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Biomedical subjects

A B Price

Publications and source records attributed to A B Price.

At least 37 records · Page 2Linked to original sources

Intestinal metaplasia subtyping: evaluation of Gomori's aldehyde fuchsin for routine diagnostic use.

AIMS: Intestinal metaplasia (IM) has been implicated in the pathogenesis of gastro-oesophageal carcinoma, but because of its common occurrence, its specificity for use in cancer surveillance is low. IM subtypes characterized by mucin phenotype have been studied to try and improve specificity. METHODS AND RESULTS: On balance, type III IM seems the most promising for use in gastric cancer surveillance. The situation is problematic at the gastro-oesophageal junction where the normal occurrence of acidic mucins raises doubt on the value of subtyping. High iron diamine-Alcian blue combination (HID-AB) is commonly used for IM subtyping, but its potential toxicity and long staining period (up to 24 hours) precludes widespread clinical use. This study has compared the sulphomucin staining ability of Gomori's aldehyde fuchsin-Alcian blue combination (GAF-AB) against HID-AB for identifying and subtyping IM in gastric and oesophageal biopsies. CONCLUSIONS: Compared to HID-AB, a sensitivity of 85%, a specificity of 100% and a staining time of less than 30 minutes, shows this stain to be a simple and effective technique for identifying and subtyping IM in routine laboratories.

Biopsy↗

An unusual case of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent self-limiting attacks of joint, chest and abdominal pain associated with fever. The most serious complication in FMF is the development of amyloidosis, which usually leads to death from renal failure within a year. The use of colchicine has dramatically reduced this complication. We describe a 56-yr-old female patient with FMF in whom the arthropathy became the dominant clinical feature, resulting in the development of an erosive large and small joint arthritis during the course of the disease. The patient was treated with colchicine, but despite this, later developed amyloidosis confirmed on rectal biopsy, and chlorambucil was added to her treatment. For 10 yr, she also suffered intermittent abdominal pain and had terminal ileal changes suggestive of Crohn's disease. However, she was found to have ischaemic colitis at post mortem secondary to amyloidosis. Ischaemic bowel disease is an extremely unusual event in FMF. Other factors which may have contributed to the terminal ischaemia in this patient include anaemia secondary to blood loss and a drug-induced myelodysplasia, as well as hypotension during the final septicaemic illness. Clinicians should consider an ischaemic colitis as a possible differential diagnosis of abdominal pain in patients with FMF even in the absence of other clinical evidence of systemic amyloidosis.

Abdominal Pain↗

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

BACKGROUND: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds. AIM: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage. METHODS: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs). A dose-response study with flurbiprofen (single doses of 5, 10, 20, and 40 mg/kg) and equimolar doses of nitroxybutyl-flurbiprofen was performed; assessing their effect on intestinal permeability (at 18-20 hours), with 51Cr EDTA, and the number of pointed (< 5 mm) and longitudinal (> 5 mm) small intestinal ulcers at 24 hours. RESULTS: Flurbiprofen, but not nitroxybutyl-flurbiprofen, stimulated coupled respiration in vitro. Both drugs, however, uncoupled in vivo; in the case of nitroxybutyl-flurbiprofen possibly because hydrolysis of its ester bond released free flurbiprofen. Intestinal permeability was uniformly and equally increased with both drugs compared with controls. The number of small intestinal ulcers, pointed and longitudinal, was significantly reduced with nitroxybutyl-flurbiprofen apart from the number of longitudinal ulcers with the highest dose. CONCLUSIONS: These studies show that nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbiprofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestine, suggesting that its beneficial effect is on the later pathogenic stages of the damage.

Animals↗

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

BACKGROUND: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM: To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS: The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION: Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

Acetaminophen↗

Interchange between collagenous and lymphocytic colitis in severe disease with autoimmune associations requiring colectomy: a case report.

BACKGROUND: Collagenous colitis and lymphocytic colitis present with a similar clinical picture. Whether these conditions are separate entities or whether they represent different pathological stages of the same condition is an unresolved issue. PATIENT: This is a case of collagenous colitis following a fulminant course in which a colectomy was necessary. In the operative specimen the thickened collagen plate, which had been present only two weeks preoperatively had been lost and the pathology was of a lymphocytic colitis. Six months postoperatively this patient developed a CREST syndrome and primary biliary cirrhosis. CONCLUSIONS: This case shows the lability of the collagen plate and the common ground between collagenous and lymphocytic colitis, and presents evidence that these two conditions are different manifestations of the same disease. It also describes for the first time an association between collagenous colitis and CREST syndrome and primary biliary cirrhosis.

