Search Results - (Author, Cooperation:D. J. Morgan)

2016-02-16

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

2016-02-27

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

1471-0528

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Objective To determine the longitudinal changes in the incidence of bacterial vaginosis in pregnancy.Design A prospective study of women during pregnancy.Setting A District General Hospital in North-West London.Subject Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture.Results Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10 (59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P 〈 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P 〈 0.001).Conclusion Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.

Electronic Resource

1365-2494

Blackwell Publishing Journal Backfiles 1879-2005

Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition

Four sheep in a 4 × 4 Latin Square experiment were offered ad libitum grass meal pellets alone or supplemented with lactic acid at 600, 800 or 1000 mmol per kg dry matter (DM) intake, either mixed into the feed or continuously infused intraruminally for 6-d periods. When added to the feed lactic acid did not significantly affect DM intake but when infused intraruminally it significantly reduced DM intake especially at the highest rate of infusion.In a second 4 × 4 Latin Square experiment, four sheep were offered ad libitum grass meal pellets alone or supplemented with lactic acid mixed into the pellets at 900, 1200 and 1500 mmol per kg DM for 15-d periods. There was a small reduction in intake on the three lactic acid treatments but this was not significant.In a third experiment the effects of intraruminal infusion with lactic acid was studied further with four sheep which received infusions of lactic acid at a fixed daily rate of 40 mmol per kg W−0·75 per d or of an equal volume of distilled water for 3-d periods while being offered grass meal pellets ad libitum. Infusion with lactic acid resulted in reduced DM intake but the effect was less consistent than in Experiment 1.In all three experiments lactic acid supplementation had little effect on the pH and total volatile fatty acid concentration of rumen

Electronic Resource

1365-2044

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Plasma total and unbound concentrations of thiopentone were investigated during exponentially decreasing infusions in seven patients undergoing cardiopulmonary bypass. Total plasma thiopentone concentrations reached a plateau (10.2, SD 2.1 μg|ml) soon after the initial bolus dose and commencement of the infusion. Concentrations were maintained until the onset of cardiopulmonary bypass, whereupon total plasma thiopentone concentration fell abruptly to 50.0 (SD 5.8) percent of the prebypass level. The unbound fraction of thiopentone increased from 16.6 (SD 1.9) percent before bypass to a maximum to 29.3 (SD 5.6) percent during bypass (p 〈 0.01), decreased to 22.9 (SD 3.3) percent at the end of bypass (p 〈 0.01), hut was still elevated 5–7 hours later (20.5, SD 2.5 percent). The result of the changes in binding was a smaller decline in unbound thiopentone concentration at the onset of bypass to 76.4 (SD 15.7) percent of the prebypass level. Also, unbound levels returned to the prebypass level by the end of bypass, whereas total levels remained low.

Electronic Resource

1365-2044

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The plasma concentrations and elimination half-life of pentobarbitone were determined in 14 surgical patients receiving a continuous, exponentially decreasing, influsion of thiopentone (mean total dose, 1.05 g; SD 0.34; mean duration of infusion 2.4 hours, SD 0.7) as the primary anaesthetic agent. The plasma pentobarbitone concentration increased gradually, to reach a maximum of 1.49 μ/ml (SD 0.61) at the end of the thiopentone infusion, which was 15.5 per cent (SD 6.04) of the plasma thiopentone concentration. The elimination half-life of pentobarbitone measured over the following 70 hours in nine of the patients was 34.3 hours (SD 8.2), which is within the range of values reported previously in several studies in which pentobarbitone was administered directly to volunteers. It was concluded that the formation of this active metaholite during 2–3 hour thiopentone infusions was unlikely to be of clinical relevance, but that significant concentrations may occur with longer thiopentone infusions.

