Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We prospectively evaluated the initial presenting symptoms in 261 patients with Zollinger-Ellison syndrome (ZES) over a 25-year period. Twenty-two percent of the patients had multiple endocrine neoplasia-type 1 (MEN-1) with ZES. Mean age at onset was 41.1 +/- 0.7 years, with MEN-1 patients presenting at a younger age than those with sporadic ZES (p < 0.0001). Three percent of the patients had onset of the disease < age 20 years, and 7% > 60 years. A mean delay to diagnosis of 5.2 +/- 0.4 years occurred in all patients. A shorter duration of symptoms was noted in female patients and in patients with liver metastases. Abdominal pain and diarrhea were the most common symptoms, present in 75% and 73% of patients, respectively. Heartburn and weight loss, which were uncommonly reported in early series, were present in 44% and 17% of patients, respectively. Gastrointestinal bleeding was the initial presentation in a quarter of the patients. Patients rarely presented with only 1 symptom (11%); pain and diarrhea was the most frequent combination, occurring in 55% of patients. An important presenting sign that should suggest ZES is prominent gastric body folds, which were noted on endoscopy in 94% of patients; however, esophageal stricture and duodenal or pyloric scarring, reported in numerous case reports, were noted in only 4%-10%. Patients with MEN-1 presented less frequently with pain and bleeding and more frequently with nephrolithiasis. Comparing the clinical presentation before the introduction of histamine H2-receptor antagonists (pre-1980, n = 36), after the introduction of histamine H2-receptor antagonists (1981-1989, n = 118), and after the introduction of proton pump inhibitors (PPIs) (> 1990, n = 106) demonstrates no change in age of onset; delay in diagnosis; frequency of pain, diarrhea, weight loss; or frequency of complications of severe peptic disease (bleeding, perforations, esophageal strictures, pyloric scarring). Since the introduction of histamine H2-receptor antagonists, fewer patients had a previous history of gastric acid-reducing surgery or total gastrectomy. Only 1 patient evaluated after 1980 had a total gastrectomy, and this was done in 1977. The location of the primary tumor in general had a minimal effect on the clinical presentation, causing no effect on the age at presentation, delay in diagnosis, frequency of nephrolithiasis, or severity of disease (strictures, perforations, peptic ulcers, pyloric scarring). Disease extent had a minimal effect on symptoms, with only bleeding being more frequent in patients with localized disease. Patients with advanced disease presented at a later age and with a shorter disease history (p = 0.001), were less likely to have MEN-1 (p = 0.0087), and tended to have diarrhea more frequently (p = 0.079). A correct diagnosis of ZES was made by the referring physician initially in only 3% of the patients. The most common misdiagnosis made were idiopathic peptic ulcer disease (71%), idiopathic gastroesophageal reflux disease (GERD) (7%), and chronic idiopathic diarrhea (7%). Other less common misdiagnosis were Crohn disease (2%) and various diarrhea diseases (celiac sprue [3%], irritable bowel syndrome [3%], infectious diarrhea [2%], and lactose intolerance [1%]). Other medical disorders were present in 55% of all patients; patients with sporadic disease had fewer other medical disorders than patients with MEN-1 (45% versus 90%, p < 0.00001). Hyperparathyroidism and a previous history of kidney stones were significantly more frequent in patients with MEN-1 than in those with sporadic ZES. Pulmonary disorders and other malignancies were also more common in patients with MEN-1. These results demonstrate that abdominal pain, diarrhea, and heartburn are the most common presenting symptoms in ZES and that heartburn and diarrhea are more common than previously reported. The presence of weight loss especially with abdominal pain, diarrhea, or heartburn is an important clue suggesting the presence of gastrinoma. The presence of prominent gastric body folds, a clinical sign that has not been appreciated, is another important clue to the diagnosis of ZES. Patients with MEN-1 presented at an earlier age; however, in general, the initial symptoms were similar to patients without MEN-1. Gastrinoma extent and location have minimal effects on the clinical presentation. Overall, neither the introduction of successful antisecretory therapy nor widespread publication about ZES, attempting to increase awareness, has shortened the delay in diagnosis or reduced the incidence of patients presenting with peptic complications. The introduction of successful antisecretory therapy, however, has dramatically decreased the rate of surgery in controlling the acid secretion and likely led to patients presenting with less severe symptoms and fewer complications. (ABSTRACT TRUNCATED)
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PMID:Zollinger-Ellison syndrome. Clinical presentation in 261 patients. 1114 36

