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Biomedical subjects

M Marshall

Publications and source records attributed to M Marshall.

At least 37 records · Page 2Linked to original sources
PubMed2003

Observer variation in the detection of colorectal neoplasia on double-contrast barium enema: implications for colorectal cancer screening and training.

AIM: To assess inter-observer error for the diagnosis of neoplasia on double contrast barium enema (DCBE) in the light of claims that no additional interpretative training would be needed for implementation in a national screening programme. MATERIALS AND METHODS: 10 experts, 10 consultants, and 10 experienced trainees each reported 20 DCBE studies, of which two showed cancer, three showed large polyps, four showed small polyps, and 12 were normal. Inter-observer variation was compared using odds ratios with the trainee group as reference (baseline group). RESULTS: Experts were significantly more likely to correctly identify neoplasia on DCBE than trainees. The odds of a correct diagnosis for experts were 2.79 (95% CI 2.04, 3.81) for cancer, 2.36 (1.88, 2.97) for large polyps, and 3.50 (1.98, 6.18) for small polyps. While consultants were more likely to correctly diagnose a large polyp than trainees, 1.45 (1.15, 1.84), there was no significant difference between these two groups for the correct diagnosis of either cancer, 1.24 (0.52, 2.96), or small polyps, 1.26 (0.83, 1.90). A cancer was missed by 6 (60%) experts, 9 (90%) consultants, and 8 (80%) trainees. Large polyps were missed by 4 (40%) experts, 5 (50%) consultants, and 6 (60%) trainees. There was no significant difference between any group when false positive diagnoses were considered. CONCLUSIONS: There is considerable inter-observer perceptive error for the diagnosis of neoplasia on DCBE. Experts performed significantly better than other observers but the overall standard of performance was poor, even amongst experts.

Aged↗
PubMed2003

Nitric oxide releasing acetaminophen (nitroacetaminophen).

The nitric oxide releasing derivative of acetaminophen (nitroacetaminophen) exhibits potent anti-inflammatory and anti-nociceptive activity in a variety of animal models. On a mol for mol basis nitroacetaminophen is some 3-20 times more potent than acetaminophen. Nitroacetaminophen exhibits little or no hepatotoxicity following administration in rat or mouse and indeed protects against the hepatotoxic activity of acetaminophen. Nitroacetaminophen does not affect blood pressure or heart rate of anaesthetised rats but has similar potency to acetaminophen as an anti-pyretic agent. The enhanced anti-inflammatory and anti-nociceptive activity of nitroacetaminophen and the reduced hepatotoxicity in these animal models is likely to be secondary to the slow release of nitric oxide from the molecule. As yet the precise molecular mechanism(s) underlying these actions of nitroacetaminophen are not clear. Evidence for inhibition of cytokine-directed formation of pro-inflammatory molecule production (e.g. COX-2, iNOS) by an effect on the NF-kappaB transduction system and/or nitrosylation (and thence inhibition) of caspase enzyme activity has been reported. Data described in this review indicate that the profile of pharmacological activity of nitroacetaminophen and acetaminophen are markedly different. The possibility that nitroacetaminophen could be an attractive alternative to acetaminophen in the clinic is discussed.

Acetaminophen↗
PubMed2003

A subtle governance: 'soft' medical leadership in English primary care.

In many countries governments are recruiting the medical profession into a more active, transparent regulation of clinical practice. Consequently the medical profession adapts the ways it regulates itself and its relationship to health system managers changes. This paper uses empirical research in English Primary Care Groups (PCGs) and Primary Care Trusts (PCTs) to assess the value of Courpasson's concept of soft bureaucracy as a conceptualisation of these changes. Clinical governance in PCGs and PCTs displays important parallels with governance in soft bureaucracies, but the concept of soft bureaucracy requires modification to make it more applicable to general practice. In English primary care, governance over rank-and-file doctors is exercised by local professional leaders rather than general managers, harnessing their colleagues' perception of threats to professional autonomy and self-regulation rather than fears of competition as the means of 'soft coercion'.

Attitude of Health Personnel↗
PubMed2002

Predictive value of internal anal sphincter thickness for diagnosis of rectal intussusception in patients with solitary rectal ulcer syndrome.

