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Biomedical subjects

P Jones

Publications and source records attributed to P Jones.

At least 19 recordsLinked to original sources

Nuclear isomers in superheavy elements as stepping stones towards the island of stability.

A long-standing prediction of nuclear models is the emergence of a region of long-lived, or even stable, superheavy elements beyond the actinides. These nuclei owe their enhanced stability to closed shells in the structure of both protons and neutrons. However, theoretical approaches to date do not yield consistent predictions of the precise limits of the 'island of stability'; experimental studies are therefore crucial. The bulk of experimental effort so far has been focused on the direct creation of superheavy elements in heavy ion fusion reactions, leading to the production of elements up to proton number Z = 118 (refs 4, 5). Recently, it has become possible to make detailed spectroscopic studies of nuclei beyond fermium (Z = 100), with the aim of understanding the underlying single-particle structure of superheavy elements. Here we report such a study of the nobelium isotope 254No, with 102 protons and 152 neutrons--the heaviest nucleus studied in this manner to date. We find three excited structures, two of which are isomeric (metastable). One of these structures is firmly assigned to a two-proton excitation. These states are highly significant as their location is sensitive to single-particle levels above the gap in shell energies predicted at Z = 114, and thus provide a microscopic benchmark for nuclear models of the superheavy elements.

Journal Article↗

Collectivity and configuration mixing in 186,188Pb and 194Po.

Lifetimes of prolate intruder states in 186Pb and oblate intruder states in 194Po have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in 188Pb up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |beta2|=0.29(5) and |beta2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.

Journal Article↗

Inguinal hernia repair: are ASA grades 3 and 4 patients suitable for day case hernia repair?

The American Society of Anaesthesiologists (ASA) 3 and 4 patients are generally considered unsuitable for day case hernia repair. There are minimal data regarding the acceptability of day case repair in these patients. This study analysed day case hernia rates with special emphasis on ASA grades. A retrospective review of all adult inguinal hernia repairs, under the care of one surgeon over a 9-year period, was performed. The data collected included demographics, ASA grades, the mode of anaesthesia and early complications. 577 patients underwent inguinal hernia repair during the study period. 204 (35%) patients were ASA grade 1, 214 (37%) ASA grade 2, 132 (23%) ASA grade 3 and 29 (5%) ASA grade 4. Day case rates for ASA grades 1-4 under LA were 86, 83, 77 and 76% and under GA, 59, 36, 32 and 0%, respectively (P<0.05). There was no significant difference in the wound complication rates for different ASA grades under GA and LA. ASA grades 3 and 4 patients can undergo day case inguinal hernia repair, with similar complication rates to ASA grades 1 and 2 patients, when surgery is performed under local anaesthesia. ASA grades 3 and 4 patients need not be excluded from day case hernia repair.

Adolescent↗

Antibiotic treatment and factors influencing short and long term outcomes of acute exacerbations of chronic bronchitis.

BACKGROUND: The MOSAIC study compared moxifloxacin with three standard antibiotic regimens in patients with Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes and their value for clinical research. METHODS: Outpatients aged > or =45 years were screened between AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7-10 days after study treatment, and followed monthly until a new AECB or for up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB). RESULTS: In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second (FEV1) <50% predicted (OR 0.48; 95% CI 0.35 to 0.67), and > or =4 AECBs in the previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR 1.57; 95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68) and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), age > or =65 years (HR 1.22; 95% CI 1.01 to 1.47), FEV1<50% predicted (HR 1.27; 95% CI 1.05 to 1.53), > or =4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients aged > or =65 years. CONCLUSION: Despite selection of a homogeneous population of patients with chronic bronchitis, between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease, and use of concomitant medications. The design of future clinical trials should take these factors into account.

Acute Disease↗

Aldehyde oxidase and its contribution to the metabolism of a structurally novel, functionally selective GABAA alpha5-subtype inverse agonist.

