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Biomedical subjects

A W Jones

Publications and source records attributed to A W Jones.

At least 55 records · Page 3Linked to original sources
PubMed2000

Within- and between-subject variations in pharmacokinetic parameters of ethanol by analysis of breath, venous blood and urine.

AIMS: To evaluate the prerequisites for using ethanol dilution to estimate total body water, we studied the within- and between-subject variation in the parameter estimates of a two-compartment model for ethanol pharmacokinetics with parallel Michaelis-Menten and first-order renal elimination. Because sampling of breath might be preferable in some clinical situations the parameter estimates derived from breath and venous blood were compared. METHODS: On two occasions, ethanol 0.4 g kg-1 was given by intravenous infusion to 16 volunteers after they had fasted overnight. The proposed model was fitted by means of nonlinear regression to concentration-time data measured in the breath, venous blood and urine during 360 min. The model contained six parameters: Vmax and Km (Michaelis-Menten elimination constants), CLd (intercompartmental distribution parameter), VC and VT (volumes of the central and tissue compartment, respectively) and CLR (renal clearance). The volume of distribution, Vss, was calculated as the sum of VC and VT. RESULTS: The mean +/- total s.d. of the parameter estimates derived from blood data were Vmax 95 +/- 25 mg min-1, Km 27 +/- 19 mg l-1, CLd 809 +/- 232 ml min-1, VC 14.5 +/- 4.3 l, VT 21. 2 +/- 4.4 l, CLR 3.6 +/- 2.0 ml min-1 and Vss 35.8 +/- 4.3 l. The variation within subjects amounted to 3%, 9%, 21%, 21%, 17%, 26% and 2%, respectively, of the total variation. Breath samples were associated with a similar or lower variation than blood, both within and between subjects. About 1.5% of the infused ethanol was recovered in the urine. CONCLUSIONS: The low within-subject variation of the key parameter Vss (only 2%) suggests that ethanol dilution analysed by the pharmacokinetic model applied here may be used as an index of the total body water. Breath samples yielded at least as good reproducibility in the model parameters as venous blood.

Adult↗
PubMed2000

Ethanol metabolism in patients with liver cirrhosis.

Aspects of human metabolism of ethanol are reviewed with the main focus on the rate of ethanol clearance from blood in patients suffering from liver cirrhosis. Studies in humans and experimental animals do not support the notion of a slower rate of ethanol metabolism in patients with liver cirrhosis compared with those with normal liver function. The rate of ethanol disappearance from blood in healthy non-alcoholic subjects falls within the range 9-20 mg/dL/h and there is no compelling evidence to suggest that this should be much different in cirrhotic patients.

Journal Article↗
PubMed2000

Misleading results of ethanol analysis in urine specimens from rape victims suffering from diabetes.

We report appreciably high concentrations of ethanol (82 and 102 mg/dL) in specimens of urine collected from two victims of date rape. Both girls (aged 15 and 18 years) suffered from diabetes mellitus, but adamantly denied drinking any alcohol before or after the incident. The presence of glycosuria and high risk of fungal infections in female diabetics suggests that ethanol was produced in vitro by fermentation after voiding. Making a routine test for sugar in the urine and ensuring that the sampling tubes contain sufficient sodium or potassium fluoride to inhibit glycolysis are recommended practices. A specific marker for post-sampling synthesis of ethanol might also be used such as the 5HTOL/5HIAA ratio.

Journal Article↗
PubMed2000

Selective transport of adenosine into porcine coronary smooth muscle.

Adenosine (ADO), an endogenous regulator of coronary vascular tone, enhances vasorelaxation in the presence of nucleoside transport inhibitors such as dipyridamole. We tested the hypothesis that coronary smooth muscle (CSM) contains a high-affinity transporter for ADO. ADO-mediated relaxation of isolated large and small porcine coronary artery rings was enhanced 12-fold and 3.4-fold, respectively, by the transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI). Enhanced relaxation was independent of endothelium and was selective for ADO over synthetic analogs. Uptake of [(3)H]ADO into freshly dissociated CSM cells or endothelium-denuded rings was linear and concentration dependent. Kinetic analysis yielded a maximum uptake (V(max)) of 67 +/- 7.0 pmol. mg protein(-1). min(-1) and a Michaelis constant (K(m)) of 10. 5 +/- 5.8 microM in isolated cells and a V(max) of 5.1 +/- 0.5 pmol. min(-1). mg wet wt(-1) and a K(m) of 17.6 +/- 2.6 microM in intact rings. NBTI inhibited transport into small arteries (IC(50) = 42 nM) and cells. Analyses of extracellular space and diffusion kinetics using [(3)H]sucrose indicate the V(max) and K(m) for ADO transport are sufficient to clear a significant amount of extracellular adenosine. These data indicate CSM possess a high-affinity nucleoside transporter and that the activity of this transporter is sufficient to modulate ADO sensitivity of large and small coronary arteries.

