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Biomedical subjects

J P Wright

Publications and source records attributed to J P Wright.

At least 19 recordsLinked to original sources
PubMed2002

Pressurised metered dose inhalers versus all other hand-held inhaler devices to deliver beta-2 agonist bronchodilators for non-acute asthma.

BACKGROUND: A number of different inhaler devices are available to deliver beta2-agonist bronchodilators in asthma. These include hydrofluoroalkane (HFA) or chlorofluorocarbon (CFC)-free propelled pressurised metered dose inhalers (pMDIs) and dry powder devices. OBJECTIVES: To determine the clinical effectiveness of pMDI compared with any other available handheld inhaler device for the delivery of short-acting beta-2 agonist bronchodilators in non-acute asthma in children and adults. SEARCH STRATEGY: The Cochrane Collaboration Clinical Trials register was searched for studies as well as separate additional searches carried out on MEDLINE, EMBASE, CINAHL and also on the Current Contents Index as well as the Science Citation Index. In addition, 17 individual online respiratory journals and 12 electronically available clinical trial databases were also searched. The UK pharmaceutical companies who manufacture inhaled asthma medication were contacted in order to obtain details of any published or unpublished studies. SELECTION CRITERIA: - The full texts of all potentially relevant articles were reviewed independently by two reviewers. DATA COLLECTION AND ANALYSIS: Fixed and random effect models were used. Dichotomous outcomes were assessed using Odds Ratios or Relative Risks (RR) with 95% Confidence Intervals (95%CI). MAIN RESULTS: Eighty-four randomised controlled trials were included in this review, but few could be combined to assess a specific outcome for a given delivery device comparison. Only two studies required demonstration of adequate pMDI technique as an entry requirement. There were no difference between a standard CFC containing pMDI and any other device for most outcomes. Regular use of HFA-pMDI containing salbutamol reduced the requirement for short courses of oral corticosteroids (3 trials, 519 patients: RR 0.67; 95% CI 0.49, 0.91); however the total number of exacerbations were unchanged (3 trials, 1271 patients: RR 1.0; 95% CI 0.75, 1.33). REVIEWER'S CONCLUSIONS: In patients with stable asthma, short-acting beta-2 bronchodilators in standard CFC-pMDI's are as effective as any other devices. The effect of HFA-pMDI on requirement for oral corticosteroid courses to treat acute exacerbations should be confirmed. Effectiveness studies that use an intention-to-treat analysis are required.

Adrenergic beta-Agonists↗
PubMed2001

Long range charge ordering in magnetite below the Verwey transition.

The crystal structure of Fe(3)O(4) below the 122 K Verwey transition has been refined using high-resolution x-ray and neutron powder diffraction data. The refinements give direct evidence for charge ordering (CO) over four independent octahedral Fe sites, two with a charge of +2.4 and the other two of +2.6. CO schemes consistent with our model do not meet the widely accepted Anderson condition of minimum electrostatic repulsion. Instead we propose that CO is driven primarily by a [001] electronic instability, which opens a gap at the transition through a charge density wave mechanism.

Journal Article↗
PubMed2001

Lack of efficacy of ridogrel, a thromboxane synthase inhibitor, in a placebo-controlled, double-blind, multi-centre clinical trial in active Crohn's disease.

