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Biomedical subjects

R J Bailey

Publications and source records attributed to R J Bailey.

At least 19 recordsLinked to original sources

Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and ribavirin in clinical practice.

BACKGROUND: Pegylated interferon alfa-2a (40 KD) plus ribavirin therapy induces sustained virological response rates up to 63% in randomized-controlled trials. AIM: To conduct a prospective open-label programme to examine the efficacy and safety of this therapy in routine clinical practice. METHODS: Treatment-naive patients with chronic hepatitis C received, at the discretion of the investigator, pegylated interferon alfa-2a 180 microg/week + ribavirin 800 mg/day for 24 or 48 weeks. In total, 508 patients were enrolled [334 non-cirrhotic; 174 cirrhotic (defined as stage F3 and F4)]. RESULTS: In genotype 1 patients treated for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and 34% in cirrhotics. Sustained virological response rates in genotype 2 or 3 non-cirrhotics were 79% (24 weeks) and 72% (48 weeks). Corresponding values for cirrhotic genotype 2/3 were 66% and 44%. The negative predictive value of an early virological response at week 12 was 94%. Predictive factors for sustained virological response on multivariate analysis were genotype (2/3 vs. 1), low viral load and degree of fibrosis. Rates of serious adverse events (<or=5%) and adverse events inducing withdrawal (<or=8%) were comparable with the phase III trials. CONCLUSION: Efficacy and safety of pegylated interferon alfa-2a + ribavirin in clinical practice is comparable with results of randomized-controlled trials.

Adult↗

Campylobacter curvus-associated hepatic abscesses: a case report.

Campylobacter curvus was isolated from blood cultures of a patient with liver abscesses. Bacterial identification involved Gram staining, biochemical analysis, gas-liquid chromatography, and 16S rRNA sequencing. The difficulty in isolation, identification, and growth of the species confirms previous work that these organisms may be overlooked by conventional detection methods.

Bacterial Typing Techniques↗

Infliximab salvage therapy after cyclosporine in an acute flare of chronic ulcerative colitis.

Although infliximab (Remicade, Schering Canada Inc, Quebec) therapy has been well studied in steroid refractory Crohn's disease, its use remains controversial in chronic ulcerative colitis. A 24-year-old woman with a 14-year history of well controlled left sided ulcerative colitis presented with an acute flare. Clinical, endoscopic and biopsy evidence of an acute flare of ulcerative pancolitis were present. There was no response to intravenous steroids but improvement was seen after receiving 14 days of intravenous cyclosporine (4 mg/kg/day continuous infusion). The patient was discharged from hospital with azathioprine (2.5 mg/kg/day) and low dose oral cyclosporine (4 mg/kg/day). She presented with worsening symptoms seven days after discharge. Because of the patient's unwillingness for surgery, she instead received two injections of infliximab 5 mg/kg at week 0 and week 2. An initial response occurred, but her clinical improvement was not durable. Colectomy was performed four weeks later. This is the first report of infliximab as a salvage therapy in an acute flare of chronic ulcerative colitis following failure of cyclosporine.

Acute Disease↗

Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis.

Primary systemic amyloidosis (AL) is a plasma cell (PC) dyscrasia with clinical similarities to multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), but its molecular basis is poorly understood. Translocations at the immunoglobulin heavy-chain (IgH) locus, 14q32, are likely early genetic events in both MM and MGUS and involve several nonrandom, recurrent, partner chromosomes such as 11q13, 16q23, and 4p16.3. Given the similarities between MM, MGUS, and AL, bone marrow clonal PCs were evaluated in 29 patients with AL using interphase fluorescence in situ hybridization (FISH) combined with immunofluorescence detection of the cytoplasmic light-chain (cIg-FISH) for the presence of 14q32 translocations and the t(11;14)(q13;q32). Of 29 patients studied, 21 (72.4%) showed results compatible with the presence of a 14q32 translocation, and 16 (76.2%) of those had translocation (11;14)(q13;q32) for an overall prevalence of the abnormality of 55%. IgH translocations are common in AL, especially the t(11;14)(q13;q32).

Adult↗

Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy.

