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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 343 records · Page 19Linked to original sources
PubMedDate not supplied

Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease.

The influence of prednisone(PR), sulfasalazine(SZ), cimetidine(CM), and phenobarbital(PB) on the pharmacokinetics of metronidazole was investigated in six Crohn's patients. Metronidazole was first administered alone (250 mg bid, po) and then with prednisone (10 mg bid, po), sulfasalazine (1 g bid, po), cimetidine (600 mg bid) or phenobarbital (60 mg bid, po). Each regimen was followed for 6 days and sampling of blood and urine was carried out on the 7th day after the first dose of each regimen. Plasma and urine samples were analysed for the drug and its two principal metabolites, hydroxymetronidazole and metronidazole-1-acetic acid, by HPLC. When given alone, metronidazole had a mean volume of distribution of 0.667 +/- 0.15 lkg-1, a half-life of 9.7 +/- 3.1 h and an oral clearance of 0.852 +/- 0.23 (ml-1 min) kg-1. The disposition kinetics of metronidazole and its metabolites was not altered by CM and SZ. Induction of metabolism of metronidazole by PR was made manifest in significant increases in oral clearance of the former and urinary excretion of the hydroxy metabolite, and significant decrease in AUC of the parent compound. PB also induced the metabolism of metronidazole. This induction was reflected in significant increases in the oral clearance of metronidazole and AUC of the hydroxy metabolite as well as significant decreases in AUC, half-life, and urinary excretion of the parent drug.

Chromatography, High Pressure Liquid↗
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Early nutrition with a high-cholesterol diet alters normal age-related changes in intestinal active transport.

This study was undertaken in the young and growing rabbit to establish the effect of feeding a high-cholesterol (2%) diet on the intestinal in vitro uptake of glucose, galactose, leucine, and cholic acid. Three groups of animals were fed standard Purina chow for 14, 28, and 42 days. A fourth group was fed chow for 14 days followed by high-cholesterol diet for 10 days followed by chow for 4 days. A fifth group was fed chow for 14 days followed by the high-cholesterol diet for 10 days followed by chow for 18 days. Short-term feeding with a high-cholesterol diet reversed the normal developmental decline in the jejunal uptake of some nutrients (e.g., glucose), enhanced the age-related uptake of other nutrients (e.g., galactose and leucine), but had no effect on others (e.g., jejunal uptake of cholic acid). Two weeks after stopping the high-cholesterol diet, there was enhanced jejunal uptake of all nutrients. Colonic uptake of glucose, galactose, and leucine was unresponsive to the effects of early development or of a high-cholesterol diet, whereas the colonic uptake of cholic acid did increase. This altered uptake is not explained by nonspecific mechanisms such as changes in body weight gain, intestinal mass, or effective resistance of the intestinal unstirred water layer. In summary, early feeding of rabbits for a short interval with a high-cholesterol diet is associated with transport changes that may persist, progress, or appear for the first time when the animals are switched from the high-cholesterol diet back to chow. Thus, early feeding with a high-cholesterol diet alters the normal development of intestinal transport function.

Aging↗
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Helicobacter pylori highlights from the first Canadian Digestive Disease Week.

The first annual Canadian Digestive Disease Week (CDDW) took place in Banff, Alberta from March 4 to 10, 1996. The CDDW meeting was attended by over 600 Canadian physicians, fellows and researchers, and included a Gastroenterology Fellows' Program, as well as Practitioners' and Scientific Programs. It was apparent from the posters and presentations that Helicobacter pylori research ongoing in Canada is at the leading edge. World leaders in H pylori research spoke on topics ranging from the genetics of H pylori and the pathogenesis of its associated diseases, to the clinical challenge of successful eradication of infection. This overview summarizes the information about H pylori presented at the 1996 CDDW.

Anti-Bacterial Agents↗
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Small bowel review--Part I.

The small bowel has undergone intense study. Part I of this two-part review of the small bowel focuses on gastrointestinal peptides; intestinal infections and human immunodeficiency virus; drugs; intestinal growth-mucosal proliferation and differentiation; nucleic acids, nucleotides and nucleosides; vitamins and minerals; Whipple's disease; radiation; and early development.

