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Biomedical subjects

Peter Jones

Publications and source records attributed to Peter Jones.

At least 37 records · Page 2Linked to original sources
PubMed2005

Variables affecting initial stability of impaction grafting for hip revision.

Impaction grafting allows restoration of bone stock in hip revision, but there are reports of massive early subsidence. The aim of this study was to determine prognostic factors for stem and cup migration in a group of 56 consecutive patients followed up from 1 to 5 years. Cup and stem migration was correlated with 13 predictors including stem design, stem positioning, femoral anatomy, patient characteristics, and bone graft density. All migration occurred mainly during the first 3 months after surgery. Stem alignment changed by an average of 4.8 degrees . Fifty percent of the change in stem alignment was explained by four variables: age, femoral diameter, stem design, and density of the graft at the tip of the stem. Stem subsidence averaged 2.7 mm, and cup migration averaged 3.0 mm. None of the predictors explained the wide variation of migration of the cup or distal migration of the stem. It may be necessary to determine implant stability at the time of surgery.

Adult↗
PubMed2005

Fatal inflammatory heart disease in a bonobo (Pan paniscus).

We report the first probable identification of encephalomyocarditis virus (EMCV) in a bonobo (Pan paniscus) that had been part of a forest re-introduction programme. Clinical presentation was of episodic acute on chronic heart failure and cerebral infarction with end-stage renal failure rather than sudden death which is more commonly associated with EMCV infection. A postmortem diagnosis of probable EMCV was made using gross pathological and histopathological examination. Findings included acute on chronic heart failure combined with the unusual but characteristic histopathological features of non-suppurative necrotizing myocarditis with mononuclear, inflammatory infiltration of the brain.

Animals↗
PubMed2005

Developing career pathways for new nurses: lessons from inner London.

Inner city primary care trusts (PCTs) often have difficulty in recruiting nursing staff, while newly qualified nurses are often unaware of what opportunities community settings offer. This article reports the development of a rotational scheme designed to reduce recruitment problems and to assist understanding by newly qualified nurses of the interface between hospital and primary care. The scheme was jointly run by a PCT, a hospital and an academic unit. Various difficulties were encountered, as revealed in an interim evaluation. For example, the impression was created among some participating staff nurses and their mentors and managers that they had student status, which limited their opportunities both to learn and to provide care. The scheme was re-designed in the light of the evaluation, and a further evaluation found that participating staff nurses appreciated the opportunities the scheme offered, and that their work was valued by placement mentors and managers.

Career Mobility↗
PubMed2005

Rosuvastatin is cost-effective in treating patients to low-density lipoprotein-cholesterol goals compared with atorvastatin, pravastatin and simvastatin: analysis of the STELLAR trial.

BACKGROUND: Rosuvastatin calcium (CRESTOR) has demonstrated superior efficacy in reducing low-density lipoprotein cholesterol (LDL-C). However, healthcare providers and authorities require information on its cost-effectiveness in the treatment of dyslipidaemia. DESIGN: A retrospective pharmacoeconomic analysis was performed using data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. The cost-effectiveness of rosuvastatin 10-40 mg was compared with atorvastatin 10-80 mg, pravastatin 10-40 mg and both branded and generic simvastatin 10-80 mg in achieving Third Joint European Task Force LDL-C goals in patients with hypercholesterolaemia. METHODS: The analysis was conducted from the perspective of the UK National Health Service, using clinical data from the STELLAR trial and drug acquisition costs. Cost-effectiveness was compared using incremental cost-effectiveness ratios (ICERs), with sensitivity analyses applied to both efficacy and cost parameters. RESULTS: In terms of patients achieving goal, rosuvastatin 10 mg dominated (was more effective at equal or lower cost) atorvastatin 10 and 20 mg, pravastatin 20 and 40 mg, branded simvastatin 10-80 mg and generic simvastatin 40 and 80 mg. Where rosuvastatin 10 mg did not dominate, ICERs ranged from 36 pounds sterling to 162 pounds sterling per extra patient to goal. Rosuvastatin 20 and 40 mg were cost-effective compared with milligram-equivalent and higher doses of other branded statins. Sensitivity analyses showed that the results were robust to variations in both statin efficacy and price. CONCLUSION: In patients with hypercholesterolaemia, rosuvastatin is a cost-effective statin option in treating to LDL-C goals.

Atorvastatin↗
PubMed2005

Pathology robotic systems excel.

The role of robotic sample processing in the modernisation of pathology services at Manchester Royal Infirmary is described by Peter Jones, centralised in vitro diagnostics market manager at Roche Diagnostics. Stemming from the modernisation are valuable pointers for managers of facilities and designers of healthcare premises.

