Forty nine 35 mm transparencies (17 with no retinopathy, eight with background, five with preproliferative, and 19 with proliferative retinopathy) were digitised and subjected to JPEG compression by 90%, 80%, 70%, and 0%. The 196 images were randomised and graded on a portable computer. Two masked graders assessed the images for grade of retinopathy and image quality (0-10). The sensitivity and specificity of retinopathy grading were calculated with a weighted kappa for grading agreement between levels of compression. RESULTS: The sensitivity of retinopathy grading was reduced by JPEG compression. At 90%, 80%, 70%, and 0% compression the sensitivities were 0.38, 0.50, 0.65, and 0.72, respectively; the specificity results were 1.00, 1.00, 0.83, and 0.84, respectively; and the weighted kappa scores were 0.60, 0.75, 0.77, and 0.84, respectively. The quality scores for 90%, 80%, 70%, 0% compression were 2.9 (SD 1.1, 95% CI; 2.7-3.2), 4.6 (SD 1.1, 95% CI; 3.0-5.6), 5.8 (SD1.5, 95% CI 5.0-6.6), 6.3 (SD1.4, 95% CI; 5.4-7.2) (p<0.01 for each intergroup comparison). CONCLUSION: The results demonstrate significant loss of sensitivity to the features of diabetic retinopathy with JPEG compression; this was compounded by the thin film transistor (TFT) screen. The authors found the quality of uncompressed images on TFT screens too poor to give grading sensitivities which reach current guidelines for diabetic retinopathy screening.

Computer Terminals↗
PubMed2001

Osteoporosis in primary biliary cirrhosis revisited.

BACKGROUND: Primary biliary cirrhosis (PBC) is increasingly being diagnosed in the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC is frequently complicated by osteoporosis. Whether this association holds true for the broader spectrum of PBC patients now recognised has not as yet been studied. AIMS: To examine the extent to which osteoporosis occurs more commonly in PBC patients than in normal individuals of the same age and sex. DESIGN: Retrospective review of a large cohort of well characterised PBC patients. PATIENTS: A total of 272 PBC patients with definite or probable PBC followed up for a mean of 10.1 years (total follow up 2726 patient years) who had at least one bone mineral density measurement (BMD). RESULTS: In this unselected group of PBC patients, mean Z scores (number of SDs from age and sex matched normal mean values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement (7 (6) years after PBC diagnosis) were -0.1 (1.4) and 0.1 (1.4), respectively. At first BMD measurement, 18 PBC patients had Z scores less than -2.0 and 85 had T scores less than -2.5. No factors predictive of osteoporosis were found in affected patients. A total of 957 BMD measurements were performed (0.35 per patient year of follow up); 220 patients had two or more measurements. No patient went on to develop de novo osteoporosis during follow up. In the 51 patients (who were clinically representative of the whole group) who received no PBC or bone related treatment during follow up, %BMD changes per year at the NOF and LS were -1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD measurement was seen in patients receiving PBC modulating agents (including prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant improvement at the LS was seen in patients undergoing liver transplantation. CONCLUSIONS: Osteoporosis is not a specific complication of PBC.

Absorptiometry, Photon↗
PubMed2001

Protein tyrosine phosphatase-dependent proteolysis of focal adhesion complexes in endothelial cell apoptosis.

Adenosine and/or homocysteine causes endothelial cell apoptosis, a mechanism requiring protein tyrosine phosphatase (PTPase) activity. We investigated the role of focal adhesion contact disruption in adenosine-homocysteine endothelial cell apoptosis. Analysis of focal adhesion kinase (FAK), paxillin, and vinculin demonstrated disruption of focal adhesion complexes after 4 h of treatment with adenosine-homocysteine followed by caspase-induced proteolysis of FAK, paxillin, and p130(CAS). No significant changes were noted in tyrosine phosphorylation of FAK or paxillin. Pretreatment with the caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone prevented adenosine-homocysteine-induced DNA fragmentation and FAK, paxillin, and p130(CAS) proteolysis. Asp-Glu-Val-Asp-ase activity was detectable in endothelial cells after 4 h of treatment with adenosine-homocysteine. The PTPase inhibitor sodium orthovanadate did not prevent endothelial cell retraction or FAK, paxillin, or vinculin redistribution. Sodium orthovanadate did block adenosine-homocysteine-induced FAK, paxillin, and p130(CAS) proteolysis and Asp-Glu-Val-Asp-ase activity. Thus disruption of focal adhesion contacts and caspase-induced degradation of focal adhesion contact proteins occurs in adenosine-homocysteine endothelial cell apoptosis. Focal adhesion contact disruption induced by adenosine-homocysteine is independent of PTPase or caspase activation. These studies demonstrate that disruption of focal adhesion contacts is an early, but not an irrevocable, event in endothelial cell apoptosis.

