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Biomedical subjects

A B Price

Publications and source records attributed to A B Price.

At least 19 recordsLinked to original sources

Molecular, immunological, and biological characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile.

A cytotoxigenic Clostridium difficile strain that fails to produce toxin A but causes hemorrhage and bloody fluid accumulation in ligated ileal loops of rabbits and hemorrhage and diarrhea in hamsters is described. The lack of reaction of DNA from this strain in hybridization studies with a toxin A gene-specific 4.5-kb probe and polymerase chain reaction studies with six toxin A-specific primers indicate the absence of the toxin A gene. The cytotoxin produced by this strain was not responsible for the enterotoxic or hemorrhagic activity and shared characteristics with toxin B, i.e., its cytotoxicity was neutralized by antibodies to toxigenic strains of C. difficile and Clostridium sordellii. Polymerase chain reaction studies with toxin B-specific primers showed that the DNA from this strain produced a 690-bp product in addition to the expected 591-bp product.

Animals

The pathology of rat lung isografts following 48 or 72-hour cold storage and subsequent reperfusion in vivo for up to 1 month.

Using a left lung orthotopic isograft model in adult male AS strain rats, the pathology of lungs which were stored for 48 or 72 hours using a simple organ flush technique followed by low temperature (0 degrees C) immersion has been investigated. Lungs were examined after cold storage alone and after storage followed by either brief (up to 1 hour) or extended (30 days) reperfusion with blood in vivo. Grafts were flushed with either isotonic saline (NaCl) or hypertonic citrate solution (HCA) alone, or with HCA containing either verapamil (a Ca(2+)-channel blocker) or prostacyclin (PGI2 which has both anti-platelet and vasodilator actions). Controls included fresh non-flushed lungs and fresh HCA-flushed lungs which were transplanted immediately after harvest. After prolonged (48 or 72-hour) cold ischaemia alone the only clear change in lung morphology was of nuclear swelling. Early reperfusion changes included: (i) oedema (interstitial and alveolar); (ii) vascular congestion; and (iii) intra-alveolar haemorrhage. Features (i) and (ii) were diffuse whilst haemorrhage was patchy. Lungs which remained in vivo for up to 30 days showed focal scarring and chronic inflammation with numerous macrophages containing haemosiderin; the extent of the changes observed in individual grafts tended to mirror the gross macroscopic outcome. Attempts to improve the cold ischaemic tolerance with added agents (verapamil and prostacyclin PGI2) failed to produce a clear advantage.

Animals

Natural history of indeterminate colitis.

The long-term outcome of patients with a pathological diagnosis of indeterminate colitis on a colectomy specimen was investigated. The case records of 46 such patients operated on for inflammatory bowel disease between 1960 and 1983 were reviewed. Using the preoperative clinical information, pathological and radiological reports, it was possible to divide the patients into three groups: group 1, probable Crohn's disease (19 cases); group 2, probable ulcerative colitis (11 cases); and group 3, indeterminate colitis (16 cases). The patients were followed for a minimum of 2.5 years (median 10, range 2.5-28 years). During this period the probable diagnosis changed in five cases only. One patient in group 1 (Crohn's disease) was subsequently considered to have ulcerative colitis (group 2). The other four patients were all in group 3. Three were reclassified as ulcerative colitis and the fourth as Crohn's disease on the finding of a single granuloma in a rectal biopsy. No case in group 3 required subsequent small bowel surgery. These data suggest that patients continuing with a diagnosis of indeterminate colitis in spite of careful preoperative and postoperative assessment are unlikely to show features of Crohn's disease in the long term. This may be important when considering a subsequent restorative proctectomy.

Adolescent

Anatomy and development of the fontanelle.

Anterior fontanelles from 19 fetuses over a range of gestational ages (from 8 weeks to full term) were obtained to study the anatomy and development in relation to the application of the principles of fontanometry. The most important feature was the development of an elastic membrane by 23 weeks' gestation; a subcutaneous layer of fat had appeared by 28 weeks' gestation.

Gestational Age

The British Society of Gastroenterology early gastric cancer/dysplasia survey: an interim report.

This presentation describes interim findings in a series of 319 patients referred from 41 hospitals on the basis of histopathological findings of 'early gastric cancer', 'dysplasia', or 'worrying mucosal appearances'. Data were recorded using a predefined proforma, and histopathological material circulated amongst a 'panel' of three further pathologists. After this process, 132 patients were classified as having early gastric cancer and 63 as dysplasia. There was good agreement between pathologists as to whether the cases had cancer or dysplasia - but 39 cases said by referring pathologists to have early gastric cancer were classified by the panel as having more extensive disease. Most early gastric cancer cases were diagnosed only after histopathological examination. Cancer or 'possible cancer' was only mentioned after 36% of the radiological investigations and 40.5% of the endoscopies. Computer aided analysis of the patients' symptoms placed 91.3% of the early gastric cancer cases into a 'high risk' group - but was unable to distinguish between early gastric cancer and dysplasia. The five year survival rate of the cases agreed to be early gastric cancer by the panel was well over 90%, but the four year survival rate of cases registered as 'early gastric cancer' but said by the panel to have more advanced disease was under 75%. These findings may account for some of the differences between series, and emphasise the need for precise, widely agreed criteria for the diagnosis of early gastric cancer and gastric dysplasia.

Follow-Up Studies

"Diaphragm-like" strictures of the small bowel in patients treated with non-steroidal anti-inflammatory drugs.