(3-Tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d] [1,2,4]triazine was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5-containing receptors, which enhances performance in animal models of cognition. The routes of metabolism of this compound in rat, dog, rhesus monkey and human in vitro systems, and in vivo in rat, dog and rhesus monkey have been characterized. The current study demonstrates that both a cytosolic oxidative reaction and cytochrome P450 play important roles in the metabolism of the compound. Chemical inhibition studies showed the oxidation in human cytosol to be catalysed predominantly by aldehyde oxidase rather than the related enzyme, xanthine oxidase. The aldehyde oxidase-mediated metabolites were present in vitro and in vivo in both rat and rhesus monkey, and also in vitro in man. They were absent both in vitro and in vivo in dog.

Aldehyde Oxidase↗

Evaluation of a primary care-oriented brief counselling intervention for obesity with and without orlistat.

OBJECTIVE: There is a significant need for an obesity treatment model suitable for the primary care environment. We examined the effectiveness of a brief counselling intervention alone, in combination with orlistat, and drug-alone in a 12-month randomized-clinical trial at a medical school obesity centre. METHODS: Participants (N = 250) with body mass index (BMI) >or=27 were randomized. Changes in body weight, lipids, blood pressure and serum glucose were examined. Drug adherence and attendance were also evaluated. RESULTS: Completers analysis was conducted on 136 participants with data at baseline, 6 and 12 months and intention-to-treat analyses (ITT) for the total sample. Amongst completers, participants in the drug only (P = 0.012) and drug + brief counselling (P = 0.001) groups lost more weight (mean +/- SD: -3.8 +/- 5.8 kg and -4.8 +/- 4.4 kg, respectively) than participants in the brief counselling only group at 6 months (-1.7 +/- 3.3 kg), but there were no significant group differences at 12 months. ITT model results were similar to completers at 6 months and remained significant at 12 months, but the weight losses were more modest (<3 kg) for both groups receiving orlistat. For brief counselling alone, participants gained weight (1.7 +/- 4.2 kg). Cardiovascular disease (CVD) parameter changes were negligible. CONCLUSIONS: Pharmacotherapy alone or combined with brief counselling resulted in modest weight losses that had minimal impact on cardiovascular parameters, but were greater than brief counselling alone. Whilst brief interventions and primary pharmacotherapy have been suggested as viable treatments for implementation in primary care settings, our study suggests that such minimal interventions provide minimal benefits.

Adult↗

The association between domestic violence and self harm in emergency medicine patients.

AIMS: This study compared rates of self harm among victims of domestic assault presenting to an emergency department (ED) with those rates among other ED patients. It also explored the temporal and numeric relation between domestic assaults and self harm. METHODS: A retrospective matched cohort study was conducted using the medical records of a single ED. The cases were patients who had presented to the ED as a consequence of domestic assault. Two control groups matched for age, sex, and Cambridge postcode were randomly generated from the ED patient list. The second control group cases were also matched for postcode sector as a surrogate approximate for socioeconomic status in addition to age and sex. Cases and controls were followed up between November 1996 and 1 October 2004 documenting the number and timing of episodes of self harm reported in the study period. RESULTS: Altogether, 294 cases and 558 controls were followed up. Patients suffering domestic assault were more likely to present with self harm than controls (RR 3.6 95% CI 2.1-6.5). This effect appeared to be independent of deprivation. Patients suffering domestic assault had more ED contacts than controls. There was a moderate correlation between the number of episodes of self harm and number of assaults (Spearman's rho 0.3 p<0.001). Socioeconomic status was a poor predictor of self harm. Emergency physicians should consider asking about suicidal ideation in victims of domestic assault.