Electronic Resource

1467-6435

Blackwell Publishing Journal Backfiles 1879-2005

Sociology

Economics

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Omeprazole has been shown in previous studies to inhibit the hepatic metabolism of selected drugs. Quinidine is an antiarrhythmic and antimalarial agent with a low therapeutic index. We therefore examined the effect of 40 mg omeprazole daily for one week or placebo on the pharmacokinetics and pharmacodynamics of a single 400 mg dose of quinidine in 8 healthy volunteers in a double-blind crossover study.During placebo and omeprazole treatment, there was no significant difference in area under the time–plasma quinidine concentration curve, (17.0 ± 4.83 μg.h/ml, 18.6 ± 4.43 μg.h/ml, respectively; P 〉 0.2) or renal clearance of quinidine (56.2 ± 26.0 ml/min, 55.6 ± 12.7 ml/min, respectively; P 〉 0.5). Quinidine unbound fraction in plasma (0.170 ± 0.041 vs. 0.166 ± 0.041 in the presence of omeprazole; P 〉 0.5) was not altered by omeprazole. Peak plasma quinidine concentration and the time this occurred did not differ. Omeprazole also had no effect on these parameters for the metabolite 3-hydroxyquinidine. There was no significant difference in the change in the corrected Q—T interval on the electrocardiogram due to quinidine (mean area under the time versus ±Q–Tc curve = 351 ± 192 ms. h, placebo; 414 ± 303 ms. h, omeprazole) showing that quinidine pharmacodynamics were unaltered by omeprazole. We conclude that omeprazole does not affect the pharmacokinetics of quinidine.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Most major pathways of hepatic drug metabolism are dependent on oxygen. Hepatic mixed-function oxidases use oxygen directly as a substrate, while many other enzyme systems are indirectly dependent on oxygen for the generation of essential co-factors, such as NAD- and ATP. Studies in vitro show that many of these oxygen-dependent reactions are impaired by relatively minor reductions in oxygen supply, of a magnitude likely to be encountered in vivo. Phase I metabolism by mixed-function oxidases appears to be more sensitive to hypoxia than phase II drug conjugation, although the oxygen requirements of conjugation reactions, such as glucuronidation, may be greatly enhanced by poor nutrition or fasting. Studies in humans are few, but in general they affirm the potential importance of the effects of hypoxaemic states on hepatic drug elimination. On present evidence, special care should be taken in hypoxic patients with drugs extensively metabolized by the liver, particularly those which have a low therapeutic ratio.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Fig. 1 CO2 evolution profiles obtained from: a, 0.2%; b, 500 p.p.m.; and c, 50 p.p.m. nominal concentrations of carbonate minerals in alumina. Evolution profiles in a and b were obtained using a carrier gas flow rate of 300 ml min"1 and in c with a flow rate of 100 ml min"1. Fig. 2 Plot of ...

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] In the present investigation an apparatus has been designed for the accurate determination of percentage retention of radioactive vapours when inhaled by human subjects. The first compound chosen for investigation was methyl iodide, which is of interest because it could constitute the major hazard ...

Electronic Resource

1572-8889

Aphytis melinus ; Aonidiella aurantii ; experience ; learning

Springer Online Journal Archives 1860-2000

Biology

Abstract Aphytis melinus recognizes and accepts covers of its host, California red scale, Aonidiella aurantii (Maskell) (Homoptera: Diaspididae), before assessing the size or quality of the scale body beneath. We evaluated the role of a non-volatile kairomone, O-caffeoyltyrosine, and prior experience with hosts on the recognition (antennal drumming) and acceptance (ovipositor probing) of scale covers differing in age and, therefore, size. We tested several hypotheses concerning the role of experience with hosts on host recognition and acceptance. The first predicts that experience with a particular host size leads to increased selection of that host size in the future. The second predicts that the “quality” of the experience with hosts sets a threshold of quality for future acceptance. We manipulated the quality of wasp experience with hosts by exposing some wasps to high-quality hosts (large scale insects under large covers) and other wasps to low-quality hosts (small scale insects under small covers and small scale insects under large covers). Control (naive) wasps were held without experience with hosts. Wasps were then offered five size classes of covers directly after removal from the scale insects (unmanipulated) or after removing the kairomone from the covers (kairomone-free). For covers with natural levels of kairomone, no effect of experience with hosts on host recognition was observed. When the kairomone was removed, however, any experience with hosts increased recognition compared to naive wasps. Moreover, experienced wasps preferentially recognized covers of the size to which they had experience. Results for host acceptance differed from those for host recognition. Wasps given experience with large hosts accepted more covers with kairomone than wasps in other treatments, but the size preference did not vary among treatments. When the kairomone was removed, however, wasps given experience with large hosts under large covers preferred larger covers. Host recognition and acceptance are controlled by different behavioral mechanisms. Prior experience with hosts does not alter host recognition but does affect the rate of acceptance. The quality of the experience does not affect the acceptance of covers containing natural levels of kairomone but does affect host acceptance when the kairomone is removed. Experience with hosts alters the motivation of wasps to accept covers, and the direction of this effect is determined by the size (quality) of body the wasps were given during the experience.

