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)

Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).
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PMID:Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study. 196 Oct 42

Tick-borne rickettsiae of the genus Ehrlichia have recently been recognized as a cause of human illness in the United States. In the years 1986-1988, 10 cases of ehrlichiosis were diagnosed in children in Oklahoma. Fever and headache were universal: myalgias, nausea, vomiting, and anorexia were also common. Rash was observed in six patients but was a prominent finding in only one. Leukopenia, lymphopenia, and thrombocytopenia were common laboratory abnormalities. Six patients were treated with tetracycline, three with chloramphenicol, and one was not treated with antibiotics: all recovered. The onset of illness in spring and early summer for most cases paralleled the time when Amblyomma americanum and Dermacentor variabilis are most active, suggesting that one or both ticks may be vectors of human ehrlichiosis in Oklahoma.
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PMID:Ehrlichiosis in children. 198 31

We describe the clinical features, liver histology, and ultrastructure in reversible diclofenac-induced hepatitis and review previous reports of this entity. Although rarely reported, diclofenac hepatitis may be severe, and even fatal. Symptoms, which develop from 1 week to 11 months after starting the drug, include jaundice, pruritus, fever, abdominal pain, nausea, vomiting, and rash. Bilirubin and alkaline phosphatase are mildly elevated, transaminases often markedly so. The nature of the idiosyncratic injury appears variable, some cases having features of a hypersensitivity reaction, most being more suggestive of a toxic metabolic effect. Light microscopy shows a nonspecific hepatitis with portal and lobular activity, and focal hepatocellular injury that may progress to zonal or massive necrosis. The ultrastructural features in our case are typical of drug or toxin injury. This may be of value in distinguishing this entity from other forms of hepatitis, which is important in view of the frequent reversibility of this potentially lethal form of injury.
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PMID:Reversible hepatitis associated with diclofenac. 203 30

Autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies is associated with high relapse rates. Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal. However, high-dose chemoradiotherapy and ABMT might increase patients' susceptibility to IL-2 toxicity, and might interfere with immunologic responses to IL-2 in vivo. Therefore, to determine safety, tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT, IL-2 was administered by continuous intravenous infusion to 16 patients 14 to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or multiple myeloma. Patients were sequentially assigned to escalating IL-2 "induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6) U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever, nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose-limiting toxicities were hypotension and thrombocytopenia. All toxicities reversed on stopping the IL-2 infusions, and all patients completed "maintenance." Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose levels. With the higher IL-2 doses, increased percentages of patients' PBMC expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting the induction of natural killer and circulating LAK effector activities. Increased LAK precursor activity was exhibited by patients at all IL-2 dose levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and pronounced immunomodulatory effects were observed with the higher IL-2 doses. These studies support the planned use of IL-2 and LAK cells after ABMT in an attempt to reduce relapses of advanced hematologic malignancies.
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PMID:Toxicity and immunomodulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologic malignancies. 204 62

Precise knowledge of the undesirable effects of chloroquine and hydroxychloroquine allows better exploitation of their therapeutic effects. Retinopathy can be avoided by observing a maximum daily dosage of 3.5-4 mg/kg ideal body weight for chloroquine and 6-6.5 mg/kg for hydroxychloroquine. In this way, both can be used for long-term therapy. The pharmacokinetics of chloroquine (storage in deep compartments with long plasma half-life) means that it can cumulate, especially with higher dosages and in the presence of renal or hepatic insufficiency. A high plasma concentration reinforces the side-effects without reinforcing the therapeutic effects. Besides subjective symptoms (e.g. anorexia, diarrhoea, nausea), the following undesirable reactions are significant. On the skin exanthema, hyperpigmentation and photodynamic reactions can develop. The hair can become white in blonde and red-haired men. In the eye, chloroquine deposits in the cornea and disturbances of accommodation can occur, besides retinopathy. Neuromyopathy and central nervous system disturbances (e.g. psychosis) are rare, as is impairment of auditory function or blood cells. During pregnancy there is a risk of potential fetal damage (hearing loss, abortion). An acute overdose is extremely dangerous: the lethal dose is 1 g for children and 4 g for adults. As death occurs rapidly, chloroquine has to be stored where it is absolutely inaccessible to children.
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PMID:[Chloroquine and hydroxychloroquine: side effect profile of important therapeutic drugs]. 205 62

Through the European Network in the Treatment of AIDS, a multicenter trial is being conducted to compare the efficacy and safety of pyrimethamine (50 mg/day) plus clindamycin (2.4 g/day) with the regimen of pyrimethamine (50 mg/day) and sulfadiazine (4.0 g/day) for induction and maintenance treatment of toxoplasmic encephalitis. By 1 September 1990, 281 patients had been randomized to enter the study. Preliminary data show that 77% of the 148 patients evaluated showed a complete response or improvement with minor sequelae during therapy. Twenty percent of the patients deteriorated. This was due to toxoplasmosis in only 10% of the patients. Side-effects were common in all patients regardless of treatment regimen and consisted mainly of rash (52 cases), fever (31 cases), diarrhea (17 cases) and nausea (12 cases). The final analysis should be available by the middle of 1991.
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PMID:Evaluation of the efficacy and safety of clindamycin plus pyrimethamine for induction and maintenance therapy of toxoplasmic encephalitis in AIDS. 206 May 27

