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E Melzer

Publications and source records attributed to E Melzer.

63 records · Page 4Linked to original sources

[Megacystis].

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Child, Preschool↗

Alpha interferon has no effect on lidocaine metabolism in the rat.

Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine elimination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blood was drawn from the arterial catheter for lidocaine determination every 3 min for 20 min. 7 rats were pre-treated with intramuscular rat alpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rats were given saline i.m. The lidocaine elimination rate constant was unchanged, 0.065 min-1 and 0.063 min-1 for the control and IFN groups, respectively. To investigate lidocaine extraction, the isolated perfused rat liver was used. Perfusate samples from the portal and hepatic veins were drawn at 2 min intervals for 20 min, and lidocaine extraction determined. Extraction was determined in two groups of 6 rats each. The first group served as control and these rats were injected with saline only, while in the second group, the rats were pre-treated with rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated perfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded that the rat alpha-IFN affects neither the elimination nor the extraction of lidocaine.

Animals↗

Omeprazole has no effect on acetaminophen kinetics in the rat.

We investigated in the rat the effect of the H+/H(+)-ATPase inhibitor, omeprazole, on the kinetics of acetaminophen. Two groups of rats were treated with either omeprazole 50 mg/kg/day or the vehicle for 7 days. On day seven, the pharmacokinetic parameters of acetaminophen clearance were determined in the conscious rat. Elimination rate constant, elimination half life time, clearance and volume of distribution of acetaminophen were not disturbed by omeprazole. It is concluded that in the rat, omeprazole does not affect acetaminophen kinetics and, therefore, will not increase susceptibility to acetaminophen toxicity.

Acetaminophen↗

Double-blind controlled trial of flumazenil in patients who underwent upper gastrointestinal endoscopy.

The antisedative effect of flumazenil, a benzodiazepine antagonist, was studied in a double-blind placebo controlled trial in 61 patients who underwent upper gastrointestinal endoscopy and sedation with benzodiazepines. The efficacy of flumazenil in reversing the effect of both benzodiazepines, diazepam and midazolam, was significantly higher than placebo (p less than 0.0001). The effect of flumazenil was prompt and was clearly noticed at the first assessment, 5 min after its administration. In none of the patients was a relapse of the sedative effect of the benzodiazepines noticed. The administration of flumazenil was free of major side effects. Flumazenil administration permits an earlier discharge of patients following endoscopy. Its availability in the endoscopy suite may improve the outcome of serious but rare side effects related to benzodiazepines.

Anesthesia, Intravenous↗

Triazolo- and tetrazolopyridazine derivatives and their hypotension and heart rate activity.

6-Chloro-, 6-morpholino- and 6-N-methylpiperazino-1,2,4-triazolo[4,3-b]- or 1,2,3,4-tetrazolo[1,5-b]pyridazines [II-VII] were synthesized from 3-chloro-6-hydrazinopyridazine [I]. Positive effect of a series of tetra- and triazolopyridazines for lowering blood-pressure without affecting the heart rate was found in tests on rats. Their lipophilicity and other properties are discussed.

Animals↗

Accuracy of endoscopic ultrasonography for preoperative staging of esophageal malignancy.

Surgery for esophageal cancer carries a high mortality rate and a low rate of resectability for cure. Accurate preoperative staging is therefore of utmost importance. Staging is based on computerized tomography (CT), and recently, the use of endoscopic ultrasonography (EUS). We performed EUS and CT on 10 patients with esophageal cancer. Tumors were staged according to the TNM classification. According to the CT results, seven patients had a T3 tumor, one T1-2 and two T0. All patients were diagnosed as T3 by EUS. One patient, who was treated by combined modality treatment with chemotherapy and radiotherapy, converted to T0. Six patients were operated on, and in five, pathological findings were of an invasive tumor. The T stage was predicted correctly in five patients by CT and in all six patients by EUS. N stage was correctly diagnosed in two patients by CT and in five by EUS. It is concluded that EUS is superior to CT for preoperative staging of esophageal tumors. EUS should be undertaken as a routine procedure prior to surgery for esophageal cancer.

Adenocarcinoma↗

In vitro cytostatic activity of 1,2,4-triazolo- and 1,2,3,4-tetrazolo pyridazines.

Out of a series of fourteen 1,2,4-triazolo(4,3-b)-, and 1,2,3,4-tetrazolo-(1,5-b)pyridazine derivatives, 4 compounds have been found to reveal high cytostatic activity in KB and HeLa human cancer cell lines in vitro with ED50 activity values ranging from 0.25 to 3.0 micrograms/cm3 (0.009-0.158 x 10(-4) mole/l), and according to DR and D, NCI, NIH Bethesda criterion were qualified for further in vivo screening investigation. 6-Chloro-8-(N,N-dimethylaminosulfonylmethyl)-1,2,3,4-tetrazolo+ ++-(1,5-b)- pyridazine exhibited the strongest in vitro cytostatic activity (ED50 = 0.009 x 10(-4) mole/l), comparable with the best standards, and higher in comparison with a standard cytosine arabinoside (ED50 = 0.03-0.04 x 10(-4) mole/l). The presence of chlorine atom at C-6 position in the pyridazine ring determines the cytotoxic activity of tetrazolopyridazines as the primary factor and C-8 substituents, which influence their better solubility seems to be a secondary one, as confirmed by the results of the structure-activity and solubility-activity relationship analysis. However, for the exhibition of the triazolopyridazine activities the presence of two chlorine atoms at C-6 and C-3 position was essential.

Antineoplastic Agents↗