Electronic Resource

1436-5073

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Zusammenfassung Die Reaktion mit salpetriger Säure eignet sieh zur Bestimmung sekundärer Amine. Die Versuchsbedingungen wurden bei einigen Aminen untersucht. Dabei wurde festgestellt, daß die Reaktion rasch verläuft und daß hohe und reproduzierbare Ausbeuten an Nitrosaminen erhalten werden. Die Reaktionsbedingungen brauchen nicht besonders genau eingehalten zu werden. Die Konfiguration des Amins beeinflußt die Ausbeute an Nitrosamin und dessen UV-Spektrum, aber dieser Einfluß ist so gering, daß er vom Dimethylamin bis zum Di-n-hexylamin außer Betracht bleiben kann. Eine spektrophotometrische Methode wird beschrieben, die sich für 0,1 bis 1,0 Millival Amin eignet. Die untere Grenze läßt sich durch Änderungder Reaktionsbedingungen bis auf 0,01 Millival herabsetzen. Eine Einzelbestimmung dauert etwa 45 Minuten, bis zu 6 Parallelbestimmungen lassen sich in 2 bis 2 1/2 Stunden ausführen. Ohne besondere Vorsichtsmaßregeln läßt sich eine Genauigkeit von etwa 3% erzielen. Primäre aliphatische Amine stören durch Bildung von Nitrolsäuren, aber dieser Fehler läßt sich durch Messung der optischen Dichte bei zweierlei Wellenlängen ausschalten. Tertiäre Amine bilden sehr geringe Mengen Nitrosamin. Daher ist auch ein großer Überschuß an tertiären Aminen zu tolerieren, ehe eine ernstliche Störung eintritt.

Résumé Un moyen commode de doser les amines aliphatiques secondaires est leur réaction sur l'acide nitreux. On a étudié les conditions de la réaction pour plusieurs amines; on a montré que cette réaction est rapide et que les rendements en nitrosamines sont élevés et reproductibles. Les conditions de la réaction ne sont d'ailleurs pas critiques. La configuration de la molécule de l'amine affecte simultanément le rendement en nitrosamine et son spectre ultraviolet; cet effet est cependant assez faible pour qu'il puisse être négligé dans la série comprise entre la diméthylamine et la dihexylamine normale. On décrit une méthode spectrophotométrique de dosage pour des quantités d'amines comprises entre 0,1 et 1,0 milliéquivalent. La limite inférieure peut d'ailleurs être abaissée à 0,01 milli-équivalent en changeant les conditions de la réaction. Une détermination isolée nécessite environ 45 mn, tandis que 6 déterminations parallèles ne durent que de 2 heures à 2 heures et demie. Il est possible d'atteindre une exactitude d'environ 3% sans prendre de précautions spéciales. Les amines aliphatiques primaires sont gênantes car elles donnent lieu à la formation d'acides nitroliques mais il est possible d'un tenir compte en effectuant les calculs de densité optique pour deux longueurs d'onde différentes. Les amines tertiaires donnent lieu à formation de très faibles quantités de nitrosamines mais il en faut un excès considérable pour qu'elles deviennent vraiment gênantes.

