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Gastrointestinal manifestations of diabetes mellitus.

This review briefly outlines the gastrointestinal manifestations of diabetes mellitus. Usually, gastrointestinal abnormalities are asymptomatic. Severe gastrointestinal dysfunction may be quite debilitating, however. Gastrointestinal symptoms that are a consequence of diabetes may be confused with other primary gastrointestinal disorders. We attempt to provide a clinical approach to differentiating the basis of symptoms and outline the therapeutic plan that we generally employ. Much additional research is necessary to clarify our understanding of the pathophysiology of the gastrointestinal complications of diabetes and to develop improved therapeutic strategies.

Biliary Tract Diseases↗

Gastrointestinal problems in the handicapped child.

Gastrointestinal issues are a major chronic problem in 80 to 90% of children with cerebral palsy and in children with neurodevelopmental disabilities who are at special risk of developing malnutrition because of uncoordinated swallowing, gastroesophageal reflux, and constipation. In addition to poor linear growth, there is a decrease in muscle strength and coordination, impaired cerebral function leading to decreased motivation and energy. Significant neurodevelopmental progress can be achieved with improved nutritional status. A multidisciplinary approach, with input from neurologists, gastroenterologists, nurses, occupational therapists, and dieticians, can make a major contribution to the medical wellbeing and quality of life of these children. Different neurological diseases ( eg, spinal dysraphism, syringomyelia, tethered cord syndromes) can give rise to gastrointestinal dysfunction and symptoms that may need different gastrointestinal or surgical management. The introduction of new drugs, including proton pump inhibitors and innovative endoscopic and surgical techniques in the management of gastroesophageal reflux disease and constipation also may have an impact on the treatment of neurologically handicapped children in the future.

Child↗

Helicobacter pylori infection and gastric function in primary autonomic neuropathy.

Helicobacter pylori (Hp) infection in diabetic patients has been related to impaired gastric clearance of bacteria due to autonomic neuropathy. Gastrointestinal dysfunction has been described in primary autonomic failure (AF). The aim of the study was to evaluate, for the first time, the presence of Hp infection and gastric function in patients with primary AF Twelve patients with primary AF (aged 58-78), 31 healthy controls (aged 48-75) and 31 patients affected by type 2 diabetes (aged 46-75) were studied. A 13C-urea breath test was performed to assess the presence of Hp infection. To evaluate gastric function, AF patients underwent two non-invasive tests: 1) 13C-octanoic acid breath test (OBT) to evaluate gastric emptying, and 2) electrogastrogram (EGG) to evaluate gastric electrical activity. Hp infection was found in 100% of AF patients, in 48% of controls and in 71% of diabetic patients (p = 0.02 between groups). Electrical or mechanical gastric function was altered in 50% of AF patients. In particular, 1) after OBT, half-time gastric emptying was delayed in 6 out of 12 patients, and 2) EGG showed the presence of gastric dysrhythmias in 6 out of 12 patients. In conclusion, Hp infection was detected in all AF patients studied; as previously demonstrated in diabetes, such a finding might be related to autonomic neuropathy causing mechanical or electrical gastric dysfunction. Hp detection might be important for the gastrointestinal and extradigestive complications of such infection.

Aged↗

Multiple organ dysfunction syndrome due to ingestion of fish gall bladder.

OBJECTIVE: To investigate changes in renal function, urine N-acetyl-beta-D-glucosaminidase enzyme (N-AG),liver function, myocardial enzymes, the pathology of renal damage and the mechanism of acute renal failure (ARF) associated with fish gall bladder poisoning. METHODS: Eleven patients with acute fish gall bladder poisoning were consecutively admitted to our hospital from September 1997 to October 1999. Renal function, urine N-AG enzyme, liver function, and myocardial enzymes were assayed before and after treatment. One patient consented to a kidney biopsy and the pathology of renal damage was observed under light and electron microscopes. RESULTS: All patients had multiple organ dysfunction syndrome (MODS) and 11 patients suffered from ARF. Ten patients had liver dysfunction, ten patients had poisonous myocarditis, and 8 patients had gastrointestinal dysfunction. Renal function, urine N-AG enzyme, liver function, and myocardial enzymes were significantly improved after treatment compared with those of before treatment (P < 0.05). Kidney biopsy showed that the main damage site was the proximal renal tubule. All eleven patients recovered and were discharged from the hospital. CONCLUSIONS: Ingestion of fish gall bladder leads to kidney damage, as well as liver, heart and gastrointestinal tract injury. The mechanism of acute renal function failure is the serious tubular damage, confirming the location of kidney damage. Necrosis of the proximal tubules plays an important role in the development of ARF. Immediate hemodialysis is the most effective treatment.

