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Biomedical subjects

A W Jones

Publications and source records attributed to A W Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

Changes in the concentrations of ethanol, methanol and metabolites of serotonin in two successive urinary voids from drinking drivers.

The urine-ethanol concentration (UEC), the urine-methanol concentration (UMC) and the ratio of serotonin metabolites, 5-hydroxytryptophol (5HTOL) to 5-hydroxyindoleacetic acid (5HIAA), were determined in two successive voids from apprehended drunk drivers (n = 35). The blood-ethanol concentration (BEC) ranged from 0-3.00 g/l (mean 1.87 g/l, median 2.03 g/l) compared with 0-3.96 g/l (mean 2.48 g/l, median 2.73 g/l) in the first urinary void and 0-3.56 g/l (mean 2.24 g/l, median 2.47 g/l) in the second void. The UEC decreased significantly from 2.48 +/- 0.99 g/l to 2.24 +/- 0.95 g/l (mean +/- S.D.) between first and second voids as did the UEC/BEC ratios, changing from 1.33 +/- 0.15 to 1.20 +/- 0.10. The BEC and UEC were highly correlated; r = 0.97 +/- 0.04 (p < 0.001) for the first void and r = 0.98 +/- 0.03 (p < 0.001) for the second void. The UMC increased from 7.51 +/- 4.95 mg/l to 8.01 +/- 5.04 mg/l between the first and second voids and the mean difference of 0.50 +/- 0.78 mg/l was statistically highly significant (p < 0.001). The ratios of 5HTOL/5HIAA were 771 +/- 363 pmol/nmol and 728 +/- 377 pmol/nmol in first and second voids, respectively and the difference was not statistically significant (p > 0.05). Finding raised concentrations of methanol and a high 5HTOL/5HIAA ratio in urine specimens provides additional evidence to confirm recent drinking. These biochemical markers might prove useful whenever the integrity of blood or urine specimens is questioned, for example, owing to contamination with extraneous ethanol during collection or microbial synthesis of ethanol in vitro after sampling.

Alcoholic Intoxication↗
PubMed1998

Referral patterns and recognition of depression among African-American and Caucasian patients.

A retrospective review of psychiatric consultations was conducted for African-American and Caucasian patients for a 2-year period. Reasons for referral, assigned diagnoses, accuracy rates, and discordance and concordance rates were assessed. Referrals for depression comprised 24.6% of all consults for Caucasian and African-American inpatients. Only 40.3% of patients referred for depression were diagnosed with a depressive disorder; 54.4% of patients diagnosed with depressive disorders were referred for other reasons. African-American patients were referred for evaluation of depression and diagnosed with depressive disorders significantly less often than Caucasian patients. No significant differences were obtained between African-Americans and Caucasians in the accuracy rates of patients referred for depression. Discordance and concordance rates for the two groups were comparable. Diagnoses assigned to African-Americans and Caucasians incorrectly referred for depression did not differ significantly. For depressed African-Americans and Caucasians referred for reasons other than depression, the only difference noted was in the referral rates for adjustment of psychotropics. The nonpsychiatric staff fails to recognize depression and often refer depressed patients inappropriately. Depressed patients are primarily referred for suicide assessment and disruptive behaviors. Referrals for depression may be a secondary concern to nonpsychiatric staff. In addition, cultural variables and racial differences between hospital staff and patients may account for the differences in referral patterns. Awareness of the needs of African-American patients is required.

Black or African American↗
PubMed1998

Endothelin-1 activates phospholipases and channels at similar concentrations in porcine coronary arteries.