Summary Reaction with nitrous acid provides a convenient means of determining secondary aliphatic amines. Reaction conditions have been investigated for several amines and it has been shown that reaction is rapid and that yields of nitrosamines are high and reproducible. Reaction conditions are not critical. The configuration of the amine molecule affects both the yield of nitrosamine and its ultra-violet spectrum but this effect is sufficiently small to be ignored for the series dimethylamine to di-n-hexylamine. A spectrophotometric method is described which is suitable for amounts of amines in the range 0.1 to 1.0 milli-equivalent. The lower limit may be extended to 0.01 milli-equivalent by changing the reaction conditions. A single determination requires approximately 45 min. and up to six parallel determinations may be completed in 2 to 2 1/2 hours. An accuracy of approximately 3% is obtainable without special precautions. Primary aliphatic amines interfere through the formation of nitrolic acids but may be allowed for by calculation from optical density measurements at two wavelengths. Tertiary amines form very small amounts of nitrosamine but a large excess of tertiary amine can be tolerated before interference becomes serious.

Electronic Resource

1436-5073

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Zusammenfassung Sekundäre aliphatische Amine lassen sich im Mikromaßstab durch Umsetzung mit salpetriger Säure und nachfolgende Extraktion der alkalischen Lösung mit Hexan gut bestimmen. Eine einzige Eichung des Spektrophotometers genügt für die Amine vom Di-n-Propylamin bis zum Di-n-Hexylamin; Diäthylamin kann auf der Grundlage derselben Eichung, aber mit einem etwas größeren Fehler bestimmt werden. Auf Dimethylamin ist die Methode nicht anwendbar. Wird bei 50° C nitrosiert, so stören auch große Mengen primärer und tertiärer Amine nicht wesentlich. Gegenüber geringfügigen Veränderungen der Reaktionsbedingungen ist das Verfahren nicht empfindlich.

Résumé Les amines aliphatiques secondaires peuvent être promptement déterminées, à l'échelle microanalytique, par réaction sur l'acide nitreux suivie d'une extraction par l'hexane de la solution alcaline. Un seul étalonnage du spectrophotomètre suffit pour la série allant de la di-n-propylamine à la di-n-hexylamine: il est possible de déterminer également la diéthylamine avec la même courbe d'étalonnage mais avec une erreur légèrement supérieure. La méthode n'est pas applicable à la diméthylamine. Lorsque la nitrosation est effectuée à 50° C, la présence de proportions élevées d'amines primaires et secondaires ne perturbe pas sensiblement le dosage. Les conditions de la réaction ne sont pas critiques.

Summary Secondary aliphatic amines are readily determined on the micro scale by reaction with nitrous acid, followed by hexane extraction of the alkaline solution. A single spectrophotometer calibration suffices for the series from di-n-propylamine to di-n-hexylamine: diethylamine can be determined using the same calibration graph with a slightly greater error. The method is not applicable to dimethylamine. By nitrosating at 50° C, large amounts of primary and tertiary amines can be tolerated without serious interference. Reaction conditions are not critical.

Electronic Resource

0037-783X

Sociology

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] A study of the urinary excretion of iodide after inhalation of labelled ethyl iodide was also carried out on the same subject during a period of 4-5 h. As shown in Fig. 1, excretion of the labelled inorganic iodide occurred at a somewhat slower rate than after he had inhaled methyl iodide. It is ...

Electronic Resource

1432-1041

thiopentone ; anaesthesia ; intravenous anaesthesia ; multi-stage infusion ; exponential infusions ; pharmacokinetics

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 µg/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10–20 µg/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates.

Electronic Resource

1432-1041

etidocaine ; protein binding ; pregnancy ; alpha1-acid glycoprotein ; labour ; free fatty acids