2-Chloroadenosine↗
PubMed2000

Endogenous ethanol 'auto-brewery syndrome' as a drunk-driving defence challenge.

The concentration of ethanol in blood, breath or urine constitutes important evidence for prosecuting drunk drivers. For various reasons, the reliability of the results of forensic alcohol analysis are often challenged by the defence. One such argument for acquittal concerns the notion that alcohol could be produced naturally in the body, hence the term 'auto-brewery' syndrome. Although yeasts such as Candida albicans readily produce ethanol in-vitro, whether this happens to any measurable extent in healthy ambulatory subjects is an open question. Over the years, many determinations of endogenous ethanol have been made, and in a few rare instances (Japanese subjects with very serious yeast infections) an abnormally high ethanol concentration (> 80 mg/dl) has been reported. In these atypical individuals, endogenous ethanol appeared to have been produced after they had eaten carbohydrate-rich foods. A particular genetic polymorphism resulting in reduced activity of enzymes involved in hepatic metabolism of ethanol and a negligible first-pass metabolism might explain ethnic differences in rates of endogenous ethanol production and clearance. Other reports of finding abnormally high concentrations of ethanol in body fluids from ostensibly healthy subjects suffer from deficiencies in study design and lack suitable control experiments or used non-specific analytical methods. With reliable gas chromatographic methods of analysis, the concentrations of endogenous ethanol in peripheral venous blood of healthy individuals, as well as those suffering from various metabolic disorders (diabetes, hepatitis, cirrhosis) ranged from 0-0.08 mg/dl. These concentrations are far too low to have any forensic or medical significance. The notion that a motorist's state of intoxication was caused by endogenously produced ethanol lacks merit.

Adult↗
PubMed1999

Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride.

AIMS: To examine the influence of cisapride on the pharmacokinetics of ethanol and the impact of gastric emptying monitored by the paracetamol absorption test. METHODS: Ten healthy male volunteers took part in a cross-over design experiment. They drank a moderate dose of ethanol 0.30 g kg-1 body weight exactly 1 h after eating breakfast either without any prior drug treatment or after taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption of ethanol to monitor gastric emptying. Venous blood was obtained at 5-10 min intervals for determination of ethanol by headspace gas chromatography and paracetamol was analysed in serum by high performance liquid chromatography (h.p.l.c.). Results The maximum blood-ethanol concentration (Cmax ) increased from 3.8+/-1.7 to 5.6+/-2.3 mmol l-1 (+/-s.d.) after treatment with cisapride (95% confidence interval CI on mean difference 0.28-3.28 mmol l-1 ). The area under the blood-ethanol curve (AUC) increased from 6.3+/-3.5 to 7.9+/-2.6 mmol l-1 h after cisapride (95% CI -0. 74-3.9 mmol l-1 h). The mean blood ethanol curves in the cisapride and no-drug sessions converged at approximately 2 h after the start of drinking. Both Cmax and AUC were highest when the ethanol was ingested on an empty stomach (Cmax 9.5+/-1.7 mmol l-1 and AUC 14. 6+/-1.9 mmol l-1 h), compared with drinking 1 h after a meal and regardless of pretreatment with cisapride. CONCLUSIONS: A small but statistically significant increase in Cmax occurred after treatment with cisapride owing to faster gastric emptying rate as shown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in Cmax and AUC, was greatest after drinking the alcohol on an empty stomach. The cisapride-ethanol interaction probably lacks any clinical or forensic significance.

Acetaminophen↗
PubMed1999

Storage of specimens at 4 degrees C or addition of sodium fluoride (1%) prevents formation of ethanol in urine inoculated with Candida albicans.

The microbial synthesis of ethanol was investigated in urine specimens containing 0.5% or 1.0% (w/v) glucose and inoculated with the yeast Candida albicans (100 cfu/mL). Aliquots (10 mL) of urine were dispensed into plastic tubes containing enough sodium fluoride to give final concentrations of 0.1%, 0.25%, 0.5%, 0.75%, 1%, and 2% (w/v), and C. albicans was added. The tubes were tightly stoppered and allowed to stand either at room temperature (22 degrees C) or in a refrigerator (4 degrees C) for up to 34 days before concentrations of ethanol were determined by headspace gas chromatography. Urine samples stored at 22 degrees C without sodium fluoride produced 0.25 g/L ethanol after two days, and the concentration increased to 2.10 g/L and 4.50 g/L after eight days for specimens containing 0.5% (w/v) and 1% (w/v) glucose, respectively. The ratio of the serotonin metabolites 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5HTOL/5HIAA) in urine remained within the reference range (< 15 pmol/nmol) despite high concentrations of ethanol being produced. Urine samples kept at 4 degrees C did not produce any ethanol (< 0.01 g/L) even without sodium fluoride present as a preservative. The production of ethanol by C. albicans was stopped completely by adding 1% or 2% (w/v) sodium fluoride but not by concentrations of 0.75% (w/v) or less. The microbial synthesis of ethanol in urine samples initially stored at room temperature without sodium fluoride was slowed down considerably by moving them into a refrigerator at 4 degrees C. In conclusion, the production of ethanol in urine by C. albicans can be prevented by storage of samples in a refrigerator at 4 degrees C or by adding sodium fluoride > or = 1% (w/v). Measuring the ratio of 5HTOL/5HIAA can help to distinguish postsampling production of ethanol from metabolism and excretion processes.

