Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 31-year-old secundipara with eclampsia developed the HELLP syndrome after delivery. Clinically, along with very high blood pressure values (29.3/17.3 kPa) and eclamptic attacks, an intense pain in the upper abdomen and nausea were dominant. The patient also had severe thrombocytopenia (18 x 10(9)/L), hemolysis, and increased liver enzymes (SGOT up to 220 U/L and SGPT up to 100 U/L). An intensive therapy, including--together with usual interventions in serious EPH gestoses--also plasmapheresis, antithrombin III substitution, freshly frozen plasma, and transfusion of blood and thrombocytes, proved successful in achieving the normalization of the blood pressure, blood count and liver enzymes, as well as a clinical improvement, so that 18 days after delivery it was possible for the patient to go home, provided with necessary instructions.
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PMID:[The HELLP syndrome--a case report]. 174 83

Although glucocorticoids have been universally implemented to stimulate fetal lung maturity, their effectiveness and side effects are still widely contested. In search of alternative drugs a double-blind study was conducted between June 1981 and June 1984 comparing betamethasone, a conventional corticoid, and ambroxol, a bromhexine metabolite for efficacy and tolerance in prenatal prevention of the respiratory distress syndrome (RDS) in premature infants and full-term neonates. The therapeutic efficacies of betamethasone and ambroxol for this indication proved to be comparable. Since the possible risks of corticoid therapy in abnormal pregnancies are repeatedly discussed in the literature and in daily clinical practice. 137 patients with EPH gestosis, placental insufficiency, diabetes mellitus, and premature rupture of the membranes were selected from the original group of 308 patients. Only minor side effects (e.g. nausea) were present in a few of the 137 cases undergoing treatment with the 2 test substances. No side effects were observed in the neonates. The incidence of fetal RDS was comparable in both groups (2.9% with ambroxol, 2.2% with betamethasone). Transient and mild RDS cases were slightly more frequent in the ambroxol group than in the betamethasone group. To date, contraindications to ambroxol treatment in abnormal pregnancies are unknown and since generally the rate of potential side effects is considered to be lower in comparison with corticoid treatment, the use of ambroxol especially in abnormal pregnancies corresponding indication can be recommended.
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PMID:[Ambroxol versus betamethasone for the promotion of antepartum lung maturity in pathological pregnancies]. 240 30

2B1 is a bispecific murine monoclonal antibody (BsMAb) with specificity for the c-erbB-2 and Fc gamma RIII extracellular domains. This BsMAb promotes the targeted lysis of malignant cells overexpressing the c-erbB-2 gene product of the HER2/neu proto-oncogene by human natural killer cells and mononuclear phagocytes expressing the Fc gamma RIII A isoform. In a Phase I clinical trial of 2B1, 15 patients with c-erbB-2-overexpressing tumors were treated with 1 h i.v. infusions of 2B1 on days 1, 4, 5, 6, 7, and 8 of a single course of treatment. Three patients were treated with daily doses of 1.0 mg/m2, while six patients each were treated with 2.5 mg/m2 and 5.0 mg/m2, respectively. The principal non-dose-limiting transient toxicities were fevers, rigors, nausea, vomiting, and leukopenia. Thrombocytopenia was dose limiting at the 5.0 mg/m2 dose level in two patients who had received extensive prior myelosuppressive chemotherapy. Murine antibody was detectable in serum following 2B1 administration, and its bispecific binding properties were retained. The pharmacokinetics of this murine antibody were variable and best described by nonlinear kinetics with an average t 1/2 of 20 h. Murine antibody bound extensively to all neutrophils and to a proportion of monocytes and lymphocytes. The initial 2B1 treatment induced more than 100-fold increases in circulating levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 8 and lesser rises in granulocyte-monocyte colony-stimulating factor and IFN-gamma. Brisk human anti-mouse antibody responses were induced in 14 of 15 patients. Several minor clinical responses were observed, with reductions in the thickness of chest wall disease in one patient with disseminated breast cancer. Resolution of pleural effusions and ascites, respectively, were noted in two patients with metastatic colon cancer, and one of two liver metastases resolved in a patient with metastatic colon cancer. Treatment with 2B1 BsMAb has potent immunological consequences. The maximum tolerated dose and Phase II daily dose for patients with extensive prior myelosuppressive chemotherapy was 2.5 mg/m2. Continued dose escalation is required to identify the maximally tolerated dose for patients who have been less heavily pretreated.
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PMID:Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII. 755 34