Deletions of the long arm of chromosome 13 (13q-) are observed in patients with multiple myeloma (MM), are rarely observed in the monoclonal gammopathy of undetermined significance (MGUS) and have been associated with a worsened prognosis in MM. However, no minimally deleted region in the 13q arm has been defined at 13q, and consequently no tumor suppressor genes have yet been identified that are important for disease pathogenesis. We attempted to characterize these chromosome 13q deletions at the molecular cytogenetic level. We studied 351 newly diagnosed patients, entered into the E9486/E9487 clinical study of the Eastern Cooperative Oncology Group. Fluorescent in situ hybridization (FISH) combined with immune fluorescent detection (cIg-FISH) of clonal plasma cells (PC) and cytomorphology were used to analyze interphase, bone marrow (BM) cell, cytospin slides. We simultaneously used DNA probes for the following locus specific probes (LSI); LSI 13 (Rb) and D13S319, which hybridize to 13q14. We subsequently studied distal deletions using the D13S25 probe (13q14.3) and a subtelomeric probe (13qSTP) for the 13q-arm (D13S327) in 40 cases with documented LSI 13 (Rb)/D13S319 deletion and 40 without deletion of these loci. Of 325 evaluable patients, we found 13q deletions in 176 (54%) using LSI 13 (Rb) and D13S319 probes. Of 40 patients with LSI 13 (Rb)/D13S319 deletions, 34 (85%) had coexistent deletion of both D13S25/13qSTP. These results indicate that chromosome 13 deletions in MM involve loss of most if not all of the 13q arm perhaps even indicating monosomy. In six cases the 13qSTP signal was conserved, but D13S25 was lost indicating large interstitial deletions involving 13q14. In 39 of the 40 cases without LSI 13 (Rb)/D13S319 deletions, the normal pattern of two pairs of signals was observed for D13S25/13qSTP. Deletions involving 13q14 are very common in MM as detected by cIg-FISH. These deletions appear to predominantly involve loss of large segments of the 13q arm or monosomy 13, and only occasionally represent an interstitial deletion.

Adult↗

Mild phenotype in two siblings with distal monosomy 12p13.31-->pter.

We report two sibs with trisomy for the region 2p25.1--> pter and monosomy for the region 12p13.31--> pter, due to adjacent-1 segregation of a maternal balanced reciprocal translocation, 46,XX,t(2;12)(p25.1;p13.31). These sibs presented with a mild phenotype, but nevertheless showed features of each of the contributing aneusomies. Monosomy 12p has previously been considered to have a variable and indistinct phenotype. Comparison of these patients with previous reports showed that many features, including microcephaly, facial dysmorphia, developmental and growth delay and dental and digital anomalies are frequently associated with monosomy for 12p. Many of these features are common to other aneusomies, thereby mitigating against a distinct 12p monosomy syndrome at this time. However, the combination of digital and dental anomalies may suggest the presence of this particular monosomy. The proband and his sister had some of the more non-specific features of 2p trisomy syndrome, and comparison with previous reports suggested that the characteristic 2p trisomy syndrome is more usually associated with larger or more proximal trisomies of 2p.

Child↗

Diagnostic utility of fluorescence in situ hybridization in mantle-cell lymphoma.

Mantle-cell lymphoma (MCL) has a poorer prognosis than other small B-cell lymphomas, thus a definitive diagnosis is essential. The t(11;14)(q13;q32) associated with MCL juxtaposes portions of CCND1 (11q13) and IGH (14q32), resulting in over-expression of cyclin D1. In this study, a highly sensitive two-colour fluorescence in situ hybridization (FISH) method was developed to detect t(11;14)(q13;q32) in nuclei isolated from paraffin-embedded tissue. Twenty-three MCLs, 13 normal controls and nine small B-cell lymphomas other than MCL were studied by FISH. Each MCL had been previously investigated to detect genomic IGH-CCND1 fusion by polymerase chain reaction (PCR) using DNA extracted from frozen tissue. The IGH-CCND1 fusion detection rate in the MCLs was 96% by FISH compared with 35% by PCR. By FISH, one MCL and three small B-cell lymphomas other than MCL harboured abnormalities involving only IGH. Less than 1% of cells showed false-positive IGH-CCND1 fusion in normal specimens by FISH. Thus, this highly sensitive FISH assay is very useful in confirming the diagnosis of MCL, has wide applicability as it may be performed on both paraffin-embedded and fresh tissue, and may also facilitate detection of translocations involving these loci in tumours other than MCL.