Functional (nonulcer) dyspepsia refers to upper abdominal pain or discomfort with or without symptoms of early satiety, nausea, or vomiting with no definable organic cause. The current Rome II criteria help to diagnose functional dyspepsia and avoid misdiagnosis of gastroesophageal reflux disease and irritable bowel syndrome as functional dyspepsia. Assessment of gastric emptying with scintigraphy or breath testing may be useful in identifying delayed gastric emptying in patients with dyspeptic symptoms and may be helpful in patient management. Electrogastrography is a noninvasive test that evaluates for gastric dysrhythmias. Satiety testing is being evaluated as an indirect test for impaired fundic relaxation and visceral hypersensitivity. The symptom response to Helicobacter pylori therapy in patients with functional dyspepsia and a negative endoscopy examination but a positive H. pylori test is marginal. Lifestyle modifications often are suggested for initial treatment of functional dyspepsia. Dietary changes such as frequent small meals, low-fat diet, and avoidance of certain aggravating foods may improve symptoms. Additional measures include cessation of smoking, avoiding excess alcohol intake, and minimizing coffee intake. Antacids and over-the-counter histamine type 2 receptor antagonists may be helpful as an "on-demand" therapy for intermittent symptoms. They are safe and relatively inexpensive. Different subgroups of functional dyspepsia are based on the predominant symptom and may help in choosing an appropriate drug to initiate therapy. If the predominant symptom is epigastric pain (ulcer-like functional dyspepsia), histamine-2 receptor antagonists or proton pump inhibitors are the initial treatment of choice. If fullness, bloating, early satiety or nausea is the predominant complaint (dysmotility-like functional dyspepsia), a prokinetic agent may help. Metoclopramide is the only available effective prokinetic agent at present. If metoclopramide is used, short-term treatment and discussion of possible side effects with the patient are advised. If there is no response to these initial treatments, switching therapy from proton pump inhibitor to prokinetic or vice versa can be tried. If these treatment options fail, patient re-evaluation for other disorders (including other functional bowel disorders) is advised. A low-dose tricyclic antidepressant at bedtime may be helpful for treatment of visceral hypersensitivity.
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PMID:Functional (Nonulcer) Dyspepsia. 1187 96

There is some evidence to support a psychosocial link to GERD,although it is a weak one. The little research that has been done in this area is, in general, poor and inconclusive. Better designed studies must be done. The elements that seem to offer the best possibilities for research in GERD are the psychological variables involved in care seeking and the variations between care seekers and non-care seekers. In addition, research on psychosocial predictors of response to proton pump inhibitors, prokinetic agents, and antidepressants and other pain-modulating drugs need to be better understood. The psychosocial link to NCCP is stronger with regard to panic disorder,but much research needs to be done. Despite the paucity of well done,rigorously controlled studies in NCCP patients, that there is a high prevalence of psychiatric disturbance in this group. Parental health and childhood trauma are intriguing areas for further research, particularly in light of the connection between abuse and IBS and other functional GI disorders.Finally, panic disorder has been established as an important comorbidity of NCCP. It also merits more research, particularly into the pathophysiology that may link these two disorders.
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PMID:The psychological aspects of noncardiac chest pain. 1506 38

Idiopathic dyspepsia refers to pain and/or discomfort perceived in the epigastrium that is not secondary to organic, systemic, or metabolic diseases. Symptoms may overlap with those of gastroesophageal reflux disease and irritable bowel syndrome. Gastrointestinal motor disorders, hypersensitivity to mechanical or chemical stimuli, and psychosocial factors can act individually or in concert to induce the symptoms of dyspepsia. Accordingly, there is no single therapy, and treatment must be individualized. Eradication of Helicobacter pylori infection rarely achieves symptom improvement. Treatment of idiopathic dyspepsia should begin by reassuring the patient about the benign nature of the syndrome and educating them on the knowledge that has been achieved in recent years regarding potential causes of the syndrome. Both prokinetic and antisecretory drugs have been reported to improve dyspeptic symptoms, but results are not completely convincing. Although well-designed studies demonstrate superiority of proton pump inhibitors over placebo, it should be noted that patients with nonerosive gastroesophageal reflux disease were invariably included; when these patients are excluded, the benefit of antisecretory medications is questionable. We suggest that patients with idiopathic dyspepsia be initially treated according to the predominant symptom. Those with epigastric pain/burning should receive a trial with standard doses of proton pump inhibitors for 4 to 8 weeks, whereas prokinetic patients should be prescribed at recommended doses for similar periods of time to patients with nonpainful dyspeptic symptoms such as posprandial fullness, early satiety, nausea, or vomiting. Nonresponders may benefit from combination therapies or short trials with higher doses of drugs. Visceral analgesics and antidepressants can also be prescribed alone or in combinations with other therapeutic strategies. Recent studies demonstrate utility for psychologic therapy and hypnotherapy, although truly controlled studies are difficult in this area. Herbal medicines deserve further evaluation.
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PMID:Idiopathic Dyspepsia. 1576 39

