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Biomedical subjects

S Bower

Publications and source records attributed to S Bower.

At least 55 records · Page 3Linked to original sources
PubMed1993

Antiplatelet and anticoagulant therapy.

Antiplatelet therapy is clearly indicated for long-term secondary prevention after transient ischemic attack and ischemic stroke. In stroke-free patients with atrial fibrillation, oral anticoagulants reduce the risk of stroke, and antiplatelet agents may be a lower risk alternative. For the early treatment of the acute phase of ischemic stroke, the role of antiplatelet and anticoagulant therapy is unclear, but is being evaluated in large clinical trials.

Aspirin↗
PubMed1993

Improved prediction of preeclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging.

OBJECTIVE: To assess the value of the early diastolic notch and color Doppler imaging of the uterine arteries at 24 weeks' gestation in a two-stage Doppler screening test for preeclampsia. METHODS: Two thousand fifty-eight unselected women had an initial screening study with continuous-wave Doppler at 18-22 weeks' gestation. Color Doppler imaging was used at 24 weeks' gestation to examine both uterine arteries in 273 women with initial abnormal results (high resistance index or diastolic notch). RESULTS: Three hundred twenty-nine women (16%) had abnormal flow velocity waveforms at the first stage and 104 (5.1%) at the second stage of Doppler screening. The presence of an early diastolic notch in the flow velocity waveform was significantly better than a high resistance index at predicting preeclampsia at both 20 and 24 weeks; the relative risk of developing significant preeclampsia for a woman with a persistent notch at 24 weeks was increased 68-fold. All women delivered before 34 weeks because of severe preeclampsia had abnormal waveforms at both stages of screening. CONCLUSION: An early diastolic notch in the flow velocity waveform is a better predictor of preeclampsia than are conventional impedance indices. Preeclampsia can be predicted effectively by two-stage Doppler screening.

Adult↗
PubMed1992

Effects of different hepatic pathologies on disposition of alfentanil in anaesthetized patients.

We have studied the influence of different hepatic pathologies on the disposition of alfentanil in 23 unpremedicated patients (six healthy control subjects, six patients with liver dysfunction of alcoholic aetiology and 11 patients with non-alcohol related liver disease). All patients received a bolus of alfentanil 500 micrograms i.v. as supplement to 67% nitrous oxide and isoflurane in oxygen anaesthesia. Plasma drug concentrations were measured in venous blood samples at intervals up to 24 h by radio-immunoassay and protein binding was determined by equilibrium dialysis. Kinetic estimates were determined using non-compartmental analysis. Patients with non-alcoholic liver disease had lesser plasma clearance (114.8 (range 66.8-213.5) ml min-1) than the alcoholic group (158.8 (100.0-220.7) ml min-1) or controls (187.4 (125.2-269.5) ml min-1). In all three groups, there was considerable intersubject variability, with a bimodal distribution in the non-alcoholic group. This group also had a smaller apparent volume of distribution at steady state. Mean residence time was prolonged in the alcoholic group compared with controls (284.9 (217.8-362.2) min vs 226.8 (201.2-250) min). Protein binding was decreased in the alcoholic group compared with controls (84.9 (SD 4.2)% vs 89.3 (2.1)%); this was attributable to a lesser plasma alpha 1-acid glycoprotein concentration (0.55 (0.18) g litre-1 vs 0.89 (0.21) g litre-1). Free drug clearance was reduced in both liver dysfunction groups compared with controls.

Adult↗
PubMed1991

Plasma concentrations of bupivacaine following combined sciatic and femoral 3 in 1 nerve blocks in open knee surgery.

We administered combined femoral 3 in 1 and sciatic nerve blocks to provide postoperative pain relief in 22 consecutive patients undergoing elective knee replacement surgery under spinal anaesthesia. The patients were allocated randomly to two groups. In group A (n = 11) the blocks were performed with 0.5% bupivacaine (with adrenaline) 3 mg/kg body weight and in group B (n = 11) 0.5% plain bupivacaine in the same dose was used. Serial plasma concentrations of bupivacaine were measured for up to 2 h and the duration of postoperative analgesia was measured in both groups. No significant differences were found between the two groups. There were no clinical signs or symptoms of bupivacaine toxicity in each group. This study demonstrated that, after combined sciatic and 3 in 1 femoral block, concentrations of bupivacaine associated with toxicity were not reached, even though the dose of bupivacaine administered exceeded the manufacturer's recommended dose by 50%.

