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Biomedical subjects

S Bower

Publications and source records attributed to S Bower.

66 records · Page 4Linked to original sources
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↗
PubMed1978

Modification by monoamine oxidase inhibitors of the analgesic, hypothermic and toxic actions of morphine and pethidine in mice.

A single injection of phenelzine 100 mg kg-1 given 18 h before, decreased the analgesia and hypothermia induced by morphine, but potentiated the analgesic and hypothermic effects of pethidine, when the analgesics were administered either intraperitoneally, or intracerebroventricularly. The modification of pethidine analgesia and hypothermia, but not morphine analgesia, was antagonized by methysergide (10 mg lg-1, s.c.). The LD50 of pethidine, but not that of morphine, was 30-40% lower in mice treated with phenelzine tranylcypromine or iproniazid 6 h before the test. The increased lethality of a single dose of pethidine induced by phenelzine was also prevented by methysergide. Pretreatment of mice with 100 mg kg-1 phenelzine was followed by a significant rise in both brain tryptophan and 5-hydroxytryptamine (5-HT) concentrations which lasted for 24 h. Therefore, the changes in pethidine effects could have been due to raised brain tryptophan and 5-HT concentrations.

Analgesics↗
PubMedDate not supplied

Mitochondrial DNA in stroke and migraine with aura.

Patients presenting with thrombotic stroke of unexplained etiology and or migraine with aura were screened for mitochondrial (mt) DNA mutations associated with cytopathies given that both migraine and stroke-like episodes are recognised with certain mt DNA mutations. Mutations usually associated with either mitochondrial encephalopathy, lactic acidosis and stroke-like episode, myoclonic epilepsy with ragged red fibres, or those strongly linked to Leber's hereditary optic neuropathy (LHON) were not detected in patients or controls. However, increased levels of two of the secondary LHON mutations were found. The T-->C mutation at nucleotide 4216 was more common than expected in patients aged 35 years or less, as was the 13708 G-->A mutation in young stroke patients. This data lends support to the possibility that an accumulation of minor mt DNA mutations may contribute to the pathoaetiology of stroke and migraine with aura in some young patients.

Adolescent↗