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)

Elsamitrucin (BMY-28090) is an antitumor antibiotic first described in 1985 that has significant oncolytic activity against a number of murine tumors including P388, L1210, B16 and M5076, as well as against MX1 and HCT116 xenografts. Preclinical toxicology studies of elsamitrucin revealed edema of multiple organs associated with hypoproteinemia and, at lethal doses, severe multiorgan toxicity. We conducted a phase I clinical trial (31 patients) of elsamitrucin administered as a 10-min i.v. infusion every 3 weeks. The starting dose (0.6 mg/m2) was 1/3 of the dog low toxic dose. The maximum tolerated dose was 30 mg/m2. Dose-limiting toxicity was reversible hepatic dysfunction manifested by elevated transaminase levels not associated with bilirubin, alkaline phosphatase, or lactate dehydrogenase elevations. Other toxicities included nausea, vomiting, malaise, and phlebitis. Because the hepatic toxicity was brief and reversible, a subsequent study (18 patients) was conducted with elsamitrucin administered every 2 weeks. Reversible grade 3 hepatotoxicity was again observed at 30 mg/m2. Plasma and urine samples from patients receiving doses of 0.6-36 mg/m2 were analyzed for drug content. The maximum plasma concentration and area under the plasma concentration versus time curve values increased linearly with doses up to 25 mg/m2 but not at higher doses. The terminal half-lives, total body clearances, and volume of distribution were 36-60 h, 10-19 liters/h/m2, and 400-1100 liters/m2, respectively. Less than 5% was excreted in the urine in 24 h as parent compound. Bile was collected from one patient with an indwelling biliary catheter. Approximately 22% of the dose was excreted in 48 h, suggesting that biliary excretion of elsamitrucin may be an important route of drug elimination. Based on reversible hepatic toxicity, the phase II recommended dose of elsamitrucin is 25 mg/m2 every 2 weeks.
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PMID:Phase I trial and clinical pharmacology of elsamitrucin. 154 Sep 49

In this study, local and systemic tolerance and pharmacokinetics of trospectomycin sulfate in human beings were evaluated for the first time. Trospectomycin sulfate (U-63,366F; trospectomycin) or sterile saline was administered to 96 healthy male volunteers in doses ranging from 0.25 ml (75 mg) to 3.3 ml (1,000 mg) in a single intramuscular injection in a double-blind, randomized design. Volunteers were screened to establish baseline vital signs and laboratory test values. Pain and tenderness at the injection site, which occurred at doses of 450 mg and above, were the most common side effects; they were mild in severity and transient. Adverse drug experiences reported by subjects included nausea, dizziness, light-headedness, diaphoresis, costal pain, and perioral numbness. The perioral numbness (paresthesia) experienced at doses of 750, 900, and 1,000 mg was probably drug related. No Clostridium difficile toxin was detected in fecal samples. Pharmacokinetic calculations based on data obtained by high-performance liquid chromatography showed that after a 1,000-mg intramuscular dose of trospectomycin (3.3 ml), the serum mean half-life was 1.85 h (1.70 to 2.02 h), mean area under the serum concentration-time curve was 140.2 micrograms.h/ml and was linear with dose, mean peak concentration was 28.3 micrograms/ml (20.4 to 34.7 micrograms/ml), mean time to maximum concentration was 71 min (30 to 120 min), and the elimination rate constant was 0.307 h-1. The elimination rate constant and half-life did not vary with dose. Little trospectomycin was detected in 2-day fecal collections. A few randomly occurring abnormal clinical laboratory test values and vital signs were observed. For the trospectomycin-treated group, creatinine phosphokinase increased substantially for 24 h after injection and then decrease through day 5, while serum glutamic oxalacetic transaminase and lactate dehydrogenase increased slightly.
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PMID:Human safety and pharmacokinetics of a single intramuscular dose of a novel spectinomycin analog, trospectomycin (U-63,366F). 215 Sep 7

