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PubMed2006

Endoscopic approaches to enteral nutritional support.

Enteral is preferred to parenteral nutritional support for acute and chronic diseases because it is more physiological and associated with fewer infection complications. Nasal tube feedings are generally used for 30 days or less and percutaneous access for the longer-term. Feeding by naso-gastric tubes is appropriate for most critically ill patients. However, trans-pyloric feeding is indicated for those with regurgitation and aspiration of gastric feeds. Deep naso-jejunal tube feeding is appropriate for patients with severe acute pancreatitis. There are several methods for endoscopic placement of naso-enteric tubes. Percutaneous endoscopic gastrostomy is used for most persons requiring long-term support. Long-term jejunal feeding is most often used for persons with chronic aspiration of gastric feeds, chronic pancreatitis intolerant to eating, or persons in need of concomitant gastric decompression. Percutaneous endoscopic gastrostomy with a jejunal tube extension is fraught with tube dysfunction and dislocation. Direct percutaneous endoscopic jejunostomy tubes may be more robust, but are less commonly performed.

Endoscopy, Gastrointestinal↗

PubMed1988

Endoscopic esophageal varix ligation: technique and preliminary results in children.

A technique for treating esophageal variceal hemorrhage in children using endoscopically placed rubber ligatures was evaluated in six children. The method offers a major advantage over chemical obliteration of varices by sclerosants in the absence of systemic, local, or distant organ reactions and, perhaps, in the avoidance of esophageal motor dysfunction.

Adolescent↗

PubMed2002

Effects of mosapride citrate, a 5-HT4 receptor agonist, on colonic motility in conscious guinea pigs.

It is known that 5-HT(4) receptors in the colon of guinea pigs show a distribution similar to that in humans. Thus, we examined the effects of mosapride citrate (mosapride) and cisapride, two 5-HT(4)-receptor agonists, on colonic motility in conscious guinea pigs implanted with force transducers. Mosapride and cisapride administered intragastrically at doses of 3 - 30 mg/kg significantly enhanced the colonic motility. The enhancing effect of mosapride was antagonized by atropine or GR113808, a 5-HT(4)-receptor antagonist, but not by methysergide, a 5-HT(1)- and 5-HT(2)-receptor antagonist; ondansetron, a 5-HT(3)-receptor antagonist; or CP-99994, a tachykinin NK(1)-receptor antagonist. In vitro receptor autoradiography showed that mosapride and cisapride inhibit the specific binding of [(125)I]-SB207710, a selective radioligand of 5-HT(4) receptors, in the colon of guinea pigs. These results suggest that mosapride enhances colonic motility through the 5-HT(4)-receptor activation in guinea pigs and may be useful for treating constipation in patients with colonic motility dysfunction.

Animals↗

PubMed2004

Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction.

BACKGROUND & AIMS: We established the concept that transient enteric infection may lead to persistent gut dysfunction, evident in vitro, in nematode-infected mice. The present study determined whether gut dysfunction in this model involves motor and sensory changes reminiscent of changes found in patients with postinfective irritable bowel syndrome (PI-IBS) and investigated underlying mechanisms. METHODS: Mice infected up to 70 days previously with Trichinella spiralis (Tsp) underwent videofluoroscopy with image analysis to assess upper gastrointestinal motility. Pseudoaffective responses to colorectal distention (CRD) were assessed using a barostat and validated by single fiber recordings from spinal nerves during CRD. Tissues were examined at different time points for histology, immunohistochemistry, and cytokine analysis. Some mice received dexamethasone intraperitoneally on days 23-25 PI or Tsp antigen orally on days 29, 43, and 57 PI. RESULTS: From day 28 PI, no discernible inflammation was present in the gut. Frequency and propagation velocity of intestinal contractions decreased, and retroperistalsis increased at days 28 to 42 PI. CRD induced an allodynic and hyperalgesic response in PI mice, which was accompanied by increased single unit discharge. Gavage of Tsp antigen induced T-cell responses and sustained gut dysfunction for 70 days PI. Administration of dexamethasone postinfection normalized dysmotility and visceral hyperalgesia. CONCLUSIONS: Long-lasting gut dysmotility and hyperalgesia develop in mice after transient intestinal inflammation. These changes are maintained by luminal exposure to antigen and reversed by corticosteroid treatment. The findings prompt consideration of this as a model of PI-IBS.

