Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women.

BACKGROUND & AIMS: Bisphosphonates are effective treatment for osteoporosis, but upper gastrointestinal injury associated with some compounds has caused concern. This study compared the incidence of gastric ulcers after treatment with risedronate, a pyridinyl bisphosphonate, and alendronate, a primary amino bisphosphonate. Esophageal and gastroduodenal injury assessed by endoscopy scores was a secondary endpoint. METHODS: Healthy, postmenopausal women (n = 515) received 5 mg risedronate (n = 255) or 10 mg alendronate (n = 260) for 2 weeks. At baseline and on days 8 and 15, subjects underwent endoscopy and evaluator-blinded assessment of the esophageal, gastric, and duodenal mucosa. RESULTS: Gastric ulcers were observed during the treatment period in 9 of 221 (4.1%) evaluable subjects in the risedronate group compared with 30 of 227 (13.2%) in the alendronate group (P < 0.001). Mean gastric endoscopy scores for the risedronate group were lower than those for the alendronate group at days 8 and 15 (P </= 0.001). Mean esophageal and duodenal endoscopy scores were similar in the 2 groups at days 8 and 15. Esophageal ulcers were noted in 3 evaluable subjects in the alendronate group, compared with none in the risedronate group, and duodenal ulcers were noted in 1 evaluable subject in the alendronate group and 2 in the risedronate group. CONCLUSIONS: At doses used for the treatment of osteoporosis, risedronate was associated with a significantly lower incidence of gastric ulcers than alendronate. These findings confirm that bisphosphonates differ in their potential to damage the gastroesophageal mucosa.

Adult↗

PubMed2000

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Adult↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

Small bowel review: part I.

In the past year, there have been many advances in the area of small bowel physiology and pathology. More than 1500 papers were assessed in preparation for this review. Some were selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist. Relevant review articles have been highlighted, and important clinical learning points have been stressed. The topics are varied in scope, and wherever possible show a logical progression from basic physiology to pathophysiology to clinical disorders and management.

Bile Acids and Salts↗

PubMed2000

Applications of recombinant DNA technology in gastrointestinal medicine and hepatology: basic paradigms of molecular cell biology. Part B: eukaryotic gene transcription and post-transcriptional RNA processing.

The transcription of DNA into RNA is the primary level at which gene expression is controlled in eukaryotic cells. Eukaryotic gene transcription involves several different RNA polymerases that interact with a host of transcription factors to initiate transcription. Genes that encode proteins are transcribed into messenger RNA (mRNA) by RNA polymerase II. Ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs) are transcribed by RNA polymerase I and III, respectively. The production of each mRNA in human cells involves complex interactions of proteins (ie, trans-acting factors) with specific sequences on the DNA (ie, cis-acting elements). Cis-acting elements are short base sequences adjacent to or within a particular gene. While the regulation of transcription is a pivotal step in the control of gene expression, a variety of molecular events, collectively known as 'RNA processing' add an additional level of control of gene expression in eukaryotic cells. (Pour le résumé, voir page suivante)

Animals↗

PubMed2000

From bench to bedside to bug: an update of clinically relevant advances in the care of persons with Helicobacter pylori- associated diseases.

In-depth meetings of the XIth International Workshop on Gastroduodenal Pathology and Helicobacter pylori led to the presentation and discussion of extensive new data on H. pylori and its diseases. The mode of transmission of H. pylori remains unclear, and it remains unknown why only a small proportion of infected individuals develop duodenal or gastric ulcer disease and even fewer develop gastric cancer. The role of H. pylori eradication in persons with uninvestigated dyspepsia remains controversial. New clinical trials of H. pylori treatment show symptom relief and improvement in the quality of life of persons with functional dyspepsia, especially in those with ulcer-like or reflux-like dyspepsia. Clearly the move is toward symptom-based management of persons with dyspepsia, with fewer endoscopies being needed in the otherwise healthy young dyspeptic patients. It remains controversial whether eradicating H. pylori in duodenal ulcer or functional dyspepsia increases the risk of subsequent development of gastroesophageal reflux disease. The one-week proton pump inhibitor-based triple regimens remain the gold standard of H. pylori therapy, but some of the ranitidine bismuth citrate plus two antibiotic regimens also achieve an 80% H. pylori eradication rate on an intention-to-treat basis. While the urea breath test remains the noninvasive test of choice, interesting new data are available on the use of stool antigen testing to diagnose H. pylori infection. The number of H pylori-associated gastroduodenal diseases grows to include possible liver, vascular, immune and skin conditions.

Anti-Bacterial Agents↗

PubMed2000

Implications of antibiotic resistance in the management of Helicobacter pylori infection: Canadian Helicobacter Study Group.

Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori-associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori, formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

Anti-Bacterial Agents↗

PubMed2000

Applications of recombinant DNA technology in gastrointestinal medicine and hepatology: basic paradigms of molecular cell biology. Part A: eukaryotic gene structure and DNA replication.