Sensitivity of endothelin-1 (ET-1)-ion channel interactions has been proposed to exceed that of ET-1-phospholipase activation in vascular smooth muscle. We wanted to determine whether short-circuiting ion channels with staphylococcal alpha-toxin pores would shift the ET-1-force relation to the right as predicted from the above proposal. Medium size porcine coronary arteries (outer diameter 0.7-1.5 mm) were mounted on isometric force transducers. ET-1 concentration response curves were compared between intact rings and those subjected to alpha-toxin treatment with Ca buffered at 0.1 microM. The EC50 for treated rings (1.5 +/- 1.0 nM, n = 5 pigs) was similar to that for intact rings (1.9 +/- 0.4 nM). The Ca sensitivity of the alpha-toxin-treated rings (EC50 = 0.43 +/- 0.08 microM) was similar to that reported by other laboratories for intact and alpha-toxin-treated arteries and was shifted eightfold to the left by a high concentration of ET-1 (10 nM). Measurements of [32P]phosphatidic acid ([32P]PA) levels were used to evaluate phospholipase activity in intact arteries. The time courses for [32P]PA production and contraction were similar in response to high (100 nM) and to low (1 nM) ET-1. Significant increases in both steady-state contraction and [32P]PA occurred over a wide range of ET-1 concentrations tested (0.3-100 nM). Our findings support the concept that ET-1-phospholipase coupling is operative over the whole concentration range that induces contractile responses. It is suggested that both Ca entry and Ca sensitization processes are activated by ET-1 at low concentrations (<EC50) and that both processes contribute significantly to the integrated response.

Animals↗
PubMed1997

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis.

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (i.v.) infusion over 45 min. After removing a mean fluid volume of 2.46 +/- 0.48 liters (+/- SD), span 1.76-3.43 liters by hemodialysis, the same subjects received a second i.v. infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05-1.10). The rate of ethanol disappearance from blood (beta-slope) was faster (0.185 +/- 0.013 versus 0.157 +/- 0.022 g/l/h), the Co value was higher (0.79 +/- 0.08 versus 0.73 +/- 0.10 g/l) and the apparent volume of distribution (Vd) of ethanol was lower (0.507 +/- 0.049 versus 0.558 +/- 0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher (P < 0.001) before dialysis (88.6 +/- 1.97 g/100 ml) compared with after dialysis (87.4 +/- 2.01 g/100 ml). The higher Vd for ethanol and lower Co as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood (beta-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.

Central Nervous System Depressants↗
PubMed1997

Mechanisms of altered contractile responses to vasopressin and endothelin in canine coronary collateral arteries.

BACKGROUND: Mature coronary collateral arteries are hyperresponsive to vasopressin; in contrast, contractile responses of collaterals to endothelin are attenuated. Our goal was to determine the cellular mechanisms underlying these differences in reactivity using two sizes of canine collateral arteries isolated from hearts subjected to chronic coronary occlusion. METHODS AND RESULTS: Contractile responses to vasopressin (100 mmol/L) were enhanced threefold to fourfold in near-resistance (approximately 200 microns lumen diameter) and conduit (approximately 500 microns lumen diameter) collateral arteries compared with similarly sized noncollateral coronary arteries (P < .01). In contrast, contractions of both sizes of collaterals in response to endothelin (0.01 to 30 nmol/L) were smaller than responses of size-matched noncollateral arteries (P < .05). Pretreatment with either indomethacin (5 mumol/L), a cyclooxygenase inhibitor, or NG-nitro-L-arginine methyl ester (100 mumol/L), a nitric oxide synthase inhibitor, did not alter the relative responsiveness of collateral arteries to vasopressin or endothelin compared with noncollateral arteries. Vasopressin produced greater increases of intracellular free Ca2+ (measured by use of fura-2 microfluorometry and Ca(2+)-dependent 42K+ efflux) in smooth muscle of collateral arteries than in smooth muscle of noncollateral arteries (P < .05). Surprisingly, endothelin-induced increases of Ca2+ were not different in smooth muscle of collateral and noncollateral arteries (P > .05). CONCLUSIONS: We conclude that altered contractile responsiveness of collateral arteries to vasopressin and endothelin does not result from altered synthesis/release of nitric oxide or prostaglandins. Parallel enhancement of vasopressin-mediated Ca2+ and contractile responses suggests increases in vasopressin receptor number, affinity, and/or efficiency of coupling mechanisms in collateral smooth muscle. The dissociation between endothelin-induced contractile and Ca2+ responses of collaterals indicates that the mechanisms involved in increasing Ca2+ sensitivity of contractile proteins during endothelin stimulation may be altered in collateral arteries.