BACKGROUND: Thromboxanes are produced in excess and platelets are activated in active Crohn's disease. Preliminary reports have suggested that ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist, may have therapeutic benefit in patients with inflammatory bowel disease. AIMS: To investigate the efficacy of ridogrel in patients with active Crohn's disease. PATIENTS AND METHODS: This was an international, multicentre, randomized, double-blind, placebo-controlled trial of 5 mg/day oral ridogrel for 12 weeks in 85 patients with moderately active Crohn's disease. Sixty patients were randomized to receive ridogrel, and 25 to placebo. The Crohn's disease activity index (CDAI) was used to assess disease activity: remission was defined as a CDAI < 150. Changes in clinical condition, as assessed by the Harvey-Bradshaw index, global evaluation by the investigator and the patient, and blood measures of inflammation, were used as secondary outcomes. RESULTS: The patients' mean (s.d.) CDAI at recruitment was 277 (68) in the ridogrel treated group and 265 (70) in the placebo group. At their final assessment, 20 out of 60 (35%) patients who had been given ridogrel in an intention-to-treat analysis and seven out of 25 (28%) patients given placebo were in remission (no significant difference). No significant differences in Harvey- Bradshaw index or global evaluation were noted between patients given ridogrel and those given placebo. Adverse events were similar in both groups. CONCLUSION: A 5-mg dose of oral ridogrel was not more effective than placebo in inducing remission in patients with moderately active Crohn's disease. If thromboxane synthesis and platelet function are to be targeted for the treatment of Crohn's disease, more potent agents require development and assessment.

Adult↗
PubMed2001

High level excretion of Norwalk-like virus following resolution of clinical illness.

We report the case of an elderly woman excreting high levels (about 5 x 10(5) virions per gram of faeces) of Norwalk-like virus (NLV) in the absence of any clinical symptoms of gastroenteritis. Analysis by reverse transcription, polymerase chain reaction and DNA sequencing was carried out on a 342-nucleotide region of open reading frame 1. This indicated that the NLV belonged to genogroup 2 and was more closely related to the Camberwell subgroup, the most common circulating in southeast Australia at present, than to the Norwalk and Mexico viruses.

Aged↗
PubMed1999

Sucralfate and methylprednisolone enemas in active ulcerative colitis: a prospective, single-blind study.

In order to investigate the role of sucralfate in active ulcerative colitis, 60 patients were randomized to receive either sucralfate enemas (20 g/100 ml) or methylprednisolone enemas (20 mg/100 ml). The enemas were administered twice daily for one week, and then once daily for three weeks. Clinical evaluation was documented at entry and at two weeks and four weeks. The sigmoidoscopic appearance of the rectal mucosa was scored, and rectal biopsies taken at entry and at four weeks. Results indicated similar reduction in diarrhea and rectal bleeding at two weeks and at four weeks. Sigmoidoscopy demonstrated similar significant improvement in the macroscopic appearance of the rectal mucosa in both groups (8.28 to 6.20 in sucralfate group, P < 0.02; and 8.72 to 6.36 in the methylprednisolone treated group, P < 0.04). Histologic assessment, likewise, showed similar improvements in the two groups. This study indicates that sucralfate enemas may be useful in the treatment of ulcerative proctosigmoiditis.

Administration, Topical↗
PubMed1998

A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group.

BACKGROUND: Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both. METHODS: In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02). CONCLUSIONS: In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine.

Administration, Topical↗
PubMed1997

Reovirus variants selected during persistent infections of L cells contain mutations in the viral S1 and S4 genes and are altered in viral disassembly.

Reoviruses isolated from persistently infected cultures (PI viruses) can grow in the presence of ammonium chloride, a weak base that blocks acid-dependent proteolysis of viral outer-capsid proteins during viral entry into cells. We used reassortant viruses isolated from crosses of wild-type (wt) reovirus strain, type 1 Lang, and three independent PI viruses, L/C, PI 2A1, and PI 3-1, to identify viral genes that segregate with the capacity of PI viruses to grow in cells treated with ammonium chloride. Growth of reassortant viruses in ammonium chloride-treated cells segregated with the S1 gene of L/C and the S4 gene of PI 2A1 and PI 3-1. The S1 gene encodes viral attachment protein sigma1, and the S4 gene encodes outer-capsid protein sigma3. To identify mutations in sigma3 selected during persistent reovirus infection, we determined the S4 gene nucleotide sequences of L/C, PI 2A1, PI 3-1, and four additional PI viruses. The deduced amino acid sequences of sigma3 protein of six of these PI viruses contained a tyrosine-to-histidine substitution at residue 354. To determine whether mutations selected during persistent infection alter cleavage of the viral outer capsid, the fate of viral structural proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after treatment of virions of wt and PI viruses with chymotrypsin in vitro. Proteolysis of PI virus outer-capsid proteins sigma3 and mu1C occurred with faster kinetics than proteolysis of wt virus outer-capsid proteins. These results demonstrate that mutations in either the S1 or S4 gene alter acid-dependent disassembly of the reovirus outer capsid and suggest that increased efficiency of proteolysis of viral outer-capsid proteins is important for maintenance of persistent reovirus infections of cultured cells.