Anesthesia, Spinal↗
PubMed1991

Doppler velocimetry studies of the uterine artery in the early prediction of pre-eclampsia and intra-uterine growth retardation.

Pre-eclampsia/proteinuric pregnancy-induced hypertension (PPIH) and intra-uterine growth retardation (IUGR) are associated with incomplete trophoblastic invasion of the uterus in the first half of pregnancy. The uteroplacental circulation can be observed using Doppler ultrasound. We have performed two mid pregnancy screening studies of our antenatal population in the last three years, to assess the use of Doppler velocimetry studies at that time in predicting the subsequent development of PPIH and IUGR. In the first study continuous wave Doppler ultrasound was used to study the uterine circulation. The Resistance Index (RI) was measured once in both uterine arteries in 925 patients between 16 and 24 weeks gestation. There was a significant association between an abnormal RI (greater than 95th centile) and the subsequent development of PPIH, IUGR and severe complications of pregnancy. However, even though the specificity (95%) was high the sensitivity was low (25%). There was no significant association with nonproteinuric hypertension. In an attempt to improve the sensitivity for the second study, colour flow imaging and the use of a diastolic notch as well as an elevated RI were introduced. 2437 patients had continuous-wave Doppler studies of the uterine circulation performed at 20 weeks gestation. 16% had abnormal waveforms, persisting in 5.4% at 24 weeks and 4.6% at 26 weeks when measured with colour/pulsed Doppler. The high sensitivity (76%) of this innovation at 20 weeks is retained at 24 and 26 weeks, while the specificity (from 86% to 97%) and positive predictive value (13% to 44%) improve progressively with gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1990

Middle cerebral artery flow velocity waveforms in fetal hypoxaemia.

In 81 small-for-gestational age fetuses (SGA) colour flow imaging was used to identify the fetal middle cerebral artery for subsequent pulsed Doppler studies. Impedence to flow (pulsatility index; PI) was significantly lower, and mean blood velocity was significantly higher, than the respective reference ranges with gestation. Fetal blood sampling by cordocentesis was performed in all SGA fetuses and a significant quadratic relation was found between fetal hypoxaemia and the degree of reduction in the PI of FVWs from the fetal middle cerebral artery. Thus, maximum reduction in PI is reached when the fetal PO2 is 2-4 SD below the normal mean for gestation. When the oxygen deficit is greater there is a tendency for the PI to rise, and this presumably reflects the development of brain oedema.

Blood Flow Velocity↗
PubMed1989

Disposition of alfentanil in patients receiving a renal transplant.

The disposition of alfentanil has been investigated in 10 anaesthetized patients with chronic renal failure undergoing kidney transplantation and compared with eight age matched anaesthetized patients with normal renal function. Plasma samples were collected to 660 min following intravenous administration of alfentanil 3-5 mg (50 micrograms kg-1). Drug concentrations were measured by RIA; and alfentanil binding to plasma proteins by equilibrium dialysis against 0.1 M phosphate buffer, pH 7.4. Alfentanil binding to plasma proteins was 87.6% (s.d. 2.0) in the patients with chronic renal failure, and 89.7% (1.2) in patients with normal renal function (P = 0.025). There was no correlation between alfentanil binding and plasma albumin, total plasma proteins, plasma urea or plasma creatinine concentrations. In both groups, the drug concentration-time profile decayed in a curvilinear manner; in the chronic renal failure patients, restoration of function did not influence the decay profile. Elimination half life, mean residence time and apparent volume of distribution at steady state were not different in the two groups of patients (mean values: 142.4 and 120.2 min; 128.5 and 136.0 min; and 40.5 and 27.6 L, respectively in chronic renal failure patients and patients with normal renal function). Total drug clearance and Vd area were significantly increased in the chronic renal failure patients: 341.9 vs 211.8 mL min-1; and 69.3 and 35.5 L. There were no differences in intrinsic clearance or apparent volume of distribution at steady state for unbound drug between the two patient groups.

