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Ovarian hormone modulates 5-hydroxytryptamine 3 receptors mRNA expression in rat colon with restraint stress-induced bowel dysfunction.

AIM: To examine the effects of ovarian hormone on the expression of 5-hydroxytryptamine 3 receptors (5-HT3R) in rat colon of restraint stress-induced bowel dysfunction. METHODS: Twenty-four female Sprague-Dawley rats were randomly divided into three groups of 8 each: sham operation, ovariectomy (OVX) and ovariectomy with estrogen (E2) and progesterone (P) replacement therapy (OVX+E2+P). The rats were subjected to 1-h restraint stress 4 wk after operation. The changes of defecation were monitored by collection of fecal pellets. The gonadal steroids were measured in duplicate by radioimmunoassay (RIA). The expression of 5-HT3R mRNA in the colon was studied by RT-PCR. RESULTS: Compared with sham group and OVX+E2+P group, OVX group showed increase in fecal pellets and decrease in the time of vitreous pellets excretion (P<0.01). Serum levels of E2 and P were suppressed in OVX group and restored following treatment with ovarian steroids (P<0.01), and the levels of 5-HT3R mRNA in the colon of ovariectomized rats were significantly increased, the expression of 5-HT3R mRNA was significantly decreased in hormone replacement therapy group (P<0.01). CONCLUSION: Ovarian hormone plays a role in the regulation of 5-HT3R expressions in restraint stress-induced bowel dysfunction of rats. The interactions between ovarian steroids and gastrointestinal tract may have major pathophysiological implications in 5-HT-related disorders, such as irritable bowel syndrome (IBS).

Animals↗

[Side effects of interferon alfa].

Interferons are a class of glycoproteins whose properties include antiviral, immunomodulatory and antiproliferative effects. Immunotherapy with interferons is used in a variety of diseases, such as haemato-oncological disorders, solid tumours, viral hepatitis and multiple sclerosis. Due to their involvement in the regulation of a large number of physiological functions, many different side effects can occur. Flu-like syndromes, gastrointestinal complaints, fatigue, pain, increased susceptibility to infections, thyroid dysfunction and psychiatric side effects occur frequently with alfa-interferon. Side effects frequently necessitate interruption and dose reduction. Severe or even life-threatening side effects are not frequent but do occur. Patient education is an important promotor of patient compliance, as are proper detection and symptomatic treatment of the side effects.

Antineoplastic Agents↗

[The relationship between abnormalities of cell-mediated immunity and gut origin endotoxemia in a rat model of thermal injury].

This study was conducted to determine the relationship between abnormalities of cell-mediated immunity and gut-derived endotoxemia in rats following burns. Animals were subjected to a 40% full-thickness scald injury, and randomly divided into control and selective decontamination of the digestive tract (SDD) treated groups. It was found that thermal injury resulted in marked reductions in splenocyte proliferative response to concanavalin A or phytohemagglutinin, interleukin 2 (IL-2) production, and T helper/suppressor (Th/Ts) cells ratio. Prophylactic treatment with SDD significantly reduced the incidence of endotoxemia, prevented suppressive mitogenic response and inadequacy in IL-2 production (P < 0.05-0.01), but did not affect the abnormal ratio of Th/Ts in blood (P > 0.05). We conclude that bacteria/endotoxin translocation from the gastrointestinal tract appears to be involved in cellular immune dysfunction after thermal injury. Pretreatment with SDD might attenuate systemic immunosuppression by preventing translocation events.

Animals↗

[Disturbances of the autonomic nervous system in gastroesophageal reflux disease].

GERD (Gastroesophageal Reflux Disease) is a common clinical problem, which affects the upper part of the gastrointestinal tract. The pathophysiology of GERD is associated with dysfunction of the various mechanisms called "the anti-reflux barrier". Lately, the disturbances of the autonomic nervous system (ANS) have been stressed in the pathogenesis of the different diseases (including GERD). The HRV examination (Heart Rate Variability) seems to be the best non-invasive method to evaluate the disturbances of ANS. The aim of our study was to detect possible ANS disturbances in GERD patients. 23 persons (healthy volunteers and GERD patients) took part in the examinations. 24-h-esophageal pH-metry and the resting, "deep breathing" (DB) test, as a short-term measurement of heart rate variability, were performed in every person. The results proved that the GERD patients have abnormal low values of the basic components that make up the HRV spectrum (LF and HF obtained from rest record and HF from record during DB). We demonstrated the evidence of functional ANS disturbances, which may be responsible for the changing the HRV parameters of the frequency domain analysis in GERD patients. The disturbances mentioned above are supposed to influence the normal modulation of the X (vagus) nerve, which plays an important role in the maintaining the physiological LES function.

