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Biomedical subjects

R M Feakins

Publications and source records attributed to R M Feakins.

At least 19 recordsLinked to original sources
PubMed2005

Preliminary findings from tests of a microwave applicator designed to treat Barrett's oesophagus.

Barrett's oesophagus is considered to increase the risk of cancer 30-fold. Helical microwave antennas have been developed for ablative treatment of Barrett's. A microwave balloon applicator was tested in an initial animal study using adult white pigs. For treatment, a balloon filled with tissue-equivalent material encapsulated the antenna. A range of different treatment temperatures and durations was used to investigate a range of thermal ablations of the oesophageal epithelium. Eight animals were investigated, five non-survival and three with a 1-week survival period. The balloon was fitted with an array of temperature sensors, which gave an indication of the treatment in situ and allowed modifications to be performed in real time. Temperature data were recorded from all four quadrants of the balloon throughout and test sites were collected and analysed histologically. All experiments were successfully completed without perforation, serious adverse effects or death. Sites of discrete ulceration were induced in the survival tests, whereas the non-survival tests yielded little reproducible tissue modification. Results suggested that an activation temperature of approximately 55 degrees C needed to be reached during the treatment for tissue damage to be induced. Once damage had been triggered the severity was related to the mean temperature attained during the treatment period. A mean temperature of 52 degrees C or more resulted in substantial damage, whilst a mean temperature of approximately 50 degrees C resulted in the desired surface damage with sparing of subjacent tissues.

Animals↗
PubMed2005

Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial.

BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease, and to increase disease activity. AIM: To study prospectively the effects of oral iron in patients with and without inflammatory bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non-inflammatory bowel disease controls, all with iron deficiency anaemia, were assessed with symptom diaries, a quality of life questionnaire (Inflammatory Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood tests to measure iron repletion, disease activity and antioxidant capacity before and after starting 4 weeks of oral iron. In patients with ulcerative colitis, sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite production were performed before and after iron therapy. RESULTS: All groups showed increases in haemoglobin and ferritin. Iron intolerance occurred in about a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease patients had a relapse during treatment. Symptoms worsened in ulcerative colitis, but not in Crohn's disease or non-inflammatory bowel disease patients; Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis. Laboratory markers of disease activity, sigmoidoscopic scores, histological scores, antioxidant capacity levels and reactive oxygen metabolite production did not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny minority of inflammatory bowel disease patients relapse in association with use of oral iron therapy.

Administration, Oral↗
PubMed2005

The expression of p53 and bcl-2 in gastrointestinal stromal tumours is associated with anatomical site, and p53 expression is associated with grade and clinical outcome.

AIMS: To compare the expression of p53 and bcl-2 in gastrointestinal stromal tumours (GISTs) with anatomical site, National Institutes of Health (NIH) risk category (grade), pathological features, and clinical outcome. METHODS AND RESULTS: The immunohistochemical expression of p53 and bcl-2 in 105 GISTs (71 gastric, 20 small intestinal, four colonic, 10 rectal) was recorded. When all GISTs were assessed, there was p53 positivity in 28% and bcl-2 positivity in 77%. Gastric tumours had a lower prevalence of p53 positivity (20%) than intestinal (40-50%). Rectal GISTs had the lowest prevalence of bcl-2 positivity (20%) and gastric and small intestinal the highest (80% and 90%, respectively). In GISTs from all sites, p53 positivity was associated with size > 50 mm, epithelioid cell shape, nuclear atypia, mucosal invasion, and mitotic count > 5/50 high-power fields. In gastric GISTs the associations were the same, apart from size and mitotic count. In GISTs from all sites and in gastric GISTs, p53 expression correlated with NIH risk category. When GISTs from all sites were subjected to univariate survival analysis, an adverse outcome was associated with p53 positivity, NIH risk category, and several established prognostic factors. When gastric GISTs were assessed, the associations were similar although size was not prognostic. In multivariate survival analysis, p53 expression was independently prognostic for gastric GISTs in some models, while it was never independently prognostic for GISTs from all sites. Whether all GISTs or gastric GISTs were assessed, bcl-2 showed no association with clinical outcome or risk category. CONCLUSIONS: Anatomical site influences p53 and bcl-2 expression in GISTs. p53 expression is associated with NIH risk category, various pathological features, and clinical outcome, and may be independently prognostic for gastric GISTs. Bcl-2 expression has no prognostic value.

