Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors reviewed the liver histopathology and the clinical features of eight patients with liver metastases from colorectal cancer who were treated by hepatic arterial infusion chemotherapy (HAIC) via an implantable pump (Infusaid). Before HAIC, these patients had no evidence of hepatitis, and results of liver biopsies performed on three patients showed only minor morphologic alterations. All the liver tumors responded to HAIC, but all patients developed hepatitis. Clinical findings included nausea, vomiting, abdominal pain and jaundice. Serum transaminases, alkaline phosphatase and bilirubin levels were increased. Clinical observations suggested that 5-fluoro-2'-deoxyuridine (FUDR), the predominant drug given, was the hepatotoxic agent. Toxic effects were hepatocyte necrosis, steatosis, cholestasis, central vein sclerosis, and alterations in the portal triad. In addition, central vein lesions like those in veno-occlusive disease, and micronodular cirrhosis resembling that induced by alcohol, were encountered. Although individual susceptibility to FUDR appeared to vary, portal triad fibrosis was present in all eight cases and, together with central vein sclerosis and cirrhosis, appeared to be related to the dose and duration of HAIC.
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PMID:Liver pathology following hepatic arterial infusion chemotherapy. Hepatic toxicity with FUDR. 294 Nov 40

The seeds and roots of Heliotropium lasocarpium, contain a pyrrolizidine alkaloid which causes toxic liver injury and veno-occlusive disease (VOD), characterised by an occlusive lesion of the centrolobular veins of the liver, when consumed by humans. The Farkhar region of Southern Tadjikistan, was blockaded from May to November 1992. This led to a famine and a delay of two months in the wheat harvest. Heliotropium lasocarpium had time to grow in the fields and their seeds were therefore collected with the wheat. The contaminated wheat was distributed to the population, who milled it and made bread. The first case of liver toxicity was six weeks after the first consumption of the contaminated bread. By March 1993, 3,906 cases had been recorded (attack rate = 4%). The attack rate were 0.4%, 5.4%, 4.0%, 2.8% and 1.5% for the less than 1 year, 1-14 years, 15-30 years, 31-50 years and over 50 years age groups respectively. The overall case fatality ratio (CFR) was 1.3% and increased with age from 0 to 5.9% in the same age groups. Two of the ten collective farms represented 83.3% of the cases attack rate of 16.9% and 23.6%. Four stages of illness were defined. Stage I corresponds to abdominal pain, nausea or vomiting, and asthenia. All stage I patients (55.5%) recovered rapidly. Stage II is an association of Stage I and hepatomegalia (29.9%). Stage III includes ascites in addition to these symptoms (13.7%) and stage IV alteration of consciousness (0.9%). The last case was reported on March 4th 1993.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An outbreak of Heliotrope food poisoning, Tadjikistan, November 1992-March 1993]. 792 99

Pretransplant conditioning therapy with i.v. BuCy followed by allogeneic hematopoietic stem cell transplantation (BMT) was investigated in a phase II trial in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We gave i.v. Bu at a dose of 0.8 mg/kg every 6h x 16 doses, followed by Cy 60 mg/kg daily for 2 days. Twenty-six AML patients (18 males/eight females) were treated, only eight of whom were in CR1. The rest were either refractory to induction chemotherapy (four patients) or in a more advanced stage of their disease (14 patients). In addition, nine patients with MDS (1M/8F) were treated. Their median age was 41 years (range 21-64). Engraftment to > or =500 neutrophils/microl was reached at 14 days (range 10-29 days) post BMT, and the median time of neutropenia was only 11 days (range 4-28 days). The most common regimen-related toxicity was grade 2-3 nausea. In the post-BMT period (including BMT day +30), two patients died, one each from pulmonary hemorrhage secondary to CMV pneumonia and hepatic veno-occlusive disease (VOD), for an early treatment-related mortality (TRM) of 5.7%. Three patients developed VOD and two of them died. There was no direct regimen-related pulmonary or neurologic toxicity. Overall, the clinical side-effect spectrum was analogous to what would be expected from a high-dose oral Bu-based regimen; there was no unique toxicity experienced with the used solvent system. The disease-free survival in the high-risk subgroup (all patients not in CR1) at 1 and 2 years post transplant was 44% and 31%, respectively. The 13 patients still alive in CR have been followed for a median of 24 months (range 18-32). Pharmacokinetic analysis showed very good interdose reproducibility, and limited interpatient variability in area under the plasma concentration vs time curve, peak concentration, and clearance of Bu after this i.v. formulation. We conclude, that this new i.v. Bu formulation is well tolerated; it has an impressive safety profile, and we suggest that it should be considered as appropriate replacement for oral busulfan in pretransplant conditioning therapy prior to allogeneic BMT for patients with AML or MDS.
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PMID:Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy). 1093 85

