PubMed Health⌕ Search

Biomedical subjects

T Wright

Publications and source records attributed to T Wright.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants.

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log(10) reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV.

Adenine↗
PubMed2000

A randomized, placebo-controlled study to evaluate the efficacy of 12-month famciclovir treatment in patients with chronic hepatitis B e antigen-positive hepatitis B.

We conducted a randomized, placebo-controlled clinical study evaluating famciclovir (500 mg 3 times daily and 1.5 g once daily) for 1 year (6 months post-treatment follow-up) in patients with chronic hepatitis B e antigen (HBeAg)-positive hepatitis B virus (HBV) infection. The study was conducted in 80 centers in North America, Europe, and Australia/New Zealand. A total of 417 patients with histologically documented chronic hepatitis B (histologic activity index [HAI] 9.5-11.0) received famciclovir (500 mg 3 times daily or 1.5 g once daily) or placebo. Famciclovir 500 mg 3 times daily significantly reduced HBV DNA and median HAI scores versus placebo. By week 8, median HBV DNA decreased from 1,645 to 283 MEq/mL (famciclovir 500 mg 3 times daily) and from 1,147 to 304 MEq/mL (famciclovir 1.5 g once daily), while increasing for placebo (1,617 to 1,685 MEq/mL). Median change in HBV DNA at the end of therapy was -76% (famciclovir 500 mg 3 times daily; P <.01) and -60% (famciclovir 1.5 g once daily; P =.25) versus -37% for placebo. Median change in HAI was -1.5 points (famciclovir 500 mg 3 times daily; P =.02) and -1.0 point (famciclovir 1.5 g once daily; P =.35) and zero for placebo. Fifty percent of patients receiving famciclovir 500 mg 3 times daily (P =.07) and 43% receiving 1.5 g once daily (P =.41) experienced >/=2 points improvement in HAI versus 37% for placebo. Nine percent of patients treated with famciclovir 500 mg 3 times daily underwent anti-HBeAg seroconversion with undetectable HBV DNA at end of follow-up versus 3% in the placebo group (P =.05). Famciclovir was well tolerated; the incidence of post-treatment alanine transaminase (ALT) elevations was comparable with placebo. In conclusion, famciclovir 500 mg 3 times daily gave modest suppression of viral replication, but translated into significant histologic improvement in median HAI score at 1 year.

2-Aminopurine↗
PubMed2000

Load carriage energy expenditure with and without hiking poles during inclined walking.

The purpose of this study was to compare load carriage energy expenditure with and without using hiking poles. Twenty male volunteers aged 20-48yr (Mean=29.8yr) completed two randomly ordered submaximal treadmill trials with poles (E) and without poles (C). Poles and load (15 kg backpack) were fitted for each subject according to the manufacturers' suggestions. Heart rates (HR), minute ventilation (V(E)), oxygen consumption (O2), caloric expenditure (Kcal), and rating of perceived exertion (RPE) were recorded at the end of each minute. Two trials separated by one week consisted of a constant treadmill speed of 1.5 mph and 1 min at 10% grade, 2 min at 15% grade, 2 min at 20% grade, and 10 min. at 25% grade. Mean HR (E = 144.8 +/- 24.4 b x min(-1); C = 144.0 +/- 25.7 b x min(-1)) and mean V(E) (E=51.4 +/- 15.8L x min(-1); C=50.8 +/- 17.0L x min(-1)), VO2 (E = 26.9 +/- 6.1 ml x kg(-1) x min(-1); C = 27.4 +/- 6.6 ml x kg(-1) x min(-1)), and Kcal (E = 10.6 +/- 2.9 Kcal x min(-1); C = 10.8 +/- 3.1 Kcal x min(-1)) were not significantly different between the two conditions. RPE (E = 13.28 +/- 1.2; C = 14.56 +/- 1.2) was significantly lower (P < 0.05) with hiking poles. Analysis of paired time points yielded no significant differences in HR, VO2, V(E), and Kcal, however, RPE means were significantly lower for 5 of the last 7 trial minutes with the use of poles. These results suggest that during load carriage on moderate grade, the weight and use of hiking poles does not increase energy expenditure but may provide reduced perceptions of physical exertion.

