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Biomedical subjects

M Atkinson

Publications and source records attributed to M Atkinson.

At least 73 records · Page 4Linked to original sources
PubMed1992

Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen.

Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I produce about half the normal amount of type I procollagen, as a result of decreased synthesis of one of its constituent chains, pro alpha 1 (I). To test the hypothesis that decreased synthesis of pro alpha (I) chains results from mutations in the COL1A1 gene, we used primer extension with nucleotide-specific chain termination to measure the contribution of individual COL1A1 alleles to the mRNA pool in fibroblasts from affected individuals. A polymorphic MnlI restriction endonuclease site in the 3'-untranslated region of COL1A1 was used to distinguish the transcripts of the two alleles in heterozygous individuals. Twenty-three individuals from 21 unrelated families were studied. In each case there was marked diminution in steady-state mRNA levels from one COL1A1 allele. Loss of an allele through deletion or rearrangement was not the cause of the diminished COL1A1 mRNA levels. Primer extension with nucleotide-specific chain termination allows identification of the mutant COL1A1 allele in cell strains that are heterozygous for an expressed polymorphism. It is applicable to sporadic cases, to small families, and to large families in whom key individuals are uninformative at the polymorphic sites used in linkage analysis, making it a useful adjunct to the biochemical screening of collagenous proteins for OI.

Alleles↗
PubMed1992

A comparison of tenoxicam and piroxicam in the treatment of rheumatoid arthritis.

Tenoxicam 20 mg OD was compared with piroxicam 20 mg OD for patients with rheumatoid arthritis (RA). One hundred and two patients from 5 centers were enrolled: 51 in the tenoxicam group and 51 in the piroxicam group. Evaluation of the primary efficacy variables demonstrated no difference in efficacy between treatment groups. The overall incidence of adverse clinical/laboratory experiences was similar between treatment groups. Six patients discontinued the study because of gastrointestinal intolerance, 3 from each treatment group. Our study demonstrates that tenoxicam 20 mg OD and piroxicam 20 mg OD have similar efficacy and safety in patients with active RA.

Adult↗
PubMed1991

Achalasia and diet: assessment of the effect of achalasia on the diet of patients and their spouses.

The effect of achalasia on the diet of patients and their spouses was investigated using a validated questionnaire. The discordance between the diet of the patients and their respective spouses was compared with matched controls. There is no statistically significant difference between the discordance of case couples and control couples. Patients with achalasia, and their spouses, eat a normal diet.

Adult↗
PubMed1991

A prospective comparison of laser therapy and intubation in endoscopic palliation for malignant dysphagia.

There is little objective long-term follow-up comparing laser therapy with intubation for palliation of malignant dysphagia. In a prospective, nonrandomized two-center trial 43 patients treated with the neodymium:yttrium-aluminum-garnet laser were compared with 30 patients treated by endoscopic intubation; the two groups were comparable for mean age and tumor position, length, and histology. Dysphagia was graded from 0 to 4 (0, normal swallowing; 4, dysphagia for liquids). Pretreatment mean dysphagia grades were similar: laser-treated group, 2.9 (SD, 0.6); intubated group, 3.2 (SD, 0.55). For thoracic esophageal tumors, the percentage of patients achieving an improvement in dysphagia grade by greater than or equal to 1 grade initially and over the long term was similar (laser, 95% and 77%; intubation, 100% and 86%). For tumors crossing the cardia, intubation was significantly better (laser, 59% and 50%; intubation, 100% and 92%, respectively; P less than 0.001). In patients palliated over a long period, however, the mean dysphagia grade over the remainder of their mean dysphagia grade over the remainder of their lives (mean survival: laser, 6.1 months; intubation, 5.1 months) was better in the laser group (1.6 vs. 2.0; P less than 0.01); 33% of laser-treated and 11% of intubated patients could eat most or all solids (P less than 0.05). For long-term palliation, laser-treated patients required on average more procedures (4.6 vs. 1.4; P less than 0.05) and days in the hospital (14 vs. 9; P less than 0.05). The perforation rate was lower in the laser-treated group (2% vs. 13%; P less than 0.02); no treatment-related deaths occurred in either group. For individual patients, the best results are likely to be achieved when the two techniques are used in a complementary fashion in specialist centers.

Aged↗
PubMed1990

What does radiotherapy add to survival over endoscopic intubation alone in inoperable squamous cell oesophageal cancer?

The place of radiotherapy in the management of squamous cell oesophageal cancer remains uncertain. Survival of oesophageal cancer patients from the Nottingham area in the years 1982-5 was reviewed. Surgical resection was attempted in 44 of 131 patients with squamous cell oesophageal cancer. Among the remainder 32 had endoscopic intubation alone, 27 had radical radiotherapy alone (six) or combined with endoscopic intubation (21), and 28 had other treatment combinations including surgical intubation and palliative radiotherapy. Patients treated by intubation alone had a mean age of 75 years. They were significantly older and metastases were more common (31%) in this group than in patients treated with radiotherapy (mean age 69 years), of whom 11% had metastases. Some 34% (11 of 32) of patients treated by intubation alone died within 30 days of diagnosis and were therefore not eligible for radiotherapy. Beyond 30 days, survival in the radiotherapy group (median survival 188 days; 95% confidence limits 133-253) was not significantly greater than that for the group treated by intubation alone (median survival 98 days (73-154)). The radiotherapy patients had a median hospital stay of 46 days compared with 23 days for the patients treated by intubation alone. In patients with squamous cell oesophageal cancer unsuitable for surgery, the survival advantage associated with radiotherapy and intubation is small and does not compensate for the extra morbidity and prolonged hospital stay. A controlled trial of radiotherapy in these patients is now needed.