BACKGROUND: The aim of this study was to determine any association between a thickened internal anal sphincter (IAS) on anal endosonography and high-grade rectal intussusception on evacuation proctography in patients with solitary rectal ulcer syndrome. METHODS: Anal endosonography was performed in 20 patients with solitary rectal ulcer syndrome and IAS thickness defined as normal or abnormal depending on age. Sphincter thickness was compared with the presence or absence of high-grade intussusception on subsequent evacuation proctography to determine any relationship between the two. RESULTS: Thirteen patients had an abnormally thick IAS, two of whom were unable to evacuate. Of the remaining 11 patients, ten showed high-grade intussusception (positive predictive value 91 per cent). Only three of seven patients with a normal IAS had high-grade intussusception (negative predictive value 57 per cent). Patients with a thick IAS were significantly more likely to have proctographic evidence of high-grade intussusception (P = 0.047). CONCLUSION: Sonographic findings of a thick IAS are highly predictive for high-grade rectal intussusception in patients with solitary rectal ulcer syndrome.

Adolescent↗
PubMed2002

Study of a selection of 10 historical types of dosemeter: variation of the response to Hp(10) with photon energy and geometry of exposure.

An international collaborative study of cancer risk among workers in the nuclear industry is tinder way to estimate direetly the cancer risk following protracted low-dose exposure to ionising radiation. An essential aspect of this study is the characterisation and quantification of errors in available dose estimates. One major source of errors is dosemeter response in workplace exposure conditions. Little information is available on energy and geometry response for most of the 124 different dosemeters used historically in participating facilities. Experiments were therefore set up to assess this. using 10 dosemeter types representative of those used over time. Results show that the largest errors were associated with the response of early dosemeters to low-energy photon radiation. Good response was found with modern dosemeters. even at low energy. These results are being used to estimate errors in the response for each dosemeter type, used in the participating facilities, so that these can be taken into account in the estimates of cancer risk.

Calibration↗
PubMed2002

Injectable silicone biomaterial for faecal incontinence due to internal anal sphincter dysfunction.

BACKGROUND: A weak or disrupted internal anal sphincter can cause passive faecal incontinence. Conservative measures may help some patients but there is no simple surgical solution for those who fail conservative treatment. A successful technique using trans-sphincteric injection of a bulking agent to augment the internal anal sphincter was developed in a previous pilot study. AIM: To determine the clinical results and underlying physiological effects of biomaterial injection. PATIENTS: Six patients (four males, median age 53 years (range 36-65)) with faecal incontinence to solid or liquid stool related to poor internal anal sphincter function, of varied aetiology, were recruited. METHODS: Silicone based biomaterial injections were performed, under local anaesthesia, with antibiotic cover. Three injections were placed circumferentially, trans-sphincterically, entering away from the anal margin and injecting at or just above the dentate line. Anorectal physiological studies, endoanal ultrasound, a bowel symptom diary, a validated incontinence score, and quality of life questionnaires were completed before treatment and on completion of follow up. RESULTS: At a median follow up of 18 months (range 15-19), five of six patients had marked symptom improvement. Faecal incontinence scores improved from a median of 14/24 (range 11-20) before to 8/24 (6-15) after injection. Short form-36 quality of life physical and social function scores improved from a median of 26/100 (5-33) to 79/100 (25-100) and from 10/100 (5-37) to 100/100 (50-100), respectively. There was a corresponding physiological increase in maximum anal resting and squeeze pressures. Ultrasound showed the Bioplastique to be retained in the correct position in the improved patients without migration. There were no complications. CONCLUSION: Trans-sphincteric injection of silicone biomaterial can provide a marked improvement in faecal incontinence related to a weak or disrupted internal anal sphincter. This is associated with improved sphincter function and quality of life.

Adult↗
PubMed2002

Research methods used in developing and applying quality indicators in primary care.

Quality indicators have been developed throughout Europe primarily for use in hospitals, but also increasingly for primary care. Both development and application are important but there has been less research on the application of indicators. Three issues are important when developing or applying indicators: (1). which stakeholder perspective(s) are the indicators intended to reflect; (2). what aspects of health care are being measured; and (3). what evidence is available? The information required to develop quality indicators can be derived using systematic or non-systematic methods. Non-systematic methods such as case studies play an important role but they do not tap in to available evidence. Systematic methods can be based directly on scientific evidence by combining available evidence with expert opinion, or they can be based on clinical guidelines. While it may never be possible to produce an error free measure of quality, measures should adhere, as far as possible, to some fundamental a priori characteristics (acceptability, feasibility, reliability, sensitivity to change, and validity). Adherence to these characteristics will help maximise the effectiveness of quality indicators in quality improvement strategies. It is also necessary to consider what the results of applying indicators tell us about quality of care.

