Prognostic markers for colorectal cancer: estimating ploidy and stroma.

Background: We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). Patients and methods: DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Results: Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001]. Conclusion: A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

Rapid infrared mapping for highly accurate automated histology in Barrett's oesophagus.

Barrett's oesophagus (BE) is a premalignant condition that can progress to oesophageal adenocarcinoma. Endoscopic surveillance aims to identify potential progression at an early, treatable stage, but generates large numbers of tissue biopsies. Fourier transform infrared (FTIR) mapping was used to develop an automated histology tool for detection of BE and Barrett's neoplasia in tissue biopsies. 22 oesophageal tissue samples were collected from 19 patients. Contiguous frozen tissue sections were taken for pathology review and FTIR imaging. 45 mid-IR images were measured on an Agilent 620 FTIR microscope with an Agilent 670 spectrometer. Each image covering a 140 µm × 140 µm region was measured in 5 minutes, using a 1.1 µm2 pixel size and 64 scans per pixel. Principal component fed linear discriminant analysis was used to build classification models based on spectral differences, which were then tested using leave-one-sample-out cross validation. Key biochemical differences were identified by their spectral signatures: high glycogen content was seen in normal squamous (NSQ) tissue, high glycoprotein content was observed in glandular BE tissue, and high DNA content in dysplasia/adenocarcinoma samples. Classification of normal squamous samples versus 'abnormal' samples (any stage of Barrett's) was performed with 100% sensitivity and specificity. Neoplastic Barrett's (dysplasia or adenocarcinoma) was identified with 95.6% sensitivity and 86.4% specificity. Highly accurate pathology classification can be achieved with FTIR measurement of frozen tissue sections in a clinically applicable timeframe.

Multi-centre Raman spectral mapping of oesophageal cancer tissues: a study to assess system transferability.

The potential for Raman spectroscopy to provide early and improved diagnosis on a wide range of tissue and biopsy samples in situ is well documented. The standard histopathology diagnostic methods of reviewing H&E and/or immunohistochemical (IHC) stained tissue sections provides valuable clinical information, but requires both logistics (review, analysis and interpretation by an expert) and costly processing and reagents. Vibrational spectroscopy offers a complimentary diagnostic tool providing specific and multiplexed information relating to molecular structure and composition, but is not yet used to a significant extent in a clinical setting. One of the challenges for clinical implementation is that each Raman spectrometer system will have different characteristics and therefore spectra are not readily compatible between systems. This is essential for clinical implementation where classification models are used to compare measured biochemical or tissue spectra against a library training dataset. In this study, we demonstrate the development and validation of a classification model to discriminate between adenocarcinoma (AC) and non-cancerous intraepithelial metaplasia (IM) oesophageal tissue samples, measured on three different Raman instruments across three different locations. Spectra were corrected using system transfer spectral correction algorithms including wavenumber shift (offset) correction, instrument response correction and baseline removal. The results from this study indicate that the combined correction methods do minimize the instrument and sample quality variations within and between the instrument sites. However, more tissue samples of varying pathology states and greater tissue area coverage (per sample) are needed to properly assess the ability of Raman spectroscopy and system transferability algorithms over multiple instrument sites.

Evaluation of a confocal Raman probe for pathological diagnosis during colonoscopy.