Adult↗

Conservative hand therapy treatments in rheumatoid arthritis--a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of three different physiotherapeutic approaches in the management of the rheumatoid hand. METHODS: In a randomized controlled trial, participants with rheumatoid arthritis (RA) recruited from a rheumatology department in Mid-Staffordshire, UK (February 1999 to January 2001) were randomized to three groups. All received joint protection (JP) information delivered by a therapist at baseline. Group 1 participants received a set of additional hand-strengthening and mobilizing home exercises, group 2 a different set of additional hand-stretching exercises and group 3 the JP information alone. The primary outcome was the Arthritis Impact Measurement Scales II (AIMS II) (upper limb; hand and finger function subscales). Outcomes were assessed at baseline and 1, 3 and 6 months. Analysis was by intention to treat. RESULTS: Sixty-seven participants (mean age 59.6 yr) were recruited: group 1 n = 21, group 2 n = 24 and group 3 n = 22. A 78% follow-up was achieved at 6 months. There was a mean fall (SD) in AIMS II upper limb function 0-6 month change scores in group 1 of 1.00 (1.07). In groups 2 and 3 there was a mean increase in AIMS II scores of 0.18 (1.54) and 0.30 (1.22), respectively. The differences in AIMS change scores between group 1 and groups 2 and 3 were statistically significant (P = 0.007) and remained so after adjustment for multiple testing (P = 0.012). CONCLUSION: Statistically significant improvements in arm function have been demonstrated following a programme of home-strengthening hand exercises in RA patients compared with simple stretches or advice alone.

Aged↗

The influence of environment on development of the mucosal immune system.

The mucosal immune system expresses active responses against pathogens and also tolerance against harmless food and commensal bacterial antigens. The mechanisms that determine which of these outcomes occur after recognition of antigens by T-cells are not clear. One possibility is that it is determined by the initial interaction between a dendritic and a naïve T-cell in organised lymphoid tissue. However, such organised structures are, evolutionarily, quite recent and the original immune system must have made appropriate responses in more diffuse immunological architecture; a second possibility is that the critical interaction is between primed T-cells and their environment, in the lamina propria of the intestine. The mucosal immune system of neonates is poorly developed and inefficient at expressing appropriate immune responses. Development is influenced by a range of environmental factors including maternally derived antigen or antibody and commensal flora and pathogens. The intestine is a complex immunological structure in which the immune system and the macro- and microenvironment interact.

Animals↗

Clinical and pathological responses of weaned pigs to atmospheric ammonia and dust.

Nine hundred and sixty weaned pigs were exposed for five weeks to controlled concentrations of atmospheric ammonia and dust in a single, multifactorial experiment. The treatments were a mean dust concentration of either 1.2, 2.7, 5.1 or 9.9 mg/m3 (inhalable fraction) and a mean ammonia concentration of either 0.6, 10.0, 18.8 or 37.0 ppm, concentrations representative of commercial conditions. The experiment was carried out over two years and the pigs were used in eight batches, each consisting of five lots of 24 pigs. Each treatment combination was replicated once, and an additional control lot (nominally 0 mg/m3 dust and 0 ppm ammonia) was included in each batch. The dust concentration was the same in the other four lots in each batch in which the four concentrations of ammonia were used; thus, the split-plot design was more sensitive to the effects of ammonia than dust. The groups of pigs were kept separately in five rooms in a purpose-built facility, and the pollutants were injected continuously into the air supply. Ammonia was supplied from a pressurised cylinder, and the endogenous dust in each room was supplemented by an artificial dust manufactured from feed, barley straw and faeces, mixed by weight in the proportions 5:1:4; its ingredients were oven-dried, milled and mixed, and then resuspended in the air supply. The health of the pigs was assessed in terms of general pathology, respiratory tract pathology, and the microbiology of the nasal cavity, trachea and lung. In each batch, postmortem examinations were carried out on 40 pigs after five weeks' exposure to the pollutants and on 30 pigs two weeks later to test for carryover and recovery--a total of 560 pigs. These examinations revealed minimal gross pathology and widespread minor pathological changes of little significance. The pigs' turbinate and lung scores were low and unaffected by exposure to pollutants. All the putative bacterial pathogens, with the exception of toxigenic Pasteurella multocida type D, were isolated from the respiratory tract of the pigs of both ages, but there were no differences between the effects of the different concentrations of pollutants.

Air Pollutants↗

Complications of transvaginal silicone-coated polyester synthetic mesh sling.

