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Correlation between oesophageal dysmotility and cardiovascular autonomic dysfunction in diabetic patients without gastrointestinal symptoms of autonomic neuropathy.

The vagal function was assessed by oesophageal scintigraphy and cardiovascular autonomic function tests in 65 diabetic patients without gastrointestinal symptoms of autonomic neuropathy and in 20 control subjects. Oesophageal radioisotope transit time was abnormal in 32% of diabetics. Values of cardiovascular function tests were normal in 34% of diabetics while definitive and early signs of cardiac autonomic neuropathy were found in 34% and 32% of diabetics, respectively. The results of oesophageal scintigraphy and cardiovascular function tests were concordant only in 54% of diabetics. Simultaneous impairment of oesophageal motility and cardiovascular (vagal) reflexes could be frequently but not uniformly observed in diabetics. Thus, vagal innervation of different organs (oesophagus and heart) might be affected to different degrees in diabetic patients.

Diabetes Mellitus, Type 1↗

[Adriamycin and Ara-C infusions in the treatment of refractory leukemia].

We have treated two pediatric patients with refractory ANLL and four with relapsed high-risk ALL with Adriamycin continuous Ara-C i.v. Four out of six patients were able to enter complete remission after first or second course of the treatment. All of them developed severe bone marrow suppression, and various degree of oral mucositis, liver dysfunction and gastrointestinal toxicity, and two patients died from side effects. Recently this combination chemotherapy is becoming a best regimen for the treatment of untreated ANLL. Although our cases are small in number, this combination therapy also seems to be effective for refractory ANLL and relapsed high-risk ALL. It is needless to say that we have to pay more attention when we use this regimen.

Acute Disease↗

[Irritable colon and constipation].

Irritable bowel syndrome is a very common clinical problem with a broad spectrum of severity. The management includes a combination of positive diagnosis of typical symptoms with limited investigations to exclude underlying structural or biochemical disorders. Therapeutic trials focus on the relief of predominant symptoms. Identification and modification of factors exacerbating symptoms, behavioural techniques and pharmacologic agents directed to the presumed gastrointestinal motor dysfunction are required. Psychological support by the physician is the most important part of treatment. Chronic constipation may be the predominant symptom of irritable bowel syndrome. Underlying organic disorders must be excluded by clinical examination and endoscopy. Severe chronic constipation requires further investigation of colonic motility and defecation. High fibre diet, osmotic laxatives and procinetic agents may lead to an improvement. In rare cases surgery may be indicated.

Chronic Disease↗

[Adverse effects of low-dose methotrexate therapy in rheumatoid arthritis].

To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population.

Adult↗

Alcohol abuse: medical effects of heavy drinking in late life.

As many as 15% of community-dwelling older persons are heavy drinkers, but their alcoholism is often hidden from their physicians. Depression, loneliness, and lack of social support are the most frequently cited antecedents to drinking for older alcoholics. Clinically, the same amount of alcohol once consumed with impunity may cause clinical symptoms in late life. Physiologic changes in volume of distribution make older patients susceptible to acute alcohol toxicity, with its CNS effects and metabolic disturbances. Liver disease, nutritional deficiencies, and impotence are consequences of chronic alcohol abuse.

Age of Onset↗

Familial association of autonomic and gastrointestinal symptoms.

Autonomic dysfunction occurs in the adult population with irritable bowel syndrome, but this association is not recognized in children. A mother and son with functional abdominal pain unresponsive to conventional treatment had complete resolution of symptoms with treatment directed at the autonomic dysfunction identified by testing. The authors recommend autonomic testing in patients with functional abdominal pain and suggest that autonomic dysfunction plays a direct and intrinsic role in the mechanism of these disorders and their symptoms.

Adrenergic beta-Antagonists↗

Gastrointestinal endoscopes cleaned without detergent substance following an automated endoscope washer/disinfector dysfunction.

OBJECTIVE: To report cases of gastrointestinal endoscopies performed with endoscopes that were reprocessed without detergent substance during a period of dysfunction of the automated endoscope reprocessor (AER). METHOD: A dysfunction of the AER for the cycles requiring detergent substance was reported at the Grenoble University Hospital on March 2005. During this period, 72 patients had potentially been exposed to a contaminated endoscope. A recall procedure was organized and serologic tests (HIV, HCV, HBV) were performed 3 and 6 months after the AER incident. RESULTS: Within the 72 patients convened, 56 (77.8%) were seen in consultation and accepted the serologic screening. Finally, serologic screening was done for 59 patients (81.9%) and no seroconversion for HIV, HCV, or HBV was observed. The final attrition rate was 13 patients (18.1%). CONCLUSION: No viral infection was transmitted during the AER dysfunction. After this AER incident, the monitoring of the endoscopic procedures and the traceability of the cleaning process were both improved to prevent further incidents.