Adult↗

Methods for decreasing postoperative gut dysmotility.

Postoperative disturbances of gastrointestinal function (postoperative ileus) are among the most significant side-effects of abdominal surgery for cancer. Without specific treatment, major abdominal surgery causes a predictable gastrointestinal dysfunction which endures for 4-5 days and results in an average hospital stay of 7-8 days. Ileus occurs because of initially absent and subsequently abnormal motor function of the stomach, small bowel, and colon. This disruption results in delayed transit of gastrointestinal content, intolerance of food, and gas retention. The aetiology of ileus is multifactorial, and includes autonomic neural dysfunction, inflammatory mediators, narcotics, gastrointestinal hormone disruptions, and anaesthetics. In the past, treatment has consisted of nasogastric suction, intravenous fluids, correction of electrolyte abnormalities, and observation. Currently, the most effective treatment is a multimodal approach. Median stays of 2-3 days after removal of all or part of the colon (colectomy) are now achievable. Recent discoveries have the potential to significantly reduce postoperative ileus in patients with cancer who have had abdominal surgery.

Abdomen↗

Gastrointestinal involvement in patients with diabetes mellitus: Part II (second of two parts). Diagnostic procedures, pharmacological and nonpharmacological therapy.

Diagnostic work-up in patients with diabetes mellitus, in whom gastrointestinal involvement is suspected comprises the assessment of gastrointestinal transit times, endoscopy, esophageal pH-metry or manometry, sonography and lactulose- or glucose-H2-breath tests. Prokinetic agents such as metoclopramide, cisapride or erythromycin and substances like loperamide, octreotide or clonidine are used to improve gastrointestinal dysfunction. Furthermore, in recent trials which aimed for the modulation of gastrointestinal transit times, cholecystokinin, proteinase inhibitors or amylin were administered in patients with diabetes mellitus. Nonpharmacological interventions include pancreas and kidney transplantation, gastric pacemakers and biofeedback training.

Diabetes Mellitus, Type 1↗

Myotonic dystrophy: correlation of clinical symptoms with the size of the CTG trinucleotide repeat.

An unstable DNA sequence of a gene encoding a protein kinase has been identified as the molecular basis of myotonic dystrophy. The correlation between different symptoms of myotonic dystrophy and the size of this unstable base triplet (CTG)n repeat was investigated in 14 patients. DNA was prepared from whole blood by standard procedures. Detailed clinical, psychological, electrophysiological (quantified measurement of myotonia, electrocardiography) and other laboratory examinations (muscle biopsy in 4 patients, slit lamp examination) were performed. Triplet size correlated significantly with muscular disability and inversely with age at onset of the disease. A greater frequency of mental and gonadal dysfunction could be observed in patients with a larger repeat size. Other symptoms, however, such as cataract, myotonia, gastrointestinal dysfunction and cardiac abnormalities were not correlated with repeat size. Somatic mosaicism with different amplification rates in various tissues might be one possible explanation for the variable phenotypes. Furthermore, other factors such as different expression of the myotonic dystrophy gene might contribute to the clinical variability of the disease at a given triplet size.

Adult↗

Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice.