The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during > or =30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett's or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other "non-categorized" disorders. Of 2,588 screened patients, 1,667 were excluded. Excluded patients by category had mild/infrequent UAD (12.5%, n=324), heartburn and UAD of equal frequency (1.1%, n=29), predominant heartburn with UAD (11.6%, n=300), endoscopic evidence of erosive esophagitis or Barrett's (6.2%, n=160), gastric and/or duodenal erosions (1.4%, n=36), gastric and/or duodenal ulcers (2.0%, n=53), IBS (7%, n=180), "other" gastrointestinal diagnoses (2.8%, n=73), or other "non-categorized" disorders (19.8%, n=512). Fifty-four percent of patients (902/1,667) had symptoms/diagnoses that would be expected to improve with PPI therapy. Individuals with IBS, "other," or "non-categorized" disorders were considered to have symptoms unlikely to respond to PPI treatment. Empiric PPI treatment would be expected to provide symptom relief to the majority of dyspepsia sufferer who present in clinical practice. PPIs represent the best currently available therapy for acid-related disorders and should be considered the first-line management approach in patients with uninvestigated dyspepsia.
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PMID:Proton pump inhibitors: effective first-line treatment for management of dyspepsia. 1734 2

The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times as much melatonin as the pineal gland; therefore, it is not surprising that research is finding that this indole plays an important role in GI functioning. In animal studies, it protects against GI ulcerations, and randomized clinical trials suggest its efficacy in treating functional dyspepsia and irritable bowel syndrome. Melatonin administration has been shown to protect against esophageal lesions in animals. Moreover, in a randomized, single-blind clinical trial of subjects with gastroesophageal reflux disease (GERD), the combination of melatonin with other natural supplements was found to be superior to omeprazole, a proton pump inhibitor (PPI). Its administration as a single treatment for GERD has not been previously reported. A 64-year-old Caucasian female who required treatment with a PPI for symptoms of GERD wished to substitute a natural treatment because of the risk of worsening her osteoporosis. She experienced a return of symptoms following each of three 20-day trials of a proprietary blend of D-limonene when attempts were made to discontinue the PPI. She then underwent a trial of a natural formula consisting of melatonin 6 mg, 5-hydroxytryptophan 100 mg, D,L-methionine 500 mg, betaine 100 mg, L-taurine 50 mg, riboflavin 1.7 mg, vitamin B6 0.8 mg, folic acid 400 microg, and calcium 50 mg. After 40 days, the PPI was withdrawn without a return of symptoms. Subsequently, an attempt to reduce melatonin to 3 mg resulted in symptoms, while all other ingredients were withdrawn with minimal symptoms during 10 months of follow-up.
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PMID:Melatonin for the treatment of gastroesophageal reflux disease. 1861 70

Some studies indicate that small intestinal bacterial overgrowth (SIBO), as measured by hydrogen breath tests (HBT), is more prevalent in patients with irritable bowel syndrome (IBS) vs. matched controls without IBS. Although the data are conflicting, this observation has led to the hypothesis that SIBO may be a primary cause of IBS. Yet, it remains unclear whether SIBO is truly fundamental to the pathophysiology of IBS, or is instead a mere epiphenomenon or bystander of something else altogether. We hypothesize that SIBO might be a byproduct of the disproportionate use of proton pump inhibitors (PPIs) in IBS, as follows: (1) IBS patients are more likely than controls to receive PPI therapy; (2) PPI therapy may promote varying forms of SIBO by eliminating gastric acid; and (3) existing studies linking SIBO to IBS have not adjusted for or excluded the use of PPI therapy. When linked together, these premises form the basis for a simple and testable hypothesis: the relationship between SIBO and IBS may be confounded by PPIs. Our article explores these premises, lays out the argument supporting this "PPI hypothesis," discusses potential implications, and outlines next steps to further investigate this possibility.
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PMID:Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors? 1908 51

