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PubMed2006

Methylnaltrexone, a novel peripheral opioid receptor antagonist for the treatment of opioid side effects.

Methylnaltrexone is an investigational peripheral opioid receptor antagonist, a quaternary derivative of naltrexone. Methylnaltrexone has greater polarity and lower lipid solubility, thus it does not cross the blood-brain barrier in humans. Methylnaltrexone offers the therapeutic potential to block or reverse the undesired side effects of opioids that are mediated by receptors located in the periphery (e.g., in the gastrointestinal tract), without affecting analgesia or precipitating the opioid withdrawal symptoms that are predominantly mediated by receptors in the CNS. This article reviews preclinical studies and clinical opioid bowel dysfunction trial data, and briefly discusses other potential roles of this compound in clinical practice.

Analgesics, Opioid↗

PubMed1997

Calcium polysulfide overdose: a report of two cases.

BACKGROUND: Calcium polysulfide or lime-sulfur solution is a common agricultural product used as a fungicide. Despite its easy availability, only two prior cases of intentional ingestion, both from Japan, have been reported in the literature. CASE REPORTS: Two cases of calcium polysulfide ingestion are presented. In the first case severe acidosis, coma and cardiac arrest occurred. Despite aggressive supportive therapy, the patient expired. Autopsy examination revealed hemorrhagic necrosis of the gastric mucosa. The second patient also exhibited altered mental status and metabolic acidosis. He experienced liver dysfunction, rhabdomyolysis, renal dysfunction, and aspiration pneumonia. He had endoscopically proven esophageal and gastric mucosal burns which developed into esophageal strictures. CONCLUSIONS: Calcium polysulfide ingestions cause direct caustic injury to the upper gastrointestinal tract, coma and severe metabolic acidosis.

Acidosis↗

PubMed2002

[The patient with refractory functional disorders of the gastrointestinal tract].

A group of patients with functional disorders of the gastrointestinal tract, manifest symptoms that are chronic, severe and invalidating. Their refractoriness to different treatments is a great challenge for physicians. They normally have a severe psychological and social dysfunction and an abnormal behavior towards their disease. All these factors lead these patients to perpetuate their illness condition. On the other hand, physicians usually have a negative reaction to their demands, leading to a non-satisfactory patient-physician relationship and to the failure of the healing process. Training in the systemic, biopsychosocial model of diseases and in interpersonal communication skills is required for an adequate management of these patients.

Colonic Diseases, Functional↗

PubMed1991

Psittacine proventricular dilatation syndrome in an umbrella cockatoo.

Psittacine proventricular dilatation syndrome (macaw wasting disease) is a fatal disease of the gastrointestinal tract and, sometimes, the CNS. The disease most often affects macaws and is thought to be of viral origin. An Umbrella cockatoo was referred with signs of neurologic dysfunction. Other unusual findings included flaccid crop, distended duodenum, and acute weight loss. Because treatment has not been reported to be effective, the affected cockatoo was euthanatized to limit spread of the disease.

Animals↗

PubMedDate not supplied

Secondary lymphoma of Waldeyer's ring: natural history and association with prior extranodal disease.

Seven of 16 patients with secondary lymphoma of Waldeyer's ring (15 with non-Hodgkin's lymphoma and one with Hodgkin's disease) had their primary diagnoses made at another extranodal site, usually the gastrointestinal tract. The median interval until development of Waldeyer's ring disease was 37 months. Presenting features were similar to those in previous reports of primary lymphoma of Waldeyer's ring except for the striking degree of cranial nerve dysfunction (83 per cent) in patients with secondary nasopharyngeal disease. Non-Hodgkin's lymphomas were predominantly diffuse (80 per cent) with large cell morphology (53 per cent). Of nine patients who obtained complete remission after Waldeyer's ring involvement, six relapsed (median, 15 months), whereas three remain in complete remission at eight, 32, and 288 months. Twelve patients died (median length of survival, 20 months), eight of whom had disseminated disease, including one patient who also developed massive thyroid lymphoma. Three patients survived at least six years after involvement of Waldeyer's ring. This study confirms the frequent association of secondary lymphoma of Waldeyer's ring with prior extranodal disease, particularly of the gastrointestinal tract. The long latent period and the prolonged survival seen in several patients suggest that occasionally secondary lymphomas of Waldeyer's ring may represent metachronous primary tumors.