Adult↗

[Hyperacute graft versus host disease after allo-stem cell transplantation, analysis of 118 cases].

OBJECTIVE: To investigate the clinical manifestations, management, prognosis, and risk factors of hyperacute graft versus host disease (hGVHD) after allo-SCT cell transplantation all-SCT. METHODS: The data of 118 patients aged 2 approximately 52 who underwent 120 times of allo-SCT were analyzed retrospectively. RESULTS: hGVHD was observed in 17 patients with an incidence rate of 14.17%. The clinical manifestations included gastrointestinal symptoms (13/17), rash (13/17), fever (8/17), and hepatic dysfunction (6/17). Another 12 cases with only one organ injured were included in atypical hGVHD group. The two-year survival rates were 30.50%, 40.00%, and 61.67% in patients with typical hGVHD, patients with atypical hGVHD, and patients without hGVHD respectively. The condition of twenty-five cases with hGVHD improved after treatment with immunosuppressive drugs. CONCLUSION: hGVHD is a common complication after allo-SCT that affects the prognosis dramatically. The risk factors of hGVHD include HLA mismatching, disease being in progressive stage just before allo-SCT, female in sex, and sex mismatching.

Acute Disease↗

[Recent development of selective cyclooxygenase-2 inhibitors].

Nonsteroidal anti-inflammatory drugs(NSAIDs) are clinically effective against the inflammatory symptoms of rheumatoid arthritis. Recent attention has been focused on selective cyclooxygenase(COX)-2 inhibitors, a type of NSAID that inhibits a subtype of COX. Because of the different actions of COX-1 and COX-2, selective COX-2 inhibitors were expected to reduce adverse reactions such as gastrointestinal disorders. Various clinical studies have confirmed that the efficacy of COX-2 inhibitors for RA is similar to that of conventional NSAIDs, but they cause fewer severe gastrointestinal disorders. The incidence of complications related to renal dysfunction, such as edema and hypertension, is not different. Patients using selective COX-2 inhibitors have recently been reported to show an increase in thrombotic complications such as myocardial infarction. Therefore, more data on adverse events should be collected in the future from large-scale clinical studies to further clarify the actual value of selective COX-2 inhibitors.

Animals↗

Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency.

In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculoskeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency.

Administration, Oral↗

Lubiprostone.

Sucampo Pharmaceuticals Inc and Takeda Pharmaceutical Co Ltd are developing, a ClC-2 chloride channel activator and a bicyclic member of a series of fatty acid compounds, for the potential treatment of a number of gastrointestinal conditions, including constipation, irritable bowel syndrome, postoperative bowel dysfunction and opioid bowel dysfunction.

Alprostadil↗

Enteral nutrition in patients with chronic neurological diseases.

BACKGROUND: Malnutrition is commonly considered an important risk factor that can produce a negative influence on the prognosis of patients with chronic neurological diseases. The reduced caloric or proteic intake due to the motor or cognitive dysfunction, the hypercatabolic state due to infections, the abnormal gastrointestinal motility are the main mechanisms responsible for a state of malnutrition. METHODS: Between January and December 1999 fourteen patients with chronic neurological diseases were treated. Ten of them had had a stroke, four due to Amyotrophic Lateral Sclerosis (ALS). After the evaluation of nutritional status the patients received enteral nutrition (EN) by placement of a nasointestinal feeding tube or a Bengmark tube. Glycaemia, blood urea nitrogen, serum creatinine, electrolytes, glycosuria, glutamic-oxalacetic and glutamic pyruvic transaminase were monitored in all patients. Polymeric enteral feeding was administered by an infusion pump. Standard nourished patients (7/14) received a 30 Kcal/kg/day support, the undernourished ones (6 low, 1 moderate malnutrition) received a 35-40 Kcal/kg/day support. RESULTS: The complete caloric supply was reached in three-four days. Both of the groups received continuous feeding infusion during hospitalization. For the patients who continued the nutritional support at home (3/14) refeeding was performed only during night-time. In the patients with stroke the optimal/standard weight was reached within one month. In these patients oral nutrition was started within 45 days of treatment taking into account the restored swallowing function. In the patients with ALS the improvement of nutritional standards was reached within the first month and complete restoration within the second/third month. CONCLUSIONS: On the basis of our experience enteral nutrition represents an effective refeeding procedure in patients with chronic neurological diseases.

