Search PubMed⌕ Search

Biomedical subjects

J N Bates

Publications and source records attributed to J N Bates.

52 records · Page 3Linked to original sources
PubMed1990

Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide.

Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium-derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S-nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide.

Animals↗
PubMed1990

Continuous epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor.

A randomized, double-blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor in nulliparous women. When the cervix was fully dilated, coded study solution was substituted for the known bupivacaine-fentanyl solution. The study solution for 29 patients was 0.0625% bupivacaine-0.0002% fentanyl; 34 patients received saline placebo. The two groups had similar pain scores during the first stage of labor. During the second stage, pain scores were significantly higher in the saline-placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation. Similarly, there was a significant difference between the two groups in global assessment of analgesia quality during the second stage, but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min. Among the women who delivered vaginally, eleven of 28 (39%) women in the bupivacaine-fentanyl group, versus five of 34 (15%) in the saline-placebo group, had surgical perineal anesthesia for vaginal delivery (P less than .05). Six of 28 (21%) women in the bupivacaine-fentanyl group, and five of 34 (15%) in the saline-placebo group, underwent instrumental vaginal delivery (P = NS). The median duration of the second stage of labor was 53 min (range = 5-283) in the bupivacaine-fentanyl group, and 63 min (range = 16-181) in the saline-placebo group (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1990

Influence of vessel size on the sensitivity of porcine coronary microvessels to nitroglycerin.

The responses of small (60-100 microns), medium (101-190 microns), and large (191-300 microns) porcine coronary microvessels to nitroglycerin were examined in vitro using a video-imaging apparatus. Large coronary microvessels, preconstricted with acetylcholine, relaxed by 90% in response to nitroglycerin, whereas small microvessels relaxed only 20% to nitroglycerin. Responses to putative metabolites of nitroglycerin, S-nitrosocysteine, and nitric oxide, were also examined. S-Nitrosocysteine produced equal relaxations in all sizes of coronary microvessels. Nitric oxide was 10 times more potent in large coronary arteries than in small but produced greater than 90% relaxation of all sizes of coronary microvessels at the highest concentrations. Bradykinin and the calcium ionophore A23187, which release endothelium-derived relaxing factor (EDRF), produced similar relaxation in small, medium, and large microvessels. The compound LY 83583 (which depletes vascular guanylate cyclase) reduced responses to nitroglycerin, nitric oxide, S-nitrosocysteine, bradykinin, and the calcium ionophore A23187 in microvessels of all sizes. Our data are compatible with the concept that nitroglycerin must undergo reductive processing to exert its vasodilator effect, likely through the formation of nitrosothiols. In small coronary microvessels, this biotransformation of nitroglycerin is diminished compared with larger coronary arteries. This may be caused by a relative deficiency of available sulfhydryl groups or a lack of enzymes necessary for conversion of nitroglycerin to its active metabolites in small coronary resistance vessels.

Animals↗
PubMed1990

Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta.

We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium-dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF.

Animals↗
PubMed1989

The influence of pH-adjusted 2-chloroprocaine on the quality and duration of subsequent epidural bupivacaine analgesia during labor: a randomized, double-blind study.

A randomized, double-blind study was performed to determine whether pH-adjustment of 2-chloroprocaine hastens the onset of epidural analgesia, and improves the quality and duration of subsequent epidural bupivacaine analgesia during labor. One milliliter of either 8.4% sodium bicarbonate or normal saline was added to a 30-ml vial of 2% 2-chloroprocaine. At 0, 5, and 7 min, each patient received 2, 5, and 3 ml of 2-chloroprocaine, respectively. At 22 min, any patient who did not yet have satisfactory analgesia received an additional 5 ml of 2-chloroprocaine. At 35, and, again, at 36 min, each patient received 5 ml of 0.25% bupivacaine. The median onset of 2-chloroprocaine analgesia was slightly more rapid in the bicarbonate group than in the saline-control group (12 versus 14 min, P less than .05). Two of 31 women in the bicarbonate group, versus 10 of 31 women in the saline-control group, required an additional 5 ml of 2-chloroprocaine at 22 min to achieve satisfactory analgesia (P = .01). There was no significant difference between groups in median duration of subsequent bupivacaine analgesia (60 min in each group) or mean (+/- SD) dosage of bupivacaine during the first stage of labor (64 +/- 43 versus 72 +/- 57 mg). Also, there was no significant difference between groups in pain scores over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia, Epidural↗
PubMed1989

Metoclopramide versus droperidol for prevention of nausea and vomiting during epidural anesthesia for cesarean section.

