Gene/Protein Disease Symptom Drug Enzyme Compound
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Gastrointestinal symptoms such as nausea, abdominal pain, and bloating are frequent complaints of patients with Parkinson's disease (PD). It has been postulated that impaired gastrointestinal function may contribute to the development of motor fluctuations such as delay on and no on in patients with PD. Gastrointestinal impaired function and symptoms may be associated with the disease itself or secondary to levodopa treatment. Thus, we assessed gastric emptying (GE) and gastric motility in PD patients to examine the association between clinical status and gastric function. GE and antral contraction (frequency and amplitude) were evaluated by scintigraphy in 29 patients with mild PD (Hoehn and Yahr [H&Y] stage 1.0-2.0); 22 patients with moderate PD (H&Y stage 2.5-3.0); and 22 healthy volunteers, following the ingestion of a labeled standard meal. Gastric emptying (mean +/- SD of T(1/2)) and antral contraction were not significantly different between patients with mild PD (63.4 +/- 28.8 minutes) and moderate PD (54.7 +/- 25.5 minutes). In the control group, GE was 43.4 +/- 10.8 minutes (range 29.0 - 61.0 minutes). The prevalence of delayed emptying (>61 minutes) was not significantly different in patients with mild disease (48.3%) as compared with patients with moderate disease (36.4%). Antral contraction, both frequency and amplitude, were not significantly different between patients with mild and moderate PD throughout the entire 100 minutes of the study. Untreated patients (n = 28) had mean GE T(1/2) of 59 +/- 30.6 minutes. Patients with smooth response to levodopa showed slower GE (n = 10; 73.6 +/- 25.3 minutes), while treated patients with motor response fluctuations when tested at the on state (n = 13), had much faster GE (49.3 +/- 16.2 minutes). This shortened GE in the on state was similar to the GE of normal volunteers. We conclude that gastric emptying time in patients with PD was delayed compared with control volunteers. It was even slower in patients treated with levodopa. This effect of levodopa treatment was reversed to pseudonormalization (normal GE) at the advanced stages of the disease, when patients developed motor response fluctuation. Other clinical features of PD were not associated with delayed gastric emptying.
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PMID:Gastric emptying time and gastric motility in patients with Parkinson's disease. 1174 35

Laparoscopic Roux-en-Y (RY) gastric bypass is an effective treatment for morbid obesity. However, little information is available regarding the gastrointestinal symptomatic outcome after laparoscopic RY gastric bypass for morbid obesity. The purpose of this study is to identify changes occurring in gastrointestinal symptoms after laparoscopic RY gastric bypass. A previously validated, 19-point gastrointestinal symptom questionnaire was administered prospectively to each patient seen for surgical consultation to treat morbid obesity. Patients rated the degree to which each symptom affected their lives on a 0 to 100 mm Liekert scale with 0 indicating absence of a symptom, 33 indicating the symptom was present occasionally, 67 indicating the symptom occurred frequently, and 100 indicating the symptom was continuous. The same survey was readministered 6 months postoperatively. The mean of each symptom (preoperative vs. postoperative value) was compared using Student's t test with significance at P<0.05. Forty-three preoperative patients (age 37.3+/-8.6 years; body mass index 47.8+/-4.9) and thirty-five, 6 months' postoperative patients (81% follow-up; body mass index 31.6+/-5.3) completed the questionnaire. The result for each symptom is expressed as mean+/-standard deviation of preoperative vs. postoperative scores. Significantly different symptoms include the following: abdominal pain 23.3+/-26.4 vs. 8.6+/-13.5, P=0.003; heartburn 34.0+/-26.6 vs. 8.0+/-14.0, P=0.0001; acid regurgitation 28.1+/-24.0 vs. 10.7+/-21.0, P=0.001; gnawing in epigastrium 19.3+/-22.7 vs. 7.5+/-16.0, P=0.01; abdominal distention 38.2+/-31.5 vs. 11.1+/-19.2, P=0.0001; eructation 27.7+/-24.4 vs. 15.5+/-16.9, P=0.01; increased flatus 40.2+/-25.7 vs. 25.2+/-25.3, P=0.005; decreased stools 5.4+/-16.8 vs. 17.4+/-20.0, P=0.0005; increased stools 23.9+/-26.7 vs. 6.5+/-11.7, P=0.0005; loose stools 29.7+/-26.5 vs. 17.5+/-20.0, P=0.03; urgent defecation 34.3+/-26.5 vs. 14.3+/-19.3, P=0.0009; difficulty falling asleep 44.1+/-38.4 vs. 27.5+/-32.9, P=0.05; insomnia 42.4+/-36.2 vs. 21.6+/-30.5, P=0.008; and rested on awakening 65.1+/-33.8 vs. 30.5+/-28.8, P=0.0001. Symptoms that did not significantly change included the following: nausea/vomiting 17.2+/-22.7 vs. 22.1+/-19.9, P=0.33; borborygmus 28.8+/-25.2 vs. 26.8+/-29.7, P=0.75; hard stools 10.3+/-22.9 vs. 7.1+/-18.6, P=0.56; incomplete evacuation of stool 17.2+/-22.8 vs. 13.4+/-21.7, P=0.45; and dysphagia 10.9+/-15.6 vs. 17.7+/-28.4, P=0.18. Laparoscopic RY gastric bypass significantly improves many gastrointestinal symptoms experienced by morbidly obese patients without adversely affecting any of the measured parameters. This information is useful in preoperative counseling to assure patients of overall symptomatic improvement after this operation in addition to significant weight loss and improvement of comorbid conditions.
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PMID:Gastrointestinal symptomatic outcome after laparoscopic Roux-en-Y gastric bypass. 1312 51

