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Biomedical subjects

P Jones

Publications and source records attributed to P Jones.

At least 37 records · Page 2Linked to original sources

Pathways to care and ethnicity. 2: Source of referral and help-seeking. Report from the AESOP study.

BACKGROUND: Previous research has found that African-Caribbean and Black African patients are likely to come into contact with mental health services via more negative routes, when compared with White patients. We sought to investigate pathways to mental health care and ethnicity in a sample of patients with a first episode of psychosis drawn from two UK centres. METHOD: We included all White British, other White, African-Caribbean and Black African patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. RESULTS: Compared with White British patients, general practitioner referral was less frequent for both African-Caribbean and Black African patients and referral by a criminal justice agency was more common. With the exception of criminal justice referrals for Black African patients, these findings remained significant after adjusting for potential confounders. CONCLUSIONS: These findings suggest that factors are operating during a first episode of psychosis to increase the risk that the pathway to care for Black patients will involve non-health professionals.

Adolescent↗

Characterization of the metabolic burden on Escherichia coli DH1 cells imposed by the presence of a plasmid containing a gene therapy sequence.

The presence of a plasmid, containing gene sequences for DNA immunotherapy that are not expressed in microbial culture, imposed a degradation in bioreactor performance in cultures of the host E. coli strain. Significant decreases in growth rate (24%) and biomass yield (7%) and a corresponding increase in overflow metabolism were observed in a strain containing a therapeutic sequence (a hepatitis B antigen under the control of a CMV promotor). The observed increase in overflow metabolism was incorporated into a Metabolic Flux Analysis (MFA) model (as acetate secretion). Metabolic flux analysis revealed an increase in TCA cycle flux, consistent with an increased respiration rate observed in plasmid-containing cells. These effects are thought to result from increased ATP synthesis requirements (24%) arising from the expression of the Kanr plasmid marker gene whose product accounted for 18% of the cell protein of the plasmid-containing strain. These factors will necessitate significantly higher aeration and agitation rates or lower nutrient feed rates in high-density cultures than would be expected for plasmid-free cultures.

Base Sequence↗

Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.

BACKGROUND: Postoperative oral nutritional supplementation has been shown to be of clinical benefit. This study examined the clinical effects and cost of administration of oral supplements both before and after surgery. METHODS: This was a randomized clinical trial conducted in three centres. Patients undergoing lower gastrointestinal tract surgery were randomized to one of four groups: group CC received no nutritional supplements, group SS took supplements both before and after surgery, group CS received postoperative supplements only, and group SC were given supplements only before surgery. Preoperative supplements were given from the time it was decided to operate to 1 day before surgery. Postoperative supplements were started when the patient was able to take free fluids and continued for 4 weeks after discharge from hospital. Data collected included weight change, complications, length of stay, nutritional intake, anthropometrics, quality of life and detailed costings covering all aspects of care. RESULTS: Some 179 patients were randomized, of whom 27 were withdrawn and 152 analysed (CC 44, SS 32, CS 35, SC 41). Dietary intake was similar in all four groups throughout the study. Mean energy intake from preoperative supplements was 536 and 542 kcal/day in the SS and SC groups respectively; that 2 weeks after discharge from hospital was 274 and 361 kcal/day in the SS and CS groups respectively. There was significantly less postoperative weight loss in the SS group than in the CC and CS groups (P < 0.050), and significantly fewer minor complications in the SS and CS groups than the CC group (P < 0.050). There were no differences in the rate of major complications, anthropometrics and quality of life. Mean overall costs were greatest in the CC group, although differences between groups were not significant. CONCLUSION: Perioperative oral nutritional supplementation started before hospital admission for lower gastrointestinal tract surgery significantly diminished the degree of weight loss and incidence of minor complications, and was cost-effective.

Adult↗

Defining the needs of patients with intellectual disabilities in the high security psychiatric hospitals in England.