AIM: Raman spectroscopy of human tissue can provide a unique biochemical 'fingerprint' that alters with disease progression. Light incident on tissue is scattered and may be altered in wavelength, which can be represented as a Raman spectrum. A confocal fibreoptic Raman probe designed to fit down the accessory channel of a colonoscope has been constructed. This in-vitro study evaluated the accuracy of pathological diagnosis in the colon using probe-based Raman spectroscopy. METHOD: Biopsy samples were collected at colonoscopy, snap frozen and stored at -80 °C. Raman spectra with 10-s and 1-s acquisition periods were measured with the probe tip in contact with the mucosal surface of thawed specimens. Mathematical modelling using principal component analysis followed by linear discriminant analysis was used to correlate Raman spectra with histopathological diagnoses. RESULTS: Three-hundred and seventy-five Raman spectra were measured from a total of 356 colon biopsies (81 of normal colon mucosa, 79 of hyperplastic polyps, 92 of adenomatous polyps, 64 of adenocarcinoma and 40 of ulcerative colitis) from 177 patients. Spectral classification accuracies comparing pathology pairs ranged from 72.1 to 95.9% for 10-s acquisitions and from 61.5 to 95.1% for 1-s acquisitions. For a three-group model of normal, adenomatous and adenocarcinoma tissue, accuracies were 74.1% for 10-s acquisitions and 63.5% for 1-s acquisitions. CONCLUSION: The confocal Raman probe system can distinguish between different colorectal pathologies. The probe has potential to establish Raman spectroscopy as a clinical tool for instant diagnosis at colonoscopy.

High-Density Geometric Morphometric Analysis of Intraspecific Cranial Integration in the Barred Grass Snake (Natrix helvetica) and Green Anole (Anolis carolinensis).

How do phenotypic associations intrinsic to an organism, such as developmental and mechanical processes, direct morphological evolution? Comparisons of intraspecific and clade-wide patterns of phenotypic covariation could inform how population-level trends ultimately dictate macroevolutionary changes. However, most studies have focused on analyzing integration and modularity either at macroevolutionary or intraspecific levels, without a shared analytical framework unifying these temporal scales. In this study, we investigate the intraspecific patterns of cranial integration in two squamate species: Natrix helvetica and Anolis carolinensis. We analyze their cranial integration patterns using the same high-density three-dimensional geometric morphometric approach used in a prior squamate-wide evolutionary study. Our results indicate that Natrix and Anolis exhibit shared intraspecific cranial integration patterns, with some differences, including a more integrated rostrum in the latter. Notably, these differences in intraspecific patterns correspond to their respective interspecific patterns in snakes and lizards, with few exceptions. These results suggest that interspecific patterns of cranial integration reflect intraspecific patterns. Hence, our study suggests that the phenotypic associations that direct morphological variation within species extend across micro- and macroevolutionary levels, bridging these two scales.

Non-invasive ventilation for weaning, avoiding reintubation after extubation and in the postoperative period: a meta-analysis.

Non-invasive ventilation (NIV) is a supportive therapy that improves mortality in acute respiratory failure (RF). It may also be used in patients recently extubated in intensive care units (ICUs), after operation, and to aid weaning from mechanical ventilation (MV) by reducing the morbidity and mortality associated with further MV. A meta-analysis of the available evidence was performed on the use of NIV in three areas: weaning, reduction in reintubation rates post-extubation on ICU, and reduction in RF after major surgery. Sixteen relevant randomized controlled trials were identified by three reviewers after a detailed search of identified medical databases. A meta-analysis of summary statistics relating to predetermined endpoints (ICU and hospital length of stay, ICU and hospital mortality, reintubation, pneumonia) was performed. NIV reduced the ICU length of stay when used for weaning (5.12 days) and post-surgery (0.44 days). NIV reduced reintubation rates post-surgery [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.12-0.50] and the incidence of pneumonia in weaning (OR 0.12, 95% CI 0.05-0.31) and post-surgery (OR 0.27, 95% CI 0.09-0.77). There was insufficient evidence to suggest that NIV improves ICU survival, but an increased hospital survival in post-surgery (OR 4.54, [corrected] 95% CI 1.35-15.31) and a reduction after weaning (OR 0.55, 95% CI 0.31-0.98) [corrected] was seen. A meta analysis of NIV use in selected subgroups of recently extubated patients suggests that the judicious NIV use may reduce ICU and hospital length of stay, pneumonia, and reintubation rates and hospital survival.

New relationships between breast microcalcifications and cancer.

