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Biomedical subjects

P D Fairclough

Publications and source records attributed to P D Fairclough.

At least 19 recordsLinked to original sources
PubMed2005

Endoscopic ultrasound in the localisation of pancreatic islet cell tumours.

The role of endoscopic ultrasound (EUS) in the evaluation of entero-pancreatic endocrine tumours has evolved in conjunction with advances in other imaging methods. The high spatial resolution of this technique allows the detection of very small lesions and their precise anatomical localisation. In patients with biochemically proven insulinoma, EUS can be effectively used as a first line investigation, with a sensitivity of 94%. Combined with thin section CT, the sensitivity rises to 100%. There is also high sensitivity in diagnosing intrapancreatic gastrinomas but lower for those arising in the duodenal wall which require detailed duodenal evaluation at surgery. EUS in conjunction with Somatostatin Receptor Scanning (SRS) has a combined sensitivity of 93% for gastrinomas. EUS is recommended for screening of asymptomatic patients with genetically proven MEN1. There is a limited role for EUS guided biopsy in pancreatic endocrine tumours.

Endosonography↗
PubMed2002

Expression of 25-hydroxyvitamin D-1-alpha-hydroxylase mRNA in individuals with colorectal cancer.

Vitamin D prevents proliferation, promotes differentiation, and induces apoptosis of colon cells, and reduced intake or insufficiency of the vitamin in the body are associated with increased risk of colorectal cancer. Results of previous studies have suggested that mRNA that codes for 25-hydroxyvitamin D-1-alpha-hydroxylase (1 alpha OHase), which converts 25-hydroxyvitamin D to its active metabolite, might be up regulated in human colon carcinomas. We used real-time reverse transcription PCR assays to measure absolute 1 alpha OHase mRNA concentrations in the colonic mucosa of 44 individuals without cancer, and in paired healthy colon and cancerous colon samples taken from 27 individuals with the disease, to ascertain whether or not such up regulation takes place. Our results suggest that concentrations of 1 alpha OHase mRNA in tumour samples and in healthy colon samples from individuals without cancer are similar, but that concentrations are significantly lower in the paired, phenotypically healthy mucosa of individuals with cancer.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2001

Changing patterns of sedation use for routine out-patient diagnostic gastroscopy between 1989 and 1998.

BACKGROUND: Knowledge of sedation trends for upper gastrointestinal endoscopy is important for health service planning, particularly in view of rapidly increasing demands on endoscopy services. However, no data are available on sedation trends in Britain over the past 10 years. AIM: To determine sedation use for routine gastroscopy in a single endoscopy unit between 1989 and 1998. METHODS: This was a retrospective study of 9795 consecutive adults (mean age 56 years, range 18-100 years; 4512 females) who had undergone a gastroscopy between 1989 and 1998. Clinical, pharmacological and endoscopic data were retrieved from a computerized database. RESULTS: Over the 10-year study period, the sedation rate remained constant for patients undergoing therapeutic endoscopy (P=0.99) and those undergoing in-patient diagnostic examinations (P=0.63). In contrast, the sedation rate for out-patient diagnostic endoscopy decreased by 54%, from a high of 70% in 1990 to 32% in 1998 (P < 0.0001). Logistic regression analysis showed that the decline in sedation use was greater in females (P < 0.0001) than males and in procedures performed by non-consultant compared to consultant staff (P=0.01). CONCLUSIONS: If our results form part of a national trend, they will have important implications for cardiopulmonary monitoring strategies, recovery room practices and for complication rates due to the use of sedation for upper gastrointestinal endoscopy.

Adolescent↗
PubMed2001

Increased levels of insulin-like growth factor binding protein-2 in sera and tumours from patients with colonic neoplasia with and without acromegaly.