The radiological findings are described in four patients who developed strictures of the small bowel, and who had received non-steroidal, anti-inflammatory drugs (NSAIDs) for 1.5-15 years. Clinical presentation was that of subacute small bowel obstruction. Small bowel barium studies showed multiple discrete strictures. Some strictures were indistinguishable from those of regional enteritis. Others however were narrow "diaphragm-like" septae encroaching on and markedly narrowing the ileal lumen, and shown histologically to be due to submucosal fibrosis. It is suggested that these strictures are likely to be consequent on NSAIDs administration and that radiologists and surgeons need to be aware of these "diaphragms" which can be very difficult to detect on barium examination, either small bowel follow-through or enteroclysis, and at laparotomy.

Adult

Ethanol-induced skeletal muscle myopathy: biochemical and histochemical measurements on type I and type II fibre-rich muscles in the young rat.

Rats were pair-fed either a nutritionally complete liquid diet containing 36% of total calories as ethanol or isovolumetric amounts of the same diet in which ethanol was substituted by isocaloric glucose. Chronic ethanol feeding caused a preferential decline in the wet weight of the plantaris (predominantly Type II muscle fibres) which was accompanied by a reduction in the total DNA content. The soleus (a predominantly Type I fibre muscle) was relatively unaffected. Chronic ethanol exposure had no effect on the biochemical index of cell size (protein/DNA ratio) in either the plantaris or soleus. Quantitative histochemistry of Type II fibres in the plantaris demonstrated that ethanol caused an increase in the proportion of fibres with smaller diameters. Similar effects were observed for Type II fibres in the soleus. In contrast, ethanol exposure was associated with an increase in the relative proportion of Type I fibres with higher diameters, in both plantaris and soleus. Light microscopic examination of myopathic muscle sections demonstrated that lesions occurred without evidence of inflammation, fibrosis or other infiltration by non-muscle cells. It is concluded that chronic exposure of rats to ethanol is associated with skeletal muscle atrophy. The lesion appears to be specific for Type II fibres, irrespective of the predominant fibre type in the particular muscle.

Alcohol Drinking

Pernicious anaemia and Campylobacter like organisms; is the gastric antrum resistant to colonisation?

Gastric biopsies from 86 patients with pernicious anaemia were examined for Campylobacter like organisms with particular attention to those showing an antral gastritis in addition to the usual pattern of body gastritis. All the patients had chronic atrophic gastritis in the body but Campylobacter like organisms were found at this site in only three patients. Thus the Type A pattern of gastritis (autoimmune) seen in patients with pernicious anaemia is only rarely associated with Campylobacter like organisms. Forty four of these patients had biopsies from body and antrum, 16 showed an antral gastritis of whom only one had Campylobacter like organism present. Twenty five of this latter group of patients were rebiopsied after five years. There was no change in the pattern of gastritis, and the same single patient remained colonised. The frequency of an antral gastritis in patients with pernicious anaemia was 36% yet the frequency of antral colonisation by Campylobacter like organisms was very low (6%). These results show that, as in the body, Campylobacter like organisms are not associated with gastritis when it occurs at this site in pernicious anaemia. The antral gastritis that may accompany body gastritis in pernicious anaemia seems more likely therefore to be an extension of primary type A body gastritis (autoimmune) rather than a secondary type B (chronic) gastritis and, it is argued, the antrum may exhibit resistance to colonisation.

Adult

Effect of vertical banded gastroplasty on the natural history of gastritis in patients with morbid obesity: a follow-up study.

Vertical banded gastroplasty is an accepted surgical treatment for morbid obesity. The aim of this study was to evaluate its effect on the natural history of gastritis, as the occurrence of gastritis and dysplasia have been reported after gastric bypass, another type of bariatric surgery. Thirty-four patients who underwent vertical banded gastroplasty between 1983 and 1987 were studied, and the follow-up varied from 1 to 47 months (mean 22 months). We found no increase of gastritis and intestinal metaplasia after surgery, and we did not observe any case of gastric dysplasia. Only one patient with pre- and postoperative specimens showed a deterioration in gastric histology after surgery, and this was of a minor degree. These initial results are encouraging for surgeons interested in the treatment of morbid obesity.

Adult

Clinicopathological features of nonsteroidal antiinflammatory drug-induced small intestinal strictures.

The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two patients had rheumatoid arthritis and 2 patients had osteoarthritis; all had received nonsteroidal antiinflammatory drugs for 1.5-30 yr. Three patients had an initial illness characterized by diarrhea, profound weight loss, and hypoalbuminemia. Intestinal radiology at this stage ranged from subtle changes to those of Crohn's disease. Three patients underwent surgery. At operation the bland external appearance contrasted with the striking mucosal appearances of multiple concentric, circumferential, diaphragmatic strictures that caused luminal stenosis to a pinhole. These septa were due to submucosal fibrosis and the histopathological picture appears to represent a new nosological entity.

Adult

Observer variation in the assessment of dysplasia in ulcerative colitis.

Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only 'fair' or 'moderate'. As expected, agreement over the two categories 'dysplasia' vs 'no dysplasia' was better, ranging from 68% to 84%, and for 'atypia present' (reactive atypia, low- and high-grade dysplasia) vs "no atypia' two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of "atypia, significance uncertain', so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Colitis, Ulcerative

Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs.

Operative small bowel resection specimens received over a period of 16 years were reviewed to assess whether any intestinal disease could be directly attributed to the use of non-steroidal anti-inflammatory drugs (NSAID). Seven cases of intestinal disease associated with the use of NSAID were identified, all of which occurred in the final six years of the survey, which may reflect the increasing use of these compounds. A spectrum of patterns was found from multiple pathognomonic ileal mucosal diaphragms to broad strictures similar to those seen as a complication of enteric potassium. It seems likely that the formation of diaphragm lesions requires an additional factor, but what is not known as yet is whether the effects of NSAID are local or systemic.

Adult