Diffusion of Innovation↗
PubMed2004

DNA binding ligands with improved in vitro and in vivo potency against drug-resistant Staphylococcus aureus.

Potent in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA) has been difficult to achieve with previously reported DNA binding antibacterials. Herein, we describe an efficient access to a focused library of new analogues yielding compounds with improved activity in a mouse peritonitis model. The most potent molecules (14 and 19) exhibit efficacy against MRSA at ED50 values of approximately 1 and approximately 5 mg/kg, respectively, and display excellent in vitro activity against vancomycin-resistant S. aureus.

Animals↗
PubMed2004

DNA binding ligands with in vivo efficacy in murine models of bacterial infection: optimization of internal aromatic amino acids.

DNA binding ligands with potent antimicrobial activity against Gram-positive bacteria were further optimized by variation of the internal aromatic amino acids. This modification led to compounds with improved in vivo efficacy in lethal murine models of peritonitis (methicillin-resistant S. aureus, MRSA) and lung infection (S. pneumoniae).

Amino Acids, Aromatic↗
PubMed2004

Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study.

OBJECTIVE: Based on clues from epidemiology and animal experiments, low vitamin D during early life has been proposed as a risk factor for schizophrenia. The aim of this study was to explore the association between the use of vitamin D supplements during the first year of life and risk of developing schizophrenia. METHOD: Subjects were drawn from the Northern Finland 1966 Birth Cohort (n=9,114). During the first year of life, data were collected about the frequency and dose of vitamin D supplementation. Our primary outcome measures were schizophrenia, psychotic disorders other than schizophrenia, and nonpsychotic disorders as diagnosed by age 31 years. Males and females were examined separately. RESULTS: In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR)=0.08, 95% CI 0.01-0.95; RR=0.12, 95% CI 0.02-0.90, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23, 95% CI 0.06-0.95) compared to those on lower doses. There were no significant associations between either the frequency or dose of vitamin D supplements and (a) schizophrenia in females, nor with (b) nonpsychotic disorder or psychotic disorders other than schizophrenia in either males or females. CONCLUSION: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia.

Adult↗
PubMed2004

DEF6, a novel PH-DH-like domain protein, is an upstream activator of the Rho GTPases Rac1, Cdc42, and RhoA.

In this paper, we describe the characterization of DEF6, a novel PH-DH-like protein related to SWAP-70 that functions as an upstream activator of Rho GTPases. In NIH 3T3 cells, stimulation of the PI 3-kinase signaling pathway with either H2O2 or platelet-derived growth factor (PDGF) resulted in the translocation of an overexpressed DEF6-GFP fusion protein to the cell membrane and induced the formation of filopodia and lamellipodia. In contrast to full-length DEF6, expression of the DH-like (DHL) domain as a GFP fusion protein potently induced actin polymerization, including stress fiber formation in COS-7 cells, in the absence of PI 3-kinase signaling, indicating that it was constitutively active. The GTP-loading of Cdc42 was strongly enhanced in NIH 3T3 cells expressing the DH domain while filopodia formation, membrane ruffling, and stress fiber formation could be inhibited by the co-expression of the DH domain with dominant negative mutants of either N17Rac1, N17Cdc42, or N19RhoA, respectively. This indicated that DEF6 acts upstream of the Rho GTPases resulting in the activation of the Cdc42, Rac1, and RhoA signaling pathways. In vitro, DEF6 specifically interacted with Rac1, Rac2, Cdc42, and RhoA, suggesting a direct role for DEF6 in the activation of Rho GTPases. The ability of DEF6 to both stimulate actin polymerization and bind to filamentous actin suggests a role for DEF6 in regulating cell shape, polarity, and movement.

Actin Cytoskeleton↗
PubMed2004

DNA binding ligands targeting drug-resistant Gram-positive bacteria. Part 2: C-terminal benzimidazoles and derivatives.

The synthesis and in vitro potency of DNA minor-groove binding antibacterials lacking the C-terminal amide bond are described. The crescent shaped molecules bear the positively charged amino group at an internal pyrrole unit instead of the C-terminus. Three structural parameters were investigated: the N-terminal unit, the internal amino group, and the C-terminal ring system. Several compounds demonstrated good in vitro potency against various Gram-positive bacteria and some molecules were moderately active against Escherichia coli, a representative Gram-negative strain.

Anti-Bacterial Agents↗
PubMed2004

Spectroscopic and electrochemical characterization of an aqua ligand exchange and oxidatively induced deprotonation in diiron complexes.

