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Biomedical subjects

R Enns

Publications and source records attributed to R Enns.

At least 19 recordsLinked to original sources

CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial.

BACKGROUND: Targeting tumour necrosis factor alpha (TNF-alpha) has demonstrated efficacy in Crohn's disease. AIM: To evaluate CDP571, a humanised antibody to TNF-alpha, for treating active Crohn's disease. PATIENTS: A total of 396 patients with moderate to severe Crohn's disease. METHODS: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinical response (a decrease in the Crohn's disease activity index (CDAI) to > or =100 points or remission (CDAI score < or =150 points)) at week 28. A secondary outcome measure was clinical response (using the same definition) at week 2. RESULTS: Clinical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 90/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) > or =10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo, 9/58 (15.5%); p<0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1%); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups. CONCLUSIONS: CDP571 is modestly effective for short but not long term treatment of unselected patients with moderate to severe Crohn's disease. The clinical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (> or =10 mg/l). CDP571 is well tolerated.

Adult↗

Capsule endoscopy: a single-centre experience with the first 226 capsules.

BACKGROUND: Capsule endoscopy (CE) refers to a novel diagnostic method of imaging the gastrointestinal tract using a wireless capsule that transmits images to a data recorder while the device traverses the small intestine. OBJECTIVE: To review the authors' experience with CE to determine the indications, outcomes and management of positive findings. METHODS: Patients were prepared for CE with a single dose of magnesium citrate. Following an 8 h fast, a sensor array system was applied to the abdomen, the capsule was swallowed and the images were transmitted to a data recorder worn on the patient's side. Typically, the battery life of the capsule is 8 h, following which the data recorder is returned, downloaded to a computer workstation and reviewed. RESULTS: To date, 226 capsule studies have been performed in 209 patients. The indications included obscure bleeding (167 studies: 88 overt, 79 occult), anemia (14 studies), evaluation for inflammatory bowel disease (12 studies), screening for polyps (10 studies), pain (19 studies) and abnormal radiological imaging (4 studies). In the setting of obscure bleeding, a definitive source of bleeding was discovered in 85 studies. This included angiodysplasia (52 studies), mitotic lesions (10 studies) and ulcers (23 studies). A probable source of bleeding was found in another 10 capsule studies. In the setting of anemia without evidence of bleeding, the definitive findings included ulcers (three studies), angiodysplasia (two studies), mitotic lesions (one study) and celiac disease (one study). Of four patients with abnormal radiological imaging, CE demonstrated lesions in two. The results of 35 capsule studies led to laparotomy with curative surgical resection. In eight studies, the capsules became lodged within a stricture; none led to obstruction and three were managed endoscopically. CONCLUSION: The yield of CE in carefully selected patients with obscure bleeding approximates 51%. There appear to be few complications, and patient satisfaction appears high. Cost analysis and further studies of clinical outcomes are required to elucidate appropriate indications for this device.

Angiodysplasia↗

Pancreatitis in HIV infection: predictors of severity.

OBJECTIVES: Acute pancreatitis occurs at greater frequency in HIV-infected patients than in the general population. We set out to determine the frequency of severe acute pancreatitis in HIV-positive patients and to study the accuracy of The Acute Physiology and Chronic Health Evaluation (APACHE II), Ranson, and Glasgow scales for prediction of clinical disease severity. METHODS: A total of 73 HIV-infected patients with acute pancreatitis were identified retrospectively. Demographic and clinical parameters as well as clinical outcomes were established. Sensitivities and specificities of the three scales mentioned above were calculated and compared. RESULTS: Of the patients, 63 (83.6%) had AIDS. The majority of cases were medication-induced (46%) or idiopathic (26%). The incidence seemed to be declining in the late 1990s. Eleven patients (15%) had a severe course as defined by death, admission to the intensive care unit, or local complications requiring surgery. Eighteen case (24.6%) were considered severe as defined by the criteria established at the International Symposium on Acute Pancreatitis in Atlanta in 1992. APACHE II criteria best predicted outcome with an overall accuracy of 75% (Glasgow 69%, Ranson 48%). Maximal accuracy was achieved with cut-offs of 14 for APACHE II and 4 for the Glasgow and Ranson criteria. CONCLUSIONS: HIV-infected patients have a clinical outcome similar to that of the general population. Clinical predictive scales are applicable and useful in this population.

APACHE↗

Predictors of successful clinical and laboratory outcomes in patients with primary sclerosing cholangitis undergoing endoscopic retrograde cholangiopancreatography.

