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Biomedical subjects

S Loft

Publications and source records attributed to S Loft.

102 records · Page 6Linked to original sources

Increased hepatic microsomal activity after halothane anaesthesia in children.

The effect of anaesthesia and surgery on microsomal enzyme activity was studied in 19 children aged 4-9 years, scheduled for tonsillectomy. The children were randomly allocated to either halothane or ketamine anaesthesia. Antipyrine clearance was measured before and 4 days after surgery by a salivary one-sample technique. Statistically significant (p less than 0.001) increases in antipyrine clearance was found in children who received halothane anaesthesia. The antipyrine clearance was increased by a mean of 26% 4 days after surgery, compared with a pre-operative control measurement. No significant change in antipyrine clearance was observed in children who received ketamine anaesthesia. There was also a significant difference in antipyrine clearance changes after surgery between the two groups (p less than 0.05). Halothane has enzyme-inducing properties after a single exposure in children, while a single dose of ketamine does not.

Anesthesia, Inhalation

Inhibition of antipyrine elimination by disulfiram and cimetidine: the effect of concomitant administration.

We investigated the effect of concomitantly administered disulfiram and cimetidine on antipyrine elimination. On day 1, 2, 4 and 6 of two periods of 6 days one sample antipyrine saliva clearance (APC) was measured in nine healthy volunteers. From day 2 to 6 of period I disulfiram 400 mg day-1 was administered and on day 5 and 6 cimetidine 1000 mg day-1 was added. In period II only cimetidine was given (on days 5 and 6). On day 4 of period II APC was increased 1.3 fold, probably due to self-induction by repeated antipyrine administration. Taking this into account disulfiram and cimetidine separately decreased APC 0.64 and 0.70 times, respectively. When both inhibitors were given APC was reduced 0.52 times. The results suggest that the effects of cimetidine and disulfiram on antipyrine elimination are additive.

Adult

Antipyrine clearance in pneumonia.

Antipyrine clearance was estimated by a one-sample technique in 14 patients with acute fever and clinical pneumonia. Antipyrine clearance during the acute illness was 31.4 +/- 7.6 ml/min (X +/- SD). Fourteen and 28 days later during convalescence, clearance values were higher (47.8 +/- 18.9 and 49.2 +/- 15.0 ml/min, respectively). We conclude that microsomal hepatic drug metabolism in adults is impaired during pneumonia.

Adult

Increased hepatic microsomal enzyme activity after surgery under halothane or spinal anesthesia.

Thirty-two fit patients scheduled for explorative arthrotomy of the knee were allocated randomly to either halothane/oxygen anesthesia or spinal anesthesia with bupivacaine 0.25 mg X kg-1. The day before and 1, 10, and 21 days after surgery, the aminopyrine breath test (ABT) was performed. The day before and 5, 10, and 21 days after surgery, the antipyrine clearance (APcl) was measured by the single sample saliva technique. The ABT as well as the APcl were increased significantly postoperatively (P less than 0.01). The day after surgery the ABT was increased by 13 +/- 21% in the spinal anesthesia group only, whereas a late increase by 14 +/- 31% was found in the halothane group. Five days after surgery, the APcl was increased by 36 +/- 45% in the spinal anesthesia group and by 21 +/- 28% in the halothane group. Both tests returned to base line values within 3 weeks postoperatively. In five volunteers following the same sampling scheme but receiving bupivacaine 0.25 mg X kg-1 im without surgery, no change in the ABT or the APcl was observed. The authors conclude that surgery may cause microsomal enzyme induction regardless of the anesthetic agent or technique used. The mechanism of this induction remains to be elucidated.

Adolescent

Antipyrine clearance in children from single saliva samples.

The saliva clearance of antipyrine was measured in 18 children from four samples taken about 9, 13, 22 and 25 h after ingestion of 20 mg kg-1. Antipyrine clearance determined from each of the samples using a volume of distribution estimated from age (A) and body weight (BW) and height (BH) (V = 1.535 X A + 0.339 X BW + 0.300 X BH - 35.63 (1] correlated closely with clearance determined from the total elimination curve (r greater than 0.94). Random variation and systematic deviation were minimal when the 22 h sample was used for clearance determination (r = 0.98, P less than 0.001, regression curve slope = 1.00, intercept = 0.58 and residual variance = 4.02). The one-sample method for determination of antipyrine saliva clearance is non-invasive, easy to perform and acceptable to children.

Antipyrine

Jet fuel and liver function.

The impact of occupational exposure to jet fuel on antipyrine elimination was studied in 91 fuel-filing attendants. The mean antipyrine clearance was enhanced to 68.4 (SD 19.5) ml/min during exposure to jet fuel compared to 57.9 (SD 18.1) ml/min after an exposure-free period of two to four weeks. The corresponding values for 47 office workers (referents) were 62.7 (SD 22.2) ml/min and 56.4 (SD 22.3) ml/min. The median jet fuel concentration in the breathing zone of the fuel-filling attendants was 31 (range 1-1 020) mg/m3. No known inducing factor could be identified in the work environment of the office workers. No difference in the concentration of aspartate aminotransferase and alkaline phosphatase in serum was found either within or between the groups. Our study indicates that jet fuel, which is a mixture of aliphatic and aromatic organic solvents resembling gasoline and white spirit, is an inducer of hepatic drug metabolism in man.

Aerospace Medicine

Influence of moderate alcohol intake on wakening plasma thiopental concentration.

