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PubMed2001

Swallowing dysfunction in infants less than 1 year of age.

BACKGROUND: Gastroesophageal reflux (GER) occurs frequently in infants and children and is implicated as a trigger for reactive airways disease. While evaluating patients for GER by upper gastrointestinal studies (UGI), we frequently noticed laryngeal penetration or tracheal aspiration in infants < 1 year of age. We conducted this prospective study to assess the incidence of swallowing dysfunction in infants with vomiting or respiratory symptoms. METHODS: Between February 1994 and August 1997, 1,003 UGI in infants < 1 year of age were performed by two experienced pediatric radiologists. Fluoroscopy of swallowing using an appropriate image intensifier was observed as part of the UGI in all patients. In addition to evaluating premature infants, former premature infants, and infants with underlying conditions such as bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), esophageal atresia and/or tracheoesophageal fistula (EA), and neurologic disorders, we assessed swallowing in 472 full-term infants in the general population who had respiratory symptoms or suspected GER, but no other apparent abnormalities. Swallowing was not assessed in patients with congenital bowel obstruction. The presence of normal swallowing or swallowing dysfunction was recorded immediately following the study. Chest radiographs obtained on the same day as the UGI were evaluated in the study. Forty-four videotaped modified barium-swallow studies (MBSS) were obtained in 25 general-population infants and reviewed frame-by-frame to determine the length of time that barium could be visualized in the subglottic trachea. RESULTS: The incidence of swallowing dysfunction is significant in premature and former premature infants, those with BPD, CHD, EA, various syndromes, and neurologic abnormality. In the general population of full-term infants referred for evaluation of vomiting or respiratory symptoms, 63 (13.4 % of 472) had swallowing dysfunction. Forty-four had tracheal aspiration (TA) and 19 had laryngeal penetration (LP). Gastroesophageal reflux was found in 79.5 % with TA and in 68.4 % with LP. The MBSS confirmed swallowing dysfunction in all patients shown to have vocal cord penetration or tracheal aspiration by UGI. CONCLUSIONS: Careful evaluation of swallowing during an UGI can identify swallowing dysfunction in full-term infants who have respiratory problems, as well as in infants with an abnormality that predisposes the patient to aspiration. Episodes of tracheal aspiration may be fleeting and overlooked if swallowing is not assessed carefully. An MBSS can confirm the observation of swallowing dysfunction found during an UGI and assist in planning appropriate dietary therapy that minimizes the likelihood of tracheal aspiration during feeding.

Deglutition Disorders↗

PubMed1982

Progressive esophageal dysfunction in chronic granulomatous disease.

Chronic granulomatous disease of childhood (CGD), a hereditary disorder of neutrophil function, affects the gastrointestinal tract in a variety of ways. Esophageal involvement has only rarely been reported. An 11-year-old boy with CGD and progressive esophageal dysmotility is described. Repeated radiographic, endoscopic, and motility studies revealed a markedly atonic esophagus with varying function of the lower esophageal sphincter. Pharmacologic therapy and esophageal dilatations were unsuccessful in establishing adequate esophageal function. A feeding gastrostomy was required for nutritional support.

Child↗

PubMed2003

[Pandysautonomia. Severe autonomic dysfunction accompanying polyneuropathy].

The case of a young woman with complete autonomic paralysis following an event of respiratory and gastrointestinal infections is described. The diagnosis was based upon clinical, neurophysiological, and laboratory findings. In view of the occurrence of identical--although less pronounced--autonomic disturbances in some cases of Guillain-Barré syndrome and the high incidence of minor degrees of weakness, paresthesias, reflex loss, and CSF protein elevation in dysautonomic polyneuropathy, it seems likely that the latter disorder is also an immune polyneuropathy affecting the autonomic fibers within the peripheral nerves.

Adult↗

PubMed1990

Pickles, peptide hormones and pregnancy: a hypothesis.

In western societies a high frequency of heartburn, nausea and vomiting occur during pregnancy. The causes and mechanisms of these clinical symptoms remain poorly understood. Evidence suggests steroid hormones modulate gastrointestinal transit time and plasma peptide hormones, while peptide hormone modulated food intake and preferences. Since diurnal and episodic release of steroid and peptide hormones occur, it is postulated that heartburn and other digestive dysfunction during pregnancy are associated with elevated steroid and peptide (beta-endorphin, NPY) hormone interaction with innate biological rhythms controlling the gastrointestinal tract.

Body Weight↗

PubMed2004

Management of gastrointestinal disorders in children with HIV infection.