OBJECTIVES: To report a premarket multicenter trial to test the feasibility of a transvaginal silicone-coated polyester synthetic mesh sling in women with anatomic incontinence. METHODS: Fifty-one patients in four centers underwent transvaginal placement of a silicone-coated polyester synthetic mesh sling (American Medical Systems) during an 8-month period. Of the 51 patients, 31 were part of a prospective institutional review board-approved feasibility trial in three centers funded by American Medical Systems (group 1) and 20 underwent implantation by a single surgeon and their data were retrospectively reviewed (group 2). The studies were done concomitantly, and all slings were fixed transvaginally with bone anchors. All patients in group 1 were followed up at 4 weeks, 6 months, and 1 year (as applicable) with repeat questionnaires, physical examinations, and pad tests. RESULTS: In group 1, 20 patients completed 6 months of follow-up. Ten patients (32%) required a second surgical procedure at an average of 183 days (range 68 to 343) postoperatively. Eight patients (26%) had vaginal extrusion of the mesh, one (3%) required sling lysis, and one (3%) required sling removal because of infection. In group 2, 8 patients (40%) underwent sling removal for vaginal extrusion at a mean of 160 days (range 83 to 214). CONCLUSIONS: Transvaginally placed silicone-coated mesh slings used for the treatment of urinary incontinence demonstrated an unacceptably high vaginal extrusion rate in this study. Once identified, this study was immediately terminated, and this product was not marketed for this application in the United States.

Adult↗

The development of the mucosal immune system pre- and post-weaning: balancing regulatory and effector function.

The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and 'harmless' antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).

Animals↗

Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers.

Copper toxicosis is an autosomal recessive disorder affecting Bedlington terriers, characterized by elevated liver copper levels and early death of affected dogs. Genetic linkage mapping studies initially identified linkage between the disease and the microsatellite marker C04107. Subsequently, the deletion of exon 2 of the copper metabolism domain containing 1 (COMMD1) gene (formerly MURR1) was shown to be the major cause of copper toxicosis, although the deletion breakpoints were not defined. In this investigation, polymerase chain reaction (PCR)-based techniques and sequencing were used to isolate the deletion breakpoints, utilizing the newly available dog genome sequence. The breakpoints were positioned at 65.3091 and 65.3489 Mb of dog chromosome 10, in intron 1 and intron 2 of COMMD1 respectively, a deletion of 39.7 kb. The two breakpoints share sequence homology suggesting that homologous recombination may have been responsible for the deletion. Using this information, a genomic diagnostic test for the COMMD1 deletion was developed and compared with microsatellite C04107 genotypes of 40 Bedlington terriers. Results from the 40 samples showed allele 2 of C04107 to be in linkage disequilibrium with the COMMD1 deletion.

Animals↗

Review of treatment of bronchiolitis related apnoea in two centres.

AIMS: To determine whether the use of negative pressure ventilation (NPV) was associated with a lower rate of endotracheal intubation in infants with recurrent apnoea secondary to acute bronchiolitis. METHODS: Retrospective review of two paediatric intensive care units (PICU) databases and case notes; one PICU offered NPV. RESULTS: Fifty two infants with bronchiolitis related apnoea were admitted to the two PICUs (31 to the NPV centre). There were no significant differences between infants in the two centres in age and weight on admission, gestational age at birth, birth weight, history of apnoea of prematurity or chronic lung disease, days ill before referral, respiratory syncytial virus status, oxygen requirement before support, and numbers retrieved from secondary care centres. Respiratory support was provided to all 31 infants in the NPV centre (23 NPV, 8 PPV), and 19/21 in the non-NPV centre (18 PPV, 1 CPAP); the NPV centre had lower rates of endotracheal intubation rates (8/31 v 18/21), shorter durations of stay (median 2 v 7 days), and less use of sedation (16/31 v 18/21). In the two years after the NPV centre discontinued use of NPV, 14/17 (82%) referred cases were intubated, with a median PICU stay of 7.5 days. CONCLUSIONS: The use of NPV was associated with a reduced rate of endotracheal intubation, and shorter PICU stay. A prospective randomised controlled trial of the use of NPV in the treatment of bronchiolitis related apnoea is warranted.

