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Intestinal permeability in exocrine pancreatic insufficiency due to cystic fibrosis or chronic pancreatitis.

Disturbances of the intestinal integrity, reflected by an increased intestinal permeability, are reported in cystic fibrosis (CF). Controversy exists whether the increased intestinal permeability is due to CF itself or a consequence of the concomitant exocrine pancreatic insufficiency (PI). We measured intestinal permeability by the sugar absorption test in 32 PI patients: 20 CF-PI, 12 nonCF-PI with chronic pancreatitis, and 50 controls. In the sugar absorption test, the lactulose/mannitol ratio is measured in 5-h urine samples after oral ingestion of a solution of lactulose and mannitol, hyperosmolar by the addition of sucrose. The lactulose/mannitol ratio was increased in both CF-PI and nonCF-PI versus controls (p < 0.0001). In CF, the L/M ratio and permeability for lactulose and mannitol did not change by increasing pancreatic enzyme supplementation by 30-50% for 2 wk (p = 0.74, p = 0.97, p = 0.74, respectively) nor by decreasing the osmolarity of the test solution by 75% (p = 0.24, p = 0.10, p = 0.39, respectively). We conclude that an increased intestinal permeability in CF is probably a consequence of PI and is not related to the dose of pancreatic enzyme supplementation nor the osmolarity of the test solution. The increase is due to an increased permeability for lactulose which might point toward a defect in the tight junctions of the villi and/or crypts. The cause of the increased intestinal permeability in the presence of PI is still unclear. An increased intestinal permeability points toward an impaired functional integrity of the small bowel, which may contribute to gastrointestinal dysfunction in CF.

Adolescent↗

A case with glucagonoma syndrome--endocrine and metabolic studies.

The results of clinical endocrine and metabolic studies on a 57-year-old female with surgically and autopsy verified glucagonoma syndrome were presented. All of the clinical manifestations of glucagonoma syndrome so far reported in the literature were noted but there was no evidence indicating the presence of multiple endocrine adenomatosis. The plasma IRG level was always more than 20 times above the normal, and the IRG response to insulin and tolbutamide injection was abnormal and the results of the other endocrinological studies revealed less remarkable features, if any. The surgically removed metastatic tumor of the liver contained an enormous amount of IRG and an appreciable amount of IRI, indicating that the elevated plasma IRG was mainly of tumor origin. These results clearly indicate that in glucagonoma there is some abnormality in glucagon release from the tumor. In addition to these findings, hypocalcemia, cardiac left ventricular hypertrophy and gastrointestinal dysfunction reportedly due to hyperglucagonemia were also seen in this patient.

Adenoma, Islet Cell↗

Systemic hyalinosis: a distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2).

OBJECTIVE: We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood. PATIENTS AND METHODS: We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis. RESULTS: We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease. CONCLUSIONS: Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction.

Age of Onset↗

Therapeutic drug monitoring of cyclosporin. Practical applications and limitations.

Cyclosporin, a potent immunosuppressive agent used to prevent rejection of transplanted organs, has a narrow therapeutic range and various toxic effects, mostly concentration-dependent. The kinetics of this drug present a large intra- and interindividual variability due to many factors resulting in marked variations of blood cyclosporin concentrations, and in a poor correlation between administered dose and concentrations. The knowledge of cyclosporin peculiarities and of factors affecting blood concentrations can provide a rational basis for establishing an adequate therapy for the individual patient, in conjunction with other laboratory and clinical data. Cyclosporin monitoring is a method of evaluating whether the therapeutic choice is correct. Cyclosporin concentrations can be measured in blood, plasma and serum using radioimmunoassay or high performance liquid chromatography. Different results are obtained, depending on the technique and on biological fluids used. Cyclosporin measurement presents many problems and difficulties. There is a need for standardisation and for quality assessment programmes. The recent development of monoclonal antibodies may represent a significant advance for cyclosporin monitoring. The most important factors affecting blood concentrations are: type of transplant, bile deficit, gastrointestinal dysfunction, food, variations of lipoprotein concentrations, impairment of liver function, age, drug coadministration. Therapeutic drug monitoring should be undertaken on a regular basis after the initiation of therapy with cyclosporin. After discharge from the hospital the patient and the attending physician should be aware of the factors which may require changes in cyclosporin therapy.

Antibodies, Monoclonal↗

Dietary fiber in management of diabetes.