Journal Article↗

The role of immune-enhancing diets in the management of perioperative patients.

OBJECTIVE: To review the effects of immunonutrients in the perioperative patient. DATA SOURCES: Articles and published peer-review abstracts of studies reported on immune enhancing diets in patients during the perioperative period. SUMMARY OF REVIEW: Enteral nutrition is the method of choice for substrate supplementation in patients with a normal gastrointestinal tract but who are otherWise unable to eat normally. It is also a safer, more practical and less expensive alternative to the parenteral route and is now being used successfully in previously contraindicated conditions including pancreatitis and major abdominal trauma. Advances in enteral nutrition include the development of immunonutrients which have been used to attenuate the adverse effects of starvation, illness and surgery on the architecture and function of the gastrointestinal tract, implicated in the development of multiple organ dysfunction syndrome. These agents stimulate immune function and are potentially an effective strategy in improving the outcome in the peri-operative period by reducing post-operative infections and length of hospital stay. CONCLUSIONS: Immunonutrition confers an additive benefit when compared with standard enteral and parenteral nutrient preparations in the management of perioperative malnourished patients. What is less clear is at what severity of illness this benefit begins, whether there is a significant reduction in mortality and at what point the cost benefit in the reduction in complications no longer occurs.

Journal Article↗

Scleroderma renal crisis in progressive systemic sclerosis: a case report.

We report a case of progressive systemic sclerosis with scleroderma renal crisis 10 years after onset. The patient (female) had progressive renal dysfunction, hypertension which was difficult to control, and massive gastrointestinal bleeding. An angiotensin converting enzyme inhibitor (enalapril) could not control her hypertension. Only intravenous nicardipine had a slight effect on her hypertension. Hemodialysis and plasma exchange, did not reverse the renal crisis, and the patient died. Microscopic examination of her kidney showed thickening of the capillary walls and mild nephrosclerosis.

Acute Kidney Injury↗

[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration].

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.

Adult↗

[Hypercalcemia in breast cancer].

In a total of 277 patients with advanced breast cancer treated between July 1977 and November 1983 at Cancer Institute Hospital, there were 26 cases (9.4%) showing hypercalcemia (Ca greater than or equal to 11.0 mg/dl). All these patients had bone metastasis examined by either X-ray films or bone scintigram during clinical course of the disease and confirmed at the time of autopsy, thus an overall incidence of hypercalcemia in 149 patients with bone metastasis was 17.4%. Major clinical signs due to hypercalcemia were gastrointestinal symptoms such as anorexia, nausea and vomiting, renal dysfunction and neurological symptoms but there was no definitive correlation in between clinical signs and values of serum calcium. Among various treatments performed, a combination of hydration, steroids and calcitonin was the most effective. Mean survival time from the diagnosis of hypercalcemia was 288 + days for responders, and 28.8 days for non-responders (p less than 0.001). Seven patients expired due to hypercalcemia and were died suddenly, while others died of renal failures.

Adult↗

[Underdosing and overdosing with digitalis].

Incorrect dosage of digitalis occurs frequently and is due in most cases to relative over- or underdosage. The narrow therapeutic range of all cardiac glycosides and the lack of an ideal preparation form the basis, and noncompliance of the ill-informed patient as well as the changing digitalis requirement from patient to patient, and even in the same patient, are the most frequent causes of dosage errors. Important guidelines for the dosage of digoxin and digitoxin (renal failure, diseases of the liver and gastrointestinal tract, body weight, age, electrolyte disorders, hypoxia, thyroid dysfunction and drug interactions) are discussed. Symptoms, signs and treatment of underdigitalization and digitalis intoxication, a frequent and often lethal complication, are reviewed.