AIDS-Related Opportunistic Infections↗
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Influence of food on the bioavailability of an enteric-coated tablet formulation of omeprazole 20 mg under repeated dose conditions.

The objective of this study was to investigate the influence of food on the bioavailability of omeprazole (20 mg) given as an enteric-coated tablet under repeated dose conditions. This open randomized crossover study consisted of three seven-day treatment periods, each separated by a drug-free period. During each treatment period an enteric-coated tablet of omeprazole was taken once daily either under fasting conditions, or immediately before or after a standardized breakfast. On the last day of each treatment period, blood samples for the determination of plasma omeprazole concentrations were collected at baseline and at predetermined intervals over the 24 h period following drug administration. Fifty-seven male and female subjects, aged 18 to 52 years, completed the study according to the protocol. No statistically significant differences were found when comparing either the before breakfast or after breakfast treatment regimens with the fasting regimen for the estimated mean area under the plasma concentration-time curve (AUC). The maximum plasma concentration was not found to differ significantly among any of the treatment regimens. However, the lower limit of the CI for the comparison of fasting/before breakfast was not contained within the limits of bioequivalence. The time to reach maximum plasma concentration was significantly different when fasting and after breakfast regimens were compared. Thus, under repeated dose conditions, food has no influence on the bioavailability (expressed as AUC) of omeprazole given as the enteric-coated tablet formulation.

Adolescent↗
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Pharmacokinetics and pharmacodynamics during treatment with the omeprazole 20 mg enteric-coated tablet and 20 mg capsule in asymptomatic duodenal ulcer patients.

This study compared the 24 h intragastric pH profile and bioavailability at repeated dosing conditions of the omeprazole 20 mg enteric-coated tablet versus the 20 mg capsule. Forty duodenal ulcer patients in asymptomatic remission completed this randomized open two-way crossover study. Omeprazole 20 mg tablets or capsules were administered for seven days in each period. A 24 h pH recording was performed before the start of treatment and on day 7 of each treatment period. Plasma concentrations of omeprazole were determined 24 h after the dose. The treatment periods were separated by two to four weeks. The difference in percentage of time with pH of at least 3 was less than 16% in favour of the tablet (not significant). The estimated mean area under the plasma concentration-time curve as well as the maximum plasma concentration (Cmax) for omeprazole were 18% and 41% higher, respectively, for the tablet versus the capsule, with the latter percentage being statistically significant. The time to reach Cmax (tmax) with the tablet was, on average, about 0.5 h longer than to reach the tmax of the capsule. This study indicates that the enteric-coated tablet formulation of omeprazole is biodynamically equivalent to the capsule regarding their effects on intragastric pH during repeated dosing.

Adult↗
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Prevention of relapse in reflux esophagitis: a placebo controlled study of ranitidine 150 mg bid and 300 mg bid.

OBJECTIVE: To compare the efficacy and safety of long term use of ranitidine 150 mg bid, 300 mg bid and placebo in prevention of endoscopic and symptomatic relapse of reflux esophagitis in an international, double-blind, placebo controlled, parallel group study. PATIENTS AND METHODS: A total of 279 patients at least 18 years old from hospital out-patient departments with healed esophagitis (grade 0) with no or mild symptoms entered the study. Patients were randomly allocated to receive ranitidine 150 mg, 300 mg placebo twice daily for 48 weeks. Patients returned for symptom assessments at eight-week intervals and for re-endoscopy every 16 weeks. RESULTS: Both ranitidine regimens were significantly more effective than placebo in preventing endoscopic and symptomatic relapse of reflux esphagitis (p = 0.003 for ranitidine 150 mg bid; P < 0.001 for ranitidine 300 mg bid). No statistically significant differences were observed in relapse rates between the two ranitidine regiments. The percentage of patients with endoscopic relapse (grade 2) after 48 weeks were 60%, 37% and 27% for placebo, ranitidine 150 mg bid and ranitidine 300 mg bid, respectively (P = 0.002 for ranitidine 150 mg bid versus placebo; P < 0.001 for ranitidine 300 mg bid versus placebo). Ranitidine was well tolerated. CONCLUSIONS: Ranitidine 150 mg bid and 300 mg bid are safe and effective treatments in the prevention of reflux esophagitis relapse.