Apnea↗

Idiopathic osteoarthritis and contracture: causal implications.

OBJECTIVE: To use the known association of idiopathic osteoarthritis with contracture as a means of searching for its cause. There are currently two theories concerning this association, one assuming that the contracture is a consequence of the osteoarthritis and the other that it precedes and causes the osteoarthritis. This study tested both theories. METHODS: Flexion ranges in the 12 finger joints were obtained by goniometric measurement in two samples of normal female subjects, one group with a mean age of 22 years (25 subjects) and one with a mean age of 45 years (50 subjects). The results were compared with the known regional prevalence of osteoarthritis in the finger joints of women. RESULTS: The older group showed evidence of reduced flexion range consistent with development of contracture in the extensor mechanism of the fingers. The distribution of the contracture showed a strong negative correlation with the regional prevalence of osteoarthritis. CONCLUSIONS: An early dorsal contracture develops in the fingers of normal subjects, but it is neither a consequence of nor the cause of digital osteoarthritis. The most parsimonious explanation for the association is that both contracture and idiopathic osteoarthritis are independent consequences of failure to use the full movement range. If this hypothesis is correct, the disease could be preventable.

Adult↗

Early onset of effect of salmeterol and fluticasone propionate in chronic obstructive pulmonary disease.

BACKGROUND: Combined treatment with inhaled corticosteroids and long acting beta2 agonists is approved for the treatment of chronic obstructive pulmonary disease (COPD), but little is known about the onset of effect of the combination. METHODS: Data were used from 1465 patients with COPD entered into a large 1 year double blind trial with daily measurements of peak expiratory flow (PEF) and symptom scores. RESULTS: PEF was significantly higher after 1 day in patients treated with salmeterol 50 microg twice daily or the salmeterol/fluticasone propionate combination 50/500 microg twice daily than placebo. In patients treated with fluticasone propionate 500 microg twice daily alone, PEF differed from placebo after 2 days. The differences after 2 weeks compared with placebo were 16 l/min (95% confidence interval (CI) 11 to 21), 11 l/min (95% CI 6 to 16), and 27 l/min (95% CI 22 to 33) for salmeterol, fluticasone propionate, and the salmeterol/fluticasone propionate combination, respectively. For all treatments the effect on PEF after 2 weeks was comparable to that seen at the end of the study. The difference between the salmeterol/fluticasone propionate combination and placebo after 2 weeks as a percentage of baseline was similar for PEF and clinic forced expiratory volume in 1 second (FEV1). Differences in breathlessness scores were statistically significant after 1 day for the group treated with salmeterol alone and after 2 days for the combination group. The 2 week change in FEV1 was only partly indicative of a long term response in individual patients. CONCLUSIONS: The effects of salmeterol and fluticasone propionate, alone or in combination, on PEF and breathlessness are seen within days and most of the obtainable effect on these parameters is reached within 2 weeks.

Administration, Inhalation↗

Pathways to care and ethnicity. 1: Sample characteristics and compulsory admission. Report from the AESOP study.

BACKGROUND: Many studies have found high levels of compulsory admission to psychiatric hospital in the UK among African-Caribbean and Black African patients with a psychotic illness. AIMS: To establish whether African-Caribbean and Black African ethnicity is associated with compulsory admission in an epidemiological sample of patients with a first episode of psychosis drawn from two UK centres. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas were included in the (AESOP) study. For this analysis we included all White British, other White, African-Caribbean and Black African patients from the AESOP sampling frame. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. RESULTS: African-Caribbean patients were significantly more likely to be compulsorily admitted than White British patients, as were Black African patients. African-Caribbean men were the most likely to be compulsorily admitted. CONCLUSIONS: These findings suggest that factors are operating at or prior to first presentation to increase the risk of compulsory admission among African-Caribbean and Black African patients.

Adolescent↗