Progress in the basic sciences of cell and molecular biology has provided an exciting dimension that has translated into clinically relevant information in every medical subspecialty. Importantly, the application of recombinant DNA technology has played a major role in unravelling the intricacies related to the molecular pathophysiology of disease. This series of review articles constitutes a framework for the integration of the database of new information into the core knowledge base of concepts related to the pathogenesis of gastrointestinal disorders and liver disease. The goal of this series of three articles is to review the basic principles of eukaryotic gene expression. The first article examines the role of DNA in directing the flow of genetic information in eukaryotic cells.

Cell Cycle↗

PubMed2000

Critical review of acid suppression in nonvariceal, acute, uppergastrointestinal bleeding.

Nonvariceal, upper gastrointestinal (GI) bleeding is a very common source of morbidity and mortality. The concept of ulcer clot dissolution being facilitated by a low gastric pH has allowed us to better understand the pathophysiology of nonvariceal upper GI bleeding. Placebo-controlled trials have shown the benefit of oral proton pump inhibitor administration in contrast to H(2) receptor antagonists. Furthermore, our recent experience with intravenous proton pump inhibitors has reinforced these observations.

Acute Disease↗

PubMed2000

Ontogeny of intestinal nutrient transport.

Children born prematurely lack the ability to digest and to absorb nutrients at rates compatible with their nutritional needs. As a result, total parenteral nutrition may need to be given. While this nutritional support may be lifesaving, the baby who receives this therapy is exposed to the risks of possible sepsis, catheter dysfunction, and liver disease. The rodent model of postnatal development provides a useful framework to investigate some of the cellular features of human intestinal development. The up-regulation of intestinal gene expression and precocious development of intestinal nutrient absorption can be achieved by providing growth factor(s) or by modifying the composition of the maternal diet during pregnancy and nursing or the weaning diet of the infant. Accelerating the digestive and absorptive functions of the intestine would thereby allow for the maintenance of infant nutrition through oral food intake, and might possibly eliminate the need for, and risks of, total parenteral nutrition. Accordingly, this review was undertaken to focus on the adaptive processes available to the intestine, to identify what might be the signals for and mechanisms of the modified nutrient absorption, and to speculate on approaches that need to be studied as means to possibly accelerate the adaptive processes in ways which would be beneficial to the newborn young.

Adaptation, Physiological↗

PubMed1999

Therapy for H. pylori infection.

The discovery that peptic ulcers can be caused by gastroduodenal infection with Helicobacter pylori and cured by eradication of this bacterial presence has made a profound impact on ulcer management. This article reviews the principles behind such treatment and the regimens in current use, including proton pump inhibitor triple therapies and ranitidine bismuth citrate triple therapies.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Food but not a chemically defined diet interferes with maintenance of intragastric pH at a predefined level using continuous pH-stat-adjusted intravenous infusion of ranitidine in healthy volunteers.

Eight healthy volunteers were used to determine the influence of a normal diet (food) versus an isocaloric chemically defined diet (CDD) on the dose of ranitidine infused continuously over 12 hr, required to maintain the intragastric pH > or = 5 or above. The dose of ranitidine used was adjusted by the pH-stat instrument, Gastrojet, and a target pH of 5.0 was selected. The average ranitidine dose was 43.5 mg for food, 28.3 mg for CDD, and 25.7 mg for fasting. Despite the higher dose of ranitidine used with food, the control of pH was lower than the desired and preset value of pH > or = 5: the average mean pH was 3.99 for food, 5.11 for CDD, and 5.75 for fasting. The percentage of time of pH > or = 5 was 32.0% for food, 73.7% for CDD, and 80.1% for fasting. Thus, when persons are fed a normal diet there is a need for higher doses of ranitidine to maintain the gastric pH > or = 5.0. Even with frequent monitoring of intragastric pH with the Gastrojet, there is much greater variability in pH control with food than with CDD or fasting, and the preset and desired pH level was not achieved. This difficulty in achieving desired end points of pH control when switching from a fasting to a fed state needs to be considered when intravenous ranitidine is used to obtain strict control of intragastric pH.

Adult↗

PubMed1999

Small intestinal Na+,K+-adenosine triphosphatase activity and gene expression in experimental diabetes mellitus.

