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Biomedical subjects

J S Clark

Publications and source records attributed to J S Clark.

At least 55 records · Page 3Linked to original sources
PubMed1985

Pharmacological investigation of the mechanisms of platelet-activating factor induced mortality in the mouse.

Although the platelets of the mouse are refractory to the direct effects of platelet-activating-factor (PAF), tail vein injection of 10-150 micrograms/kg PAF produces lethal anaphylactic shock. Sensitivity varies with strain and source: Swiss Webster mice show a range of sensitivity and DBA/2 (complement C5-deficient) mice are very resistant. At lethal doses of PAF, animals show labored respiration and general depression; death occurs within 15-45 min. Dexamethasone administered at least 1.5 hr prior consistently protects, whereas the cyclooxygenase inhibitors do not. Antihistamines, adrenergic antagonists, and methysergide have no effect, but cyproheptadine is partially protective at near lethal doses. Calcium entry blockers and calcium chelators, tetracycline and chlortetracycline are partially protective at very high doses consistent with non-specific effects on calcium dependent processes. The arachidonic acid lipoxygenase inhibitors BW755c, phenidone, nordihydroguaiaretic acid and diphenyldisulfide provide nearly complete protection after oral administration of 50-200 mg/kg. Phosphodiesterase inhibitors and dapsone are also effective orally. The leukotriene antagonist FPL55712 administered intraperitoneally (10 mg/kg) 5 min. prior to PAF challenge provides almost complete protection. PAF-induced mortality in the mouse represents a small animal model of systemic anaphylaxis particularly useful for the systemic testing of arachidonic acid lipoxygenase inhibitors and leukotriene antagonists.

Anaphylaxis↗
PubMed1985

The fibre spectrum of the chorda nerve in the chicken (Gallus gallus var. domesticus).

Using transmission electron microscopy, the numbers and diameters of all nerve fibres were studied in the chorda tympani nerve of the domestic fowl. The mean diameter of the whole nerve was 64.6 micron and contained 203-407 (mean 302) myelinated and 205-345 (mean 265.6) unmyelinated fibres. Of the myelinated fibres (including sheath) 95% were in the range 0.5-3 micron in diameter and 94% of the unmyelinated fibres ranged from 0.2 to 0.9 micron in diameter. After section of the facial nerve within the facial canal, there was a marked reduction in the number of myelinated fibres present in the chorda tympani nerve (range 12-160, mean 103) but a less marked reduction in the unmyelinated fibres (range 94-362, mean 223). The loss of myelinated fibres was not confined to any one fibre size whereas the loss of unmyelinated fibres was mainly in the smaller fibres (range 0.1-0.5 micron). Since facial nerve section results in degeneration of efferent fibres it would seem that a large proportion of the afferent fibres are unmyelinated.

Afferent Pathways↗
PubMed1984

Gas-blood Pco2 and Po2 equilibration in a steady-state rebreathing dog preparation.

Alveolar gas and mixed venous blood PCO2 and PO2 were compared in a steady-state rebreathing dog preparation, during spontaneous breathing and mechanical ventilation, by a new null-balancing method that removes potential biases in the comparison of measurements in the blood and gas phases and includes an inert gas test to verify the equilibration between the rebreathing lung and the bag. No systematic PCO2 and PO2 differences were observed under equilibrium conditions. However, inert gas studies suggested that a high percentage of measurements obtained during spontaneous breathing were unreliable because of inadequate equilibration between blood and rebreathing bag (attributable to reduced ventilation or perfusion) and that all mechanical ventilation measurements were acceptable. The present data support the view that no PCO2 or PO2 gradients exist when the pulmonary capillary blood and alveolar gas are in equilibrium; the data also suggest that the steady-state rebreathing dog preparation may not be completely stable and that the time course of PCO2 and PO2 in the rebreathing bag may not be reliable as a means of assessing the equilibration between blood and bag.

Animals↗
PubMed1983

Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy.

In a survey of 46 randomly selected diabetic patients on biguanide therapy, 30% had malabsorption of vitamin B12. Withdrawal of the drug resulted in normal absorption in only half of those with malabsorption. In most patients with persistent malabsorption, the results of absorption tests with exogenous intrinsic factor suggested the diagnosis of coincidental intrinsic factor deficiency. Further considerations, however, led to the concept that biguanides can induce malabsorption by two different mechanisms. One of these is temporary and unrelated to intrinsic factor secretion and the other is permanent and mediated by depression of intrinsic factor secretion.

Adult↗
PubMed1983

Pharmacological action of breakdown products of atracurium and related substances.

