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R J Farrell

Publications and source records attributed to R J Farrell.

At least 19 recordsLinked to original sources

Recent advances in inflammatory bowel disease.

The last decade has seen tremendous advances in our knowledge, which has led to genuine improvements in our understanding of the pathogenesis and management of inflammatory bowel disease (IBD). The combined power of cellular and molecular biology has begun to unveil the enigmas of IBD, and, consequently, substantial gains have been made in the treatment of IBD. Refinements in drug formulation have provided the ability to target distinct sites of delivery, while enhancing the safety and efficacy of older agents. Simultaneous progress in biotechnology has fostered the development of new agents that strategically target pivotal processes in disease pathogenesis. This article addresses our current understanding of the pathogenesis of IBD, including the latest developments in animal models and covers agents currently used in the treatment of IBD as well as emerging therapies.

Animals↗

Role of virtual computed tomographic colonography in patients with colorectal cancers and obstructing colorectal lesions.

PURPOSE: The aim of this study was to assess the ability of computed tomographic colonography to diagnose colorectal masses, stage colorectal cancers, image the proximal colon in obstructing colorectal lesions, and evaluate the anastomoses in patients with previous colorectal surgery. METHODS: We prospectively performed computed tomographic colonography examinations in 34 patients (20 males; mean age, 64.2; range, 19-91 years): 20 patients had colorectal masses (defined at endoscopy as intraluminal masses 2 cm or larger), 7 patients had benign obstructing colorectal strictures, and 7 patients had a prior colorectal resection. Final tumor staging was available in all 16 patients who had colorectal cancers and 15 patients were referred after incomplete colonoscopy. The ability of computed tomographic colonography to stage colorectal cancers, identify synchronous lesions in patients with colorectal masses, and image the proximal colon in patients with obstructing colorectal lesions was assessed. RESULTS: Computed tomographic colonography identified all colorectal masses, but overcalled two masses in patients who were either poorly distended or poorly prepared. Computed tomographic colonography correctly staged 13 of 16 colorectal cancers (81 percent) and detected 16 of 17 (93 percent) synchronous polyps. Computed tomographic colonography over-staged two Dukes Stage A cancers and understaged one Dukes Stage C cancer. A total of 97 percent (87/90) of all colonic segments were adequately visualized at computed tomographic colonography in patients with obstructing colorectal lesions compared with 60 percent (26/42) of segments at barium enema (P < 0.01). Colonic anastomoses were visualized in all nine patients, but in one patient, computed tomographic colonography could not distinguish between local tumor recurrence and surgical changes. CONCLUSION: Computed tomographic colonography can accurately identify all colorectal masses but may overcall stool as masses in poorly distended or poorly prepared colons. Computed tomographic colonography has an overall staging accuracy of 81 percent for colorectal cancer and is superior to barium enema in visualizing colonic segments proximal to obstructing colorectal lesions.

Adult↗

High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.

BACKGROUND & AIMS: The multidrug resistance (MDR) gene codes for a drug efflux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocytes and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucocorticoids are known Pgp-170 substrates. METHODS: Using flow cytometry, we measured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 healthy volunteers, and assessed the relationship between PBL, mucosal intraepithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. RESULTS: Compared with controls, PBL MDR was significantly elevated in patients with Crohn's disease who required bowel resection for failed medical therapy (mean +/- SEM, 26.7 +/- 2.8 vs. 11.9 +/- 1.0; P <0.0001) and patients with ulcerative colitis who required proctocolectomy for failed medical therapy (20.3 +/- 2.5 vs. 11.9 +/- 1.0; P = 0.001). PBL MDR remained stable over time and was not influenced by disease activity or glucocorticoid therapy. Both PBL and mucosal MDR expression appeared independent of disease activity, and there was a significant correlation between PBL MDR expression and both IEL expression (r = 0.92; P < 0.0001) and EC expression (r = 0.54; P < 0.001). CONCLUSIONS: PBL and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

MR cholangiopancreatography of pancreaticobiliary diseases: comparison of single-shot RARE and multislice HASTE sequences.