BACKGROUND: Previous studies have suggested that a substantial proportion of the patients with intellectual disabilities (ID) in the high security psychiatric hospitals (HSPHs) should be transferred to more appropriate services to cater for their specific needs in the longer term. METHOD: The individual and placement needs of high secure psychiatric patients detained under the legal category of mental impairment or severe mental impairment were assessed in a cross-sectional survey. RESULTS: Patients had a large number of needs (on average 10.8), about a third of which were rated as unmet and therefore represented significant continuing problems. Approximately one-third of the sample could be moved out of HSPHs if appropriate alternatives were available. Factors associated with the continued need for high security included higher treatment and security needs, younger age, recent violent conduct and their index offence profile. CONCLUSIONS: High security services are still required for a number of patients with ID. New and existing services need to be configured to meet specific profiles of need and provide long-term rehabilitation and specialist care. DECLARATION OF INTEREST: This was part of a larger project funded by grants from the High Security Psychiatric Services Commissioning Board and Department of Health.

Adult↗

Veterinary vaccines for animal and public health.

Vaccination is without doubt the most useful single measure available to prevent animal infectious diseases. The advantages of vaccination are numerous. It is the only available method to prevent, or sometimes cure, viral animal infections in the absence of broad spectrum antivirals and avoids the alternative of mass slaughtering of livestock. Antibiotic or anthelmintic resistance, and the problem of pharmaceutical residues, promote the use of vaccines rather than chemotherapy. Vaccines are environmentally friendly and increase animal welfare by preventing suffering from disease resulting from treatment for a cure which may result in antibiotic resistance and pharmaceutical residues in food. For the management of livestock health vaccines are the best tool to achieve sustainability. Veterinary vaccines cannot only be used to protect animal health but also human health from zoonotic infections through animal vaccination as exemplified by wildlife vaccination against rabies. In animal health the focus is now on animal infections rather than on animal diseases. Vaccines should be designed to prevent infection rather than to prevent clinical signs of disease and should, wherever possible, produce sterile immunity. Available technologies allow us to design "marker" vaccines together with their companion diagnostic tests which permit the distinction between vaccinated and infected animals even if the latter were previously vaccinated. Examples will be given of foot-and-mouth disease, classical swine fever, and herpesvirus infections of livestock such as pseudorabies or infectious bovine rhinotracheitis where carrier state or latency remain an issue after vaccination.

Animal Diseases↗

Clarification of the three-body decay of 12C (12.71 MeV).

Using beta decays of a clean source of 12N produced at the IGISOL facility, we have measured the breakup of the 12C (12.71 MeV) state into three alpha particles with a segmented particle detector setup. The high quality of the data permits solving the question of the breakup mechanism of the 12.71 MeV state, a longstanding problem in few-body nuclear physics. Among existing models, a modified sequential model fits the data best, but systematic deviations indicate that a three-body description is needed.

Journal Article↗

The management of adult obesity.

Obesity is Canada's most prevalent metabolic disease: one-third of Canadians are obese. It is a major cause of type 2 diabetes, hypertension, hyperlipidaemia, and atherosclerosis. The treatment of disease caused by obesity accounts for an estimated 2.4 percent of Canada's health care expenditures for all diseases (1.8 billion dollars in 1997). This article presents a treatment algorithm based on a number of international guidelines and aimed to help physicians play a more active role in the management of adult obesity. Two problems are briefly examined: pregnancy and stopping cigarettes smoking.

Adult↗

Limited diversity of HLA-DRB1*02 alleles and DRB1-DRB5 haplotype associations in four United States population groups.

At least 60 DRB1*02 positive individuals from each of four US population groups found within a hematopoietic stem cell volunteer donor registry - Caucasoids, African Americans, Asians/Pacific Islanders, and Hispanics - were randomly selected from a database of 82,979 individuals. DRB1*02 alleles were identified by DNA sequencing. A total of five of 23 known DRB1*02 alleles were detected. DRB1*15011 was the predominant DRB1*02 allele in Caucasoids and Hispanics. The most common DRB1*02 allele observed in African Americans was DRB1*1503, and DRB1*15021 in Asians/Pacific Islanders. Caucasoids were found to be the least diversified; only DRB1*15011 and DRB1*16011 were observed. A subset of individuals was also typed for DRB5 alleles by DNA sequencing. DRB5*01011, DRB5*0102, DRB5*0103, DRB5*0108N and DRB5*0202 were detected and nine DRB1-DRB5 haplotypes defined.