The neuromuscular and cardiovascular effects of the breakdown products of atracurium and related substances have been studied in cats anaesthetized with chloralose. Laudanosine, the quaternary acid and metholaudanosine had no neuromuscular blocking activity within the dose range 0.5-4 mg kg-1. However, the quaternary monoacrylate, the quaternary alcohol and the monoquaternary analogue produced a dose-dependent neuromuscular block within this dose range. At 4 mg kg-1 mean arterial pressure was significantly reduced by 30-70 mm Hg following the administration of the quaternary monoacrylate, laudanosine, the quaternary alcohol, metholaudanosine and the monoquaternary analogue. At this dose only the monoquaternary analogue caused significant sympathetic blockade after preganglionic nerve stimulation. Significant vagal blockade occurred after 4 mg kg-1 of the quaternary monoacrylate, the quaternary acid, the quaternary alcohol and the monoquaternary analogue. In view of the low potencies of these substances, it is likely that the quantities present either as an impurity or likely to be formed after administration of therapeutic doses of atracurium (0.3-0.6 mg kg-1 i.v.) are of no pharmacological importance.

Animals↗
PubMed1983

Interaction between atracurium and drugs used in anaesthesia.

The effects of various drugs used during anaesthesia on the neuromuscular blocking activity of atracurium have been studied in anaesthetized cats. Clinically effective doses of diazepam, morphine, pentazocine, pethidine, ketamine, Althesin, methohexitone, Septrin, lignocaine, propranolol, calcium chloride or azathioprine did not significantly alter the neuromuscular blocking action of atracurium. Recovery from atracurium was not prolonged during an infusion of hexamethonium or sodium nitroprusside, indicating that, despite the severe hypotension, the inactivation of atracurium was unimpaired. Similar to that of other competitive neuromuscular blocking agents, the action of atracurium was enhanced by tubocurarine, halothane, gentamycin, neomycin and polymixin and was antagonized by adrenaline and transiently antagonized by suxamethonium. However, pretreatment with suxamethonium did not affect the subsequent block by atracurium.

Anesthesiology↗
PubMed1981

Measurement of oxygen consumption and carbon dioxide production rates by a tracer-bolus method.

A new method for measuring oxygen consumption and carbon dioxide production is described. The method is based on the injection of a helium bolus into the inspired gas for repeated breaths; the helium can be delivered through the mouth or through a nostril (the injection system being controlled by the integrated flow signal or by the signal of a thermistor, respectively). Compared with the conventional gas-collection technique, the tracer-bolus method allows more rapid and frequent measurements. The method does not necessarily require an airtight respiratory circuit, so that it can be conveniently applied in less cooperative subjects, including children. The results of validation studies based on a comparison with the standard gas-collection technique are presented; these results indicate that the measurements by the tracer-bolus method are accurate in normal subjects. In patients with obstructive lung disease, the determinations are associated with a systematic error, which is expected, the tracer-bolus method being based on a single-compartment, uniformly ventilated and perfused lung model; the error is, however, predictable from the degree of functional impairment and can be corrected using equations based on routine pulmonary function tests.

Adult↗
PubMed1981

Blood-gas analyzer calibration and quality control using a precision gas-mixing instrument.

We describe a new instrument that performs on-site mixing of oxygen (O2), carbon dioxide (CO2), and nitrogen (N2) to create compositions that can replace gases from standard premixed cylinders. This instrument yields accurate and predictable gas mixtures that can be used for two-point gas calibration of blood gas/pH analyzers or for liquid tonometry of either an aqueous buffer or blood used as quality-control material on blood-gas electrodes. The desired mixture of O2, CO2, and N2 is produced by microprocessor control of the sequential open-times on three solenoid valves that meter these pure gases through a common small-bore orifice. Any combination of O2 and CO2 can be chosen by dialing the front panel thumbwheels and pressing a button. Gas chromatographic evaluation of this gas-mixing instrument demonstrates its accuracy and precision to be better than +/- 0.1% absolute full scale for O2, CO2, and N2, making this instrument calibration and tonometry.

Blood Gas Analysis↗
PubMed1981

The effect of ranitidine hydrochloride, a new histamine H2-receptor antagonist, on intrinsic factor secretion.

The effect on intrinsic factor (IF) secretion of eight weeks' continuous treatment with a clinically relevant oral dose of ranitidine hydrochloride, a new histamine H2-receptor antagonist, has been studied in 11 patients with duodenal ulcer. There was no significant difference between the mean IF output during treatment of after drug withdrawal as compared with the control value, despite highly significant (p less than 0.001) reduction in acid output during treatment. In the short term this potent drug is unlikely to cause pernicious anemia from interference with IF secretion, although further study is necessary to exclude this possibility after long-term use.