Animals↗
PubMed1997

Evaluation of a paired creatine kinase test for the diagnosis of acute myocardial infarction in patients with a non-diagnostic electrocardiogram.

OBJECTIVE: The rate of rise of total plasma creatine kinase (CK) activity in the first 12 hours from presentation can be used to diagnose acute myocardial infarction. The aim of this study was to evaluate the performance of an abbreviated form of this test in the diagnosis of acute myocardial infarction in patients in whom the initial electrocardiogram was inconclusive. METHODS: Using a protocol that requires only two CK measurements (separated by four hours) to estimate the rate of rise, the performance of the test was investigated using data accrued from 345 consecutive admissions with suspected acute myocardial infarction. RESULTS: A CK increment (delta CK) of > 20% in the first four hours from presentation had a diagnostic sensitivity of 84.4% (95% confidence interval 75.5 to 93.3), specificity of 85.8% (80.1 to 91.5), positive predictive accuracy of 73.0% (62.9 to 83.1), and negative predictive accuracy of 92.4% (87.9 to 96.9). Using more stringent diagnostic criteria (delta CK > 20% and 4 h CK value > 160 U/litre) resulted in an increase in specificity and positive predictive accuracy to 96.5% and 91.1% respectively, and a small reduction in sensitivity and negative predictive accuracy to 79.7% and 91.3%, respectively, 94% of all infarcts were correctly identified using the ECG as the initial investigation and paired CK measurement as an additional test when this was inconclusive. In the 44 patients who received thrombolysis on the basis of an early biochemical diagnosis of acute myocardial infarction, the median time delay (75th centile) to thrombolysis was 10.75 (SD 15.0) hours. CONCLUSIONS: When the presenting ECG is non-diagnostic, sequential sampling of cardiac enzymes is a feasible alternative in the early diagnosis of patients with suspected myocardial infarction, even in the emergency setting. Further studies are required to define the optimal biochemical assay and timed sampling protocol.

Aged↗
PubMed1995

A study of a new osmotic purgative for colonoscopy. Is Golytely worth its salt?

An osmotic laxative containing polyethylene glycol and sodium sulfate (Golytely Braintree Laboratories, Inc., Braintree, MA) is widely used to clean the colon for colonoscopy. However, its salty taste makes the mixture unpalatable. We therefore tested the claim that a similar solution but without sodium sulfate (Golytely-RSS Braintree Laboratories, Inc., Braintree, MA) makes preparation of the colon more acceptable to patients in a double-blinded randomized controlled trial. Colonic preparation using polyethylene glycol with or without sodium sulfate was randomized in 100 patients due to undergo colonoscopy. The overall acceptability of the regimen was measured on a linear analogue scale and an estimate of symptoms was obtained. Body weight and serum electrolytes, urea, creatinine, hemoglobin and hematocrit were determined before and after preparation in order to assess fluid absorption. The efficacy of colonic cleansing was graded by the colonoscopist. Four patients did not complete the protocol, 47 received the regimen containing sodium sulfate and 49 received the regimen without it. The two groups did not differ in age or body mass. There was no statistical difference in the overall acceptability of the two regimens to the patients (median acceptability rating 74 for regimen with sodium sulfate, range 4-100 compared with 77 for regimen without, range 3-100, p = 0.32, Mann-Whitney test). Nor was there any difference in taste, nausea, vomiting, cramping or perianal discomfort or in the endoscopists' rating of the cleanliness of the colon. The serum sodium concentration rose slightly (mean 1.6 mmol/L) when the regimen with sodium sulfate was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Cathartics↗
PubMed1995

Mesalazine (Mesasal/Claversal) 1.5 g b.d. vs. placebo in the maintenance of remission of patients with Crohn's disease.

