Arterial supply to the bleeding diverticulum in the ascending duodenum treated by transcatheter arterial embolization- a duodenal artery branched from the inferior pancreaticoduodenal artery.

We present a case of endoscopically unmanageable hemorrhagic diverticulum in the ascending duodenum. The ventral and dorsal walls of the ascending duodenum were supplied from the first jejunal artery (1JA) and inferior pancreaticoduodenal artery (IPDA), respectively. The hemorrhage mainly occurred from IPDA. The abruptly branching of IPDA from superior mesenteric artery enabled successful catheterization of the IPDA with an angled microcatheter. Hemostasis was obtained by embolization using n-butyl cyanoacrylate. Gastroendoscopy depicted a duodenal hemi-circumferential ulcer. No symptoms related to hemorrhage were found at the last follow-up at 12 months.

Designing sustainable and economically attractive brownfield revitalization options using an integrated assessment model.

We describe the development of an integrated assessment model which evaluates redevelopment options of large contaminated brownfields and we present the application of the model in a case study. Aiming to support efficient and sustainable revitalization and communication between stakeholders, the presented assessment model integrates three pinnacles of brownfield revitalization: (i) subsurface remediation and site preparation costs, (ii) market-oriented economic appraisal, and (iii) the expected contribution of planned future land use to sustainable community and regional development. For the assessment, focus is set on the early stage of the brownfield redevelopment process, which is characterized by limited data availability and by flexibility in land use planning and development scope. At this stage, revealing the consequences of adjustments and alterations in planning options can foster efficiency in communication between the involved parties and thereby facilitates the brownfield revitalization process. Results from the case-study application indicate that the integrated assessment provides help in the identification of land use options beneficial in both a sustainable and an economical sense. For the study site it is shown on one hand that brownfield redevelopment is not automatically in line with sustainable regional development, and on the other hand it is demonstrated that additional contributions to sustainability are not intrinsically tied to increased costs.

Genetic analysis with calcium-induced calcium release test in Japanese malignant hyperthermia susceptible (MHS) families.

Some genetic studies have shown a linkage between malignant hyperthermia susceptibility (MHS) and chromosome 19q or the skeletal muscle ryanodine receptor (RYR1) gene. Some types of MHS seem to be caused by an abnormality of calcium-induced calcium release (CICR). We analyzed the linkage of RYR1 gene polymorphisms in Japanese MHS families and investigated the correlation between genetic evidence of RYR1 gene mutations and an accelerated rate of CICR. We studied 63 subjects who were referred to our institute for investigation of MHS. CICR rates were measured by the skinned fiber method in 23 subjects. DNA samples were collected from 63 individuals belonging to 22 unrelated families. Restriction fragment length polymorphism (RFLP) analyses on the RYR1 locus and hypervariable microsatellite analysis were performed. We found one family with a linkage between acceleration of the CICR mechanism and a group of RFLPs. In CICR tests, ten of the 11 patients who had presented with fulminant MH showed accelerated rates of CICR. Analysis for the mutation C1840T, which was performed in 63 samples, did not demonstrate an alteration in any of the patients. Although we found heterozygotes in RFLP studies, we did not recognize a specific relationship between the acceleration of CICR and the RFLPs. We suggest a linkage between the acceleration of CICR and an abnormal human RYR1 gene in MHS. These results also suggest that heterogeneity exists for MH. We conclude that genetic tests cannot replace CICR tests or caffeine-halothane contracture tests with muscle biopsy as a diagnosing test for MH in the near future.

19-oxygenations of 3-deoxy androgens, potent competitive inhibitors of estrogen biosynthesis, with human placental aromatase.

