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PubMed2002

Increased function of inhibitory neuronal M2 muscarinic receptors in trachea and ileum of diabetic rats.

1. Release of acetylcholine from parasympathetic nerves is inhibited by neuronal M(2) muscarinic receptors. The effects of streptozotocin-induced diabetes on prejunctional M(2) and postjunctional M(3) muscarinic receptor function in rat trachea and ileum were investigated in vitro. 2. Neuronal M(2) muscarinic receptor function was tested by measuring the ability of an agonist, pilocarpine, to inhibit and an antagonist, methoctramine, to potentiate electrical field stimulation (EFS)-induced contraction of trachea and ileum. Concentration-response curves to pilocarpine and methoctramine were shifted to the left in both to a greater degree in diabetics than controls. 3. In trachea, post-junctional M(3) muscarinic receptor function was increased since maximum contractile responses to the muscarinic agonists acetylcholine and carbachol were greater in diabetics than controls. This increase offset the increased function of the inhibitory neuronal M(2) muscarinic receptors since EFS-induced, frequency-dependent contraction was equal in control and diabetic rats. 4. In contrast, post-junctional M(3) muscarinic receptor function was unchanged by diabetes since concentration-response curves to acetylcholine and carbachol were not different between groups. Thus, EFS-induced contractions of the ileum were decreased in diabetics versus controls. 5. In conclusion, inhibitory M(2) muscarinic receptors on parasympathetic nerves in the trachea and ileum are hyperfunctional in diabetic rats. The function of post-junctional M(3) muscarinic receptors in the trachea, but not the ileum, is also increased in diabetes. 6. The dysfunction of inhibitory, neuronal M(2) muscarinic receptors in the airways may protect against hyperreactivity and in the ileum may contribute to gastrointestinal dysmotility associated with diabetes.

Animals↗
PubMed2004

Oral glutamine attenuates indomethacin-induced small intestinal damage.

The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract. In the small intestine, the effects these drugs have been shown to produce include inhibition of cyclo-oxygenase, mitochondrial dysfunction and free radical-induced oxidative changes, all of which contribute to the mucosal damage seen. Glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells. In the present study, we investigated the effect of glutamine on indomethacin-induced changes in the small intestinal mucosa. Rats were given 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine or alanine, in the diet for 7 days. Indomethacin was then administered orally at a dose of 40 mg/kg of body weight. After 1 h, the small intestine was removed and used for the measurement of parameters of oxidative stress and mitochondrial and BBM (brush border membrane) function. Evidence of oxidative stress was found in the mucosa of the small intestine of drug-treated rats, as indicated by significantly increased activity of xanthine oxidase (P < 0.001) and myeloperoxidase (P < 0.001), with corresponding decreases in the levels of several free radical scavenging enzymes and alpha-tocopherol (P < 0.001 in all cases). Levels of products of peroxidation were also significantly elevated (P < 0.001 for all the parameters measured). In addition, oxidative stress was evident in isolated intestinal mitochondria and BBMs (P < 0.001 for all the parameters measured), with associated alterations in function of these organelles (P < 0.001 for all the parameters measured). Supplementation of the diet with glutamine or glutamic acid prior to treatment with indomethacin produced significant amelioration in all the effects produced by the drug in the small intestine (P < 0.001 for all the parameters measured). Glycine and alanine were found to be much less effective in these respects.

Administration, Oral↗
PubMed1986

Whipple's disease.

Whipple's disease is a systemic bacterial infection that once was uniformly fatal and now is treatable with several different antibiotics in most cases. The exact nature of the Whipple's bacillus is unknown, since the organism cannot consistently be cultured. There is also controversy concerning the role of immunologic dysfunction in patients with Whipple's disease. In addition to the small intestine, Whipple's disease can involve the remainder of the gastrointestinal tract, as well as the lymph nodes, joints, nervous system, heart, eyes, hematopoietic system, lungs, liver, and other organs. The clinical manifestations, diagnosis, and treatment of this rare but fascinating disease will be reviewed in this article.

Bacterial Infections↗
PubMed2003

Gastroduodenal and intestinal permeability in primary biliary cirrhosis.

