Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
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Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.
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PMID:Gastrointestinal complications in renal transplant recipients. 1591 Feb 87

This phase I trial investigates the safety of combining radiation, 5-fluorouracil (5-FU) and cisplatin with the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, in patients with esophageal carcinoma. From April 2000 to January 2005, 11 patients with squamous or adenocarcinoma of the esophagus were enrolled. Patients received either 50, 100 or 150 mg oral erlotinib/day beginning on the first day of radiation (three patients in each dose cohort). Concurrent cisplatin (75 mg/m2 i.v., days 8 and 36) and 5-FU (1000 mg/m2 i.v., days 8-11 and 36-39) were also given with 50.4 Gy thoracic radiation, delivered at 180 cGy/day, 5 days/week. Toxicity was evaluated using the National Cancer Institute Common Toxicity Criteria (version 3.0). Erlotinib with concurrent 5-FU, cisplatin and thoracic radiation was well-tolerated at 50, 100 and 150 mg/day. The major toxicities were diarrhea (grade 1=18%, grade 2=18%), skin rash (grade 4=54.5%), nausea (grade 1=18%, grade 2=54%, grade 3=9%) and dehydration (grade 3=27%). All patients experienced esophagitis during treatment (grade 1=55%, grade 2=32%, grade 3=9%, grade 4=9%). Two patients were discontinued from the study secondary to non-erlotinib-related toxicities. We conclude that the phase I study demonstrates the safety and tolerability of erlotinib delivered at 150 mg/day with concurrent 5-FU, cisplatin and thoracic radiation. The major toxicities encountered were grade 1-2 diarrhea, grade 1 skin rash, grade 1-3 nausea and grade 3 dehydration. A phase II study is planned.
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PMID:Epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, and concurrent 5-fluorouracil, cisplatin and radiotherapy for patients with esophageal cancer: a phase I study. 1631 96

To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m(-2)) and etoposide (2 x 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80-98%) with a median survival time of 19.5 months (95% CI 12.8-29.2). The 1-, 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence.
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PMID:Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study. 1759 61

Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade 1 emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation.
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PMID:Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation. 1650

The purpose of this study was to assess the efficacy and toxicity of intensity-modulated radiation therapy (IMRT) in the treatment of gastric cancer. Seven patients with gastric cancer were treated with IMRT. Six patients (all Stage III) received post-operative chemoradiotherapy with concurrent 5-fluorouracil and leucovorin. One received planned pre-operative radiation, though did not proceed to surgery. All patients were planned to receive 50.4 Gy in 1.8 Gy fractions. IMRT planning was compared with opposed anterior-posterior: posterior-anterior (AP/PA) and 3-field conventional three-dimensional plans. When compared with either AP/PA or 3-field plans, IMRT significantly reduced the volume exceeding the threshold dose of the liver and at least one kidney. Target coverage with IMRT was excellent, with 98+/-1% of the target receiving >or=100% of the dose. Compared with AP/PA and 3-field plans, IMRT plans had a greater percentage of target receiving the prescribed dose, but also a greater volume receiving >110% of the dose. IMRT was well tolerated; no patients developed acute gastrointestinal toxicity greater than grade 2. All seven experienced grade 2 nausea, three had grade 2 diarrhoea and two had grade 2 oesophagitis. Weight loss ranged from 0-12% (mean 6.1% and median 5.8%). IMRT in the treatment of gastric malignancies reduces the mean and above threshold doses to critical normal tissues. In an initial cohort of seven patients, 50.4 Gy delivered by IMRT is well tolerated and safe.
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PMID:Intensity-modulated radiation therapy in the treatment of gastric cancer: early clinical outcome and dosimetric comparison with conventional techniques. 1671 52

With the ever-growing armamentarium of pharmacological agents, the gastrointestinal drug-induced side effects of dyspepsia, nausea, vomiting, diarrhoea and constipation are increasingly seen. They are often self-limiting and without serious sequelae, but of greater concern is drug-induced mucosal ulceration that can manifest as gastrointestinal haemorrhage, stricture and perforation. These complications are mainly attributable to NSAIDs and aspirin, which can injure the mucosa anywhere along the gastrointestinal tract. These iatrogenic serious side effects can be reduced with co-prescription of a proton pump inhibitor, substitution of a COX-2 inhibitor and eradication of Helicobacter pylori when the bacterium is present. Other recognised gastrointestinal complications include small intestinal diaphragm, microscopic colitis, a range of hepatotoxic effects and pancreatitis. The introduction of new classes of drugs has resulted in new adverse effects that require consideration in patients presenting with gastroenterological symptoms. These include pill oesophagitis from bisphosphonates and ischaemic colitis relating to serotonin antagonists. Here, the authors review the literature on drug-induced complications of the gastrointestinal tract and present the pertinent management issues relevant to clinical practice.
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PMID:Drug-induced side effects affecting the gastrointestinal tract. 1677 95