Adolescent↗
PubMedDate not supplied

Canadian Helicobacter pylori consensus conference. Canadian Association of Gastroenterology.

These guidelines were created to dispel confusion and provide guidance about how the isolation of Helicobacter pylori infection has led to new opportunities and initiatives to improve patient care. The guidelines are designed for practical application in management decisions, but must remain flexible and amenable to change with new information. Updated versions of the recommendations are anticipated. Although it is now clear that H pylori is a major gastrointestinal pathogen, the extent of the clinical consequences posed by this microorganism has yet to be fully defined.

Anti-Bacterial Agents↗
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Hemorrhagic intestinal Henoch-Schonlein purpura complicated by cytomegalovirus infection.

A 54-year-old man on hemodialysis for acute chronic renal failure and on corticosteroids for Henoch-Schonlein purpura developed massive hematochezia. After extensive clinical investigation, an ileal bleeding site was identified and surgically removed. Pathological examination of the diseased bowel segment revealed an extensive vasculitis with mucosal ulceration attributable to Henoch-Schonlein purpura as well as florid cytomegalovirus infection.

Acute Kidney Injury↗
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The Second Canadian Gastroesophageal Reflux Disease Consensus: moving forward to new concepts.

Gastroesophageal reflux disease (GERD) is a disease with serious consequences that may result in significant impairment in quality of life and disease morbidity. Across all grades of severity of symptoms and severity of underlying esophageal disease, proton pump inhibitors (PPIs) provide therapeutic gains over prokinetics (PKs) or H2 receptor antagonists (H2RAs). The potential cost effectiveness of using medications with higher acquisition costs that may lower health care costs overall is often disregarded when conducting cost comparisons with medications having lower 'up-front' costs. Limiting therapy to less effective agents condemns many patients to protracted suffering, repeated physician visits and needless reinvestigation of symptoms that could have been resolved by appropriate initial therapy. Based on current data, use of any classification of symptom severity as a basis for selecting one class of therapeutic agents over another for first line therapy (i.e. PKs, H2RAs for 'mild' GERD, versus a PPI for 'severe' disease) is unwarranted.

Cost of Illness↗
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Small bowel review: Part II.

In the past year there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 500 papers were assessed; some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist.

Humans↗
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Applications of recombinant DNA technology in gastrointestinal medicine and hepatology: basic paradigms of molecular cell biology. Part C: protein synthesis and post-translational processing in eukaryotic cells.

The translation of mRNA constitutes the first step in the synthesis of a functional protein. The polypeptide chain is subsequently folded into the appropriate three-dimensional configuration and undergoes a variety of processing steps before being converted into its active form. These processing steps are intimately related to the cellular events that occur in the endoplasmic reticulum and Golgi compartments, and determine the sorting and transport of different proteins to their appropriate destinations within the cell. While the regulation of gene expression occurs primarily at the level of transcription, the expression of many genes can also be controlled at the level of translation. Most proteins can be regulated in response to extracellular signals. In addition, intracellular protein levels can be controlled by differential rates of protein degradation. Thus, the regulation of both the amounts and activities of intracellular proteins ultimately determines all aspects of cell behaviour.

Biological Transport↗
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Nutritional effects of surgical and medical treatment for short bowel syndrome.

BACKGROUND: The choice of treatment options in short bowel syndrome (SBS) is hampered by a lack of comparative studies. This study uses a previously validated juvenile pig model of SBS to compare nontreated controls (C), surgical treatment with either proximal colon interposition (CI) or bowel lengthening (BL), with medical treatment with codeine and cimetidine (M). METHODS: Treatment was initiated 6 weeks after resection of 75% of the small bowel, and animals were followed until sacrifice at week 16. Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment. RESULTS: BL and M treatments resulted in improved rates of weight gain; this improvement was associated with improved absorption of dietary fat. The treatments did not affect carbohydrate or protein absorption in vivo. In vitro fatty acid absorption was not increased in any group. Active uptake of glucose was increased in the colon interposition group, but phlorizin binding (reflecting sodium glucose cotransporter activity) did not differ between groups. Gross serosal and microscopic mucosal surface areas increased in all groups; however, there were no significant differences between the treatment groups. CONCLUSIONS: These results demonstrate that bowel lengthening and medical treatment improved the rate of weight gain in this model of SBS. This appeared to be due to improvement in the absorption of dietary fat, which was not caused by alterations in in vitro uptake or mucosal surface area, suggesting these treatments have their affects by altering motility or intraluminal digestion. These findings suggest that these treatments are worthy of further study in treating patients (primary pediatric) with SBS.