A retrospective review of methotrexate (MTX) treatment assessed the clinical course in 124 rheumatoid arthritis (RA) patients. After 5 years, 39 (31%) patients continued MTX with clinical benefit. Although patients continuing MTX after 5 years were younger (45 +/- 13 v 54 +/- 12 yrs, P less than .001) and had a shorter disease duration of RA (9.3 +/- 8.1 v 14 +/- 11 yrs, P less than .05) than patients who discontinue the drug, these differences were not considered clinically significant. MTX was discontinued in 20 patients for a lack of clinical benefit, in 21 patients for non-drug-related reasons, and in 44 patients for suspected adverse drug reactions. The adverse drug reactions requiring permanent discontinuation of MTX were nausea, stomatitis, hair loss, rash, pulmonary reactions, elevated liver enzymes, hematologic abnormalities, and hepatic fibrosis. At least one adverse drug reaction was reported by 115 (93%) patients receiving MTX, but the majority did not require permanent drug discontinuation. Although the prevalence of adverse reactions increased with longer duration of therapy, no differences existed in the type of reactions reported over 5 years of treatment. There were no risk factors identified that were clearly associated with the development of toxicity. Long-term therapy was primarily limited by adverse reactions rather than loss of efficacy.
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PMID:Long-term methotrexate therapy for rheumatoid arthritis. 206 77

Thirty-one postmenopausal women with advanced breast cancer have been treated with the nonsteroidal competitive aromatase inhibitor CGS 16949A at p.o. doses of 0.3, 1, and 2 mg twice a day. All patients were assessed for response. Five patients, all treated with 1 mg twice daily, had objective evidence of response (two complete responses and three partial responses); disease stabilized in 17 patients. Minor side effects were reported by ten patients. Two further patients treated with 2 mg twice a day experienced persistent nausea which improved after dose reduction, and one patient, treated with 0.3 mg twice daily, developed a vasculitic rash requiring discontinuation of CGS 16949A. Estradiol levels measured in 24 patients were significantly suppressed 2 wk after starting CGS 16949A treatment at all doses used. Treatment with 2 mg twice a day lowered estradiol levels to a mean of 29% of pretreatment values which was significantly lower than the corresponding figure of 57% for patients treated with 0.3 mg twice daily. Aldosterone levels were significantly lowered below pretreatment values by the 1- and 2-mg twice daily doses. No clinically apparent cases of adrenocortical insufficiency occurred, although small changes in serum electrolyte levels were noted. The results indicate that CGS 16949A is an effective aromatase inhibitor, requiring further evaluation in the treatment of advanced breast cancer. The optimal dose is likely to be 1 mg twice a day.
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PMID:Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A. 213 67

Within one year three of 25 patients with rheumatoid arthritis treated with azathioprine 100 mg daily developed the following adverse reactions less than two weeks after starting treatment: patient one showed fever with chills, rash, and severe liver function abnormalities suggestive of cholestasis; the second patient had fever, nausea, diarrhoea, and moderately raised liver enzymes; the third patient showed very high fever and severe chills. In two patients the drug was rechallenged, with more rapidly arising and more severe symptoms. In one case raised liver enzymes persisted until seven months after discontinuation of azathioprine. Hypersensitivity reactions and hepatotoxicity of azathioprine are discussed.
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PMID:Azathioprine induced fever, chills, rash, and hepatotoxicity in rheumatoid arthritis. 213 7

Doxifluridine (5'-dFUR) is a prodrug of 5 fluorouracil (5-FU) synthesized in an attempt to improve the therapeutic index compared with 5-FU. In this phase I study, cohorts of three patients were treated by a 5-day continuous infusion with the dose increased daily, total doses ranging from 3.75 g/m2 to 20 g/m2/120 h. Twenty-nine patients received 54 courses (median 2, range 1-4). The dose-limiting toxicities were mucositis (Miller grade 3 in three patients and grade 4 in another) and grade 4 neutropenia and thrombocytopenia in two patients. Other toxicities included nausea, vomiting, and diarrhea, rash, and fever. Neurological toxicity was mild and no cardiovascular toxicity was recorded. Plasma and urine levels of 5'-dFUR and 5-FU were quantitated by high-performance liquid chromatography. Steady-state plasma levels between 167 ng/ml and 6,519 ng/ml were recorded and at these levels there was no evidence of saturation of doxifluridine metabolism. One patient at the maximum tolerated dose of 20 g/m2/120 h had a complete response in a nasopharyngeal carcinoma.
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PMID:A phase I study of doxifluridine as a five-day stepped-dose continuous infusion. 214 51


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