Aromatase is a cytochrome P450 enzyme complex that catalyzes the conversion of androst-4-ene-3,17-dione (AD) to estrone through three sequential oxygenations of the 19-methyl group. To gain insight into the ability of 3-deoxy derivative of AD, compound 1, and its 5-ene isomer 4, which are potent competitive inhibitors of aromatase, to serve as a substrate, we studied their 19-oxygenation by human placental aromatase and the metabolites isolated were analyzed by gas chromatography-mass spectrometry. Inhibitors 1 and 4 were found to be oxygenated with aromatase to produce the corresponding 19-hydroxy derivatives 2 and 5 and 19-oxo derivatives 3 and 6 as well as the 17beta-reduced 19-hydroxy compounds 7 and 8. Kinetic studies indicated that the 5-ene steroid 4 was surprisingly a good substrate for the aromatase-catalyzing 19-oxygenation with the V(max) value of 45 pmol/min per mg prot which was approx. four times higher than that of the other. The relative K(m) value for steroids 1 and 4 obtained in this study is opposite from the relative K(i) value obtained previously in the inhibition study. The results reveal that there is a difference between a binding suitable for serving as an inhibitor of aromatase and a binding suitable for serving as a substrate of the enzyme in the 3-deoxy steroid series and the C-3 carbonyl group of AD is essential for a proper binding as a substrate to the active site of aromatase.

[Total intravenous anesthesia with propofol is advantageous than thiopental-sevoflurane anesthesia in the recovery phase].

A randomized, prospective and multi-institutional study was performed to investigate whether different anesthetic methods affected differently the quality of recovery from anesthesia. Two hundred and eleven patients were allocated to one of two groups; total intravenous anesthesia (TIVA) with propofol and fentanyl (group P, n = 107) and general anesthesia with thiopental, sevoflurane and nitrous oxide (group TS, n = 104). The rapidity of emergence from anesthesia and postoperative incidence of nausea, vomiting, and headache were compared between the two groups. The group P showed significantly shorter emergence times for verbal command responses (7.4 +/- 5.6 min), extubation (10.0 +/- 6.0 min) and orientation (13.1 +/- 7.8 min) than the group TS (9.1 +/- 5.0 min, 11.7 +/- 6.2 min, 16.4 +/- 7.9 min, respectively). The postoperative incidence of vomiting was not significantly different between the two groups (3.7% in the group P and 9.6% in the group TS), but the postoperative incidences of nausea and headache were significantly lower in the group P compared with the group TS (10.3%, 17.8%, respectively in the group P and 34.6%, 29.8%, respectively in the group TS). We conclude that TIVA with propofol is advantageous than thiopental-sevoflurane anesthesia in the recovery phase.

Assessment of cerebral fat embolism by magnetic resonance imaging in the acute stage.

The authors assessed the characteristic appearance of magnetic resonance imaging (MRI) of cerebral fat embolism in three patients. The MRI features in the acute stage were characterized by widespread, spotty lesions in the white matter, which appeared hyperintense on T2-weighted images and iso- or hypointense on T1-weighted images. The relation between clinical features and MRI findings are discussed.

[Clinical evaluation of controlled hypotensive anesthesia with MR7S1].

Efficacy, safety and the optimal dose of MR7S1, an injectable preparation of sodium nitroprusside, were studied in 37 patients (ASA class I and II) under nitrous oxide-oxygen-enflurane anesthesia. MR7S1 was administered by intravenous infusion. The dose of MR7S1 was increased gradually starting from 0.25 micrograms.kg-1.min-1 to the dose which could achieve the target value of systolic blood pressure (80-100 mmHg). Thereafter this dose level was maintained. During the period in which the dose was increased, the blood pressure was reduced in proportion to the rate of administration. With the rate of administration of 1.0 to 3.0 micrograms.kg-1.min-1, a significant decrease in systolic blood pressure (SBP) was observed compared with the pretreatment level of SBP. During the maintenance period, the SBP was maintained around 80 to 100 mmHg at a rate of administration of 0.25 to 3.5 micrograms.kg-1.min-1. Two out of 37 patients showed a slight decrease in PaO2, but these values returned to normal without any treatment. These findings suggest that MR7S1 is a useful agent to control blood pressure for the hypotensive anesthesia.

Reaction of sevoflurane and its degradation products with soda lime. Toxicity of the byproducts.