Adenosine↗
PubMed2001

Community palliative care clinical nurse specialists' descriptions of stress in their work.

This study analysed the lived experiences of work stress of 21 community palliative care clinical nurse specialists from four centres in urban Essex, UK. Data were collected using an open-ended questionnaire and semi-structured interviews. Three major themes emerged: pressure of workload; relationships with health professionals; and the impact of the sadness of the client group. The pressure of workload was associated with nine sub-themes including staff shortages, client's or professionals' misperceptions of role, changing role, and erosion of normal support systems at work or at home. Relationships with some general practitioners seemed to cause most difficulty and social services seemed to have different priorities and to respond slowly. The impact of the sadness of the client group was only seen in four distinct situations. An overwork stress spiral is described that provides a salutary warning for managers, but also offers interesting solutions.

Adult↗
PubMed2000

Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.

One of the most common translocations in acute myeloid leukemia (AML) is the t(8;21), which produces the fusion gene AML1-MTG8. We have developed a sensitive competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for AML1-MTG8 transcripts, coupled with a competitive RT-PCR for the ABL transcript as a control to accurately estimate the level of amplifiable RNA. We have shown that AML1-MTG8 and ABL transcripts have equal degradation rates. Thus, this method is useful for multicenter studies. We studied 25 patients with t(8;21) AML by means of serial analysis done on bone marrow (BM) and peripheral blood (PB) samples from 21 patients. Our analysis showed that, in general, a successful induction chemotherapy produces a reduction of 2 to 3 log in the level of AML1-MTG8, followed by a further 2 to 3 log after consolidation/intensification chemotherapy. Levels up to 1 x 10(3) and 1 x 10(2) molecules/microg of RNA in BM and PB, respectively, were compatible with durable remission. On the other hand, 5 patients with levels of 0.71 x 10(5) to 2.27 x 10(5) molecules/microg of RNA in BM and 2.27 x 10(3) to 2.27 x 10(4) molecules/microg of RNA in PB had hematologic relapse within 3 to 6 months. Our data indicate that serial quantitation of AML1-MTG8 transcripts is useful in identifying patients at high risk of relapse and may offer an opportunity for clinical intervention to prevent hematologic relapse. This approach was applied successfully in a patient who had an allogeneic BM transplantation. We also suggest that PB may be used an alternative to BM for quantitating AML1-MTG8 transcripts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Minocycline for acne vulgaris: efficacy and safety.