Cross Infection↗

Nitric oxide and its metabolites mediate ethanol-induced microtubule disruption and intestinal barrier dysfunction.

Loss of gastrointestinal (GI) barrier integrity has been implicated in a wide range of inflammatory illnesses, including alcoholic cirrhosis. Using monolayers of Caco-2 (intestinal) cells as a model, we showed that the ability of ethanol (EtOH) to disrupt intestinal barrier integrity depends on damage to the microtubule (MT) cytoskeleton, especially oxidative injury. One drug that prevented both the MT damage and barrier disruption was L-N(6)-1-iminoethyl-lysine, a selective inhibitor of the inducible form of nitric-oxide synthase (iNOS). Because of this finding and because overproduction of nitric oxide (NO) and generation of peroxynitrite (ONOO(-)) have been proposed to be responsible for mucosal injury in other GI disorders, we sought to determine whether NO overproduction and ONOO(-) formation mediates EtOH-induced MT damage and loss of intestinal barrier function. To this end, Caco-2 monolayers were exposed to EtOH or to authentic ONOO(-) or ONOO(-) generators with or without pretreatment with iNOS inhibitors or antioxidants. We found that EtOH caused 1) iNOS activation, 2) NO overproduction, 3) increases in oxidative stress and superoxide anion production (superoxide dismutase quenchable fluorescence of dichlorofluorescein), 4) nitration and oxidation of tubulin (immunoblotting), 5) decreased levels of stable polymerized tubulin, and 6) increased levels of disassembled tubulin. EtOH also 7) extensively damaged the MT cytoskeleton and 8) disrupted barrier function. Authentic ONOO(-) or ONOO(-) donors had similar effects. Pretreatment with a selective iNOS inhibitor, L-N(6)-1-iminoethyl-lysine, or with antioxidants (ONOO(-) scavengers urate or L-cysteine; superoxide anion scavenger superoxide dismutase) attenuated damage due to EtOH or to ONOO(-) generators. We conclude that EtOH-induced MT damage and intestinal barrier dysfunction require iNOS activation followed by NO overproduction and ONOO(-) formation. These findings provide a rationale for the development of novel therapeutic agents for alcohol-induced GI disorders that inhibit this mechanism.

Antioxidants↗

Autonomic Nervous System Dysfunction in Parkinson's Disease.

Autonomic nervous system (ANS) dysfunction is common in Parkinson's disease (PD), affects 70% to 80% of patients, and causes significant morbidity and discomfort. Autonomic nervous system dysfunction symptoms in PD include sexual dysfunction, swallowing and gastrointestinal disorders, bowel and bladder abnormalities, sleep disturbances, and derangements of cardiovascular regulation, particularly, orthostatic hypotension. Autonomic nervous system dysfunction in PD may be caused by an underlying degenerative process that affects the autonomic ganglia, brainstem nuclei, and hypothalamic nuclei. Anti-parkinsonian medications can cause or worsen symptoms of ANS dysfunction. The care of a PD patient with ANS dysfunction relies on its recognition and directed treatment, including coordinated care between the neurologist and appropriate subspecialist. Pharmacotherapy may be useful to treat orthostasis, gastrointestinal, urinary, and sexual dysfunction.

Journal Article↗

A severe form of amyloidotic polyneuropathy in a Costa Rican family with a rare transthyretin mutation (Glu54Lys).

Four affected siblings in a Costa Rican family presented an aggressive polyneuropathy with widespread involvement of many visceral organs and onset during the third decade of life with rapid loss of muscle mass in the lower limbs and severe dysautonomy. The medical histories include vitreous opacity, cardiac enlargement, dermal and gastrointestinal infiltration, and autonomic dysfunction including circulatory compromise and gastrointestinal disturbances. Histological studies using Congo red stain and immunohistochemical assays with antibodies against the transthyretin (TTR) protein showed widespread deposition of amyloid in extracellular areas, including dermis and gastrointestinal lamina propia, endo- and perineural spaces, and vascular walls. A mutation search in the transthyretin (ttr) gene was performed seeking the cause of this severe form of familial amyloidotic polyneuropathy (FAP). We applied single-stranded conformational polymorphism (SSCP)-analyses followed by sequencing of the four exons of the ttr gene, revealing a point mutation in exon 3, a G to A transition that causes a Glu54Lys codon change. Western blots of plasma proteins incubated with anti-transthyretin antibodies after gel electrophoresis provided separation of wild-type and mutant TTR protein in affected family members.