Case-Control Studies↗

Crohn's disease, pregnancy, and birth weight.

OBJECTIVE: Although there is general agreement that conception should be avoided when Crohn's disease is active, many questions remain unanswered for the woman with Crohn's disease in remission who becomes pregnant. METHODS: Sixty-five charts of women with Crohn's disease quiescent at the start of pregnancy were identified between January 1993 and December 1997. Each pregnancy was matched to a healthy control pregnancy by date, age, parity, smoking status, and gestational age +/- 1 wk, and comparisons were carried out using matched analyses. RESULTS: The two groups were similar in terms of maternal height, weight, and body mass index (BMI), in addition to the matched variables. The incidence of pregnancy complications was similar for most of the complications examined, whereas the incidence of poor maternal weight gain differed significantly between the groups (17/65 vs 2/65, p < 0.001). Flare-up of the Crohn's disease was seen in 13/65 (20%) of pregnancies. The greatest differences in neonatal outcomes were in terms of birth weight (3150+/-80 g vs 3500+/-60 g) and birth weight percentile (36.7%+/-.6% vs 57.5%+/-3.4%). Overall, there were 16 (24.6%) small for gestational age (SGA) births in the Crohn's group, compared with only one (1.5%) in the control group (p = 0.0007). Multivariate analysis was performed to identify factors predictive of SGA births in the Crohn's group. Ileal Crohn's disease was a statistically significant predictor (p = 0.035), whereas previous bowel resection trended toward statistical significance (p = 0.065). CONCLUSIONS: In view of the risk of low birth weight, all women with Crohn's disease who become pregnant should be followed carefully during the pregnancy, particularly those who have ileal disease or who have previously undergone bowel resection. Furthermore, smoking cessation needs to be aggressively pursued in these patients.

Adult↗

Defining the role of fiberoptic sigmoidoscopy in the investigation of patients presenting with bright red rectal bleeding.

OBJECTIVE: This study was done to determine whether sigmoidoscopy could theoretically constitute sufficient investigation for some patients with bright red rectal bleeding. METHODS: One hundred and forty-three patients undergoing investigative colonoscopy for bright red rectal bleeding and whose source of bleeding was identified were studied. The investigation took place in a large urban hospital over an 11-month period. Data obtained included changes in stool pattern, characteristics of the bleeding, lesions identified, and the distance of the lesion from the anus. RESULTS: In patients younger than 55 yr, all serious lesions except for one malignancy in a patient with massive bleeding lay within 60 cm of the anus and theoretically within reach of the fiberoptic sigmoidoscope. The mixing of red blood with stool was commonly due to distal lesions, especially hemorrhoids. CONCLUSIONS: In young persons with bright red rectal bleeding, fiberoptic sigmoidoscopy may prove to constitute appropriate initial investigation.

Adolescent↗

Gastric cancer and other endoscopic diagnoses in patients with benign dyspepsia.

BACKGROUND: It has been suggested that endoscopy could be replaced with non-invasive assessment of helicobacter status in the initial work up of young dyspeptic patients without sinister symptoms. AIMS: To determine the incidence of gastro-oesophageal malignancy in young dyspeptic patients. METHODS: The Alberta Endoscopy Project captured clinical and demographic data on all endoscopies performed from April 1993 to February 1996 at four major adult hospitals in Alberta. The endoscopic and histological diagnosis in a subgroup of patients under 45 years of age without alarm symptoms that had undergone gastroscopy was reviewed. In addition, a random list of 200 patients was generated and their medical records reviewed in order to assess the proportion with symptoms suitable for a non-invasive management strategy. RESULTS: Gastroscopy was performed in 7004 patients under 45 years. In 3634 patients (56% female) alarm type symptoms were absent; 78.9% of patients had symptoms amenable to a non-invasive initial approach, giving a corrected sample size of 2867 patients (correction factor 0.789). Three gastric cancers, one case of moderate dysplasia, 10 biopsy proved cases of Barrett's oesophagus, and 19 oesophageal strictures/rings were detected within this sample. The corrected prevalence of gastric cancer in this select population was 1.05 per thousand patients. DISCUSSION: Endoscopy yielded three gastric cancers in this sample of under 45 year old dyspeptic patients without sinister symptoms. While initial non-invasive screening with one-week triple therapy for helicobacter positive individuals is unlikely to have a detrimental outcome the physician is advised to consider endoscopy in patients with persisting, recurrent, or sinister symptoms.