Aged↗
PubMed1990

Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81.

A previous New Zealand case-control study of asthma deaths in the 5-45 year age group during 1981-3 found that prescription of fenoterol (by metered dose inhaler) was associated with an increased risk of death in patients with severe asthma. One major criticism of this study was that drug data for the cases and controls came from different sources. A new case-control design has been used to evaluate the same hypothesis, with a different set of asthma deaths, the same source for drug information being used for both cases and controls. This depended on identifying deaths from asthma during 1977-81 from national mortality records, and ascertaining which patients from those who died had been admitted to a major hospital for asthma during the 12 months before death. The study was confined to this subgroup, which accounted for about 20% of all asthma deaths in the areas served by a major hospital. For each of the eligible patients who died four age matched controls were selected from patients admitted to hospital for asthma during the year that the death occurred who had also had an admission for asthma in the previous 12 months. For the 58 cases and 227 control subjects information on prescribed drugs was collected from the hospital records relating to the previous admission. The odds ratio of asthma death in patients prescribed inhaled fenoterol was 1.99 (95% confidence interval 1.12-3.55, p = 0.02). As in the previous study, subgroups defined by markers of chronic asthma severity were also considered. The inhaled fenoterol odds ratio was 2.98 (95% CI 1.15-7.70, p = 0.02) in patients prescribed three or more categories of asthma drugs, 3.91 (95% CI 1.79-8.54, p less than 0.01) in patients with a previous admission for asthma in the past 12 months, and 5.83 (95% CI 1.62-21.0, p = 0.01) in patients prescribed oral corticosteroids at the time of admission. In patients with the most severe asthma (defined by a previous admission for asthma during the past 12 months and prescribed oral corticosteroids at time of admission) the inhaled fenoterol odds ratio was 9.82 (95% CI 2.23-43.4, p less than 0.01). These findings add further support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

Administration, Inhalation↗
PubMed1990

Comparison of a dimethicone/antacid (Asilone gel) with an alginate/antacid (Gaviscon liquid) in the management of reflux oesophagitis.

Fifty-three patients with symptomatic reflux oesophagitis were entered into a single centre randomized study comparing the effects of a dimethicone/antacid (Asilone Gel) and an alginate/antacid (Gaviscon liquid) on symptoms and endoscopic changes over an 8-week period. Both treatments significantly improved heartburn, acid regurgitation and flatulence. Dimethicone/antacid but not alginate/antacid, produced a significant improvement in oesophagitis, oesophageal ulceration and histological grade of inflammation over the 8-week treatment period so that 14 patients treated with dimethicone/antacid and 10 with alginate/antacid had normal endoscopic oesophageal appearances at the end of the study. The difference in improvement between the two patient groups did not reach significance however, except for dimethicone/antacid improving histological changes (P less than 0.05). These findings suggest that dimethicone/antacid and alginate/antacid are equally effective in treating symptomatic reflux oesophagitis although dimethicone/antacid may have an advantage in improving oesophageal histological appearances.

Adult↗
PubMed1989

Gastroenterology services: a regional review of changes over a five year period (1981-86).

A survey of all gastroenterologists in the Trent region showed that the number of upper GI endoscopies had doubled to 7.6 per 1000 of the population from 1981 to 1986, equalling the number of barium meals. Colonoscopies had increased from 0.39 to 0.94 per 1000 of the population. There had been a large increase in the proportion of endoscopies done by surgeons. There were 0.37 ERCP examinations per 1000 of the population done in six of the 12 districts, and 0.17 variceal sclerotherapy procedures per 1000 of the population done in five districts. There was widespread dissatisfaction with the provision of facilities and staff for endoscopy. From 1981 to 1986 the number of consultants with an interest in gastroenterology had increased from 20 to 25, but none of these appointments had been anticipated in 1981. All eight senior registrars in gastroenterology in 1981 had achieved consultant status - three in the region, four in the NHS outside the region, and one abroad.

Consumer Behavior↗
PubMed1989

Quantitative assessment of the response to therapy in achalasia of the cardia.