Animals↗

PubMed2000

Clinical results of the transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of variceal bleeding.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has been popularized for the treatment of refractory variceal bleeding. The aim of this study was to assess the safety and long-term effect of TIPS in the treatment of variceal bleeding that is not controlled with pharmacological and endoscopic treatment. METHODS: Thirty-six patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) due to refractory variceal bleeding were included in the study. The effectiveness of portal decompression and bleeding control was evaluated. Upper gastrointestinal endoscopy was performed to analyse the degree of varices and portal hypertensive gastropathy (PHG) before TIPS procedure and one to three weeks after TIPS. Angiography was performed in surviving patients, if bleeding recurred, or if ultrasonography or endoscopy suggested stent dysfunction. RESULTS: TIPS were successfully placed in 36 of 38 patients (94.6%). TIPS achieved hemostasis of variceal bleeding in 34 patients (94.4%). Portal venous pressure decreased from an initial average of 28.7 +/- 7.9 to 23.2 +/- 9.4 mmHg after TIPS (p < 0.05). The portosystemic pressure gradient was significantly decreased from 15.5 +/- 6.3 to 7.8 +/- 4.1 mmHg (p < 0.01). The degree of esophagogastric varices and PHG was significantly improved after TIPS. The total length of follow-up was from one day to 54 months (mean: 355 days). The actuarial probability of survival was 83% at one year and 74% at two years. Overall, 16 episodes of stent dysfunction were diagnosed during follow-up. Stent revision by means of angioplasty was successfully performed in 14 of these episodes. CONCLUSION: TIPS is an effective and reliable nonoperative means of lowering portal pressure. This procedure has proved useful in the management of acute variceal bleeding refractory to endoscopic treatment. Surveillance by ultrasonography, endoscopy, and angiographic intervention is useful for the maintenance of shunt patency.

Adult↗

PubMed2001

Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis.

Neurological manifestations of gastrointestinal disorders are described, with particular reference to those resembling multiple sclerosis (MS) on clinical or MRI grounds. Patients with celiac disease can present cerebellar ataxia, progressive myoclonic ataxia, myelopathy, or cerebral, brainstem and peripheral nerve involvement. Antigliadin antibodies can be found in subjects with neurological dysfunction of unknown cause, particularly in sporadic cerebellar ataxia ("gluten ataxia"). Patients with Whipple's disease can develop mental and psychiatric changes, supranuclear gaze palsy, upper motoneuron signs, hypothalamic dysfunction, cranial nerve abnormalities, seizures, ataxia, myorhythmia and sensory deficits. Neurological manifestations can complicate inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease) due to vascular or vasculitic mechanisms. Cases with both Crohn's disease and MS or cerebral vasculitis are described. Epilepsy, chronic inflammatory polyneuropathy, muscle involvement and myasthenia gravis are also reported. The central nervous system can be affected in patients with hepatitis C virus (HCV) infection because of vasculitis associated with HCV-related cryoglobulinemia. Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a disease caused by multiple deletions of mitochondrial DNA. It is characterized by peripheral neuropathy, ophthalmoplegia, deafness, leukoencephalopathy, and gastrointestinal symptoms due to visceral neuropathy. Neurological manifestations can be the consequence of vitamin B1, nicotinamide, vitamin B12, vitamin D, or vitamin E deficiency and from nutritional deficiency states following gastric surgery.