Animals↗
PubMed1997

Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying.

OBJECTIVE: To determine if treatment with low-dose aspirin (ASA) influences the bioavailability of orally administered alcohol and to assess whether this is caused by altered gastric emptying as measured by the paracetamol absorption test. METHODS: In a single-center controlled crossover trial, ten healthy male medical students, aged 20-27 years, participated in two experiments in random order. Both times they took paracetamol (1.5 g together with a standardized breakfast) and drank ethanol (0.3 g/kg) 1 h after eating breakfast. On one drinking occasion, no previous medication was given. The other alcohol session was performed after the subjects had taken 75 mg ASA once daily for 7 days. On both occasions, venous blood samples were obtained at exactly timed intervals for a period of 3.5 h. RESULTS: The blood-ethanol profiles showed large interindividual variations for both experiments. After treatment with ASA, the maximum blood-ethanol concentration was distinctly lower in seven subjects, almost unchanged in two subjects and increased in one subject. Overall, a statistically significant decrease in the peak blood-ethanol concentration was observed. The time required to reach peak blood-ethanol levels was somewhat longer after treatment with ASA. Although the areas under the concentration-time profiles were smaller after ASA treatment, these differences were not statistically significant. The concentrations of paracetamol in plasma were lower when ethanol was ingested after treatment with ASA and the areas under the concentration-time curves (0-170 min) were smaller. CONCLUSIONS: Intake of low-dose ASA (75 mg daily) tends to delay the absorption of a moderate dose of ethanol, which results in lower peak blood-ethanol concentrations and smaller areas under the concentration-time curves. The underlying mechanism seems to be delayed gastric emptying as indicated by the paracetamol absorption test.

Acetaminophen↗
PubMed1997

Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol.

AIMS: To investigate whether the relative amounts of fat, carbohydrate (CHO), or protein in a meal influence the pharmacokinetics of a small dose of ethanol. METHODS: Nine healthy men received ethanol (0.30 g kg-1 body weight) on five occasions in a randomized cross-over fashion. On three occasions the dose of ethanol was consumed within 15 min of eating a standardized breakfast of similar volume and calorific value but containing different amounts of fat, CHO, and protein. On two other occasions the same dose of ethanol was ingested on an empty stomach (overnight fast) or administered by intravenous (i.v.) infusion over 30 min. RESULTS: The blood-ethanol profiles showed large inter and intraindividual variations, especially when ethanol was ingested after eating food. The peak blood-alcohol concentrations (BAC) were 16.6 +/- 4.0, 17.7 +/- 7.1, and 13.3 +/- 4.0 mg dl-1 (mean +/- s.d.) after fat, CHO, and protein-rich meals and 30.8 +/- 4.3 and 54.3 +/- 6.4 mg dl-1 after fasting and i.v. infusion, respectively. The corresponding areas under the concentration-time profiles (AUC) were 1767 +/ -549, 1619 +/- 760 1270 +/- 406 mg dl-1 min after fat, CHO, and protein-rich meals compared with 3210 +/- 527 and 4786 +/- 446 mg dl-1 min after fasting and i.v. infusion, respectively. The time required to eliminate ethanol from the blood was shortened by 1-2 h in the fed-state. CONCLUSIONS: Drinking ethanol after eating a meal, regardless of the nutritional composition, decreases the systemic availability of ethanol. Because gastric emptying is slow and more prolonged with food in the stomach, the delivery of ethanol to the duodenum and the liver will be highly variable as will the hepatic clearance of ethanol. Provided that portal venous BAC remains fairly low and ethanol metabolizing enzymes are not fully saturated then part of the dose of ethanol can be cleared by hepatic first-pass metabolism (FPM), as one consequence of Michaelis-Menten elimination kinetics.