Adult↗

Protective effects of nimesulide (COX Inhibitor), AKBA (5-LOX Inhibitor), and their combination in aging-associated abnormalities in mice.

Several inflammatory processes play a critical role in brain aging and are associated with increased vulnerability to neurodegeneration. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two enzymes involved in the oxygenation of the arachidonic acid, are upregulated in the central nervous system during aging and are associated with different aging-related brain pathologies. The present experiment was performed to study the effects of 5-LOX inhibitor, acetyl-11-keto-beta-boswellic acid (AKBA), nimesulide (preferential COX-2 inhibitor), and their combination on cognitive performance of young and aged mice, using elevated plus maze test. Chronic administration of AKBA (100 mg/kg, p.o.) and nimesulide (2.42 mg/kg, p.o.) for 15 days significantly reversed the aging-induced retention deficit in mice. Coadministration of AKBA and nimesulide enhanced the cognitive performance in aged mice when compared with that in per se treatment. The aging-related increase in oxidative damage (increased LPO and decreased GSH) was reversed by AKBA, nimesulide, and their combination. Further, per se COX and LOX inhibitors and their combination did not produce any alteration in gastrointestinal parameters; they also reversed the aging-induced motor dysfunction in the aged animals. On the basis of these observations, present findings indicated that the combination of COX and LOX inhibitors (dual inhibitors) may provide a new therapeutic innovation for the treatment of aging-related brain disorders such as Alzheimer's disease and different motor dysfunctions with adequate gastrointestinal tolerability.

Aging↗

[Bacterial infection in cirrhotic patient].

BACKGROUND: Bacterial infections at admission or during hospitalization are frequent complication of cirrhosis that occurs in about 30% of the cases. Furthermore they are responsible for 25% of deaths in this population. AIM: Evaluate the prevalence of bacterial infections in cirrhotic patients at a general hospital and determine its correlation with alcoholic etiology of liver disease; degree of hepatic dysfunction and upper gastrointestinal bleeding. PATIENTS/METHODS: Five hundred and forty one admissions were retrospectively evaluated in 426 cirrhotic patients at years 1992 to 2000. The mean age was 50.5 years (15-95), being 71.2% male. The alcoholic etiology of cirrhosis was 35.4%. The main outcome considered was discharge or death during admission. RESULTS: One hundred and thirty five episodes of bacterial infections (25%) were diagnosed. The most frequent are urinary tract infection (31.1%), spontaneous bacterial peritonitis (25.9%) and pneumonia (25.2%). The association between urinary tract infection and pneumonia occurred in 3.7% and erysipelas or cellulites in 11.1%. Bacteremia occurred in 2.9%. There was a correlation between bacterial infection and alcoholic etiology of liver disease, hepatic dysfunction and upper gastrointestinal bleeding. The mortality was higher in the infected patients (8.9%) and in those with a poor hepatic function. CONCLUSIONS: Bacterial infections are common complications in cirrhotic patients and are correlated with alcoholic etiology, Child Pugh classification and upper gastrointestinal bleeding. Furthermore, bacterial infections are correlated with poor prognosis.

Adolescent↗

Dysfunction of the lower urinary and distal gastrointestinal tracts in pediatric patients with known spinal cord problems.

Destruction of the urinary tract in children with elimination, storage, and holding dysfunction of the lower urinary and the distal GI tracts is caused primarily by high intravesical pressure. UTI accelerates this process. The LPP and the status of the urethral control mechanism and its relationship to the detrusor are the primary determinants of intravesical pressure. Intravesical pressures of more than 40 cm H2O are dangerous because they cause a pressure gradient that is transmitted proximally to the renal papillae, which results in the cessation of renal blood flow and a loss of renal function over time. Hydroureteronephrosis, VUR, UTI, urinary incontinence, and calculi formation also may occur. If these dangerously high intravesical pressures remain untreated, renal failure is likely to occur over time. These children then require dialysis or renal transplantation to survive, which is tragic and represents an enormous economic cost to society. Renal failure and upper urinary tract damage is nearly 100% preventable with early and appropriate evaluation and treatment. CIC is a crucial part of the management of these children and has been shown to be safe and effective, even in newborn boys. The use of the Credé maneuver (i.e., manual compression) to empty the bladder is obsolete and should be abandoned. The distal GI tract is inseparable from the lower urinary tract and must be treated simultaneously. Failure to treat the distal GI tract yields poor clinical results and much patient dissatisfaction and makes it difficult or impossible to treat the child's urinary tract problem successfully. Bowel-management programs must include daily high water and fiber intake, together with digital perianal stimulation or fecal extraction. Neuropathic bladder and bowel problems that are intractable to conservative medical and mechanical (i.e., CIC and digital perianal stimulation or fecal extraction, respectively) management almost always can be corrected surgically with high success rates in cooperative patients. Finally, neuropathic bladder and bowel problems can be extremely isolating and debilitating problems. Psychologic counseling and emotional support must be provided as needed. The care that these patients receive must be organized, comprehensive, and correlated with these patients' lifestyles. If these children are evaluated and treated early, they have the potential to live long, healthy, and productive lives.