Consensus↗
PubMed2001

Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro.

Mutations in the NF1 tumor suppressor gene cause neurofibromatosis type I (NF1), a disease characterized by the formation of cutaneous neurofibromas infiltrated with a high density of degranulating mast cells. A hallmark of cell lines generated from NF1 patients or Nf1-deficient mice is their propensity to hyperproliferate. Neurofibromin, the protein encoded by NF1, negatively regulates p21(ras) activity by accelerating the conversion of Ras-GTP to Ras-GDP. However, identification of alterations in specific p21(ras) effector pathways that control proliferation in NF1-deficient cells is incomplete and critical for understanding disease pathogenesis. Recent studies have suggested that the proliferative effects of p21(ras) may depend on signaling outputs from the small Rho GTPases, Rac and Rho, but the physiologic importance of these interactions in an animal disease model has not been established. Using a genetic intercross between Nf1(+/)- and Rac2(-)(/)- mice, we now provide genetic evidence to support a biochemical model where hyperactivation of the extracellular signal-regulated kinase (ERK) via the hematopoietic-specific Rho GTPase, Rac2, directly contributes to the hyperproliferation of Nf1-deficient mast cells in vitro and in vivo. Further, we demonstrate that Rac2 functions as mediator of cross-talk between phosphoinositide 3-kinase (PI-3K) and the classical p21(ras)-Raf-Mek-ERK pathway to confer a distinct proliferative advantage to Nf1(+/)- mast cells. Thus, these studies identify Rac2 as a novel mediator of cross-talk between PI-3K and the p21(ras)-ERK pathway which functions to alter the cellular phenotype of a cell lineage involved in the pathologic complications of a common genetic disease.

Animals↗
PubMed2001

Anorectic effect of dehydroepiandrosterone combined with dexfenfluramine or thionisoxetine.

Free feeding rats given supplementary 1 h access per day to a palatable dessert test meal were tested for the anorectic effect of dehydroepiandrosterone alone or in combination with either the serotonin releasing agent dexfenfluramine or the norepinephrine uptake inhibitor thionisoxetine (LY 368975). Isobolographic analysis showed that the effect of dehydroepiandrosterone combined with either dexfenfluramine or thionisoxetine was within the range predicted for additivity of action.

Animals↗
PubMed2001

Helping people with severe mental illness to obtain work: systematic review.

OBJECTIVE: To determine the most effective way of helping people with severe mental illness to obtain competitive employment-that is, a job paid at the market rate, and for which anyone can apply. DESIGN: Systematic review. PARTICIPANTS: Eligible studies were randomised controlled trials comparing prevocational training or supported employment (for people with severe mental illness) with each other or with standard community care. OUTCOME MEASURES: The primary outcome was number of subjects in competitive employment. Secondary outcomes were other employment outcomes, clinical outcomes, and costs. RESULTS: Eleven trials met the inclusion criteria. Five (1204 subjects) compared prevocational training with standard community care, one (256 subjects) compared supported employment with standard community care, and five (484 subjects) compared supported employment with prevocational training. Subjects in supported employment were more likely to be in competitive employment than those who received prevocational training at 4, 6, 9, 12, 15, and 18 months (for example, 34% v 12% at 12 months; number needed to treat 4.45, 95% confidence interval 3.37 to 6.59). This effect was still present, although at a reduced level, after a sensitivity analysis that retained only the highest quality trials (31% v 12%; 5.3, 3.6 to 10.4). People in supported employment earned more and worked more hours per month than those who had had prevocational training. CONCLUSION: Supported employment is more effective than prevocational training at helping people with severe mental illness obtain competitive employment.

Adult↗
PubMed2001

Vocational rehabilitation for people with severe mental illness.