BACKGROUND & AIMS: Although most acute enteric infections in humans resolve, some herald the onset of chronic symptomatology and persistent gastrointestinal dysfunction--so-called postinfectious irritable bowel syndrome. This entity is poorly understood, and there are no animal models for testing hypotheses. The aim of this study was to investigate changes in intestinal neuromuscular function during and after recovery from acute intestinal inflammation due to primary Trichinella spiralis infections in NIH Swiss mice. METHODS: Morphometric scores and myeloperoxidase activity were used to monitor mucosal inflammation. Neuromuscular function was assessed in vitro by pharmacological or electrical stimulation of longitudinal muscle. RESULTS: Acute inflammation resulted in an approximately 50% reduction of villus height, an approximately 50% increase in crypt depth, and a threefold increase in myeloperoxidase activity. Carbachol- and KCl-induced contractions of longitudinal muscle were also increased threefold, whereas contraction induced by electrical field stimulation of intramural nerves was decreased by 60%. Mucosal morphology and myeloperoxidase activity rapidly returned to control values, but the increased muscle contractility and the decreased excitatory neurotransmission persisted as long as 42 and 28 days after infection, respectively. CONCLUSIONS: These findings show that transient mucosal inflammation alters enteric neuromuscular function; this alteration persists after recovery from the infection and mucosal restitution.

Animals↗

Coeliac plexus block with bupivacaine reduces intestinal dysfunction in neurosurgical ICU patients.

Coeliac plexus block, an established method of treatment for pain associated with pancreatitis and cancer, was used in neurosurgical patients with gastrointestinal dysfunction. The study was performed in 16 patients whose gastric reflux volume exceeded 600 ml per day for 3 consecutive days. Patients were allocated to a block group (n = 8) or a control group (n = 8). Coeliac plexus block was accomplished with a modified Moore technique using 50 ml bupivacaine 0.25%. In the block group, gastric reflux volumes for 3 days preceding coeliac plexus block and 3 consecutive days following coeliac plexus block were analysed. In the control group, gastric reflux volumes were observed over a period of 6 days. Mean (SEM) gastric reflux volume decreased significantly following coeliac plexus block from 770 (50) ml to 60 (30) ml (p < 0.01). In the control group, gastric reflux remained unchanged over the corresponding periods (730 (60) ml c.f. 670 (50) ml). The response of gastric reflux volume to coeliac plexus block suggests that the mechanism is related to inhibition of sympathetic activity in patients whose sympathetic drive is increased due to the underlying neurological disease, and possibly due to sedation withdrawal symptoms.

Adult↗

Changes in gastric emptying in recipients of successful combined pancreas-kidney transplants.

Gastroparesis causes gastric emptying disorders in patients with chronic diabetes mellitus and it results from reduced smooth muscle contractility secondary to autonomic dysfunction. Today there has been little objective evidence of improvement in gastric emptying following correction of both uremia and diabetes by combined kidney-pancreas transplantation. We used gastrointestinal symptom scores, solid gastric emptying tests and electrogastrography to evaluate the effect of combined kidney-pancreas transplantation on gastric emptying in 8 uremic diabetic patients. The mean age of the patients was 40 years (range: 30-51 years) and the mean duration of diabetes was 24 years (range: 16-30 years). The patients had been on dialysis up to 24 months. The pretransplant A1 mean was 6.5 before improving to 4.3 after transplantation. All patients were receiving exogenous insulin. Our study data indicate that uremic diabetics have a high prevalence of symptomatic gastrointestinal dysfunction including abnormalities of gastric emptying and gastric electrical activity. Following transplantation, the gastrointestinal symptomatology improved significantly. Significant improvement in the rate of gastric emptying also correlated with improvement in the symptom complex. Gastric electrical activity also improved during the follow-up period.

Adult↗

[Serotonin (5-HT)3 receptors: antagonists and their pharmacological profiles].