Autoimmune Diseases↗

Vitamin E concentrations in the human stomach and duodenum--correlation with Helicobacter pylori infection.

BACKGROUND: Vitamin E (alpha-tocopherol) is an important endogenous antioxidant and may also act as an anticarcinogen. AIM: To determine the vitamin E status of subjects with, and without, gastroduodenal inflammation and Helicobacter pylori infection. SUBJECTS: 36 patients undergoing routine gastroscopy for investigation of dyspepsia. METHODS: High performance liquid chromatography with fluorometric detection was used to determine alpha-tocopherol values. RESULTS: In H pylori negative subjects with normal gastroduodenal histology (n = 11) median alpha-tocopherol values (ng/mg tissue weight) were significantly higher in the corpus (16.4, interquartile range (IQR) 8.9-22.6) than in the antrum (3.0, IQR 2.6-6.7, p = 0.001) or duodenum (6.7, IQR 2.5-8.4, p = 0.001). H pylori infection (n = 19) was associated with a reduction in the corpus alpha-tocopherol values (median 8.3, IQR 4.9-13.7, p < 0.05) but there was no significant change in the antral concentrations although this was the main site of inflammation and neutrophil activity. Duodenal alpha-tocopherol values were not significantly changed in the presence of duodenitis or gastric H pylori infection. alpha-Tocopherol was not detected in the gastric juice of any of the subjects. Plasma alpha-tocopherol concentrations in the H pylori negative subjects (median 10.4 mg/l, IQR 7.2-11.9) were not significantly different to the values in the H pylori positive subjects (median 11.1 mg/l, IQR 7.6-12.7). CONCLUSIONS: Concentrations of alpha-tocopherol in H pylori negative subjects are higher in the corpus than in the antrum or duodenum. In the presence of predominantly antral H pylori infection and neutrophil activity the major change seen is a reduction in corpus alpha-tocopherol values while antral concentrations are maintained. These findings may reflect a mobilisation of antioxidant defences to the sites of maximal inflammation in the stomach.

Adult↗

Diagnostic difficulty arising from rectal recovery in ulcerative colitis.

AIMS: To ascertain whether the dogma that a normal rectal biopsy precludes a diagnosis of ulcerative colitis is correct. METHODS: Rectal biopsy specimens from a prospective group of 24 asymptomatic patients, with an established diagnosis of ulcerative colitis, were examined in a blinded study alongside 10 normal rectal biopsy specimens from an age and sex matched patient cohort without ulcerative colitis. Each biopsy specimen was assessed by three pathologists and ascribed to one of four categories: normal; borderline abnormality (one or more minor nonspecific abnormalities which, when combined, did not fulfil the minimal acceptable criteria for a diagnosis of ulcerative colitis); minimal features of chronic ulcerative colitis; and unequivocal ulcerative colitis. RESULTS: Two patients with ulcerative colitis had normal biopsy specimens; nine specimens were categorised as borderline abnormality, one as showing the minimal changes of chronic ulcerative colitis, and 12 as having the typical changes of chronic ulcerative colitis. Thus, 11 (46%) of the 24 patients had a rectal biopsy specimen that was devoid of the acceptable attributes on which a diagnosis is established, despite a confident previous diagnosis. Ten of these 11 cases had disease limited to the rectum. Review of all previous histological biopsy specimens (n = 164) and clinical data, including drug treatment, failed to identify any attributes that might be prognostic markers for future rectal mucosal healing. CONCLUSIONS: A normal rectal biopsy specimen, though uncommon, may occur in longstanding colitis. Moreover, in 46% of these asymptomatic but established cases the degree of healing may preclude a diagnosis of ulcerative colitis without comprehensive clinical and radiological details. Pathologists need to be aware of this minimal end of the spectrum of disease.

Adult↗

Histology of chronic gastritis with and without duodenitis in patients with Helicobacter pylori infection.

AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90.5% H pylori positive), and 11 had other diagnoses. In the H pylori positive patients, the median gastritis score was higher in the duodenitis group (6, range 3-9) than in the chronic gastritis only group (5, range 2-8), because of greater neutrophil activity scores in patients with duodenitis (median score 2 v 1). There were no differences in the density of H pylori infection, inflammation, atrophy, or intestinal metaplasia between patients with chronic gastritis only and those with duodenitis. CONCLUSIONS: These results suggest that H pylori positive patients with duodenitis have a more severe form of gastritis than those without associated duodenal inflammation. This is because of increased neutrophil activity, which seems to be independent of the density of H pylori infection.

Adult↗

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↗