The Na+,K+-ATPase plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The effect of streptozotocin-induced diabetes mellitus (STZ-DM) on the activity and expression of Na+,K+-ATPase in the rat small intestine was examined in the present study. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (75 mg/kg) and control and STZ-DM rats were killed at day 30 (chronic diabetic state). Levels of Na+,K+-ATPase activity and numbers of sodium pumps were increased two- to threefold in the jejunum and ileum. Sodium pump kinetics were unaltered in STZ-DM. The levels of Na+,K+-ATPase alpha1 and beta1 isoform protein, corresponding mRNAs, and levels of transcription were increased in the jejunal and ileal mucosa of the chronically diabetic rat. The increases in Na+,K+-ATPase functional activity, protein expression, and mRNA were most marked at the level of the ileal mucosa. While a proximal to distal gradient in Na+,K+-ATPase activity and subunit isoform protein levels were observed in both control and diabetic rats, levels of subunit isoform mRNA abundance were similar in both regions of the small intestine in both groups of rats. The alterations in small intestinal Na+,K+-ATPase expression in the chronic diabetic state appear to involve alterations in transcriptional and posttranscriptional events and may likely represent an adaptive response that leads to increased Na+-coupled monosaccharide absorption in the context of a perceived state of nutrient depletion.

Animals↗

PubMed1999

Comparison of 200 mg cimetidine with multiple doses of antacid on extent and duration of rise in gastric pH in volunteers.

The effects on gastric pH of a single administration of 200 mg cimetidine (Tagamet HB) were compared to multiple doses of a liquid antacid (Mylanta) using a pH microelectrode. Gastric pH was monitored for 8 hr in 20 normal fasting volunteers in a crossover design to compare Tagamet HB (two 100-mg tablets administered as a single dose) with Mylanta Suspension, an initial 17.5-ml dose of antacid with additional doses given when gastric pH fell below 3.5. Both treatments increased the pH above 3.5 during the first hour following treatment, with Mylanta being more effective than Tagamet HB. Interestingly, to sustain the reduction in acidity during this 1-hr interval, a mean of 2.45 doses of antacid were administered. Although multiple doses of Mylanta kept the pH above 3.5 (for at least 25% of the time) for the first 4 hr, the single administration of 200 mg of Tagamet HB maintained gastric pH above 3.5 (greater than 25% of time) for the full 8 hr of the study. Compared to Mylanta, the percent of time gastric pH was >3.5 was significantly higher with Tagamet HB during the 3rd to 8th hour after dosing. This study demonstrates that 200 mg of cimetidine administered as Tagamet HB is significantly more effective and has a much longer duration of action in raising gastric pH >3.5 than six doses of Mylanta.

Adult↗

PubMed1999

Diet fat and oral insulin-like growth factor influence the membrane fatty acid composition of suckling rat small intestine.

BACKGROUND: Insulin-like growth factor- plays an important role in small intestine development. The presence of insulin-like growth factor-1 and the complexity of the fatty acid composition in breast milk suggests that intestinal development may be influenced by manipulating the levels of these components. METHODS: To determine whether a physiological dose of insulin-like growth factor-1 would influence sucrase and lactase activity levels, 10-day-old suckling rat pups were treated with an oral gavage of insulin-like growth factor-1. Four diets differing in fat composition were fed to lactating dams. Brush border membranes were isolated from jejunal and ileal segments of suckling rat small intestine. Fatty acid analysis of choline and ethanolamine phospholipids was performed. RESULTS: Insulin-like growth factor-1 was found to have no effect on the sucrase and lactase activities of suckling rats. Changes in the diet fat composition of the mother's diet indirectly influenced the fatty acid composition of suckling rat small intestine. Insulin-like growth factor-1 decreased ileal C20:4n-6 levels. A correlation was observed between lactase activity and C20:4n-6 and C22:6n-3 levels. As C20:4n-6 levels increased, lactase activity appeared to decline. Increased lactase activity was observed when C22:6n-3 levels increased. CONCLUSIONS: The changes observed in C20:4n-6 levels in response to oral insulin-like growth factor-1, combined with the apparent trend of increased lactase activity with declining levels of C20:4n-6, may be of significance in the development of the small intestine in early life.

Animals↗

PubMed1999

Canadian Helicobacter pylori Consensus Conference update: infections in adults. Canadian Helicobacter Study Group.

The first Canadian Helicobacter pylori Consensus Conference took place in April 1997. The initial recommendations of the conference were published in early 1998. An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations. Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it was decided that the urea breath test (not serology) should be used for routine diagnosis of H pylori infection unless endoscopy is indicated for another reason; and recommended therapies were a twice daily, seven-day regimen of a proton pump inhibitor (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) or ranitidine bismuth citrate 400 mg, plus clarithromycin 500 mg and amoxicillin 1000 mg, or plus clarithromycin 500 or 250 mg and metronidazole 500 mg. The need was reiterated to have funding for readily accessible, accurate testing for H pylori infection with the urea breath test. It was strongly recommended that regional centres be established to monitor the prevalence of antibiotic-resistant H pylori infections. The initial consensus document referred to pediatric issues that were not addressed in this update but were the subject of a subsequent Canadian Helicobacter Study Group meeting, and will be published later in 1999.

Adult↗

PubMed1999

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter pylori Infection in Children and Adolescents.

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

Adolescent↗