Confirmation of a causal relationship between hemolytic-uremic syndrome (HUS) and verotoxin-producing Escherichia coli (VTEC) infection is provided by the case of a 22-year-old West German woman. The patient presented with fatigue, nausea, and headache. Ultrasonography revealed enlarged kidneys, and laboratory investigations showed uremia, hemolytic anemia, lactate dehydrogenase, haptoglobin below the detection limit, and thrombocytopenia. She received hemodialysis and drug treatment (heparin, dopamine, and furosemide). To investigate the kinetics of the humoral response to verotoxin, the patient was followed for 3 months. Fecal specimens on day 23 yielded E coli serotype 0111:NM, and stool filtrates on days 16 and 23 showed highly cytotoxic activity for HeLa cells. While the patient's initial serum showed a high IgM immune response against purified Shiga toxin, there was a steady decline in IgM and steady increase in IgG antibodies over the ensuing 3 months. These findings are suggestive of a recent infection by a verotoxin-producing organism. This is the 1st reported case of VTEC-associated HUS with e coli 0111 infection in an adult, and the patient's 4-year history of oral contraceptives (OCs)--ethinyl estradiol and chlormadinoneacetate--is considered to be of etiologic significance. The diminished antibody coating of bacteria in the urinary tract of OC users may have facilitated invasion of verotoxin across the mucosal barrier in this patient. Severe hypertension has been reported previously in OC users with HUS. It is speculated that verotoxin may trigger HUS in longterm OC users, initiating vasoconstriction and microangiopathic hemolysis.
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PMID:Hemolytic-uremic syndrome associated with an infection by verotoxin producing Escherichia coli 0111 in a woman on oral contraceptives. 328 32

After therapy with adriamycin-containing regimens, relapsed or refractory non-Hodgkin's lymphomas (NHL) have a very poor prognosis. Although high dose chemotherapies are widely employed, their related costs and the controversial results achieved justify the development of new second-line conventional therapies. Forty-three patients with relapsed or refractory NHL were consequently treated with an outpatient polychemotherapy schedule including ifosfamide, mitoxantrone and etoposide on day 1, and vindesine, cisplatinum and cytosine arabinoside on day 15. The courses were repeated on day 29. All of the patients were pretreated with at least one chemotherapy regimen. Twenty-two patients had diffuse large cell lymphoma, 8 had bone marrow involvement, and 17 altered baseline lactate dehydrogenase (LDH) values. After a median number of 4 cycles (range 2-8), we registered 20 complete (46%) and 4 partial remissions, for an overall remission rate of 56% (95% confidence interval: 40-71%). All of the responses occurred in patients who had achieved at least partial remission during first-line therapy. Four patients are long term responders after 31, 39, 49 and 52 months, and are possibly cured. Univariate analysis of prognostic factors showed that baseline LDH values and response to front-line therapy significantly affected both time to disease progression and survival, whereas the number of previous treatments given, significantly affected only the time to progression. Therapy was administered in an out-patient setting and no life-threatening toxicity was observed. Side effects consisted of nausea/vomiting, alopecia and reversible myelosuppression. The results suggest that different treatment strategies for relapsed and refractory patients should be considered on the basis of prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Results of a salvage regimen in refractory or relapsed non-Hodgkin's lymphoma. 792 Feb 18

A retrospective study was undertaken of 14 patients (eleven men, three women; mean age 52 [33-68] years in whom haemolysis had occurred during chronic haemodialysis (n = 12) or haemofiltration (n = 2). The haemolysis was of mechanical cause in eight patients, by an osmotic mechanism in one, and of unknown cause in five. Cardinal symptoms were nausea in 14 patients, abdominal pain in nine, vomiting in eight and raised blood pressure in ten. The plasma was discoloured in all patients and there was also an increase in free haemoglobin (110-2400 mg/dl) and (or) lactate dehydrogenase (311-7403 U/l). In all of eleven patients in whom it was measured the activity of serum amylase and (or) lipase was more than doubled (to 73-2400 U/l and 473-16,740 U/l, respectively). All patients were treated symptomatically, three had a blood exchange, two others plasma separation. Eight patients recovered within a few days, but necrotizing pancreatitis developed in six, three of whom died while two had permanent sequelae. This series shows that dialysis-induced acute haemolysis can cause life-threatening pancreatitis. Narrowings within the extracorporeal circuit, not always recognized in current dialysis equipment, are the most frequent cause of the mechanical haemolysis.
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PMID:[Acute hemolysis with subsequent life-threatening pancreatitis in hemodialysis. A complication which is not preventable with current dialysis equipment]. 792 17

A 22-year-old man developed transient unconsciousness during running. He developed fever, nausea, vomiting, diarrhea and general fatigue. Next day, he was admitted to National Hospital Nayoro because of high serum CK level of 13,610U/l. Biochemical analyses revealed elevated serum myoglobin, increased CK-MM isozyme, aldolase and lactate dehydrogenase, increased serum osmolality, increased uric acid, and decreased serum potassium levels. Therefore, he was diagnosed as having rhabdomyolysis. In addition, serum CK-MB isozyme, cardiac myosin light chain I and troponin T were increased, suggesting the damage of cardiac muscle. Electrocardiogram showed elevated ST segment and inverted T on V2-4, which were not observed previously. He had no preceding infectious disease, drug ingestion or an underlying metabolic disorder. The rhabdomyolysis may be precipitated by the superimposition of dehydration and loss of potassium due to diarrhea and vomiting. The myocardial injury, probably produced by transient myocardial ischemia, should be paid attention in case of rhabdomyolysis.
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PMID:[A case of rhabdomyolysis complicated with myocardial injury]. 856 47