Adult↗
PubMed2000

Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.

BACKGROUND AND AIMS: Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS: Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS: In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01). CONCLUSION: Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.

Acute Disease↗
PubMed2000

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa, anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by > 60%, the hemoglobin dropped to > 5 g/dL (n = 17). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 24) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Biomarkers↗
PubMed1999

Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Lamivudine Transplant Group.

Hepatitis B after liver transplantation is often fatal, and no proven medical therapy exists for this condition. We chose to study the potential efficacy of lamivudine therapy for patients with chronic hepatitis B after liver transplantation. Fifty-two patients with chronic hepatitis B after liver transplantation were treated in an open label, multicenter study. Each had detectable hepatitis B virus (HBV) DNA in serum and 45 (87%) had detectable serum hepatitis B e antigen before treatment. Patients were treated for 52 weeks with lamivudine (100 mg daily). The primary endpoint was undetectability of HBV DNA; secondary endpoints included normalization of serum alanine transaminase (ALT) levels, disappearance of hepatitis B e antigen, and improvement in liver histology. After treatment, 60% of patients had undetectable HBV DNA by solution hybridization assay, 14 (31%) of the initially positive patients lost hepatitis B e antigen; hepatitis B surface antigen was undetectable in 3 (6%); and serum ALT levels normalized in 71%. Blinded histological assessments showed improvement in the histological activity index (P =.007 for periportal necrosis,.001 for lobular necrosis, and.013 for portal inflammation). YMDD variants of HBV, potentially associated with drug resistance, were detected in 14 (27%) of the patients. Repeat liver biopsies in 7 patients with the mutated virus were unchanged in 2, improved in 2, and worse in 3. We conclude that lamivudine is a potentially effective therapy for hepatitis B after liver transplantation.

Adult↗
PubMed1999

A pilot study of the CY-1899 T-cell vaccine in subjects chronically infected with hepatitis B virus. The CY1899 T Cell Vaccine Study Group.

Clinical observations suggest that eradication of the hepatitis B virus (HBV) is immune-mediated. Vigorous cytotoxic T lymphocyte (CTL) activity directed at HLA class I-bound viral epitopes are detected during acute hepatitis B, but not in chronic hepatitis B carriers. A CTL epitope derived from the hepatitis B core protein amino acids 18-27 has been incorporated into a vaccine also comprised of a T-helper cell epitope and 2 palmitic acid residues (CY-1899). The aim of this study was to determine whether repeated doses of CY-1899 given to patients with chronic hepatitis B could initiate in vivo CTL activity and viral clearance. Patients with chronic hepatitis B received up to 4 doses (ranging from 0.05 mg to 15 mg) 6 weeks apart. Following vaccination, patients were monitored for hepatitis B surface antigen and "e" status, HBV-DNA levels, liver biochemistry, CTL activity, and any adverse events. Ninety patients with chronic hepatitis B infection received CY-1899. Mean CTL responses were all low but were maximal following vaccination with 5 mg CY-1899. Peak CTL responses never exceeded 10 lytic units (LU) regardless of vaccine dose, this value being well below that seen following resolution of acute hepatitis B. No significant changes in liver biochemistry or viral serology were observed during follow-up. No serious adverse events were noted. Administration of the single-epitope vaccine, CY-1899, initiated CTL activity, but of a magnitude lower than that observed during spontaneous HBV clearance. This low-level CTL activity was not associated with viral clearance.

Adult↗
PubMed1999

The genus Deretrema Linton, 1910 (Digenea: Zoogonidae) from southern Great Barrier Reef fishes, with a description of Deretrema woolcockae n. sp.