Black or African American↗

Seventeen novel HLA-A alleles.

This paper describes 17 novel HLA-A alleles: A*0244, A*0251, A*0254, A*0309, A*1111, A*2432, A*2434, A*2504, A*2618, A*2905, A*2906, A*3106, A*3107, A*3207, A*6820, A*7407, and A*7408. Most substitutions are found in other alleles.

Alleles↗

Pharmacology of novel heteroaromatic polycycle antibacterials.

Heteroaromatic polycycle (HARP) compounds are a novel class of small (M(w), 600 to 650) DNA-binding antibacterials. HARP compounds exhibit a novel mechanism of action by preferentially binding to AT-rich sites commonly found in bacterial promoters and replication origins. Noncovalent binding in the minor groove of DNA results in inhibition of DNA replication and DNA-dependent RNA transcription and subsequent bacterial growth. HARP compounds have previously been shown to have potent in vitro activities against a broad spectrum of gram-positive organisms. The present report describes the extensive profiling of the in vitro and in vivo pharmacology of HARP antibacterials. The efficacies of representative compounds (GSQ-2287, GSQ-10547, and GSQ-11203), which exhibited good MIC activity, were tested in murine lethal peritonitis and neutropenic thigh infection models following intravenous (i.v.) administration. All compounds were efficacious in vivo, with potencies generally correlating with MICs. GSQ-10547 was the most potent compound in vitro and in vivo, with a 50% effective dose in the murine lethal peritonitis model of 7 mg/kg of body weight against methicillin-sensitive Staphylococcus aureus (MSSA) and 13 mg/kg against methicillin-resistant S. aureus (MRSA). In the neutropenic mouse thigh infection model, GSQ-11203 reduced the bacterial load (MRSA and MSSA) 2 log units following administration of a 25-mg/kg i.v. dose. In a murine lung infection model, treatment with GSQ-10547 at a dose of 50 mg/kg resulted in 100% survival. In addition to determination of efficacy in animals, the pharmacokinetic and tissue disposition profiles in animals following administration of an i.v. dose were determined. The compounds were advanced into broad safety screening studies, including screening for safety pharmacology, genotoxicity, and rodent toxicity. The results support further development of this novel class of antibiotics.

Acetamides↗

Dynamics of vascular endothelial-cadherin and beta-catenin localization by vascular endothelial growth factor-induced angiogenesis in human umbilical vein cells.

The adherens junctional molecule, vascular endothelial cadherin (VE-cadherin), functions to maintain adherens junction stability and to suppress apoptosis of endothelial cells by forming a complex with vascular endothelial growth factor (VEGF) receptor 2 and members of the armadillo family of cytoplasmic proteins. In order to investigate the dynamics of the association of VE-cadherin with adherens junctions during the initial stages of angiogenesis, human umbilical cord endothelial cells (HUVECs) were stimulated with VEGF to undergo angiogenesis in type-I collagen three-dimensional culture. In confluent monolayers of HUVECs, VE-cadherin and its signaling partner, beta-catenin, as well as the paracellular transmembrane adhesion molecule platelet-endothelial cell adhesion molecule (PECAM-1), were all present in regions of cell-cell contact. Within 3 h of stimulation of angiogenesis, VE-cadherin and beta-catenin were lost from these regions. In contrast, the distribution pattern of PECAM-1 did not alter. After 6 h the majority of endothelial cells had migrated to form a network of capillary cords with cell-cell contacts that contained all three molecules. By metabolic labeling of HUVECs it was found that de novo synthesis of VE-cadherin was not essential for the formation of new adherens junctions. Coimmunoprecipitation and immunoblotting experiments showed that the VE-cadherin and beta-catenin remained associated after they were lost from adherens junctions. Detergent extraction of cells with Triton X-100 indicted that the majority of VE-cadherin and beta-catenin was Triton soluble, indicating that they are only weakly associated with the actin-based cytoskeleton.