Sevoflurane previously has been reported to undergo extensive degradation in the presence of soda lime. To more completely characterize the extent and significnce of this reaction, we studied degradation of sevoflurane with and without soda lime, as well as the toxicity and mutagenicity of the degradation products. Two degradation products detected were CF2 = C(CF3)OCH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B). During circulation of 1%, 2%, and 3% sevoflurance in a closed anesthesia circuit for 8 h, peak concentrations of compound A were 13.3 +/- 0.27, 30.2 +/- 0.10, and 42.1 +/- 1.07 ppm at 2 h, respectively. The concentrations of compound B did not exceed 2 ppm. The temperature of the soda lime was 43.3 +/- 2.8 degrees C at 1 h and increased gradually to 47.9 +/- 1.5 degrees C after 8 h. In closed flasks with soda lime, the magnitude of the decrease in sevoflurance concentrations (3%) and of the increase in compound A concentrations was temperature dependent. The peak concentrations of compound A at 23 degrees C, 37 degrees C, and 54 degrees C were 32.8 +/- 6.8 at 2 h, 46.6 +/- 1.0 at 0.5 h, and 78.5 +/- 2.3 ppm at 0.5 h, respectively. The LC50 (50% lethal concentration) of compound A in Wistar rats was 1,090 ppm in males and 1,050 ppm in females exposed for 1 h. The LC50 was 420 ppm in males and 400 ppm in females exposed for 3 h. The chronic toxicity of compound A in Wistar rats was studied by exposing rats 24 times, for 3 h each, to initial concentrations of 30, 60, or 120 ppm in a ventilated chamber. At all concentrations, there were no apparent effects other than a loss of body weight in females (120 ppm) on the final day (P < 0.01). Compound A did not induce mutation on the reverse (Ames) test at less than 2,500 micrograms/dish (culture medium 2.7 ml) with activation by S-9 mixture, and below 1,250 micrograms/dish (culture medium 2.7 ml) without activation, in four strains of S. typhimurium and in 1 strain of E. coli. Exposure of fibroblasts to 7,500 ppm of compound A for 1 h, compound A did not induce structural change. In a study of acute toxicity of compound B, there was no toxicity in Wistar rats after 3 h of exposure at 2,400 ppm. The reverse (Ames) test for compound B was negative at 625-1,250 micrograms/dish.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in lipid peroxidation levels and lipid composition in the lungs, livers, kidneys and brains of mice treated with paraquat.

We examined lipid peroxide levels and the lipid composition of homogenates prepared from the lungs, livers, kidneys and brains of 48 male ICR mice treated with 30 mg kg-1 paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride). The mice were divided into eight groups, in which they were killed 0, 1.5, 3, 6, 12, 24, 48 and 120 h after the administration of paraquat. A significant increase in the lipid peroxide level was identified only in the liver. Change in lipid composition was identified in all the examined organs. However, the change was not a characteristic one in which there is a selective decrease of polyunsaturated fatty acids which become degraded in a lipid peroxidation reaction. It is possible that the mechanism of paraquat toxicity may differ in different organs.

Suppressive effect of vitamin E on lipid peroxidation in halothane-administered guinea pig liver.

The effect of vitamin E on halothane-induced liver damage was studied in guinea pig halothane hepatitis. Twenty animals were divided into 3 groups, consisting of a control group, a halothane group and a vitamin E + halothane (H) group. The animals in the control group (n = 6) were allowed to inhale air only. The animals in the halothane group (n = 6) and the vitamin E + H group (n = 8) were allowed to inhale 1% halothane with air. Animals in the vitamin E + H group were additionally injected with 30 mg kg-1 of vitamin E 30 minutes prior to inhalation of halothane. Blood was aspirated from the heart immediately after sacrificing to measure the serum activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). A microsomal suspension was prepared from the excised liver. Then the amount of thiobarbituric acid (TBA) reactive products in the microsomes were measured. The amount of tissue TBA-reactive products was increased by inhalation of halothane. The increase in the amount of TBA-reactive product was inhibited by the administration of vitamin E. The serum GPT activity was increased by halothane inhalation. Increased serum GOT and GPT activity were inhibited by the administration of vitamin E. These results demonstrated that vitamin E suppressed halothane-induced liver damage in the guinea pig by inhibiting lipid peroxidation.

