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PubMed1992

Use of an animal model for the study of the role of human immunodeficiency virus 1 in the human intestine.

The gastrointestinal manifestations of human immunodeficiency virus (HIV)-1 disease have centered on identifiable causes of intestinal dysfunction such as parasitic and bacterial pathogens. The lamina propria of the intestine contains cell that harbor HIV-1, but the significance of this observation remains unknown. Because limited animal models are available to evaluate the gastrointestinal effects of this infection, a system that uses human fetal intestine transplanted subcutaneously onto the back of an immunodeficient mouse was developed. After 8 weeks, fetal tissues mature into an adult-appearing tissue with a lumen. Cell-free HIV-1 was inoculated into the explants, an evidence for infection was evaluated by histological evaluation, in situ hybridization, and polymerase chain reaction. No evidence for HIV-1 incorporation into epithelial cells could be found. It was concluded that this model provides a system in which intestinal HIV-1 interaction can be evaluated. In this model, cell-free HIV-1 does not appear to infect the epithelial cell.

Animals↗

PubMed1991

The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis.

Low-dose corticosteroids (defined as less than or equal to 10 mg/d of prednisone or equivalent) are used increasingly for the management of rheumatoid arthritis. They are frequently substituted for nonsteroidal antiinflammatory drugs (NSAIDs), particularly in patients with gastrointestinal or other intolerance to NSAIDs, or as "bridge therapy" while patients await the benefits of delayed-acting, disease-modifying agents. Despite their clinical acceptance, published data concerning efficacy are meager. Adverse effects to low-dose corticosteroids are not so frequent nor so severe as those that occur with higher doses. Nevertheless, alterations in glucose metabolism, cutaneous atrophy, cataracts, and glaucoma are common. Osteoporosis, steroid-myopathy, a steroid-withdrawal syndrome, and dysfunction of the hypothalamic-pituitary-adrenal axis appear in some patients. Osteonecrosis, gastrointestinal, cardiovascular, infectious, or neurological complications probably do not occur. Fetal wastage, prematurity, or congenital malformations have not been proven with this dosage.

Adrenal Cortex Hormones↗

PubMed1994

Effect of erythromycin on gastric and gallbladder emptying and gastrointestinal symptoms in scleroderma patients is maintained medium term.

OBJECTIVES: Scleroderma patients frequently present esophageal and gastric emptying abnormalities and small bowel dysfunction. Erythromycin, a macrolide antibiotic, has been found to accelerate gastric and gallbladder emptying in both healthy subjects and diabetic patients. Our objective was to investigate the effects of 4-wk oral erythromycin administration on the gastric and gallbladder emptying, gastrointestinal symptoms (early satiety, abdominal pain, nausea, bloating, vomiting, and constipation), and motilin plasma levels of patients with scleroderma. METHODS: 12 scleroderma patients were investigated before and after 4-wk treatment with 250 mg oral erythromycin three times a day. The effect of a single i.v. dose of 2 mg/kg/h erythromycin on gastric and gallbladder emptying before starting the oral treatment was also evaluated. Gastric and gallbladder emptying after a solid meal were evaluated by sonography. RESULTS: Single i.v. administration of erythromycin before the meal reduced gastric emptying T1/2 from 121.3 +/- 14.0 to 45.5 +/- 7.3 min (p < 0.01) and accelerated gallbladder emptying without affecting the peak. Four-week oral administration of erythromycin reduced gastric emptying T1/2 from 121.3 +/- 14.0 min to 46.5 +/- 8.3 min (p < 0.01). Peak gallbladder emptying was also significantly accelerated, while total emptying remained unchanged (p < 0.01). Furthermore, 4-wk erythromycin administration reduced both motilin plasma levels (from 223.4 +/- 53.8 to 145.4 +/- 67.2 pmol/L, p < 0.01) and symptoms of nausea, vomiting, and abdominal pain (p < 0.01), and increased bowel movements in a subset of scleroderma patients with intestinal pseudo-obstruction. CONCLUSIONS: Erythromycin stimulates gastrointestinal motility in patients with scleroderma. Administered medium-term, it accelerates gastric and gallbladder emptying and alleviates gastrointestinal symptoms.

Drug Administration Schedule↗

PubMed1981

Duodenoscopic sphincterotomy in the treatment of the "sump syndrome".

