Patient choice of treatment for postpartum depression: a pilot study.

OBJECTIVE: The lack of systematic efficacy research makes the selection of optimal treatment for postpartum depression (PPD) difficult. Moreover, the treatment decisions for women with PPD who are breastfeeding are heavily influenced by their concerns about infant exposure to antidepressant medication. The objective of this pilot trial was to examine the clinical characteristics of women with PPD associated with treatment selection. METHOD: This open pilot trial offered 23 women with PPD one of 3 treatment options: sertraline, interpersonal psychotherapy (IPT), or their combination administered in an outpatient mental health setting over 12 weeks. Baseline and treatment outcome measures included the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI) and the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Completers across all 3 treatment groups (n = 18) experienced significant clinical improvement with each of the 3 treatment modalities on the HRSD (p < 0.001), BDI (p < 0.001) and EPDS (p < 0.001). There were trends for women with a prior depression to more frequently choose sertraline as a treatment (alone or with IPT, p = 0.07), and for women who were breastfeeding to choose sertraline (alone or with IPT, p = 0.10) less frequently. CONCLUSION: In this small sample of women with PPD, most women chose IPT with or without sertraline. A larger randomized study could further confirm the suggested predictors of treatment selection identified in this study: previous depression and breastfeeding status.

Pre-pouch ileitis: a disease of the ileum in ulcerative colitis after restorative proctocolectomy.

OBJECTIVE: Ileal inflammation in ulcerative colitis can occur as backwash ileitis or prestomal ileitis. After restorative proctocolectomy (RPC), ileal inflammation may be present in the pouch (pouchitis) but inflammation proximal to the pouch in the neo-terminal ileum, so called pre-pouch ileitis (PI), has also been observed. As pouchitis is increasingly common and PI can mimic it, our aim was to characterize this condition. SUBJECTS AND METHODS: A review of prospectively collected data on 571 inflammatory bowel disease patients undergoing follow-up after RPC in a single centre over 22 years was performed. The histology of biopsy material was reviewed and staining for colonic mucosal phenotypic changes was undertaken. It was not routine practice to prospectively assess all patients for pre-pouch ileitis when the database was constructed. RESULTS: Of 19 patients with inflammation of the pre-pouch neo-terminal ileum (NTI) identified three had Crohn's disease and one a NSAID stricture. The remaining 15 had a characteristic diffuse inflammation extending from the NTI-pouch junction proximally: pre-pouch ileitis. The inflammation extended proximally for up to 50 cm. Fistula formation was seen in only one. Seven (47%) of 15 had pouchitis but only two had suffered backwash ileitis pre-operatively. Seven responded to medical therapy and four to surgery. The histological appearances including staining for colonic phenotypic change were similar in PI and pouchitis. CONCLUSION: Pre-pouch ileitis is uncommon. As the patients' previous diagnosis of UC was confirmed and there was no radiological or histological evidence of Crohn's disease, PI appears to have a distinct pathogenesis from Crohn's disease.

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.

BACKGROUND AND AIMS: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. PATIENTS AND METHODS: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. RESULTS: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24-3.70)), strictures (OR 4.22; 1.08-15.54), shortened colons (OR 10.0; 1.17-85.6), tubular colons (OR 2.03; 1.00-4.08), or segments of severe inflammation (OR 3.38; 1.41-10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21-0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19-0.73), post-inflammatory polyps (2.29; 1.28-4.11), and strictures (4.62; 1.03-20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. CONCLUSIONS: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis.