Colon↗
PubMed2004

Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis.

BACKGROUND: The herbal preparation, aloe vera, has been claimed to have anti-inflammatory effects and, despite a lack of evidence of its therapeutic efficacy, is widely used by patients with inflammatory bowel disease. AIM: To perform a double-blind, randomized, placebo-controlled trial of the efficacy and safety of aloe vera gel for the treatment of mildly to moderately active ulcerative colitis. METHODS: Forty-four evaluable hospital out-patients were randomly given oral aloe vera gel or placebo, 100 mL twice daily for 4 weeks, in a 2 : 1 ratio. The primary outcome measures were clinical remission (Simple Clinical Colitis Activity Index </= 2), sigmoidoscopic remission (Baron score </= 1) and histological remission (Saverymuttu score </= 1). Secondary outcome measures included changes in the Simple Clinical Colitis Activity Index (improvement was defined as a decrease of >/= 3 points; response was defined as remission or improvement), Baron score, histology score, haemoglobin, platelet count, erythrocyte sedimentation rate, C-reactive protein and albumin. RESULTS: Clinical remission, improvement and response occurred in nine (30%), 11 (37%) and 14 (47%), respectively, of 30 patients given aloe vera, compared with one (7%) [P = 0.09; odds ratio, 5.6 (0.6-49)], one (7%) [P = 0.06; odds ratio, 7.5 (0.9-66)] and two (14%) [P < 0.05; odds ratio, 5.3 (1.0-27)], respectively, of 14 patients taking placebo. The Simple Clinical Colitis Activity Index and histological scores decreased significantly during treatment with aloe vera (P = 0.01 and P = 0.03, respectively), but not with placebo. Sigmoidoscopic scores and laboratory variables showed no significant differences between aloe vera and placebo. Adverse events were minor and similar in both groups of patients. CONCLUSION: Oral aloe vera taken for 4 weeks produced a clinical response more often than placebo; it also reduced the histological disease activity and appeared to be safe. Further evaluation of the therapeutic potential of aloe vera gel in inflammatory bowel disease is needed.

Administration, Oral↗
PubMed2003

Expression of heat shock protein 32 (hemoxygenase-1) in the normal and inflamed human stomach and colon: an immunohistochemical study.

Heat shock protein 32 (Hsp32, hemoxygenase-1) is induced by reactive oxygen metabolites (ROM) and degrades heme leading to the formation of antioxidant bilirubin. Increased mucosal generation of ROM occurs in gastritis and inflammatory bowel disease. We aimed to assess mucosal expression of Hsp32 in normal stomach and colon and to test the hypothesis that disease-related differential expression occurs in inflamed tissue. Gastric body and antral mucosal biopsies were obtained from 33 patients comprising Helicobacter pylori-negative normal controls (n = 8), H pylori-negative gastritis patients (n = 11), and H pylori-positive gastritis patients (n = 14). Forty-seven archival colonic mucosal biopsies selected comprised normal histology (n = 10), active ulcerative colitis (UC) (n = 9), inactive UC (n = 8), active Crohn's disease (CD) (n = 8), inactive CD (n = 6), and other colitides (n = 6). Hsp32 expression in formalin-fixed sections was assessed by avidin-biotin peroxidase immunohistochemistry using a polyclonal rabbit anti-Hsp32 as the primary antibody. Immunohistochemical staining identified Hsp32 in all groups. Diffuse cytoplasmic staining was seen in gastric and colonic epithelial and lamina proprial inflammatory cells. Staining scores for Hsp32 were higher in antral H pylori-positive (P = 0.002) and H pylori-negative (P = 0.02) gastritis than in controls and in body H pylori-positive gastritis than in the other 2 groups (P < 0.01). Expression of Hsp32 was increased in active UC compared with inactive disease (P = 0.03) and normal controls (P = 0.02). In conclusion, Hsp32 is expressed constitutively in normal gastric and colonic mucosa, and differential expression occurs in these tissues when they are inflamed. Upregulation of Hsp32 may be an adaptive response to protect mucosa from oxidative injury in patients with gastritis and inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed2002

Thromboxane synthase immunohistochemistry in inflammatory bowel disease.