The current study was designed to investigate direct inhibitory effects of N-acetyl-glucosaminyl-muramyldipeptide (GMDP) over the cytotoxic nature of TNF-alpha. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-alpha cytotoxicity was done in vitro on the following cell lines: A549 (human lung carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer cells). In a double-blind placebo-controlled trial, cancer patients with an elevated activity of all five LDH isoensymes were randomized to receive either a GMDP solution or a placebo; 63 patients were evaluated every third day for the mean daily number of episodes of nausea or vomiting, changes in clinical status, cell blood count and blood chemistry. A 95% inhibition of LDH release was noticed on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72% dose-dependent reduction in LDH activity. In vivo, LDH activity was decreased by 41% (+/-4%) (mean+/-SD) in all 21 subjects who were given 0.5-1.0 mg of GMDP daily. A lowering of LDH activity by 73.4% (+/-4%) was observed in 23 patients who received GMDP at a dosage of 1.5mg/kg daily. Correspondingly, a 10% (+/-2%) increase in LDH activity was noticed in 19 patients who were given a placebo (P < 0.01). During the follow-up period, the overall clinical condition of all patients treated with GMDP was improved. No side effects were observed. In nine patients who experienced nausea from tumor toxicity before treatment, the symptom subsided. In parallel, an extremely beneficial effect on lipids metabolism was noticed in all patients with elevated cholesterol and trigliceride levels. A dietary supplementation of GMDP has been shown to reduce systemic TNF-alpha cytotoxicity during tumor shock.
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PMID:Inhibition of systemic TNF-alpha cytotoxicity in cancer patients by D-peptidoglycan. 964 29

A 34-year-old obese woman with human immunodeficiency virus (HIV) infection diagnosed a year earlier was seen because of nausea, vomiting, and intermittent diarrhea for 3 weeks. Her current medications included zidovudine. Physical examination revealed tachypnea and tender hepatomegaly. Computed tomography of the abdomen showed hepatomegaly with fatty infiltration. Liver enzymes were within normal range except for elevated lactate dehydrogenase (LDH). The serum bicarbonate value was low, with a lactate level three times normal. The tachypnea and dyspnea worsened as lactate concentrations rapidly increased to 15 times normal. Although her Po2 and cardiac index were initially adequate, the patient had acute respiratory failure. She died with multiorgan dysfunction, including hepatic failure, severe lactic acidemia, disseminated intravascular coagulation, and renal failure. Autopsy revealed hepatomegaly and massive steatosis. Physicians should consider lactic acidosis in patients taking zidovudine and having unexplained tachypnea, dyspnea, and low serum bicarbonate concentrations.
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PMID:Zidovudine-associated type B lactic acidosis and hepatic steatosis in an HIV-infected patient. 1021 65

Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin's lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 x 10(9)/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 x 10(9)/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 x 10(9)/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 x 10(9)/L peripheral tumor cells (P = .0017). Due to massive side effects in the first patient treated with 375 mg/m(2) in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m(2) dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 x 375 mg/m(2) rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.
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PMID:Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). 1049 91

There is no report in which three episodes of delayed hemolytic transfusion reaction (DHTR) occurred from multiple antibodies to red cells (RBCs) in the course of treatment of a patient. This paper describes episodes of anemia and hyperbilirubinemia in concert with the development of three alloantibodies in a multiple transfused patient. The patient was a 71-year-old male suffering from valvular heart disease and hemophilia B with a history of transfusions. Although he received compatible RBCs from 14 donors as judged by a crossmatch test using the albumin-antiglobulin method, three episodes of DHTR occurred after surgery. The first hemolytic episode on day 7 after surgery was due to anti-Di(a) because of clinical and laboratory evidence which included jaundice, sudden increases in total bilirubin (T-Bil) and lactate dehydrogenase (LD) levels, and a decrease (2.2 g/dl) in hemoglobin (Hb) level. The second hemolytic episode on day 16 resulted from newly producted anti-Jk(b). The patient experienced fever, fatigue, nausea and anorexia, and laboratory data showed a second increase in T-Bil, a second decrease (3 g/dl) in Hb, and moderate elevations of blood urea nitrogen (BUN) and creatinine (CRE) levels. The third hemolytic episode on day 39 was due to anti-E. The patient complained of fever and fatigue and had a third unexplained drop (1.5 g/dl) in Hb despite no bleeding. This is the first reported case in which three episodes of DHTR occurred from different red cell antibodies.
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PMID:Three episodes of delayed hemolytic transfusion reactions due to multiple red cell antibodies, anti-Di, anti-Jk and anti-E. 1103 71


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