The "sump syndrome" is recognized as a complication of a choledochoenterostomy (choledochoduodenostomy or choledochojejunostomy) performed for recurrent stone disease. A sump (a pit or well) develops in the distal, nonfunctioning limb of the common bile duct where lithogenic bile, gastrointestinal contents, and debris accumulate. This results in obstruction of the enterostomy stoma producing either cholangitis, pancreatitis pain, and/or cholestasis. It is thought that dysfunction of the sphincter mechanism contributes to the development of this syndrome. Filling defects in the bile duct are appreciated on gastrointestinal series when barium reflexes into the biliary tree through the patent stoma. Treatment has largely been surgical, but, more recently, the availability of ERCP has enabled the endoscopist to make a major contribution to the management of this syndrome. A nonsurgical alternative to treatment is duodenoscopic sphincterotomy which has been performed in 11 patients presenting with the sump syndrome. There have been no recurrences of stones in 10 patients while stones were found in one patient with an open sphincterotomy. In follow-ups of 3-30 months, there was satisfactory relief of symptoms in all patients. Because of these results, duodenoscopic sphincterotomy is recommended as a primary treatment modality in the sump syndrome.

Adult↗

PubMed1996

Gallbladder motility in systemic sclerosis.

In 20 patients with systemic sclerosis (SSc) and 24 healthy controls, gallbladder motility was evaluated by abdominal ultrasonography after stimulation by a standard liquid meal. Results from patients with normal and disturbed oesophageal function were analysed separately in order to investigate the significance of gallbladder motility as a parameter for gastrointestinal involvement in SSc. All patients showed a marked decrease in gallbladder size after stimulation (patients 61 +/- 13%; controls 48 +/- 12%). Patients with oesophageal dysfunction (n = 12) had a slightly lower gallbladder contraction (maximal decrease = 58 +/- 13%) when compared to patients with normal oesophageal function (n = 8; 66 +/- 13%); however, this difference was not statistically significant. Gallbladder motility in patients with SSc was not reduced when compared with healthy controls. SSc-induced oesophageal dysfunction was not associated with impaired gallbladder motility. Thus, measurement of gallbladder emptying is not a helpful tool when looking for gastrointestinal involvement in SSc.

Adolescent↗

PubMed2003

Clinical implications of COX-1 and/or COX-2 inhibition for the distal gastrointestinal tract.

Side effects of the distal gastrointestinal tract after NSAID use are common and more frequent than previously recognized. Increased mucosal permeability and mucosal inflammation are often silent but appear after NSAID treatment with most dual COX inhibitors. Other clinical manifestations include: anemia, occult blood loss, malabsorption, protein-loss, ileal dysfunction, diarrhea, mucosal ulceration and strictures due to diaphragm disease. More common complications are lower gastrointestinal bleeding and perforation, which represent at least one third of all gastrointestinal complications observed with NSAID use. Studies with selective COX-2 inhibitors have shown that, in the short term, these agents do not increase mucosal permeability or induce anemia due to occult bleeding and that, when compared to dual COX inhibitors, lower gastrointestinal complications may be reduced by 50%. In order to minimize the impact of these side effects, it is important to increase the current standards of suspicion by physicians who treat these patients, since drug discontinuation may further reduce damage, and clinical experience with agents that may prevent or treat distal tract damage is very limited. From this perspective, selective COX-2 inhibitors may be the drugs of choice in the high-risk patient that needs NSAIDs. Another important area of uncertainty is the impact of NSAID use in patients with inflammatory bowel diseases. Data from different animal models of inflammatory bowel disease suggest that inhibition of both COX-1 and COX-2 derived prostaglandins affects the severity of the mucosal inflammation. However, current epidemiological and clinical data are contradictory. Since many patients.

Animals↗

PubMedDate not supplied

Intrapartum fetal asphyxial brain injury with absent multiorgan system dysfunction.