BACKGROUND: Thromboxanes are produced in excess in inflammatory bowel disease. Preliminary reports suggest that ridogrel, a thromboxane synthase inhibitor, is anti-inflammatory and may have therapeutic benefits in patients with ulcerative colitis. AIMS: To investigate the immunohistochemical expression of thromboxane synthase in the colorectal mucosa of patients with inflammatory bowel disease. METHODS: Immunostaining of colonic biopsies from patients with inflammatory bowel disease (n = 13) and controls (n = 5) was performed using a monoclonal antibody to human thromboxane synthase. The extent of staining in cells of the lamina propria was compared in patient and control groups, and was assessed in relation to disease activity scored macroscopically and histologically. RESULTS: The percentage of cells in the lamina propria staining for thromboxane synthase was higher in patients with active inflammatory bowel disease than in those with inactive disease or in controls (p = 0.02 and p = 0.002, respectively). There was a direct correlation between disease activity, measured endoscopically and histologically, and the percentage of lamina propria cells staining for thromboxane synthase (R = 0.71, p = 0.001 and R = 0.72, p = 0.001, respectively). CONCLUSIONS: Increased thromboxane synthase expression in lamina propria cells occurs in active inflammatory bowel disease. It is possible that this results in increased thromboxane synthesis, which may in turn contribute to mucosal inflammation and intramucosal thrombogenesis.

Adult↗
PubMed2000

p27(Kip1) loss does not predict survival in patients with advanced gastric carcinoma.

BACKGROUND: p27(Kip1) is a cyclin-dependent kinase inhibitor whose loss is associated with disease progression and an unfavorable outcome in several malignancies. The authors studied its expression in a consecutive series of resected gastric carcinomas. METHODS: Expression of p27(Kip1) in 71 advanced gastric carcinomas and 10 lymph nodes containing metastases was determined using an avidin-biotin-peroxidase immunohistochemical method. The relations between p27(Kip1) expression and pathologic features, patient characteristics, and survival were analyzed. RESULTS: p27(Kip1) levels in gastric carcinomas ranged from 0.63-82.97% (median, 23. 10%; mean, 27.99%). There was no association found between p27(Kip1) expression and patient gender (P = 0.21), patient age (P = 0.13), tumor stage (P = 0.17), tumor grade (P = 0.22), or histologic type (P = 0.72). Univariate analysis showed that long term survival was related to stage (P < 0.0001) and grade (P = 0.03). However, tumors with p27(Kip1) levels above and below the median value were associated with a similar outcome, regardless of whether all cases (P = 0.19) or those without metastatic disease (P = 0.50) or those with residual or metastatic disease (P = 0.92) were included. When entered into a multivariate analysis, stage (P < 0.0001) and grade (P = 0.05), but not p27(Kip1) levels (P = 0.16), were found to be related to patient outcome. In lymph node metastases, p27(Kip1) expression (median, 16.5%) was similar to that found in the corresponding primary lesion (median, 30.9%). CONCLUSIONS: p27(Kip1) may play a role in the pathogenesis and progression of gastric carcinoma, but its expression is unlikely to be useful as a prognostic indicator, at least in European patients with advanced disease.

Adult↗
PubMed2000

Congenital gastrointestinal stromal tumour is morphologically indistinguishable from the adult form, but does not express CD117 and carries a favourable prognosis.

AIMS: The histological and immunohistochemical features of a congenital stromal tumour of the jejunum are compared with those of adult gastrointestinal stromal tumours (GIST). The literature concerning the diagnosis and prognosis of congenital small intestinal stromal tumours is reviewed. METHODS AND RESULTS: A term female infant presented with intestinal obstruction, from birth. Histology of a 15-mm jejunal nodule showed a predominantly spindle-cell tumour with epithelioid areas. There was a low mitotic count and mild nuclear pleomorphism, extensive necrosis and haemorrhage, and focal calcification. Immunohistochemically, tumour cells stained for muscle specific actin and vimentin. Staining for CD117 (c-kit), S100, desmin and CD34 was negative. The features were compared to those of seven adult cases: no morphological feature was specific to the congenital tumour, which was smaller than the adult cases. There were no ultrastructural features specific for a particular line of differentiation. Immunohistochemical staining patterns were similar, except for CD117, which was strongly positive in all adult tumours, but negative in the congenital tumour. CONCLUSIONS: This congenital jejunal stromal tumour morphologically resembled adult GIST, but lack of c-kit expression suggests that it is nosologically distinct. Despite the presence of histological features which would cause the tumour to be categorized as malignant in an adult, it is apparent from previous reports of congenital small intestinal stromal tumours that the prognosis is favourable.