UNLABELLED: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with primary sclerosing cholangitis (PSC) can be a challenging and sometimes gratifying opportunity for therapeutic intervention. Although there often appears to be initial radiological improvement after ERCP, the benefit as measured by serial estimations of subsequent liver enzymes is questionable. The fluctuating course of the inflammatory process makes the interpretation of serology even more difficult. OBJECTIVES: To document and compare the liver profile and clinical status of patients before and after diagnostic and therapeutic ERCP; to determine predictors of clinical and laboratory success in patients with PSC; and to assess the complication rate of diagnostic and therapeutic ERCP in these patients. METHODS: All patients with PSC who underwent ERCP at the authors' medical centres between January 6, 1987 and January 12, 1998 were identified using a computerized database. Presenting symptoms, liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase) and bilirubin were recorded before ERCP. Clinical success was defined as resolution of the presenting symptoms. Laboratory success was defined as improvement in two of three liver enzymes by at least 50%, or resolution of jaundice. RESULTS: One hundred four patients underwent 204 ERCPs of which 56 ERCPs were diagnostic. Clinical improvement was seen in 35% of the patients after diagnostic ERCP and in 70% after therapeutic procedures (chi 2=18.4, P=0.001). Laboratory improvement was seen in 35% of patients undergoing diagnostic ERCP and in 52% of the patients undergoing therapeutic ERCP (P=0.04). The reductions in liver enzymes were significant in both the diagnostic and therapeutic groups. Serum bilirubin level decreased significantly in the therapeutic ERCP group only. In a univariate analysis, patients with common bile duct strictures, any dominant stricture and those who underwent a therapeutic procedure were most likely to have clinical and laboratory improvement. In multivariable logistic regression, the presence of a dominant stricture, endoscopic therapy and high serum bilirubin were all independent predictors of a successful clinical outcome. There was no difference in total complication rates (18% versus 14%) when comparing the diagnostic and therapeutic ERCP groups. However, all seven severe complications occurred in the therapeutic ERCP group. CONCLUSIONS: First, in PSC, clinical and laboratory improvement is more common in patients undergoing therapeutic ERCP than diagnostic ERCP. Second, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase improve following both diagnostic and therapeutic ERCP, and should therefore not be relied upon to determine the success of the procedure. Third, bilirubin levels decreased in the therapeutic group but remained unchanged in the diagnostic group, suggesting that the serum bilirubin level may be a more sensitive indicator of successful therapeutic intervention than transaminases. Fourth, common bile duct strictures, dominant strictures and bilirubin levels are important variables in determining the success of an ERCP in PSC. Finally, complication rates after therapeutic ERCP are similar to those after diagnostic ERCP in PSC patients. However, severe complications occur more commonly in the therapeutic group.

Adult↗

Endoscopic diagnosis of a right hepatic artery pseudoaneurysm.

Hepatic artery aneurysms are rare occurrences with diverse etiologies. We present a case of a right hepatic artery aneurysm, which was diagnosed at endoscopic retrograde cholangiography (ERC) and treated angiographically. This is the first report where ERC has been critical in delineating the aneurysmal cavity, suggesting the diagnosis and prompting emergency intervention.

Adult↗

ERCP-related perforations: risk factors and management.

BACKGROUND AND STUDY AIMS: Perforations during endoscopic retrograde cholangiopancreatography (ERCP) are rare, and the management of these perforations is variable, with some patients requiring immediate surgery and others only conservative management. We reviewed all ERCP-related perforations at our institution to determine: a) their incidence; b) clinical outcomes; c) which management approaches gave the best results; and d) which factors predict a perforation. PATIENTS AND METHODS: All patients who underwent ERCP and suffered perforation were reviewed. To compare the length of hospital stay of the perforation group with that of patients suffering a different complication, patients who developed post-ERCP pancreatitis were also reviewed. To evaluate predictors of ERCP-related perforations, three groups were compared: group 1 (n = 49), normal ERCP/no complications; group 2 (n = 52), ERCP complicated by pancreatitis; and group 3 (n = 33), ERCP with perforation. RESULTS: Of 33 patients with confirmed ERCP-related perforations, only seven patients required surgical intervention. The overall length of hospital stay (6.5 +/- 3.5 days) was significantly longer (P = 0.003) than that of a random group of patients with the complication of post-ERCP pancreatitis (4.7 +/- 2.6 days). According to univariate analysis, risk factors included: sphincterotomy (odds ratio [OR] 9.0, 95 % confidence interval [CI] 3.2 - 28.1); sphincter of Oddi dysfunction (OR 3.8, 95 % CI 1.4 - 11.0); and dilated common bile duct (OR 4.07, 95 % CI 1.63 - 10.18, P = 0.003). In the multivariate logistic regression analysis, additional predictive factors included the duration of procedure (OR 1.021, 95 % CI 1.006 - 1.036), and biliary stricture dilation (OR 7.2, 95 % CI 1.84 - 28.11). CONCLUSIONS: (i) The incidence of ERCP-related perforations is very low (0.35 %). (ii) Esophageal, gastric and duodenal perforations usually require surgery, but sphincterotomy- and guide wire-related perforations rarely do so. (iii) Factors which carry increased risk of an ERCP-related perforation include suspected sphincter of Oddi dysfunction, greater age, a dilated bile duct, sphincterotomy, and longer duration of the procedure.