A double scenario characterizes the epidemiology of HIV infection in children. In countries where highly active antiretroviral therapy (HAART) is available, the pattern of HIV infection is evolving into that of a chronic disease, for which control strictly depends on patients' adherence to treatment. In developing countries with no or limited access to HAART, AIDS is rapidly expanding and is loaded with a high fatality ratio, due to the combined effects of malnutrition and opportunistic infections. The digestive tract is a target of the disease in both settings. Opportunistic infections play a major role in children with severe immune impairment, with Cryptosporidium parvum being the leading agent of severe diarrhea. Several therapeutic approaches are effective in reducing fecal output, but the eradication of the parasite is rarely obtained. Other opportunistic infections may induce severe and protracted diarrhea, including atypical mycobacteria and cytomegalovirus. Diagnosis of diarrhea should be individually tailored based on presenting symptoms and risk factors. A stepwise approach is effective in limiting patient discomfort and minimizing the costs of investigations, starting with microbiologic investigation and proceeding with endoscopy and histology. Aggressive treatment of infectious diarrhea is required in severely immunocompromised children. However, antiretroviral therapy prevents the development of severe cryptosporidiosis. The liver and pancreas are also target organs in HIV infection, although functional failure is rare. The digestive-absorptive functions are impaired, with steatorrhea, nutrient malabsorption, and increased permeability occurring in 20-70% of children. Intestinal dysfunction contributes to growth failure and further immune derangement, leading to wasting, the terminal stage of AIDS. Nutritional management is crucial in HIV-infected children and is based on aggressive nutritional rehabilitation through enteral or parenteral routes and micronutrient supplementation.HIV may play a direct enteropathogenic role and is implicated in both diarrhea and intestinal dysfunction. This explains the efficacy of antiretroviral therapy in inducing remission of diarrhea and restoring intestinal function. Gastrointestinal side effects of antiretroviral drugs are increasingly observed; they are often mild and transient. Severe reactions are rare but require the withdrawal of drugs. In conclusion, severe enteric infections and intestinal dysfunction characterize the intestinal involvement of HIV infection. This is more common in, but not limited to, children who do not receive effective antiretroviral therapy. Diagnostic approaches include microbiologic and morphologic examinations and assessment of digestive processes, but immunologic and virologic data should be also carefully considered. Treatment is based upon specific anti-infectious drugs, antiretroviral therapy, and nutritional rehabilitation.

AIDS-Related Opportunistic Infections↗

PubMed2001

Quality of life in patients with irritable bowel syndrome seen in referral centers versus primary care: the impact of gender and predominant bowel pattern.

BACKGROUND: Quality of life (QOL) is reduced in patients with irritable bowel syndrome (IBS) and little is known about differences in QOL in relation to referral status, gender and predominant bowel pattern in IBS patients. This study aimed to explore these relationships. METHODS: 343 patients with IBS according to the Rome I criteria (251 females, 92 males) completed five different self-administered questionnaires to evaluate QOL. There were 119 patients with diarrhea-predominant IBS (IBS-D), 93 with constipation-predominant IBS (IBS-C) and 131 with alternating constipation and diarrhea (IBS-A). The study group comprised 209 hospital outpatients and 134 primary care patients. The questionnaires were mailed to the patients with an overall response rate of 88%. RESULTS: QOL was reduced in hospital outpatients compared to primary care patients, but only in females. IBS subgroup (IBS-D), physical fatigue and general health independently predicted referral to a gastroenterologist. Females had lower QOL than males. No differences, except in severity of diarrhea and constipation, were observed between IBS subgroups. Perceived fatigue was related to well-being, psychological and gastrointestinal symptoms. Independent predictors for fatigue were depression, trait anxiety, general health and vitality, along with eating dysfunction and female sex. CONCLUSION: IBS female patients seen in referral centers versus primary care is a highly selected group with reduced QOL. QOL in IBS is affected by gender, but not by subgroup. Our findings have implications for the generalizability of results in IBS trials. Fatigue is a common symptom in IBS that correlates to general well-being and psychological and subjective gastrointestinal symptoms.

Adolescent↗

PubMed2005

The sphincter of Oddi: understanding its control and function.