Actins↗
PubMed2000

Platelet-derived growth factor expression in phyllodes tumors and fibroadenomas of the breast.

The development of normal breast tissue and the pathogenesis of various tumors are influenced by growth factor-mediated epithelial-stromal interactions. Similar interactions may occur in fibroepithelial breast tumors. We have studied the expression of platelet-derived growth factor (PDGF) and PDGF beta receptor (PDGFRbeta) in 46 phyllodes tumors (18 benign, 15 borderline, 13 malignant), 11 fibroadenomas, and 6 samples of normal breast. There was neoplastic stromal cell positivity for PDGFRbeta in almost 50% of phyllodes tumors and for PDGF in 24%. Both were associated with prominent nuclear pleomorphism (P<.01), PDGF with high grade (P<.01), and a higher mean Ki-67 labeling index (P = .013), and PDGFRbeta with conspicuous stromal overgrowth (P<.01). Co-positivity for stromal PDGF and PDGFRbeta was found in 15% of phyllodes tumors, and for epithelial PDGF and stromal PDGFRbeta in 43%. Both types of co-positivity were associated with prominent nuclear pleomorphism and the latter type with conspicuous stromal overgrowth (all P<.01). Follow-up of 41 phyllodes tumors showed that disease-related death was associated with established histologic features of malignancy including mitotic count, stromal overgrowth, an infiltrative tumor margin, and nuclear pleomorphism. In addition, stromal PDGFRbeta positivity (P =.013) and epithelial PDGF/stromal PDGFRbeta co-positivity (P =.0075) were associated with disease-related death. Stromal PDGF and PDGFRbeta expression in fibroadenomas was less common and less extensive (P<.05) than in phyllodes tumors. The results suggest that PDGF influences the pathogenesis of fibroepithelial breast tumors and that PDGF-dependent paracrine and autocrine mechanisms may operate. Also, it is possible that assessment of PDGF and PDGFRbeta expression could contribute to the management of these tumors in the future.

Breast↗
PubMed2000

Measurement of in vivo rectal mucosal cytokine and eicosanoid production in ulcerative colitis using filter paper.

BACKGROUND: Excessive mucosal generation of cytokines and eicosanoids has been reported in vitro in ulcerative colitis (UC) using traumatising biopsy techniques, and in vivo using time consuming rectal dialysis. AIMS: To validate a simple filter paper technique to profile rectal mucosal production of cytokines and eicosanoids in vivo in patients with UC compared with controls. PATIENTS: Forty one patients with UC (21 with active disease) and 16 controls were studied. METHODS: In vitro, recovery of known concentrations of cytokine or mediator applied to filter papers was measured by ELISA following incubation in buffer. In vivo, patients and controls had filter papers apposed to the rectal mucosa briefly through a rigid sigmoidoscope. Filter papers were then incubated prior to assay by ELISA. RESULTS: In vitro validation studies showed that the filter paper technique could be used to measure mucosal release of interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), thromboxane B(2) (TXB(2)), and prostaglandin E(2) (PGE(2)), but not interferon gamma (IFN-gamma). Mucosal release of IL-1beta, TNF-alpha, TXB(2) and PGE(2) were significantly increased in active UC (p=0.001) and correlated directly with disease activity (p=0.02). CONCLUSIONS: The filter paper technique confirmed increased rectal mucosal release of cytokines and eicosanoids in UC, in proportion to disease activity. The simplicity, safety and speed of the technique make it a practicable option for use in the outpatient clinic to study the pathogenesis of inflammatory bowel disease, and potentially its response to treatment.

Adult↗
PubMed1999

p53 expression in phyllodes tumours is associated with histological features of malignancy but does not predict outcome.