Adult↗
PubMed1988

The pharmacokinetics and clinical effects of a low dose of alfentanil in elderly patients.

Alfentanil is a potent short-acting opioid analgesic which depresses respiration and can cause cardiovascular depression. The elderly can show greater sensitivity to opioid drugs which may be related to pharmacokinetic differences. The pharmacokinetics and clinical effects of alfentanil were studied in 10 elderly patients aged 68-86 years who were undergoing cystoscopy or urethrotomy under general anesthesia. After induction with thiopentone, and while the patient was breathing nitrous oxide with halothane 0.5% (enflurane 1.0% was given to one patient), a dose of alfentanil 4 micrograms/kg was given 15, 20, 30, 45 and 60 minutes after the alfentanil administration, and then every 30 minutes for 6 hours. Pulse rate (PR), systolic blood pressure (SBP), and minute volume (MV, calculated from the respiratory rate and the tidal volume) were measured at 1, 3, 5, 7 and 9 minutes after the alfentanil injection. Pharmacokinetic analysis showed Vc 82 (+/- S.D. 26) ml/kg; VDSS 277 (+/- S.D. 71) ml/kg; clearance 2.01 (+/- S.D. 0.64) ml/kg/min; t1/2 beta 117 (+/- S.D. 24) min. Comparison of these results with the results of other studies supports the view that older patients eliminate alfentanil less rapidly than younger patients, with prolongation of t1/2 beta and decreased clearance. The clinical results showed a decrease in minute volume from a mean value of 5944 ml before alfentanil to 1240 ml 1 minute after alfentanil (P less than 0.001). The minute volume was still significantly lower at 3 and 5 minutes, but had returned to the pre-alfentanil value by 7 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Alfentanil for caesarean section complicated by severe aortic stenosis. A case report.

Alfentanil 35 micrograms kg-1, was used successfully in a patient with severe aortic stenosis, in order to minimize the haemodynamic responses to intubation and surgery during Caesarean section. The baby was delivered apnoeic, unresponsive and with poor muscle tone, but responded rapidly to naloxone. Plasma alfentanil concentrations and percentage binding to plasma proteins were measured in both maternal and neonatal blood. Free drug concentrations were similar in both mother and neonate, but maternal plasma proteins had a higher affinity for alfentanil. Only 67.26% of neonatal plasma alfentanil was bound to plasma protein. This value did not differ significantly from those estimated from the blood of a further 12 healthy neonates.

Adolescent↗
PubMed1985

Acute tolerance to fentanyl during anesthesia in dogs.

The effect of fentanyl on increases in heart rate and mean arterial pressure elicited by electric stimulation of a branch of the radial nerve was studied in anesthetized, paralyzed, and artificially ventilated dogs. In one group, a bolus of 100 micrograms/kg of fentanyl depressed the evoked changes in heart rate and arterial pressure by 82 and 75%, respectively, by 5 min, and recovery occurred within 90 min. A second group was given increasing bolus doses of fentanyl from 1.5 to 100 micrograms/kg every 20 min for 200 min. The doses and intervals were chosen to give a logarithmic increase in plasma concentration of fentanyl to include a final bolus dose of 100 micrograms/kg and were predicted by a two-compartment pharmacokinetic model derived from data of the first group. In the second group, the bolus dose of 100 micrograms/kg after 5 min had no significant effect on evoked cardiovascular responses. Over the following 2 h, the evoked changes in heart rate and arterial pressure increased above those preceding the 100 micrograms/kg dose. An additional bolus dose of 100 micrograms/kg given 2 h after the first did not depress the evoked reflexes below the control values. It was concluded that tolerance to the effects of fentanyl can occur within 3 h and that for evoked responses to arterial pressure, rebound withdrawal effects can be seen within an additional 90 min.

Animals↗
PubMed1983

Chemical modification and ligand binding studies with Escherichia coli glutamate synthase.