Reaction of the unsymmetrical phenol ligand 2-((bis(2-pyridylmethyl)amino)methyl)-6-(((2-pyridylmethyl)benzylamino)methyl)-4-methylphenol (HL-Bn) or its 2,6-dichlorobenzyl analogue (HL-BnCl(2)) with Fe(H(2)O)(6)(ClO(4))(2) in the presence of disodium m-phenylenedipropionate (Na(2)(mpdp)) followed by exposure to atmosphere affords the diiron(II,III) complexes [Fe(2)(L-Bn)(mpdp)(H(2)O)](ClO(4))(2) and [Fe(2)(L-BnCl(2))(mpdp)(CH(3)OH)](ClO(4))(2), respectively. The latter complex has been characterized by X-ray crystallography. It crystallizes in the monoclinic system, space group P2(1)/n, with a = 13.3095(14) A, b = 20.1073(19) A, c = 19.4997(19) A, alpha = 90 degrees, beta = 94.471(2) degrees, gamma = 90 degrees, V = 5202.6(9) A(3), and Z = 4. The structure of the compound is very similar to that of [Fe(2)(L-Bn)(mpdp)(H(2)O)](BPh(4))(2) determined earlier, except for the replacement of a water by a methanol on the ferrous site. Magnetic measurements of [Fe(2)(L-Bn)(mpdp)(H(2)O)](BPh(4))(2) reveal that the two high-spin Fe ions are moderately antiferromagnetically coupled (J = -3.2(2) cm(-)(1)). Upon dissolution in acetonitrile the terminal ligand on the ferrous site is replaced by a solvent molecule. The acetonitrile-water exchange has been investigated by various spectroscopic techniques (UV-visible, NMR, Mössbauer) and electrochemistry. The substitution of acetonitrile by water is clearly evidenced by Mössbauer spectroscopy by a reduction of the quadrupole splitting value from 3.14 to 2.41 mm/s. In addition, it causes a 210 mV downshift of the oxidation potential of the ferrous site and a similar reduction of the stability domain of the mixed-valence state. Exhaustive electrolysis of a solution of [Fe(2)(L-Bn)(mpdp)(H(2)O)](2+) shows that the aqua diferric species is not stable and undergoes a chemical reaction which can be partly reversed by reduction to the mixed-valent state. This and other electrochemical observations suggest that upon oxidation of the diiron center to the diferric state the aqua ligand is deprotonated to a hydroxo. This hypothesis is supported by Mössbauer spectroscopy. Indeed, this species possesses a large quadrupole splitting value (DeltaE(Q) >or= 1.0 mm.s(-)(1)) similar to that of analogous complexes with a terminal phenolate ligand. This study illustrates the drastic effects of aqua ligand exchange and deprotonation on the electronic structure and redox potentials of diiron centers.

Journal Article↗
PubMed2004

The development of new density gradient media for purifying human islets and islet-quality assessments.

Successful islet transplantation is dependent on the quality and quantity of islets infused. Islets are purified on density gradients, but procedures currently used have limited capacity for pancreatic digests, islet yield, and viability. We aimed to improve islet purification with a modified gradient medium. Biocoll was diluted in University of Wisconsin solution to create linear density gradients of 1.065 to 1.095 g/mL. Properties of islets purified from 22 human pancreas digests with modified medium were compared with 15 preparations using standard medium. The modification increased the capacity of gradients for pancreatic digests from 20 to 60 mL, islet yield increased from 218,000 to 435,318 per isolation, and viability increased from 65.4% to 92.1%. Islet fractions contained greater than 95% of recovered insulin. Islets showed good physiologic responses to secretagogues and restored normoglycemia in streptozotocin-induced diabetic severe combined immunodeficiency disease mice. The new medium enhances yield, purity, and viability of human islet preparations for clinical islet transplantation.

Adenosine↗
PubMed2004

Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVE: Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis. METHODS: One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality-of-life assessments were performed. RESULTS: At 24 weeks, 56 of 95 leflunomide-treated patients (58.9%; 95% confidence interval [95% CI] 48.4-68.9) and 27 of 91 placebo-treated patients (29.7% [95% CI 20.6-40.2]) were classified as responders by the PsARC (P < 0.0001). Significant differences in favor of leflunomide were also observed in the proportions of patients achieving modified American College of Rheumatology 20% improvement criteria, improvement in the designated psoriasis target lesion, and mean changes from baseline in Psoriasis Area and Severity Index scores and quality-of-life assessments. Diarrhea and alanine aminotransferase increases occurred at higher rates in the leflunomide group. No cases of serious liver toxicity were observed. CONCLUSION: Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.

Adult↗
PubMed2004

Childhood central nervous system infections and risk for schizophrenia.