OBJECTIVE: Patients with acromegaly are at increased risk of developing colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of these neoplasms could involve a stimulatory effect of serum growth factors on colonic epithelial cell proliferation. The aim of this study was to evaluate changes in (1) serum IGF-I, IGF-II, IGFBP-3 and IGFBP-2 and (2) changes in local expression of IGFBPs and p53 in colonic epithelium in patients with colonic neoplasia with and without acromegaly. DESIGN: A cross-sectional retrospective study was performed. Fasting serum samples were obtained at the time of colonoscopy for patients with acromegaly and at the time of surgery for patients with colonic neoplasia without acromegaly. MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured using specific immunoassays. Tissue expression of IGFBP-2, IGFBP-3 and p53 status were determined by immunohistochemistry. PATIENTS: Group 1: 26 age- and sex-matched control subjects (range 40-69 years); group 2: 18 patients with acromegaly without colonic neoplasia (range 39-68 years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41-74 years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic neoplasia without endocrine disease (range 43-91 years, four = adenoma, 15 = carcinoma). Immunohistochemical staining of colonic biopsies was performed for IGFBP-2, IGFBP-3 and p53 in groups 3 and 4. RESULTS: Mean serum IGF-I and IGFBP-3 levels were significantly elevated in group 2 (371 +/- 131 microg/l and 6.5 +/- 1.8 mg/l, respectively) and group 3 (379 +/- 174 microg/l and 5.8 +/- 1.6 mg/l, respectively), and significantly reduced in group 4 (103 +/- 36 microg/l and 2.4 +/- 1 mg/l) compared to controls (165 +/- 40 microg/l and 4.7 +/- 1 mg/l; P < 0.0001, P < 0.001, respectively). However, median serum IGFBP-2 levels were significantly elevated in group 3 (P < 0.01) and group 4 (P < 0.0001). Immunostaining for IGFBP-2 showed strong areas of immunoreactivity in the cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP-3 immunostaining showed strong areas of immunoreactivity in the cytoplasm and in the nucleus of malignant and benign colonic epithelium compared to the normal epithelium. Nuclear staining for p53 was observed in three patients from group 3 (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma). CONCLUSION: Our results describe changes in IGFBP-2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation.

Acromegaly↗
PubMed2001

A prospective controlled trial of an ultrathin versus a conventional endoscope in unsedated upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: Upper gastrointestinal endoscopy is performed without sedation in many countries. Unsedated patients experience more discomfort during endoscopy than sedated patients, but few studies have examined factors which could be modified to minimize discomfort during the procedure. We assessed the effect of endoscope diameter on patient discomfort during unsedated transoral gastroscopy. PATIENTS AND METHODS: A total of 322 patients attending for unsedated endoscopy were examined using an endoscope of diameter either 6.0 mm or 9.8 mm. Patients completed a two-part questionnaire assessing tolerance of the procedure and discomfort during it. RESULTS: There was failure to complete the initial unsedated endoscopy in three of 163 patients in the 6.0 mm group and 14 of 159 in the 9.8 mm group (P = 0.009). Patients in the 6.0 mm group reported less discomfort both during endoscope insertion (P < 0.0001) and during the remainder of the procedure (P < 0.0001). 14% of patients in the 6.0 mm group indicated that they would request sedation if a further endoscopy were necessary, compared with 31% in the 9.8 mm group (P = 0.0005). CONCLUSIONS: Ultrathin endoscopes may have a role in clinical practice if randomized comparative studies with standard-bore instruments confirm that they do not compromise diagnostic quality.

Adolescent↗
PubMed2001

Factors associated with tolerance to, and discomfort with, unsedated diagnostic gastroscopy.

BACKGROUND: Identification of patients likely to experience high levels of discomfort during unsedated gastroscopy would be useful as these patients could be prospectively targeted for sedation. We prospectively assessed patient and endoscopic variables in subjects attending for endoscopy in order to identify factors associated with patients' experience of the unsedated examination. METHODS: We studied 508 patients attending for routine diagnostic gastroscopy. Clinical and endoscopic data were collected and patients completed a two-part questionnaire assessing their anxiety with, and experience of, the procedure. RESULTS: Thirty-nine subjects failed to complete the initial unsedated endoscopy. Failure to tolerate endoscopy was associated with younger age (P = 0.002) and examination with a standard-bore (> or = 9.0 mm) endoscope (P = 0.004). High levels of patient discomfort during the procedure were associated with younger age (P < 0.001), high levels of pre-endoscopic anxiety (P < 0.001), high levels of pre-endoscopic discomfort due to throat spray (P = 0.02) and examination with a standard-bore endoscope (P < 0.001). Preference for sedation during future examinations was related to female gender (P = 0.02), young age (P = 0.02), high levels of apprehension (P < 0.001), the examining doctor (P = 0.002) and use of a standard-bore endoscope (P < 0.001). CONCLUSIONS: Discrete clinical characteristics and endoscopic variables are associated with patients' experience of unsedated endoscopy. Further work might result in an algorithm for identifying patients who would benefit from sedation prior to gastroscopy.

Age Factors↗
PubMed2000

Human Peyer's patch T cells are sensitized to dietary antigen and display a Th cell type 1 cytokine profile.