The most common functional disorders of the biliary tract and pancreas are associated with disordered motility of the sphincter of Oddi (SO). The SO is a neuromuscular structure located at the junction of the bile and pancreatic ducts with the duodenum. The primary functions of the SO are to regulate the delivery of bile and pancreatic juice into the duodenum, and to prevent the reflux of duodenal contents into the biliary and pancreatic systems. Disordered motility of the SO leads to the common and painful clinical conditions of SO dysfunction and acute pancreatitis. In order to understand normal SO motility, studies have been performed addressing SO function, control of spontaneous SO activity, responses to bioactive agents, SO innervation, and reflexes with other gastrointestinal organs. These studies have led to the current understanding of how the SO functions and may permit the development of targeted therapy for SO dysfunction and acute pancreatitis. This review summarizes the current knowledge regarding the control and regulation of SO motility, highlighting laboratory based and clinical research performed over the last 5 years.

Animals↗

PubMed2005

Recombinant activated factor VII for severe gastrointestinal bleeding after chemotherapy in an infant with acute megakaryoblastic leukemia.

Recombinant activated factor VII (rFVIIa) is a major alternative for management of hemophiliac patients with inhibitors. Additionally, it has been used off-label for the treatment of massive life-threatening hemorrhage associated with various bleeding situations. Herein, we describe a 16-month-old boy with acute megakaryoblastic leukemia and severe intractable gastrointestinal bleeding controlled by rFVIIa. rFVIIa should be considered as a novel treatment alternative in severe bleeding conditions including leukemias that may have hemostatic defects and platelet dysfunction.

Factor VII↗

PubMed2000

Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat.

BACKGROUND & AIMS: Abnormal presentation of luminal constituents to the mucosal immune system, caused by dysfunction of the intestinal epithelial barrier, is a candidate theory for the cause of Crohn's disease. Increased epithelial permeability is found in subgroups of patients at high risk for the development of Crohn's disease and has been found to precede disease recurrence. Clinical observations have suggested that disease recurrence can follow times of increased psychological stress, although the underlying mechanism remains obscure. We hypothesized that environmental stress increases gastrointestinal permeability. METHODS: We evaluated site-specific gastrointestinal permeability after application of graded levels of stress in rats. RESULTS: Increased epithelial permeability after stress was shown in all regions of the gastrointestinal tract and seemed to be mediated by adrenal corticosteroids. Stress-induced increases in epithelial permeability disappeared after adrenalectomy or pharmacologic blockade of glucocorticoid receptors. Dexamethasone treatment of control animals increased gastrointestinal permeability and mimicked the effects of stress. CONCLUSIONS: Psychological stress may increase gastrointestinal permeability, allowing luminal constituents access to the mucosal immune system. This provides a potential mechanism for the observation of stress-induced disease recurrence in Crohn's disease.

Adrenal Cortex Hormones↗

PubMed1999

Recent developments in diagnostic imaging of the gastrointestinal tract of the dog and cat.

The gastrointestinal (GI) tract comprises the esophagus, stomach, small intestine, large intestine, pancreas, mesentery, and associated lymph nodes. Diseases that result in structural lesions of the GI tract and diseases that cause abnormal GI motility are potentially detectable using diagnostic imaging techniques, whereas disorders of the GI tract that are manifested as histological lesions or metabolic dysfunction are not.

Animals↗

PubMedDate not supplied

Doppler analysis of hepatic blood flow predicts liver dysfunction after major hepatectomy.

In 17 consecutive patients who underwent major hepatic resection, 9 of whom with combined resection of the gastrointestinal tract or the pancreatic head (or both), postoperative hepatic blood flow was investigated. In this study, the patients were classified into two groups according to their postoperative serum total bilirubin level: Group A comprised 7 patients with the level higher than 7 mg/dl for more than 1 week postoperatively, and group B comprised 10 patients who did not meet this criterion. For 2 weeks after surgery, the portal blood flow velocity, the hepatic artery resistive index (RI) calculated from the changes in Doppler frequency shifts, and the hepatic venous blood flow velocity were measured intermittently using color Doppler ultrasonography. Liver volume was assessed by computed tomography to provide the restoration. Significant differences in portal blood flow velocity and hepatic artery RI were noted between the two groups from the third postoperative day. In group A the portal blood flow velocity decreased below the preoperative value, and the hepatic artery RI increased above 0.75. In contrast, group B showed high portal blood flow velocity and low hepatic artery RI. In both groups the RI correlated significantly with the total bilirubin level (r = 0.74; p < 0.0001), and the growth rate of the remnant liver was proportional to the mean postoperative portal blood flow velocity (r = 0.70; p = 0.016). We concluded that measurement of the portal blood flow velocity and hepatic artery RI can be useful for predicting postoperative liver dysfunction and liver regeneration after major hepatic resection.

Adult↗

PubMed2005

A new mechanism for diverticular diseases: aging-related vagal withdrawal.