Current evidence suggests that high-fiber diets, especially of the soluble variety, and soluble fiber supplements may offer some improvement in carbohydrate metabolism, lower total cholesterol and low-density lipoprotein (LDL) cholesterol, and have other beneficial effects in patients with non-insulin-dependent diabetes mellitus (NIDDM). Diets enriched with wheat bran and guar gum induce 10-20% reductions in serum cholesterol and LDL in both normo- and hypercholesterolemic subjects and have the ability to blunt the hypertriglyceridemic effects of diets high in carbohydrate and low in fiber. In insulin-dependent diabetes mellitus (IDDM) the situation is less clear, but a decrement of the circadian glucose profile has been shown. Americans, in general, consume too little fiber. With the need to restrict fat and reduce protein, an increase in carbohydrates is mandatory. A practical goal would be to establish the present level of fiber intake (15-30 g/day) and to gradually increase it. An intake of up to 40 g of fiber per day or 25 g/1000 kcal of food intake appears beneficial; in many individuals on weight-reducing diets higher levels may be unacceptable because of gastrointestinal side effects. The level of maximum benefit has not been determined. Fiber supplementation appears beneficial only if given with a diet comprising approximately half of the calories as carbohydrate. Foods should be selected with moderate to high amounts of dietary fiber from a wide variety of choices to include both soluble and insoluble types of fiber. Insufficient data are available on the long-term safety of high-fiber supplements. People at risk for deficiencies, such as postmenopausal women, the elderly, or growing children, may require supplements of calcium and trace minerals. People with upper gastrointestinal dysfunction are at risk of bezoar formation and cautioned against a diet high in fiber of the leafy vegetable type. Careful attention must be paid to insulin dose because hypoglycemia can result if there is a radical change in fiber intake and insulin dose is not reduced appropriately. Care must be exercised in the use of "novel" fibers, including the wood celluloses, because little is known of their safety and efficacy.

Diabetes Mellitus, Type 1↗

Is the irritable gut an inflamed gut?

Recent advances in the field of neuroimmunology have provided clear demonstrations of i) the neuromodulation of immune function, and ii) the involvement of the immune system in responses induced by psychologic stress in animals and in man. This has led to speculation about the role of the immune system in psychosocial disease. The irritable bowel syndrome (IBS) is characterized by chronic gastrointestinal dysfunction, which may reflect in altered motility, epithelial function, or sensory perception in the gut. IBS is heterogeneous not only in terms of its clinical presentation but also in terms of its pathogenesis, and factors ranging from psychoneurotic behavior and emotional stress, to dietary fiber deficiency, food intolerance, and enteric infection have been implicated. There is evidence of an increase in the inflammatory cells present in the gut of some IBS patients and in an emerging literature that demonstrates the immunomodulation of the motor system of the gut. These findings invite speculation that the immune system may play a role in the pathogenesis and pathophysiology of at least a subpopulation of IBS patients.

Colonic Diseases, Functional↗

Gastrin, somatostatin, G and D cells of gastric ulcer in rats.

AIM: To investigate the relationship among gastrin, somatostatin, G and D cells in gastric ulcer and in its healing process in rats. METHODS: Fourty-nine Wistar rats were divided into 7 groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay(RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis system. RESULTS: In gastric ulcer, the level of gastrin in plasma, gastric fluid, and antral tissue increased, that of somatostatin declined, and the disorder gradually recovered to the normal level in the healing process. Immunohistochemical technique of G and D cells in antral mucosa demonstrated that the number of G cells increased and that of D cells decreased, both areas of G and D cells declined, the ratio of number and area of G/D increased in gastric ulcer, and the disorder gradually recovered in the healing process. CONCLUSION: In gastric ulcer, the increased gastrin secreted by G cells, the declined somatostatin secreted by D cells, and the disordered G/D cell ratio can lead to gastrointestinal dysfunction.

Animals↗

Alterations of intestinal mucosa structure and barrier function following traumatic brain injury in rats.