Estradiol is known to reduce food intake in many species. Recent studies have also shown that estradiol can function as an unconditioned stimulus in taste aversion paradigms, suggesting that it induces nausea and malaise in rats and mice. The experiments reported here compared the hypophagic and aversive effects of estradiol. Using mice as subjects, the first investigation examined the taste aversion properties of the estradiol receptor antagonist MER-25, which is estrogenic with respect to feeding. MER-25 induced a strong taste aversion, contrary to a previous report. Second, progesterone, which counteracts the hypophagic effects of estradiol, did not disrupt the taste aversion induced by estradiol in mice. The third investigation used the Mongolian gerbil, a species in which estradiol increases food intake, in contrast to other species. Despite increasing food intake, estradiol induced a conditioned taste aversion in the gerbil similar to that seen in rats and mice. Taken together, these results indicate that the feeding and aversive effects of estrogen are mediated by different mechanisms.
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PMID:The aversive and hypophagic effects of estradiol. 815 66

Metoclopramide, a drug used for the relief of nausea and emesis, is currently under development as a radio- and chemosensitizing agent. Its usefulness in high doses, however, is limited by its central nervous system side effects. Neu-metoclopramide (Neu-Sensamide), a novel, concentrated, phosphate-buffered, pH-adjusted (pH = 6.5-7.0) formulation of metoclopramide, has been shown to have an improved side-effect profile in animal studies. The present double-blind, four-way crossover study compared the central nervous system effects and pharmacokinetics of neu-metoclopramide (intravenously and intramuscularly at 1.8 mg/kg) with intravenous metoclopramide and intramuscular placebo in 19 healthy male volunteers. Eight participants withdrew from the study, one because of noncompliance and seven because of adverse events. A total of 28 central nervous system events were observed with intravenous metoclopramide administration, whereas 16, 15, and 6 such events were attributed to intravenous neu-metoclopramide, intramuscular neu-metoclopramide, and placebo, respectively. Extra-pyramidal effects occurred on 10 occasions: 7 after intravenous metoclopramide, 2 after intravenous neu-metoclopramide, and 1 after intramuscular neu-metoclopramide. No significant differences were observed in the pharmacokinetic profiles of the three formulations of metoclopramide. It may be speculated, therefore, that the molecular conformational changes inherent to neu-metoclopramide result in a reduced side-effect profile compared with conventional metoclopramide formulations.
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PMID:Comparative central nervous system effects and pharmacokinetics of neu-metoclopramide and metoclopramide in healthy volunteers. 908 24

This study determines the ovarian effects, contraceptive efficacy, and effects on serum levels of norethindrone acetate (NET-Ac) and ethinyl estradiol (EE) among women using a single contraceptive vaginal ring (CVR) cyclically over a period of 1 year. A total of 60 women were enrolled and used the ring according to a schedule of 3 weeks "in" and 1 week "out." Assays of serum norethindrone acetate (NET-Ac) ethinyl estradiol (EE) levels were taken twice weekly in cycles 6, 9, and 13. Despite luteal activity in some cycles, no pregnancies were noted within the 12-month study period. Heavier body weight was associated with increased probability of luteal activity. Mean serum levels decreased over the last 3 months of CVR use, accounting for the increase in luteal activity and possible ovulations in cycle 13. Among women in Sydney, by contrast with women in the other centers, a difference in the effect on lipids was seen. However, the changes in lipid levels were very small. The side effects were a little different from those experienced by women using a combined pill. Nausea and vomiting were largely confined to early cycles and most common in the first days of the first cycle. Weight gain was also not a problem, although there was a small mean increase in body weight over the 12-month treatment period. This study indicates that use of a single CVR releasing EE and NET-Ac over a period of 12 months constitutes an acceptable, safe and effective contraceptive method.
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PMID:Efficacy, bleeding patterns, and side effects of a 1-year contraceptive vaginal ring. 1049 85

HELLP syndrome belongs to the group of pathological states known as pregnancy-induced hypertension or EPH gestosis. The basic criteria for establishing the diagnosis are as follows: H for hemolysis, EL for elevated liver enzymes and LP for low platelets. A pregnant woman, 38 years of age, multipara (V pregnancy, third delivery) has been admitted to the Clinic of Gynecology and Obstetrics in Novi Sad in 36-37 week gestation complaining of nausea, vomiting, epigastric pain, general weakness, exhaustion as well as symptom of previously diagnosed preeclampsia. Due to signs of fetal distress, the patient has undergone urgent cesarean section, giving birth to a female premature newborn infant. Twenty-four hours after delivery all symptoms and signs HELLP syndrome manifested. Being in a critical state, the patient has been transferred to the Institute of Surgery, Clinic of Anesthesiology and Intensive Care with signs of multiple organ failure. With this case report of a patient with HELLP syndrome, we wished to point to importance of continual intensive clinical follow-up, laboratory monitoring and corresponding therapeutic procedures, and at the same time to this relatively rare syndrome.
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PMID:Intensive-care management of a patient with HELLP syndrome--case report. 1051 6

