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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

Effect of longterm misoprostol coadministration with non-steroidal anti-inflammatory drugs: a histological study.

Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.

Adult

Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.

Adult

The economic and quality-of-life benefits of Helicobacter pylori eradication in chronic duodenal ulcer disease--a community-based study.

A policy of Helicobacter pylori eradication in patients with duodenal ulceration on long-term acid-suppressing therapy was evaluated in a prospective study amongst a general practice population, with particular reference to economic and quality-of-life benefits. One hundred and sixty-eight patients on long-term acid-suppressing therapy had chronic duodenal ulcer disease of whom 88 were eligible for the study; 45 patients attended for review, with 42 testing positive for H pylori (as assessed by 13C-urea breath test). The median duration of acid-suppressing therapy was six years (maximum 15 years); 47.6% of the patients were using additional antacids and 80.9% still experienced epigastric discomfort. Two-thirds (28/42) of the patients eradicated H pylori. Successful eradication was associated with a highly significant reduction in all symptoms. At 12 months follow-up, heartburn had decreased from 28.7% to 7.1%, epigastric discomfort from 75% to 3.6%, nausea from 32.1% to 0% and wind from 50% to 0%. Of the patients that eradicated H pylori 96.4% reported an improvement in their general health compared to none of those that remained H pylori positive. Successful H pylori eradication therapy scored higher on satisfaction ratings than long-term acid-suppressing therapy. Eradication of H pylori resulted in 27/28 patients being able to discontinue acid-suppressing therapy, representing a 5.8% reduction in the use of such drugs per year in the local general practice population. A policy of H pylori eradication in chronic duodenal ulcer disease reduces the use of long-term acid-suppression therapy in general practice. This has important financial implications as well as offering considerable symptomatic benefits to the patients and improving their quality of life.

Adult

Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease-modifying antirheumatic drugs.

OBJECTIVE: To identify the source of intestinal blood loss in rheumatoid arthritis patients being treated with nonsteroidal antiinflammatory drugs (NSAIDs) and assess the response to sulfasalazine and other disease-modifying antirheumatic drugs (DMARDs). METHODS: Intestinal inflammation, blood loss, and gastroduodenal damage, and the response to treatment with DMARDs, were assessed in 46 patients taking NSAIDs. RESULTS: Intestinal inflammation and blood loss correlated significantly with one another (r = 0.43, P < 0.003), but not with the macroscopic or microscopic appearance of the gastroduodenal mucosa. Sulfasalazine reduced both intestinal inflammation and blood loss, whereas the other DMARDs did not. CONCLUSION: The small intestine is the main site of mild chronic blood loss in patients receiving NSAIDs, and this blood loss can be reduced with sulfasalazine treatment.

Aged

Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis.

BACKGROUND/AIMS: Cancer surveillance in patients with ulcerative colitis is of unproven benefit. This study assesses the efficacy and analyzes factors limiting the success of a surveillance program during a 21-year period in 332 patients with ulcerative colitis to the hepatic flexure and disease duration exceeding 10 years. METHODS: Clinical assessment and sigmoidoscopy with biopsy was undertaken yearly. Colonoscopy and biopsy every 10 cm throughout the colon was performed every 2 years or more often if dysplasia was found. Only biopsy specimens reported as showing dysplasia were reviewed. RESULTS: Surveillance contributed to detection of 11 symptomless carcinomas (8 Dukes A, 1 Dukes B, and 2 Dukes C), but 6 symptomatic tumors (4 Dukes C and 2 disseminated) presented 10-43 months after a negative colonoscopy. Dysplasia without carcinoma was confirmed in 12 symptomless patients who underwent colectomy. The 5-year predictive value of low-grade dysplasia for either cancer or high-grade dysplasia was 54% using current criteria. CONCLUSIONS: Surveillance identified some patients at a curable stage of cancer or with dysplasia. Limiting factors were failure to include patients with presumed distal colitis, biennial colonoscopy, the number of biopsy specimens at each colonoscopy, and variation in histological identification and grading of dysplasia.

Adenomatous Polyps

Cutaneous sarcoid-like granulomas in primary immunodeficiency disorders.

We report the occurrence of cutaneous sarcoid-like granulomas in one patient with common variable immunodeficiency and another with 'thymoma and hypogammaglobulinaemia'. To our knowledge, this is the first time that such skin lesions have been described in patients with primary immunodeficiency. These granulomas may be attributed to a combination of interleukin-2 deficiency and a profound CD4 lymphopenia. The lesions are similar to the non-infectious 'papular eruption' associated with human immunodeficiency virus infection, and might reflect a common pathogenic mechanism.

Adult

Obstructive enterocolitis: a clinico-pathological discussion.