Celiac Disease↗

PubMed1993

Myopathy with mitochondrial alterations in patients with primary biliary cirrhosis and antimitochondrial antibodies.

OBJECTIVE: To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating antimitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. METHODS: Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. RESULTS: Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. CONCLUSION: Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies.

Adult↗

PubMed1979

Subcutaneous transposition of the spleen: a method for treatment of complications in portal hypertension?

Eleven patients with portal hypertension were treated with subcutaneous transposition of a resected spleen. In eight of the patients the operation was performed after variceal bleeding. In this group there was one operative mortality--a 77-year-old woman. Another patient died after 28 months in upper gastrointestinal bleeding. Autopsy showed varices in the gastric fundus and a cancer in the cardia. The other six patients are alive and in good health after 41--60 months. The operation was performed in another three patients, who had not bled. The indication was hypersplenism and esophageal varices in two and severe thrombocytopenia in one. Two of these patients (both with advanced hepatic disease) died postoperatively. The operation is proposed as an alternative method in the treatment of portal hypertension--especially when the main problem is hypersplenism. The operation has no negative effects on liver function and does not cause encephalopathy. Hypersplenism is cured. The survival time and freedom from postoperative bleeding among those who bled preoperatively is in the present material very satisfactory. However, the operation cannot be recommended for the prophylactic treatment of patients with esophageal varices who have not bled--at least not in the patient with advanced hepatid dysfunction.

Adolescent↗

PubMed2005

Time course of depression-symptom improvement during treatment with duloxetine.

The aim of this study was to examine the longitudinal response for overall and individual symptoms during the treatment of major depressive disorder. Data were pooled from two 9-week trials, which compared duloxetine 60-mg QD (n=251) with placebo (n=261) in the treatment of MDD. Changes from baseline in the 17-item Hamilton Depression Rating Scale (HAMD17) and in the Visual Analog Scales for pain were analyzed. Compared to placebo-treated patients, duloxetine-treated patients experienced greater improvement (P<.05) in the HAMD17 total score at Week 2. The individual symptoms showing the most rapid improvements (Week 1) were depressed mood, guilt, suicidal ideation, work/activities, and psychic anxiety as well as VAS back pain and shoulder pain. At subsequent visits, significant improvements were observed in retardation (Week 2); hypochondriasis (Week 3); general somatic symptoms (Week 5); middle and late insomnia (Week 7); and gastrointestinal (GI) symptoms, genital symptoms (level of sexual interest or ease of sexual arousal), insight, and early insomnia (Week 9). Significant advantages for duloxetine were not achieved at any visit for agitation, somatic anxiety, or weight loss. At Weeks 1 and 2, placebo-treated patients had significantly lower GI symptoms and reported less weight loss compared with duloxetine-treated patients; however, differences were not significant at subsequent visits. Furthermore, duloxetine was superior to placebo on GI symptoms at endpoint compared to placebo-treated patients; duloxetine-treated patients had a significantly higher response rate at Week 2 and a higher remission rate at Week 5. These results may help clinicians establish more accurate expectations regarding treatment with duloxetine.

Adult↗

PubMed2001

A review of the potential role of methylnaltrexone in opioid bowel dysfunction.

Opioids are widely used analgesics in patients with advanced cancer. However, their effectiveness for pain relief is often limited by the most frequently occurring side effect, opioid bowel dysfunction (OBD). Because conventional laxation measures are often ineffective in treating OBD, alternative approaches need to be investigated. Opioid action on the gut appears to be mediated mainly by receptors in the gastrointestinal (GI) tract rather than by those in the central nervous system (CNS). Opioid antagonists, such as naloxone, naltrexone, and nalmefene, have been studied as a means of antagonizing the peripheral effects of opioids, but these agents can enter the CNS and reverse analgesia or cause opioid withdrawal symptoms. Methylnaltrexone (MNTX) is a novel quaternary derivative of naltrexone that does not cross the blood-brain barrier and acts as a selective peripheral opioid receptor antagonist. In normal volunteers, intravenous or oral MNTX reverses opioid-induced reduction in bowel motility without affecting analgesia. Bioavailability of MNTX is low after oral administration, and plasma levels do not correlate with its actions in the gut, suggesting a predominantly local luminal action of MNTX on the gut. In patients receiving long-term opioid therapy, MNTX administered intravenously or orally was effective in reducing the delay in oral-cecal transit and eliciting laxation responses in all subjects without causing withdrawal symptoms. MNTX is a peripherally selective opioid antagonist that may have clinical utility in managing OBD with minimal adverse effects.