In a randomized, double-blind study, we compared the efficacy of metoclopramide hydrochloride with that of low-dose droperidol for prevention of nausea and vomiting during and after elective cesarean section with epidural anesthesia. Immediately after the umbilical cord was clamped, each patient received fentanyl (50 micrograms) and the study drug intravenously over 30 to 60 seconds. In one study group, 40 women received metoclopramide (15 mg); in the other group, 41 women received droperidol (0.5 mg). Twelve women (30%) in the metoclopramide group, versus eight (20%) in the droperidol group, had intraoperative, postdelivery nausea (P = NS). One woman (3%) in the metoclopramide group, versus two women (5%) in the droperidol group, had intraoperative, postdelivery vomiting (P = NS). During the first four postoperative hours, five women (12%) in each group complained of nausea. Three women (7%) in each group had postoperative vomiting. We conclude that metoclopramide (15 mg) and droperidol (0.5 mg) were similarly effective.

Adult↗
PubMed1988

Continuous infusion epidural analgesia during labor: a randomized, double-blind comparison of 0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine.

The analgesic efficacy of the continuous epidural infusion of 0.0625% bupivacaine/0.0002% fentanyl was compared with the infusion of 0.125% bupivacaine alone in a randomized, double-blind study of nulliparous women. Each patient received, in sequence: 1) 3 ml of 0.5% bupivacaine with 1:200,000 epinephrine; 2) 6 ml of study solution 1 (bupivacaine-fentanyl group: 0.125% bupivacaine/0.0008% fentanyl; bupivacaine-only group: 0.25% bupivacaine alone); and 3) a continuous epidural infusion of study solution 2 at a rate of 12.5 ml/h (bupivacaine-fentanyl group: 0.0625% bupivacaine/0.0002% fentanyl; bupivacaine-only group: 0.125% bupivacaine alone). The epidural infusion was discontinued at full cervical dilatation, but patients who lacked perineal anesthesia received one or two 5-ml boluses of study solution 3 (bupivacaine-fentanyl group: 0.0625% bupivacaine alone; bupivacaine-only group: 0.125% bupivacaine alone). During the first stage of labor, 36 of 41 (88%) women in the bupivacaine-fentanyl group, and 37 of 39 (95%) women in the bupivacaine-only group, had analgesia of excellent or good quality (P = NS). During the second stage, 22 of 37 (59%) women in the bupivacaine-fentanyl group, and 23 of 35 (66%) women in the bupivacaine-only group, rated their analgesia as excellent or good (P = NS). Women in the bupivacaine-only group were more likely to have motor block at full cervical dilatation (P less than .001). There was no significant difference between groups in duration of the second stage of labor, duration of pushing, position of the vertex before delivery, method of delivery, Apgar scores, or umbilical cord blood gas and acid-base values.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1987

Stabilization of the reduced halocarbon-cytochrome P-450 complex of halothane by N-alkanes.

Under anaerobic conditions, various halogenated compounds, when metabolized by cytochrome P-450, form complexes which are spectrally detectable. Previous studies have shown that halothane forms such a complex with cytochrome P-450, and the result is a strong absorption at 470 nm. Stabilization of this proposed intermediate carbanion complex has never been demonstrated in a biological system. Data are presented which show that several organic solvents (C5-C7N-alkanes) will stabilize the complex formed between halothane and cytochrome P-450. Stabilization allowed the decay of the complex to be studied, and it is demonstrated that the product of decay was chlorodifluoroethylene, which substantiates the hypothesis that the complex is a two electron-reduced carbanion. Carbon tetrachloride and benzyl bromide, which also produce spectrally visible intermediate complexes, were not stabilized by this treatment. Stabilization of the halothane complex in a biological system may facilitate studies to identify precisely the halothane-cytochrome P-450 complex and to clarify the mechanisms of halothane reduction by cytochrome P-450.

Alkanes↗
PubMed1987

The influence of continuous epidural bupivacaine analgesia on the second stage of labor and method of delivery in nulliparous women.