BACKGROUND AND AIMS: Colonoscopic surveillance for cancer in longstanding extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies. Chromoendoscopy can aid detection of subtle mucosal abnormalities. We hypothesised that routine pancolonic indigo carmine dye spraying would improve the macroscopic detection of dysplasia and reduce the dependence on non-targeted biopsies. PATIENTS AND METHODS: One hundred patients with longstanding extensive ulcerative colitis attending for colonoscopic surveillance underwent "back to back" colonoscopies. During the first examination, visible abnormalities were biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic indigo carmine (0.1%) was used during the second colonoscopic examination, and any additional visible abnormalities were biopsied. RESULTS: Median extubation times for the first and second colonoscopies were 11 and 10 minutes, respectively. The non-targeted biopsy protocol detected no dysplasia in 2904 biopsies. Forty three mucosal abnormalities (20 patients) were detected during the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both were considered to be dysplasia associated lesions/masses. A total of 114 additional abnormalities (55 patients) were detected following dye spraying, of which seven (five patients) were dysplastic: all were considered to be adenomas. There was a strong trend towards statistically increased dysplasia detection following dye spraying (p = 0.06, paired exact test). The targeted biopsy protocol detected dysplasia in significantly more patients than the non-targeted protocol (p = 0.02, paired exact test). CONCLUSIONS: No dysplasia was detected in 2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine dysplastic lesions, seven of which were only visible after indigo carmine application. Careful mucosal examination aided by pancolonic chromoendoscopy and targeted biopsies of suspicious lesions may be a more effective surveillance methodology than taking multiple non-targeted biopsies.

Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading.

BACKGROUND AND AIMS: Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers. METHODS: After redefining atrophy as the 'loss of appropriate glands' and examining histological samples from different gastric compartments, three categories were identified: (i) negative; (ii) indefinite; (iii) atrophy, with and without intestinalization. Atrophy was graded on a three-level scale. Interobserver reproducibility of the classification was tested by kappa statistics (general and weighted) in a series of 48 cases. RESULTS: The medians of the general agreement and weighted kappa values were 0.78 and 0.73, respectively. The weighted kappa coefficients, obtained by cross-tabulating the evaluation of each pathologist against all others, were, with only one exception, > 0.4 (moderate to excellent agreement). CONCLUSIONS: By using the definition of atrophy as the loss of appropriate glands and distinguishing the two main morphological entities of metaplastic and non-metaplastic types, a high level of agreement was achieved by a group of gastrointestinal pathologists trained in different cultural contexts.

Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.

AIMS: To determine whether the presence and location of giant cells or granulomas in relation to crypts distinguishes between ulcerative colitis and Crohn's disease. METHODS AND RESULTS: Twenty-nine large bowel mucosal biopsy specimens showing giant cells and/or granulomas in a background more typical of ulcerative colitis than Crohn's disease were collected between 1986 and 1996. Each was subject to detailed independent analysis by three histopathologists. Follow-up of the cases was by examination of all previous and subsequent gastrointestinal surgical or biopsy material and by scrutiny of the clinical notes by a gastroenterologist. On the basis of the accumulated histological data 10 of these 29 cases were accorded the diagnosis of ulcerative colitis. In nine of these 10 cases the clinical diagnosis, where known, was in keeping with this and all nine contained only crypt-associated giant cells and/or granulomas. The tenth case contained a solitary free-standing granuloma and clinically the patient had perianal disease, suggesting that the true diagnosis was Crohn's disease. CONCLUSIONS: Isolated giant cells and well-defined epithelioid granulomas distant from crypts do not, as a rule, occur in ulcerative colitis, and hence their presence in a colonoscopic biopsy showing features of chronic inflammatory bowel disease is a strong pointer towards the diagnosis of Crohn's disease. Crypt-associated giant cells and granulomas can occur in ulcerative colitis and in themselves are unreliable features for the discrimination between Crohn's disease and ulcerative colitis.

Differential expression of cell adhesion molecules within inflamed ileal pouch mucosa: relationship to recruited cell subtypes.