AIMS: We prospectively compared two breath-hold magnetic resonance cholangiopancreatography (MRCP) sequences: single-shot rapid acquisition with relaxation enhancement (RARE) and multislice half-Fourier acquisition single-shot turbo spin echo (HASTE) in imaging the pancreaticobiliary system. PATIENTS AND METHODS: The diagnostic accuracy of single-shot RARE and multislice HASTE was studied in 34 subjects who had undergone conventional cholangiopancreatography. Overall image quality, duct conspicuity, image artifact, signal intensity and contrast-to-noise ratios were assessed independently by two radiologists who were unaware of the underlying diagnosis. RESULTS: Both sequences had comparable diagnostic accuracy regarding a normal biliary system, choledocholithiasis, extra-hepatic and intra-hepatic strictures. Single-shot RARE was superior to multislice HASTE in diagnosing a normal pancreatic system, pancreatic and intrahepatic duct strictures, while providing significantly better image quality (mean +/- SE 3.7 +/- 0.07 vs 3.3 +/- 0.08: P = 0.02) and significantly less image artifact (mean +/- SE 3.6 +/- 0.07 vs 3.2 +/- 0.08: P = 0.01). Single-shot RARE provided significantly better duct conspicuity regarding the pancreatic duct within the body (2.7 +/- 0.2 vs 2.1 +/- 0.2: P = 0.003) and tail (2.4 +/- 0.2 vs 1.6 +/- 0.2;P = 0.0001), as well as the intrahepatic ducts (3.0 +/- 0.1 vs 2.6 +/- 0.1: P = 0.004) but there was no significant difference regarding the remainder of the biliary tree. CONCLUSION: Single-shot RARE provides superior image quality, duct conspicuity with the added advantage of less image artifact and shorter acquisition time. However, volume averaging can cause common bile duct stones to be missed. Therefore, multislice HASTE sequences should still be acquired if choledocholithiasis is suspected. Larger studies are required to assess the diagnostic efficacy of single-shot RARE sequences in pancreatic duct and intra-hepatic duct disease.Morrin, M. M. (2000). Clinical Radiology55, 866-873.

Adolescent↗

Clinical experience with infliximab therapy in 100 patients with Crohn's disease.

OBJECTIVE: The aim of this study was to assess our clinical experience with infliximab, a monoclonal antitumor necrosis factor antibody, following its approval for treatment of refractory Crohn's disease (CD). METHODS: We followed 100 consecutive patients with CD (53 women and 47 men; mean age, 41 yr) who received a total of 233 infliximab (5 mg/kg) infusions. Adverse events were noted and clinical response assessed every 2 wk for 6 months after each infusion using the Harvey Bradshaw Index (HBI) for active disease, the Perianal Disease Activity Index (PDAI) for fistulous disease, and steroid withdrawal rates for steroid-sparing efficacy. RESULTS: Indications for therapy were active disease (n = 57), perianal fistulous disease (n = 33), and steroid dependency (n = 10). Significant infusion reactions occurred in 16 patients (6.9% of infusions) including anaphylactic shock in one patient. Fourteen patients experienced infectious adverse events, 13 of whom were on concurrent steroids. Sixty percent of patients with active disease experienced > or = 50% HBI reduction at 2 wk; mean duration of response, 8.2 wk. Three of 26 first-time nonresponders with active disease (12%) responded to a second infusion. Sixty-nine percent of patients with fistulous disease experienced >50% reduction in their PDAI at 2 wk; mean duration of response, 10.9 wk. Four of 10 steroid-dependent patients (40%) discontinued steroid therapy, one of whom recommenced steroid therapy at 24 wk. CONCLUSIONS: Our clinical response rates mirror the efficacy reported in the controlled trials for active and fistulous disease. Steroid-sparing efficacy was seen in 40% of steroid-dependent patients. Concurrent steroids did not reduce the risk of significant infusion reactions (6.9%), but did increase the risk of infections.

Adult↗

Increased incidence of non-Hodgkin's lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low.

BACKGROUND: There is concern that the incidence of non-Hodgkin's lymphoma (NHL) will rise with increasing use of immunosuppressive therapy. AIMS: Our aim was to determine the risk of NHL in a large cohort of patients with inflammatory bowel disease (IBD), and to study the association between IBD, NHL, and immunosuppressive therapy. METHODS: We studied 782 IBD patients (238 of whom received immunosuppressive therapy) who attended our medical centre between 1990 and 1999 (median follow up 8.0 years). Standardised incidence ratios (SIRs) and 95% confidence intervals (CI) were calculated. Expected cases were derived from 1995 age and sex specific incidence rates recorded by the National Cancer Registry of Ireland. RESULTS: There were four cases of NHL in our IBD cohort (SIR 31.2; 95% CI 2.0-85; p=0.0001), all of whom had received immunosuppressive therapy: azathioprine (n=2), methotrexate (n=1), and methotrexate and cyclosporin (n=1). Our immunosuppressive group had a significantly (59 times) higher risk of NHL compared with that expected in the general population (p=0.0001). Three cases were intestinal NHL and one was mesenteric. Mean age at NHL diagnosis was 49 years, mean duration of IBD at the time of NHL diagnosis was 3.1 years, and mean duration between initiation of immunosuppressive therapy and diagnosis of NHL was 20 months. CONCLUSIONS: Although underlying IBD may be a causal factor in the development of intestinal NHL, our experience suggests that immunosuppressive drugs can significantly increase the risk of NHL in IBD. This must be weighed against the improved quality of life and clinical benefit immunosuppressive therapy provides for IBD patients.