The pharmacology of 5-HT and the classification of 5-HT receptors have become increasingly complex. However, recent advances have produced a new nomenclature system for 5-HT receptors. 5-HT3 receptors are neuronal receptors coupled directly to cation channels. Recently, many selective 5-HT3-receptor antagonists including tropisetron, zacopride, ondansetron, granisetron, zatosetron, nazasetron, YM060 and YM114 (KAE-393) have been developed. Many actions attributable to the 5-HT3-receptor have been described in both the peripheral and central nervous systems, and clinical trials are already showing the potential use of these 5-HT3 receptor antagonists in a number of disorders of the gastrointestinal tract and central nervous system, such as nausea and vomiting induced by cancer chemotherapy, anxiety, depression, schizophrenia and migraine. In addition, endogenous 5-HT is suggested to be one of the substances that mediate stress-induced responses in gastrointestinal function, i.e., increase in fecal pellet output and diarrhea. Moreover, YM060, YM114 (KAE-393) and granisetron have been reported to inhibit restraint stress- and 5-HT-induced increases in fecal pellet output and diarrhea in rats and mice, indicating that endogenous 5-HT may mediate stress-induced changes in bowel function through the 5-HT3 receptor. Therefore, 5-HT3-receptor antagonists are new therapeutic drugs for stress-induced gastrointestinal dysfunctions like irritable bowel syndrome (IBS).

Animals↗

Preservation of the pylorus in pancreaticoduodenectomy a follow-up evaluation.

We have previously reported our efforts to minimize postgastrectomy symptoms in two patients with benign disease who underwent resection of the head of the pancreas and the duodenum. In these cases the pylorus and first portion of the duodenum were preserved during pancreaticoduodenectomy. Our experience has now been extended to encompass 18 patients, eight of whom were available for comprehensive evaluation an average of six months postoperation. These studies have attempted to differentiate malabsorption of pancreatic insufficiency from possible gastrointestinal dysfunction of the new alimentary connection. Pancreatic insufficiency was evaluated by a 72-hour stool collection and radioactive trioctanoate (RATO) test. Gastrointestinal absorption was evaluated by D-xylose excretion and the Schilling test, as well as serum vitamin. A, vitamin B-12, carotene, folate, iron, and total iron binding capacity. Gastrointestinal secretion and motility were assessed by using pyloric fluoroscopy, gastric barium emptying, the Hunt test, and gastric acid analysis. Finally, a questionnaire regarding clinical symptoms of postgastrectomy syndromes and malabsorption was answered. Although every patient exhibited marked pancreatic insufficiency by laboratory tests, 88% described normal formed bowel movements, and weight loss was claimed by only 25%. Other test findings were generally normal. While the follow-up period has been limited to three years, the current data demonstrate that gastrointestinal function subsequent to preservation of the pylorus has not thus far predisposed to postgastrectomy syndromes or marginal ulcers. All of the patients required intensive pancreatic enzyme replacement.

Adolescent↗

Enteric neuroplasticity evoked by inflammation.

Neuroplastic changes in the enteric nervous system (ENS) may be observed in physiological states, such as development and aging, or occur as a consequence of different pathological conditions, ranging from enteric neuropathies (e.g., Hirschsprung's disease) to intestinal (e.g., inflammatory bowel disease) or extra-intestinal diseases (e.g., Parkinson's disease). Studying ENS plasticity may help to elucidate the pathophysiology of several diseases and have a bearing on the development of new pharmacological interventions. In the present review, we would like to focus on neuronal plasticity evoked by gastrointestinal inflammation occurring in inflammatory bowel disease and in a subset of patients with severe derangement of gut motility due to an enteric neuropathy characterized by an inflammatory infiltrate of the enteric plexuses. Major features of neuroplasticity within the enteric microenvironment encompass structural abnormalities ranging from nerve re-arrangement (e.g., hypertrophy and hyperplasia) to degeneration and loss of enteric ganglion cells; altered synthesis, content and release of neurotransmitters as well as up- or down-regulation of receptor systems; gastrointestinal dysfunction characterized by sensory-motor and secretory impairment of the gut. Interestingly, neuronal changes may also occur in segments of the gastrointestinal tract remote from the site of the original inflammation, e.g. the ileum may show neuroplastic changes during colitis. Sometimes, the inflamed site may even be outside the gut. Among potential mechanisms underlying ENS plasticity, neurotrophins and enteric glia deserve special attention. A better comprehension of ENS plasticity during inflammation could be instrumental to develop new therapeutic options for patients with IBD and inflammatory enteric neuropathies.