Adult↗

Omeprazole and ranitidine in the prevention of relapse in patients with duodenal ulcer disease.

BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse. PATIENTS AND METHODS: In a double-blind, parallel-group clinical trial of 928 patients (from 70 centres in 16 countries) with duodenal ulcers who after a short term study had relief of symptoms and healed ulcers proved endoscopically, 308 were randomly assigned to receive omeprazole 10 mg in the morning, 308 to receive omeprazole 20 mg in the morning and 312 to receive ranitidine 150 mg at bedtime for up to 12 months. Symptoms were assessed every three months and endoscopy repeated at three, six and 12 months, or more often if indicated by recurrence of symptoms. The safety screening included basal serum gastrin concentrations and gastric mucosal histopathology. RESULTS: The remission rates up to 12 months were 87% for the omeprazole 20 mg group, 71% for the omeprazole 10 mg group and 63% for the ranitidine group. Omeprazole 20 mg differed significantly from both omeprazole 10 mg (P=0.0001, 95% CI 9 to 23) and ranitidine (P=0.0001, 95% CI 17 to 31). There was no statistically significant difference between omeprazole 10 mg and ranitidine over the 12-month period, but the 95% confidence interval allowed differences between 0% and 16% in favour of omeprazole at 12 months. A Cox regression analysis revealed that longer treatment courses to heal, smoking, a long ulcer history and young age negatively contributed to the odds of staying in remission. The treatments were well tolerated. There was a slight increase in basal serum gastrin concentrations, reflecting the different degrees of acid inhibition induced by the three treatments. No dysplastic or neoplastic lesions were found in any biopsies. CONCLUSIONS: More duodenal ulcer patients are maintained in remission with omeprazole 20 mg daily than with omeprazole 10 mg daily or with ranitidine 150 mg at bedtime.

Adolescent↗

The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms.

OBJECTIVE: The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms. METHODS: A total of 742 patients underwent endoscopy for symptoms of GERD. Endoscopists recorded the therapy before endoscopy, the findings of endoscopy, and the treatment recommendations after endoscopy. RESULTS: There was no difference in pre-endoscopy therapy or grade of esophagitis in subjects undergoing endoscopy for failed therapy versus GERD symptoms alone. After endoscopy, the most common strategy for patients taking omeprazole was to maintain or increase the dose. For those taking an H2 blocker before endoscopy, the most common outcome was to switch the patient to omeprazole, independent of the grade of esophagitis. CONCLUSIONS: Most patients undergoing endoscopy for symptoms of GERD were switched to omeprazole regardless of the endoscopic findings. No esophageal cancer was identified and the incidence of Barrett's esophagus was low. It appears that endoscopy itself did not change the management of patients receiving H2-blocker therapy. A trial of a proton pump inhibitor before endoscopy should be considered.

Adolescent↗

A randomized, placebo-controlled, double-blind trial of mesalamine in the maintenance of remission of Crohn's disease. The Canadian Mesalamine for Remission of Crohn's Disease Study Group.

BACKGROUND & AIMS: The efficacy of mesalamine for the maintenance of remission in patients with Crohn's disease is controversial. The aim of this study was to conduct a double-blind, placebo-controlled study of mesalamine (750 mg four times a day for 48 weeks) in maintaining remission in 293 patients with Crohn's disease. Patients were stratified according to the method of induction of remission (medical or surgical). METHODS: Patients were assessed at weeks 4, 12, 24, 36, and 48. Relapse was defined as a Crohn's Disease Activity Index of >150 (+60 points over baseline). RESULTS: Of the 293 patients, 246 (84%) returned for at least 4 weeks of follow-up and were included in the final analysis. Thirty of the 118 (25%) who received mesalamine had a relapse compared with 47 of 128 (36%) receiving placebo (P = 0.056). Among those with relapse, the time to relapse was 119 days for the mesalamine-treated patients compared with 109 days for placebo-treated patients (P = NS). However, 25% of mesalamine-treated patients had relapsed by 249 days of follow-up compared with 154 days for placebo-treated patients. Subgroup analysis showed that patients with ileocecal-colonic disease or patients who were women had fewer relapses on mesalamine therapy than placebo-treated patients (21% vs. 41%, P = 0.018; and 19% vs. 41%, P = 0.003, respectively). CONCLUSIONS: Mesalamine treatment reduced relapse compared with placebo treatment, although conventional statistical significance was not achieved.