BACKGROUND: Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state. METHODS: A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue. RESULTS: The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P<0.001) between microcalcification chemical composition (carbonate content and protein matrix : mineral ratios) and distinct pathology grades (benign, in-situ carcinoma and ICs). Furthermore, a significant correlation (P<0.001) was observed between carbonate concentrations and carcinoma in-situ sub-grades. Using the two measures of pathology-specific calcification composition (carbonate content and protein matrix : mineral ratios) as the inputs to a two-metric discriminant model sensitivities of 79, 84 and 90% and specificities of 98, 82 and 96% were achieved for benign, ductal carcinoma in situ and invasive malignancies, respectively. CONCLUSIONS: We present the first demonstration of a direct link between the chemical nature of microcalcifications and the grade of the pathological breast disease. This suggests that microcalcifications have a significant association with cancer progression, and could be used for future objective analytical classification of breast pathology. A simple two-metric model has been demonstrated, more complex spectral analysis may yeild greater discrimination performance. Furthermore there appears to be a sequential progression of calcification composition.

Polypoid mucosal prolapse complicating low rectal adenomas: beware the inflammatory cloacogenic polyp!

AIMS: Polypoid mucosal prolapse near the anorectal junction mimics adenomas endoscopically and histopathologically. The aim was to describe the phenomenon of polypoid mucosal prolapse arising secondary to adenomas at the anorectal junction. METHODS AND RESULTS: Four cases of low rectal adenoma with polypoid mucosal prolapse were assessed histopathologically, as well as with p53 and Ki67 antibodies. Two were male and two female; the mean age was 45 years. Available follow-up has revealed no recurrence in any patient. All cases showed mucosal expansion with ulceration or erosion, crypt architectural irregularity, fibromuscular proliferation between crypts and variable epithelial serration and inflammation. Each case also showed unequivocal dysplasia, often co-mingled with features of prolapse, highlighted by p53 and Ki67 immunohistochemistry, which demonstrated positivity within dysplastic areas. CONCLUSIONS: Histopathologists must recognize the potential for adenomatous/dysplastic foci in anorectal lesions to superficially resemble inflammatory cloacogenic polyps. We recommend use of immunomarkers p53 and Ki67 to aid the interpretation of challenging cases. We believe that polypoid mucosal prolapse changes can be a secondary phenomenon, due to adenomas close to or at the anorectal junction.

Monitoring of Polycyclic Aromatic Hydrocarbons (PAHs) in Scottish Deepwater environments.

Polycyclic aromatic hydrocarbons (PAHs) were measured in environmental samples (sponges, fish and sediment) collected in 2014 and 2016 from the Faroe-Shetland Channel and Rosemary Bank Seamount. These data could be used to provide a baseline against which any changes can be assessed in the event of an oil spill and contribute to any environmental impact assessment. Concentrations in all samples were low, often below the detection limits, and were typical of reference sites. Sponges can be used as an alternative indicator species to mussels for monitoring PAHs in the marine environment as they can accumulate PAHs from both the dissolved and particulate phase. PAH concentrations in marine sponges from Scottish waters have not previously been reported. Concentrations were low, but contained a higher proportion of heavier 4- to 6-ring PAHs compared to the fish samples.

Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease.

BACKGROUND: Preliminary data have suggested that interleukin-2 receptor blockade with basiliximab may increase steroid sensitivity. We have previously reported a small case series demonstrating the potential of basiliximab as a novel agent for the treatment of steroid-resistant ulcerative colitis. AIM: To report further experience of the efficacy and safety of treatment with the interleukin-2 receptor blocking monoclonal antibody basiliximab, in addition to steroids, for the treatment of severe and moderate steroid-resistant ulcerative colitis. METHODS: Twenty patients were enrolled - 13 patients with moderate steroid-resistant ulcerative colitis (Ulcerative Colitis Symptom Score: >or=6) and seven patients with severe steroid-resistant ulcerative colitis. All were given a single dose of 40 mg basiliximab plus standard steroid therapy in an open-label, uncontrolled trial. Primary end point was clinical remission within 8 weeks (Ulcerative Colitis Symptom Score:

Restitution of contractility in single ventricular myocytes of guinea pig heart.