Biophysical Phenomena↗

Intestinal mucosal enzymes in the diagnosis of gastrointestinal metabolic disease.

The small intestinal mucosa is an actively metabolizing, rapidly proliferating, absorptive epithelium with nutritional and homeostatic functions. A metabolic dysfunction of this organ might, therefore, be expected to cause not only gastrointestinal dysfunction, but also systemic symptoms. Several diseases characterized by primary or secondary gastrointestinal metabolic alterations are discussed.

Acrodermatitis↗

Gastrointestinal manifestations of septic patients with scrub typhus in Maharat Nakhon Ratchasima Hospital.

Scrub typhus is an acute febrile illness caused by Orientia induced vasculitis, which is common in Asia and the Pacific Islands and is sometimes also encountered in Western countries. Even though it can cause multi-organ dysfunctions, there is limited information regarding the relationship between scrub typhus infection and gastrointestinal dysfunction. Therefore, a cross-sectional study was conducted to discover the gastrointestinal manifestations of septic patients with scrub typhus infection. During the study period, 80 septic cases were recruited, and according to the results of immunofluorescent antibody testing (IFA), 20 (25%) were found to have scrub typhus infection. The most common gastrointestinal symptoms of scrub typhus patients were vomiting 13 (65%), nausea 12 (60%), diarrhea 9 (45%), and hametamesis or melena 5 (25%). Gastrointestinal signs included hepatomegaly 8 (40%), jaundice 7 (35%), and abdominal pain 4 (20%). Elevation of SGOT, SGPT, and alkaline phosphatase were 16 (80%), 14 (70%), and 16 (80%), respectively. Direct bilirubin was elevated in 19 (95%) of the cases and half of the cases had a low serum protein level. Of scrub typhus cases, 8 (40%) had eschars. The sites of eschars were mostly in hidden areas, such as on the back, genitalia and abdomen. Three of the five patients with eschar had hepatomegaly on ultrasound examination. The significant findings of the scrub typhus septic patients with eschar on endoscopic examination were gastritis in two cases, gastritis with gastric erosion in two cases, and one case showed a duodenal ulcer and erosion. The differentiating point for endoscopic findings in scrub typhus compared to the other causes was that the stomach lesions were more frequent and severe than the duodenal lesions. According to our endoscopic findings, physicians should be aware of gastric and duodenal lesions in febrile patients with gastrointestinal symptoms, such as abdominal pain or discomfort and indigestion. Scrub typhus can cause gastrointestinal and liver dysfunction.

Adult↗

Gastrointestinal problems in the neurologically impaired child.

Damage to the developing central nervous system may result in significant dysfunction in the gastrointestinal tract and is reflected in impairment in oral-motor function, rumination, gastro-oesophageal reflux, with or without aspiration, delayed gastric emptying and constipation. These problems can all potentially contribute to feeding difficulty in disabled children. Early recognition of an infant with neurological impairment that is compromising the normal feeding process is crucial. Detailed assessment of the nature of the feeding difficulties will help to predict the anticipated future nutritional needs and will allow decisions to be made about the appropriateness of input from different professionals (speech therapy, dietitians, gastroenterologists). Only when such information has been carefully assembled will rational and directed medical and surgical therapy be possible. Nutritional rehabilitation of disabled children can be associated with increased mortality and morbidity secondary to gastro-oesophageal reflux, retching, dumping syndrome or aspiration. It may also entail an increased work for care givers and increase costs of care. It is therefore necessary to document the impact of such rehabilitation on growth and quality of life for both patient and care giver.

Cerebral Palsy↗