Adherens Junctions↗

Prediction of colorectal cancer by a patient consultation questionnaire and scoring system: a prospective study.

BACKGROUND: Current NHS guidelines for referral of patients with colorectal symptoms classify many as high risk but fail to identify a significant number of cancers in the low-risk group. We describe a practical scoring method to predict colorectal cancers. METHODS: From October, 1999, 2268 patients with distal colonic symptoms, referred by general practitioners, completed a patient consultation questionnaire linked to a computerised record. Referrals were prioritised with a malignancy risk score by a senior colorectal surgeon separately from the general practitioner's letter and from the questionnaire. A weighted numerical score was derived from weighting of primary symptoms and symptom complexes and was calculated automatically when the questionnaire data were entered into the computer program. Analysis by receiver-operating characteristics assessed the scoring systems. Sensitivities and specificities of scoring systems were compared with McNemar's test. FINDINGS: Of the 2268 patients, 95 had colorectal cancer. The average weighted numerical score was significantly higher for patients with cancer than for non-cancer patients (mean 76.5 [95% CI 72.2-80.9] vs 44.5 [43.6-45.4]; p<0.0001). At similar cancer detection rates, the malignancy risk score derived from the patient consultation questionnaire and the weighted numerical score graded lower proportions of referrals as urgent than did the current NHS guidelines (43.1% and 39.8% vs 49.8%; p<0.0001). INTERPRETATION: The patient consultation questionnaire depends on history alone and is easily reproducible. In conjunction with the weighted numerical score, which removes operator bias, it can be used as an accurate system for prediction of symptomatic colorectal cancer.

Adult↗

Changing the minimum legal drinking age--its effect on a central city emergency department.

AIMS: To quantify the effect of a recent national law change on the presentation of ethanol intoxicated patients to a central city Emergency Department (ED). METHODS: All records of ethanol intoxicated patients presenting to the ED for twelve months before and after the change to the minimum legal drinking age were studied. Each patient was classified as having laboratory confirmed intoxication, clinical suspicion only, or no record of intoxication. Three age groups were identified, 15-17 year olds, eighteen and nineteen year olds and over 20 year olds. Within each age group the proportion of presentations with ethanol intoxication was compared across the two time periods. RESULTS: The number of intoxicated 18 and 19 year olds increased in the twelve months after the national law change from 66 to 107 (52 to 80 for laboratory confirmed intoxication and fourteen to 27 for clinical suspicion only). This represented an increase in the proportion of presentations in this age group with intoxication (p=0.009) from 2.9% to 4.4%, a 50% increase (RR=1.51, 95%CI 1.11-2.03). There was no evidence of an increase in the proportion intoxicated for those over nineteen years (3.4% vs 3.3%, p=0.48, RR=0.97, 95%CI=0.89-1.06) although the numbers increased slightly (963 to 992). However there was a worrying trend for an increase in the 15-17 year olds, with numbers increasing from 72 to 95 and the proportion increasing from 5.0% to 6.7% (p=0.07, RR=1.35, 95%CI=0.98-1.88). CONCLUSION: The recent lowering of the minimum legal drinking age from 20 to eighteen years has resulted in increased presentations to the ED of intoxicated eighteen and nineteen year olds. A similar trend was seen in the 15-17 year olds.

Adolescent↗

Liquid chromatography/electrospray ionisation mass spectrometric investigations of imidazoline corrosion inhibitors in crude oils.

The so-called imidazolines (2-alkyl-1-[ethylalkylamide]-2-imidazolines and 2-alkyl-1-ethylamine-2-imidazolines) are a group of surface-active compounds, complex mixtures of which are used by various industries as surfactants and corrosion inhibitors. Although their industrial synthesis was reported over 100 years ago, few methods for the determination of individual imidazolines in mixtures, including industrial matrices such as crude oils, have been reported. Here we demonstrate that spiking of crude oils with synthetic imidazolines followed by solid-phase extraction and liquid chromatography/electrospray ionisation multistage mass spectrometry (LC/ESI - MS(n)) allows an estimation of low (<10) parts per million concentrations of individual imidazolines in crude oils. Whilst non-optimised at present, the method is a significant advance and may prove useful not only for improving an understanding of the mechanisms of industrial imidazoline synthesis and for monitoring downhole and topside oilfield operations, but also for the determination of the fate of imidazoline-based oilfield corrosion inhibitors and surfactants in the environment.