BACKGROUND: Unemployment rates are high amongst people with severe mental illness, yet surveys show that most want to work. Vocational rehabilitation services exist to help mentally ill people find work. Traditionally, these services have offered a period of preparation (Pre-vocational Training), before trying to place clients in competitive (i.e. open) employment. More recently, some services have begun placing clients in competitive employment immediately whilst providing on-the-job support (Supported Employment). It is unclear which approach is most effective. OBJECTIVES: To assess the effects of Pre-vocational Training and Supported Employment (for people with severe mental illness) against each other and against standard care (in hospital or community). In addition, to assess the effects of: (a) special varieties of Pre-vocational Training (Clubhouse model) and Supported Employment (Individual Placement and Support model); and (b) techniques for enhancing either approach, for example payment or psychological intervention. SEARCH STRATEGY: Searches were undertaken of CINAHL (1982-1998), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1887-1998). Reference lists of eligible studies and reviews were inspected and researchers in the field were approached to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials of approaches to vocational rehabilitation for people with severe mental illness. DATA COLLECTION AND ANALYSIS: Included trials were reliably selected by a team of two raters. Data were extracted separately by two reviewers and cross-checked. Authors of trials were contacted for additional information. Relative risks (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Continuous data were presented in tables (there were insufficient continuous data for formal meta-analysis). A sensitivity analysis was performed, excluding poorer quality trials. MAIN RESULTS: Eighteen randomised controlled trials of reasonable quality were identified. The main finding was that on the primary outcome (number in competitive employment) Supported Employment was significantly more effective than Pre-vocational Training; for example, at 18 months 34% of people in Supported Employment were employed versus 12% in Pre-vocational Training (RR random effects (unemployment) 0.76 95% CI 0.64 to 0.89, NNT 4.5). Clients in Supported Employment also earned more and worked more hours per month than those in Pre-vocational Training. There was no evidence that Pre-vocational Training was more effective in helping clients to obtain competitive employment than standard community care. REVIEWER'S CONCLUSIONS: Supported employment is more effective than Pre-vocational Training in helping severely mentally ill people to obtain competitive employment. There is no clear evidence that Pre-vocational Training is effective.

Employment↗
PubMed2001

Day hospital versus out-patient care for psychiatric disorders.

BACKGROUND: This review considers the use of day hospitals as an alternative to out-patient care. Three types of day hospital are covered by the review: 'day treatment programmes', 'day care centres' and 'transitional' day hospitals. Day treatment programmes offer more intense treatment for patients who have failed to respond to out-patient care (usually patients with affective or personality disorders). Day care centres offer structured support to patients with long-term severe mental disorders (mainly schizophrenia), who would otherwise be treated in the out-patient clinic. Transitional day hospitals offer time-limited care to patients who have just been discharged from in-patient care. OBJECTIVES: The review had three objectives. First, to assess the effectiveness of day treatment programmes versus out-patient care for people with treatment-refractory disorders. Second, to assess the effectiveness of day care centres versus out-patient care for people with severe long term disorders. Third, to assess the effectiveness of transitional day hospital care for people who had just been discharged from hospital. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (January 1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to December 2000), Psyc LIT (1966 to December 2000), and the reference lists of articles. Researchers were approached to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing day hospital care (including day treatment programme, day care centre, and transitional day hospital) against out-patient care. Studies were ineligible if a majority of participants were under 18 or over 65, or who had a primary diagnosis of substance abuse or organic brain disorder. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and cross-checked. Relative risks and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. MAIN RESULTS: There was evidence from one trial suggesting that day treatment programmes were superior to continuing out-patient care in terms of improving psychiatric symptoms. There was no evidence that day treatment programmes were better or worse than out-patient care on any other clinical or social outcome variable, or on costs. There was no evidence that day care centres were better or worse than out-patient care on any clinical or social outcome variable. There were some inconclusive data on costs suggesting that day care centres might be more expensive than out-patient care. There was evidence from one trial suggesting that transitional day hospital care was superior to out-patient care in keeping patients engaged in treatment, however there was insufficient evidence to judge whether it was better or worse on any other clinical or social outcome variable, or on costs. REVIEWER'S CONCLUSIONS: There is only limited evidence to justify the provision of day treatment programmes and transitional day hospital care, and no evidence to support the provision of day care centres.

Aftercare↗
PubMed2001

Different treatment regimens and the development of tolerance to nicotine's anxiogenic effects.

The effects of different treatment regimens were investigated on the development of tolerance to the anxiogenic effect of nicotine (0.45 mg/kg) in the social interaction test of anxiety. Rats received nicotine (0.45 mg/kg/day) by intravenous injections (5 days/week), subcutaneous injections (5 or 7 days/week) or continuous infusion by osmotic minipump. In all groups, 4 days of nicotine treatment resulted in significant decreases in social interaction compared with the vehicle control groups, without changes in locomotor activity, indicating a specific anxiogenic effect. These significant anxiogenic effects persisted even after 4 weeks of treatment although they were less marked, indicating development of partial tolerance. No significant changes in the time spent in social interaction were found when rats were tested undrugged 24 and 72 h after the termination of nicotine treatment. There was no evidence that the treatment regimen affected the rate of development of tolerance, despite very different peak plasma nicotine concentrations.

Animals↗