It is widely believed that diverticulosis, a common condition among the elderly, results from repeated colonic barotrauma related to low dietary fiber and low stool bulk. Recent evidence has challenged the dietary-barotrauma hypothesis. We propose an alternative hypothesis that diverticulosis may be attributable to colonic smooth muscle dysfunction that results from vagal attrition associated with aging. We previously proposed that broad aging-related attrition of autonomic nerves may unmask intrinsic sympathetic bias of end-organs, leading to the compendium of familiar conditions associated with senility. Unexplained cholinergic hypersensitivity and receptor over-expression in bowel affected by diverticulosis have recently been observed. These findings are highly suggestive of a compensatory response to loss of vagal innervation. The resulting autonomic dysregulation may induce bowel smooth muscle dysfunction, setting the stage for diverticula formation. Thus, diverticular bowel disease may be a manifestation of the aging-related systemic vagal withdrawal. The framework may extend to diverticula formation in other parts of the gastrointestinal and genitourinary tracts. For instance, aging-related vagal attrition may represent the common upstream mechanism that induces both sphincter of Oddi dysfunction and peri-ampullary duodenal diverticula, conditions that frequently occur together. Novel approaches to preventing and treating diverticular diseases by promoting vagal activity are proposed including the electrical or pharmacologic modulation of the autonomic system.

Aging↗

PubMed2002

Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments.

In recent years there has been an increasing appreciation of the complexity of functional gastrointestinal disorders. These represent a spectrum of conditions which may affect any part of the gastrointestinal tract in which there appears to be dysregulation of visceral function and afferent sensation and a strong association with emotional factors and stress. There is a clear psychological dimension, with up to 60% of irritable bowel syndrome (IBS) patients reported to have psychological co-morbidities and altered pain perception is also common in comparison with control populations. The role of the enteric nervous system, the sensory pathways and the brain as well as the influence of the latter on sympathetic and parasympathetic outflow have likewise attracted increasing interest and have led to exciting new methods to study their complex interactions. The concept of low-grade inflammation, such as might occur after infection, acting as a trigger for neuromuscular dysfunction has also led to the broad integrative hypotheses that help to explain the biopsychosocial dimensions seen in functional gastrointestinal disease. The multi-component model places a major emphasis on neurogastroenterology and enteric and neuro-immune interactions where new approaches to pharmacotherapy lie. Drugs may affect motility, visceral sensation and other aspects of gut function such as secretion or absorption. More particularly, however, has been the search for and attempts to influence important mediators of these primary gut functions. Such targets include serotonin and selected 5-HT receptors, which are involved in gut motility, visceral sensation and other aspects of gut function, CCK receptors which are involved in the mediation of pain in the gut and nociception in the CNS, opioid receptors involved in pain in the brain, spinal cord and periphery, muscarinic M3-receptors, substance P and neurokinin A and B receptors which are involved in motor adaptation and pain transmission in association with inflammation, gabba receptors involved in nociception and cannabinoid receptors which are involved in the control of acetyl choline release in the gut. With a better understanding of the structures and pathways involved in visceral perception and hyperalgesia, in the CNS, spinal cord and the gut and new pharmacological tools we will be better able to elucidate the neuropharmacology of visceral perception and its relationship to gut dysfunction. It is likely that there will be multiple therapeutic options based on the spectrum of abnormalities capable of causing the spectrum of symptoms of functional gastrointestinal disorders in any individual patient.

Autonomic Nervous System↗

PubMed1977

Postganglionic cholinergic dysautonomia.

A 9-year-old boy presented with symptoms and signs of marked postganglionic cholinergic autonomic dysfunction manifested by bilateral internal ophthalmoplegia, impaired secretion of tears and saliva, lack of gastrointestinal motility, atony of the bladder, generalized absence of sweating, and hypertension. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic system and showed evidence of postdenervation supersensitivity to parasympathomimetic drugs. The patient was treated in the early phase of his illness by the administration of carbachol, and eventually he made a slow and partial spontaneous recovery. Histoimmunofluorescent studies on a skin biopsy specimen suggested an autoimmune origin for his disease, with IgG antibodies being produced against postganglionic cholinergic autonomic fibers.

Autoimmune Diseases↗

PubMed2004

Regional anaesthesia, local anaesthetics and the surgical stress response.