UNLABELLED: INVESTIGATORS: This multicentre study was conducted by 29 principal investigators in 11 countries. AIMS: To compare the safety and efficacy of oral mesalazine (Mesasal/Claversal, 5-ASA) 1.5 g b.d. in comparison with placebo in the maintenance of remission in 286 patients with Crohn's disease. MATERIALS AND METHODS: Patients had to score less than 150 in their Crohn's Disease Activity Index (CDAI), and had to have had one period of clinical activity (CDAI > 150) within 18 months of the study start. Patients were randomized to receive 5-ASA 1.5 g b.d. daily or matching placebo for 12 months. Study visits were scheduled for months 1, 3, 6, 9 and 12, or when symptoms suggested a relapse of the disease. Relapse was defined as a CDAI score greater than 150, with at least a 60-point increase from the baseline index score. None of the patients used glucocorticoids or immunosuppressants during the trial. RESULTS: In the first group, 207 patients with Crohn's colitis or ileocolitis were randomized: there were 101 females and 106 males, in age range 18-71 years. A total of 106 patients (51 in the 5-ASA group and 55 in the placebo group) were withdrawn from the study due to adverse events, insufficient therapeutic effect, or for other reasons. This left 101 patients (51 in the 5-ASA group and 50 in the placebo group) who completed the 12-month trial. In the second group, 79 patients with Crohn's ileitis were randomized to treatment. There were 53 females and 26 males, age range 18-66 years. A total of 41 patients (19 in the 5-ASA group and 22 in the placebo group) were withdrawn from the study. This left 38 patients (17 in the 5-ASA group and 21 in the placebo group) who completed the 12-month trial. The primary efficacy variable was the CDAI. A protocol-eligible analysis and an intent-to-treat analysis were performed. No statistical differences were noted between the two analyses. In patients with Crohn's colitis or ileocolitis, or in those with ileitis, no statistically significant differences were noted with respect to the relapse rates between the 5-ASA and the placebo treatment groups. Adverse events in the gastrointestinal system were the most frequently reported in both treatment groups. Many of the events such as diarrhoea or abdominal pain are symptoms of Crohn's disease. The majority of the events reported were mild or moderate in severity. In neither study was the prevalence of adverse events or the proportion of drop-outs different between patients in the treatment or in the placebo groups. The site of the Crohn's disease had no effect on the frequency of adverse events. CONCLUSION: The relapse rates of Crohn's disease were similar for up to 12 months in both the 5-ASA 1.5 g b.d. and the placebo treatment groups.

Adult↗
PubMed1995

The value of an elimination diet in the management of patients with ulcerative colitis.

Debate exists about the role of diet in both the aetiology and the management of ulcerative colitis. To examine the latter, a group of patients with documented ulcerative colitis was studied at the Groote Schuur Hospital Gastro-intestinal Clinic. A total of 18 subjects, 9 female and 9 male, were randomised into active or control groups and followed up weekly for 6 weeks. Subjects in the control group were asked to document but not alter their intake of food and drink. Those in the experimental group had their diets systematically manipulated to exclude foods that appeared to provoke symptoms. The symptoms, sigmoidoscopy and biopsy findings of all subjects were compared before and after. 'Remission' was defined as the passage of normal stools with absence of rectal bleeding. 'Improvement' was defined as a decrease in the number of diarrhoeal stools and/or a diminution of rectal bleeding. At the end of the trial the diet group displayed significantly fewer symptoms than did the controls (P = 0.009; Fisher's exact test). Sigmoidoscopic findings improved in 8 subjects in the diet group compared with 2 of the controls. Histological findings improved in 3 of the diet group as well as in 3 of the controls. There were no foods that provoked symptoms in all patients, though spiced and curried foods and fruits, especially grapes, melon and the citruses, commonly caused diarrhoea. In only 2 patients were symptoms reproduced consistently on reintroduction of a particular food, pork in 1 case and yellow cheese in another.