AIM: Gastrointestinal dysfunction is a common complication in patients with traumatic brain injury (TBI). However, the effect of traumatic brain injury on intestinal mucosa has not been studied previously. The aim of the current study was to explore the alterations of intestinal mucosa morphology and barrier function, and to determine how rapidly the impairment of gut barrier function occurs and how long it persists following traumatic brain injury. METHODS: Male Wistar rats were randomly divided into six groups (6 rats each group) including controls without brain injury and traumatic brain injury groups at hours 3, 12, 24, and 72, and on day 7. The intestinal mucosa structure was detected by histopathological examination and electron microscopy. Gut barrier dysfunction was evaluated by detecting serum endotoxin and intestinal permeability. The level of serum endotoxin and intestinal permeability was measured by using chromogenic limulus amebocyte lysate and lactulose/mannitol (L/M) ratio, respectively. RESULTS: After traumatic brain injury, the histopathological alterations of gut mucosa occurred rapidly as early as 3 hours and progressed to a serious state, including shedding of epithelial cells, fracture of villi, focal ulcer, fusion of adjacent villi, dilation of central chyle duct, mucosal atrophy, and vascular dilation, congestion and edema in the villous interstitium and lamina propria. Apoptosis of epithelial cells, fracture and sparseness of microvilli, loss of tight junction between enterocytes, damage of mitochondria and endoplasm, were found by electron microscopy. The villous height, crypt depth and surface area in jejunum decreased progressively with the time of brain injury. As compared with that of control group (183.7 +/- 41.8 EU/L), serum endotoxin level was significantly increased at 3, 12, and 24 hours following TBI (434.8 +/- 54.9 EU/L, 324.2 +/- 61.7 EU/L and 303.3 +/- 60.2 EU/L, respectively), and peaked at 72 hours (560.5 +/- 76.2 EU/L), then declined on day 7 (306.7 +/- 62.4 EU/L, P<0.01). Two peaks of serum endotoxin level were found at hours 3 and 72 following TBI. L/M ratio was also significantly higher in TBI groups than that in control group (control, 0.0172 +/- 0.0009; 12 h, 0.0303 +/- 0.0013; 24 h, 0.0354 +/- 0.0025; 72 h, 0.0736 +/- 0.0105; 7 d, 0.0588 +/- 0.0083; P<0.01). CONCLUSION: Traumatic brain injury can induce significant damages of gut structure and impairment of barrier function which occur rapidly as early as 3 hours following brain injury and lasts for more than 7 days with marked mucosal atrophy.

Animals↗

Outbreak of hemorrhagic fever with renal syndrome among U.S. Marines in Korea.

Fourteen of 3,754 U.S. Marines who participated in a joint United States-Republic of Korea training exercise during the autumn of 1986 developed hemorrhagic fever with renal syndrome (HFRS). Clinical and laboratory findings among cases included fever, headache, fatigue, gastrointestinal dysfunction, thrombocytopenia, and proteinuria. Ten individuals were hospitalized; 2 died. No subclinical infections were identified through a post-deployment screen of sera obtained from 2,053 exercise participants. Analysis of questionnaires identified no environmental, occupational, or temporal factors as risks for developing disease. However, 13 of the 14 cases occurred among individuals housed at 1 of the 2 base camps used during the exercise. This outbreak represents the largest cluster of HFRS cases among U.S. personnel in the Republic of Korea since the Korean conflict.

Adult↗

Renal failure in surgical patients. Treatment with intravenous essential amino acids and hypertonic glucose.

Solutions containing balanced quantities of essential L-amino acids, hypertonic glucose, and other essential nutrients were administered by vein to ten patients who had acute or chronic renal failure associated with or resulting from catastrophic complications precluding use of the gastrointestinal tract for alimentation. Weight gain, wound healing, and positive nitrogen balance occurred uniformly during periods of total intravenous nutrition, while blood urea nitrogen remained stable or decreased and the signs and symptoms of azotemia resolved. Restoration of nutritional balance and achievement of protein synthesis is possible in patients who have renal failure and gastrointestinal dysfunction by the judicious administration of high biologic value diets exclusively by vein.

Adult↗

Environmental stress causes mast cell degranulation, endothelial and epithelial changes, and edema in the rat intestinal mucosa.

OBJECTIVE: Mental stress has been shown to produce intestinal disease, but the effects of a mild environmental stress on intestinal physiology have not been elucidated. This study was performed to determine the effects of environmental stress on the ultrastructure of the intestinal mucosa, using the rat as an experimental model. METHODS: One group of rats (group A, n = 3) was examined immediately upon arrival at the animal care facility. Groups B (n = 6) and C (n = 6) were housed in rooms with high and low personnel activity, respectively, for up to 4 wk. Group D (n = 8) was housed in the high activity room for 3 to 4 wk followed by 1, 2, or 3 in the low activity room. RESULTS: Rats in group B had the greatest number of degranulated intestinal mucosal mast cells, and activated goblet cells. Intestinal villi were edematous and epithelial cells were detaching from the basement membrane at villus tips. Changes were observed in capillary endothelial ultrastructure. In group B there were greater numbers of vesicles and multilamellar fenestral diaphragms compared to group C. Rats in groups A and C had the lowest numbers of degranulated mast cells and activated goblet cells. Intestinal villi showed normal ultrastructure. Group D was in a recovery phase and the condition of the intestinal mucosa was improved relative to group B, but the number of degranulated mast cells was not significantly reduced. CONCLUSIONS: This study demonstrates that environmentally induced stress causes pathological changes in the rat intestinal mucosa that compromise the epithelial-endothelial exchange barrier. These results emphasize the importance of closely monitoring the environment of experimental animals and provide evidence to stimulate further research into the mechanisms linking mental stress to gastrointestinal dysfunction in humans.