This article reviews the safety and tolerability profile of tegaserod, a novel selective partial agonist of the serotonin 5-HT(4) receptor. Tegaserod was recently approved for the treatment of women with irritable bowel syndrome (IBS) with constipation. Tegaserod exhibits rapid absorption from the small intestine, and is excreted unchanged in the faeces and as metabolites in the urine. Meal ingestion decreases its bioavailability. There is little effect of age or gender on pharmacokinetics, although plasma levels may be slightly higher in the elderly. Tegaserod has no effect on plasma levels of other drugs metabolised by cytochrome P450 enzyme systems. Gastrointestinal symptoms are the most common adverse effects of tegaserod therapy. In data pooled from phase III randomised controlled trials (RCTs) in IBS with constipation patients, diarrhoea was reported by 8.8% of patients treated with tegaserod 6mg twice daily versus 3.8% of patients receiving placebo. Similar rates have been observed in international post-US marketing RCTs. In most patients, tegaserod-induced diarrhoea was mild and transient. In RCTs, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of IBS patients discontinued tegaserod due to diarrhoea. Since its release, rare cases of more severe diarrhoea and ischaemic colitis have been reported. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea, and flatulence) has been similar among tegaserod-treated patients and placebo-treated patients. Pooled analysis of phase III RCTs and post-US marketing RCTs have not demonstrated significant differences between tegaserod-treated patients and placebo-treated patients in the incidence of abdominal-pelvic surgery. There is no convincing evidence that rebound gastrointestinal symptoms occur upon termination of tegaserod therapy. Pooled analysis of phase III RCTs demonstrated an increase in the incidence of headaches among tegaserod-treated patients (6mg twice daily) compared with placebo-treated patients (15% vs 12.3%, respectively, p < 0.05), although post-US marketing RCTs have not observed this increase. Other extra-gastrointestinal adverse events occur with similar frequency among tegaserod-treated patients and placebo-treated patients. Tegaserod-treated patients in RCTs have not demonstrated significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. Supra-therapeutic doses in healthy volunteers did not effect electrocardiographic parameters. Laboratory parameters are mostly unaffected by tegaserod, although several individuals have exhibited increased eosinophil counts. In summary, tegaserod exhibits a favourable safety and tolerability profile in IBS patients based on data from clinical trials. Diarrhoea is the most common adverse event associated with tegaserod use. Continued post-US marketing surveillance will further define the safety and tolerability profile of tegaserod.
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PMID:Safety profile of tegaserod, a 5-HT4 receptor agonist, for the treatment of irritable bowel syndrome. 1523 Jun 44