Adult↗
PubMed1994

Primary sclerosing cholangitis. Requiem for biliary drainage operations?

OBJECTIVE: To review the outcome of a consecutive number of patients with primary sclerosing cholangitis (PSC) treated at one institution to define prognostic variables and determine the influence of surgery on outcome. DESIGN: Case series of patients with PSC seen in Cape Town, South Africa, between 1981 and 1991. SETTING: Tertiary referral center. PATIENTS: Thirty-six patients with PSC were studied. Diagnosis was based on cholangiographic findings of multiple strictures of the bile ducts together with compatible clinical and biochemical features. Thirty-two patients were followed up prospectively for up to 9 years. MAIN OUTCOME MEASURES: Patient outcome was defined as good (stable or slowly progressive disease) or poor (death or liver transplantation). RESULTS: During the follow-up period, seven patients with PSC died and two underwent liver transplantation. Actuarial survival at 5 years was 52%. An increased serum bilirubin concentration was the only variable at presentation that independently predicted a poor outcome. Cholangiography was unhelpful in predicting patient outcome. Six patients who developed obstructive jaundice associated with advanced liver disease underwent biliary drainage operations for surgically correctable strictures, but this did not seem to prevent progression of the disease. Two patients who progressed to end-stage liver disease went on to have liver transplantation and were alive with functioning grafts at 7 and 14 months, respectively. CONCLUSIONS: Symptomatic PSC is a progressive disorder with a poor prognosis. Our experience suggests that patients with advanced liver disease caused by PSC should be considered directly for liver transplantation rather than biliary bypass operations.

Adolescent↗
PubMed1993

Olsalazine in maintenance of clinical remission in patients with ulcerative colitis.

Frequent minor side effects are associated with sulfasalazine. The realization that it is the 5-aminosalicylic acid moiety that is the active component of sulfasalazine and that the side effects are probably due to the sulfapyridine has prompted the search for a similar but safer compound. Olsalazine, consisting of two molecules of 5-ASA without sulfasalazine may avoid the problems due to sulfasalazine. One hundred one patients were entered into a double-blind placebo-controlled study of the use of olsalazine (2 g daily) in preventing relapse in patients who had recently recovered from an acute attack of ulcerative colitis. Patients were treated for 12 months. Forty-nine were randomized to olsalazine (39 with limited and 10 with extensive disease) and 52 to placebo (42 with limited and 10 with extensive disease). Life-table analysis showed that the median time to relapse in patients on olsalazine was 342 days, which was significantly longer than the 100 days in the placebo group (P = 0.024). The most important side effect experienced with olsalazine that necessitated withdrawal from the study was "drug-induced diarrhea" in 16% (8/49). There was a similar incidence of minor side effects reported in the two groups, and in no patients were major or dangerous side effects reported. In patients who did not develop diarrhea, olsalazine was well tolerated and successfully prevented rapid relapse in the recently ill patients entered into this study.

Adult↗
PubMed1993

Incidence of surgical resection for Crohn's disease.

One hundred fifty-two of 399 Crohn's patients (38 percent) diagnosed over 20 years, who lived within a geographically defined area at the time of diagnosis, underwent at least one operation. One hundred seventy-one resections were performed in 160 operations during a mean follow-up of 60 months. Forty-eight percent of patients had undergone their first resection within 10 years of diagnosis, and 39 percent of these had undergone a second resection within 10 years of the first. There was no difference between smokers and nonsmokers in the timing of their surgery.

Adult↗