Journal Article↗

Lower prevalence of pre-morbid neurological illness in African-Caribbean than White psychotic patients in England.

BACKGROUND: It has been suggested that the increased incidence of psychosis in African-Caribbeans living in England may be due to illnesses in which social stress plays an important aetiological role. If this is the case, the prevalence of factors associated with psychosis that predate illness onset such as obstetric complications, pre-morbid neurological illness and poor childhood social adjustment may be expected to be lower in African-Caribbean than Whites psychotic patients. METHOD: Details of obstetric complications, pre-morbid neurological illness, and pre-morbid social adjustment were obtained for 337 psychotic patients by patient interview, interviews of mothers and chart review. The proportions of patients with each 'risk factor' in the African-Caribbean (N = 103) and White (N = 184) groups were compared using regression analysis; age, sex, social class, diagnosis and referral status were possible explanatory variables. RESULTS: African-Caribbean patients were less likely to have suffered a pre-morbid neurological disorder than their White counterparts (odds ratio 0.19, 95% CI 0.06-0.61). There was no significant difference in pre-morbid social adjustment or obstetric complications between the two groups, though fewer obstetric complications were reported in the African-Caribbean group (21.5%) than the White group (30.9%). CONCLUSIONS: African-Caribbean patients with psychosis have experienced less pre-morbid neurological illness.

Black or African American↗

Novel HLA-A locus alleles including A*01012, A*0306, A*0308, A*2616, A*2617, A*3009, A*3206, A*3403, A*3602 and A*6604.

This paper describes 10 novel HLA-A alleles that have been characterized by DNA sequencing. Seven alleles, A*0308, A*2616, A*3009, A*3206, A*3403, A*3602 and A*6604 carry motifs observed in other HLA-A alleles, suggesting that gene conversion has created this diversity. The remaining three alleles, A*01012, A*0306 and A*2617, contain polymorphisms not previously found in any "classical" class I allele. All alleles were identified due to unexpected probe hybridization patterns during routine SSOP typing. Exons 2 and 3 of each allele were subsequently characterized by DNA sequencing.

Alleles↗

Trialling a new way to learn clinical skills: systematic clinical appraisal and learning.

AIM: To describe and evaluate the effectiveness of a new method of teaching clinical skills designed to increase students' active and self-directed learning as well as tutor feedback. METHODS: A total of 22 consenting Year 4 medical students undertaking general practice and general surgery clinical experience were involved in a pre- and post-test research design. In the initial period of the study, students were taught clinical skills in a traditional manner. In the second phase a clinical teaching strategy called systematic clinical appraisal and learning (SCAL) was utilised. This learning strategy involved active and self-directed learning, holistic care and immediate feedback. Students independently saw a patient and were asked to make judgements about the patient's potential diagnosis, tests required, management, psychosocial needs, preventive health requirements, and any ethical problems. These judgements were then compared with those of the clinical supervisor, who saw the same patient independently. Students recorded details for each consultation. Comparisons were made of the two study periods to examine whether the use of SCAL increased the number of students' independent judgements, perceived student learning, tutor feedback and self-directed learning. RESULTS: During the SCAL learning period, students reported making a greater number of statistically significant independent judgements, and receiving significantly increased tutor feedback in both general practice and general surgery. The number of learning goals set by students was not found to differ between the two periods in surgery but significantly increased in general practice in the SCAL period. Students' perceptions of their learning significantly increased in the SCAL period in surgery but not in general practice. During the traditional learning period in both settings, there was limited student decision-making about most aspects of care, but particularly those relating to prevention, psychosocial issues and ethics. CONCLUSIONS: The SCAL approach appears to offer some advantages over traditional clinical skills teaching. It appears to encourage active and independent decision-making, and to increase tutor feedback. Further exploration of the approach appears warranted.

Clinical Competence↗