A randomized, double blind, placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.125% bupivacaine beyond a cervical dilatation of 8 cm in nulliparous women. When the cervix was greater than or equal to 8 cm dilated, coded study solution was substituted for the known 0.125% bupivacaine solution. The study solution for 46 patients was 0.125% bupivacaine; 46 patients received saline. During the first stage of labor, 44 (96%) women in the bupivacaine group, and 45 (98%) in the saline group, had analgesia of excellent or good quality. During the second stage, 36 (82%) women in the bupivacaine group, versus 18 (41%) women in the saline group, had analgesia of excellent or good quality (P less than .0001). Six (13%) women in each group underwent cesarean delivery after the start of the study solution. Among the women who delivered vaginally, the mean (+/- S.D.) duration of the second stage of labor was 124 (+/- 70) min in the bupivacaine group, versus 94 (+/- 54) min in the saline group (P less than .05). Twenty-one of 40 (53%) women in the bupivacaine group, versus 11 of 40 (28%) in the saline group, underwent instrumental vaginal delivery (P less than .05). Twenty-eight of 40 (70%) women in the bupivacaine group, versus six of 40 (15%) in the saline group; had surgical perineal anesthesia for vaginal delivery (P less than .0001). There were no significant differences between groups in Apgar scores or umbilical cord blood acid-base values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Stimulatory effects of halothane and isoflurane on fluoride release and cytochrome P-450 loss caused by metabolism of 2-chloro-1,1-difluoroethene, a halothane metabolite.

The structural similarity of the halothane metabolite, 2-chloro-1,1-difluoroethene (CDE), to haloethenes that are metabolized by and inactivate cytochrome P-450, suggests that CDE may undergo secondary metabolism and degrade these isozymes. This possibility was examined in hepatic microsomes by determining fluoride release and cytochrome P-450 loss due to CDE metabolism in the presence of several anesthetics. CDE alone decreased cytochrome P-450 from phenobarbital-treated rats by as much as 37%, but the addition of isoflurane or halothane to incubations containing CDE increased the loss of cytochrome P-450 nearly twofold. Fluoride release was enhanced approximately 2.5 to 3 times by halothane or isoflurane; however, fluroxene inhibited fluoride release and did not enhance the loss of cytochrome P-450. Extrapolation of these results to the clinical situation suggests that the metabolism of CDE produced during halothane anesthesia and the accompanying cytochrome P-450 loss may contribute to the inhibition of drug metabolism produced by halothane.

Animals↗
PubMed1987

Effect of intravenous administration of Ringer's lactate on maternal capillary blood glucose before elective cesarean section.

Capillary blood glucose concentrations were determined before and after intravenous infusion of 20 mL/kg of Ringer's lactate (RL) in 35 women scheduled for elective cesarean section. Mean (+/- SD) capillary blood glucose concentrations before and after infusion of RL were 84.7 +/- 13.2 and 89.0 +/- 16.5 mg/dL, respectively (P = NS). No parturient had a glucose level less than 60 mg/dL before or after infusion of RL. There were no instances of neonatal hypoglycemia. We conclude that large volumes of RL without dextrose may be rapidly infused into healthy pregnant women undergoing elective cesarean section without risk of dilutional hypoglycemia in the mother or neonate.

Adult↗
PubMed1987

Continuous infusion epidural analgesia with lidocaine: efficacy and influence during the second stage of labor.

A randomized double-blind study evaluated the analgesic efficacy and influence of maintaining a continuous epidural infusion of 0.75% lidocaine during the second stage of labor in nulliparous women. When the cervix was 8 cm or more dilated, unidentified study solution was substituted for the known 0.75% lidocaine solution and continued until delivery. The study solution for 26 patients was 0.75% lidocaine; 27 subjects received saline. During the first stage of labor, 88% of women in the lidocaine group and 81% of women in the saline group had analgesia of excellent or good quality, a nonsignificant difference. During the second stage, there was a tendency (not statistically significant) toward improved analgesia quality in the lidocaine patients, but there was no significant difference in the frequency of perineal anesthesia (23% lidocaine, 7% saline). There was no difference between the groups in the duration of the second stage of labor (73 +/- 63 versus 76 +/- 48 minutes). Operative delivery frequency was similar (31 and 37%), as were umbilical cord blood acid-base values. It is concluded that maintenance of the continuous epidural infusion of 0.75% lidocaine did not prolong the second stage of labor, but it also did not significantly differ from saline in quality of second stage analgesia or frequency of perineal anesthesia.

