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 combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.
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PMID:Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects. 749 66

The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I dose escalation trial in patients with refractory Hodgkin's lymphoma. The IT was constructed by linking the monoclonal antibody RFT5 via a sterically hindered disulfide linker to deglycosylated ricin-A. All patients in this trial were heavily pretreated with a mean of 5 (range, 2 to 8) different prior therapies, including autologous bone marrow transplantation in 8 of 15. The mean age was 29 years (range, 19 to 34 years). Thirteen of 15 patients had advanced disease (stage IV) with massive tumor burdens and 6 of 15 had B symptoms. The IT was administered intravenously over 4 hours on days 1, 3, 5, and 7 for total doses per cycle of 5, 10, 15, or 20 mg/m2. Patients received one to four cycles of treatment. The peak serum concentration of intact IT varied from 0.2 to 9.7 micrograms/mL. The serum half life (T1/2) of the IT ranged from 4.0 to 10.5 hours (mean, 6.1 hours). Side effects were related to vascular leak syndrome (VLS), ie, decreases in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. Two patients had a National Cancer Institute (NCI) grade 2 allergic reaction with generalized urticaria and mild bronchospasm. At 15 mg/m2, 1 patient experienced a grade 3 myalgia. All 3 patients receiving 20 mg/m2 experienced NCI grade 3 toxicities (edema, nausea, dyspnea or tachycardia) and 1 patient had NCI grade 4 myalgia. Thus, the maximal tolerated dose was 15 mg/m2. Seven of 15 patients made human antiricin antibodies (> or = 1.0 microgram/mL) and 6 of 15 developed human antimouse antibodies (> or = 1.0 microgram/mL). Clinical response included 2 partial remissions, 1 minor response, 3 stable diseases, and 9 progressive diseases. As has been predicted from the preclinical tests, these data seem to indicate clinical efficacy of this new IT in heavily pretreated Hodgkin's patients, thus warranting further clinical investigation.
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PMID:A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. 900 41

Basiliximab is a chimeric anti-intcrleukin-2 receptor monoclonal antibody. Basiliximab is a glycoprotein produced by recombinant technology. It is used to prevent white blood cells from acute renal transplantation rejection. It specifically binds to and blocks the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T-lymphocytes. Due to its monoclonal nature it provides safer and more predictable therapeutic, that is, immunosuppressive response of the polyclonal antibodies. The most common adverse effects in adult patients are constipation, infections, pain, nausea, peripheral oedema, hypertension, anaemia, headache, hyperkalacmia, hypercholesterolemia, increase in serum creatinine, and hypophosphataemia.
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PMID:Basiliximab, mechanism of action and pharmacological properties. 1564 37

Counting mast cells in gastrointestinal (GI) mucosal biopsies is becoming an increasingly common practice. The primary reason for this exercise is to evaluate for possible involvement by systemic mastocytosis (SM). However, the features of mastocytosis in GI biopsies are not well described. In addition, recent studies have suggested that increased mast cells may be involved in the pathogenesis of some cases of diarrhea-predominant irritable bowel syndrome (IBS); the term "mastocytic enterocolitis" has been proposed for such cases. As the baseline mast cell density in colonic biopsies from normal patients has not been established in large cohorts, there is no widely accepted threshold for what constitutes increased mucosal mast cells. The aims of this study were (1) to determine the utility of GI biopsies for the diagnosis of SM, (2) to characterize the clinical, histologic, and immunohistochemical features of mastocytosis in the GI tract, (3) to determine mast cell density in normal colonic mucosa from a large cohort of asymptomatic patients, and (4) to compare these findings with those from patients with diarrhea-predominant IBS. Twenty-four patients with SM involving the GI tract, 100 asymptomatic patients, and 100 patients with IBS (the latter 2 groups with histologically normal colonic biopsies) were included. For the mastocytosis group, 107 biopsies (70 involved by mastocytosis; 67 mucosal, 3 liver) from 20 women and 4 men were evaluated (median age 59 y). The most commonly involved site was the colon (19 patients, 95%), followed by ileum (86%), duodenum (80%), and stomach (54%). In 16 cases (67%), the first diagnosis of SM was made on the basis of GI biopsies. Seventeen patients had documented cutaneous mastocytosis. Fifteen of 17 patients who underwent bone marrow biopsy had marrow involvement by SM. Eighteen patients had indolent disease, and 6 had aggressive disease (including all 3 with liver involvement). The most common GI symptom was diarrhea, followed by abdominal pain, nausea, weight loss, bloating, vomiting, or reflux. Liver disease presented with hepatomegaly and ascites. Endoscopic abnormalities (observed in 62%) included erythema, granularity, and nodules. Histologically, involved biopsies were characterized by infiltrates of ovoid to spindle-shaped mast cells in aggregates or sheets in the lamina propria, sometimes forming a confluent band underneath the surface epithelium; 25% of biopsies had only focal involvement (single aggregate). Prominent eosinophils were seen in 44% of involved colonic/ileal biopsies and 16% of duodenal biopsies. Mast cells were highlighted by diffuse membranous staining for KIT and CD25. In the nonmastocytosis groups, all biopsies contained singly dispersed mast cells with no aggregates. The mean highest mast cell counts (in a single high-power field) for asymptomatic patients and IBS patients were 26 (range, 11 to 55) and 30 (range, 13 to 59), respectively. In summary, GI (especially colonic) biopsies can establish a diagnosis of SM in patients with GI symptoms. GI involvement is usually subtle and is often associated with prominent eosinophils, which may obscure the mast cell infiltrate. KIT and CD25 are invaluable markers for the diagnosis. Mast cell density in colonic mucosa from asymptomatic patients is highly variable. Although patients with diarrhea-predominant IBS on average have mildly increased mast cells, the overlap in range with that of control patients is too great for this difference to be clinically useful. These findings argue against the utility of counting GI mucosal mast cell in patients with chronic diarrhea.
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PMID:A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. 2461 5