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)

A 33-year-old man was admitted 8 hours after voluntary ingestion of 1875 mg of chlorophacinone (C'Operat 750 mL). The examination revealed excitation and nausea, with a normal prothrombin index (PI). Comprehensive testing for abused and therapeutic drugs in blood confirmed chlorophacinone (maximum plasma level: 27.6 mg/L), an antivitamin K (AVK) rodenticide. In a search for easy toxicological management of chlorophacinone poisoning treated by phytomenadione and a cytochrome P450 inducer (phenobarbital), PI and chlorophacinone plasma levels were monitored concomitantly during 17 days. A simple HPLC procedure for the determination of chlorophacinone in human plasma is reported for that purpose. Under phenobarbital 200 mg/day, chlorophacinone exhibited an apparent elimination half-life (3.27 days) shorter than in previously reported cases. If PI is useful for planning phytomenadione treatment and used for therapeutic monitoring of AVK, the chlorophacinone concentrations follow-up may provide a better estimation of the duration of hospitalisation. Chlorophacinone accumulation in target cells or existence of an unidentified metabolite may explain persistence of the hypocoagulability syndrome at low plasmatic concentrations of chlorophacinone. This case illustrates how toxicological management may facilitate toxicokinetics and therapeutic data acquisition.
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PMID:Toxicological management of chlorophacinone poisoning. 1021 74

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

Objective: To investigate the early recognition and management of acute fatty liver of pregnancy (AFLP) to improve the maternal and fetal survival.Study Design: Eight cases presenting with AFLP managed in our hospital during the past 212 years were studied retrospectively with emphasis on presenting symptoms, laboratory findings, and the time for liver biopsy. Also, to report the maternal and fetus outcomes in such cases.Result: The mean gestational age at onset was 34 +/- 2 weeks (range 30-37 weeks). All cases were primigravida. In the early stages, all presented with malaise, nausea, vomiting, and epigastric distress followed by jaundice in the third trimester of pregnancy. Three of eight presented with polyuria and polydipsia. Laboratory findings: all had raised transaminases and serum bilirubin (2.9-29.9 mg/dL), hypoalbuminemia (22.4-30 g/L), hypofibriogenemia (< 180 mg/dL), prolonged prothrombin time, and prolonged partial thromboplastin time. Maternal complication was frequent, including hepatic encephalopathy (6), ascites (6), hypoglycemia (5), hematemesis (2), postpartum hemorrhage (5), and preeclampsia (4). Cesarean was performed in 3 cases. One mother died of fulminant hepatic failure, the other cases were survival. There were no fetal deaths. Liver biopsy was done in 8 cases. It is suggested that percutaneous liver biopsy should not be done until the coagulation tests become normal, the amounts of ascites decrease and platelet counts increase after delivery.Conclusion: With increasing awareness, especially in the early recognition of AFLP cases and prompt progressive management, including early termination of pregnancy, and using large-dose infusion of fresh frozen plasma or albumine alternatively, the prognosis of AFLP is obviously improved.
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PMID:Acute fatty liver of pregnancy: an experience in diagnosis and management of eight cases. 1083 62

The present study was designed to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PKs), and antitumor activity of the protein kinase C-alpha antisense oligonucleotide ISIS 3521 (ISIS Pharmaceuticals, Inc., Carlsbad, CA) when administered in combination with 5-fluorouracil (5-FU) and leucovorin (LV). Patients with refractory solid tumors received ISIS 3521 as a 21-day continuous infusion administered simultaneously with 5-FU and LV given daily for 5 days repeated every 4-5 weeks (one cycle). 5-FU and ISIS 3521 PK analysis were performed on samples taken during the first cycle in all patients. Fifteen patients received ISIS 3521 at one of three dose levels: (a) 1.0 (n = 3 patients); (b) 1.5 (n = 3 patients); and (c) 2.0 (n = 9 patients) mg/kg/day. All patients simultaneously received 5-FU (425 mg/m(2)/day) and LV (20 mg/m(2)/day) for 5 consecutive days. Grade 1-2 toxicities included alopecia, fatigue, mucositis, diarrhea, anorexia, nausea/vomiting, and tumor pain. One patient had grade 3 chest pain considered to be related to 5-FU therapy, another patient had dose-limiting grade 3 mucositis resolving in <7 days, and one patient with a history of gastritis had an acute upper gastrointestinal bleed thought to be 5-FU-induced toxicity. Five patients developed cycle 1 grade 4 neutropenia, which resolved without colony-stimulating factors before the next treatment cycle. There were no effects on prothrombin time and activated partial thromboplastin time. A clinically defined MTD was not reached. The character and severity of these toxicities do not seem to be dose related, and, as such, there was no classical dose-limiting toxicity defining the MTD. ISIS 3521 PKs in the presence of 5-FU was consistent with those reported previously. 5-FU PK parameters were also similar in the presence or absence of ISIS 3521. Six of 14 patients ( approximately 43%) across all dose cohorts had an improvement in measurable tumor response ranging from minor reduction in tumor size (4 patients) to objective partial response (>50% reduction in tumor size, 2 patients). ISIS 3521 is tolerable at its recommended single-agent dose when given with 5-FU and LV. There is no apparent PK interaction between ISIS 3521 and 5-FU and LV. Antitumor activity was observed with the combination; however, it is uncertain whether clinical activity is a result of enhanced drug interaction. Our study warrants further exploration of efficacy in a Phase II and/or Phase III clinical trial setting.
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PMID:Phase I clinical and pharmacokinetic study of protein kinase C-alpha antisense oligonucleotide ISIS 3521 administered in combination with 5-fluorouracil and leucovorin in patients with advanced cancer. 1194 11