Adult↗

Clinical and histological predictors of response to medical therapy in collagenous colitis.

OBJECTIVES: Collagenous colitis (CC) is an uncommon form of inflammatory bowel disease. The response to typical medical therapies (antimotility agents, 5-aminosalicylic acid [5-ASA], and corticosteroids) is variable. We aimed to determine if there are clinical or histological variables that can predict response to medical therapy. METHODS: All cases of CC were identified in three tertiary care medical centers. All charts of included patients were reviewed and clinical variables (age, gender, duration of symptoms, frequency of bowel movements, and the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) were recorded. Available histology slides were reviewed by one GI pathologist. Intraepithelial inflammation, epithelial loss or detachment, inflammation in the lamina propria, presence of eosinophilia, crypt inflammation, Paneth's cell metaplasia, and collagen layer thickness were recorded. Depending on their response to therapy, patients were divided into three groups: 1) spontaneous recovery or response to antidiarrheal agents alone, 2) response to 5-ASA agents, and 3) response to corticosteroids after failure of antidiarrheal agents and 5-ASA. RESULTS: Ninety-four patients with CC were identified. Of these, 62 patients were included. The median age was 58 (range = 20-85), and 88% were female. Among the histological parameters only the degree of inflammation in the lamina propria significantly differed between the three response groups (p = 0.007). Patients who required corticosteroids had greater inflammation. Among the clinical parameters age at presentation and use of NSAIDs significantly differed between groups. In the antidiarrheal group, patients tended to be more elderly, and in the corticosteroid group, more patients were on NSAIDs. CONCLUSIONS: 1) The degree of lamina propria inflammation can be used as a histological predictor to guide treatment in patients with CC. 2) Patients who responded to antidiarrheal agents or had spontaneous remissions were significantly older than those patients requiring 5-ASA compounds or corticosteroids. 3) Patients who were taking NSAIDs were more likely to require corticosteroid therapy, presumably reflecting more severe disease.

Adrenal Cortex Hormones↗

Acute lower gastrointestinal bleeding: part 1.

Acute lower gastrointestinal (LGI) bleeding is typically caused by vascular malformations, diverticuli and neoplasia. Although endoscopic evaluation of the colon is relatively standard in stable patients with LGI bleeding, those with significant ongoing hemorrhage are often more difficult to evaluate endoscopically. Other investigative techniques such as nuclear scintigraphy, angiography and surgical exploration have been commonly used in unstable patients with LGI bleeding when the exact site is unknown. These investigative techniques have had variable measures of success. This two-part review evaluates the literature in an attempt to review the optimal investigative approach in patients with LGI hemorrhage, in particular patients who have had significant and ongoing bleeding. Part 1 of this article concentrates on the etiology of LGI hemorrhage, followed in a subsequent article by diagnostic and management strategies. Following the review, a consensus update will be included with guidelines for clinical use.

Adolescent↗

Acute lower gastrointestinal bleeding: part 2.

Diagnostic strategies for lower gastrointestinal bleeding include nuclear scintigraphy, mesenteric angiography and endoscopic evaluation of the lower gastrointestinal tract. Each method has inherent advantages and disadvantages. Nuclear scintigraphy is simple and noninvasive, but high rates of false localization have led most clinicians to insist on confirmation of the bleeding site by another method before considering surgical intervention. Angiography is very specific, but is invasive and not as sensitive as nuclear scintigraphy. Colonoscopy is sensitive and specific, and can offer therapeutic value but can be technically challenging in the face of acute lower gastrointestinal hemorrhage. These strategies and the evidence behind them are discussed.

Colonic Diseases↗

Dieulafoy's lesions of the rectum: a rare cause of lower gastrointestinal bleeding.

Dieulafoy's lesions located outside of the stomach are rare occurrences. Lesions found within the colon typically present with painless, massive hematochezia (ie, greater than 5 U). If they can be accurately located, endoscopic therapy in the form of adrenaline injection, sclerotherapy or cauterization appears to have long term success. The present report details the case of a 72-year-old man who presented with massive hematochezia and who was discovered to have a Dieulafoy's lesion within the rectum. The lesion was located just distal to a previous surgical anastomosis, and was successfully treated with adrenaline and electrocautery. Colonic Dieulafoy's lesions are rare but should always be considered in the differential diagnosis of massive hematochezia, because endoscopic therapy appears to result in complete cessation of bleeding.