OBJECTIVE: Our aim was to assess the extent to which changes in intracellular Ca2+ stores contribute to mechanical restitution in heart muscle. METHODS: Single, isolated guinea pig ventricular cells were voltage clamped at -45 mV and stimulated continuously at 0.5 or 2 Hz with 200 ms depolarizing pulses (35 degrees C). The recoveries of the peak of contraction force (Fp) and the calcium current (ICa) between beats were measured in contractions interpolated at various intervals (td) after a conditioning twitch. Recovery of SR Ca2+ load was inferred from the peak magnitude (Cp) of similarly interpolated contractures, induced by rapid application of 5 mM caffeine. RESULTS: For a conditioning stimulus rate of 0.5 Hz, both Fp and ICa were very small for small td and recovered along similar time courses with a t1/2 of about 50 ms. Cp was maximal at as early a time after a previous contraction as could be measured, at which time Fp was 56% of maximal. Cp declined throughout the stimulus interval to about 50% of its maximal value. Similar results were obtained for a conditioning stimulus rate of 2 Hz, at which rate both Fp and Cp were increased by a factor of 2. CONCLUSIONS: The time course of mechanical restitution is coincident with the recovery of ICa from inactivation. Caffeine-releasable intracellular calcium stores are fully recovered soon after a contraction and well before mechanical restitution is complete.

Epithelial misplacement in Peutz-Jeghers polyps. A diagnostic pitfall.

Early difficulties with the interpretation of the histopathology caused overdiagnosis of cancer in the Peutz-Jeghers syndrome; and there is still controversy about the magnitude of risk of gastrointestinal carcinoma. Most workers now believe that there is a small but definite increase in the incidence of gastrointestinal carcinoma in Peutz-Jeghers polyps and most of these cancers occur in the upper gastrointestinal tract. In a review of 491 Peutz-Jeghers polyps in the records of St. Mark's Hospital Pathology department, misplacement of epithelium was found in approximately 10% of small intestinal polyps and closely mimicked adenocarcinoma. This "pseudoinvasion" was not observed in polyps of the stomach or colon. The epithelial misplacement may involve all layers of the bowel wall; and the most helpful histological discriminators include a lack of cytological atypia, the presence of the normal epithelial cell subtypes and a brush border, hemosiderin deposition, and intramural mucinous cysts. Epithelial misplacement may account for the overdiagnosis of carcinoma arising in Peutz-Jeghers polyps as reported in the literature.

Primary lymphoma of the small intestine. A clinicopathological study of 119 cases.

Small bowel lymphomas account for 20 to 40% of primary gut lymphomas in Western populations and are among the most common malignant tumours of the small bowel. We studied 119 cases of primary small bowel lymphoma presenting over 4 decades. Two thirds of the patients were men with a peak age incidence in the 7th decade. Common presenting features included abdominal pain, weight loss, small bowel obstruction, and acute abdomen. Tumours were classified using the Kiel European Association for Haematopathology Geneva Workshop scheme and phenotyped on paraffin sections; 66% were B cells, and 34% were T cell. In all cases, the antibodies L26 and polyclonal CD3 reliably distinguished between B- and T-cell tumours. Of the B-cell lymphomas, 62% were diffuse high grade, 20% were low-grade lymphomas of mucosa-associated lymphoid tissue, 11% had both low- and high-grade components, and 7% were other low-grade types. Of the T-cell lymphomas, 83% were high grade, and 49% were enteropathy associated. Most T-cell lymphomas were ulcerated plaques or strictures in the proximal small bowel; B-cell lymphomas tended to be annular or polypoid masses in the distal and terminal ileum. Survival data showed that low-grade B-cell lymphomas had the best outcome and T-cell lymphomas the worst. Adverse prognostic features included perforation, high-grade histology, multiple tumours and advanced stage.