Acute liver failure and haemolytic syndrome appeared quite suddenly as the first manifestations of Wilson disease (WD) in five of our patients previously regarded as healthy persons (although an interview showed that 2-4 weeks prior to the illness the patients complained of several non-specific symptoms, such as abdominal pain, headaches, fever, weakness or behavioural changes). All the patients were young women (17-23 years), none of them had any history of liver disease. They were admitted with icterus, nausea, vomiting and symptoms of increasing haemolysis. The diagnosis of WD was given as disturbed copper metabolism. After a short period of observation ascites and anasarca occurred, haemorrhagic diathesis and other symptoms of liver failure increased. Levels of clotting factors decreased rapidly. Despite treatment with D-penicillamine, plasmapheresis, and symptomatic drugs, three of the women died in irreversible liver coma, due to the unavailability of liver transplantation. The fourth woman was carried to the Transplantation Centre, due to aggravation of the symptoms of liver failure, where liver transplantation was performed. Histopathologically micronodular cirrhosis was shown in all these cases. The fifth patient survived having undergone the above treatment without liver transplantation. The main differences between the patient who survived and those who died or underwent transplantation were relatively higher activity of alkaline phosphatase (26 U/l vs. 10-20 U/l), slightly higher levels of clotting factors and prothrombin time, which never fall below 68% of the control (versus 14-44% in other patients). Only in the surviving patient was the Kayser-Fleischer ring present. In four of our patients we found family members who were carriers of WD.
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PMID:Acute haemolytic syndrome and liver failure as the first manifestations of Wilson's disease. 1221 29

A 37-year-old woman presented with increasing abdominal pain and jaundice. Six weeks before admission, she developed persistent diarrhea and jaundice of the skin. She also bruised easily, and her gums bled. In the subsequent weeks, her appetite decreased, she was fatigued, and she had nausea, vomiting, and abdominal distension. She had a history of drinking 1 quart of vodka every day for 20 years, with brief periods of abstinence; she stopped consuming alcohol 11 days before admission because it no longer provided symptomatic relief. Her past medical history was also notable for depression, including a suicide attempt 4 years earlier. She did not smoke, use illicit drugs, or have unprotected sexual intercourse. She had received no blood transfusions and had not traveled recently. She took no medications, except for occasional ibuprofen. On physical examination, she was thin and deeply jaundiced, and she trembled and responded slowly to questions. She was afebrile but tachypneic, and she had orthostatic hypotension. Her HEENT examination was notable for scleral and sublingual icterus, as well as crusted blood on her gums and teeth. The jugular veins were flat. The cardiac examination revealed tachycardia (heart rate, 103 beats per minute) without murmurs, rubs, or gallops. The abdomen was nontender and protuberant, with hypoactive bowel sounds; the spleen was not palpable, and there was no fluid wave or caput medusae. The liver percussed to 18 cm, with a smooth edge extending 10 cm below the costal margin. She had cutaneous telangiectases on her chest and bilateral palmar erythema. There was no peripheral edema. The neurologic examination was notable for asterixis. Her stool was guaiac positive. Laboratory studies revealed the following values: hematocrit, 21.2%; white blood cells, 17,310/mm(3); ammonia, 42 micromol/L; serum creatinine, 3.9 mg/dL; serum urea nitrogen, 70 mg/dL; albumin, 2.1 g/dL; total bilirubin, 26.8 mg/dL; alanine aminotransferase, 14 U/L; aspartate aminotransferase, 77 U/L; alkaline phosphatase, 138 U/L; prothrombin time, 103 seconds (international normalized ratio, 10.6); and urinary sodium, <5 mg/dL. Urinalysis revealed an elevated specific gravity and numerous muddy granular casts. Hepatitis A, B, and C serologies were negative. On abdominal ultrasound examination, there was no ascites, and the liver was echogenic. The portal and hepatic veins were patent, and the hepatic arteries were normal. The spleen measured 14 cm. What is the diagnosis?
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PMID:Cases from the Osler Medical Service at Johns Hopkins University. 1258 38