In an earlier study, an inverse correlation between thiopental-induced sleeping time and alcohol intake in the preceding week was demonstrated in women undergoing termination of pregnancy. In order to investigate the mechanism behind the apparent cross-tolerance, the relationship between alcohol consumption in the week preceding thiopental/nitrous oxide/oxygen anesthesia and wakening plasma thiopental concentration on one hand and sleeping time on the other was examined in 68 women scheduled for termination of pregnancy and in 37 women scheduled for diagnostic uterine dilatation and curettage. In terms of pure alcohol, the weekly intake (mean +/- s.d.) was 1.17 +/- 2.07 ml . kg-1 in the former and 1.49 +/- 1.70 ml . kg-1 in the latter group. A positive correlation between alcohol consumption and wakening plasma thiopental concentration was found in both groups, reaching statistical significance (P less than 0.05) in the group undergoing termination of pregnancy, but not in the other. The inverse correlation found earlier between alcohol intake and sleeping time was not reproduced significantly in any of the groups. The results indicate that moderate alcohol intake may induce cerebral tolerance to thiopental.

Abortion, Induced

Influence of moderate alcohol intake on thiopental anesthesia.

The relationship between alcohol intake over the week preceding anesthesia and various anesthetic parameters was examined in 119 women scheduled for termination of pregnancy under thiopental-nitrous oxide anesthesia. In terms of pure alcohol, the weekly intake was 1.03 +/- 1.09 ml.kg-1 (mean +/- s.d.), range 0-5.93, i.e. below average consumption in Denmark. Alcohol intake was negatively correlated with anesthetic sleeping time (P less than 0.01). Time and quality of anesthesia induction and frequency of anesthetic complications were not significantly correlated with the use of alcohol. Preanesthetic anxiety was not significantly correlated with any of the above data. Induction time and postoperative awareness were positively and sleeping time negatively correlated with age (P less than 0.05). The results indicate cross-tolerance between alcohol and thiopental, even when the regular intake of the former is low, and increasing thiopental requirements with increasing age.

Abortion, Induced

8-Hydroxydeoxyguanosine as a urinary biomarker of oxidative DNA damage.

Living organisms are continuously exposed to reactive oxygen species as a consequence of biochemical reactions as well as external factors. Oxidative DNA damage has been implicated in aging, carcinogenesis and other degenerative diseases. The urinary excretion of the DNA repair product 8-hydroxydeoxyguanosine (8OHdG) has been proposed as a noninvasive biomarker of oxidative DNA damage in humans in vivo. We have developed a three-dimensional HPLC analysis with electrochemical detection for the analysis of 8OHdG in urine and studied factors affecting the excretion of this biomarker in 83 healthy humans and in various laboratory animals, including dog, pig, and rat. Previously, other groups have used comparable HPLC methods or gas chromatography-mass spectrometry with selective ion monitoring for measuring the excretion of 8OHdG in humans, rats, mice, and monkeys. In the 169 humans studied so far, the average 8OHdG excretion was 200-300 pmol/kg per 24 h with a sevenfold range, and the coefficient of variation was 30-40%. This excretion corresponds 140-200 oxidative modification of guanine bases per cell per day. Thirty-two smokers from our study population excreted 50% (31-69%; 95% confidence interval) more 8OHdG than 53 nonsmokers. This indicates a 50% increased rate of oxidative DNA damage from smoking, adding to the other well-known health hazards of smoking. The biochemical-physiological basis is unknown but may be related to smoke constituents including or generating reactive oxygen species and/or consuming antioxidants and/or the well-known enhancing effect of smoking on the metabolic rate. In our 83 healthy subjects the 8OHdG excretion correlated with body composition. Thus, lean and/or male subjects excreted more than obese and/or female subjects, possibly related to differences in metabolic rate. In accordance, the excretion of 8OHdG decreased after calorie restriction, which will cause a decline in the metabolic rate. Across the investigated species, humans, dogs, pigs, and rats, the excretion of 8OHdG correlated with the specific metabolic rate, confirming data from other groups on humans, monkeys, rats, and mice. The excretion of 8OHdG decreased with age in rats in parallel with the decline in metabolic rate with advancing age. The excretion of 8OHdG reflects the formation and repair of only one out of approximately 20 described oxidative DNA modifications. So far, methods are not available for the determination of the corresponding repair products, except 8OHdG and thymidine glycol, in urine. Moreover, the importance in terms of mutagenicity, particularly regarding tumour suppressor genes and oncogenes, is mainly documented for 8OHdG in DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Hydroxy-2'-Deoxyguanosine

Energy restriction and oxidative DNA damage in humans.

The cancer-preventive effect of energy restriction in rodents has been related to a decrease in oxidative damage to DNA. We have investigated the effect of energy restriction on the rate of oxidative DNA modification estimated from the urinary excretion of the repair product, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in healthy, normal weight men. Before and after 10 weeks on a diet containing 80 (n = 16) or 100% (n = 8) of the estimated weight-maintaining energy, resting metabolic rate (RMR) was measured and 24-h urine was collected for 8-oxodG determination by HPLC. During the study, the weight loss was 10 and 2.5% of the initial weight, mostly in terms of fat, and the RMR decreased by 13 and 8% in the energy-restricted and control groups, respectively. With the use of t tests there was no significant difference within or between groups with respect to 8-oxodG excretion. However, if RMR was included as a covariate in multifactorial ANOVA, an average relative 17% (2-31%; 95% confidence interval) increase in 8-oxodG excretion in the energy-restricted group was significantly different from the corresponding value of the control group (P < 0.02). In the energy-restricted group the change in 8-oxodG excretion was correlated closely with the decrease in RMR (r = 0.63; P = 0.013). In the present study, 20% energy restriction for 10 weeks did not reduce oxidative DNA damage; we question a beneficial effect on cancer risk in normal weight humans.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2'-Deoxyguanosine