Misplacement of dysplastic epithelium in Peutz-Jeghers Polyps: the ultimate diagnostic pitfall?

Peutz-Jeghers syndrome is characterized by multiple polyps throughout the gastrointestinal tract in association with mucocutaneous pigmentation. Small bowel polyps in the syndrome may exhibit epithelial misplacement, into the submucosa, the muscularis propria, and even the subserosa. The authors demonstrate two patients in whom there is also misplacement of dysplastic epithelium into the submucosa and muscularis propria of the small bowel. Epithelial misplacement is recognized to mimic invasive malignancy. Such mimicry is heightened substantially when the misplaced epithelium is dysplastic. Correct interpretation of the histologic changes is aided by the use of special stains, which demonstrate the associated lamina propria and the lack of a desmoplastic response, and immunohistochemistry, which shows that the misplaced dysplastic epithelium is accompanied by non-neoplastic mucosa. There is an increased prevalence of gastrointestinal malignancy in Peutz-Jeghers syndrome. However, the presence of perplexing histologic features, caused by epithelial misplacement, especially when some of that epithelium is dysplastic, in small bowel polyps at least has the potential for the overdiagnosis of malignancy in the syndrome.

The histopathology of treated Barrett's esophagus: squamous reepithelialization after acid suppression and laser and photodynamic therapy.

Columnar metaplasia of the lower esophageal epithelium (Barrett's esophagus) occurs in response to acid reflux, and its most important long-term complication is malignancy. In view of this, techniques are being explored for the eradication of Barrett's esophagus, and histopathologists will increasingly be required to assess response to these therapies in esophageal biopsy samples. The histopathologic features before and after treatment were studied in biopsy samples from 16 patients receiving omeprazole only, 10 treated by KTP laser photoablation, and five who underwent photodynamic therapy. All the treatment modalities resulted in histologic changes with at least partial squamous reepithelialization of the metaplastic columnar epithelium. The histologic findings suggest three main mechanisms for this: encroachment of adjacent squamous epithelium at the squamocolumnar junction, extension of epithelium from the submucosal gland duct to form squamous islands, and squamous metaplasia within the Barrett's columnar mucosa itself. The latter mechanism implies the existence of pluripotential stem cells within Barrett's mucosa. A relatively common finding was residual glandular mucosa, nonneoplastic and dysplastic, beneath squamous epithelium indicating the requirement for histologic confirmation of endoscopically suspected complete squamous reepithelialization with sufficiently deep biopsies.

Regression of columnar-lined (Barrett's) oesophagus with omeprazole 40 mg daily: results of 5 years of continuous therapy.

BACKGROUND: We have previously reported the effect of 2 years of omeprazole 40 mg daily on columnar-lined (Barrett's) oesophagus (CLO). AIMS: In the present study, follow-up has been extended to 5 years to assess the macroscopic and microscopic effects of continuing therapy. PATIENTS AND METHODS: The 23 patients have been followed for up to a further 3 years. Endoscopy with multiple biopsies was performed at the end of years 3, 4 and 5. RESULTS: Although there had been a statistically significant regression in the length of CLO after 2 years, there was no overall further measurable change after 5 years. However, one patient showed complete macroscopic and microscopic regression. The number and size of macroscopic squamous islands within the CLO continued to increase, and there was a further increase in microscopic squamous re-epithelialization of surface mucosa, gland ducts and Barrett's gland tissue. Low-grade dysplasia was found consistently in one patient in biopsies taken up to the end of year 3 but it could not be detected thereafter. CONCLUSIONS: Omeprazole 40 mg daily appears to have beneficial effects on CLO, although it rarely induces a complete regression. Whether the benefits will reduce the risk of malignant transformation is unknown.