Animals↗
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Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats.

BACKGROUND: Intestinal adaptation is a complex physiological process that is not completely understood. Systemic administration of short-chain fatty acids (SCFAs) has been shown to facilitate adaptation to small bowel resection; however the mechanisms underlying this phenomena are unknown. METHODS: Forty-six male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. After surgery, rats were randomly assigned to receive standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous TPN supplemented with SCFAs. On day 3 or 7 after surgery, ileal samples were removed for determination of mucosal wet weight, DNA, RNA, and protein concentrations. Total cellular RNA was extracted for use in Northern blot analysis to quantify proglucagon and ornithine decarboxylase messenger RNAs (mRNAs). RESULTS: Total, mucosal, and submucosal weights were increased (p < .05) in the SCFA group both 3 and 7 days after surgery. Ileal DNA and RNA concentrations were increased (p < .05) in the SCFA group at both time points; however ileal protein concentration did not differ between groups until 7 days after resection. Levels of proglucagon and ornithine decarboxylase messenger RNAs were higher (p < .05) in the SCFA group at both time points. CONCLUSION: The upregulation of proglucagon and ornithine decarboxylase gene expression may be the mechanism by which SCFAs facilitate intestinal adaptation.

Adaptation, Physiological↗
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Lipids in total parenteral nutrition solutions differentially modify lipids in piglet intestinal brush border and microsomal membranes.

BACKGROUND: Fats in the diet modify the lipid composition and function of the intestinal brush border membrane (BBM) as well as the enterocyte microsomal membrane (EMM). METHODS: This study was undertaken in pigs to establish the effect of 3 weeks of total parenteral nutrition (TPN) on the fatty acids in the major phospholipids, (phosphatidylcholine [PC] and phosphatidylethenolamine [PE] in the jejunal and ileal BBM and EMM. RESULTS: In a comparison of 21-day-old milk-fed piglets and newborn animals, there were differences in the major fatty acids (palmitic, 16:0; stearic, 18:0; oleic, 18:1 omega 9, and linoleic acid, 18:2 omega 6) in PC and PE in BBM and EMM. Age-matched (3-week-old) animals fed a lipid-free glucose-containing TPN solution had different membrane fatty acids than did milk-fed piglets, or animals given a soybean oil-containing TPN solution for 21 days. Substituting fish oil or fish oil plus soybean oil altered BBM and EMM fatty acids, compared with the soybean oil-based TPN solutions. These changes varied between the class of phospholipids (PC vs PE), between intestinal site (jejunum vs ileum), and between the type of membrane (BBM vs EMM). CONCLUSIONS: The jejunum and ileum have distinctive control mechanisms for varying their membrane lipids in response to TPN. There is some postmicrosomal modification of lipids between the EMM and BBM. It remains to be established whether the lipid content of the membranes of other organs, and therefore their function, is modified by the lipid composition of parenterally infused lipids.

Aging↗
PubMedDate not supplied

Ontogeny of the small intestine.

During development the gastrointestinal tract undergoes marked changes in many physiological and anatomic properties. The remarkable degree of coordination between the development of the gastrointestinal function suggests that the processes may be signalled by some factors, such as weaning, nutrient intake, growth and hormones. The interactions between nutrition and intestinal development begin when fetuses start swallowing amniotic fluid and extend past weaning. Hormonal control plays a major role in the ontogeny of the small intestine. There are late effects of early nutrition, and the normal progress of ontogeny may be important to ensure that the intestine is capable of adaptation in later life.

Animals↗