Animals↗

Postoperative gastric rupture in children with cerebral palsy.

Children with cerebral palsy (CP) develop difficulties with swallowing and bowel motility, although the underlying etiology of these disorders is unclear. The authors identified three children treated at their institution in the past 6 years who developed severe gastrointestinal dysfunction leading to gastric rupture after orthopaedic surgery; all three had a history that included CP (subtype spastic quadriparesis), low cognitive function, and gastrointestinal motility disorders. All three cases were fatal; in two patients the diagnosis was made at autopsy. No case of postoperative gastric rupture has been identified in children undergoing orthopaedic surgery without concomitant CP at the authors' institution. In this case series, they describe the preoperative and postoperative course of these three children. Since the only cure for gastric rupture is prompt surgical attention, orthopaedists should consider gastric rupture in the differential diagnosis of a postsurgical CP patient who becomes acutely unstable.

Adolescent↗

Stress-induced changes in intestinal transit in the rat: a model for irritable bowel syndrome.

Stress in humans commonly results in gastrointestinal dysfunction, which is characterized by its symptomatology because the etiology is completely unknown. We developed an animal model in which to study the effects of stress on the gastrointestinal tract, and characterized the model as a stressor by evaluating endocrine and analgesic responses to mild restraint. Mild restraint (wrap restraint) elevated plasma levels of adrenocorticotropic hormone and beta-endorphin, and caused analgesia. The different regions of the gastrointestinal tract responded differently to the stress stimulus. Gastric emptying was not affected, small intestinal transit was inhibited, and large intestinal transit was stimulated by stress, and there was an associated increase in fecal excretion. Wrap-restraint stress did not result in the formation of ulcers. There was a strong correlation between stress-induced adrenocorticotropic hormone release and stress-induced intestinal dysfunction over a 24-h period that suggested a circadian influence. However, neither exogenous adrenocorticotropic hormone nor beta-endorphin had any effect on intestinal transit. Furthermore, neither adrenalectomy nor hypophysectomy prevented the response of the intestine to stress, suggesting that neither adrenal nor pituitary-derived factors are responsible for mediating the effects of stress on the gut. We conclude that wrap-restraint stress produces different effects on different regions of the intestine, suggesting that the small and large intestines are independently regulated and can respond differently to different stimuli. There were similarities between the intestinal effects of wrap-restraint stress in rats and intestinal symptoms associated with stress and irritable bowel syndrome in humans. Therefore, wrap restraint may be an appropriate animal model in which to study stress-related intestinal dysfunction. The mechanisms by which stress affects intestinal transit are still unresolved; however, the intestinal effects of stress are not mediated by either pituitary or adrenally derived factors.

Adrenocorticotropic Hormone↗

Late cytomegalovirus disease with atypical presentation in renal transplant patients: case reports.

Cytomegalovirus (CMV) disease typically occurs 1 to 4 months (median 35 days) after solid organ transplantation. Recent reports documented that the natural history of CMV disease associated with solid organ transplantation has been modified as a result of the widespread use of potent immunosuppressents and antiviral prophylaxis. We herein report three pretransplant CMV seropositive recipients (with unknown donor status) who were diagnosed recently to display late and atypical CMV disease. Two men and one woman included two patients who presented with allograft dysfunction at 12 years and at 3 years after transplantation. Both patients showed increased serum creatinine approximately from baseline 200 to >400 micromol/L over 3 months in the absence of features of rejection or cyclosporine toxicity. A renal biopsy was refused by both patients. Two of the three patients presented with symptoms of enterocolitis (diarrhea, nausea, weight loss), which had persisted for more than 6 months. Other symptoms and signs of overt CMV disease (fever, leukopenia) were absent. None had pulmonary, hepatic, or other major organ involvement. In all patients IgG antibodies and CMV DNA by polymerase chain reaction were positive with negative IgM antibodies. The immunosuppressive regimen consisted of mycophenolate mofetil (MMF), steroids, and calcineurin inhibitors. The kidney function significantly improved in both patients with renal dysfunction. Gastrointestinal symptoms resolved completely with gradual weight gain. The recognition and early diagnosis of late atypical CMV disease in kidney transplant patients presenting with allograft dysfunction and/or other organ systems is important. The MMF has a red herring effect in our cases due to its GI side effects.