Adrenergic Agonists↗

Infliximab for the treatment of Crohn's disease: efficacy, safety and pharmacoeconomics.

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. From the perspective of the patient, symptoms of the disease significantly impair quality of life and interfere with activities of daily living. Conventional medical treatment of Crohn's disease includes the use of nonspecific anti-inflammatory drugs, immunosuppressives and antibiotics. These therapies are characterized by a delayed onset of action, incomplete response rates and a substantial risk of adverse effects. Although surgery is frequently used to treat complications, postoperative recurrence is an important problem. Infliximab, a chimeric monoclonal antibody directed toward tumour necrosis factor alpha, is highly effective for the treatment of active Crohn's disease. In randomized, placebo-controlled clinical trials, 82% of patients who received 5 mg/kg of infliximab had a clinically significant response, compared with 17% of those given placebo (P<0.001). Moreover, infliximab is the only medical therapy that has been shown to be effective for the treatment of fistulizing Crohn's disease. Infusion reactions are the most common adverse effect. Whether treatment with infliximab is associated with an increased risk of neoplasia, infection or autoimmune disease is unknown. Therefore, further long term safety studies are required. Despite the relatively high cost of drug acquisition, preliminary pharmacoeconomic analysis indicates that infliximab is cost effective compared with existing treatments. Infliximab is recommended for the treatment of active Crohn's disease refractory to conventional drugs, and is the treatment of choice for fistulizing Crohn's disease.

Antibodies, Monoclonal↗

Gastric tolerance of high-dose pulse oral prednisone in multiple sclerosis.

BACKGROUND: Prednisone and methylprednisolone are well absorbed orally and have lower treatment costs than IV methylprednisolone, but concern that low-dose corticosteroid may cause increased disease activity and that high oral doses may cause gastric ulceration inhibits use of oral therapy for MS attacks. METHODS: Gastric mucosal injury, detected by measurement of gastric permeability, was examined after five alternate day doses of IV methylprednisolone (1 g) or oral prednisone (1,250 mg) in 21 patients with MS. A triple sugar test solution was consumed at bedtime, and urine was collected overnight. Urine sugar concentrations were determined by high-pressure liquid chromatography. Gastric permeability was expressed as total mg of sucrose excreted. RESULTS: Seventeen patients completed the protocol (12 oral, 5 IV). Baseline sucrose excretion was normal in all. Both groups demonstrated an increase in gastric permeability after steroid treatment, but there was no difference between the two groups (95% CI 95 to 91 mg, p = 0.96). After treatment, three (25%) patients in the oral group, and two (40%) patients the IV group, had modestly abnormal gastric permeability (95% CI 34 to 64%, P = 0.6). CONCLUSIONS: Short-term high-dose oral prednisone is not associated with greater gastric damage, as measured with permeability tests, than IV methylprednisolone. High-dose oral prednisone should be considered a first-line treatment option for MS attacks.

Administration, Oral↗

Endoscopic nasobiliary drain placement facilitates subsequent percutaneous transhepatic cholangiography.

BACKGROUND: Percutaneous biliary drainage is an established alternative to ERCP for managing bile duct obstruction. Although generally safe and effective, percutaneous drainage has its risks and is technically more difficult in patients with nondilated bile ducts. We report the use of nasobiliary drains and subsequent nasobiliary drain cholangiography to facilitate percutaneous biliary drainage by providing a target for accessing intrahepatic bile ducts. METHODS/RESULTS: Nine patients who were identified as requiring percutaneous biliary drainage underwent nasobiliary tube placement at completion of ERCP. Five of 9 patients had generalized intrahepatic ductal dilatation; in 4 patients, dilatation was focal or absent. Following nasobiliary drain cholangiography, percutaneous needle puncture of a bile duct was successful in all patients, in most cases with only a single puncture of the liver capsule. No procedural complications were encountered. CONCLUSION: Nasobiliary drain placement with subsequent nasobiliary drain cholangiography facilitates percutaneous biliary drainage and may be especially helpful in patients with nondilated intrahepatic bile ducts.

Catheterization↗

Review article: the treatment of acute biliary pancreatitis.

World-wide, gallstones are the commonest cause of acute pancreatitis (AP), a potentially life-threatening condition. Scoring systems based on radiologic findings and serologic markers help predict which patients may have retained bile duct stones. Endoscopic decompression of the biliary tree (by sphincterotomy and stone extraction during ERCP) is safer than surgery, which carries high morbidity and mortality in AP. Four prospective, randomized clinical trials confirm the utility of this approach, however careful patient selection is necessary. Medical therapy for AP is supportive; no agent or medical intervention has been shown consistently to abort or ameliorate the course of AP. Drugs that inhibit inflammatory cytokine production, however, are showing promise.

Acute Disease↗