Two species of Deretrema (Zoogonidae) are reported from labrid fishes from the Great Barrier Reef. D. nahaense Yamaguti, 1942 is recorded from the gall-bladders of the labrids Thalassoma hardwicke (Bennett), T. jansenii (Bleeker), T. lunare (Linnaeus) and T. lutescens (Lay & Bennett). This species is recognised, despite having been formerly synonymised with D. pacificum Yamaguti, 1942. In addition to morphological distinction, D. nahaense appears to have strict host-specificity for the genus Thalassoma. D. woolcockae n.sp. is described from the gallbladder of Hemigymnus fasciatus (Bloch). The new species is close to D. acutum Pritchard, 1963 and D. plotosi Yamaguti, 1940, but differs slightly in the distribution of the vitelline follicles, the sucker-ratio and the position of the cirrus-sac. In addition, this species also appears to have a distinct host-specificity, being restricted to one labrid species.

Animals↗
PubMed1999

An action of erythromycin in the intestine that is not mediated via motilin receptors.

1. Erythromycin lactobionate caused a concentration-dependent inhibition of nerve-mediated contractions of the longitudinal muscle of the guinea-pig ileum, with a threshold for effect of 10-30 mumol/L. The non-antibiotic derivative of erythromycin ABT-229 had a similar effect, but was approximately 10-fold less potent. At a greater concentration (1 mmol/L), erythromycin also depressed the direct contractile effect of 10 mumol/L carbachol on the muscle. 2. Human/porcine motilin (up to 100 mumol/L) did not reduce the nerve-mediated contractions, although it did contract the muscle (threshold 30 mumol/L). Antagonists of motilin receptors (phe3leu13motilin, up to 1 mumol/L, and GM-109, up to 3 mumol/L) did not reduce responses to erythromycin. 3. Erythromycin contracted the longitudinal muscle of the rabbit duodenum, with a threshold concentration of 0.1 mumol/L and ABT-229 contracted this tissue at a threshold concentration of 0.01 mumol/L. Effects of both agonists were antagonized by the motilin receptor antagonists phe3leu13motilin (0.3 mumol/L) and GM-109 (1 mumol/L). 4. It is concluded that the site(s) at which erythromycin acts in the guinea-pig ileum is not a motilin receptor and that ABT-229 is selective for the motilin receptor in comparison with non-motilin erythromycin sites and is unlikely to act at the latter site in therapeutic doses.

Animals↗
PubMed1999

Erythromycin derivatives ABT 229 and GM 611 act on motilin receptors in the rabbit duodenum.

1. The present study was undertaken to determine whether the macrolide antibiotic erythromycin, its stable motilide derivatives ABT 229 and GM 611 and motilin act at the same receptors on intestinal muscle 2. Each compound contracted the longitudinal muscle of the rabbit duodenum in a concentration-dependent manner that was unaffected by 1 mumol/L tetrodotoxin. The potency order (pEC50 values in brackets) was motilin (8.4), ABT 229 (7.6), GM 611 (7.5) and erythromycin (6.0). 3. The motilin receptor antagonists GM 109 and [phe3, leu13]-motilin, both shifted the concentration-response curves for each agonist to the right, but did not affect concentration-response relationships for the muscarinic agonist carbachol. Schild regression analysis yielded similar pA2 values for GM 109 (in the range 7.2-7.5) for all agonists. This analysis was not done for [phe3, leu13]motilin, which was a non-competitive antagonist and partial agonist. 4. It is concluded that erythromycin, the motilides and motilin act at the same (motilin) receptor on rabbit duodenal muscle and do not have any detectable actions at other receptors in this preparation.

Animals↗
PubMed1999

Assessment of a simple scoring system applied to a screening questionnaire of asthma in children aged 5-15 yrs.