Animals↗

Autonomic nervous system and smooth muscle cell involvement in systemic sclerosis: ultrastructural study of 3 cases.

OBJECTIVE: To investigate morphological abnormalities in nerve and smooth muscle structures of the anorectal wall underlying gastrointestinal dysfunction in patients with systemic sclerosis (SSc). METHODS: We performed deep rectal biopsy in 3 patients with limited scleroderma of relatively recent onset and intestinal symptoms. RESULTS: We found ultrastructural signs of axonal degeneration and cytoskeletal abnormalities in the bundles of unmyelinated fibers. There was also focal degeneration of smooth muscle cells, often in association with the presence of partially degranulated mast cells. Many mast cells were also observed in close relation to nerve fibers and vessels. The enteric vessels often showed basal lamina reduplication and hypertrophied endothelial cells with obliterated lumen. No significant fibrosis was found. CONCLUSION: Our findings indicate early involvement of the autonomic nervous system and to a lesser extent of smooth muscle cells. We confirmed the presence of early vascular lesions and involvement of mast cells in the pathological process.

Adult↗

Auricular-plaster therapy plus acupuncture at zusanli for postoperative recovery of intestinal function.

In order to relieve the abdominal distension and other discomforts due to gastrointestinal dysfunction after abdominal operations, the patients were treated by auricular-plaster therapy plus acupuncture at Zusanli (ST 36). 12 (92.4%) of the 13 cases in the treatment group showed recovery of normal peristalsis within 72 hours after operations, while that in 13 cases of the control group was 46.1%, indicating that auricular-plaster therapy plus acupuncture at Zusanli (ST 36) may promote postoperative recovery of the intestinal function.

Acupressure↗

[Value of prokinetics in enteral nutrition intolerance].

Malnutrition is associated with an increase in morbidity and mortality and therefore a raise in hospitalization's costs. Nevertheless, an early nutritional support can reverse this trend. Gastrointestinal dysfunctions (gastroparesis, abdominal distension, high gastric residues) in patient on enteral nutrition, may appear and very likely generate an increasing risk of regurgitations, pulmonary aspiration and infection. These symptoms represent the main factors limiting dosage in administering enteral nutrition. Prokinectics agents (metoclopramid, cisaprid and erythromycin) which improve gastric motility are often used in order to maintain enteral nutrition and to cover the energetic needs of patients. This revenue shows some way of using prokinectics in case of enteral nutrition intolerance and propose a step-by-step guideline on how to start and increase progressively enteral nutrition.

Clinical Trials as Topic↗

[Changes of ultrastructure characteritics of Cajal interstitial cell in intestinal tract of diabetic rats].

OBJECTIVE: This study is to clarify the changes of the ultrastructure characteristic of Cajal interstitial cell of diabetic rats intestinal tract. METHODS: Male SD rats were randomly divided into two groups: group A (diabetic), group B (control). 45 mg/kg Alloxan was injected into the group A, group B was injected with saline instead, after 12 weeks, the tissues of small intestine, colon were observed through electric telescope. RESULTS: The major change of Cajal interstitial cell of diabetic rat were showed as below: the number of the gap junctions between Cajal interstitial cell and neuron cells, between Cajal interstitial cell and myocyte, and between themselves were decreased significantly, and the structure of those gap junctions rested were also damaged; mitochondrion was swelling, vacuoles, dissolving; cytoplasm was dissolving, vacuoles were formed; the organelle were decreased. CONCLUSIONS: The ultrastructure of Cajal interstitial cell of diabetic had striking changes, these changes are closely related with the changes of their function, so it is very possible that these changes are one of the mechanisms of diabetic gastrointestinal dysfunction.