The acceptability of 2 and 3 month injectable contraceptives was assessed and compared, and the acceptability of the injectables was further compared with that of oral contraceptives (OCs) and IUDs among a random sample of women, who attended a clinic in Alexandria, Egypt. The study was conducted by the University of Alexandria. The sample included 100 acceptors of the 2-month injectable, norethisterone oenanthate (NET-O EN), 100 acceptors of the 3-month injectable, depo-medroxy pregesterone acetate (DPMA), 60 OC acceptors, and 60 IUD acceptors. The women were interviewed prior to treatment and 2 or 3 times during the 6 months following their initial acceptance of the methods. Women who discontinued at any time during the 6-month period were interviewed concerning their reasons for discontinuing. The data was analyzed by calculating means and % distribution and by testing for significance. The percent lost to follow up was 12% for the NET-O EN group, 12% for DPMA users, and 0% for IUD and OC acceptors. The mean age of the acceptors was 30.4 years for NET-O EN, 30.7 years for DMPA, 28.3 years for OCs, and 25.2 years for IUDs. For these acceptor groups, the respective mean number of years of schooling was 6.1, 5.2, 7.2, and 7.5, and the respective mean number of pregnancies was 5.6, 5.4, 3.8, and 2.9. All 320 of the women were married, and 319 were Muslim. 99.4% lived in urban areas. 10% had no living male children, and 23.7% had no living female children. 2/3 of the injectable acceptors previously used 2 or more fertility control methods. A higher percent of IUD and OC acceptors, compared to injectable acceptors, reported using only 1 or no previous method. More than 1/2 of the injectable acceptors reported disruptions in their normal bleeding patterns. NET-O EN acceptors were more likely to experience heavy or prolonged bleeding while DPMA acceptors were more likely to report amenorrhea or a decreased flow. IUD acceptors were also bothered by bleeding problems. Almost all the women who reported changes in bleeding patterns were unhappy about the changes. Many of the women who reported amenorrhea worried that they might be pregnant. Women who experienced heavy or unpredictable bleeding worried about anemia and complained that bleeding interfered with their daily routines. 47.6% of the women reported weight gains, but this was generally viewed as an advantage. Nausea was the major side effect associated with OC use. 32% of the OC users, 28.0% of the NET-E ON users, 30.0% of the DMPA users, and none of the IUD users reported nausea. For all 4 groups, convenience and effectiveness were the major advantages the women attributed to their chosen method. Continuation rates were 68% for NET-O EN, 70% for DMPA, 75% for OCs, and 75% for IUDs. The major reason for discontinuation of injectables was bleeding problems. Among injectable users, a higher proportion of discontinuers (49%) than of continuers (20%) reported amenorrhea. The findings suggest that continuation for injectables could be improved if patients were given more detailed information about possible side effects and if they were advised to return to the clinic for treatment of any symptoms they experience.
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PMID:Acceptability study of the two versus three monthly injectable contraceptives. 1217 96

SU5416 is a small molecule antiangiogenic agent that inhibits vascular endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor. In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was tested whereby an initial 5-day loading dose was followed by weekly maintenance infusions. The start dose was 20 mg/m(2) for the loading dose followed by 65 mg/m(2) for the weekly infusions. Dose escalations occurred at 33% until a final dose of 65 mg/m(2) (loading dose) and 190 mg/m(2) (weekly infusion) was obtained. Twenty-two patients were treated at five dose levels; tumor types included gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most common serious drug-related toxicity was headache, often associated with nausea and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting, asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of 19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data revealed that the weekly infusion schedule prevented the reported 50-60% induction in SU5416 clearance observed with either daily or twice weekly dosing. Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m(2).
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PMID:Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. 1223 19

PTK787/ZK 222584 (PTK/ZK) is an oral potent and selective inhibitor of the vascular endothelial growth factor (VEGF)-mediated Flt-1 and KDR receptor tyrosine kinases. PTK/ZK has been shown to reduce growth and microvasculature in subcutaneously implanted human tumor xenografts in nude mice. A clinical difficulty in evaluating angiogenesis inhibitors has been the usefulness of conventional study endpoints. Therefore, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been studied as a pharmacodynamic marker of efficacy of PTK/ZK. Phase I studies are under way evaluating the optimum dose and schedule of oral PTK/ZK administered continuously to patients with advanced cancers of types known to overexpress VEGF. To date, particularly in patients with liver metastases from colorectal cancer treated with PTK/ZK, DCE-MRI has been a useful predictor of the biological response of VEGF-receptor inhibition. Toxicities have been manageable and have included lightheadedness, ataxia, nausea, vomiting, and hypertension. Stabilization of disease for >/= 6 months has been seen in heavily pretreated patients receiving PTK/ZK at higher doses. Preliminary data suggest that PTK/ZK can be administered safely on a continuous daily dosing schedule, efficacy data look promising, and DCE-MRI correlates with biological response. DCE-MRI will be used to guide dose optimization of PTK/ZK and perhaps of other angiogenesis inhibitors in future studies.
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PMID:Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK 222584. 1280 93


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