Cytomegalovirus (CMV) disease typically occurs 1 to 4 months (median 35 days) after solid organ transplantation. Recent reports documented that the natural history of CMV disease associated with solid organ transplantation has been modified as a result of the widespread use of potent immunosuppressents and antiviral prophylaxis. We herein report three pretransplant CMV seropositive recipients (with unknown donor status) who were diagnosed recently to display late and atypical CMV disease. Two men and one woman included two patients who presented with allograft dysfunction at 12 years and at 3 years after transplantation. Both patients showed increased serum creatinine approximately from baseline 200 to >400 micromol/L over 3 months in the absence of features of rejection or cyclosporine toxicity. A renal biopsy was refused by both patients. Two of the three patients presented with symptoms of enterocolitis (diarrhea, nausea, weight loss), which had persisted for more than 6 months. Other symptoms and signs of overt CMV disease (fever, leukopenia) were absent. None had pulmonary, hepatic, or other major organ involvement. In all patients IgG antibodies and CMV DNA by polymerase chain reaction were positive with negative IgM antibodies. The immunosuppressive regimen consisted of mycophenolate mofetil (MMF), steroids, and calcineurin inhibitors. The kidney function significantly improved in both patients with renal dysfunction. Gastrointestinal symptoms resolved completely with gradual weight gain. The recognition and early diagnosis of late atypical CMV disease in kidney transplant patients presenting with allograft dysfunction and/or other organ systems is important. The MMF has a red herring effect in our cases due to its GI side effects.
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PMID:Late cytomegalovirus disease with atypical presentation in renal transplant patients: case reports. 1535 Apr 93

Gastrointestinal symptoms are the most common side-effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post-US marketing randomized controlled trials. In most patients, tegaserod-induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod-treated and placebo-treated patients. Pooled analysis of Phase III and post-US marketing randomized controlled trials did not demonstrate significant differences between tegaserod-treated and placebo-treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod-using patients in any Phase III or post-marketing randomized controlled trials, and post-marketing surveillance indicated that the rate of ischaemic colitis in tegaserod-using patients was lower than that in non-tegaserod-using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod-treated (6 mg b.d.) vs. placebo-treated patients (15% vs. 12.3%, respectively; P < 0.05), although post-US marketing randomized controlled trials did not demonstrate this increase. Other extra-gastrointestinal adverse events occurred with similar frequency in tegaserod-treated and placebo-treated patients. Tegaserod-treated patients in randomized controlled trials did not demonstrate significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.
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PMID:Review article: the safety profile of tegaserod. 1552 52

Gastrointestinal symptoms are extremely common during pregnancy. Increased levels of female sex hormones cause or contribute to symptoms such as heartburn, nausea, vomiting and constipation. If these symptoms do not respond adequately to lifestyle and dietary changes, drug therapy is often warranted to improve quality of life and to prevent complications. Physicians, therefore, need to be familiar with the low-risk treatment options available. Treatment of chronic conditions such as IBD or chronic liver disease during pregnancy can be demanding. In women with IBD, maintenance of adequate disease control during pregnancy is crucial. Most IBD drugs can be used during pregnancy, but the benefits and risks of specific drugs should be discussed with the patient. Liver diseases can be coincidental or pregnancy-specific. Pregnancy-specific liver diseases include not only benign disorders such as intrahepatic cholestasis of pregnancy, but also pre-eclampsia, eclampsia and HELLP syndrome (hemolytic anemia, elevated liver enzymes and low platelet count). Accordingly, the spectrum of therapeutic measures ranges from expectant management to urgent induction of delivery. During pregnancy, lamuvidine therapy for chronic hepatitis B can be continued; however, interferon and ribavirin therapy for chronic hepatitis C is contraindicated. This Review provides an overview of the spectrum and therapy of motility disturbances that occur during pregnancy, and discusses pregnancy-specific aspects of IBD and liver diseases.
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PMID:The spectrum and treatment of gastrointestinal disorders during pregnancy. 1925 5

The patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI-SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI-SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing (n = 126), and completed the PAGI-SYM questionnaire. Relationships between scores for the six subscales (heartburn/regurgitation, nausea/vomiting, fullness/satiety, bloating, upper abdominal pain, lower abdominal pain) and gastric function were analysed using Pearson's linear correlation, multiple regression analysis, chi-square and Student's t-tests. Gastric emptying was significantly correlated with scores for heartburn/regurgitation (r = 0.26), nausea/vomiting (r = 0.19), fullness/satiety (r = 0.20), bloating (r = 0.21) and lower abdominal pain (r = 0.22; all P < 0.05). Patients with delayed emptying had significantly higher scores for each of these subscales (all P < 0.05). Discomfort volume during gastric distension was significantly correlated with scores for fullness/satiety (r = -0.27), bloating (r = -0.23), heartburn/regurgitation (r = -0.21), and upper abdominal pain (r = -0.20). Patients with hypersensitivity to distension had significantly higher scores for fullness/satiety (P < 0.05). At different cut-off levels of symptom severities, consistent associations were found between fullness/satiety and gastric discomfort volume, between preprandial volumes and upper abdominal pain, compliance and upper abdominal pain, and between bloating and gastric discomfort volume. Multiple regression analysis revealed that gastric emptying rate contributed significantly to models for the severity of these subscales. The importance of discomfort volume disappeared in favour of gender when sex was included in the model. No significant correlations were found with HP status or with gastric accommodation. PAGI-SYM scores are mainly correlated with gastric emptying rate and with gastric hypersensitivity. Multivariate analysis suggests that the questionnaire may be useful in the evaluation of gastroprokinetics. Its role in the evaluation of drugs that alter gastric sensitivity is less clear.
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PMID:Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia. 1966 3

Systemic Lupus Erythematosus (SLE) is an autoimmune disease, with multisystemic involvement. Gastrointestinal symptoms are common, like nausea, vomiting and dyspepsia. Acute pancreatitis is an unusual manifestation of SLE, being an important differential diagnosis in evaluation of abdominal pain. The patients usually presents with pain of variable intensity, some occasions simulating acute abdomen. Several factors have been implicated in the pathogenesis of this condition, such as vasculitis, drugs and antiphospholipid antibodies. The role of corticosteroids as etiologic factor remains controversial. Due to the rarity of SLE associated to pancreatitis, we report two cases of patients with severe inflammatory process. In one case, it was used corticosteroids in high doses during treatment, with good outcome. In another, the patient died because of pancreatic pseudocyst rupture and its postoperative hemodynamic complications. In the reported cases, predisposing factors for acute pancreatitis were not verified, so it was considered a primary manifestation of SLE activity.
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PMID:[Acute pancreatitis and spontaneous rupture of pancreatic pseudocyst in systemic lupus erythematosus]. 2071 Oct 96

Varenicline is a drug specifically developed for smoking cessation. Gastrointestinal symptoms are among the most common side effects (nausea, vomiting, and constipation). Here, we described the case of a 75 year-old man who suffered from functional adynamic ileus while taking varenicline. Adynamic ileus is a rare condition on treatment with varenicline. Clinicals should be aware of this side effect due to it could lead to varenicline withdrawal and reconsideration of patient smoking cessation strategy.
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PMID:Adynamic ileus induced by varenicline. 2124 Dec 40

Ciguatera toxicity is a poisoning from consuming reef fish that had fed on dinoflagellates such as Gambierdiscus toxicus found along coral reefs. The toxin is oil soluble, odorless, colorless, tasteless, heat stable, and is concentrated in larger carnivorous fish such as amberjack, barracuda, eel, grouper, red snapper, sea bass, and Spanish mackerel. Onset of symptoms is usually within 6-12 hours after ingestion. Gastrointestinal symptoms lasting 1-2 days include abdominal pain, nausea, vomiting, and diarrhea. Neurological symptoms may persist for weeks or several months or--rarely--years and include circumoral and extremity paresthesias, temperature sensation reversal, itching, weakness, ataxia, and others. A patient with burning hands and feet who had not found relief using other methods had diagnosis of ciguatera toxicity assisted by hypnotically refreshed memory followed by rapid relief with hypnotic suggestions in 1 session and remained free of symptoms.
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PMID:Hypnosis to alleviate the symptoms of ciguatera toxicity: a case study. 2244 20


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