Alloxan↗

[Recurrent retrieval of the core episode referred to as the onset of schizophrenia--psychopathological study on the autobiographical memory of the onset of the illness].

OBJECTIVE: In this study, we explore the onset of psychotic episodes in schizophrenia. Patients with schizophrenia have sometimes reported specific life-events at the period of onset. For example: "It started on my 22nd birthday. From that day onward, my life was colored with extremes of happiness and tragedies", or "It was when I was playing with a cat in the park of S temple that I realized suddenly that my 'I'-ness had completely changed." In each case, patients referred to a specific event as a critical moment when the meaning of selfness and the surrounding world had changed. Interestingly, these moments were reported repeatedly throughout the history of their illnesses. We termed these clinical phenomena "Recurrent retrieval of the core episode referred to as the onset of schizophrenia" and investigated their psychopathologic implication. METHOD: The autobiographical memory of nine schizophrenic patients with "Recurrent retrieval of the core episode referred to as the onset of schizophrenia" was investigated. Four representative cases are described in detail. Samples of subjective statements were collected from medical records and analyzed. RESULTS: 1) Form and content of the statement: Patients clearly referred to a specific moment in their life. They usually reported that their image of self or the world had completely changed. The content of their reports were always about the same theme. 2) Chronological pattern of the repetition: Although the reported life event occurred just before onset, the reminiscence usually occurred not only at the beginning of the refractory period but also at the beginning of the recovery period. Patients did not report such events when they were stable. In the refractory period, distinct symptoms of schizophrenia were observed after the reminiscence. In the recovery period, the reminiscence was accompanied by minor physical symptoms, such as fever elevation or gastrointestinal dysfunction. 3) Subjective characteristics of repetitive reminiscence: In the refractory period, patients relived the onset of schizophrenia by reporting it reminiscently. They were excited, in a state of high-tension, or feeling oppressed. In contrast, in the recovery period, they reported the critical moment in an emotionally stable state, and even recollected it with humor. They were able to maintain some emotional distance from the reminiscence. 4) Predictive factor on prognosis: Reminiscence in the recovery period predicted a good prognosis. Seven of nine such cases were in remission. Two patients with whom the reminiscence was observed only in the refractory period were chronically ill. Therefore, two patterns of repetitive reminiscence of the critical moment should be discriminated. DISCUSSION: 1. The statements of patients were developed on the possibility that the critical event had not happened. Therefore, it can be postulated that their statements reconstructed a temporality open to any possible future: the moment just before the critical event might not have happened. The proper temporality associated with repetitive reminiscence should be distinguished from that of repetition of a traumatic memory in post-traumatic stress disorder. 2. From a therapeutic viewpoint, it is important to know to whom the discourse of the patient was addressed. In the refractory period, patients reported the repetitive reminiscence to anyone in a non-discriminating fashion. In contrast, in the recovery period, their discourse on the reminiscence was directed to a particular person with whom they were in close contact. The structure of the latter discourse was similar to that of neurotic patients in that they both demand acceptance from others. That is, the discourse structure of our patients was drastically changed in the recovery period. Reconstruction of the critical moment found in the recovery period was accomplished by the patient's discourse directed to another person, one from whom they could realize self-acceptance.

Adolescent↗

Early neurochemical changes in the autonomic neuropathy of the gut in experimental diabetes.

Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes.

Animals↗

Experience with treatment of gastroschisis and omphalocele.

From 1982 to 1990, 31 neonates with omphalocele and 54 with gastroschisis were treated at Mackay Memorial Hospital. The overall survival rate for omphalocele was 71%, while it was 85% for gastroschisis. The rate of primary fascial closure for omphalocele (85%) and gastroschisis (87%) was similar. The mortality from omphalocele was almost exclusively due to the presence of serious associated congenital anomalies. Two cases of Cantrell's pentalogy and two of cloacal exstrophy were found. The incidence of major malformation with gastroschisis was 6%. Sepsis, inadequate perioperative resuscitation and prolonged gastrointestinal dysfunction were the major causes of death in gastroschisis. Among survivors, the hospital stay was significantly longer in the silon pouch group than in the primary fascial closure group (71.5 vs 31.3 days for gastroschisis, 41 vs 14 days for omphalocele). Advances in surgical technique, neonatal intensive care and ventilatory support have made primary fascial closure a superior approach without jeopardizing the babies' chance for survival. An improved survival rate and increased primary closure rate are the main features in the treatment of abdominal wall defects in the last decade.

Abdominal Muscles↗