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At least 775 records · Page 43Linked to original sources
PubMed1990

A century of home parenteral nutrition for Crohn's disease.

During an 11-year period, 41 patients with Crohn's disease were placed on home parenteral nutrition (HPN) for a mean of 1,083 days (range: 33 to 3,258 days). Data were retrospectively analyzed to determine whether HPN had an effect on the course of their disease, i.e., on the number of operative procedures performed and the intensity of required medical therapy. Data represented information obtained during a total of 121 patient-years of HPN for Crohn's disease. The main indications for HPN were short bowel syndrome (66%) and high stoma output. Twenty-four of 41 patients (59%) underwent surgery for Crohn's disease during the course of HPN. There was no significant difference between the number of procedures performed per patient per year of Crohn's disease during pre-HPN and HPN periods (p greater than 0.25). Although there was no significant change in body weight, both serum albumin and transferrin levels increased during HPN (p less than 0.01 and p less than 0.01, respectively). Twenty-nine percent of patients were taking prednisone while on HPN, compared with 54% of patients during the pre-HPN period (p less than 0.01). HPN appeared to result in a significant improvement in the numerically assessed quality of life. During the HPN period, 24 patients had 1 or more HPN-related complications that required 1 to 13 hospital admissions (mean: 1.8). These complications included catheter sepsis in 19 patients, blocked or damaged catheters in 15 patients, and dehydration and/or electrolyte imbalance in 5 patients. Eight patients died, with 7% of deaths secondary to catheter-related sepsis. Although permanent HPN is associated with an identifiable morbidity and mortality and is not associated with a reduction in the frequency of surgery for Crohn's disease, benefits include a decrease in the intensity of medical therapy, an improvement in patients' nutritional state, and a significant perceived improvement in patients' quality of life. Without HPN, we believe all patients would have died secondary to malnutrition and/or dehydration.

Adult↗
PubMed2003

No effect of MDR1 C3435T variant on loperamide disposition and central nervous system effects.

BACKGROUND: The MDR1 gene encodes the efflux transporter P-glycoprotein, which is highly expressed in the small intestine and in the blood-brain barrier. A major function of P-glycoprotein is to limit the absorption and central nervous system exposure of numerous xenobiotics. A genetic polymorphism in the MDR1 gene (C3435T) has been associated with changes in the intestinal expression level and function of P-glycoprotein. The aim of this study was to investigate the effect of this polymorphism on disposition and brain entry of the P-glycoprotein substrate loperamide. METHODS: Healthy white volunteers were genotyped for the MDR1 C3435T polymorphism, and a 16-mg oral dose of loperamide was administered to 8 subjects with the 3435TT genotype and 8 subjects with the 3435CC genotype. Plasma levels of loperamide were determined by liquid chromatography-tandem mass spectrometry. Loperamide-induced respiratory depression was detected as the ventilatory response to carbon dioxide and was used as a measure of central nervous system side effects. RESULTS: We found no significant difference in loperamide pharmacokinetics between individuals homozygous for the C and the T alleles in position 3435 of MDR1, as follows: peak plasma drug concentration, 3164 +/- 1053 pg/mL and 3021 +/- 984 pg/mL; area under the concentration-time curve from 0 to 8 hours, 14414 +/- 4756 pg. h/mL and 14923 +/- 6466 pg. h/mL; and time to peak plasma drug concentration, 3.9 +/- 1.4 hours and 3.9 +/- 2.6 hours for the MDR1 3435CC and 3435TT genotypes, respectively (P >.05, for all parameters). Hypercapnic ventilatory response changed only minimally after ingestion of loperamide (the coefficient of variation during the 0- to 8-hour period was 21% +/- 14% for the sample population), and there was no MDR1 3435 genotype-related effect on respiratory response. Carriers of the 2 major MDR1 haplotypes, MDR1*1 and MDR1*13, did not differ in their response to loperamide. CONCLUSION: There was no association between the MDR1 C3435T variation and plasma levels or central nervous system effects of the P-glycoprotein substrate loperamide in a white study population. The MDR1 haplotype structure was quite variable and supports the use of haplotypes instead of single nucleotide polymorphisms in determining clinical consequences of genetic variation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Octreotide acts on anorectal physiology: a dynamic study in healthy subjects.

BACKGROUND: Somatostatin is localized in the intestinal and pelvic nerves of the anorectum and it seems to act as an important neurotransmitter. However, previous analyses of octreotide (a somatostatin analog) effects on anal function showed conflicting results. By use of a dynamic model in healthy subjects, with comparison to the myogenic effect of glucagon, the aim of our study was to further investigate the pharmacologic targets of octreotide. METHODS: This was a placebo-controlled, randomized, double-blinded crossover study performed in 12 healthy volunteers who received octreotide, glucagon, or placebo intravenously on separate days. During each sequence, several pressure steps in 3 different protocols of rectal isobaric distension were applied with an electronic barostat. Manometric responses of the anal canal, adaptative volumes, and perception scores of the rectum were recorded. RESULTS: During both phasic and stepwise distensions, a significant drug effect was encountered at the anal level. Compared with placebo, octreotide significantly increased pressures at both upper and lower levels of the anal canal. In contrast, glucagon decreased pressures at the upper part of the anal canal. Octreotide significantly decreased rectal volumes to phasic distension, but glucagon did not induce any change on rectal adaptation. In addition, neither drug modified perception scores. CONCLUSION: This study suggests that octreotide acts on reflex arcs and rectal myenteric neurons rather than on anal myogenic targets that respond to glucagon.