Candida albicans↗
PubMed1999

The effect of hypermetabolism induced by burn trauma on the ethanol-oxidizing capacity of the liver.

OBJECTIVE: To study the rate of elimination of ethanol after a major burn trauma. DESIGN: Prospective, controlled study. SETTING: National burns unit in a Swedish university hospital. PATIENTS AND SUBJECTS: Eight consecutive patients suffering from 18%-72% total burned surface area and nine healthy male control subjects. INTERVENTIONS: The patients received ethanol, 0.35-0.60 g/kg body weight intravenously, during 1 hr. This was repeated daily during the first week postburn. The control subjects received the same amount of ethanol once. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn at 20- to 30-min intervals during 5 hrs after the start of the infusion. Serum ethanol was determined by headspace gas chromatography. The rate of elimination of ethanol was calculated from the concentration time profile. In the control subjects, the median elimination rate was 0.074 g/kg/hr (range, 0.059-0.083 g/kg/hr). In the patients, it was already 0.138 g/kg/hr (range, 0.111-0.201 g/kg/hr) on the first day; this increased even further over the following 6 days, reaching 0.183 g/kg/hr (range, 0.150-0.218 g/kg/hr) on the seventh day. CONCLUSIONS: Ethanol elimination is augmented postburn. A more effective reoxidation of reduced nicotinamide adenine dinucleotide seems the most likely explanation for the increased rate of ethanol elimination in these hypermetabolic trauma patients. This finding suggests that the oxidative capacity of the liver may be assessed by studying the rate of ethanol elimination in burn victims.

Adult↗
PubMed1999

Endothelin-1 sensitivity of porcine coronary arteries is reduced by exercise training and is gender dependent.

We tested the hypothesis that exercise training reduces the sensitivity of coronary smooth muscle to endothelin-1 (ET-1), with the adaptation being greater in male than in female miniature swine. The efficacy of training was similar in males and females. Cumulative ET-1 contractile responses of coronary branches and left circumflex artery were significantly shifted to the right in exercise-trained (Ex) males but not in Ex females. Analyses of the excitatory concentration causing a 50% response (EC(50)) showed a 1.7- to 2.2-fold shift in Ex males with no change in maximum tension. Nonselective blockade of K-channel activity with tetraethylammonium (TEA; 30-50 mM) significantly shifted the EC(50) to a lower concentration in both Ex males (1.25-fold) and Ex females (2.2-fold) but not in sedentary (Sed) groups. Females (combined Sed and Ex) exhibited a greater response to TEA than did combined Sed and Ex males. Changes in [(32)P]phosphatidic acid ([(32)P]PA) provided an indicator of ET-1-induced phospholipase activity. The magnitude of the [(32)P]PA response was reduced by Ex in both males and females without affecting the EC(50). It is concluded that the contractile sensitivity of coronary arteries to ET-1 is influenced by physical activity in a gender-dependent manner. It is unclear why the contractile sensitivity in females was not reduced by Ex as in the males, because Ex significantly affected responses to TEA and ET-1 stimulation of [(32)P]PA production in both males and females. A potential gender difference in K-channel function may contribute to this discrepancy.

Adaptation, Physiological↗
PubMed1999

The drunkest drinking driver in Sweden: blood alcohol concentration 0.545% w/v.

