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Biomedical subjects

P J Ravenscroft

Publications and source records attributed to P J Ravenscroft.

17 recordsLinked to original sources
PubMed1992

Measurement of dothiepin and its major metabolites in plasma by high-performance liquid chromatography.

This paper describes a reversed-phase high-performance liquid chromatographic method which will simultaneously measure dothiepin and its three major metabolites (northiaden, northiaden-S-oxide and dothiepin-S-oxide) in plasma using trimipramine as internal standard. Sample preparation involved a basic extraction using diethyl ether followed by an acid back-extraction. The method we report is linear over the range 50-1000 ng/ml (r = 0.999), for all analytes. Total imprecision is less than 11% (coefficient of variation) and accuracy is greater than 94% (n = 20). Recovery of analytes varied considerably from 51.7% for northiaden-S-oxide to 90.2% for dothiepin-S-oxide.

Chromatography, High Pressure Liquid↗
PubMed1992

High-performance liquid chromatographic method for the simultaneous determination of monoethylglycinexylidide and lignocaine.

An accurate and sensitive high-performance liquid chromatographic method with UV detection was developed for the simultaneous measurement of monoethylglycinexylidide (MEGX) and lignocaine in human plasma and serum, using organic solvent extraction and trimethoprim (TMP) as an internal standard. The mean recoveries for MEGX, TMP and lignocaine were 86.1 +/- 3.7, 98.3 +/- 1.8 and 77.0 +/- 4.7%, respectively (n = 6). The relative standard deviations for MEGX concentrations of 10 and 200 ng/ml were less than 4% and for lignocaine concentrations of 200 and 1200 ng/ml they were less than 8%.

Chromatography, High Pressure Liquid↗
PubMed1992

Pharmacokinetics and efficacy of rectal versus oral sustained-release morphine in cancer patients.

Sustained-release morphine (MST) given by the rectal route was compared with oral MST in an open randomised cross-over trial in ten patients with cancer who received stable doses of MST. No significant difference was found in the areas under the curve of the concentration-time profiles (AUC) following oral or rectal administration for parent morphine. The AUCs determined for morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) after oral administration were approximately twice those obtained following rectal administration. The maximal concentration achieved was lower and the time to maximal concentration was longer following rectal administration for morphine, M6G and M3G. The relative mean arrival times following rectal administration were significantly longer for morphine and M3G but not for M6G. These findings suggest slower absorption but less first-pass metabolism of MST after rectal administration. No significant difference was noted between the oral and the rectal route in measurements on visual-analogue scales for pain or side effects. We recommend the rectal route as being suitable for MST administration when the oral route is no longer available. In changing from oral to rectal administration, the same dose and dose interval may be used, but dose adjustment may be needed.

Administration, Oral↗
PubMed1992

The influence of vancomycin concentration and the pH of plasma on vancomycin protein binding.

A review of numerous studies of the protein binding of vancomycin suggests major discrepancies among their results. The reported percent protein binding of vancomycin varies from 0% to 98%. The influence of pH and concentration on the protein binding of vancomycin was investigated in this study. There was a significant difference (p < 0.001) in percent protein binding in vancomycin-spiked plasma samples across the pH range of 7.0-8.0. There was no significant difference (p > 0.05) in percent protein binding in vancomycin-spiked plasma samples across the concentration range of 2-80 mg/L. It is likely that some of the variation reported to date may be due to a lack of control of pH during the measurement of protein binding of vancomycin.

Blood Proteins↗
PubMed1992

A quick, sensitive high-performance liquid chromatography assay for monoethylglycinexylidide and lignocaine in serum/plasma using solid-phase extraction.

Recent advances in the investigation of liver disease and transplantation have seen the introduction of lignocaine as a probe of liver function. For this purpose, an assay that is sensitive and rapid is required for the major metabolite of lignocaine, monoethylglycinexylidide (MEGX). We have developed an accurate, low-cost high-performance liquid chromatography (HPLC) method using Bond-Elut phenyl (1 cc) cartridges for sample preparation. The total preparation time for five samples is less than 10 min and the run time is approximately 10 min/sample. Each cartridge can be used at least four times. Simultaneous measurement of another metabolite of lignocaine, glycinexylidide (GX), can be achieved by adjustment of the mobile phase and flow rate. The chromatogram is monitored with an UV detector at 210 nm. The inter- and intra-assay coefficients of variation for MEGX (10-250 micrograms/L) and lignocaine (100-2,000 micrograms/L) are less than 9.5 and less than 2%, respectively, with recoveries for MEGX, trimethoprim (internal standard), and lignocaine all greater than 85%. This method offers a rapid, sensitive assay that is clinically useful in the new role for lignocaine/MEGX in dynamic liver function testing.