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a relatively recently known and not very often diagnosed form of ischemic bowel disease of low incidence und unknown etiology. We present the case of a patient who after presentation of inconclusive signs of epigastric pain and rectal bleeding suddenly developed right abdominal pain with local peritonism. Suspecting intestinal ischemia or perforated appendicitis we first performed laparoscopy, which showed an inflammable tumor of cecum, ascending colon and appendix with massive adhesions to the abdominal wall. We performed an open right hemicolectomy with primary anastomosis. The patient developed a deep vein thrombosis of the vena tibialis post. and vena saphena parva. After 12 months our patient is free of complaints and recurrence. Investigations carried out showed no evidence of hypercoagulopathy. The presentation of MIVOD can range from chronic inflammatory bowel disease with recurrent abdominal pain in combination with nausea, emesis and bloody diarrhea to acute abdomen. Therefore diagnostic misinterpretation and mistherapy as well as underdiagnosis is common. Histologic investigation shows a variable inflammatory infiltration of multiple veins of the intestinal wall and the mesentery as well as thrombotic vessel occlusion in different stages without involvement of the arteries. All forms of hypercoagulopathy, parasitic disease, sepsis and malignancy have to be excluded. Therapeutic success can only be achieved with surgical resection of the affected bowel, whereon in general no recurrence will occur.
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PMID:[Mesenteric inflammatory veno-occlusive disease (MIVOD)--a rare cause of intestinal ischemia]. 1639 91

Reports of eosinophilic infiltration of the colon causing obstruction are few. It is even less common to find associated extensive intestinal venulitis, which is similar to and lumped together with so called Mesenteric Inflammatory Veno-Occlusive Disease (MIVOD) or Self-Limited Intestinal Venulitis. Eosinophilic necrotizing lymphadenitis, such as what we report here, has never been reported in association with this disease. A 41-year-old female presented with cramping lower abdominal pain, hematochezia, nausea, and vomiting. Computed tomography revealed the presence of the mass and thickening of the illeocecal wall. Endoscopy confirmed a cecal mass with surface ulceration suggestive of cecal adenocarcinoma. Patient underwent right hemicolectomy with the clinical and radiologic diagnosis of adenocarcinoma. Microscopic examination of the resected bowel showed an ulcerated mass in the cecum composed of markedly edematous tissue showing transmural eosinophilic infiltration and extensive eosinophilic and lymphocytic venulitis with and without thrombosis. This was associated with a necrotizing lymphadenitis.
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PMID:Eosinophilic venulitis of colon presenting as ileocecal mass. 2216 8

On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin (GO; Mylotarg; Pfizer, New York City, NY) for treatment of relapsed or refractory (R/R) CD33-positive acute myeloid leukemia (AML) in patients 2 years of age and older. GO is a CD33-directed antibody drug conjugate linked to the cytotoxic antibiotic calicheamicin. It originally received accelerated approval for treatment of older patients with relapsed CD33-positive AML in 2000, but it was withdrawn from the market in 2010 when the confirmatory trial failed to demonstrate clinical benefit among safety concerns, such as a higher rate of induction fatalities on the GO combination arm compared with chemotherapy alone. In addition, GO was associated with hepatic veno-occlusive disease (VOD), which has substantial morbidity and mortality. Pharmacokinetic analyses suggested a lower maximum concentration of GO would result in less VOD without affecting target saturation or efficacy. A meta-analysis across dose schedules of GO in patients with R/R AML showed that a lower-dose "fractionated" schedule of 3 mg/m2 days 1, 4, and 7 was associated with less early mortality, hemorrhage, and VOD, without an apparent decrease in complete remission (CR) rate. MyloFrance 1 was a single-arm study evaluating response rates in patients with relapsed CD33-positive AML treated with the lower-dose fractionated GO regimen. The CR rate was 26% (95% confidence interval 16%-40%). Common adverse reactions were fever, infections, nausea, vomiting, constipation, bleeding, increased liver enzymes, and mucositis. There were no cases of VOD. These results supported the approval of GO as monotherapy for R/R CD33-positive AML using the lower-dose fractionated regimen.
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PMID:FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia. 2965 Jun 83