Adult↗

PubMed2002

Acute ingestion poisoning with insecticide formulations containing the pyrethroid permethrin, xylene, and surfactant: a review of 48 cases.

BACKGROUND: Forty-eight patients poisoned with insecticide formulations containing permethrin (a Type I pyrethroid insecticide), xylene, and surfactants are reported here. These patients were diagnosed and treated in the Chang Gung Memorial Hospital in Taiwan from January 1987 to June 1999. Ten patients ingested permethrin in error and 38 patients attempted suicide. Gastrointestinal tract signs and symptoms were most common (35/48; 73%), and included sore throat, mouth ulcerations, dysphagia, epigastric pain, and vomiting. Pulmonary abnormalities were documented in 29% (14/48) of patients. Aspiration pneumonitis occurred in eight patients, including onefatal case. Pulmonary edema was observed in two patients. Sixteen patients (33%) had central nervous system involvement including confusion (6/48; 13%), coma (10/48; 21%), and seizures (4/48; 8%). Cardiovascular symptoms in 3/48 (7%) patients were limited to arrhythmias and shock. Mild renal and hepatic dysfunction was found in 5/48 (10%) and 3/48 (6%) of patients, respectively. Leukocytosis occurred in 16 patients (33%) but was not associated with infection. Only one death occurred during this 12.5-year period. CONCLUSION: Poisoning caused by ingesting insecticides containing permethrin, xylene, and surfactant manifests primarily gastrointestinal tract symptoms and signs. The involvement of the central nervous system and lungs were less common, but clinically more significant. The relative contributions of the 20% permethrin, 70% xylene, and 10% surfactant to these toxic manifestations, however, is uncharacterized.

Adult↗

PubMed2002

Endothelial dysfunction in acute coronary syndrome without ST segment elevation in the presence of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) infection is one of the most common chronic infections in humans. While a causative relationship between H. pylori infection and several gastrointestinal disorders has been well established, the association between this condition and the development of atherosclerosis and coronary artery diseases (CAD) is less clear. AIM: To examine the relationship between H. pylori infection and endothelial function in patients with acute coronary syndrome (ACS) without ST segment elevation. METHODS: The study group consisted of 31 patients (17 males aged 38-78 years and 14 females aged 45-80 years) with ACS and without ST segment elevation in whom we measured antibodies to H. pylori and haemostatic factors indicating endothelial function, such as von Willebrand factor (vWF), thrombomodulin (TM), tissue plasmin activator (tPA:Ag), tPA inhibitor (PAI-1:Ag) and fibrinogen. RESULTS: The proportion of patients with H. pylori seropositivity was 93.5%. No significant relationship between parameters of endothelial function and IgG antibodies to H. pylori were found. There was a significant association between antibodies to p54 protein and vWF (p=0.027) and between antibodies to p33 protein and PAI:Ag concentration (p=0.019). CONCLUSIONS: These results suggest that the type of H. pylori antigens and antibodies to these antigens rather than the presence of IgG antibodies to H. pylori may play a role in the development of CAD.

Journal Article↗

PubMed2006

Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors.

BACKGROUND: Sunitinib malate is an oral tyrosine kinase inhibitor recently approved for the treatment of gastrointestinal stromal tumors and renal cell carcinoma. Because the ret proto-oncogene is also inhibited by this agent, clinical evaluation of thyroid function was performed. OBJECTIVE: To describe the prevalence and clinical presentation of thyroid dysfunction related to sunitinib therapy. DESIGN: Prospective, observational cohort study. SETTING: Tertiary care hospital. PATIENTS: 42 patients treated for a median of 37 weeks (range, 10 to 167 weeks). MEASUREMENTS: Following analysis of serial thyroid-stimulating hormone (TSH) measurements collected prospectively during a clinical trial of sunitinib, the authors determined the proportion of patients with thyroid dysfunction. RESULTS: Abnormal serum TSH concentrations were documented in 26 of 42 patients (62%): 15 (36%) developed persistent, primary hypothyroidism; 4 (10%) developed isolated TSH suppression; and 7 (17%) experienced transient, mild TSH elevations. The risk for hypothyroidism increased with the duration of sunitinib therapy. Six of 15 (40%) hypothyroid patients had suppressed TSH concentrations before developing hypothyroidism, suggesting thyroiditis. Two hypothyroid patients evaluated with thyroid ultrasonography had no visualized thyroid tissue despite normal baseline thyroid function. LIMITATIONS: The exploratory nature of this study precluded more frequent biochemical and sonographic analysis that may better define the mechanism of sunitinib-associated thyroid dysfunction. CONCLUSION: Hypothyroidism is a frequent complication of sunitinib therapy. Regular surveillance of thyroid function is warranted in patients receiving the drug. Although the mechanism by which this complication occurs is unknown, the observations of preceding TSH suppression and subsequent absence of visualized thyroid tissue in some patients suggest that sunitinib may induce a destructive thyroiditis through follicular cell apoptosis. This provides a rationale for further investigation of sunitinib treatment in patients with advanced thyroid cancer.