Current understanding of the physiologic mechanisms of intrapartum fetal asphyxial brain injury has suggested a strong association with multiorgan system injury. Thus the purpose here is to describe 14 cases of severe fetal brain injury with absent multiorgan system dysfunction (MSD). The study population was drawn from a national registry for brain injured infants. MSD was defined by clinical criteria demonstrated to reflect asphyxial injury to the pulmonary, renal, cardiac, hematologic, hepatic, and gastrointestinal systems. Involvement of one other organ in addition to the brain was defined as multiorgan system dysfunction. All infants were diagnosed with hypoxic-ischemic encephalopathy (HIE) in the neonatal period and went on to have permanent central nervous system (CNS) injury and MSD criteria were not met. Of the 292 term, singleton infants with HIE and permanent neurologic injury, 57 (20%) satisfied the entry criteria; of these, 14 (36%) had no MSD. The underlying basis for the fetal brain injury were: uterine rupture, 6 (43%), prolonged FHR deceleration, 5 (36%), fetal exsanguination, 1 (7%), cord prolapse, 1 (7%), and maternal cardiopulmonary arrest, 1 (7%). The mean duration of the prolonged FHR deceleration was 32.1 +/- 9.1 (range 19-51) minutes. All infants were later diagnosed with cerebral palsy. Intrapartum fetal asphyxial brain injury may not necessarily proceed through a physiologic mechanism in which the fetal circulation is centralized and endorgans damaged. These acute injuries, associated with a prolonged FHR deceleration, may be linked to severely decreased cardiac output and hypotension that cause vulnerable portions of the brain to be injured before other organs.

Asphyxia Neonatorum↗

PubMed1983

Gastrointestinal complications of congenital immunodeficiency states. The surgeon's role.

Ninety-one congenitally immunodeficient patients treated from 1972 to 1981 were reviewed to assess the incidence and nature of gastrointestinal complications. Thirty-three of these patients (36%) developed 59 complications. Patients with immunodeficiencies characterized by neutrophil dysfunction--chronic granulomatous disease (20 patients) and cyclic neutropenia (eight patients)--developed 22 surgical infections, 22 of which required operation. In patients with neutrophil defects, postoperative morbidity was frequent and severe. Gastrointestinal symptoms were common in patients with isolated defects of B or T lymphocytes. Ten of forty-one patients with congenital hypogammaglobulinemia developed gastrointestinal complications, as did one of four patients with DiGeorge Syndrome, and the single patient with secretory IgA deficiency. However, operation was not required for these patients with isolated disorders of lymphocyte function. Patients with combined B and T cell disorders developed gastrointestinal disease, requiring operative therapy at intermediate rates. Gastrointestinal symptoms developed in four of nine patients with severe combined immunodeficiency and three of eight with Wiskott-Aldrich syndrome. Operative therapy was required in two of these seven symptomatic patients.

Agammaglobulinemia↗

PubMed1990

Side-effect profile of cyclosporin A in patients treated for psoriasis.

This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to-moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential.

Creatinine↗

PubMed2002

Incidence of occult rectal prolapse in patients with clinical rectoceles and defecatory dysfunction.

OBJECTIVE: The purpose of this study was to determine the incidence of occult rectal prolapse (rectal intussusception) by defecating proctography in patients with clinical rectoceles and defecatory dysfunction. STUDY DESIGN: Patients who were seen from September 2000 through August 2001 with defecatory dysfunction and clinical rectoceles underwent single contrast defecating proctography. Radiologists who specialized in gastrointestinal fluoroscopy interpreted the results, which were retrieved from a computerized database. Study Design: Sixty patients who met the inclusion criteria were evaluated. Twenty patients (33%) had intussusception; 58 patients (97%) had rectocele; 1 patient (1.7%) had sigmoidocele, and 6 patients (10%) had anismus (paradoxic contraction of the puborectalis). RESULTS: All but 1 case of intussusception was associated with a rectocele radiographically. Anismus was associated with rectoceles radiographically, except in 1 patient for whom it was the sole finding. CONCLUSION: The data suggest a 33% incidence of occult rectal prolapse in patients with clinical rectoceles and defecatory dysfunction. This is highly clinically significant because one third of patients who are examined for defecatory dysfunction and rectocele may require sigmoid resection rectopexy along with other reconstructive procedures to restore pelvic floor function and prevent symptomatic recurrence.

Constipation↗

PubMed2005

Electrogastrography: basic knowledge, recording, processing and its clinical applications.