OBJECTIVE: This article examined drinking drivers (N = 81) who had unusually high blood alcohol concentrations (BAC > or = 0.400% w/v) when apprehended. These drinking drivers were investigated in relation to age, gender, weekday and time of day of arrest, amount of alcohol in the body and the rate of disappearance of alcohol from the blood. METHOD: The concentration of ethanol in whole blood was determined in triplicate by headspace gas chromatography and the rate of disappearance of ethanol (burn-off rate) was calculated when two blood specimens were taken about 1 hour apart (mean = 65 minutes, range = 33-110 minutes). RESULTS: Seven of the 81 drunk drivers were women (9%) with a mean age of 40 years (range = 29-52 years) and 74 were men (91%) with a mean age of 44 years (range = 28-68 years). The mean, median and range of BACs for the women were 0.422% w/v, 0.413% w/v and 0.403-0.451% w/v, compared with BACs of 0.425% w/v, 0.416% w/v and 0.400-0.545% w/v for the men, respectively (p > .05). The BAC was not dependent on subjects' age (F = 1.04, 7/73 df, p > .05) nor the weekday when they were apprehended (F = 1.62, 6/74 df, p > .05). Most drunk drivers (49%) were apprehended between 12 noon and 6 PM, 40% were involved in traffic accidents and 17% did not hold a valid driving license. The mean (+/-SD) disappearance rate of ethanol from blood was 0.023% +/- 0.01% w/v per hour (N = 26), with a range of 0.013 to 0.061% w/v per hour. CONCLUSIONS: Drinking alcohol to reach a BAC of 0.400% w/v or more and attempting to drive a motor vehicle indicates an exceptionally high cellular tolerance to the impairment caused by this drug. The alcohol burn-off rate was relatively high in these heavy drinkers (mean = 0.023% w/v per hour), which probably reflects the development of metabolic tolerance as well.

Accidents, Traffic↗
PubMed1999

Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (approximately 0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. An attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt. Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) or a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same or higher than venous BAC (mg/dL). In the post-peak phase, the BAC always exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5-min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.

Adult↗
PubMed1999

Monitoring ethanol exposure in a clinical setting by analysis of blood, breath, saliva, and urine.

BACKGROUND: Several new technologies have been developed for estimating blood alcohol concentration (BAC), among others, by the analysis of alcohol in saliva specimens. The Q.E.D. is a new quantitative test designed for measuring ethanol in saliva and promising results have been obtained in various experimental settings. METHODS: In the present study, venous BAC was determined in 28 patients on arrival and when they were discharged from a detoxification unit. The results were compared with breath, saliva, and urine alcohol concentrations. Headspace gas chromatography was used for analysis of ethanol in blood and urine, and breath alcohol was determined with an Alcolmeter S-D2 instrument. RESULTS: The concentration of alcohol in urine was always higher than the BAC (mean difference, 0.62 mg/ml) and individual values were highly correlated (n=42; r=0.92). The handheld breath-alcohol instrument (Alcolmeter S-D2) showed good agreement with venous BAC (n=52; r=0.97; mean difference, 0.04 mg/ml). The saliva-alcohol test failed to perform well in our tests (n=36; r=0.75; mean difference, 0.55 mg/ml) mainly because of problems encountered in obtaining a sufficient sample for analysis in highly intoxicated patients. CONCLUSIONS: Because of the relatively low cost of the Q.E.D. ' saliva test, in comparison with a breath alcohol analyzer, the saliva test could be a cost-effective alternative in public health settings where mildly to moderately intoxicated persons are encountered.

Alcoholism↗
PubMed1999

Time course and reproducibility of urinary excretion profiles of ethanol, methanol, and the ratio of serotonin metabolites after intravenous infusion of ethanol.

BACKGROUND: The aim of this study was to determine the time course and reproducibility of urinary excretion profiles of ethanol, methanol, and ratio of serotonin metabolites, 5-hydroxytryptophol (5HTOL) to 5-hydroxyindoleacetic acid (5HIAA), under strictly controlled conditions. METHODS: Nine healthy volunteers (6 women and 3 men) received 0.40 g of ethanol/kg of body weight on two occasions by constant rate intravenous infusion 30 min. Urine was voided before administration of ethanol and thereafter every 60 min for a total of 8 hr. Concentrations of ethanol and methanol in urine were determined by headspace gas chromatography, and the serotonin metabolites 5HTOL and 5HIAA were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively. RESULTS: The peak concentration of ethanol in urine occurred at 30 or 60 min after the infusion ended. The peak concentration of methanol and the 5HTOL/5HIAA ratio developed more gradually, reaching a plateau at 213 to 220 min and 200 to 220 min postinfusion, respectively. The concentration-time profiles of ethanol and the 5HTOL/5HIAA ratio varied more between subjects than within subjects (p < 0.001), whereas the inter- and intraindividual variation in the pharmacokinetics of methanol were not significantly different (p > 0.05). The concentration of methanol and the 5HTOL/5HIAA ratio remained above the endogenous levels at 8-hr postinfusion despite the fact that urinary ethanol was no longer measurable (<0.01 g/liter) after 5 to 6 hr. CONCLUSIONS: Measuring the concentrations of methanol and the ratio of serotonin metabolites (5HTOL/5HIAA) in urine is a more sensitive way to monitor recent drinking, compared with analysis of ethanol in body fluids. Moreover, the concentration-time profiles of methanol and the 5HTOL/5HIAA ratio showed a good test-retest stability. The present intravenous infusion experiment confirms previous work on these markers when ethanol was given perorally. The urinary methanol and the 5HTOL/5HIAA ratio have applications in forensic and clinical medicine as indicators of acute alcohol consumption.

Adult↗