AIMS: To study p53 protein expression in phyllodes tumours of the breast, with particular attention to its prevalence and to its relationship with histological features and clinical outcome. METHODS AND RESULTS: Stromal and epithelial p53 immunohistochemical expression was studied in 57 phyllodes tumours (27 benign, 17 borderline, 13 malignant) using an avidin-biotin peroxidase method. High levels of expression (> 30% of stromal nuclei) were found in eight phyllodes tumours (14%). p53 expression was associated with tumour grade (P = 0.001), prominent stromal overgrowth (P = 0.0003), prominent stromal nuclear pleomorphism (P = 0.006), high stromal mitotic count (P = 0.05), and an infiltrative tumour margin (P = 0. 05). Six patients were lost to follow-up after surgery. Mean follow-up time of the remaining 51 patients was 7.3 years (median 4. 3, range 0.5-25) or until death. Sixteen patients (31%) experienced tumour recurrence. Recurrence was more likely if there was an infiltrative tumour margin (P = 0.006) or prominent stromal overgrowth (P = 0.04) but not p53 expression (P = 0.55). A minority of recurrences expressed p53 more extensively than their primary counterparts. There were five tumour-related deaths (10% of patients). Death was associated with high grade (P = 0.0002), prominent stromal overgrowth (P = 0.0001), an infiltrative margin (P = 0.0002), prominent nuclear pleomorphism (P = 0.005), a high mitotic count (P = 0.01) and tumour size (P = 0.03). Again, p53 expression was not associated with tumour-related survival (P = 0. 13). CONCLUSIONS: p53 abnormalities occur in a minority of borderline and malignant phyllodes tumours. p53 expression is associated with known negative prognostic factors, but does not appear to be a useful determinant of tumour recurrence or long-term survival.

Adolescent↗
PubMed1999

Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?

The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine.

Adolescent↗
PubMed1998

Appendiceal inflammation in ulcerative colitis.

AIMS: Previous uncontrolled reports have suggested that appendiceal inflammation may occur as a discontinuous lesion in ulcerative colitis. This study aims semiquantitatively to compare the prevalence and histological features of appendiceal inflammation in patients with ulcerative colitis and Crohn's disease, using colonic carcinoma and acute appendicitis specimens as controls. METHODS AND RESULTS: Surgical pathology records and original histological slides for the period 1980-1994 were examined. The prevalence of appendiceal inflammation in ulcerative colitis (24/50, 48%), was higher than in colonic carcinoma (5/65, 8%, P < 0.001), but was similar to that in Crohn's disease (14/27, 52%). Appendiceal inflammation with caecal sparing was seen in nine out of 24 specimens with ulcerative colitis (37%), two out of nine (22%) with Crohn's disease and five out of 65 (8%) with colonic carcinoma. Inflamed appendixes from patients with inflammatory bowel disease showed histological features typical of ulcerative colitis and Crohn's disease rather than acute appendicitis and were significantly less likely to have transmural inflammation. There had been a previous appendicectomy in 3% of ulcerative colitis patients compared with 8% of colonic carcinoma specimens and 21% (P < 0.01) Crohn's disease controls. CONCLUSION: In ulcerative colitis, as in Crohn's disease, appendiceal inflammation commonly occurs as a skip lesion and histologically resembles the colonic disease rather than acute appendicitis. The low prevalence of appendicectomy supports the hypothesis that the appendix itself may have a central role in the pathogenesis of ulcerative colitis.

Adolescent↗
PubMed1997

Basal cell carcinoma of the vulva: a clinicopathologic study of 45 cases.

Basal cell carcinoma (BCC) of the vulva is rare, accounting for 4.9% of primary vulvar cancers in our material. We present a study of 45 of these cases. Patients' age at presentation ranged from 60 to 92 years (mean 76 years). Symptoms were not specific, the most common being vulvar pruritus, and no specific etiological factors were apparent. Delayed treatment was frequent. The gross appearance was of a nodule or polyp, ulcer, or area of pigmentation or depigmentation; few were diagnosed as BCC before microscopic examination. Histologically, almost half were of infiltrative type, none was of morpheic type, and six contained areas of adenoid BCC. There were lymph node metastases from one large, deeply invasive BCC. After follow-up of 1 to 112 months (mean 59 months), four (9%) tumors recurred, three of which had been incompletely excised. The metastasizing tumor recurred locally after 23 months, despite apparent complete excision, and resulted in the only death from disease. Unrelated disease killed 19 patients, and 25 were alive at last follow-up. Our findings indicate that vulvar BCC usually behaves in a benign fashion, but is potentially fatal.

Aged↗