Adult↗
PubMed2001

Early pregnancy termination with vaginal misoprostol combined with loperamide and acetaminophen prophylaxis.

The objectives of this prospective non-concurrent cohort study were to confirm the efficacy of vaginal misoprostol for early pregnancy termination and to determine whether the incidence of side effects is lower with prophylactic loperamide and acetaminophen. Two-hundred women with an intrauterine pregnancy < or =56 days gestational age seeking medical pregnancy termination in an ambulatory research clinic were enrolled in the study. One-hundred participants (group 1) ingested 4 mg of loperamide and 500 mg of acetaminophen before the vaginal placement of 800 mirog of misoprostol moistened with 2 mL of saline. If abortion had not occurred, the same regimen was repeated every 24 h (maximum three doses). One-hundred participants (group 2) from the same clinic who previously underwent the same misoprostol regimen without prophylactic medication served as a control group for comparison with respect to abortion success and the incidence of side effects. The rate of successful abortion was not statistically significantly different between the two groups (group 1 93%, group 2 89%). The incidence of opiate analgesic use was significantly less in group 1 (4%) compared with group 2 (16%) (OR 0.22, 95% CI 0.06-0.73, p = 0.01). There was a significantly lower incidence of diarrhea in group 1 (23%) compared with group 2 (44%) (OR 0.38, 95% CI 0.20-0.73, p = 0.003). There was no difference in the incidence of fever/chills or the incidence of emesis between the two groups. Vaginal misoprostol is effective for termination of pregnancy < or = 56 days and the incidence of diarrhea and the use of opiate analgesia is significantly reduced with prophylactic loperamide and acetaminophen.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

The role of cannabinoid receptors in intestinal motility, defaecation and diarrhoea in rats.

We have studied the effects of the cannabinoid receptor agonists (R)-(+)[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2, 3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN 55,212-2, 0. 3-5 mg/kg, i.p.) and (-)-cis-3-[2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) (CP 55,940, 0.03-1 mg/kg, i.p.), the cannabinoid CB(1) receptor antagonist (N-piperidin-1-yl)-5-(4-chlorophenyl)-1-2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A, 0. 3-5 mg/kg, i.p.) and the cannabinoid CB(2) receptor antagonist N-[-(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le- 3-carboxamide (SR144528, 1 mg/kg, i.p.) on intestinal motility, defaecation and castor-oil (1 ml/100 g rat, orally)-induced diarrhoea in the rat. SR141716A, but not SR144528, increased defaecation and upper gastrointestinal transit, while WIN 55,212-2 and CP 55,940 decreased upper gastrointestinal transit but not defaecation. WIN 55,212-3 (5 mg/kg), the less active enantiomer of WIN 55,212-2, was without effect. A per se non-effective dose of SR141716A (0.3 mg/kg), but not of SR144528 (1 mg/kg) or the opioid receptor antagonist, naloxone (2 mg/kg i.p.), counteracted the inhibitory effect of both WIN 55,212-2 (1 mg/kg) and CP 55,940 (0.1 mg/kg) on gastrointestinal motility. WIN 55,212-2 did not modify castor-oil-induced diarrhoea, while CP 55,940 produced a transient delay in castor-oil-induced diarrhoea at the highest dose tested (1 mg/kg), an effect counteracted by SR141715A (5 mg/kg). These results suggest that (i) intestinal motility and defaecation could be tonically inhibited by the endogenous cannabinoid system, (ii) exogenous activation of cannabinoid CB(1) receptors produces a reduction in intestinal motility in the upper gastrointestinal tract but not in defaecation, (iii) endogenous or exogenous activation of cannabinoid CB(2) receptors does not affect defaecation or intestinal motility and (iv) the cannabinoid receptor agonist, CP 55, 940, possesses a weak and transient antidiarrhoeal effect while the cannabinoid receptor agonist, WIN 55,212-2, does not possess antidiarrhoeal activity.

Analgesics↗
PubMed2002

The role of kinin B1 in the plasma extravasation of carrageenin-induced pleurisy.