Administration, Oral↗
PubMed1997

Altered reactivity of coronary arteries located distal to a chronic coronary occlusion.

The coronary vasculature located distal to a chronic occlusion (collateral-dependent) has been shown to exhibit altered reactivity to vasoactive agonists. Thus we evaluated effects of chronic coronary artery occlusion on vasomotor responsiveness of collateral-dependent arteries isolated from a canine model of Ameroid occlusion of the left circumflex (LCX) coronary artery. We compared in vitro responses of large (approximately 1.3- to 1.4-mm-ID) and small (approximately 0.6-mm-ID) LCX arteries located distal to an occlusion with responses of similar-sized segments of the unoccluded left anterior descending (LAD) coronary artery. Alpha-adrenergic receptor-mediated contractile responses to norepinephrine (10(-9)-10(-4) M) and phenylephine (10(-9)-10(-4) M) in the presence of propranolol were markedly enhanced in large LCX arteries compared with LAD arteries (P < 0.001). Prazosin (1 microM), an alpha1-adrenergic receptor antagonist, abolished contractile responses of LCX and LAD arteries to norepinephrine. Inhibition of nitric oxide synthesis with N(omega)-nitro-L-arginine methyl ester (100 microM) enhanced norepinephrine-induced contractions of LAD arteries to a greater extent than contractions of LCX arteries. We simultaneously measured myoplasmic free Ca2+ (fura 2 fluorescence ratio) and contractile responses in LCX and LAD arteries denuded of endothelium; norepinephrine-induced increases in myoplasmic free Ca2+ and contractile tension were significantly enhanced in LCX arteries compared with LAD arteries. In addition, large and small LCX arteries exhibited impaired relaxation in response to adenosine (10(-8)-10(-3) M) compared with LAD arteries (P < 0.05). In contrast, relaxation in response to the beta-adrenergic agonist isoproterenol (10(-9)-10(-4) M) and sodium nitroprusside (10(-10)-10(-4) M) was not significantly different in LCX and LAD arteries. Thus collateral-dependent coronary arteries exhibit enhanced alpha-adrenergic vasoconstriction and impaired vasorelaxation in response to adenosine. The enhanced alpha-adrenergic contractile responsiveness involves at least two mechanisms: 1) enhanced alpha1-adrenergic reactivity of smooth muscle and 2) decreased alpha-adrenergic-induced synthesis of nitric oxide by the endothelium.

Adrenergic beta-Agonists↗
PubMed1997

Concentration-time profiles of ethanol in arterial and venous blood and end-expired breath during and after intravenous infusion.

Ethanol (0.40 g/kg) was administered to 13 healthy men by intravenous (i.v.) infusion at a constant rate for 30 min. The concentrations of ethanol in arterial blood (ABAC), venous blood (VBAC), and end-expired breath (BrAC) were measured at 17 exactly timed intervals. Blood-ethanol was determined by headspace gas chromatography and breath-ethanol was measured with a quantitative infrared analyzer (DataMaster). BrAC was multiplied by 2300 to estimate the concentrations of alcohol in blood. During the infusion of ethanol, ABAC exceeded VBAC by about 10 mg/dL on the average and ABAC was also higher than BrAC x 2300 by about 4 mg/dL on average. When infusion of alcohol ended, ABAC, VBAC, and BrAC were 94.8 +/- 2.06 (+/- SE), 84.7 +/- 1.54, and 89.3 +/- 2.10 mg/dL, respectively. The concentrations of alcohol in blood (ABAC and VBAC) and breath decreased abruptly after the administration of alcohol stopped and by 5 min postinfusion, the A-V differences in concentration of ethanol were small or negligible. The mean apparent half-life of the distribution plunge was 7 to 8 min, being about the same for ABAC, VBAC, and BrAC. The disappearance rate of ethanol was 15.5 +/- 0.55 mg/ dL/h (mean +/- SE) for arterial blood, 15.2 +/- 0.49 mg/dL/h for venous blood, and 16.3 +/- 0.73 mg/230 L/h for breath; no significant differences were noted (p > 0.05). We conclude that A-V differences in the concentration of ethanol exist during the loading phase but are rapidly abolished when the administration of ethanol terminates. In the post-absorptive phase of ethanol kinetics, when alcohol has mixed with the total body water, VBAC exceeds ABAC by about 1-2 mg/100 mL on average.