The slow wave (SW) of the gastrointestinal (GI) tract mainly functions to trigger the onset of spike to elicit smooth muscle contraction, which provides the essential power of motility. Smooth muscle myogenic control activity or SW is believed to originate in the interstitial cells of Cajal (ICC). The electrical coupling promotes interaction between muscle cells, and ICC additionally contribute to SW rhythmicity. Stomach SW originates in the proximal body showing the continuous rhythmic change in the membrane potential and propagates normally to the distal antrum with a regular rhythm of approximately 3 c.p.m. A technique using electrodes positioned on the abdominal skin to pick up stomach rhythmic SW refers to electrogastrography (EGG). The stomach SW amplitude is very weak, while many visceral organs also produce rhythmic electricities, for example heartbeat, respiration, other organs of the GI tract and even body movements. Thus noise other than SW should be filtered out during the recording, while motion artifacts are visually examined and deleted. Finally, the best signal among all recordings is selected to compute EGG parameters based on spectral analysis. The latter is done not only to tranform frequency domain to time domain but also to provide information of time variability in frequency. Obtained EGG parameters include dominant frequency/power, % normal rhythm, % bradygastria, % tachygastria, instability coefficient and power ratio. Clinical experience in EGG has been markedly accumulated since its rapid evolution. In contrast, lack of standardized methodology in terms of electrode positions, recording periods, test meals, analytic software and normal reference values makes the significance of EGG recording controversial. Unlike imaging or manometrical studies, stomach motility disorders are not diagnosed based only on abnormal EGG parameters. Limitations of EGG recording, processing, computation, acceptable normal parameters, technique and reading should be known to conduct subjective assessments when EGG is used to resolve stomach dysfunction. Understanding basic SW physiology, recording methodology and indications may open EGG as a new domain to approach the stomach motor dysfunction.

Action Potentials↗

PubMed2004

Treatment with botulinum neurotoxin of gastrointestinal smooth muscles and sphincters spasms.

Local injections of botulinum neurotoxin are now considered an efficacious treatment for neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum neurotoxin provides benefit in diseases of the gastrointestinal tract. Botulinum neurotoxin inhibits contraction of gastrointestinal smooth muscles and sphincters; it has also been shown that the neurotoxin blocks cholinergic nerve endings in the autonomic nervous system, but it does not block nonadrenergic responses mediated by nitric oxide. This aspect has further promoted the interest to use botulinum neurotoxin as a treatment for overactive smooth muscles, such as the anal sphincters to treat anal fissure and outlet-type constipation, or the lower esophageal sphincter to treat esophageal achalasia. Knowledge of the anatomical and functional organization of innervation of the gastrointestinal tract is a prerequisite to understanding many features of botulinum neurotoxin action on the gut and the effects of injections placed into specific sphincters. This review presents current data on the use of botulinum neurotoxin to treat diseases of the gastrointestinal tract and summarizes recent knowledge on the pathogenesis of disorders of the gut due to a dysfunction of the enteric nervous system.

Anti-Dyskinesia Agents↗

PubMed1989

A subacute rabbit model for hepatobiliary dysfunction during total parenteral nutrition.

Total parenteral nutrition (TPN) in children is associated with the complicating syndromes of cholestasis and cholelithiasis. The causes of these syndromes are not completely clear. Gastrointestinal hypomotility associated with enteral fasting may be involved in the pathogenesis of both syndromes. We compared weanling rabbits maintained solely on TPN with chow pair-fed and free-fed controls over a 10-day period. Gastrointestinal transit time, assessed with a solid marker technique, was significantly greater in the TPN-treated animals. No difference in intestinal or biliary bacterial flora was demonstrated by aerobic or anaerobic cultures. Gallbladder bile contained a higher percentage of lithocholic acid, unconjugated bilirubin, and total calcium in the TPN-treated animals. Markers of hepatic dysfunction were elevated in the serum of the TPN-treated animals. Mild steatosis and edema were the only histologic differences in the livers of the TPN-treated animals. We conclude that gastrointestinal hypomotility associated with enteral fasting plays a role in the pathophysiologic changes leading to TPN-associated hepatobiliary dysfunction. This dysfunction may be mediated by an increase in the absolute and relative concentrations of lithocholic acid in the bile of TPN-treated animals.

Animals↗

PubMed2006

Pathophysiological changes of the gastrointestinal tract in ischemic stroke.