An Eudragit-coated prednisolone preparation for ulcerative colitis: pharmacokinetics and preliminary therapeutic use.

Prednisolone metasulphabenzoate, a steroid with poor colonic absorption, was coated with the pH-dependent acrylic resin Eudragit S, as a means of delivering an orally administered preparation to the proximal colon. The therapeutic potential of delivering this steroid with potentially less systemic side-effects to the proximal colon was assessed in extensive ulcerative colitis. Plasma and urine prednisolone profiles in 6 healthy volunteers confirmed minimal absorption from Eudragit S-coated prednisolone metasulphabenzoate compared to prednisolone acetate: peak plasma prednisolone concentrations 29 +/- 21 ng/ml vs. 570 +/- 185 ng/ml (P less than 0.01), area under curve measurements 204 +/- 214 vs. 2724 +/- 1236 ng.h/ml (P less than 0.01). Prednisolone metasulphabenzoate coated with Eudragit S (30-60 mg daily) was then administered for 12 weeks to 12 patients with colonoscopically proven extensive ulcerative colitis in relapse. Symptoms, sigmoidoscopic appearances and rectal histological abnormalities all improved during therapy. Complete clinical remission occurred in 7 patients, a partial response in 2 patients and no response in 3 patients. Cortisol responses to tetracosactrin demonstrated no significant adrenal suppression following treatment. Eudragit S-coated prednisolone metasulphabenzoate may be a useful treatment for extensive ulcerative colitis, without risk of systemic steroid side-effects.

Regression of columnar lined (Barrett's) oesophagus with continuous omeprazole therapy.

Twenty-three adult patients with a columnar lined (Barrett's) oesophagus are being treated with long-term omeprazole, 40 mg daily. Twelve had never undergone anti-reflux surgery (Group 1), the other eleven having previously had insertion of an Angelchik anti-reflux prosthesis (Group 2). Endoscopy was carried out six months before, immediately before and six months, one year and two years into treatment. Multiple and standardized biopsies were taken at each endoscopy. Results from the two groups were similar. During the 6-month run-in period there was a statistically non-significant increase in the linear extent of the columnar mucosa, but this showed a progressive, statistically significant decrease during the two years of treatment. Other evidence for regression of the Barrett's mucosa includes the emergence of large numbers of macroscopic squamous islands within the abnormal mucosa, an increase in the number of microscopic squamous islands, and microscopic squamous encroachment of the abnormal mucosa at the squamo-columnar junction. Histological assessment showed a reduction in the proportion of sulphomucin-rich intestinal metaplasia, but this only achieved statistical significance in Group 1. The results substantiate the importance of acid in the pathogenesis of Barrett's oesophagus. Omeprazole may have a therapeutic role in bringing about regression of the metaplastic epithelium.

Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

BACKGROUND: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant. AIM: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study. METHODS: Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab. RESULTS: Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab. CONCLUSIONS: Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Exogenous pigment in Peyer's patches.

Dark brown granular pigment was found consistently in macrophages in the deep aspect of adult Peyer's patches. Tissue sections from intestinal resections of 35 patients with a variety of pathologic diagnoses and of seven postmortem cases with no evidence of gastrointestinal disease were examined for the presence of this pigment. It was found in all patients over the age of 6 years (34 cases) but was not found in any children below that age (eight cases). Scanning electron microscopy with secondary and backscattered electron imaging and x-ray energy spectroscopy were performed on routine histologic sections. The pigmented macrophages contained aluminum and silicon, diffusely present throughout the cytoplasm, and numerous discrete foci of titanium. Pigment containing these same elements has also been found around dilated submucosal lymphatics, in mesenteric lymph nodes, and in some transmural inflammatory aggregates of Crohn's disease. The pigment probably is derived from the diet and actively taken up by Peyer's patches, which are able to incorporate inert particulate matter.