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Biomedical subjects

G A Thomas

Publications and source records attributed to G A Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1999

A comparison of two rapid whole-blood tests and laboratory serology, in the diagnosis of Helicobacter pylori infection.

OBJECTIVE: To compare two rapid whole-blood serology tests for Helicobacter pylori and a laboratory serology assay against a gold standard. DESIGN: Prospective comparison of tests in 81 patients. SETTING: A hospital rapid access endoscopy clinic. PARTICIPANTS: Dyspeptic patients requiring assessment of H. pylori status. INTERVENTIONS: Measurement of H. pylori antibody status by Quickvue One-step, Helisal, and Premier H. pylori test; 13C urea breath test for H. pylori, and gastric biopsies for histology, culture and rapid urease test. MAIN OUTCOME MEASURE: Sensitivity and specificity of Quickvue One-step, Helisal and Premier tests, compared to a gold standard based on 13C urea breath test, biopsy culture, histology and urease test. RESULTS: The Quickvue assay has significantly greater sensitivity (81%) than Helisal (67%), but without appreciable loss of specificity (86% and 93%, respectively). The Premier laboratory assay is significantly more sensitive than both of the rapid blood tests (96%), with comparable specificity to the Quickvue assay. CONCLUSION: The rapid serology tests used in this study are quick and convenient to use, but do not approach the sensitivity of a laboratory assay in detecting H. pylori status in this group of dyspeptic patients attending an endoscopy clinic.

Adolescent↗
PubMed1999

Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel.

BACKGROUND: Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. OBJECTIVE: To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. METHODS: Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. RESULTS: Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution. CONCLUSION: Intra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.

Adult↗
PubMed1999

Evaluation of a computer-aided learning program in removable partial denture framework designing.

Assessment of a computer-assisted learning (CAL) program dealing with designing removable partial dentures was performed as both formative and summative evaluation. Formative evaluation was obtained through open-ended questions in a written questionnaire administered to 60 junior students from two Australian Dental Schools and through observation of four groups of these students as they worked through the program. Formative evaluation, fundamental to completion of the program, led to several changes and additions. Observation of the students using the program during its final stages of development was one of the most informative and helpful parts of the evaluation. It allowed nuances of expression and body language to be noted that would not have been apparent in written or numerical data. Summative evaluation was obtained through structured questions in the questionnaire and through a post-CAL test under examination conditions. Summative assessment showed that students could attain a desired standard of knowledge if a lecture series was replaced by the CAL program; that the program was user-friendly, even for students with little or no computer experience; and that most students considered it to be a useful learning resource. More than half the students were concerned about using CAL to replace human instruction. It is significant that students were particularly impressed by aspects of the program that could not be duplicated by a book; the interactive nature of the learning process and the ability to rotate the diagnostic casts. This highlights the need for CAL programs to use the full potential of computer capability, rather than merely replicate a textbook on a screen.

Computer-Assisted Instruction↗
PubMed1999

High prevalence of RET/PTC rearrangements in Ukrainian and Belarussian post-Chernobyl thyroid papillary carcinomas: a strong correlation between RET/PTC3 and the solid-follicular variant.

A sharp increase in the incidence of pediatric thyroid papillary cancer was documented after the Chernobyl power plant explosion. An increased prevalence of rearrangements of the RET protooncogene (RET/PTC rearrangements) has been reported in Belarussian post-Chernobyl papillary carcinomas arising between 1990 and 1995. We analyzed 67 post-Chernobyl pediatric papillary carcinomas arising in 1995-1997 for RET/PTC activation: 28 were from Ukraine and 39 were from Belarus. The study, conducted by a combined immunohistochemistry and RT-PCR approach, demonstrated a high frequency (60.7% of the Ukrainian and 51.3% of the Belarussian cases) of RET/PTC activation. A strong correlation was observed between the solid-follicular subtype of papillary carcinoma and the RET/PTC3 isoform: 19 of the 24 RET/PTC-positive solid-follicular carcinomas harbored a RET/PTC3 rearrangement, whereas only 5 had a RET/PTC1 rearrangement. Taken together these results support the concept that RET/PTC activation plays a central role in the pathogenesis of thyroid papillary carcinomas in both Ukraine and Belarus after the Chernobyl accident.

Adolescent↗
PubMed1998

Power output of pericardium-lined skeletal muscle ventricles, left ventricular apex to aorta configuration: up to eight months in circulation.