INTRODUCTION: Endothelial-bound cell adhesion molecules are important in recruiting inflammatory cells to the mucosa in inflammatory bowel disease (IBD). Little is known of the expression of these molecules in relation to the recruitment of particular cell subtypes in the early course of mucosal inflammation. We therefore studied the expression of several adhesion molecules to examine their potential correlation with the cellular infiltrate in the inflamed ileal pouch, a possible disease model for ulcerative colitis. METHODS: Eleven patients (group 1) with familial adenomatous polyposis (FAP) with no evidence of ileal pouch inflammation and 14 patients (group 2) with ileal pouch inflammation (all with a prior diagnosis of ulcerative colitis) underwent pouch endoscopy with biopsy. Cryostat sections of biopsies were immunostained using a three-stage immunoperoxidase method for the adhesion molecules intercellular adhesion molecule (ICAM-1), vascular cellular adhesion molecule (VCAM-1), E-selectin and mucosal addressin cell adhesion molecule 1 (MAdCAM-1). These results were correlated with immunostaining for the cell markers CD3, CD4, CD8, CD45RO, CD14 and CD15, which were quantified by computer image analysis. RESULTS: MAdCAM-1, ICAM-1 and VCAM-1 were expressed to similar degrees on the endothelia of groups 1 and 2. In contrast, E-selectin was significantly increased in group 2 (P = 0.003) and correlated with immunostaining for CD15 (r = 0.72), CD4 (r = 0.55) and CD14 (r = 0.53). MAdCAM-1 expression did not correlate with any cell subset. CD15 was the only cell marker to be altered significantly, being increased in group 2 (P = 0.002). CONCLUSIONS: The inflammatory process seen in ileal pouch inflammation is characterized by up-regulation of E-selectin and recruitment of CD15-positive cells, emphasizing the role of neutrophil recruitment and migration to the epithelium in the pathogenesis of this condition.

Late results of selective axillary surgery based on contact cytology in women with operable breast cancer.

BACKGROUND: Interest in the possibility of intraoperative analysis of sentinel lymph nodes to select patients with operable breast cancer for immediate axillary clearance encouraged this review of a long-term experience of selective axillary surgery based on intraoperative contact cytology of conventionally sampled nodes. Survival was assessed as a potential marker for understaging. METHODS: Records of 437 patients who had surgery between 1991 and 1994 were reviewed to compare rates of axillary recurrence in patients who had contact cytology only with those who had contact cytology and axillary clearance. RESULTS: Axillary recurrence occurred in seven (3 per cent) of 219 patients who had negative contact cytology, three (4 per cent) of 75 patients who had positive contact cytology with axillary clearance and one (1 per cent) of 93 who had axillary clearance alone. In patients with positive contact cytology, 131 (78 per cent) of 168 positive nodes were in the sample specimen, which included all positive nodes on 19 occasions. Survival probability at 36, 72 and 96 months was 92, 87 and 84 per cent respectively for patients with negative contact cytology, and 85, 73 and 71 per cent for patients with positive cytology and axillary clearance. CONCLUSION: A selective approach to axillary surgery based on intraoperative contact cytology of sampled lymph nodes gave good long-term control of axillary disease.

Morphometric assessment of gastric antral atrophy: comparison with visual evaluation.

AIMS: As part of a multinational effort to reach a consensus in the definition and evaluation of atrophic gastritis, we applied morphometric techniques to 22 antral biopsy specimens examined visually by 12 experienced gastrointestinal pathologists. METHODS AND RESULTS: Atrophy was defined as loss of glands. Each pathologist graded atrophy with both non-standardized and standardized approaches. Discriminant function analyses of morphometric measurements were conducted to validate and grade atrophy. Kappa statistics were used to compare the performance of each pathologist against the group mode and against the discriminant functions' grading of atrophy. Three morphometric indexes showed significant differences among categories of atrophy utilizing non-standardized as well as standardized visual atrophy grades: (i) the ratio of glandular length to total mucosal thickness; (ii) the proportion of the secretory compartment area occupied by glands; and (iii) the number of glandular cross sections per 40x microscopic field. The discriminant function analyses verified all cases classified visually as either non-atrophic, or moderately/severely atrophic; it verified as mildly atrophic 40% of the cases classified visually as mildly atrophic; and classified the remaining 60% as moderately or severely atrophic. The kappa statistics were good or excellent for the majority of pathologists. CONCLUSIONS: The evaluation of antral atrophy, simply defined as loss of glands, can be reliable and reproducible. The visual grading of atrophy as absent, moderate and severe is entirely consistent with objective morphometric observations.

Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen.

BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS: Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS: Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS: Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments. INTERPRETATION: Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

What is the significance of muciphages in colorectal biopsies? The significance of muciphages in otherwise normal colorectal biopsies.