Enzyme inhibition by analgesic and hypnotic agents on anaerobic dehalogenation of halothane.

Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp(2)) and NADH-ferricyanide reductase (fp(1)) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656 microM and 2570 microM), chlorpromazine (49.7 microM and 68.1 microM), ketamine (24.9 microM and 64.4 microM), fentanyl (23.9 microM and 34.6 microM), hydroxyzine (19.2 microM and 50.8 microM), diazepam (17.0 microM and 13.9 microM), buprenorphine (11.2 microM and 22.4 microM), and pentazocine (1.96 microM and 6.67 microM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp(2) and fp(1) did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp(2) and fp(1) which are flavoproteins existing in the microsomal electron transport system.

Knee-chest position improves pulmonary oxygenation in elderly patients undergoing lower spinal surgery with spinal anesthesia.

STUDY OBJECTIVE: To define the effect of the knee-chest position on pulmonary oxygenation in patients who underwent lower spinal operations under spinal anesthesia. DESIGN: Clinical, prospective study. SETTING: Inpatient anesthesia and orthopedic surgery clinic at a municipal hospital. PATIENTS: Fifty-six patients (30 males and 26 females) who underwent lower spinal surgery under spinal anesthesia. INTERVENTIONS: After administering hyperbaric tetracaine solution and fixing the anesthesia level in the supine position for 15 minutes, patients were turned to the knee-chest position. They breathed room air normally. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas tensions were measured in the supine position 15 minutes after administration of the tetracaine solution and 15 minutes after turning patients to the knee-chest position. Patients were classified into six groups according to their age: patients in their teens and 20s, 30s, 40s, 50s, 60s, and 70s. In the supine position, the mean values of the alveolar arterial oxygen tension difference (A-aDO2) of patients in their 50s, 60s, and 70s were significantly higher than those of patients in their teens and 20s, 30s, and 40s. In the knee-chest position, these high values of A-aDO2 in the older patient groups decreased significantly, thereby eliminating any significant difference in A-aDO2 among all age groups. To determine the mechanism of the improvement of pulmonary oxygenation in the elderly patients, the effect of the knee-chest position on lung volumes was studied in eight young volunteers. CONCLUSION: A significant improvement of pulmonary oxygenation was seen in elderly patients who underwent lower spinal operation with spinal anesthesia when they were turned to the knee-chest position. The knee-chest position has a beneficial effect on pulmonary oxygenation in elderly patients who are given spinal anesthesia.

Dose-related sevoflurane metabolism to inorganic fluoride in rabbits.

Serum concentrations and urinary excretion of inorganic fluoride (fluoride ion), a metabolite of sevoflurane, were measured by an ion-chromatographic analyzer after inhalation of three different concentrations of sevoflurane in adult, male Japanese white rabbits weighing 2.6-3.6 kg. Sevoflurane was administered at concentrations of 0% (control), 1%, 2% and 3% (Groups I, II, III and IV, respectively) through a sevoflurane vaporizer for 2 hr under controlled ventilation. Blood and urine samples were collected during and after termination of sevoflurane inhalation at scheduled time intervals for 24 hr. The total volume of urine, the urinary pH and the osmolality of serum and urine were not significantly different among any of the groups. Osmolality of the serum and urine was within normal range in all groups of animals. The mean serum peak values of fluoride ion were 0.7 +/- 0.5, 22.8 +/- 8.7, 31.8 +/- 11.0 and 41.5 +/- 13.2 microM (mean +/- SD) in groups I, II, III and IV, respectively. Peak values were recorded within 15 min after the termination of inhalation. The cumulative amounts of fluoride ion excreted in urine in 24 hr were calculated to be 5.0 +/- 1.6, 26.1 +/- 6.7, 41.4 +/- 11.3 and 64.3 +/- 18.0 mumol (mean +/- SD) in groups I, II, III and IV, respectively. Regression analysis revealed significant correlations between the formation and excretion of fluoride ion, and the dose of sevoflurane (r = 0.85, p less than 0.05 and r = 0.89, p less than 0.05, respectively). The authors conclude that the formation and excretion of fluoride ion after sevoflurane anesthesia is dependent on the dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobic dehalogenation of halothane showing different substrate dependency from anaerobic dehalogenation in liver microsomes of guinea pig.