Radionuclide oesophageal transit studies and manometry have been carried out in 15 patients with achalasia of the cardia, before treatment, after a course of nifedipine and after pneumatic bag dilatation. Transit studies were also done in 10 patients after cardiomyotomy and in 10 normal subjects. Images were recorded with the subjects seated in front of a gamma camera while swallowing a 10 ml bolus of 99Tcm-tin colloid and then after a further drink of 50 ml water. There was marked retention of tracer in the oesophagus in patients with achalasia compared with rapid clearance in control subjects. Bag dilatation significantly reduced lower oesophageal sphincter pressure but there was no significant difference in the 50% clearance time or percentage dose retained at 100s before and after the treatments. Oesophageal clearance of tracer after the additional drink of water, was improved by bag dilatation. Oesophageal transit in the patients after cardiomyotomy was similar to that in patients who had undergone bag dilatation. There was considerable retention of the tracer in the oesophagus overnight, but this did not result in pulmonary aspiration. Radionuclide oesophageal transit studies provided a quantitative assessment of therapy in achalasia and the proportion of tracer retained after the additional drink proved to be a sensitive measure of response to treatment. Nifedipine proved ineffective as a treatment for achalasia. Bag dilatation and cardiomyotomy were of similar value.

Administration, Sublingual↗
PubMed1989

Value of DNA image cytometry in the prediction of malignant change in Barrett's oesophagus.

DNA image cytometry was performed on Feulgen stained sections from 91 biopsies obtained during prospective endoscopic surveillance of 55 patients with Barrett's oesophagus. Aneuploid cells were detected in specimens from six of these patients. Four subsequently developed dysplasia and adenocarcinoma but, in the other two, biopsies had been reported as showing specialised epithelium only, with no apparent dysplasia and no evidence of malignancy on clinical follow up to date. In two of the four patients who subsequently developed carcinoma, aneuploid cells were only found in biopsies showing overt dysplasia or carcinoma but in the two other patients aneuploid cells were present in biopsies taken early in the clinical course before any dysplasia had been identified on the original reports. The presence of aneuploid cells on cytometry of these 'benign' biopsies allowed us, on histological review, to identify areas of atypia which were interpreted as mild dysplasia. In this series aneuploidy was always associated with some morphological abnormality varying from mild dysplasia to frank carcinoma. Aneuploid cells were not shown in material from one patient who had an oesophagectomy for dysplasia or in biopsy material from four patients showing 'indefinite dysplasia'. DNA cytometry combines an objective assessment of epithelial atypia with the advantage of detecting rare cellular aneuploidy and the ability to correlate these events with morphology. It should assist in the more accurate diagnosis of dysplasia and prove useful in identifying those patients with Barrett's oesophagus who are at greater risk of subsequently developing malignancy.

Aneuploidy↗
PubMed1989

Treatment of reflux oesophagitis with trimoprostil.

Forty-four patients with symptomatic endoscopically proven mild to moderate reflux oesophagitis were enrolled in a single-centre, double-blind, clinical trial comparing trimoprostil 750 micrograms taken 4 times daily with placebo. Patients treated with trimoprostil but not placebo experienced a significant reduction in the frequency (p less than 0.005) and duration (p less than 0.02) of heartburn. Both groups reported a reduction in the severity of heartburn and resulting sleep disturbance during the trial, but differences between them in these respects at the end of the trial did not reach statistical significance. There was a significant reduction in the severity of oesophagitis seen at endoscopy after treatment with trimoprostil (p less than 0.01) but not placebo. Trimoprostil was well tolerated and appears to be more effective than placebo in the treatment of mild to moderate symptomatic reflux oesophagitis. Although this agent's mode of action was not investigated, we speculate that it may be protective to human squamous oesophageal mucosa.

Adult↗
PubMed1988

Lack of necessity for corrections for pyloric losses and duodenogastric reflux in the performance of gastric secretory studies.

Gastric secretory studies are subject to considerable error owing to incomplete collections and to contamination by reflux of alkaline duodenal contents. Corrections for these sources of error have been defined, and they have been extensively applied in a research setting. In order to assess their utility in the performance of routine gastric secretory studies, the value of such corrections was assessed in 56 studies in patients with duodenal ulceration (10), previous surgical vagotomy (8), reflux oesophagitis (30) and primary oesophageal motility disorders (8). The effect of such corrections was small, and there were close correlations between uncorrected and corrected acid outputs in all four groups. The status of the vagal efferent gastric fibres was assessed by comparing the acid output after insulin hypoglycaemia with the maximal acid output after pentagastrin (insulin: pentagastrin ratio). The application of the corrections did not alter the conclusion regarding the assessment of vagal status in 55 of the 56 studies performed. It is concluded that such corrections are not necessary in the routine performance of gastric secretory studies.

Adult↗
PubMed1988

Value of endoscopic surveillance in the detection of neoplastic change in Barrett's oesophagus.

Fifty-six patients with Barrett's oesophagus diagnosed between 1977 and 1986 were prospectively studied by 6-monthly endoscopic surveillance and biopsy. During follow-up to-date, four patients have developed high-grade dysplasia and three have adenocarcinoma of the oesophagus. Two of the adenocarcinomas were preceded by progressively severe dysplastic changes but in the third no dysplasia had been previously detected. The incidence of adenocarcinoma was 1 per 56 patient-years of follow-up. Changes in symptomatology or gross endoscopic appearances were usually absent, even after adenocarcinoma had developed, indicating that biopsy is essential for early diagnosis. The high risk of malignant change makes endoscopic surveillance advisable in all patients with Barrett's oesophagus.

Adenocarcinoma↗