Animal studies have demonstrated that feeding Ags induces regulatory (Th2, Th3) cells in Peyer's patches (PP), which migrate to the periphery and produce immunomodulatory cytokines such as IL-4, IL-10, or TGF-beta. In this work we have attempted to extend this paradigm to man by analyzing the response of human PP T cells to in vitro challenge with the common dietary Ag beta-lactoglobulin (betalg) of cow's milk. PP T cells stimulated with betalg showed enhanced proliferation compared with blood T cells from the same patient. Increased expression of CD25 and the Th1-associated chemokine receptor CCR5 was also seen on CD4(+) and CD8(+) PP T cells, but not blood T cells, stimulated with betalg. By enzyme-linked immunospot assay and RT-PCR, the PP T cell recall response to betalg and casein was dominated by IFN-gamma, with negligible IL-4, IL-5, IL-10, or TGF-beta. To help explain the PP T cell response to betalg, we examined IL-12 expression. Both IL-12p40 and -p35 transcripts were abundantly expressed in PP, but not in adjacent normal ileal mucosa. Immunoreactive IL-12p40-containing cells were present below the PP dome epithelium. Furthermore, in culture, PP, but not paired PBMC, spontaneously released IL-12p70. These results suggest that the human response to oral Ags in the gut may be different from that in rodents.

Adolescent↗
PubMed2000

Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly.

Patients with acromegaly are at increased risk of colorectal neoplasia and, by analogy with high-risk nonacromegalic patients, may require regular colonoscopic screening. However, it is unknown whether the risk is equal in all patients or whether some should be regarded as carrying a particularly high risk. The aims of this study were: 1) to establish the natural history of colorectal neoplasia in acromegaly; 2) to establish which patients are at increased risk of developing neoplasia; and 3) to elucidate the influence of insulin-like growth factor I (IGF-I) in adenoma formation. A prospective colonoscopic evaluation of the development of new premalignant adenomas in the colon was performed in 66 patients with biochemically proven acromegaly who had previously undergone colonoscopic screening and removal of all visible polyps. Twenty-five patients (38%) had a total of 37 polyps detected at the second colonoscopy: nine (14%) had at least one adenoma, and 18 (27%) had one or more hyperplastic polyps (2 patients had both). The development of new adenomas, but not hyperplastic polyps, was associated both with elevated serum IGF-I (P < 0.005) and, to a lesser extent, with a previous adenoma at the original colonoscopy (P < 0.07). In summary, patients with acromegaly and in whom serum IGF-I remains elevated and/or who have had a previous adenoma should be regarded as having an especially high risk for the development of subsequent colorectal neoplasia. Serum IGF-I seems to be implicated in the development of colorectal neoplasia in acromegaly, although the exact mechanisms remain uncertain.

Acromegaly↗
PubMed2000

Dilutional diarrhoea: under-diagnosed and over-investigated.

We report two cases of factitious diarrhoea caused by stool dilution. In the first report stools from a patient with chronic diarrhoea were found to have been diluted with urine, and the diarrhoea further compounded by surreptitious laxative misuse. In the second report, after prolonged investigation of high output ileostomy, the patient's ileal effluent was found to have been diluted with water. We conclude that factitious diarrhoea, in particular dilutional diarrhoea, is over-investigated and underdiagnosed. Stool weights, complete input/output measurement, analysis of stool osmolality and electrolytes, and laxative screening are essential in the investigation of chronic watery diarrhoea.

Cathartics↗
PubMed1999

Selective COX-2 inhibitors and human inflammatory bowel disease.

BACKGROUND: Much recent effort has been made to produce selective inhibitors of cyclo-oxygenase-2 (COX-2) in the belief that these will lack the gastrointestinal damaging effects of traditional non-steroidal anti-inflammatory drugs (NSAIDs). Inflammatory bowel disease is associated with increased local production of prostanoids. These prostanoids, particularly PGE2 and PGI2, may well be protective as inflammatory bowel disease is aggravated by NSAID use. AIM: To examine the effects of a traditional NSAID and a highly selective COX-2 inhibitor on the production of these prostanoids in human inflammatory bowel disease. METHODS: Colonic mucosal biopsies were obtained from patients undergoing routine colonoscopy and biopsy for diagnostic or surveillance purposes. Biopsies were incubated in culture medium containing 10% foetal calf serum and antibiotics, plus test drugs or vehicle for 24 h, after which time the medium was removed and the content of PGE2, PGI2 (measured as 6 keto-PGF1alpha) and thromboxane (Tx) A2 (measured as TxB2) determined. RESULTS: Biopsies obtained from diseased colonic mucosa produced significantly more PGE2, PGI2 and thromboxane A2 than did controls (for example, PGE2: ulcerative colitis, 4.17+/-1.06; Crohn's disease, 3.97+/-1.66; control, 0.12 +/-0.13 ng/mL, n = 8-12). These increases were inhibited to a similar extent by either a highly selective COX-2 inhibitor (L-745,337) or a traditional non-selective NSAID (indomethacin). CONCLUSIONS: Until selective COX-2 inhibitors have been assessed adequately in human inflammatory bowel disease, these compounds should not be assumed to be safe for the gastrointestinal tract in inflammatory bowel disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Early experience with intrasphincteric botulinum toxin in the treatment of achalasia.