We managed bleeding crisis in 10 consecutive severe haemophilic patients with inhibitors (eight had an inhibitor level of >5 BU mL(-1)) mainly with the antifibrinolytic agent, i.e. epsilon amino caproic acid (EACA). EACA was used by local, oral or intravenous routes either in combination or separately. Five patients developed inhibitors postoperatively and among the remaining five, four had recurrent haemarthrosis or soft tissue bleeds and one patient presented with severe gastrointestinal bleeding without demonstrable lesion. In all the patients, addition of EACA to their management protocol resulted in stoppage and/or reduced frequency of bleeding. In six of 10 patients, the results were excellent; of these six patients, five developed inhibitors postoperatively. Although a reduction in the frequency of bleeding was observed in patients with haemarthrosis and soft tissue bleed, it was not spectacular and the patients required additional therapy. Hence the results could be described as poor. No patient needed to stop the medicine because of the side-effect of EACA. Symptoms like mild nausea and vertigo were seen as the side-effects of this medicine when high intravenous dosage was administered. EACA thus appears to be an excellent adjuvant therapy for haemophilic patients with inhibitors. Besides its well-recognized antifibrinolytic activity, EACA may have additional mechanisms of action in haemophilic patients with inhibitors. More extensive use of this cheap and safe product is warranted in haemophilic patients with inhibitors. If larger studies confirm this observation, then using antifibrinolytics will allow substantial reduction of FEIBA or activated prothrombin complex (APCC) usage in such patients without necessarily increasing the thrombotic complications or reduction of the clinical efficacy, when compared with higher dosage of FEIBA or APCC alone. This will lead to substantial financial savings in countries where up to 35% of severe haemophilia A patients develop inhibitors.
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PMID:Role of epsilon amino caproic acid in the management of haemophilic patients with inhibitors. 1496 21

We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.
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PMID:Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant. 1516 53

We report clinical findings, risk factors and neurological and cognitive long-term outcome in three Italian children aged 7, 8 and 5, respectively, who experienced cerebral venous sinus thrombosis (CVST). All children presented with headache, associated to nausea, vomiting and papilloedema. None suffered from epileptic seizures. In two of them a paresis of the sixth cranial nerve with diplopia was found. Diagnosis was confirmed by magnetic resonance imaging angiography (angio MRI) in all cases. In all patients plasma levels of protein C, protein S, antithrombin III (AT III), antiphospholipid antibodies (ApA) and homocysteine were detected. Furthermore, factor V Leiden mutation, prothrombin mutation G20210A and MTHFR mutation were searched for. A Protein C reduction was detected in all patients at onset; this finding, however, was not confirmed at follow-up in all of them. At one-year follow-up, neurological examination was normal in all children and neuropsychological assessment, aimed at excluding linguistic and non-linguistic cognitive deficits, revealed normal performances in two of them. In the third child, cognitive assessment confirmed a previously diagnosed developmental dyslexia.
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PMID:Cerebral venous sinus thrombosis in childhood: clinical aspects and neurological and cognitive long-term outcome in three cases. 1562 88

The vast majority of acute iron toxicity cases occur in children less than 5 years of age. Moreover, clinical hepatic injury is uncommon with most symptoms stemming from the intestinal tract (eg, nausea, vomiting, diarrhea). Therefore, physicians, particularly those who do not routinely treat pediatric patients, are often unfamiliar with hepatotoxicity related to iron overdose. Nevertheless, hepatotoxicity caused by acute iron poisoning is associated with a high mortality rate. We report a case of severe hepatic injury in an adult who overdosed on iron tablets with suicidal intent. Tests for other hepatotoxins (eg, acetaminophen), hepatatrophic viruses, and other causes of acute liver injury were negative. Although peak serum iron level (340 microg/dL) was significantly lower than that reported to cause hepatotoxicity (>1,700 microg/dL), rapid and significant elevations in aminotransferases (>4,000 U/L), total bilirubin (5 mg/dL), and prothrombin time (50 seconds) occurred within 48 hours. Treatment with deferoxamine was prompt and followed by empiric N-acetylcysteine once liver injury was apparent. The patient was minimally symptomatic and she eventually had a full recovery.
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PMID:Acute liver failure due to iron overdose in an adult. 1575 60


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