OBJECTIVES: To evaluate gastrointestinal permeability in primary biliary cirrhosis (PBC), using a sensitive method to detect epithelial damage, and to correlate it with the Mayo score, histological stage, ascites, spontaneous bacterial peritonitis, endoscopic signs of portal hypertension and Helicobacter pylori infection. METHODS: Fifty consecutive patients with PBC and 39 patients with cirrhosis of other aetiologies (non-PBC) were enrolled in the study. Coeliac disease was initially ruled out in all participants. Permeability was assessed using sucrose (gastro-duodenum) and lactulose-mannitol (intestine). RESULTS: Sucrose excretion was above the limit in both PBC and non-PBC patients. Twenty-two per cent of PBC patients had an increased result for the lactulose-mannitol test compared to 12.8% of non-PBC cirrhotic patients. PBC patients had high sucrose excretion levels irrespective of the presence of any oesophageal varices, which significantly increased the gastroduodenal permeability in non-PBC patients only when associated with hypertensive gastropathy. Sucrose excretion was significantly enhanced by hypertensive gastropathy in non-PBC patients (P < 0.001) but not in PBC patients. No significant correlation was found in either group between gastrointestinal permeability and the other parameters. CONCLUSIONS: Gastrointestinal permeability is increased in PBC. Portal hypertension contributes to altered gastric mucosal permeability in non-PBC cirrhosis, whereas different epithelial dysfunction can be hypothesized in PBC.

Adult↗
PubMed2006

The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease.

Disruption of the epithelial barrier function of tight junctions by the proinflammatory cytokine interferon (IFN)-gamma plays a fundamental role in the pathogenesis of inflammatory bowel disease and other gastrointestinal disorders, but its precise mechanism has not been established. This Perspective provides an overview of how IFN-gamma triggers barrier dysfunction and bacterial translocation in intestinal epithelial cells, and highlights the roles of internalization of tight-junction transmembrane proteins, as well as rearrangements of the cortical actin cytoskeleton, in intestinal inflammation.

Animals↗
PubMed2002

Practical approaches to migraine management.

Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact pathophysiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause. Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications. Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT(1B/1D) agonists (the 'triptans') and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids. Preventative medication therapy is indicated for patients experiencing frequent and/or refractory attacks.

Adrenergic alpha-Agonists↗
PubMed2002

Recurrent abdominal pain in children: past, present, and future.

The management of recurrent abdominal pain (RAP) in children remains a challenge for physicians. RAP describes a diverse array of clinical presentations. These presentations usually involve abdominal pain and other nonspecific symptomatology for which no organic cause can be found. Long-term recurrence of symptoms is fairly high. RAP was once thought to be a physical manifestation of psychological stressors in children. Past research has neither confirmed nor ruled out the possibility of an organic or psychological etiology. Current theory contends that the clinical presentation of RAP represents a complex interplay between psychosocial and organic factors. New diagnostic subgroups for functional gastrointestinal diseases have been proposed. These subgroups are based on symptoms, since functional disease is often accompanied by no evidence of organic dysfunction. Future research will provide further information on the diagnostic distinctions and different indications for treatment between these subgroups that make up the broader category of RAP.

Abdominal Pain↗
PubMed2003

Mycophenolate mofetil in pediatric renal transplantation.

Since mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), has been approved for maintenance immunosuppressive therapy also in children after renal transplantation it has become an important part of immunosuppressive protocols. By inhibiting inosine monophosphate dehydrogenase, the key enzyme in the de novo purine biosynthesis of proliferating T and B lymphocytes, MMF acts as a relatively specific inhibitor of human lymphocyte proliferation. MMF is more effective than azathioprine in combination with cyclosporin A (CsA) and corticosteroids and distinctly reduces the incidence of acute rejection episodes in the 1st year post-transplant in adults as well as in children. Beneficial effects on steroid-resistant rejection and chronic allograft dysfunction have been shown. In general, MMF is well tolerated. Major adverse events in pediatric renal transplant recipients include leukopenia, infections and gastrointestinal problems. Pharmacokinetic monitoring of MPA can help to optimise MMF therapy after renal transplantation, as associations between the risk of acute rejection episodes and MPA-AUC values and MPA predose levels have been demonstrated. The incidence of MMF-related side effects such as leukopenia and/or infections, however, is associated with pharmacokinetic parameters of free MPA. Reference data of relevant pharmacokinetic parameters are available. The possible steroid-sparing potential of MMF is an important issue in pediatric renal transplantation. Preliminary data demonstrate improved longitudinal growth, less cushingoid habitus and lower blood pressure after steroid-withdrawal in pediatric renal transplant recipients under MMF and CsA therapy.

Adrenal Cortex Hormones↗
PubMedDate not supplied

[Effect of disorders of thyroid function on phenazone pharmacokinetics].

Phenazone elimination test, as a marker of metabolic efficiency of the liver, was carried out in 11 hypothyroid patients. 20 hyperthyroid patients, 10 persons after hyperthyroidism treatment and in 20 healthy persons as a control group. In hyperthyroid patients the acceleration, and in hypothyroid patients the delay of phenazone elimination, in comparison with a control group was observed. Moreover, the impairment of phenazone gastrointestinal absorption was shown in hypothyroid patients and in persons after hyperthyroidism treatment. Similar alterations may be expected in persons with thyroid dysfunctions to whom the drugs with pharmacokinetic properties similar to phenazone are administered.

