Gene/Protein Disease Symptom Drug Enzyme Compound
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 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The question of whether the HELLP syndrome exists as a distinct entity or is part of a spectrum of pregnancy complications, which have in common hemolysis, elevated liver enzymes, and thrombocytopenia, has long been a source of speculation and debate among obstetricians and internists. A review of the literature indicates a definite need for a uniform definition, diagnosis, and management of this syndrome. Patients manifesting this syndrome usually are seen before term (less than 36 weeks' gestation) complaining of malaise (90%), epigastric or right upper-quadrant pain (90%), and nausea or vomiting (50%), and some will have nonspecific viral-syndrome-like symptoms. Hypertension and proteinuria may be absent or slight. Thus some of these patients may have a variety of signs and symptoms, none of which are diagnostic of classic preeclampsia. In consideration of the high maternal and perinatal mortality and morbidity reported with the presence of this syndrome, I recommend that all pregnant women having any of these symptoms should have a complete blood cell count with platelet and liver enzyme determinations irrespective of maternal blood pressure.
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PMID:The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? 240 34

Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect. The present phase I trial utilized a weekly x 3 bolus infusion schedule, repeated every 5 weeks. Biochemical measurements of GTP and dGTP were performed in patients at each dose level. Twelve patients received 16 courses of the drug in doses ranging from 1100 to 2050 mg/m2 weekly x 3. The dose limiting toxicities were pericarditis and clinical symptoms suggestive of a more generalized serositis (chest and abdominal pain). Other toxicities included reversible elevations in CPK (MM band only) and SGOT, nausea, vomiting, and arthralgias. Neurotoxic effects were generally mild, including headaches, anxiety, and malaise. Only 1 of 6 patients evaluated for tiazofurin's biochemical activity showed a sustained depletion of guanine nucleotide pools. No antitumor activity was observed. The maximally tolerated dose of tiazofurin on this intermittent weekly x 3 schedule was 1650 mg/m2. Toxicity and the overall lack of biochemical and biologic effect at clinically achievable doses may preclude further clinical evaluation of this drug on a weekly schedule. The toxicities observed in our study were similar to those reported for phase I investigations using a considerably higher dose intensity with daily x 5 schedules.
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PMID:Phase I trial and biochemical evaluation of tiazofurin administered on a weekly schedule. 234 2

Brequinar sodium is a quinoline carboxylic acid derivative that has shown antitumor activity in a number of in vivo murine and human tumor xenograft models. Its mechanism of action is blockade of de novo pyrimidine biosynthesis by inhibition of dihydroorotic acid dehydrogenase. In vitro and in vivo studies demonstrate the superiority of prolonged drug exposure in achieving tumor growth inhibition. This phase I study evaluated the administration of brequinar sodium by short, daily i.v. infusion for 5 days repeated every 4 weeks. Fifty-four subjects were enrolled in the study and received drug in doses ranging from 36-300 mg/m2. The dose-limiting toxicities were mucositis and diffuse skin rash. Other toxicities included myelosuppression, nausea, vomiting, malaise, and burning at the infusion site. The maximum tolerated dose on the "daily times 5" schedule was 300 mg/m2. The recommended phase II dose is 250 mg/m2. Pharmacokinetic analysis of the day 1 drug clearance curves in 51 subjects showed slight nonlinearity in the relationship between dose and area under the clearance curve (AUC). The dose versus AUC relationship was well described using a Michaelis-Menten model of brequinar elimination kinetics with Vmax = 45 (micrograms/ml)/h and Km = 123 micrograms. Analysis of the day 5 drug clearance curves revealed a diminution in Vmax to 30 (micrograms/ml)/h. As a consequence of the reduction in Vmax brequinar plasma concentrations on day 5 were higher than predicted from day 1 drug kinetics. Pharmacodynamic analysis of the day 1 kinetic parameters and the toxicities occurring during the first cycle of drug therapy revealed significant correlations between mucositis and dose, AUC, and peak brequinar concentration; between leukopenia and AUC and peak drug concentration; and between thrombocytopenia and beta elimination rate.
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PMID:Phase I and pharmacokinetic study of brequinar sodium (NSC 368390). 236 34

During holidays in Suriname a six year old boy fell ill with high fever, general malaise, pain in the extremities and abdomen and vomiting. Because of a tentative diagnosis of acute rheumatism or bacterial enteritis amoxicillin and salicylates were started. After his return to the Netherlands an increased ESR and impaired renal and hepatic functions were found. The history revealed contact with sewage water. Further analysis established the diagnosis of Leptospirosis. This comparatively rare clinical entity, seldom mentioned in paediatric literature, is discussed.
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PMID:[A patient with fever and pain in the extremities]. 237 42

A phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NCS 286193, tiazofurin) was conducted using a 5-day i.v. bolus schedule, every 21 days. Thirty one patients with advanced cancer were entered on the trial. A total of 106 cycles were administered with doses ranging from 550 to 2750 mg/m2. Concomitant administration of Allopurinol was necessary to prevent hyperuricemia. Tiazofurin was difficult to evaluate and many side effects were variable and sporadic. The dose limiting toxicities were nonhematologic consisting particularly of myalgias, headaches and general malaise. Other toxicities included nausea, vomiting, stomatitis, lethargy, sleeping difficulty, sinus bradycardia, skin rash, desquamation of the palms and soles, photophobias and burning of the eyes. Hematologic toxicity was mild and not dose related though it led to a neutropenic septic death in one patient at 2750 mg/m2. Anemia was documented in 60% of cycles. Biochemical abnormalities consisted of mild hyperglycemia, hyperuricemia and elevated skeletal creatinine phosphokinase levels which did not correlate with the incidence or degree of myalgias. Though some patients were able to tolerate higher doses, the recommended dose for phase 2 study is 1650 mg/m2. Further studies will be required to achieve a better understanding of this interesting drug.
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PMID:Phase I study of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). 238 15

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
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PMID:A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. 238 96

Both the systemic and local reactions caused by the immunization with the vaccine against diphtheria, tetanus and whooping cough were studied. Side-effects, 48 hours after the vaccination were determined in 730 children between the ages of two months and five years and 11 months. Over 13% of the children were free from side-effects. Eighty-seven percent of the children immunized showed the following side-effects in percentages of frequency: fever, 66.0%; malaise, 37.8%; loss of appetite, 25.0%; sleep disorders, 20.4%; vomiting, 7.9%; and continuous crying, 7.6%. With respect to local disturbances: pain, 41.6%; reddening, 28.0% and subcutaneous nodules, 20.1%. None of the children had convulsions, hypotonic episodes or immediate neurological damage. Two types of DTP vaccines, one from the Connaught (Canadian) Laboratory and another from the National Institute of Hygiene (Venezuelan) were used. No significant differences were found in the appearance of the side-effects between the both, except for localized pain (P less than 0.01) with the national vaccine. The results obtained in relation to age and the number of doses were: there was a significant increase of localized pain as ages increased (P less than 0.01). There were significantly greater number of localized pain and subcutaneous nodules with greater numbers of doses (P less than 0.01).
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PMID:[Side effects of the vaccine against diphtheria, tetanus and whooping cough]. 239 Jan 82

Acute fatty liver of pregnancy is considered an uncommon disorder that may complicate the third trimester of pregnancy, with high fetal and maternal mortality rates. However, in recent years it has become clear that the course of the disorder can be less fulminant than previously believed. The diagnosis is also made more frequently. The case histories of three patients are described followed by a review of the clinical and diagnostic features. It is concluded that with all women showing symptoms of malaise, nausea, vomiting and upper abdominal pain in the third trimester of pregnancy liver enzymes should be measured. If evidence of liver dysfunction is found, acute fatty liver of pregnancy should be considered in the differential diagnosis. Only early recognition and prompt treatment will improve both fetal and maternal survival.
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PMID:[Acute fatty degeneration of the liver in pregnancy]. 239 79

A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.
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PMID:Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation. 240 63

Combined chemotherapy with cisplatin was performed in patients with advanced esophageal cancer. Two types of administration schedule were used: method I (three-drug combination of cisplatin, bleomycin and methotrexate) and method II (combination of cisplatin, peplomycin and methotrexate). Of 16 cases, 6 (37.5%) showed partial remission. With regard to the method of administration, the response rate for method I was 33%, and that for method II was 43%. Nausea (84%), vomiting (56%), loss of appetite (94%), malaise (75%) and alopecia (25%) were observed as side effects. Nausea and vomiting were ameliorated by use of metoclopramide. In bloodchemistry, anemia (87%), leukopenia (56%), thrombopenia (31%) and increase of BUN (63%) were observed. However, these changes were ameliorated by hydration or blood transfusion. Combined chemotherapy with CDDP should be a more useful future treatment for esophageal cancer.
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PMID:[Combined chemotherapy with cisplatin in esophageal cancer]. 244 65


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