The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation.

Effects of several volatile anesthetics on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pig.

The effects of various volatile anesthetics on intramuscular Ca(2+)-related functions were studied with the skinned fiber technique in guinea pig skeletal muscles. All the volatile anesthetics tested significantly enhanced Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) at clinical concentrations with negligible effects both on Ca2+ sensitivity of the contractile system and on Ca2+ uptake by the SR. A comparison was made of the enhancing effect of several volatile anesthetics on CICR at clinical concentrations. Halothane was the most potent, followed by methoxyflurane, isoflurane, enflurane, sevoflurane and diethyl ether. If CICR plays an important role in triggering MH, this order of volatile anesthetics on their enhancing effect on CICR, also corresponds to their potency in triggering MH.

Effect of calcium channel blocking agents on the reductive metabolism of halothane.

The effect of calcium channel blocking agents on the reductive metabolism of halothane in liver microsomes of guinea pigs was investigated. The reaction mixture for the measurement of the end products consisted of microsomal suspension, 5 mM NADPH, calcium channel blocking agents (verapamil, diltiazem, nicardipine and nifedipine) and halothane in 0.1 M phosphate buffer (pH 7.4). The reductive metabolism of halothane was inhibited competitively by verapamil, diltiazem and nicardipine. The binding spectra for the interaction of these three drugs with cytochrome P-450 in microsomes were investigated. Verapamil caused the reverse type I difference spectrum and diltiazem caused the type I difference spectrum. However, the change caused by nicardipine was not observed by the presence of its specific spectra. NADPH-cytochrome P-450 reductase activity in microsomes did not change by the addition of these three drugs. These results suggest that these three calcium channel blocking agents inhibit the production of radical intermediates during the reductive metabolism of halothane.

Mesenteric lymphatic vasomotion following hemorrhage and retransfusion in the rat.

The effect of hemorrhage and retransfusion on the rhythmic contraction of mesenteric lymphatic vessels was studied in 24 rats, anesthetized with pentobarbital. The rats were divided into four groups according to the amount of blood withdrawn: 0.5ml/100g body weight (BW), 1ml/100g, 2ml/100g, and 2.5ml/100g. Immediately following hemorrhage at the rate of 0.5ml/100g/min, lymphatic contraction frequencies were decreased to 67 +/- 12.5, 45 +/- 24.7, 43 +/- 33.1, and 31 +/- 17.8% of the prehemorrhage values in each of the above four groups, respectively (p less than 0.01). Twenty minutes after hemorrhage, lymphatic contraction frequencies were decreased to 70 +/- 17.2, 46 +/- 36.8, and 34 +/- 41.3% in the 0.5ml/100g, 2ml/100g, and 2.5ml/100g, respectively (p less than 0.05). Immediately following hemorrhage, the lymphatic contracted diameters were also reduced to 77 +/- 9.7 and 61 +/- 9.0% of the prehemorrhage values in the 1ml/100g and 2.5ml/100g groups, respectively (p less than 0.01). Twenty minutes after hemorrhage, all withdrawn blood was reinfused. Lymphatic contraction frequency and contracted diameter recovered after retransfusion in each group but 20 minutes after retransfusion, the lymphatic contraction frequency in the 2ml/100g group was still decreased to 42 +/- 30.3% (p less than 0.01). Lymphatic contraction frequency not only decreased proportionately with hypotension during hemorrhage but after retransfusion contraction frequency correlated directly with the mean arterial pressure 20 min after hemorrhage. These data suggest that mean arterial pressure and by inference capillary blood flow and tissue oxygenation are major factors regulating lymphatic vasomotion.