BACKGROUND: Minocycline is a tetracycline antibiotic that is commonly used in the treatment of moderate to severe acne vulgaris. Although it is more convenient for patients to take than first-generation tetracyclines, as it only needs to be taken once or twice a day and can be taken with food, it is more expensive. Concerns have also been expressed over its safety following the deaths of two patients taking the drug. There is a lack of consensus among dermatologists over the relative risks and benefits of minocycline. As most acne prescribing is undertaken by general practitioners, it is important that guidelines issued to them are based on the best available evidence rather than personal judgements. OBJECTIVES: To collate and evaluate the evidence on the clinical efficacy of minocycline in the treatment of inflammatory acne vulgaris. Specific objectives were to compare the efficacy of minocycline with other drug treatments for acne and to collate information on the incidence of adverse drug reactions. SEARCH STRATEGY: Randomised controlled trials (RCTs) of minocycline for acne vulgaris were identified by searching the following electronic databases; MEDLINE, EMBASE, Biosis, Biological Abstracts, International Pharmaceutical Abstracts, Cochrane Skin Group's Trial Register, Theses Online, BIDS ISI Science Citation Index and Bids Index to Scientific and Technical Proceedings. Other strategies used were scanning the references of articles retrieved, hand-searching of major dermatology journals and personal communication with trialists and drug companies. SELECTION CRITERIA: To be eligible for the review, studies had to be RCTs comparing the efficacy of minocycline at any dose to active or placebo control, in subjects with inflammatory acne vulgaris. Diagnoses of papulo-pustular, polymorphic and nodular acne were also accepted. Trials were not excluded on the basis of language. DATA COLLECTION AND ANALYSIS: 27 randomised controlled trials met the inclusion criteria and were included in this review. The comparators used were placebo (2 studies), oxytetracycline (1), tetracycline (6), doxycycline (7), lymecycline (2), topical clindamycin (3), topical erythromycin/zinc (1), cyproterone acetate/ ethinyloestradiol (1), oral isotretinoin (2), topical fusidic acid (1) and there was one dose response study. One study is ongoing and it remains to be clarified whether one further study is a RCT. Major outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and patients' global assessments, adverse drug reactions and drop out rates. The quality of each study was assessed independently by two assessors and an effect size calculated where possible. MAIN RESULTS: The trials were generally small and of poor quality and in many cases the published reports were inadequate for our purpose. Pooling of the studies was not attempted due to the lack of common outcome measures and endpoints and the unavailability of some primary data. Although minocycline was shown to be an effective treatment for acne vulgaris, in only two studies was it found to be superior to other tetracyclines. Both of these were conducted under open conditions and had serious methodological problems. A third study showed it to be more effective than 2% fusidic acid, applied topically, against inflammatory lesions in mild to moderate acne. Differences in the way adverse drug reactions were identified could have accounted for the wide variation between studies in numbers of events reported. This meant that no overall evaluation could be made of incidence rates of adverse events associated with minocycline therapy. No RCT evidence was found to support the benefits of minocycline in acne resistant to other therapies and the dose response has only been evaluated up to eight weeks of therapy. (ABSTRACT TRUNCATED)

Acne Vulgaris↗
PubMed2000

Screening colonoscopy in asymptomatic average-risk African Americans.

BACKGROUND: Recent data indicate that colorectal cancer incidence and mortality in white Americans have been declining since 1985 at a rate of 2% to 3% per year. In African Americans, however, mortality from colorectal cancer appears to be increasing. We sought to evaluate the prevalence of colonic neoplasia in asymptomatic African Americans. METHODS: We performed a cross-sectional colonoscopy screening study to determine the prevalence of colonic neoplasia in asymptomatic African Americans older than 50 years of age. RESULTS: One hundred sixty-six subjects were evaluated for the study of whom 121 (69 women) were deemed to be asymptomatic average-risk persons and completed colonoscopy. Forty-two individuals (35%) had a total of 72 adenomas (67 tubular and 5 tubulovillous); 47 (65.3%) of these were proximal to the splenic flexure. Three subjects had an adenoma 1 cm or greater in diameter and none had severe dysplasia. CONCLUSIONS: The overall prevalence of adenomas in asymptomatic average-risk African Americans was comparable to that of previously described populations. The predominance of right-sided adenomas in this study confirms previous findings and is an area requiring further study. Until this issue is resolved, we suggest the use of colonoscopy rather than sigmoidoscopy for screening for colorectal neoplasia in asymptomatic, average-risk African Americans.

Adenomatous Polyps↗
PubMed2000

Change in primary health care: new wine in old bottles?

Describes the findings from the first year of an evaluation of change at a PMS+ site in West Cumbria. The study has used qualitative methods including non-participant observation at the site; face to face interviews with 28 clinical staff; group interviews with administrative and secretarial staff; and the collection of documents. Analysis of the data against a set of "outcome indicators" shows that significant progress has been made towards implementing the model of primary care delivery described in the pilot proposal. Multidisciplinary working is developing in the clinical action groups and the establishment of a primary care emergency unit has changed general practitioner workloads. The new organisation structure is not yet working wholly as anticipated but recently initiated changes are intended to strengthen the role and authority of the management board.

Data Collection↗