Analgesics, Opioid↗

PubMed2002

L-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine.

Although cis-diamminedichloroplatinum (II) (cisplatin) is a potent anticancer drug, clinical use of this agent is highly limited predominantly because of its strong side effects on the kidney and gastrointestinal tracts. We found that cisplatin impaired respiratory function and DNA of mitochondria in renal proximal tubules and small intestinal mucosal cells, thereby inducing apoptosis of epithelial cells. Cisplatin-induced mitochondrial dysfunction and DNA (mtDNA) injury, lipid peroxidation, and apoptosis of epithelial cells in the kidney and small intestine were strongly inhibited by L-carnitine. However, carnitine had no appreciable effect on the tumoricidal action of cisplatin against cancer cells inoculated in the peritoneal cavity. These results indicate that L-carnitine may have therapeutic potential for inhibiting the side effects of cisplatin and other anticancer agents in the kidney and small intestine.

Animals↗

PubMed2012

Crohn's disease.

Crohn's disease is a relapsing systemic inflammatory disease, mainly affecting the gastrointestinal tract with extraintestinal manifestations and associated immune disorders. Genome wide association studies identified susceptibility loci that--triggered by environmental factors--result in a disturbed innate (ie, disturbed intestinal barrier, Paneth cell dysfunction, endoplasmic reticulum stress, defective unfolded protein response and autophagy, impaired recognition of microbes by pattern recognition receptors, such as nucleotide binding domain and Toll like receptors on dendritic cells and macrophages) and adaptive (ie, imbalance of effector and regulatory T cells and cytokines, migration and retention of leukocytes) immune response towards a diminished diversity of commensal microbiota. We discuss the epidemiology, immunobiology, amd natural history of Crohn's disease; describe new treatment goals and risk stratification of patients; and provide an evidence based rational approach to diagnosis (ie, work-up algorithm, new imaging methods [ie, enhanced endoscopy, ultrasound, MRI and CT] and biomarkers), management, evolving therapeutic targets (ie, integrins, chemokine receptors, cell-based and stem-cell-based therapies), prevention, and surveillance.

Colonic Diseases↗

PubMed1998

[The value of electrogastrography for the diagnosis of gastroenterologic function].

BACKGROUND AND OBJECTIVE: Abnormalities of gastric myoelectric activity can be measured by electrogastrography (EGG). Such dysfunctions can be associated with disorders of gastric motility. It was the aim of this study to investigate the relationship between gastric electrical activity and motility in patients with dyspepsia due to gastrointestinal or extraintestinal disease. PATIENTS AND METHODS: 135 consecutive patients with dyspepsia (standardized score) were enrolled in this prospective study including patients with functional dyspepsia (FD) (n = 25), dyspepsia in diabetes mellitus type II (n = 27), hyperthyroidism (n = 23), progressive systemic scleroderma (PSS) (n = 20), chronic alcoholism (n = 20), and 20 patients with gastric lesions: gastric ulcer (n = 10) or gastric cancer (n = 10). The EGG measurements were performed over 60 min pre- and post-prandially state after ingestion of a solid-liquid test meal (370 kcal). The following parameters were measured: dominant electrical frequency (DF), percentage of DF in the normal frequency range (2-4 cpm), bradygastria (< 2 cpm), tachygastria (4-10 cpm), dominant frequency instability coefficient (DFIC), and power ratio. The data were compared with results in 40 healthy persons. The gastric emptying was determined by the gastric retention of 99mTc colloid after 60 min (gamma camera). RESULTS: Nearly 50% of FD patients had delayed gastric emptying (gastric retention after 60 min > 68%): they patients exhibited significantly more tachygastrias than those with normal gastric emptying (P < 0.05). Patients with diabetes mellitus type II, PSS and chronic alcoholism showed normal electrical activity, although gastric emptying was delayed in nearly 50%. The hyperthyroid patients had increased tachygastria without abnormal gastric motility. Gastric lesions did not produce pathological electrogastrograms. The dyspepsia score did not correlate with either EGG or radioscintigraphy in the various patient groups. CONCLUSIONS: Electrogastrography can detect tachygastrias, which are significantly increased in some patients with functional dyspepsia. Because of therapeutic consequences electrogastrography seems to be indicated in patients with functional dyspepsia.