OBJECTIVE: The purpose of this experiment was to evaluate the potential for a skeletal muscle ventricle connected to the circulation between the left ventricle and the aorta to provide effective, long-term cardiac assist. METHODS: Skeletal muscle ventricles were constructed from the latissimus muscle in 10 dogs. After conditioning, the skeletal muscle ventricles were connected to the left ventricle and the aorta with 2 valved conduits. The skeletal muscle ventricle was programmed to contract during diastole. RESULTS: At time of implantation, skeletal muscle ventricles stimulated at 33 Hz and in a 1:2 ratio with the heart significantly decreased left ventricular work by 56% (P <.01) and at 50 Hz by 65% (P <.01). At a 1:2 ratio, the power output of the skeletal muscle ventricles was 59% of left ventricular power output at 33 Hz (P <. 01) and 93% at 50 Hz (P <.01). Animals survived 7, 11, 16, 17, 72, 99, 115, 214, and 249 days. Three deaths were directly related to the skeletal muscle ventricle. One animal is alive at 228 days. In the animal that survived 249 days, skeletal muscle ventricle power output at 8 months with a 33 Hz stimulation frequency and a 1:2 contraction ratio was 57% of left ventricular power output and 82% at 50 Hz. At a 1:1 ratio, skeletal muscle ventricle power output was 97% and 173% of the left ventricle at 33 and 50 Hz, respectively. CONCLUSIONS: Left ventricular assist with a skeletal muscle ventricle connected between the left ventricle and the aorta is the most hemodynamically effective configuration we have tested and can maintain significant power output up to 8 months.

Animals↗
PubMed1998

An interactive multimedia solution to learning removable partial denture design.

Surveys of the dental profession and dental laboratories show that up to 60% of cases received by laboratories have little or no input from dentists into the design of their patients' removable partial dentures (RPD). Thus, there is a clear mandate for dental schools to teach RPD design in new ways that will give their students confidence and allow their graduates to approach the task readily and easily. This computer-aided learning program addresses that need. In designing it, we have exploited the unique properties of computers as a learning tool. The program uses Quicktime VR to simulate a three-dimensional perspective of diagnostic casts. It is also possible to incorporate animated diagrams to illustrate various points. Control of timed answers promotes the use of inquiry-based learning and allows the program to be interactive and completely problem-oriented. Students can practice at their own pace, on a variety of virtual cases, and thus learn the craft behind the art of designing RPDs. With this foundation, discussions with experts in the field regarding the patients they treat in senior years and as graduates can be conducted at a higher and more productive level. Student evaluation so far has been very encouraging.

Computer-Assisted Instruction↗
PubMed1998

Inflammatory bowel disease and smoking--a review.

The relationship between smoking and inflammatory bowel disease is a curious but well-established one. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. It also has opposite influences on the clinical course of the two conditions with possible beneficial effect in ulcerative colitis and detrimental effect in Crohn's disease. The diametrically "opposite" relationship of smoking status with the two conditions has been the subject of much interest in the hope that it may reveal pathogenic mechanisms responsible for the two conditions and possibly offer the key to alternative therapeutic options. Nicotine may be the principal agent in smoking responsible for the association; trials have shown it to be of some benefit in ulcerative colitis, but further research is required to establish its therapeutic role and possible mechanisms of action. In this article, we review the historical, clinical, and therapeutic aspects of the association between smoking and inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1998

Clinical status of ulcerative colitis in patients who smoke.

OBJECTIVES: Ulcerative colitis (UC) is largely a disease of nonsmokers. There are few patients who are current smokers, but we have identified a group and reviewed their clinical status, disease activity, and nicotine exposure to examine whether they remain well controlled while smoking. METHODS: Fifty-one patients from three centers with verified UC were reviewed. RESULTS: Thirty of the group were men; mean age 50 yr, with a mean age of onset of 37 yr. Twenty-two patients had proctosigmoid disease, 12 involvement of left colon, and 17 total colitis. All were current smokers; 41 were cigarette smokers averaging 17 daily. At the onset of colitis 30 were nonsmokers, 25 of them were ex-smokers and 19 developed colitis within 2 yr of stopping smoking. Twenty-eight believed smoking improved disease activity and none felt smoking had a detrimental effect on their UC. Eleven were receiving no medication for UC, 40 were receiving 5-ASA (5-aminosalicylic acid) preparations, and only two took oral steroids. All were in clinical remission, with the exception of one patient; mean St. Marks score was 1.5, out of a possible total of 22. Sigmoidoscopic grades were inactive in all patients except three. Histological assessment showed significant activity in only five. Median serum nicotine was 8 ng/ml (range, 0.4-24.4), median serum cotinine 180 ng/ml (range, 20-453), with corresponding salivary cotinine of 255 ng/ml (range, 34-683). Median rise in nicotine 2 min after a cigarette in 35 patients was 12.1 ng/ml (range, 0.4-44). CONCLUSIONS: Because most current smokers with UC have inactive disease, smoking may contribute to the clinical remission in these patients.