Adult↗

Utility of intravenously administered contrast material at CT colonography.

PURPOSE: To determine if intravenously administered contrast material improves overall reader confidence in the assessment of the colon, large-bowel wall conspicuity, and diagnostic accuracy in the detection of colorectal polyps and cancers at computed tomographic (CT) colonography. MATERIALS AND METHODS: Two hundred patients underwent CT colonography in both supine and prone positions. A five-point scale was used to assess the effect of contrast enhancement on overall reader confidence and bowel wall conspicuity. Eighty-one patients underwent CT colonography with complete colonoscopic or surgical correlation; diagnostic accuracy was compared in 48 patients who received contrast material and 33 who did not. RESULTS: Bowel preparation was ideal in 38 (19%) of 200 patients. Enhanced prone CT images had significantly better scores for reader confidence (4.9 +/- 0.1 vs 4.6 +/- 0.1, P: <.005) and bowel wall conspicuity (4.6 +/- 0.2 vs 4.2 +/- 0.2, P: <.005) compared with those of nonenhanced prone images despite no significant difference in bowel distention (3.8 +/- 0.2 vs 3.9 +/- 0. 1, P: =.8). Enhancement significantly improved the ability to depict medium (6-9-mm) polyps (75% vs 58%, P: <.05). Three large (10-19-mm) polyps were detected only with contrast enhancement; two remained submerged despite dual positioning. CONCLUSION: The use of intravenously administered contrast material significantly improved reader confidence in the assessment of bowel wall conspicuity and the ability of CT colonography to depict medium polyps in suboptimally prepared colons.

Adult↗

Radiation exposure of the families of outpatients treated with radioiodine (iodine-131) for hyperthyroidism.

Patients who receive radioiodine (iodine-131) treatment for hyperthyroidism (195-800 MBq) emit radiation and represent a potential hazard to other individuals. Critical groups amongst the public are fellow travellers on the patient's journey home from hospital and members of the patient's family, particularly young children. The dose which members of the public are allowed to receive as a result of a patient's treatment has been reduced in Europe following recently revised recommendations from ICRP. The annual public dose limit is 1 mSv, though adult members of the patient's family are allowed to receive higher doses, with the proviso that a limit of 5 mSv should not be exceeded over 5 years. Unless the doses received during out-patient administration of radioiodine can be demonstrated to comply with these new limits, hospitalisation of patients will be necessary. The radiation doses received by family members (35 adults and 87 children) of patients treated with radioiodine at five UK hospitals were measured using thermoluminescent dosimeters mounted in wrist bands. Families were given advice (according to current practice) from their treatment centre about limiting close contact with the patient for a period of time after treatment. Doses measured over 3-6 weeks were adjusted to give an estimate of values which might have been expected if the dosimeters had been worn indefinitely. Thirty-five passengers accompanying patients home after treatment also recorded the dose received during the journey using electronic (digital) personal dosimeters. For the "adjusted" doses to infinity, 97% of adults complied with a 5-mSv dose limit (range:0.2-5.8 mSv) and 89% of children with a 1-mSv limit (range: 0.2-7.2 mSv). However 6 of 17 children aged 3 years or less had an adjusted dose which exceeded this 1 mSv limit. The dose received by adults during travel was small in comparison with the total dose received. The median travel dose was 0.03 mSv for 1 h travel (range: 2 microSv-0.52 mSv for 1 h of travel time). These data suggest that hyperthyroid patients can continue to be treated with radioiodine on an out-patient basis, if given appropriate radiation protection advice. However, particular consideration needs to be given to children aged 3 years or younger. Admission to hospital is not warranted on radiation protection grounds.

Adolescent↗

Guided versus blind liver biopsy for chronic hepatitis C: clinical benefits and costs.