Muciphages (mucin-containing macrophages), first described in 1966 by Azzopardi & Evans, are a common feature of biopsies of large intestinal mucosa, even in the absence of other abnormalities such as active inflammation or evidence of chronic inflammatory bowel disease. Should they be mentioned in diagnostic reports? Do muciphages reliably indicate previous mucosal disease, now quiescent? In the following articles, Salto-Tellez & Price review what is known about muciphages and conclude that they reflect previous occult and clinically unimportant mucosal damage and that, in an otherwise normal colorectal mucosa, they have no diagnostic significance; and Shepherd draws attention to a wide range of clinically much more significant mucosal infiltrates that could be mistakenly regarded as muciphages and thus overlooked.

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

BACKGROUND: The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. AIMS: To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat. METHODS: We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a 'topical' effect and (iii) the two together, using (iv) indomethacin as a positive control. RESULTS: Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro- and microscopic appearances of intestinal ulcers were similar to indomethacin. CONCLUSIONS: These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.

Gastroduodenal mucosal vitamin-C levels in Helicobacter pylori infection.

BACKGROUND: Vitamin C is an important endogenous antioxidant, and epidemiologic evidence suggests that it may protect against the development of gastric cancer. We therefore determined mucosal vitamin-C levels in the stomach and duodenum of subjects with and without Helicobacter pylori infection. METHODS: The patients were 30 subjects undergoing routine gastroscopy for investigation of dyspepsia. High-performance liquid chromatography with electrochemical detection was used to determine mucosal ascorbic acid and total vitamin-C levels. RESULTS: In H. pylori-negative subjects with normal gastroduodenal histology the antrum contained significantly higher levels of ascorbic acid and total vitamin C than the corpus or duodenum (P < 0.05). No significant changes were seen in gastric mucosal ascorbic acid or total vitamin-C levels in the presence of H. pylori infection and related inflammation. The presence of gastric atrophy did not affect mucosal ascorbic acid or total vitamin C levels. Duodenal ascorbic acid and total vitamin-C levels did not change significantly in the presence of gastric H. pylori or duodenal inflammation. CONCLUSIONS: Although high levels of vitamin C are present in the gastroduodenal mucosa, these are not altered in the presence of H. pylori infection and inflammation. These observations suggest that the mucosal antioxidant potential of vitamin C is not impaired by H. pylori infection.

Observer agreement on the grading of gastric atrophy.

AIMS: Assessment of lesser or doubtful degrees of gastric atrophy can be difficult, especially in the antrum, since well established criteria are lacking. At the Houston Working Party on Gastritis in 1994 a visual analogue scale was designed for the grading of histopathological parameters. This was done to promote uniformity in grading by acting as a reference. The purpose of the present study was to measure interobserver variation between pathologists familiar with the Houston visual analogue scale in a specifically selected set of biopsies from patients with lesser or doubtful degrees of atrophy. METHODS AND RESULTS: Thirty cases with biopsies of the antrum and corpus from a long-term follow-up study on Helicobacter pylori gastritis comprised the current study material. The cases were selected from that study because there had been uncertainty or disagreement on the presence of gastric atrophy. The study set of haematoxylin and eosin (H & E) slides was circulated amongst gastrointestinal pathologists familiar with the visual analogue scale who were unaware of the source of the study set nor had any other clinical information. Interobserver variability was analysed using kappa statistics. The overall agreement for the grade of atrophy in antral biopsies was 0.461; the kappa value was 0.18 (95% confidence limits 0.12-0.24), which is considered poor agreement. The kappa value was nevertheless statistically significant (P < 0. 01). The overall agreement on the grade of atrophy in the corpus biopsies was apparently good (0.833), but the kappa which adjusts for chance agreement was only moderate (0.48; 95% confidence limits 0.42-0.55; P < 0.001). CONCLUSION: The studied series comprised a self-selected sample in which there was doubt about the grade of atrophy and such a sample will produce lower kappa values than a random sample of gastric biopsies. The results nevertheless confirm that better guidelines and firm criteria are needed to properly diagnose and grade gastric atrophy. It is suggested that the use of two grades, low- and high-grade atrophy, akin to that in use for grading inflammatory bowel disorder (IBD)- associated dysplasia, could improve agreement. Furthermore optimal biopsy quality with full thickness mucosa and proper orientation appears important for grading gastric atrophy.