Adult↗
PubMed1998

Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study.

BACKGROUND: It has been suggested that Mycobacterium paratuberculosis is the cause of Crohn's disease. In a previous report the immediate effect of two years treatment with antituberculous chemotherapy showed no clinical benefit. AIMS: To assess both the immediate and longer term effect of treatment on the disease. METHODS: Patients were followed for five years from their date of entry to the study. One hundred and thirty patients entered the initial study, and of these 111 (81%) were followed regularly. RESULTS: Overall, there was no evidence of consistent benefit or disadvantage from antituberculous chemotherapy in any of the assessments made, including the number of acute relapses, surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period. CONCLUSION: The absence of any benefit at the end of the initial two year trial period, and during the three year subsequent follow up, fails to support the hypothesis that mycobacteria play an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.

Antitubercular Agents↗
PubMed1998

Mutation of the RET proto-oncogene is correlated with RET immunostaining in subpopulations of cells in sporadic medullary thyroid carcinoma.

Mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, are associated with the pathogenesis of medullary thyroid carcinoma (MTC). Somatic mutations in RET, predominantly at codon 918, and very rarely at codon 883, have been found in a proportion of sporadic MTC. We have previously shown that approximately 80% of sporadic MTCs had at least one subpopulation with a somatic RET mutation. Uneven distribution of somatic mutation within a single tumor or among metastases from a single individual was notable. In the present study, we sought to correlate RET expression, as demonstrated by RET immunohistochemistry, with mutation status in sporadic MTC for each tumor. Seventy evaluable subpopulations, belonging to 28 unrelated sporadic cases, comprising primary MTC and metastases, were immunostained with two different polyclonal antibodies raised against the C-terminus of RET. The regional presence of codon 918 or 883 seemed to coincide with increased RET immunopositivity in at least 62 of 70 (89%, P < 0.000001) tumor subpopulations. The reasons for this concordance are not entirely clear but could be related to either RNA or protein stability. Preliminary studies have suggested that the presence of somatic codon 918 mutation in MTC has a prognostic significance. If these preliminary results prove true, then given our data, we can further explore the feasibility of RET immunocytochemistry as a rapid assessment for the presence of somatic codon 918 for molecular diagnostic and prognostic purposes.

Carcinoma, Medullary↗
PubMed1998

Nicotine carbomer enemas--pharmacokinetics of a revised formulation.

AIMS: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine has therapeutic benefit but causes frequent side-effects. We have previously developed a topical enema combining nicotine with a polyacrylic carbomer; pharmacokinetic parameters were similar in healthy volunteers and patients with active ulcerative colitis. This enema was reformulated to reduce and delay nicotine absorption, thereby improving tolerance. METHOD: Pharmacokinetic observations and side-effects with both formulations are compared in the same 8 healthy volunteers--all non-smokers, 3 male, mean age 33 years. Six milligrams of nicotine were complexed with 400 mg of carbomer in a 100 ml liquid enema. The original formulation was buffered with potassium/phosphate to pH 5.5, kinematic viscosity was 3 mNm; the revised preparation incorporated trometamol 1% solution to buffer to pH 4.2, viscosity 5 mNm. All subjects had the two formulations on separate occasions at least a month apart, with serial blood measurements and side-effect profile recorded for 8 hours. RESULTS: The revised enema formulation significantly reduced Cmax for nicotine from 8.3 +/- 2.7 to 6.6 +/- 2.1, p = 0.03 with some reduction in nicotine absorption and improved tolerance. Although there was considerable intersubject variation in profiles for nicotine and cotinine, they were similar for each subject on both occasions. CONCLUSIONS: The lower pH and greater viscosity reduced the amount of free nicotine in its unionised form available for absorption, but made it possible to expose colonic mucosa to the same nicotine dose. In other drug formulations where side-effects are a limiting factor these modifications may also be relevant.

Acrylic Resins↗
PubMed1997

Somatic mutation of the glucose-6-phosphate dehydrogenase (g6pd) gene in colonic stem cells and crypt restricted loss of G6PD activity.