Chemistry Techniques, Analytical↗
PubMed1992

Plasma morphine-3-glucuronide, morphine-6-glucuronide and morphine concentrations in patients receiving long-term epidural morphine.

Plasma morphine concentrations were measured in five cancer patients receiving long-term epidural morphine administration. Peak concentrations were observed within 1 h of dosage and concentrations then declined biexponentially. Plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations were measured in two patients and plasma M3G concentrations were observed to be much higher than plasma M6G and morphine concentrations. Peak plasma M6G concentrations occurred within 1.0 h of dosing and plasma M6G concentrations then remained higher than plasma morphine concentrations.

Analgesia, Epidural↗
PubMed1991

Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus.

The effects of metformin on glycaemia, insulin and c-peptide levels, hepatic glucose production and insulin sensitivity (using the euglycaemic, hyperinsulinaemic clamp) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol: Stage 1--no metformin for four weeks; stage 2--metformin 500mg mane; stage 3--metformin 500mg thrice daily; stage 4--metformin 1000mg thrice daily. Results are expressed as Mean +/- SEM. Fasting blood glucose decreased from basal values (9.7 +/- 1.0 mmol/L) by 13% at stage 2, 34% at stage 3 and 41% at stage 4 (p less than 0.02 vs basal for all stages; p less than 0.02 stage 2 vs stage 3). Post-prandial glycaemia was significantly improved only with metformin 3000mg/day (p less than 0.05). Fasting, meal-stimulated and total insulin and c-peptide levels showed no change. Hepatic glucose output did not change significantly with metformin. Insulin sensitivity, measured as total glucose utilisation during hyperinsulinaemia, increased from stage 1 (10.3 +/- 2.1 mumoL/kg/min) by 23% at stage 3 (p less than 0.05) and by 29% at stage 4 (p less than 0.02). Basal metabolic clearance of glucose increased compared to stage 1 (1.69 +/- 0.16 mL/kg/min) by 30% at stage 2, 53% at stage 3 and 44% at stage 4 (all p less than 0.02). This study demonstrates that improved efficiency of glucose utilisation, both basally and under conditions of euglycaemic hyperinsulinaemia, is the basis of metformin's antihyperglycaemic action.

Adult↗
PubMed1989

Comparison of Sawchuk-Zaske and Bayesian forecasting for aminoglycosides in seriously ill patients.

1. Individual pharmacokinetic parameters and predicted steady-state serum concentrations of aminoglycosides were calculated by Sawchuck-Zaske (SZ) and Bayesian methods. 2. Predicted concentrations were compared with observed steady-state concentrations for 36 seriously ill patients with systemic infections. Four aminoglycoside concentrations were used for the SZ method. Differing numbers of serum aminoglycoside samples were used in the Bayesian parameter estimation: one sample Bayesian used one post-infusion concentration, two sample Bayesian used a trough plus one post-infusion concentrations and four sample Bayesian used a trough plus three post-infusion concentrations. 3. 79% of the SZ predictions were with +/- 2 mg l-1 of the observed peak concentrations, and 72% of the two sample Bayesian predictions were within the same range. 82% of SZ and the two sample Bayesian predictions were within +/- 1 mg l-1 of the observed trough concentrations. 4. A confidence interval comparison of estimated pharmacokinetic parameters and precision for the predicted concentrations showed no important differences between the SZ and the two sample Bayesian. The four sample Bayesian was the most precise method. 5. We conclude that the Bayesian forecasting method utilizing a trough plus one post-infusion concentrations is as useful as the SZ method which requires three to four serum concentrations in individualizing aminoglycoside therapy for seriously ill patients.

Adolescent↗
PubMed1987

Temelastine does not affect theophylline pharmacokinetics in normal subjects.

The pharmacokinetics of theophylline (i.v. aminophylline 250 mg) were studied in a balanced, double-blind crossover following the administration of oral temelastine (100 mg) or placebo, twice daily for 7 days, to 10 normal volunteers. Comparison of volumes of distribution, elimination rate constants, elimination half-lives and areas under the plasma concentration-time curve indicated that temelastine had no significant effect on theophylline pharmacokinetics.

Adult↗
PubMed1978

Simple mandatory minute volume.

An easily constructed system for mandatory minute volume is described, using a Brompton Manley ventilator, a thin polyvinylchloride bag in a glass jar, and an Ambu "E" valve.

Anesthesiology↗
PubMed1977

Differential effects of digoxin at comparable concentrations in tissues of fetal and adult sheep.