Angina Pectoris↗

[Alternative combination chemotherapy with mitomycin C, vincristine, methotrexate, 5-fluorouracil, cis-platinum and adriamycin for adenocarcinoma of the lung].

Efficacy of an alternative combination chemotherapy with MMC, VCR, MTX, 5-FU, CDDP and ADM for adenocarcinoma of the lung is reported. Forty-one advanced cases (stage III: 9; IV: 32) were chosen for the chemotherapy. Two combination chemotherapies MMC + VCR + MTX + 5-FU + CDDP: MVMFP; MMC + VCR + MTX + 5-FU + ADM: MVMFA were repeated alternatively for 8 consecutive weeks with 2 interposed rest weeks, and this regimen was completed in 34 cases. All 41 cases were evaluable. Three and 26 cases achieved complete and partial responses, respectively. The response rate was 70.7%, and the median survival time was 13 months. The adverse effects of the chemotherapy observed were tolerable: alopecia (63.4%), gastrointestinal symptoms (14.5%), bone marrow toxicity (12.2%) and liver dysfunction (4.8%). These results indicate that our MVMFP/MVMFA alternative chemotherapy is quite effective for adenocarcinoma of the lung, comparable or superior to conventional chemotherapies.

Adenocarcinoma↗

[Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis].

Pancytopenia and interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse methotrexate (MTX) in treating rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and liver dysfunction occurred in 9 patients. Four patients (1.4%) developed pancytopenia, and six patients (2.1%) developed interstitial pneumonitis. All patients who developed pancytopenia were old female with long history of active, deforming rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time pancytopenia developed. Impaired renal function, hypoalbuminemia, and multiple medication were observed, and antinuclear antibodies were positive in most patients. It should be noted that severe stomatitis preceded or accompanied with pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and antinuclear antibodies appeared to be risk factors for interstitial pneumonitis. All patients recovered with high dose of corticosteroid and mechanical ventilation. Such clinical characteristics that are associated with MTX-induced pancytopenia or interstitial pneumonitis should be reminded in the treatment of rheumatoid arthritis with MTX.

Aged↗

Prognostic factors for continued or rebleeding and death from gastrointestinal haemorrhage in the elderly.

We analysed 103 episodes of upper gastrointestinal bleeding in 88 elderly patients (age 76 +/- 7.7 years) to determine which of a group of 52 clinical and laboratory variables, measured on admission, best predicted continued or rebleeding, and death in these patients. Variables which related directly to the size of the bleed (blood urea, haemoglobin, pulse rate, systolic blood pressure) were all strongly predictive of both outcomes (P less than 0.001). Of the variables unrelated to the size of the bleed, prolonged prothrombin time and elevated serum creatinine were most strongly predictive of a poor outcome, suggesting that haemostatic dysfunction may be a major contributor to death from upper gastrointestinal haemorrhage in elderly patients. Other variables with strong predictive potential were age (P less than 0.001), the presence of multiple disease states (P less than 0.01), therapy with multiple drugs (P less than 0.01) and acute stroke or obtundation on admission (P less than 0.01). In general terms the size of the bleed was as significant as the premorbid condition of the patient in predicting the outcome. This, together with the fact that half the patients died of hypovolaemia, suggests that death from upper gastrointestinal bleeding in the elderly is not inevitable and that further reduction in mortality from this cause is attainable.

Aged↗

The radiologic manifestations of idiopathic intestinal pseudoobstruction.

Six patients with idopathic intestinal pseudoobstruction underwent extensive radiographic evaluation of the gastrointestinal tract. Propulsive motor activity was consistently absent. All had smooth muscle dysfunction of the esophagus, small bowel, and colon, and two had abnormal gastric emptying. Two forms of the syndrome were observed, characterized by either hyper- or hypoactive smooth muscle. In the hyperactive form chaotic, spontaneous contractions of the esophagus and small intestine occurred and extensive diverticular disease of the colon was present. In the hypoactive form the esophagus was atonic and there was marked widening and hypomotility of the small intestine and colon. The presence of two forms of smooth muscle dysfunction suggests that the syndrome has a heterogeneous pathology and pathophysiology.

Adolescent↗