Central nervous system (CNS) viral infections have been suggested to increase the risk of schizophrenia, although most of the evidence is indirect and comes from rather few studies on exposure to various infections in general. In the Northern Finland 1966 Birth Cohort the association between schizophrenia and other psychoses and childhood CNS infections has been analysed, and in this paper we present the follow-up results up to the end of 1994 and 1997. Data regarding the infections were collected prospectively between 1966-1980 and data on psychoses from 1982. The registered psychiatric diagnoses were validated using the DSM-III-R classification. Out of the 11017 subjects (96% of all births in that year) 145 had suffered a CNS infection during childhood, which in 102 cases was a viral infection. In the follow-up to the end of 1994, 76 had schizophrenia, and their number increased to 100 to the end of 1997. In addition, up to the end of 1994, 52 patients had a non-schizophrenic psychosis. Four cases in the schizophrenia patient group and none of the patients with other psychosis had suffered a viral CNS infection. None of the schizophrenia cases and two of the patients with other psychosis had had a bacterial infection. The adjusted odds ratio for schizophrenia after a viral CNS infection was 4.8 (95% confidence intervals [CI] 1.6-14.0) in the follow-up to the end of 1994 and 2.5 (0.9-7.0) in the follow-up to the end of 1997. The clinical course variables did not differ between the schizophrenia patients with or without CNS infection. Our results suggest that viral CNS infections during childhood may have a role as a risk factor for schizophrenia. Their role may be modest at the population level due to their relative rareness.

Adolescent↗
PubMed2004

The effect of acupuncture on the symptoms of knee osteoarthritis--an open randomised controlled study.

BACKGROUND: Using an open randomised controlled study, we examined the effectiveness of manual and electroacupuncture on symptom relief for patients with osteoarthritis of the knee. METHODS: Patients with symptomatic osteoarthritis of the knee were randomised to one of three treatment groups. Group A had acupuncture alone, group B had acupuncture but continued on their symptomatic medication, and group C used their symptomatic medication for the first five weeks and then had a course of acupuncture added. Patients receiving acupuncture were treated twice weekly over five weeks. Needles were inserted (with manual and electrical stimulation) in acupuncture points for pain and stiffness, selected according to traditional acupuncture theory for treating Bi syndrome. Patients were assessed by a blinded observer before treatment, after five weeks' treatment and at one month follow up, using a visual analogue pain scale (VAS) and the Western Ontario McMaster (WOMAC) questionnaire for osteoarthritis of the knee. RESULTS: The 30 patients in our study were well matched for age, body mass index, disease duration, baseline VAS pain score and baseline WOMAC scores. Repeated measure analyses gave a highly significant improvement in pain (VAS) after the courses of acupuncture in groups A (P = 0.012) and B (P=0.001); there was no change in group C until after the course of acupuncture, when the improvement was significant (P = 0.001). Similarly significant changes were seen with the WOMAC pain and stiffness scores. These benefits were maintained during the one month after the course of acupuncture. Patients' rating of global assessment was higher than that of the acupuncturist. CONCLUSION: We conclude that manual and electroacupuncture causes a significant improvement in the symptoms of osteoarthritis of the knee, either on its own or as an adjunct therapy, with no loss of benefit after one month.

Acupuncture Points↗
PubMed2004

Loss of heterozygosity at chromosome 9q22-31 is a frequent and early event in ovarian tumors.

Loss of heterozygosity (LOH) studies in ovarian tumors, have highlighted the chromosomal regions at 9q22-31 and 9q32-34 as being potentially important in tumor development. We have investigated LOH at 9q22-31 in 85 patients with epithelial ovarian cancer, 15 with non-epithelial tumors and 16 with benign disease. Varying patterns of LOH were observed across the markers used between different tumors, the most common (71%) being interstitial discontinuous losses. LOH was frequent, and was detected at equally high levels in malignant (71%) and benign tumors (70%). LOH occurred in epithelial invasive tumors, borderline tumors, fibromas and dermoid tumors. In malignant epithelial tumors LOH at 9q22-31 was not significantly associated with patient clinical and pathological parameters; however, survival was 29 months at the 50th centile survival, in those women whose tumors displayed LOH compared with 60 months in women whose tumors retained heterozygosity. LOH at 9q22-31 was significantly associated with LOH at the p53 locus (p=0.02) and the ovarian suppressor locus at 3p21 (p=0.05). We conclude that the chromosome region at 9q22-31, flanked by the microsatellite markers D9S1796 and D9S53, is a frequent and early event in ovarian tumorigenesis. With the of extent of discontinuous LOH, high density deletion mapping of this region using LOH as a strategy to identify candidate genes may be problematic. However with the completion of the human genome sequencing project several candidate genes are identified.

Adenocarcinoma, Clear Cell↗