Electrocardiogram (ECG) electrodes and carotid arterial and superior vena caval (SVC) catheters were placed in eight nonpregnant ewes and 11 fetuses (109-129 days gestation) to measure heart rate, arterial presssure, P-R interval, left ventricular pre-ejection period (PEP), and left ventricular ejection time (LVET), before and after digoxin infusion into the SVC. After the ewes were killed, the steady state concentration of digoxin in plasma was related to the concentration in midbrain and left ventricular free wall. Although concentrations of digoxin in tissue differed between fetuses and ewes, tissue-plasma ratios were similar; the myocardial-plasma ratio was 87 for fetuses and 90 for ewes and the midbrain-plasma ratios were 6.4 and 5.3, respectively. In spite of these similarities, physiological and toxic effects differed at comparable plasma concentrations. Reduction in PEP/LVET ratio was greater in ewes than fetuses, and P-R interval prolongation was linearly related to digoxin concentration in fetuses but uncommon at plasma concentrations below 2 ng/ml in ewes. Arrhythmias occurred in six ewes, but in only one fetus, even though the mean steady state concentration of digoxin in plasma was 4.5 ng/ml in the fetuses and 2.3 ng/ml in the ewes. Atropine had little effect on digoxin-induced P-R interrval prolongation, and isoproterenol produced no tachyarrhythmias in the fetuses. Age-related differences in inotropic and arrhythmogenic effects of digoxin exist exist and are related to differences in drug response rather than drug kinetics; this provides experimental support for the different dosage responses.

Animals↗
PubMed1975

Intestinal amoebiasis and amoebic liver abscess in Brisbane, 1956 to 1973. Clinical syndromes and the results of medical and surgical management.

Nineteen patients presented to teaching hospitals in Brisbane with symptomatic amoebiasis from 1965 to 1973. The majority of patients gave a history of overseas travel or residence. Intestinal amoebiasis most frequently occurred in its non-dysenteric form, so that there were some problems in differentiating it from more commonly occurring forms of colitis. The potential for amoeboma to be mistaken for a neoplasm was evident. Amoebic liver abscess was confirmed in 10 cases and, in nine of these, the abscess was localized to the right lobe of the liver. A total colectomy had been performed in one case and an abdominoperineal resection of the rectum in another before hospital admission in Brisbane and confirmation of the diagnosis of amoebiasis. Five of the patients with amoebic liver abscess underwent laparotomy soon after admission because of upper abdominal symptoms and signs which resembled those of other surgical conditions. Although the indirect haemagglutination test was of considerable assistance in diagnosing amoebiasis, it was apparent that attention to detail in the collection and examination of faecal specimens remained of major importance. A trial of metronidazole, which is both effective and relatively safe, is advocated in cases of diagnostic difficulty, when amoebiasis is suspected but unproven, and when the adoption of an alternative diagnosis would lead to the initiation of less satisfactory drug therapy or involve otherwise unnecessary surgery.

Adult↗
PubMed1975

Abnormal renal urate homeostasis in systemic disorders.

Abnormalities of renal handling of urate occur in a wide variety of physiological and pathological conditions and are mediated by factors including renal blood flow, glomerular filtration rate, urine flow rate, urinary constituents, metabolites, hormones and drugs. The determination of the aetiological factors in each abnormal situation is complex and the problem is discussed in relation to a variety of conditions including renal tubular disorders and mental intoxications, hypertension, toxaemia of pregnancy, glycogen storage disease, fructose administration, hereditary fructose intolerance, as well as obesity, regular alcohol consumption and hyperlipoproteinaemia. Apart from those diseases, usually genetically determined, which are associated with excessive production of urate, the most common causes of hyperuricaemia act at a renal level and result in a reduction in the net renal excretion of urate.

Alcoholism↗
PubMedDate not supplied

Survival after unexpected high serum methotrexate concentrations in a patient with osteogenic sarcoma.

An 18-year-old female patient receiving adjuvant chemotherapy for osteogenic sarcoma developed a pruritic erythematous rash during infusion of the eighth dose of methotrexate (8 g/m2) in the series. In other respects, the infusion proceeded normally but the 24-hour serum concentration of methotrexate was unexpectedly and extremely high, 574 mumols/L. Dosing error was excluded, as was the hypothesis that the high concentrations were due to the presence of methotrexate-specific antibodies. Acute oliguria and renal failure were the primary manifestations of the drug-induced toxicity and the high concentrations can be attributed to decreased renal elimination of the drug over the first 24 hours. Treatment consisted of folinic acid rescue, forced diuresis, sequential charcoal haemoperfusion and haemodialysis, and repeated oral doses of activated charcoal. After examination of the contribution of the extracorporeal procedures and the charcoal to the elimination of the drug, the relative lack of morbidity was attributed primarily to the folinic acid rescue and the intensive supportive care.

Adolescent↗