Obstructive colitis is a condition that is not widely appreciated by pathologists. It is defined as an ulcero-inflammatory lesion(s) proximal to a colonic obstruction from which it is separated by a variable length of normal mucosa. Five cases are described which illustrate the clinico-pathological spectrum of the condition. All presented surgically as acute intestinal obstruction, secondary to adenocarcinoma in four cases and a diverticular stricture in one case. Pathologically, the severity of colitis ranged from a single discrete ulcer to an extensive area of fulminant colitis indistinguishable from colitis indeterminate. Furthermore, two cases represented 'obstructive enteritis', a variant of obstructive disease not previously reported. Microscopically, all cases were characterized by distinctive areas of localized ulceration and active inflammation, the features of which were quite unlike those of Crohn's disease or ischaemia, separated by islands of normal mucosa. The role of mural hypoperfusion and secondary localized ischaemia in the pathogenesis of this disorder is discussed. It is suggested that colitis indeterminate represents the final common pathological pathway of the intestine to a wide range of initial insults, be they obstructive or inflammatory.

Adenocarcinoma

Studies on the enteropathy associated with primary hypogammaglobulinaemia.

Twelve patients with primary hypogammaglobulinaemia with diarrhoea not associated with known microbial pathogens were investigated. Histological evidence of inflammation was common in the stomach and jejunum. Moreover, eight of 10 patients undergoing colonoscopy had low grade 'microscopic colitis' with raised intraepithelial lymphocytes and an intact crypt architecture. Five of 12 patients had small intestinal inflammation on 111indium leucocyte scintigrams and all had increased faecal excretion (normal < 1%) of 111indium (over four days), which varied in intensity from mild (faecal excretion of 111indium = 1-3%) to that comparable with moderately active (7-14.5%) Crohn's disease. Three patients had small intestinal strictures superficially resembling Crohn's disease. Histologically, however, these lacked characteristic diagnostic features of Crohn's disease in two and the third patient had non-steroidal anti-inflammatory drug induced diaphragm like strictures. Six of seven who were most severely symptomatic were successfully treated with an elemental diet with rapid improvement of symptoms. The faecal excretion of 111indium was repeated in five and all improved but histologically the colitis remained unchanged. These studies show that some patients with primary hypogammaglobulinaemia have intestinal inflammation unlike that found in classic inflammatory bowel disease. Elemental diet is a useful temporary measure in the treatment of these patients.

Agammaglobulinemia

Intraoperative assessment of nodal status in the selection of patients with breast cancer for axillary clearance.

Preliminary axillary node sampling with intraoperative reporting of imprint cytology to detect positive nodes was assessed in 50 consecutive patients with T1 or T2 breast cancer undergoing axillary clearance, 21 of whom were histologically node positive. A mean of 3.5 (range 1-4) nodes were sampled. Axillary clearance yielded a mean of 11.7 (range 4-32) nodes. Of node-positive patients, sampled nodes detected 18 of 21 on immediate processing, one on subsequent paraffin sections, and failed to detect two (one of ten and one of 17 positive nodes). If the technique had been used during operation to select patients for axillary clearance, 29 of 50 would have avoided the operation, one of two node-positive patients would have required delayed axillary treatment and two of 21 with minimal axillary disease would not have received further axillary treatment or adjuvant therapy. The technique may be useful in reducing the morbidity of breast cancer surgery without increasing the risk of locoregional or distant recurrence.

Adult

Gastritis in patients on non-steroidal anti-inflammatory drugs.

This study investigated the spectrum of gastric mucosal pathology, including the prevalence of reactive gastritis in patients on non-steroidal anti-inflammatory drugs (NSAIDs). The histological findings were correlated with upper gastrointestinal symptom status and endoscopic findings and were also compared with the histological appearances of the gastric mucosa in a corresponding age-matched control group of 75 patients not receiving NSAIDs or any other drug therapy. Reactive gastritis of the gastric antrum was more common in the NSAID group and was observed in 34 patients (45.3%), as an isolated phenomenon in 24 patients (32%) and with evidence of coexistent chronic gastritis in 10 patients (13.3%). In the control group reactive gastritis of the antrum was seen in 10 patients (13.3%), as an isolated finding in eight cases (10.7%) and with accompanying chronic gastritis in two cases. Chronic antral gastritis of usual type was observed in 36 patients on NSAIDs (48%) and Helicobacter-like organisms were identified histologically in 18 of these (50% carriage rate). These organisms were not seen in any of the patients in whom the picture of reactive gastritis was present. In the control group chronic antral gastritis was seen in 51 patients (68%) with organisms in 34 (66.6% carriage rate). No correlation was found between the presence or absence of upper gastrointestinal symptoms, endoscopic findings and the histological appearances of the gastric mucosa. We conclude that NSAIDs are an independent cause of reactive gastritis in the antrum and do not appear to alter gastric mucosal colonization by Helicobacter-like organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

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