Adult↗

PubMed1986

Liver transplantation in a 23-year-old tyrosinaemia patient: effects on the renal tubular dysfunction.

Orthotopic liver transplantation was performed on a 23-year-old female with hereditary tyrosinaemia. The disorder was diagnosed at 7 years of age due to severe rickets, and the patient was treated with a diet restricted in phenylalanine and tyrosine. Nineteen months before the transplantation she had an acute episode of diffuse gastrointestinal bleeding due to portal hypertension. Three subsequent bleeding episodes with accompanying ascites and signs of encephalopathy were considered life-threatening. Nine months after the liver transplantation the patient is well, but serum transaminases are slightly elevated. Without dietary restrictions serum tyrosine and inorganic phosphate are normalized, no succinylacetone can be detected in serum, and urinary excretion of p-hydroxyphenyllactate and p-hydroxyphenylpyruvate is normal. Excretion of amino acids, glucose and beta 2-microglobulin decreased significantly after the transplantation but is still elevated. The succinylacetone concentration in urine is about 20% of the preoperative level. After an oral tyrosine load, succinylacetone excretion increased sevenfold but no deterioration of the renal tubular function was observed and no tyrosine metabolites were detectable in serum. The findings indicate that the defective tyrosine metabolism occurs in the kidneys, but does not produce tubular dysfunction. The residual tubular dysfunction of the patient is probably due to irreversible damage of the tubular epithelium.

Adult↗

PubMed1990

Esophageal motility, heartburn, and gastroesophageal reflux: variations in clinical presentation of esophageal dysphagia.

Dysphagia is a potentially important symptom, often leading to the finding of an anatomical or motility disorder of the esophagus. Dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders. To explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders, we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory. A clear statistical association of symptomatic dysphagia and heartburn was established; however, no pattern diagnostic of a specific motility disorder was discernible. A sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility. A significant portion of dyspeptic patients exhibited both normal motility and acid exposure. The differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients.

Adult↗

PubMed1980

Pathophysiology of gastrointestinal hormones. Implications for paediatrics.

Gastrointestinal hormones (GI hormones) have received growing interest in endocrinology, gastroenterology and neuroendocrinology. Because of new methodological techniques, they can be measured in plasma and therefore be related to different pathophysiological conditions. In childhood, our present knowledge is as yet limited to the physiological rôle of gastrin at different ages and in some diseases (gastrinoma; Verner-Morrison syndrome) caused by humoral dysfunction. The present review relates the clinical important GI hormones to chemically classified families. The diagnostic value of determining endogenous hormone concentration in plasma and the validity of function tests carried out by administration of exogenous hormones are pointed out. Particular emphasis is given to the trophic action of GI hormones in the development and function of the gastrointestinal tract during childhood. More speculatively, GI hormones are involved in the complex function of the central nervous system, thus making food intake a trophotropic action in a broader sense.

Adenoma, Islet Cell↗

PubMed1986

Oesophageal emptying in patients with gastro-oesophageal reflux.

A reproducible radionuclide technique for measurement of oesophageal emptying of a solid bolus has been used to study normal control subjects, patients with gastro-oesophageal reflux and a subgroup of these patients before and after fundoplication. The number of swallows to empty the oesophagus was significantly delayed in the gastro-oesophageal reflux group compared to controls (P less than 0.001). As a group, patients describing dysphagia had slower oesophageal emptying than patients without dysphagia (P less than 0.001). The presence or absence of pre-existing oesophagitis did not influence oesophageal emptying significantly. Following fundoplication patients did not show any significant alteration in their oesophageal emptying compared with their pre-operative studies, although individually changes were noted in two patients. The solid bolus oesophageal emptying test is easily performed, well tolerated by patients and is a useful method for studying oesophageal dysfunction.