Adult↗

PubMed1999

Evaluating the tolerability of the newer antidepressants.

Given their equal efficacy, the choice of a specific antidepressant is largely influenced by side effect (SE) profiles. A number of new agents have recently become available. However, data directly comparing the side effects of these agents are scarce. As suggested by AHCPR guidelines, we used the 1998 Physicians' Desk Reference (PDR) to construct a comparison table using treatment emergent, placebo-adjusted incidence rates for the major (gastrointestinal, central nervous system, and sexual) side effects caused by nine antidepressants (fluoxetine, paroxetine, sertraline, fluvoxamine, nefazodone, bupropion SR, mirtazapine, venlafaxine XR, and citalopram). The results were tabulated to show the relative propensity of each drug to cause a particular side effect. Bupropion SR had the most favorable overall side-effect profile, and fluvoxamine the least favorable. However, there are several limitations in using the PDR to compare the newer antidepressants. Clinical studies directly comparing SEs of newer antidepressants are needed. Sexual SEs substantially affected total SE liability. A simplified summary table, with its advantages and some limitations, is not simple to construct. Pitfalls in this process are discussed.

Antidepressive Agents↗

PubMed1999

The effect of diazepam in the recovery of rabbits from acute acetaminophen intoxication.

We have recently shown that diazepam can reduce mortality of acute iron overdose in rats. The mechanism for that effect is not yet defined. Our objective in the present study was to assess whether diazepam can similarly reduce mortality of experimental acute acetaminophen intoxication. Survival of rabbits was compared among four groups receiving 3 g/kg (body weight) of acetaminophen (LD40) orally each, followed by: 1) nothing (group I), 2) one oral dose of 140 mg/kg N-acetylcystein (NAC) an hour later (group II), 3) intramuscular injection of 7 mg/kg diazepam (group III), 4) intramuscular injection of 7 mg/kg diazepam and one oral dose of 140 mg/kg NAC an hour later (group IV). 37.5% of rabbits in group I died after 16 hours, whereas none of the rabbits in group III died, (p = 0.04). No animal died during the 96-hour observation period in groups II and IV. Two and four hours post drug administration, acetaminophen plasma concentrations (APC) were significantly lower among rabbits in group III than in group I (p = 0.0007 and 0.01, respectively) and significantly lower among rabbits in group IV than in those in group II (p<0.0001 and p = 0.03, respectively). Acetaminophen plasma concentrations 2 hours after drug administration were also significantly lower among rabbits in group III than in those in group II (p = 0.0002). Seven and 24 hours after dosage, APC tended to be higher among rabbits in group III than in those in group I, but not significantly so. Administration of diazepam without NAC did not prevent liver and renal dysfunction. We conclude that early administration of diazepam in acute experimental acetaminophen overdose in rabbits reduced APC and mortality, probably by slowing intestinal motility, which resulted in delayed acetaminophen absorption from the gastrointestinal tract.