The role of des-Arg9-bradykinin (des-Arg9-BK) and kinin B1 receptor in the plasma extravasation of rat carrageenin-induced pleurisy was investigated employing B1 receptor agonist and antagonists and kininogen-deficient rats. Expression of the B1 receptor mRNA in pleura was induced from 3 to 5 h after the injection of carrageenin into the pleural cavity of Sprague-Dawley rats. Exogenous injection of des-Arg9-BK into the pleural cavity provoked a significant increase in plasma extravasation in 5 h carrageenin-induced pleurisy, but not in 20 min kaolin-induced pleurisy. The level of immunoreactive des-Arg9-BK in the exudate of 5 h carrageenin-induced pleurisy was higher than that of bradykinin (BK). Administration of the B1 receptor antagonists, des-Arg9-[Leu8]-BK or des-Arg9-D-Arg-[Hyp3, Thi5, D-Tic7,Oic8]-BK significantly reduced the exudation rate. However, intrapleural administration of des-Arg9-BK to plasma kininogen-deficient. Brown Norway-Katholiek rats did not result in a further increase in the plasma extravasation. In conclusion, endogenously generated des-Arg9-BK could contribute to the plasma extravasation in carrageenin-induced pleurisy via mediation of the inducible B1 receptor.

Animals↗
PubMed2002

Effect of quercitrin on the early stages of hapten induced colonic inflammation in the rat.

Quercitrin is a flavonoid with antiinflammatory activity in experimental colitis, associated with an antioxidative action and amelioration of water absorption in vivo. However, its mechanism of action is unclear. This study focuses on the effect of quercitrin (1 and 5 mg/kg) in the early stages (24 h) of trinitrobenzene sulfonic acid colitis. Treatment with the flavonoid prevented the increase in colonic malondialdehyde and inhibited nitric oxide synthase and alkaline phosphatase activity but had no significant effects on observable damage. No effect on neutrophil infiltration (myeloperoxidase) was observed. On the other hand, quercitrin exerted complex effects on colonic hydroelectrolytic transport, showing a slight potentiation of water absorption in vivo (5 mg/kg) as well as a normalization of carbachol stimulated electrogenic ionic transport in the proximal colon in vitro (5 mg/kg). It is concluded that the beneficial effects of quercitrin on trinitrobenzene sulfonic acid chronic colitis arise from an early downregulation of the inflammatory cascade that is associated with amelioration of the disturbances in hydroelectrolytic transport.

Alkaline Phosphatase↗
PubMed2000

Diarrhea.

Diarrhea is a common symptom of many conditions, and making an accurate diagnosis can be daunting. Research efforts have expanded the differential diagnosis of chronic diarrhea and have provided improved methods for the evaluation and management of patients with diarrheal diseases. This article discusses some of these trends and presents the emerging consensus regarding appropriate pathways of caring for patients with diarrheal diseases.

Acute Disease↗
PubMed1978

Chronic diarrhea. A practical approach.

Many patients who present with chronic diarrhea are not found to have an important organic disease. Most will have "functional" diarrhea. The history, the physical examination and the initial laboratory tests should lead to a provisional diagnosis, with respect to the organic or functional origin, and the location of disease in the small or the large bowel. Specific tests are then done to define particular organic causes of which malabsorption, inflammatory bowel diseases, carcinoma of the large bowel, parasitic infections, and metabolic disorders are most common. Patients with suspected functional diarrhea should be investigated at least by stool analysis, proctosigmoidoscopy, and barium enema. Functional diarrhea is common and these patients are no less susceptible to severe disease than is the rest of the population.

Adult↗
PubMed2002

Comparison of the peripheral and central effects of the opioid agonists loperamide and morphine in the formalin test in rats.

The effects of the peripherally restricted opioid agonist loperamide were compared to those of morphine in the formalin test in rats. Both loperamide and morphine were efficacious in producing antihyperalgesia after both subcutaneous and intracisternal administration. The antihyperalgesic effects of peripherally administered loperamide and morphine were antagonized by both naloxone and its quaternary derivative naloxone methiodide. The effects of intracisternally administered loperamide and morphine were antagonized by naloxone SC. However, quaternary naloxone SC did not block the effects of intracisternally administered loperamide, and, quaternary naloxone blocked intracisternally morphine only at a dose approximately 10-fold higher than that required to block peripherally administered morphine. In addition, approximately 10-fold higher doses of naloxone administered SC were required to antagonize loperamide compared to doses required to antagonize morphine when the agonists were administered subcutaneously, suggesting that the effects of loperamide might be mediated by opioid receptors different from those which mediated the effects of morphine. However, neither the kappa-receptor selective antagonist nor-binaltorphimine nor the delta-receptor selective antagonist naltrindole blocked the effects of either opioid agonist. The present results are consistent with the interpretation that the antihyperalgesic effects of opioid agonists can have both a peripheral and a central component of action, and that the peripheral component of action is sufficient to produce antihyperalgesia in the formalin test after peripheral administration. The present results provide further evidence that peripherally restricted opioid agonists might provide clinically useful treatment of some pain states, in particular pain states that might involve sensitization of peripheral nociceptors.

Analgesics, Opioid↗