Adult↗

PubMed2000

[Practice Guidelines of the Spanish Society of Cardiology in the postoperative course of congenital heart diseases].

Improvements in myocardial protection, surgical techniques, and perioperative care have made it possible to achieve better prognosis in most congenital heart defects. This requires a coordinated, multidisciplinary approach to patient care, based on the preservation of adequate oxygen delivery to vital organs. It is important to have an understanding of normal postoperative status after cardiac surgery so that abnormal postoperative convalescence can be identified and treated.The causes of abnormal convalescence may be grouped into three categories: a) the pathophysiology of the defect before surgery and the acute changes in physiology that result from surgery; b) the effects of hypothermic cardiopulmonary bypass and deep hypothermic circulatory arrest on organ function, and c) the presence of residual anatomic defects. These conditions may result in prolonged convalescence as well as increased morbidity and mortality. Three primary hemodynamic pathophysiologic disturbances may occur during the postoperative period and lead to abnormal convalescence: left ventricular dysfunction, right ventricular dysfunction and pulmonary hypertension. Though sometimes not directly related to either the cardiac defect or surgery, specific problems involving different organs may alter the normal postoperative period. Neurologic, pneumologic, renal, gastrointestinal and infective complications are discussed separately.

Adult↗

PubMed1999

Role of Interstitial Cells of Cajal and their relationship with the enteric nervous system.

The term 'Interstitial cells of Cajal' (ICC) designates several groups of mesenchymal cells present along the gastro-intestinal tract (GI), in close association with smooth muscle cells and elements of the enteric nervous system (ENS). For years, transmission electron microscopy (TEM) has been the only reliable tool to study ICC. Whilst TEM remains the golden standard for identification of ICC, the observation that the tyrosine kinase receptor c-kit plays a crucial role in their development recently resulted in numerous immunohistochemical studies and also led to a better characterization of their roles. ICC form extensive networks of electrically coupled cells and certain groups of ICC are currently regarded as the source of the spontaneous slow waves of the gut musculature (pacemaker cells). Other ICC appear to be involved in the transduction of the relaxation of smooth muscle triggered by nitric oxide. Abnormal distribution of ICC has been reported in several human diseases and abnormal functioning of ICC might actually be involved in many disorders of GI transit. This review addresses (1) the morphology and relationships of ICC along the GI tract in man and mouse, mainly based on data from immunohistochemistry and confocal microscopy, (2) the emerging role of ICC in the pathophysiology of human diseases, like infantile hypertrophic pyloric stenosis (a common disorder with a dysfunction of the pyloric sphincter), Hirschsprung's disease (aganglion-osis coli) and intestinal pseudo-obstruction, (3) developmental issues, (4) recent reports suggesting a possible link between ICC and gastrointestinal stromal tumors.

Animals↗

PubMed2006

Effect of dutasteride on the symptoms of benign prostatic hyperplasia, and patient quality of life and discomfort, in clinical practice.

OBJECTIVE: To assess the improvements in symptoms, quality of life (QoL), discomfort and satisfaction in patients with symptomatic benign prostatic hyperplasia (BPH) treated with dutasteride in clinical practice. PATIENTS AND METHODS: In a prospective, multicentre open-label study, we evaluated the efficacy and safety in clinical practice of dutasteride, 0.5 mg/day for 24 weeks, in patients with symptomatic BPH. The primary endpoint was the proportion of patients achieving at least a 3-point decrease from baseline in the International Prostate Symptom Score (IPSS) after 24 weeks of treatment. The secondary endpoints included changes from baseline in measures of QoL (IPSS item 8 and BPH Impact Index score, BII), and patient discomfort and satisfaction (visual analogue scales, VAS) at 12 and 24 weeks. RESULTS: Of the 366 patients assessed, 72.5% achieved at least a 3-point reduction in IPSS at 24 weeks; the IPSS decreased from 15.3 at baseline to 10.2 at 12 weeks, and to 9.1 at 24 weeks. There were significant (P < 0.001) decreases in all the individual IPSS items at 12 and 24 weeks, with more marked improvements in voiding symptoms than storage symptoms. There were also significant (P < 0.001) improvements in the BII and VAS scores for patient discomfort and satisfaction at both times. CONCLUSIONS: Dutasteride treatment for 24 weeks significantly improved BPH symptoms, QoL and patient discomfort and satisfaction, and was well tolerated in clinical practice.