The aim of the present study was to validate a simple scoring system using a parent-completed screening questionnaire to identify children aged 5-15 yrs who may have asthma. A stratified random sample of 157 children of 1,808 whose parents had answered a postal respiratory questionnaire underwent detailed clinical evaluation. The results were reviewed by three independent paediatricians whose opinions were combined to reach, for each child, decisions regarding three standards: 1) "possible asthma" defined as >50% likelihood of having asthma; 2) "possible asthma" defined as meriting a clinical trial of asthma medication; and 3) "probable asthma" defined as >90% likelihood of having asthma. The combined decisions were compared to three sets of questionnaire scores, in order to determine the positive predictive value, sensitivity and specificity of each set in identifying children with probable/possible asthma. The three sets of chosen questionnaire scores all had positive predictive values of 79-96% for predicting possible asthma, using either the combined expert opinion ">50% likelihood of asthma" or that of "warrants a trial of treatment" as the definition. This suggests that a low proportion of false positives would be obtained were this scoring system to be used for a screening programme. The combined decision >90% chance of asthma could be used as a means of estimating prevalence of asthma in the survey. When used for this, the prevalence of asthma in the surveyed population was 18.8% (95% confidence interval 13.1-26.3). In conclusion, the present scoring system, based on a simple respiratory questionnaire, provides a valid method of identifying children likely to have asthma, and who, if unknown to the medical services, would benefit from clinical review.

Adolescent↗
PubMed1999

The Japanese Pharmacological Society 72nd annual meeting. 22-25 March 1999, Sapporo, Hokkaido, Japan.

The Japanese Pharmacological Society 72nd Annual Meeting was held in the city of Sapporo on the northern Japanese island of Hokkaido. The meeting attracted a host of pharmacologists, physiologists and molecular biologists from both industry and academia and provided a unique window on the current state of Japanese pharmacological R and D as we approach the millennium. The meeting was attended by over 1800 scientists and hosted 334 oral presentations and almost 700 posters. Molecular pharmacology was the subject of many presentations, focusing on the use of transgenic animals and genome analysis in drug research, while antimicrobials were largely absent.

Journal Article↗
PubMed1998

Spruce budworm elastase precipitates Bacillus thuringiensis delta-endotoxin by specifically recognizing the C-terminal region.

A gut juice protein from Choristoneura fumiferana (spruce budworm) larvae that precipitates certain delta-endotoxins shows a unique specificity for the C-terminal amino acid sequence. Using homolog scanning mutants, we have identified a contiguous region of the Cry1Aa toxin which interacts with the 75-kDa toxin precipitating protein (TPP-75)' resulting in precipitation. The contiguous region from Cry1Aa can be transferred to Cry1Ac and results in an identical precipitation reaction. The precipitation reaction occurs rapidly and is unique in that the ratio of precipitating protein to toxin is low (estimated at 0.01), unlike antibody-antigen reactions which exhibit mole ratios close to 1. TPP-75 has been characterized as an elastase-like serine protease. We have taken advantage of this serine protease character and incorporated a radiolabel using an irreversible inhibitor. The radiolabel has allowed us to show the coincidence of the catalytically-inhibited TPP-75 with the toxin in a blotting assay and to follow the degradation of TPP-75 during storage. TPP-75 represents the first evidence that gut juice proteins may selectively attenuate the activity of delta-endotoxins, prior to binding to putative receptors on susceptible cells. TPP-75 should be evaluated as a possible resistance mechanism for those larvae that do not exhibit a receptor-based resistance.

Animals↗
PubMed1998

Allelotype analysis of oesophageal adenocarcinoma: loss of heterozygosity occurs at multiple sites.

Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Hyperbaric oxygen in the treatment of migraine with aura.

Cephalalgia is one of the most common medical complaints and the search continues for relief. Early treatments for migraine included inhalation of 100% oxygen. It has been theorized that the increased levels of oxygen in the blood act as an alpha-adrenergic agent to alleviate headache pain through vasoconstriction and local metabolic effects. The presence of muscle tenderness during some migraine headaches has also been established. The purpose of this study was to document relief of cephalalgia through use of a visual analog pain scale, algometry, and manual palpation. Female subjects with confirmed migraine were randomly assigned to begin with either the control (100% oxygen, no pressure) or hyperbaric treatment (100% oxygen, pressure). Manual palpation and algometry of 10 sites were done, bilaterally, by a trained specialist. Pain was evaluated with a visual analog scale. Resolution of tenderness and edema following both treatments was observable by manual palpation while algometry showed no differences between the two. Subjective pain was significantly decreased following hyperbaric oxygen treatment but not following the control treatment. Results suggest that hyperbaric oxygen treatment reduces migraine headache pain and that the patient's subjective assessment was the best indicator of relief.

Adult↗