Adult↗
PubMed1985

[Liver function disorders and damage in critically ill intensive care patients].

The course of the disease of critically ill patients is complicated and prognosis worsened by failure of one or more organs. During intensive care monitoring and treatment of vital functions most attention usually is paid to the cardio-pulmonary and renal system; liver function is neglected rather often. In a retrospective study 100 critically ill patients were evaluated, who had serum bilirubin levels above 3,0 mg/dl, but no primary liver disease. Excluded were patients who had liver destruction caused for instance by liver abscess or metastases, and patients with acute hemolysis and extrahepatic cholestasis. Severe infection was the primary cause of disease in 64% of these critically ill patients without primary liver dysfunction; 52% patients had septicemia, 37% patients were in a post-operative or post-traumatic status, 28% patients had severe gastrointestinal complications, 23% had myocardial pump failure, 32% had protracted shock, 29% had hematological disease, 59% had lung failure, and 58% renal failure. It was tried to find a correlation between the different liver function parameters in this group of patients. In spite of rather pronounced pathological findings a statistically significant correlation could only be found between SGPT and SLDH. This study demonstrates the importance of liver involvement in critically ill patients on the one side and the necessity of comprehensive and repeatedly performed investigations of liver function in such patients on the other side.

Adolescent↗
PubMed1984

[The irritable colon].

Gut dysfunction can be demonstrated in 20-30% of normal adults without ever developing real illness. Irritable bowel syndrome is not merely a gastrointestinal disturbance, but involves the whole organism. With respect to etiology a number of factors such as constitution, mental state and environment, colonic motility, gastrointestinal peptides, low residue diet, food intolerance and infections all seem to play a role. Positive diagnosis by electromyography has not gained any clinical relevance. Treatment of gastrointestinal functional disorders is characterized by a considerable positive response to placebo and is oriented towards individual symptoms. Bran and bulking agents are effective when constipation is present, opiate-agonists have a positive influence in diarrhoea, anti-cholinergics may be of some value in abdominal pain, antidepressants and sedatives given for a limited period of time may be beneficial in psychiatric symptoms. The combination most often used in therapy of irritable bowel syndrome consists of sedatives, anticholinergics and bulking agents. Psychotherapy can prolong the positive effects of medical therapy even beyond the treatment period. Long-term follow-up reveals a satisfactory response of the symptomatology in the majority of patients.

Adult↗
PubMed1982

[The irritable colon].

Irritable bowel syndrome is the most common gastrointestinal disorder. The motility disturbance determines the clinical presentation and two types are distinguished, i.e. spastic colon and painless diarrhea. The motor dysfunction is probably related to abnormal myoelectric activity of the colon. In contrast to healthy persons, slow electrical waves with a frequency of 3 cycles per minute predominate. Although irritable bowel syndrome is a disease of unknown etiology, psychological factors and fibre-deficient diet may be involved. The work-up should take into account the fact that irritable bowel syndrome remains a diagnosis by exclusion. The effect of current therapy on the chronic-relapsing course of this disease is only slight.

Adult↗
PubMed1999

Review article: an integrated approach to the irritable bowel syndrome.

Our understanding of the pathophysiology of irritable bowel syndrome (IBS) has evolved from a disorder of motility to a more integrated understanding of enhanced motility and visceral hypersensitivity associated with brain-gut dysfunction. Psychosocial factors contribute to the predisposition, precipitation and perpetuation of IBS symptoms, and affect the clinical outcome. Newer brain imaging techniques (e.g. PET, fMRI) may help us understand the relationship between altered emotional states with pain enhancement and other gastrointestinal symptoms. Diagnosis using symptom-based (e.g. Rome) criteria and a conservative diagnostic approach is recommended. Treatment is based on an effective physician-patient relationship and a combined pharmacological and behavioural approach. Newer medications acting at the 5-HT receptor may help in reducing pain and bowel dysfunction. For more severe pain, antidepressants may be considered.

Colonic Diseases, Functional↗
PubMed2006

Canadian consensus on medically acceptable wait times for digestive health care.