The structure and function of Escherichia coli glutamate synthase were studied by ligand binding and chemical modification experiments. Binding of NADP+ was to a single dinucleotide site per alpha beta protomer with a Kd of approximately 5 microM. Phenylglyoxal modified an essential arginyl residue required for binding of NADP+. E. coli glutamate synthase thus employs a single dinucleotide binding site which functions in the NADPH to flavin electron transfer for glutamine-dependent glutamate synthase and for direct reduction of 2-iminoglutarate by NADPH in the NH3-dependent reaction. Binding of 2-oxoglutarate was complex. "Half of the sites" binding of 2-oxoglutarate (Kd less than 0.25 microM) was obtained in the absence of glutamine. Binding to half of the sites was pH independent. In the presence of glutamine, the 2-oxoglutarate binding ratio was approximately 1 equiv per protomer (Kd = 2-3 microM) at pH 7.5. This binding was pH dependent and varied between 0.43 equiv per protomer at pH 6.7 and 2.3 equiv per protomer at pH 9.0. Correlation of half of the sites binding with negative cooperativity for 2-oxoglutarate saturation indicates the utilization of low-Kd 2-oxoglutarate sites for NH3-dependent glutamate synthase. Binding of glutamine promotes a conformational change that exposes additional 2-oxoglutarate sites having a Kd of 2-3 microM which are utilized in the glutamine-dependent reaction. Chemical modification with pyridoxal 5'-phosphate caused inactivation of glutamine-dependent but not NH3-dependent glutamate synthase. Inactivation was ascribed to modification of one to two lysyl residues per protomer by Schiff base formation. The essential lysyl residue has a role in the binding of glutamine.

Escherichia coli↗
PubMed1982

Comparative pharmacokinetics of fentanyl and alfentanil.

The pharmacokinetics of fentanyl and alfentanil were compared by the simultaneous i.v. administration of both drugs, measurement of plasma concentrations and compartmental analysis. In addition, plasma protein binding, erythrocyte:plasma partition, and heptane:water partition were compared. Alfentanil was found to have a very much smaller apparent volume of distribution, smaller total clearance, and shorter terminal half-time in plasma. Alfentanil was also found to have a greater plasma protein binding, but in contrast to fentanyl, no binding to erythrocytes. It is concluded that alfentanil is less cumulative than fentanyl, has restricted hepatic clearance, and will exhibit non-linear kinetics at very high doses. An appendix describes the model-fitting procedure in detail.

Adult↗
PubMed1982

Plasma protein binding of fentanyl: the effect of hyperlipoproteinaemia and chronic renal failure.

Hyperlipoproteinaemic patients with raised pre beta-, or pre beta- and beta-lipoprotein fractions showed a significant (P less than 0.001) increase in binding of fentanyl to whole plasma, compared with normal subjects. The presence of chylomicra had no significant effect on binding. In patients with chronic renal failure, a correlation of probability P less than 0.07 was found between percent binding and concentrations of pre beta-lipoprotein (P = 0.001), serum albumin (P = 0.0101), total protein minus albumin (P = 0.0576) and beta-lipoprotein (P = 0.0625). There was no significant correlation of binding with elevation of alpha- or gamma-globulins, with urea or creatinine concentrations, or with age or sex (P greater than 0.223). The magnitude of changes in the free fraction found in these patients should not produce a clinical effect as the total distribution volume of fentanyl exceeds 200 litres.

Adult↗
PubMed1982

The uptake of fentanyl by erythrocytes.

Fentanyl passed rapidly into and out of erythrocytes to equilibrate with plasma concentration, and a red cell/plasma partition coefficient of 1.01 +/- 0.0083 s.e.m. was found in 15 normal subjects. Most of the binding of fentanyl by red cells was by haemoglobin. 10% was bound by the cell membrane. Partition was unaffected by haematocrit, pH, or the concentration of fentanyl up to 0.5 mg ml-1 of blood. Dilution of plasma proteins, and replacement of plasma by buffer showed that uptake of fentanyl by red cells is a linear function of the concentration of free drug in plasma. A partition coefficient for red cells/buffer of 4.91 +/- 0.032 s.e.m. was found. This relation was confirmed where binding to plasma proteins was altered in uraemia or hyperlipoproteinaemia, or by competitive displacement of fentanyl by aspirin and phenylbutazone thereby changing the size of the free fraction of fentanyl in plasma. Quinidine, however, inhibited the binding of fentanyl to plasma proteins and red cells equally, to maintain a partition coefficient of unity.

Blood Proteins↗