Adult↗
PubMed1996

Phospholipase D in platelets and megakaryocytic cells.

Phospholipase D (PLD) is stimulated in platelets by various agents. Phosphatidylcholine is the major substrate for PLD. This enzymatic pathway generates phosphatidic acid selectively. Guanine nucleotides also stimulate PLD in platelet membranes. Furthermore, tyrosine kinase may also be involved in platelet PLD regulation. It appears that multiple signals acting sequentially or in parallel converge on PLD. Among others, PLD has been proposed to play a role in platelet secretion and PLA2 regulation. PLD is also present in platelet percursor megakaryocytric cells and can be activated by platelet agonists. In these cells both PKC and G-proteins (e.g. Rho) may regulate PLD activity. The significance of PLD in megakaryocytes awaits investigation. These recent developments offer new avenues of research to further elucidate the biochemistry of platelet and megakaryocyte function.

Animals↗
PubMed1996

The life and work of Erik M. P. Widmark.

Erik M. P. Widmark (1889-1945) was among the first researchers to study in a systematic way the absorption, distribution, and elimination of ethanol in the body; in addition, he formulated his results in mathematical terms. Widmark's research during the first decades of this century paved the way for innovative traffic safety legislation that stipulated punishable limits of alcohol in the blood of a person driving a car. The 50th anniversary of Widmark's death was commemorated in 1995. His contributions have gained enormous respect and are still widely cited in forensic science, especially in connection with the crime of driving under the influence of alcohol. The Widmark equations and the factors beta and r are now part of the vocabulary of all those trained in forensic alcohol analysis and toxicology.

Accidents, Traffic↗
PubMed1996

Laboratory testing for recent alcohol consumption: comparison of ethanol, methanol, and 5-hydroxytryptophol.

The ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid (5HTOL/5HIAA) in urine was compared with concentrations of ethanol and methanol as a way to monitor recent alcohol consumption. During detoxification of alcohol-dependent subjects, ethanol persisted longer in urine than in breath or plasma. Blood and urinary methanol remained increased for 2-6 h after blood ethanol had returned to background concentrations, whereas 5HTOL/5HIAA remained increased for 6-15 h. In healthy volunteers who had ingested alcohol (range 3-98 g) the previous afternoon or evening, 87% (for men) and 59% (for women) of all drinking occasions exceeding 7 g of alcohol were identified by an increased 5HTOL/5HIAA in the first morning urine void. This compared with 32% and 12%, respectively, identified by analysis of ethanol (>200 micromol/L). No gender difference in the excretion pattern of 5HTOL/5HIAA was seen. The results demonstrate that 5HTOL/5HIAA provides a specific and more sensitive method to detect recent alcohol consumption than does ethanol or methanol.

Adult↗
PubMed1996

Variability of the blood/breath alcohol ratio in drinking drivers.