A comparative study on reductive dehalogenation of halothane in liver, kidney and lung of the rabbit.

The contents of cytochrome P-450 (P-450) and cytochrome b5, and the activity of NADPH-cytochrome c reductase and the reductive metabolites of halothane, 2-chloro-1, 1-difluoroethylene (CDE) and 2-chloro-1, 1, 1-trifluoroethane (CTE) were measured in microsomes from the liver, kidney and lung of phenobarbital (PB) pretreated and untreated Japanese white strain rabbits. Microsomal P-450 levels in the liver, kidney (renal cortex) and lung of the rabbits were 1.91 +/- 0.35, 0.19 +/- 0.04 and 0.42 +/- 0.11 nmol/mg protein (mean +/- SD), respectively. In vivo phenobarbital pretreatment (PB-pretreatment) increased the content of P-450 to 2.95 +/- 0.40 nmol/mg protein (154%) in the liver and to 0.40 +/- 0.11 nmol/mg protein (211%) in the kidney, but had little effect in the lung. The activity of CDE formation was 0.72 +/- 0.10, 0.08 +/- 0.04 and 0.03 +/- 0.01 nmol/mg protein/min in the liver, kidney and lung, respectively. PB-pretreatment enhanced the activity of CDE formation to 1.59 +/- 0.49 nmol/mg protein (221%) in the liver, and to 0.29 +/- 0.16 nmol/mg protein/min (363%) in the kidney, but showed little enhancement in the lung. The activity of CTE formation was 1.30 +/- 0.19, 0.12 +/- 0.04 and 0.09 +/- 0.02 nmol/mg protein/min, in the liver, kidney and lung, respectively. PB-pretreatment enhanced the activity of CTE formation to 1.80 +/- 0.44 nmol/mg protein/min (138%) in the liver, but caused only slight enhancement in the kidney and lung. PB-pretreatment markedly enhanced the activity of CDE formation in the kidney. The authors conclude that cytotoxicity by reductive dehalogenation of halothane is possible not only in the liver but also in the kidney with PB-pretreatment.

Effects of in vivo pretreatment with various barbiturates on anaerobic halothane metabolism in rat liver microsomes.

The effects of in vivo pretreatment with phenobarbital (PB), thiopental (TP), thiamylal (TA), pentobarbital (PT), and secobarbital (SB) on hepatic microsomal enzymes, and the effects on anaerobic halothane dehalogenation, aminopyrine N-demethylation, and aniline hydroxylation in the microsomes were studied in male Wistar rats. Three hundred twenty mumol/kg (0.1 ml) of PB, TP, TA, PT, SB, or 0.1ml of 0.9% saline were administered daily, intramuscularly, for periods of one day up to ten days. Daily administration of PB, TP, TA, or PT induced cytochrome P-450, NADPH-cytochrome P-450 reductase and/or cytochrome b5. However, administration of SB did not induce these enzymes. The potency of these enzyme inductions ranged in descending order as follows: PB, TP, TA, and PT. After five days of daily administration of PB, TP, or TA, the production of the anaerobic halothane metabolite, CDFE, increased to 187%, 134%, and 130% of the control, respectively. The production of another halothane metabolite, CTFE, likewise increased to 197%, 168%, and 163%. However, pretreatment with PT or SB had no effect on anaerobic halothane dehalogenation. Aminopyrine N-demethylation also increased after five days of daily administration of PB, TP, and TA. However, aniline hydroxylation decreased after five days of daily administration of TA. Other barbiturates had no effect on aniline hydroxylation. In this study we showed that whereas PT and SB did not enhance anaerobic halothane dehalogenation, PB, TP and TA did. We conclude that not only PB, and also TP and TA, may be enhancing factors in halothane hepatotoxicity. We recommend that, if barbiturates are necessary, SB and PT be used in the preadministration of halothane anesthesia.