Acetaminophen↗

PubMed2000

Treatment guidelines for HIV-associated wasting.

Patients with acquired immunodeficiency syndrome (AIDS) often suffer from weight loss manifested by a loss of body cell mass (BCM). The causes of human immunodeficiency virus (HIV)-associated wasting may include anorexia, malabsorption, and a variety of altered metabolic states. Malabsorption and diarrhea may result from gastrointestinal tract opportunistic infections or from direct effects of HIV on the gastrointestinal tract. Infection with HIV may produce metabolic derangements that alter nutrient utilization, resulting in loss of BCM. Nutritional assessment of the patient with AIDS should include an evaluation of BCM and physical and psychosocial functioning. Antiretroviral therapy and eradication of opportunistic infections do not always reverse wasting. Treatment should include nutritional counseling. Total parenteral nutrition is sometimes of benefit, particularly in patients with damaged gastrointestinal tracts. Dronabinol and megestrol acetate may promote weight gain; however, dronabinol may have adverse effects, and most of the gain with megestrol acetate is in fat rather than BCM. If gonadal dysfunction is present, testosterone replacement therapy should be included in the treatment plan. Some studies suggest that oral anabolic steroids may improve muscle strength and body composition. In randomized, placebo-controlled trials, mammalian-derived human growth hormone (rhGH[m]) has produced sustained weight and BCM gains in AIDS patients. If a patient continues to lose BCM after the above factors have been addressed and corrected, a 12-week course of rhGH[m] is indicated. Halting the progression of HIV-associated wasting may improve survival, enhance physical and social functioning, and enrich quality of life.

Body Composition↗

PubMedDate not supplied

Significance of asymptomatic biliary tract disease in heart transplant recipients.

Biliary disease in conjunction with heart transplantation was encountered in 13 of 33 patients: in the past history (three patients), at pretransplant evaluation (nine patients), and appearing de novo after transplantation (one patient). Four patients with asymptomatic cholelithiasis underwent transplantation: biliary complications requiring emergency and/or urgent surgery occurred in all, with two deaths. Potentially complicating factors included (1) untoward effects of steroids on tissue healing and infection and (2) interaction between liver dysfunction and/or external bile loss and cyclosporine metabolism. Therapeutic lessons learned from this experience involve (1) selection of monoclonal antibodies over methylprednisolone for rejection control, (2) return of drained bile to the gastrointestinal tract, and (3) careful cyclosporine level and dosage monitoring. Five candidates with asymptomatic cholelithiasis underwent elective pretransplant biliary surgery; despite their compromised heart function, all patients had an uncomplicated postoperative course. We conclude that asymptomatic biliary disease is frequent in transplant candidates, can lead to serious morbidity and/or mortality after transplantation, and ideally can and should be treated before transplantation.

Adult↗

PubMed1986

[Phase I study of 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). Phase I Study Group].

A phase I study on TA-077, a water-soluble nitrosourea, was performed by a 9-institution clinical group using 89 patients with various malignant tumors. The study consisted of single-dose i.v. administration and daily i.v. administration for 3-6 consecutive days. The dose-limiting factor was delayed leukopenia and thrombocytopenia which reached nadirs about 5 weeks and about 4 weeks after the initiation of administration and recovered in 2 to 3 weeks, respectively. Gastrointestinal toxicity, such as nausea, vomiting and anorexia, appeared in the early stage of treatment, although most of these symptoms were mild or moderate. Other side effects, including transient liver and renal dysfunctions observed in a few cases, were mild and appeared not to be dose-dependent. M.T.D. in single administration was considered to be more than 3,000 mg/m2 and M.T.D. in 5-day consecutive administration was considered to be 1,000 mg/m2/day. The recommended dose schedule for initiation of the phase II study was assumed to be 700 to 900 mg/m2/day for 5 consecutive days.

Antineoplastic Agents↗