BACKGROUND: Delays in access to health care in Canada have been reported, but standardized systems to manage and monitor wait lists and wait times, and benchmarks for appropriate wait times, are lacking. The objective of the present consensus was to develop evidence- and expertise-based recommendations for medically appropriate maximal wait times for consultation and procedures by a digestive disease specialist. METHODS: A steering committee drafted statements defining maximal wait times for specialist consultation and procedures based on the most common reasons for referral of adult patients to a digestive disease specialist. Statements were circulated in advance to a multidisciplinary group of 25 participants for comments and voting. At the consensus meeting, relevant data and the results of voting were presented and discussed; these formed the basis of the final wording and voting of statements. RESULTS: Twenty-four statements were produced regarding maximal medically appropriate wait times for specialist consultation and procedures based on presenting signs and symptoms of referred patients. Statements covered the areas of gastrointestinal bleeding; cancer confirmation and screening and surveillance of colon cancer and colonic polyps; liver, biliary and pancreatic disorders; dysphagia and dyspepsia; abdominal pain and bowel dysfunction; and suspected inflammatory bowel disease. Maximal wait times could be stratified into four possible acuity categories of 24 h, two weeks, two months and six months. FUTURE DIRECTIONS: Comparison of these benchmarks with actual wait times will identify limitations in access to digestive heath care in Canada. These recommendations should be considered targets for future health care improvements and are not clinical practice guidelines.

Canada↗
PubMed2004

Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans.

The gut is a neurological organ, which implies that many neuroactive drugs such as opioid analgesics can seriously disturb gastrointestinal function, because many of the transmitters and transmitter receptors present in the brain are also found in the enteric nervous system. One of the most common manifestations of opioid-induced bowel dysfunction is constipation which results from blockade of peristalsis and intestinal fluid secretion. The discovery of opioid receptor antagonists with a peripherally restricted site of action, such as N-methylnaltrexone and alvimopan, makes it possible to normalize bowel function in opiate-treated patients without compromising central opioid analgesia. There is emerging evidence that opioid receptor antagonists may also have prokinetic actions, reversing pathological states of gastrointestinal hypomotility that are due to overactivity of the enteric opioid system.

Analgesics, Opioid↗
PubMedDate not supplied

Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract.

Functional disorders of the gastrointestinal tract comprise a common but ill-defined group of diseases; they primarily afflict women. Although predominantly involving nerve and muscle, the cellular and molecular bases of the pathogenesis of these functional disorders are unknown. Clinical studies indicate that some result from neural dysfunction within the enteric nervous system, others may be due to muscular problems, and the causes of still others remain unknown. Laboratory studies have shown that ovarian products such as progesterone, luteinizing hormone, human chorionic gonadotropin, and relaxin (but not estrogen), are neural antagonists of gastrointestinal motility. The production and secretion of these ovarian substances are controlled by gonadotropin-releasing hormone (GnRH) released from the hypothalamus; they probably act on gamma-aminobutyric acid receptors and alter chloride influx into the cell. GnRH analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal axis and inhibit the secretion of gonadal products involved in such hormone-dependent diseases as endometriosis and prostate cancer. Acting on the GnRH receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH analogs are also effective neural modulators in such disorders as functional bowel disease. These analogs are a promising new group of compounds that may be used to treat difficult gastrointestinal problems.

Chorionic Gonadotropin↗
PubMed1998

Angiotensin converting enzyme inhibitor therapy in severe postcardiotomy dysfunction: a prospective randomized study.

BACKGROUND: Occurrence of severe postcardiotomy dysfunction requiring prolonged postoperative support with intra-aortic balloon counterpulsation (IABP) and inotropes, complicating surgery for coronary artery disease and valvular heart disease carries important hospital morbidity and mortality. This study evaluated the impact of angiotensin converting enzyme inhibitor (captopril) therapy in these patients in the early postoperative period. METHODS: During a 5-year period, 298 patients with prolonged diminished cardiac output required support (> 48 to 72 hours) with IABP plus two or three inotropes. This cohort was randomized to two groups, group A (195 patients) who were continued on IABP and inotropes alone and group B (103 patients) who were given an angiotensin converting enzyme (ACE) inhibitor, captopril 48 to 72 hours postoperatively and continued on IABP and inotropes. RESULTS: Tissue perfusion and hemodynamic parameters improved (p < 0.0001) in group B with early termination of IABP (duration of support mean 86 hours in group B vs 169 hours in group A) and inotropes. Peak improvement in tissue perfusion and hemodynamic parameters correlated with decreased serum angiotensin converting enzyme levels. Hospital mortality occurred in 31% of patients in group A and 14.5% in group B. Morbidity complications developed in 37% of patients in group A and 20% in group B. The average length of hospital stay in group A was 27 days and 17 days in group B. Cardiac, pulmonary, infective, gastrointestinal, renal, and neurological complications were common in both groups. CONCLUSION: Administration of ACE inhibitors in the early postoperative period to patients with severe postcardiotomy dysfunction caused improvement in tissue perfusion with decreases in mortality, morbidity, and length of hospital stay. These drugs, by effectively limiting physiological effects induced by renin angiotensin-aldosterone axis and other mechanisms, caused recovery of stunned myocardium. More randomized trials are needed before recommending these drugs for routine use in similar patients.

Angiotensin-Converting Enzyme Inhibitors↗