Studies comparing pH-metrically well-characterized gastro-oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24-h pH-monitoring (pH+), defined as pH<4 > or = 6% of time. A symptom index (SI) > or = 50% was considered positive, as well as a symptom association probability (SAP) > or = 95%. We included 84 GORD patients with physiological acid exposure (pH-) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND-36 quality of life scale. pH- patients were younger (45 vs 50 years, P = 0.003), more often female (60%vs 39%, P = 0.001), smoked more (31%vs 19%, P = 0.021) and reported proton pump inhibition failure more often (47%vs 32%, P = 0.027). A hypotensive lower oesophageal sphincter was less common in pH- patients (18%vs 34%, P = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P = 0.045). pH- patients had hiatal hernia and oesophagitis less often (48%vs 73%, P < 0.0005; 36%vs 54%, P = 0.012 respectively). pH- patients less often reported no other symptoms besides GORD (20%vs 34%, P = 0.015). pH- patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P < 0.0005; dyspepsia 54 vs 38 out of 156, P < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.
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PMID:Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum. 1923 23

Dyspepsia affects up to 40 percent of adults each year and is often diagnosed as functional (nonulcer) dyspepsia. The defining symptoms are postprandial fullness, early satiation, or epigastric pain or burning in the absence of causative structural disease. These symptoms may coexist with symptoms of functional gastrointestinal disorders, such as gastroesophageal reflux and irritable bowel syndrome, as well as anxiety and depression. The history and physical examination can help identify other possible causes of the symptoms. Warning signs of serious disease, such as cancer, are unintended weight loss, progressive dysphagia, persistent vomiting, evidence of gastrointestinal bleeding, and a family history of cancer. In these cases, more extensive laboratory investigation, imaging, and endoscopy should be considered as clinically indicated. During the initial evaluation, a test-and-treat strategy to identify and eradicate Helicobacter pylori infection is more effective than empiric treatment and more cost-effective than initial endoscopy. Eradication of H. pylori helps one out of 15 patients with functional dyspepsia diagnosed by endoscopy, but may not be cost-effective. Treatment options that may be beneficial for functional dyspepsia include histamine H2 blockers, proton pump inhibitors, and prokinetic agents. Although psychotropic medications and psychological interventions have no proven benefit in patients with functional dyspepsia, they are appropriate for treating common psychiatric comorbidities.
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PMID:Update on the evaluation and management of functional dyspepsia. 2201 Jul 61

Although studies indicate that small intestinal bacterial overgrowth (SIBO) is prevalent in irritable bowel syndrome (IBS), it remains unclear whether SIBO causes IBS. This review presents an epidemiologic and evolutionary inquiry that questions the bacterial overgrowth hypothesis of IBS, as follows. (1) Although the hypothesis may be biologically plausible, there is also a strong rationale for competing hypotheses; it is unlikely that SIBO is the predominant cause of IBS in all comers, because competing explanations are sensible and defensible. Moreover, data indicate that the test used to promulgate the SIBO hypothesis - the lactulose hydrogen breath test - may not have measured SIBO in the first place. (2) We do not have evidence of SIBO being absent before IBS symptoms, and present after IBS emerges. (3) There is not a dose-response relationship between small intestinal microbiota and IBS symptoms. (4) The relationship between SIBO and IBS is highly inconsistent among studies. (5) Many effective IBS therapies do not address SIBO at all, yet have a more favorable "number needed to treat" than antibiotics. (6) IBS does not behave like a traditional infectious disease, suggesting that microbes may not principally cause the syndrome. (7) Other factors may confound the relationship between SIBO and IBS, including proton pump inhibitors. (8) Whereas the brain-gut hypothesis is evolutionary sensible, the bacterial hypothesis is harder to defend from an evolutionary perspective. The article concludes that bacteria may contribute to some IBS symptoms, but that bacteria cannot be the only explanation, and a causal link between SIBO and IBS is not secure.
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PMID:Questioning the bacterial overgrowth hypothesis of irritable bowel syndrome: an epidemiologic and evolutionary perspective. 2139 24


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