BACKGROUND/AIMS: Our objectives were: (1) to assess the clinical benefits and costs of performing ultrasound-guided liver biopsy with an automated needle compared to blind biopsy with a conventional Trucut needle in patients with chronic hepatitis C; (2) to compare the histological yield of automated needles with Trucut needles. METHODS: We prospectively studied 166 patients with hepatitis C virus who underwent either ultrasound-guided biopsy using automated ASAP needles or blind biopsy using conventional Trucut needles. Both groups were matched for age, sex, cirrhosis, needle gauge and operator experience. Patient tolerance, complications and histological adequacy were assessed. In a separate in vitro study, we assessed the histological adequacy of liver biopsy specimens obtained using automated and Trucut needles from 10 fresh autopsy cases. RESULTS: Ultrasound-guided biopsy caused significantly less biopsy pain (36.4% vs. 47.3%; p < 0.0001) and significantly less pain-related morbidity (1.8% vs. 7.7%, p < 0.05). Although, there was no significant difference in diagnostic yield between guided and blind biopsy (98% vs. 94%, p = 0.15), 3 blind biopsies (3.3%), including 2 which yielded extra-hepatic tissue, had to be repeated. The additional expense of performing guided liver biopsy with automated needles was 42 Irish Pounds per patient. In vitro, automated ASAP 15G needles provided liver specimens comparable to Trucut 15G needles and had the highest histopathologic score among the automated needles assessed. CONCLUSIONS: Even in the absence of major complications, ultrasound-guided liver biopsy with an automated needle in HCV patients is safer, more comfortable and only marginally more expensive than blind Trucut biopsy.

Adult↗

Mesalamine-associated thrombocytopenia.

We describe a case of a 25-yr-old woman with ulcerative colitis who developed marked thrombocytopenia during treatment and upon rechallenge with oral mesalamine. In contrast to its parent drug, sulfasalazine, which has often been reported to cause serious blood disorders, particularly agranulocytosis, mesalamine has rately been implicated as a cause of serious blood disorders. Although previous cases of hematological toxicity have been described in patients taking mesalamine, none of these patients were rechallenged in an effort to prove causality between 5-aminosalicyclic acid and the hematological abnormality as well as outrule the possible "autoimmune" contribution of inflammatory bowel disease to the hematological toxicity of these agents. This report demonstrates that mesalamine has the potential, like sulphasalazine, to cause marked thrombocytopenia in an idiosyncratic fashion. All patients receiving mesalamine therapy, either orally or topically should have regular, complete blood profiles.

Adult↗

Virtual colonoscopy: a gastroenterologist's perspective.

Virtual colonoscopy is an exciting new imaging technique with potential to alter current diagnostic approaches to colonic diseases, particularly colonic neoplasms. Although colonoscopy continues to offer the highest sensitivity and specificity for evaluation of the colon, virtual colonoscopy may offer greater safety, less discomfort, and consequently greater patient acceptance. In addition, virtual colonoscopy offers shorter procedure time, more accurate lesion location, and potentially lower cost as a screening test. Limited data are currently available to define virtual colonoscopy's full clinical role. This article describes the technical considerations, current clinical status, limitations, and potential indications of this new and exciting technology which gastroenterologists should not fear but embrace.

Colonoscopy↗

Endoluminal CT colonography after an incomplete endoscopic colonoscopy.

OBJECTIVE: We evaluated the clinical usefulness of endoluminal CT colonography after an incomplete colonoscopy. SUBJECTS AND METHODS: We prospectively studied 40 patients in whom the cecum could not be reached endoscopically despite adequate bowel preparation. Endoluminal CT colonography (120 kVp, 120 mA, 3-mm collimation, pitch of 2, 1.5-mm interval reconstruction) was performed within 2 hr of incomplete colonoscopy. Two-dimensional multiplanar reformatted images and three-dimensional endoluminal images were analyzed. Twenty-six patients (65%) underwent barium enema immediately after endoluminal CT colonography. We analyzed colonic distention; duration of endoluminal CT colonography; patient tolerance; number of colonic segments seen at colonoscopy, endoluminal CT colonography, and barium enema; and reasons for incomplete colonoscopy as well as colonic and extracolonic findings. RESULTS: Duration of endoluminal CT colonography was 14.2 +/- 4.6 min (mean +/- SD). Endoluminal CT colonography was better tolerated than colonoscopy or barium enema (p < .001). Probable causes for incomplete colonoscopy were identified at endoluminal CT colonography in 74% of 40 patients. Baseline colonic distention in the region of the transverse and right colon was considered adequate before additional air insufflation; however, the addition of air significantly enhanced colonic distention throughout the entire colon (p < .001). Endoluminal CT colonography adequately revealed 96% of all colonic segments; in comparison, barium enema adequately revealed 91% of all segments (p < .05). CONCLUSION: In patients with incomplete colonoscopy, endoluminal CT colonography successfully showed the previously unrevealed colon in more than 90% of patients. Endoluminal CT colonography is a rapid, well-tolerated technique that provides clinically useful colonic and extracolonic information and should be considered for all patients who undergo incomplete colonoscopy.

Adult↗