Classification of gastritis--yesterday, today and tomorrow.

The major landmark in the recent history of gastritis was the discovery of Helicobacter pylori as the cause for approximately 90% of cases of chronic gastritis. This was followed by an attempt to rationalise classification from the many conflicting nomenclatures in existence to one, the Sydney System, that might gain more universal acceptance and allow studies from around the world to be compared. In the decade since its inception, including an appropriate update, the system has partially achieved this aim. It is based on documenting the topography of the gastritis, this reflecting the range of possible clinical outcomes and point of progress along the gastritis-metaplasia-dysplasia-carcinoma cascade. The rapidly expanding molecular knowledge about host mucosal immunology, determinants of bacterial virulence and dietary constituents makes it likely "tomorrow's" classification will be an algorithm to include several such factors. From this an exact "peptic" patient profile could be constructed. However one must also speculate that interest in gastritis and its classification could whither just as quickly as it blossomed with the advent of a successful vaccine.

Plasma free radical activity and antioxidant vitamin levels in dyspeptic patients: correlation with smoking and Helicobacter pylori infection.

BACKGROUND: The pathological processes by which Helicobacter pylori infection leads to the development of gastroduodenal disease are still incompletely understood. Oxygen-derived free radicals are important mediators of inflammation and potential carcinogens. Furthermore, dietary studies have suggested that antioxidant vitamins may protect against gastric cancer. OBJECTIVE: To determine plasma free radical activity and antioxidant vitamin levels in dyspeptic patients and to correlate the results with H. pylori infection and tobacco smoking. SUBJECTS: Forty-three patients undergoing routine endoscopy for investigation of dyspepsia. METHODS: Plasma free radical activity was determined by measurement of thiobarbituric acid-reactive substances (TBARS). Plasma samples were also assayed for the antioxidant vitamins A, C and E. Gastroduodenal biopsies were obtained from all patients for histological examination. RESULTS: Plasma TBARS levels were significantly higher in H. pylori positive versus negative subjects (P < 0.03), smokers versus non-smokers (P < 0.04) and males versus females (P < 0.01). Multiple regression analysis revealed that after correcting for male sex and smoking there was no significant association between plasma free radical activity and H. pylori infection. Smokers had significantly lower levels of plasma vitamin C than non-smokers (P< 0.05); no differences were seen in vitamin A and E levels. Gender and H. pylori infection did not significantly affect plasma antioxidant vitamin levels. Gastroduodenal disease was present in all of the smokers compared with 67% of the non-smokers (P < 0.05); 69% of the smokers were H. pylori positive versus 53% of the non-smokers. CONCLUSIONS: Tobacco smoking and male sex, both recognized risk factors for gastroduodenal disease, appear to be the major determinants of increased plasma free radical activity in dyspeptic subjects, rather than H. pylori infection. The reason for the higher prevalence of H. pylori infection and gastroduodenal disease in dyspeptic smokers is unclear but may relate to weakened antioxidant defences.

Expression of mdm2 and p53 in epithelial neoplasms of the colorectum.

AIMS: To evaluate the respective roles of mdm2 (murine double minute 2) and p53 in the development of colorectal carcinoma. METHODS: Formalin fixed, paraffin wax embedded tissues from 72 sporadic adenomas and 55 carcinomas were investigated by means of immunohistochemistry for mdm2 and p53. RESULTS: mdm2 was expressed weakly in 17 of 72 (23.6%) adenomas and in 14 of 55 (25.4%) carcinomas. p53 was expressed in 19 of 72 (26.4%) adenomas and in 23 of 55 (41.8%) carcinomas. Four adenomas and five carcinomas showed positive staining for both proteins. Overexpression of p53 in adenomas was associated with moderate and severe dysplasia but not with tumour size. No associations were found between the expression of mdm2 and either the degree of dysplasia or tumour size. In carcinomas, neither the expression of p53 nor mdm2 correlated with Dukes's stage, metastasis, or differentiation. No associations were found between the expression of p53 and mdm2 in either adenomas or carcinomas. CONCLUSIONS: Although mdm2 has been reported to be an oncogene, it does not appear to play a major role in the development of colorectal carcinoma.

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.