Adult↗

Ranitidine bismuth citrate with clarithromycin for the eradication of Helicobacter pylori and for ulcer healing.

BACKGROUND: In a pilot study, ranitidine bismuth citrate (RBC; Pylorid, Tritec) in coprescription with clarithromycin achieved a Helicobacter pylori eradication rate (based on 13C urea breath test alone) of 83%. The aim of the current study was to validate this finding by using three diagnostic tests and a larger group of H. pylori-positive patients with active duodenal ulcer. METHODS: In a blinded study, 95 patients were given either 4 weeks of treatment with RBC, 400 mg bid, alone (RBC400, n = 31) or RBC, 400 mg bid or 800 mg bid, in coprescription with clarithromycin, 250 mg qid for 14 days, followed by 14 days of RBC, 400 mg bid, alone (RBC400 + CLAR and RBC800 + CLAR, respectively; n = 32 for each). Rates of ulcer healing at week 4 and of H. pylori eradication (assessed by antral and corpus urease tests and histology and by 13C urea breath test) at week 8 were compared, together with the incidence of adverse events. RESULTS: All three regimens were effective at duodenal ulcer healing and were tolerated well. The coprescription regimens gave significantly higher observed H. pylori eradication rates (82% and 74% for RBC400 + CLAR and RBC800 + CLAR) compared with RBC400 (0%; p < .001). CONCLUSIONS: RBC in dual therapy with clarithromycin provides excellent H. pylori eradication therapy and is an effective duodenal ulcer healing drug.

Adult↗

Endoscopists' opinions of indications for upper gastrointestinal endoscopy.

OBJECTIVE: To determine whether endoscopists and general internists agreed with the characterization of appropriateness for endoscopy of various clinical scenarios, as previously reported by the RAND Corporation. DESIGN: Mail survey. STUDY SAMPLE: All endoscopists in western Canada and a random sample of general internists who did not perform endoscopy. METHODS: Questionnaires were sent to 179 endoscopists in western Canada who were asked to rate the 53 scenarios for endoscopy on a nine-point scale ranging from most appropriate to most inappropriate. A similar questionnaire was sent to 39 general internists practising in the province of Alberta. RESULTS: Response rate was 72% of endoscopists (n = 128) and 64% of general internists (n = 25). Among the endoscopists, there was agreement with the RAND classification for 32 scenarios. All 18 indications previously thought to be appropriate were considered to be appropriate. However, endoscopists agreed with only six of 16 equivocal and eight of 19 indications considered inappropriate. Discrepancies were reviewed by five experienced endoscopists and most appeared to be related to a concern regarding possible malignancy linked in part with the definition of failure to respond to medical therapy; and to a refusal to request a barium meal before endoscopy. Among general internists, there was agreement with RAND in 26 scenarios. When the appropriateness rankings of endoscopists and general internists were compared, there was agreement in 40 of 53 scenarios. Significant discrepancies in ratings were identified in scenarios in which barium studies were described as being normal, known or not done. CONCLUSIONS: The equivocal and inappropriate ratings developed by the RAND Corporation are not uniformly accepted by the endoscopy community or general internists. Use of the RAND indications for assessing quality assurance can be challenged.

Adult↗

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used. SURGERY: Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation. HEALTH ECONOMICS: There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.

Canada↗

Is the Mayo model for predicting survival useful after the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis?

Treatment of patients with primary biliary cirrhosis (PBC) using ursodeoxycholic acid (UDCA) leads to a reduction in serum bilirubin. The first objective of this study was to assess the performance of certain prognostic indicators for PBC after the introduction of treatment with UDCA. Serum bilirubin is an important prognostic indicator for PBC and an important component of the Mayo model for grading patients into risk categories. In an analysis of patients enrolled in the Canadian multicenter trial, the Mayo score was calculated before and after treatment with UDCA. After treatment, the Mayo score continued to divide patients with PBC into groups with varying risk. In addition, the serum bilirubin alone was shown to do the same even after the introduction of treatment with UDCA. A second objective was to establish whether UDCA had an effect on long-term (2- to 6-year) survival in patients with PBC.

Adult↗