OBJECTIVE: Dysphagia is common after stroke and represents a marker of poor prognosis. After ischemic stroke, dysphagia represents only one part of the clinical spectrum of changes in the gastrointestinal (GI) tract and includes GI hemorrhage, delayed GI emptying, and colorectal dysfunction. State-of-the-art imaging techniques have started to revolutionize to study the cortical and brainstem control of these GI symptoms. It has become increasingly obvious that GI alterations after stroke are complex and its recovery following stroke is even more so. METHODS: In this review, an electronic database research was performed in MEDLINE, EMBASE, and the COCHRANE database using the terms stroke, dysphagia, GI motility, or cortical reorganization; an extensive manual searching was additionally conducted. RESULTS: Cerebral ischemia may lead to an interruption of the axis between central nervous system and GI system. This altered interrelation between the central nervous system and the GI system may cause, among other things, mainly dysphagia, GI dysmotility, and GI hemorrhage. The consecutive clinical symptoms can often be directly attributed to specific cerebral ischemic lesions involving the brain stem as well as certain cortical and subcortical structures. However, in some cases the pathophysiological mechanisms leading to GI symptoms are incompletely understood. Recent improvement of imaging techniques, especially in functional imaging, has lead to new insights of the central control of the GI tract, suggesting that its cortical and medullar organization is multifocal, and bilateral with handness-independent hemispheric dominance. CONCLUSIONS: Following stroke, patients may have swallowing impairment and other changes of the GI tract that could affect nutritional and hydration status and that lead to aspiration pneumonia. Impaired nutritional status is associated with reduced functional improvement, increased complication rates, and prolonged hospital stays.

Deglutition Disorders↗

PubMed2000

Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation.

Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining (NHEJ). Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc-/- mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic, cellular and organismal response to ionizing radiation.

Animals↗

PubMed2004

Establishment of enteral nutrition: prokinetic agents and small bowel feeding tubes.

PURPOSE OF REVIEW: Nutritional support is vital to improving the clinical outcomes in patients in the intensive care unit. Enteral nutrition should be administered early and aggressively, thereby reducing the need for parenteral nutrition. Because nasogastric feeding is often associated with gastrointestinal intolerance, recent research has focused on the use of prokinetic agents or small bowel feeding tubes to enhance the successful establishment and maintenance of enteral nutrition. RECENT FINDINGS: Prokinetic agents (such as metoclopramide and erythromycin) improve markers of gastric emptying and appear to improve tolerance of enteral nutrition, although their effects on clinical outcomes are not as well established. In comparison with nasogastric feeding, small bowel feeding allows the dysfunctional stomach of the critically ill to be bypassed, thereby reducing the rate of gastrointestinal complications and probably the risk of pneumonia. Small bowel tubes are more difficult to place than nasogastric tubes, although the new Tiger tube appears very promising. SUMMARY: Nasogastric feeding is preferred for almost all patients in the intensive care unit. Metoclopramide is the preferred prokinetic agent, although whether it or erythromycin should be administered to all patients in the intensive care unit or only those with gastrointestinal intolerance remains unknown. Small bowel feeding is not currently recommended for all patients in the intensive care unit because the benefits do not appear to outweigh the logistic and cost considerations. Nevertheless, when gastrointestinal intolerance develops in a nasogastrically fed patient, a small bowel feeding tube should be inserted at the earliest opportunity.

Australia↗

PubMed1991

Idiopathic gastroparesis in patients with unexplained nausea and vomiting.

Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation.

Adult↗

PubMed2002

Neurogenic bladder, neurogenic bowel, and sexual dysfunction in people with spinal cord injury.

The purpose of this article is to review the literature related to the effects of spinal cord injuries on genitourinary, gastrointestinal, and sexual function. These important areas of function are profoundly affected by spinal cord injuries, with the effects of injury being dependent on the specific level and degree of neurologic dysfunction. Our ability to manage neurogenic bladder dysfunctions and neurogenic bowel dysfunctions has improved over the past few years; however, in general the techniques used have not significantly changed. In contrast, a significant amount of new information has been made available regarding the effects of specific neurologic injuries on sexual response, particularly female sexual response. Moreover, techniques to remediate erectile dysfunction and infertility in the male have vastly improved the fertility potential of men with spinal cord injuries. Further research is warranted in all of these areas.

Fecal Incontinence↗