Anesthesia, Epidural↗
PubMedDate not supplied

Metabolism of 2-chloro-1,1-difluoroethene to glyoxylic and glycolic acid in rat hepatic microsomes.

The complete metabolic fate of the volatile anesthetic halothane is unclear since 2-chloro-1,1-diflurorethene (CDE), a reductive halothane metabolite, is known to readily release inorganic fluoride upon oxidation by cytochrome P-450. This study sought to clarify the metabolism of CDE by determining its metabolites and the roles of induce cytochrome P-450 forms in its metabolism. Upon incubation of [14C]CDE with rat hepatic microsomes, two major radioactive products were found which accounted for greater than 94% of the total metabolites. These compounds were determined to be the nonhalogenated compounds, glyoxylic and glycolic acids, which were formed in a ratio of approximately 1 to 2 of glyoxylic to glycolic acid. No other radioactive metabolites could be detected. Following incubation of CDE with hepatic microsomes isolated from rats treated with cytochrome P-450 inducers, measurement of fluoride release showed that phenobarbital induced CDE metabolism to the greatest degree at high CDE levels, isoniazid was the most effective inducer at low CDE concentrations, and beta-naphthoflavone was ineffective as an inducer. These results suggest that CDE biotransformation primarily involves the generation of an epoxide intermediate, which undergoes mechanisms of decay leading to total dehalogenation of the molecule, and that this metabolism is preferentially carried out by the phenobarbital- and ethanol-inducible forms of cytochrome P-450.

Animals↗
PubMedDate not supplied

Comparative defluorination and cytochrome P-450 loss by the microsomal metabolism of fluoro- and fluorochloroethenes.

Halogenated ethenes are oxidatively metabolized by cytochrome P-450 to intermediates which inactivate cytochrome P-450 by destroying heme and to epoxides which may react with cellular macromolecules or decompose to other products. To determine the relative capabilities of fluoroethenes to inactivate cytochrome P-450 and undergo metabolism, fluoride release, cytochrome P-450 loss, and heme loss due to the metabolism of trifluorochloroethene (TFCE), chlorodifluoroethene (CDE), difluoroethene (DFE), and trifluoroethene (TFE) were compared in rat hepatic microsomes. Fluoride release, in order of decreasing amounts of fluoride released, followed the order: CDE greater than TFCE much greater than TFE greater than DFE. In contrast, in order of each compound's decreasing effectiveness to destroy both cytochrome P-450 and heme, the following sequence was obtained: TFE greater than CDE greater than TFCE greater than DFE. In phenobarbital-induced hepatic microsomes, TFE inactivated up to 67% of the cytochrome P-450, whereas DFE inactivated only up to 17%. The results of this study indicate that chloro substituents enhance defluorination of the ethenes, and that cytochrome P-450 inactivation by the fluoroethenes is highly dependent on the degree and nature of the halogen substituents.

Animals↗
PubMedDate not supplied

Metabolic activation of the halothane metabolite, [14C]2-chloro-1,1-difluoroethene, in hepatic microsomes.

Halothane is reduced to 2-chloro-1,1,1-trifluoroethane (CTE) and 2-chloro-1,1-difluoroethene (CDE) by cytochrome P-450. These compounds may potentially undergo secondary metabolism in vivo, but their capacity to undergo metabolic activation and bind to macromolecules is unknown. This study, therefore, compared the abilities of CDE and CTE to bind to microsomal components in relation to that of halothane in hepatic microsomes. The results show that CDE, in addition to halothane, binds to microsomes under conditions of cytochrome P-450 activity. While halothane bound predominantly to lipids under nitrogen, CDE bound mainly to protein under oxygen. No CTE binding under any conditions could be detected. On an equimolar basis, CDE binding to protein was approximately one-third of that of halothane under oxidative conditions, however, CDE binding was enhanced in the presence of halothane. The results support the hypothesis that CDE metabolism may contribute to the metabolic binding due to halothane exposures.

Anaerobiosis↗