BACKGROUND: Recent reports have suggested that intrasphincteric injection of botulinum toxin is effective and long-lasting in the treatment of achalasia. AIM: To report our experience of botulinum toxin injection in a prospective series of consecutive patients with achalasia. METHODS: Eleven consecutive patients with achalasia (eight male, mean age 55 years, range 20-87) were treated with 60 units of botulinum toxin (Dysport; Speywood Pharmaceuticals Ltd, UK) into each of four quadrants at the lower oesophageal sphincter. Patients were assessed pre-treatment and 1 month after treatment using a symptom score and oesophageal manometry. Median follow-up was 12 months (range 6-28). RESULTS: The injection procedure was simple to perform and free of adverse effects. Although treatment had a beneficial effect on dysphagia (median pre-treatment score 3 [interquartile range 3-3]; post-treatment score 2 [0-3]: P=0.03) 1 month following therapy, there was no significant improvement in chest pain or regurgitation scores. Similarly, no significant reduction in median lower oesophageal sphincter pressure was observed (29.5 mmHg [21-42] pre-treatment, 28.5 [17.5-55.5] post-treatment P=0.67). Four patients (36%) required further therapy within 3 months and the overall relapse rate was 73% (eight of 11) within 2 years. CONCLUSION: Although botulinum toxin injection was well tolerated, these results using Dysport at a dose of 240 mouse units question its efficacy as a treatment for achalasia.

Adult↗
PubMed1999

Characterisation of penicillin G uptake in human small intestinal brush border membrane vesicles.

BACKGROUND: Many beta lactams are well absorbed by the small intestine, although the reasons for this are poorly understood. AIMS: To characterise the uptake of penicillin G into human small intestinal brush border membrane vesicles (BBMV) and to compare the uptake characteristics to those of rabbit BBMV. METHODS AND RESULTS: Uptake of penicillin G was studied in human BBMV. Penicillin G was actively transported into the lumen of BBMV via an H+ dependent, Na+ independent uptake system. The carrier mediated process was saturable and adhered to Michaelis-Menten kinetics (Vmax 52 nmol penicillin G per mg protein per 30 seconds, Km 13.9 mM). These results are similar to those previously reported in rabbit BBMV. CONCLUSIONS: It is suggested that penicillin G can be used as a model molecule for peptide and beta lactam transport studies as it is cheap and readily available in isotopically labelled form. Furthermore, rabbit BBMV may be used as an acceptable substitute for human BBMV for the study of penicillin transport.

Animals↗
PubMed1998

Ultrathin endoscopy in the assessment and treatment of upper and lower gastrointestinal tract strictures.

BACKGROUND: Ultrathin (</= 6 mm diameter) endoscopes have recently been introduced into clinical practice. METHODS: We retrospectively assessed the role of a 6 mm diameter videoendoscope in 15 patients with tight gastrointestinal tract strictures. RESULTS: The ultrathin endoscope was successfully passed through 9 of 12 esophageal strictures not amenable to endoscopy with a standard-diameter endoscope allowing stricture dilatation or nasogastric tube placement in 8 of these. Ultrathin endoscopy was also successful in passing 3 lower gastrointestinal tract strictures caused by Crohn's disease that were impassable using larger-diameter endoscopes. CONCLUSION: Ultrathin endoscopy is potentially useful in the assessment and treatment of some upper and lower gastrointestinal tract strictures.

Adult↗
PubMed1998

General practitioner access to gastroscopy: is 'censorship' valuable?

An audit was carried out on the activities of a one stop clinic where patients referred by GPs for endoscopy are first interviewed by a gastroenterologist, directly before the procedure. Such a barrier to open access endoscopy did not seem to reduce the workload or the rate of normal examinations.

Adult↗