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Preliminary studies of the ultrafiltration method for measuring the extent of plasma protein binding of etidocaine showed that etidocaine binding was both pH and concentration dependent. Etidocaine (1 µg/ml) was found to bind avidly to a physiological concentration (74 mg/dl) of α1-acid glycoprotein (α1-AGP) (7.23±0.64%, mean ± SD, unbound). In vitro investigation of etidocaine binding in plasma obtained from blood bank donors and from 19 pregnant women prior to induction of labour, during early labour, mid-labour and delivery showed no difference in etidocaine binding (10.3±3.3%, 7.06±2.66%, 8.15±2.57%, 7.84±3.74% and 9.28±6.06% unbound respectively). There was a significant increase in the mean plasma total free fatty acid (FFA) concentration from pre-labour (0.535±0.240 mM) to delivery (0.948±0.28 mM), while plasma albumin and β-lipoprotein concentrations remained constant. α1-Acid glycoprotein concentration tended to increase slightly from pre-labour to early labour (p〈0.1) but was still within the normal physiological range. There was no correlation between etidocaine binding ratio and the concentrations of FFA or plasma proteins except for a poor correlation with the α1-AGP concentration (r=0.361, p〈0.05). Storage of plasma and inadequate control of plasma pH during ultrafiltration appeared to give spurious binding values. These studies with the extensively bound basic drug etidocaine suggest that unlike many acidic drugs which are bound predominantly to serum albumin, the binding of α1-AGP — bound basic drugs may be unaffected by pregnancy and labour.

Electronic Resource

1432-1041

Etidocaine ; epidural ; total blood clearance ; metabolism ; plasma protein binding ; placental transfer

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Following epidural administration of etidocaine hydrochloride to non-pregnant and pregnant patients, a similar rate of absorption was observed and there was no significant difference in total systemic blood clearance (Clsb) of etidocaine in the two groups. There were no major differences in the urinary excretion of etidocaine and metabolites in 48 h urine in both groups. The ability of pregnant women to form the N-glucuronide of the metabolite ABX (2-amino-2′-butyroxylidide) was similar to that of non-pregnant individuals. In vitro experiments showed that the blood/plasma concentration ratio (λ) of etidocaine was significantly higher in pregnant females than in males, presumably due to the lower haematocrit in females. The fraction unbound in plasma (fp) of etidocaine was low in control subjects (mean 0.057) and was not significantly different in pregnant women of 35 to 37 weeks gestation. A marked increase in fp was observed in pregnant women during delivery (mean 0.264). This finding has potentially serious clinical implications because it is the unbound drug in blood which is pharmacologically important. Placental transfer of etidocaine was rapid and the cord/maternal venous blood concentration ratio at delivery (CMb) was, with one exception, always less than unity (mean 0.342). Following epidural administration of etidocaine to pregnant women in labour, measurable concentrations of mono-dealkylated metabolites of etidocaine, PABX (2-N-propylamino-2′-butyroxylidide) and EABX (2-N-ethylamino-2′-butyroxylidide) were detectable in maternal blood within 5 min and cord blood within 30 min. The CMb for PABX and EABX was 0.401 and 0.658 respectively.

Electronic Resource

1432-1041

cimetidine ; intravenous infusion ; pharmacokinetics ; peptic ulcer ; duration of infusion ; acute dose

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary The use of cimetidine administered by bolus intravenous injection to critically ill patients has been associated with serious cardiac arrhythmias, due presumably to high initial plasma concentrations. The aim of this study was to determine the range of infusion times of a single 200 mg dose of cimetidine which would avoid high initial drug concentrations while maintaining a duration of effective concentrations no less than that resulting from bolus injection. Computer simulations of both maximum plasma cimetidine concentrations and duration of effective plasma cimetidine concentrations versus duration of infusion were based on mean pharmacokinetic date from 6 peptic ulcer patients who had received cimetidine 200 mg i.v. over 5 min. The simulations indicated that to reduce maximum plasma cimetidine concentrations by at least 50%, while maintaining the duration of effective plasma concentrations, the infusion time should be at least 30 min and no longer than 4.5 h. The validity of the simulations was subsequently tested in 4 of the patients, who received cimetidine 200 mg i.v. over 30 min. The mean maximum plasma concentration for the 30 min infusion (4.57±0.53 µg/ml) was, as predicted, approximately half that corresponding to bolus administration in these patients (8.97±1.96 µg/ml). Moreover, the duration of effective concentrations for the infusion (1.43±0.28 h) was significantly greater than that for the 5 min infusion (1.21±0.31 h). We suggest that where an acute intravenous dose of cimetidine (200 mg) is indicated, it should be administered over at least 30 min rather than as a bolus.

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