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Biomedical subjects

J A David

Publications and source records attributed to J A David.

29 records · Page 2Linked to original sources
PubMed1982

Differential accessibility to two insect neurones does not account for differences in sensitivity to alpha-bungarotoxin.

The nicotinic acetylcholine receptor probe alpha-bungarotoxin (1.0 x 10(-7) M) blocks the depolarising response to ionophoretic application of acetylcholine onto the cell body membrane of the fast coxal depressor motoneurone (Df) of desheathed cockroach (Periplaneta americana) metathoracic ganglia, but at the same concentration is completely ineffective in blocking the depolarising action af acetylcholine on dorsal unpaired median (DUM) neurones in the same ganglion. The possibility that this is due to differences in accessibility of the toxin to the neurones has been tested by a combination of ionophoretic injection of horseradish peroxidase into single neurones with a study of the distribution of the exogenous tracer lanthanum, which is of similar effective size to alpha-bungarotoxin. The peripherally located cell body membranes and the fine axonal processes of Df and DUM neurones of desheathed metathoracic ganglia are equally accessible to lanthanum. Differential accessibility to the two cell types does not account therefore for the differences in sensitivity to alpha-bungarotoxin.

Acetylcholine↗
PubMed1982

The effects of axotomy upon the extrasynaptic acetylcholine sensitivity of an identified motoneurone in the cockroach Periplaneta americana.

The effects of axotomy on the sensitivity of the fast coxal depressor motoneurone (Df) of the cockroach (Periplaneta americana) to applied acetylcholine (ACh) and carbamylcholine (CCh) have been investigated. ACh and CCh applied to the soma membrane either by bath perfusion or by ionophoresis caused depolarization; repeated application of large doses of these agonists resulted in a relatively rapid desensitization and depression of the response. Axotomy performed 3-10 days before recordings were made caused an approximately threefold increase in the sensitivity to ACh but had no affect upon the sensitivity to CCh. The resting potential, input resistance and membrane time-constant remained within the normal range. In addition there was no change in the rise-times of the responses or of the ACh reversal potential, or in the apparent number of ACh molecules needed to combine with individual cholinoceptors to produce a response. The anticholinesterases physostigmine and neostigmine potentiated the ACh response at relatively low concentrations (10(-7) M-10(-6) M). This potentiation was significantly greater in the normal cells than in the axotomized cells. It is therefore concluded that the increase in ACh sensitivity of this motoneurone results at least partly from a fall in the activity of cholinesterase in the region of the applied drug.

Acetylcholine↗
PubMed1980

Pharmacokinetics of intravenous erythromycin lactobionate.

In a previous study with erythromycin lactobionate it was shown that a 12-hour intravenous infusion of 2 g produced peak plasma erythromycin concentrations well above the required levels to inhibit the growth of all standard erythromycin-sensitive pathogens (including Haemophilus influenzae). Unfortunately two subjects vomited after receiving 2 litres of normal saline (in which the erythromycin lactobionate was infused). For this reason it was decided to administer half the previous dose of erythromycin lactobionate in 500 ml of 0.9N saline over 1 hour. The present study shows that the latter dose regime produces therapeutic plasma erythromycin base concentrations in the plasma in all subjects, five of whom also participated in the previous study. The infusions were well tolerated in every participant. More rapid administration enabled the baseline pharmacokinetics of this parenteral erythromycin salt to be established by two different computer programmes in healthy volunteers. It is hoped that the data outlined in this paper will prove a useful baseline for future studies with erythromycin lactobionate in healthy volunteers and patients with severe infections who receive this antibiotic.

Adult↗
PubMed1980

HDL-cholesterol concentration and severity of coronary atherosclerosis determined by cine-angiography.

We studied 226 adult male subjects (mean=52yr) who underwent coronary arteriography. Their serum lipid and lipoprotein levels [total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C), LDL-C, HDL-phospholipid (HDL-P), HDL-TG, HDL-C/TC, HDL-P/TC, LDL-C/TC, LDL-C/HDL-C and LDL-C/HDL-P] were correlated with the severity of coronary artery disease (CAD). Studies showed a slight but statistically significant correlation (linear regression) between CAD and HDL-P/TC (r=-0.24, P < 0.001), HDL-C/TC (r=-0.20, P < 0.002), followed by LDL-C/HDL-P (r=0.19, P < 0.004) and HDL-P (r=-0.18, P < 0.008). HDL-C, LDL-C and TC were significant at the P < 0.05 level; P value of TG was non-significant. Subjects were conveniently grouped based on degree of coronary artery narrowing: normal, mild (1-50%); moderate-severe (51-99%) and very severe (100% occlusion). Of the 11 lipid variables, the best predictor of the stage of the CAD was HDL-P/TC as measured by one-way analysis of variance. This trend was unaltered even after adjustment for covariates. HDL-P, LDL-C/HDL-P and HDL-C/TC were also significant, but the other lipid parameters were not. The study indicates that HDL-C, by itself, is not as effective a predictor of CAD as HDL-P/TC. Also, the small but statistically significant inverse relationship between HDL-P/TC and CAD suggests that a low HDL-P/TC ratio can be considered a risk factor for CAD but not as a dependable clinical diagnostic aid for predicting the severity of CAD on an individual basis.

Adult↗
PubMed1978

Plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin during total hip replacement after intravenous bolus injection of magnapen.

1. A rapid intravenous bolus injection of 4.0 g Magnapen (which contains 2.0 g of ampicillin and 2.0 g of flucloxacillin) was to seven patients undergoing total hip replacement immediatly before induction of general anesthesia. Postoperatively the patients patients received 2.0 g Magnapen by intramuscular injection every 6 h for up to 72 h until removal of the wound drains. 2. The plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin were measured by a differential small plate microbiological assay method using Sarcina lutea and a penicillinase producing Staph. aureus Russell as the test organisms. 3. The mean +/- s.e. mean concentrations of ampicillin after this regimen were 4222.2 +/- 285.0 microgram/ml (plasma), 65.6 +/- 1.3 microgram (g (hip capsule), 19.1 +/- 3.8 microgram/g (cancellous bone), and 211.1 +/- 65.6 microgram/g (ground up bone) respectively. 4. The mean +/- s.e. mean flucloxacillin concentrations after this regime were 137.2 +/- 28.4 microgram/ml (plasma), 61.8 +/- 15.0 microgram/g (hip capsule), 47.1 +/- 9.5 microgram/g (cancellous bone) and 139.4 +/- 21.8 microgram/g (ground up bone) respectively. 5. An intravenous bolus injection of Magnepen (4.0 g), given immediately before induction of general anaesthesia, provides concentrations of ampicillin and flucloxacillin in plasma, hip capsule, cancellous and ground up bone, and drain fluid that exceed the MICs of these antibiotics against Staph. aureus and E. coli. 6. The plasma, hip capsule, cancellous and ground up bone concentrations of ampicillin after this dose of Magnapen do not, however, exceed the MICs of the Gram negative anaerobes that sometimes cause postoperative wound infections in these patients.

Aged↗