Epidural anaesthesia has the potential to improve patients' outcome after major surgical procedures by reducing postoperative morbidity and duration of recovery. Possible benefits include the attenuation of cardiac complications, an earlier return of gastrointestinal function associated with an increase in patients' comfort overall, decreased incidence of pulmonary dysfunction, beneficial effects on the coagulation system and a reduction in the inflammatory response. The underlying mechanisms, however, remain unclear. Since local anaesthetics (LAs), reabsorbed from the epidural space, seem to contribute to these effects, it is not easy to differentiate between the systemic effects of LAs and the effects of neuraxial blockade by epidural anaesthesia. Thus, in patients not able or willing to receive intra- and/or postoperative epidural analgesia, systemic administration of LAs may be considered to be a new therapeutic approach for the prevention of postoperative disorders by modulation of the peri- and postoperative inflammatory.

Anesthesia, Conduction↗

PubMed2026

The mechanism by which long-term exposure to TDCIPP promotes cognitive impairment in 3 ×Tg-AD mice: Insights from multi-omics studies.

Tri(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a commonly used organophosphate ester that has the potential to adversely affect human health. Although previous studies have closely associated TDCIPP with cognitive impairment, the underlying mechanisms remain unclear. To elucidate the neurotoxic effects of TDCIPP and its mechanistic contribution to cognitive impairment in 3 ×Tg-AD mice, a multi-omics approach incorporating proteomics, untargeted metabolomics, and 16S ribosomal RNA (rRNA) gene sequencing was employed to evaluate the impact of TDCIPP exposure on neurobehavioral function. TDCIPP exposure promoted cognitive impairment in 3 ×Tg-AD mice. Proteomic analyses revealed that this promotion is associated with disturbances in the hippocampal mitochondrial autophagy pathway. Furthermore, TDCIPP may interfere with the PINK1/Parkin-mediated mitophagy pathway at the functional level, without altering PINK1 protein abundance. Untargeted metabolomic analysis of urine samples demonstrated that TDCIPP exposure altered the metabolic profile of 3 ×Tg-AD mice, with 58 metabolites upregulated and 11 downregulated. Additionally, 16S rRNA sequencing revealed substantial modifications in gut microbiome composition following exposure to TDCIPP. Notably, significant correlations were identified between the perturbed bacterial genera and the differential metabolites. In conclusion, exposure to TDCIPP promotes cognitive impairment in 3 ×Tg-AD mice, which is associated with the interference with the PINK1/Parkin-mediated mitophagy pathway, as well as alterations in the urinary metabolome and gut microbiota. These findings suggest the potential to mitigate such cognitive impairment by targeting the microbiota-gut-brain axis.

Animals↗

PubMed2005

Uremic bleeding: pathophysiology and clinical risk factors.

Renal insufficiency appears clinically to be associated with a bleeding tendency. This has been documented in clinical settings including as a complication of medical interventions such as surgery and also in spontaneous bleeding events at gastrointestinal and intracranial sites. The pathophysiology that underlies this tendency appears to involve platelet dysfunction and an imbalance of mediators of normal endothelial function. It is also may be complicated by the co-morbidities in this population, such as vascular disease, hypertension and anemia, and the medical interventions required to treat such co-morbidities. This article reviews the evidence, the pathophysiology and the risk factors for increased bleeding in patients with chronic renal insufficiency.

Hemorrhage↗

PubMed1996

Neonatal complications in newborns with an umbilical artery pH < 7.00.

OBJECTIVE: Our purpose was to determine the significance of an umbilical artery pH < 7.00 in relation to neonatal morbidity and mortality. STUDY DESIGN: Between 1986 and 1993 acid-base assessment of the umbilical artery was performed routinely in 10,699 deliveries. In a retrospective cohort study 84 nonanomalous neonates with an umbilical artery pH < 7.00 were individually matched with 84 neonates with an umbilical artery pH > 7.24. Matched variables included year of delivery, gender, parity, maternal age, delivery mode, fetal presentation, gestational age, and birth weight. Differences in morbidity between the two groups during the neonatal period (until 28 days after delivery) were investigated. RESULTS: Neonates with an umbilical artery pH < 7.00 versus > 7.24 showed significant differences in the following: neonatal condition directly post partum; neurologic, respiratory, cardiovascular, and gastrointestinal complications; and neonatal intensive care unit admissions. No significance was found in renal dysfunction and mortality rate. The proportion of premature infants (< 37 weeks) was 17% in both groups. In the acidotic group a 1-minute Apgar score < or = 3 and a 5-minute Apgar score < 7 was predictive for neonatal complications. CONCLUSIONS: Severe intrapartum asphyxia, quantified by an umbilical artery pH < 7.00, poses a threat to the neonate's health.

Acidosis↗