Azasteroids↗

PubMed2005

Deficiency in expression of the signaling protein Sin/Efs leads to T-lymphocyte activation and mucosal inflammation.

Our studies have concentrated on elucidating the role of the signaling protein Sin in T-lymphocyte function. We have previously shown that Sin overexpression inhibits T-lymphocyte development and activation. Here we show that Sin-deficient mice exhibit exaggerated immune responses characterized by enhanced cytokine secretion and T-cell-dependent antibody production. Excessive T-cell responses in young mice correlate with spontaneous development of inflammatory lesions in different organs of aged Sin(-/-) mice, particularly the small intestine. The intestinal inflammation is characterized by T- and B-cell infiltrates in the lamina propria, which correlate with crypt enlargement and marked villus expansion and/or damage. Similar to the human intestinal inflammatory disorder Crohn's disease (CD), and in contrast to most mouse models of mucosal inflammation, inflammatory lesions in the gastrointestinal tract of Sin(-/-) mice are restricted to the small bowel. Taken together, these results suggest that Sin regulates immune system and T-lymphocyte function and that immune system dysfunction in the absence of Sin may underlie the pathogenesis of tissue-specific inflammation and enteropathies such as CD.

Adaptor Proteins, Signal Transducing↗

PubMed1992

Irritable bowel syndrome in the general population.

OBJECTIVE: To determine the prevalence of symptoms compatible with a clinical diagnosis of irritable bowel syndrome in the general population. DESIGN: Validated postal questionnaire sent to 2280 subjects randomly selected in 10 year age bands from the lists of eight general practitioners. The Manning criteria were used to define irritable bowel syndrome. SETTING: Urban population in Southampton and mixed urban-rural population in Andover, Hampshire. RESULTS: A response of 71% yielded 1620 questionnaires for analysis, of which 412 (25%) reported more than six episodes of abdominal pain in the preceding year, with 350 (22%) reporting symptoms consistent with the diagnosis of irritable bowel syndrome. The male: female ratio was 1:1.38. More subjects with irritable bowel syndrome had constipation and diarrhoea and 35% with the syndrome reported rectal bleeding compared with an overall prevalence of 20%. Other symptoms and conditions including heartburn, dyspepsia, flushing, palpitations, migraine, and urinary symptoms were significantly more common in the group with irritable bowel syndrome. Abdominal pain in childhood was more common in the subjects with irritable bowel syndrome (12%) than without (3%). One third of the group with irritable bowel syndrome had sought medical advice during the study period (male:female ratio 1:1.21); consultation behaviour was influenced by age and the presence of associated symptoms, varied considerably among patients registered with different general practitioners, and was poorly correlated with symptom severity. CONCLUSION: Symptoms consistent with a diagnosis of irritable bowel syndrome are present in almost one quarter of the general population and tend to be associated with a number of other complaints and conditions, some of which may reflect smooth muscle dysfunction.

Adult↗

PubMed2006

Hepatic encephalopathy: from pathophysiology to treatment.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome due to hepatic dysfunction and porto-systemic shunting of the intestinal blood. Cirrhosis is the most frequent liver disease causing HE. On most occasions, HE appears due to a superimposed precipitating factor (gastrointestinal bleeding, infections, renal and electrolyte disturbances, etc.). Ammonia produced in colon by intestinal bacteria is the main toxic substance implicated in the pathogenesis of HE. Other mechanisms, such as changes in the GABA-benzodiazepine system, accumulation of manganese into the basal ganglia of the brain, changes in blood-brain barrier and neurotransmission disturbances are also present. Clinical manifestations of HE may vary widely, from minimal neurologic changes, only detected with specific tests, to deep coma. Treatment of HE should be directed to controlling the precipitating factors, as well as therapies aimed at correcting the above-mentioned pathophysiological changes, mainly reduction of blood ammonia levels. Artificial liver support systems may play a role in the future. Liver transplantation should be evaluated as a definitive therapy in all cases of HE.

Ammonia↗