The ratio of blood-alcohol concentration (BAC) to breath-alcohol concentration (BrAC) was determined for 799 individuals apprehended for driving under the influence of alcohol (DUI) in Sweden. The BrAC was determined with an infrared analyzer (Intoxilyzer 5000S) and venous BAC was measured by headspace gas chromatography. The blood samples were always taken after the breath tests were made and the average time delay was 30 +/- 12 min (+/- SD), spanning from 6 to 60 min. The blood/breath ratios of alcohol decreased as the time between sampling blood and breath increased (F = 15.4, p < 0.001), being 2337 +/- 183 (6 to 15 min), 2302 +/- 202 (16 to 30 min), 2226 +/- 229 (31 to 45 min), and 2170 +/- 225 (46 to 60 min). When the BAC was corrected for the metabolism of alcohol at a rate of 0.019 g%/h, the mean blood/breath ratios were 2395 +/- 193 (6 to 15 min), 2416 +/- 211 (16 to 30 min), 2406 +/- 223 (31 to 45 min), and 2407 +/- 210 (45 to 60 min); no significant differences (F = 0.197, p > 0.05). The overall mean time-adjusted blood/breath ratio (+/- SD) was 2407 +/- 213 and the 95% limits of agreement (LOA) were 1981 and 2833. During 1992, 1993, and 1994, the mean blood/breath ratios of alcohol were remarkably constant, being 2409 +/- 288, 2407 +/- 206, and 2421 +/- 235, respectively, and the values were not significantly influenced by the person's age, gender, or blood-alcohol content. In 34 individuals (4.3%), the blood/breath ratio was less than 2100 after compensating for metabolism of alcohol between the times of sampling blood and breath. This compares with 156 individuals (19.6%) having a blood/breath ratio less than 2100:1 without making any correction for the metabolism of alcohol.

Adult↗
PubMed1996

Influence of age, gender, and blood-alcohol concentration on the disappearance rate of alcohol from blood in drinking drivers.

The rate of disappearance of alcohol from the blood (beta-slope) was determined in drinking drivers by taking two blood samples about 60 min apart (mean 68 min, span 30 to 120 min). The results were compared for men and women as a function of their age and the prevailing blood-alcohol concentration (BAC). The material consisted of 1090 double blood samples from 976 men and 114 women with mean age 36.6 +/- 12.9 y (+/- SD) and 38.0 +/- 12.3 y (+/- SD), respectively. The mean BAC for the male DUI suspects was 1.88 +/- 0.748 mg/mL (+/- SD) compared with 1.86 +/- 0.702 (+/- SD) for the females. The relationship between beta-slope (y) and BAC (x) was y = 0.175 + 0.009x with a small positive correlation (r = 0.13) and standard error estimate (Syx) of 0.049 mg/mL. The mean beta-slope for female DUI suspects was 0.214 +/- 0.053 mg/mL/h (+/- SD), compared with 0.189 +/- 0.048 mg/mL/h in the male suspects, and this small difference was statistically highly significant (t = 5.21, p < 0.001). The overall mean rate of alcohol elimination from blood in drinking drivers was 0.191 +/- 0.049 mg/mL/h (+/- SD), and the 95% limits of agreement (LOA) spanned from 0.09 to 0.29 mg/mL/h. The value of the beta-slope was slightly steeper starting from a high initial BAC but was not much influenced by the person's age.

Adult↗
PubMed1995

Determination of isoprene in human breath by thermal desorption gas chromatography with ultraviolet detection.

We describe a new, highly sensitive and specific method for the analysis of isoprene (2-methyl-1,3-butadiene) in human breath. A known volume of expired air (150 ml) was drawn through a solid sorbent material to capture trace organic substances, followed by thermal desorption at 200 degrees C and subsequent determination of isoprene by gas chromatography with diode-array ultraviolet detection. The calibration plot was linear (r = 0.99) over a wide range of breath isoprene concentrations (0-12 nmol/l), and levels down to 0.10 nmol/l were easily measurable. In sixteen healthy subjects (six men and ten women), all of whom were non-smokers, the mean, median and spread of breath isoprene concentrations were 3.73, 3.36 and 1.60-10.33 nmol/l, respectively. No statistically significant differences in the concentrations of breath isoprene were observed between the sexes. The mean (+/- S.D.) concentration of breath isoprene in nine consecutive tests with the same subject was 3.69 +/- 0.60 nmol/l, and the coefficient of variation was 16.3%. Much larger variations in exhaled isoprene were seen during the day and also between days when the same subject was tested repeatedly. The excretion patterns of isoprene in human breath can be investigated with high selectivity and sensitivity with this new analytical method.

Breath Tests↗