The study of somatic mutation frequency, particularly stem cell somatic mutation, is important to the understanding of mechanisms of carcinogenesis. The models currently in use for studies in stem cell tissues such as the colon infer the presence of stem cell somatic mutation from alteration in enzyme function, when this has shown to be mutagen dose dependent, restricted to the unit of clonal architecture, and persistent. The present study identifies and characterises somatic mutations in the g6pd gene in individual mouse colonic crypts showing histochemically demonstrable loss of G6PD activity. Microdissection of single crypts, showing either normal or low G6PD activity by histochemistry was performed in mice treated with ethylnitrosourea (ENU), and the presence of point mutations sought by PCR and direct sequencing. Because of the limitation of the small amount of partially degraded (due to fixation) DNA available from each crypt, only about 20% of the coding region of the g6pd gene could be sequenced. Despite this, somatic mutations were identified in 3 of the 9 crypts analysed which showed loss of G6PD activity, but in none of the crypts with normal activity. Each of the mutations identified would be predicted to lead to a decrease in enzyme activity. We conclude that we have confirmed that the crypt restricted loss of G6PD activity is indeed due to stem cell somatic mutation in the g6pd gene, and suggest that the G6PD model can be used as a paradigm for other models where somatic mutation is inferred from a change in histochemically identifiable gene expression.

Animals↗
PubMed1997

A glucose-6-phosphate dehydrogenase (G6PD) splice site consensus sequence mutation associated with G6PD enzyme deficiency.

A glucose-6-phosphate dehydrogenase (G6PD) deficient strain of mouse (GPDX) which was developed using the ethylating agent ethylnitrosourea (ENU) has been used to study clonality in epithelial tissues. While the biochemical defect has been quantified, the genetic basis of the deficiency is unknown. The G6PD gene is composed of 13 exons. Exon 1 is not translated, and the ATG start site is near the 5' end of exon 2. Direct sequencing of the exonic regions of the gene from GPDX, C3H, 101, C57BL/6 and BALB/c mice was carried out. The coding region, in which (with a single exception) all mutations found to cause G6PD deficiency in man are situated, showed identical sequences in three of the four strains studied (101 coding region sequence was not examined). However, the G6PD gene in the GPDX mouse showed a single base difference from the other four strains and from the published mouse G6PD sequence (BALB/c) in the 5' splice site consensus sequence at the 3' end of exon 1, part of the untranslated region. The difference was confirmed in four different GPDX mice. This mutation was of the type (A to T transversion) that is known to be induced by ENU; its effect is likely to be exerted through a defect in transcription, splicing or translation, leading to a reduction in protein levels. By Western blot we have found a marked decrease in the G6PD protein levels in the GPDX mouse, with the C3H X GPDX heterozygote showing a lesser decrease. Recently, an increasing number of mutations in the untranslated regions of genes have been found which have effects on protein levels. We believe that the reduced enzyme activity in the GPDX mouse is due to the mutation in the 5' untranslated region (UTR), and that similar mutations may be relevant in other inherited conditions.

Alternative Splicing↗
PubMed1997

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.

Acrylic Resins↗
PubMed1997

Nicotine enemas for active ulcerative colitis--a pilot study.

BACKGROUND: Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side-effects, an alternative in the form of topical therapy with nicotine enemas has been developed. METHODS: In an open study, 22 patients with active colitis, all non-smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre-trial treatment using mesalazine (n = 16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks. RESULTS: Seventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3-94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side-effects. CONCLUSION: Topical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.

Adult↗
PubMed1997

Effect of nicotine on large bowel mucus thickness, eicosanoids and faecal proteinase in ferrets.

BACKGROUND: Following observations on the effect of subcutaneous nicotine on rectal mucosal eicosanoids and mucus in the rabbit we have repeated the work in ferrets which may be a more suitable animal model. AIMS AND METHODS: The effect of nicotine on mucosal eicosanoids, the adherent mucus layer, and faecal proteinases in the large bowel of ferrets was examined in forty animals randomly allocated to five groups, a control and four treatment groups. They were given subcutaneous saline or nicotine via an Alzet pump in doses of 0.3, 0.6, 1.2 and 2.0 mg/kg/day for 10 days and then sacrificed; measurements were made of serum nicotine and cotinine levels, rectal mucosal eicosanoids, adherent rectal and colonic mucus thickness, and faecal proteinases. RESULTS: No significant differences were observed for any measurements, except for serum nicotine and cotinine levels, which were raised consistent with the dose given. CONCLUSION: Nicotine had no effect on measurements, which may possibly be important in the relationship between smoking and ulcerative colitis.

Animals↗