Aged↗

Ileal pouch-anal anastomosis, conventional ileostomy and ileorectal anastomosis modify cholesterol metabolism.

Proctocolectomy modifies the enterohepatic circulation and activity of bacterial enzymes depending on the structure of the stoma and function of the terminal ileum. We evaluated in our comparative study effects of different colectomy constructions on cholesterol metabolism. Levels of lipoprotein cholesterol and triglycerides, noncholesterol sterols, and squalene in serum, fecal fat, and bile acids, cholesterol absorption efficiency, and cholesterol metabolism by sterol balance technique were analyzed in human subjects with ileal pouch-anal anastomosis (n = 34), conventional ileostomy (n = 8), ileorectostomy (n = 6), and controls (n = 29). Malabsorption of bile acids, but not of fat, and low serum levels of total and low-density lipoprotein cholesterol, but high levels of high-density lipoprotein cholesterol and increased cholesterol synthesis were evident in the colectomy groups. In contrast to the ileorectostomy group, expressing high absorption and biliary secretion of cholesterol, a low cholesterol absorption percentage accompanied by elevated serum proportions of cholesterol precursor sterols and phytosterols characterized the ileal pouch-anal anastomosis and conventional ileostomy groups. After colectomy, fecal excretion of secondary bile acids was low, whereas relative proportions of identifiable bile acids remained the same in each study group. Low serum levels of total and low-density lipoprotein cholesterol of colectomized subjects may decrease the risk of premature atherosclerosis. The favorable serum lipid profile was due to enhanced fecal loss of cholesterol as bile acids despite abnormally high cholesterol synthesis. Ileal dysfunction probably diminished cholesterol absorption in subjects with ileal pouch-anal anastomosis and conventional ileostomy, with no explanation for those with ileorectostomy with no clinical gastrointestinal dysfunction. Relative synthesis of identifiable primary bile acids remained unchanged postoperatively, but formation of secondary bile acids was weak due to scarce bacterial flora.

Anal Canal↗

Oesophageal involvement in rheumatoid arthritis patients: a study with oesophageal radionuclide transit using 81Krm.

Rheumatoid arthritis (RA) is an inflammatory disease affecting mainly the joints. In addition, signs of systemic disease are likely to be present although they are not always clinically evident. Oesophageal motility dysfunction, present in 75% of progressive systemic sclerosis patients, was also reported in various other connective tissue diseases. The present study involved 32 rheumatic patients devoid of any gastrointestinal complaints or diseases: 16 RA, nine Raynaud's syndrome and seven mild osteoarthritis as controls. Oesophageal transit was assessed by using 81Krm radionuclide scan, a sensitive and non-invasive technique. Diffusing lung capacity for carbon monoxide (DLCO) was performed as evidence of subclinical systemic involvement. Abnormal oesophageal transit was observed in 5/16 RA (31%). Two of them were subsequently discarded due to the presence of asymptomatic goiter and asymptomatic gastrointestinal reflux leaving 3/14 RA for analysis. They all had extra-articular features (EAF) (pericarditis, nodules) and two of them had diminished DLCO. Two with Raynaud's syndrome had abnormal oesophageal transit but none of the controls had abnormal oesophageal transit. Upper gastrointestinal dysfunction after exclusion of symptomatic patients appears thus to be not very frequent in RA, even when a sensitive technique is used. Radionuclide transit scanning of the oesophagus is not a more useful method than others in detecting early EAF in RA.

Adult↗