ReQuest is a self-reported questionnaire developed to assess, during clinical trials investigating GERD with or without oesophagitis, not only heartburn and acid regurgitation, but the broad spectrum of GERD symptoms. ReQuest comprises 2 sub-scales: ReQuest-GI which covers the 4 dimensions related to gastrointestinal symptoms (acid complaints, upper abdominal/stomach complaints, lower abdominal/digestive complaints, and nausea) and ReQuest-WSO which analyses the three other dimensions (general well-being, sleep disturbances, and other complaints). This self-reported questionnaire, which is completed daily, is available in two forms: a short version quantifying the intensity (10-cm VAS) and frequency (7-point Likert scale) of each of the six main dimensions of the scale and the intensity only of the general well-being dimension, and a longer version which includes, in addition to a global evaluation, a detailed analysis of all the symptoms contributing to each dimension. ReQuest is a tool with proven metrological strengths, enabling the investigators to follow--on a daily, multidimensional and reliable basis--the evolution of GERD in the course of clinical trials. Both versions, the long and the short, have identical metrological qualities.
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PMID:ReQuest: a new questionnaire for the simultaneous evaluation of symptoms and well-being in patients with gastro-oesophageal reflux. 1748 36

We sought to determine the cause of gastrointestinal (GI) intolerance of a ketogenic diet (KD) using an endoscopic investigation, and to examine the relationship between endoscopic lesions and dietary tolerance. Thirty-five patients were enrolled in this study and underwent gastrofiberscopy prior to initiation of the KD. We observed the relationship between abnormal endoscopic findings and prior use of antiepileptic drugs (AEDs) and symptoms of GI disturbance. We treated patients with GI symptoms, and observed whether the KD was subsequently better tolerated. Of the 35 patients enrolled, 20 patients (57%) had abnormal endoscopic findings: ten cases of erosive gastritis, four of duodenitis, three of hemorrhagic gastritis, two of esophagitis, and one case of duodenal ulcer. The incidence of abnormal endoscopic lesions was 78% in the polypharmacy group (14/35) and 81% in steroid consumers (16/35). Symptoms of GI disturbance, such as nausea, vomiting, unusual irritability, cramping abdominal pain, and diet refusal for over a day, were observed in 17 (85%) of those patients with abnormal endoscopic lesions and in five (33%) patients without such lesions. Steroids and polypharmacy with more than three AEDs were factors associated with abnormal endoscopic lesions (p < 0.05). After active management with GI medications, GI symptoms subsided, and in all cases except one, patients were able to continue the KD treatment. In conclusion, symptoms of GI disturbance were frequently associated with abnormal endoscopic findings prior to initiation of the KD. Active management with GI medications increased the tolerability of the KD in patients treated with multiple AEDs and steroids.
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PMID:Improving tolerability of the ketogenic diet in patients with abnormal endoscopic findings. 1822 66

Eosinophilic esophagitis is a growing problem in adults in Western countries. It is characterized by nausea, vomiting, dysphagia, food impaction, epigastralgia, heart burn and chest pain. Histologic survey is the most potent diagnostic tool. The diagnostic hallmark is the presence of more than 20 eosinophils per high-powered field on esophageal specimen and the absence of mucosal eosinophilia in the stomach. We herein report an asymptomatic Chinese male with eosinophilic esophagitis, which to the best of our knowledge is the first reported case in Asia. The unusual feature of the current case was the lack of symptoms. This case confirms that a dense infiltration of esophageal eosinophils can occur asymptomatically.
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PMID:Eosinophilic esophagitis in an asymptomatic Chinese. 1929 28

The herbicide, pendimethalin, is used worldwide, but its acute toxicity is not yet widely known. There have been some reported acute pendimethalin poisoning cases in humans and most of them intentionally ingested the concentrated formulation. We describe a 73-year-old man who developed corrosive gastroduodenal injury after accidental ingestion of the diluted (300 times with water) pendimethalin formulation. He had a history of reflux oesophagitis and had been taking omeprazol (10 mg/day) for a year. He consumed alcohol two hours after the accidental ingestion and then had nausea and epigastric pain. Endoscopy performed three days post-exposure revealed gastroduodenal injury. As he had consumed alcohol every day for years and had no history of gastroduodenal ulcer, the accidental ingestion may be associated with this injury. He was successfully treated by increasing his dosage of omeprazol (20 mg/day) for two weeks. This case indicates that ingestion of a small quantity of pendimethalin can provoke gastroduodenal injury.
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PMID:Acute gastroduodenal injury after ingestion of diluted herbicide pendimethalin. 1935 52


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