Adolescent↗
PubMed1981

New gas-liquid equilibration method: syringe tonometer.

This new apparatus for gas-liquid equilibration (tonometry) in a transportable vessel is designed for tonometry of blood or buffer solution in a specially designed syringe. Gas enters the syringe chamber through small holes in the tip of the syringe plunger and bubbles upward through the sample. The syringe plunger is a second chamber, which is used for warming and humidifying the gas before it enters the tonometer chamber. The entire syringe is housed in a transparent, temperature-controlled environment during equilibration. After equilibration, the sample is easily entered into a blood-gas analyzer. At most, gas-liquid O2/CO2 equilibration for 2.5 mL of buffer or blood requires less than 13 min. Comparisons with a standard thin-film tonometer show good agreement for pO2 and pCO2 over the range 0-93 kPa (0-700 mmHg) and 2-20 kPa (14-150 mmHg), respectively. The syringe tonometer eliminates contamination of the sample during transfer and transport to the analyzer, thus making tonometry more technique-independent. The apparatus is simple and easy to use, with definite advantages over existing methods of tonometry.

Blood Gas Analysis↗
PubMed1978

Activation of hypothalamic neuronal activity by the electrolytic deposition of iron into the preoptic area.

Changes in brain activity after electrochemical stimulation of the preoptic area of pro-oestrous rats were studied by the measurement of the electro-encephalogram (EEG) of the frontal cortex and the recording of single neurones in the anterior hypothalamus. All rats were anaesthetized with urethane between 10.00 and 12.00 h to allow prolonged electrophysiological recording and to block the spontaneous surge of LH during the afternoon. Electrochemical stimulation was applied, between 12.00 and 14.00 h, as an anodal current through an implanted steel electrode; this caused the electrolytic deposition of iron and evoked the release of LH and ovulation. Electrochemical stimulation of the preoptic area changed the cortical EEG, either immediately or after a delay of a few minutes, from a labile pattern with alternate periods of arousal and slow-wave sleep, to a stage of continuous arousal which persisted for the remainder of the recording period (2--3 h). Conversely, the EEG pattern of the cortex was not disturbed by electrolytic lesions placed in the preoptic area through a platinum electrode. Electrochemical stimulation of the arcuate region of the hypothalamus, the lateral septal area, the medial amygdaloid complex and the anterior parts of the thalamus caused no obvious change in the EEG patterns. Ipsilateral anterior hypothalamic neurones, about 1 mm caudal to the focus of electrochemical stimulation, displayed an immediate decrease in electrical activity after application of the current. After 10--20 min however, the rates of discharge of action potentials in 9 out of the 16 neurones under consideration increased progressively from 0.5 to 15--25 action potentials/s and these rates were maintained until the recordings were lost after 90--230 min. No such acceleration in electrical activity was observed in neurones on the contralateral side. Iron deposited during electrochemical stimulation was precipitated as sulphide and stained by Timm's method. There was a central damaged area of radius 0.6 mm surrounded by an 'undamaged' area with considerable infiltration of iron, up to a distance of 1.7 mm from the electrode tip. Cells within the area of infiltration did not stain for iron 10 min after electrochemical stimulation, but after 30 min, neural elements in this peripheral zone were stained in a manner similar to the Golgi method. The concentrations of LH in the plasma remained unchanged in all rats for 10--15 min after electrochemical stimulation. Thereafter, the concentrations increased progressively and approximately in parallel to the changes in action potential activity until, after 2 h, the individual concentrations of 300--600 ng LH/ml were more than six times the values obtained before stimulation. Bilateral electrochemical stimulation resulted in appreciably higher concentrations of LH and produced values close to those observed during the pro-oestrous surge of the hormone...

Action Potentials↗
PubMed1978

Shunt quantification by mathematical analysis of indicator dilution curves.

Mathematical models are presented for describing and analyzing indicator dilution curves recorded in patients with intracardiac and great vessel shunts. The models treat individual segments of the circulation as linear system blocks, each having, at its output, a characteristic time response to a rapid injection of indicator at its input. These blocks are combined in feedback and feed-forward configurations to simulate left-to-right, right-to-left, and bidirectional shunts. A shunt analysis algorithm, using discrete analogs of the linear system models, was implemented in a computer program and used to analyze thermodilution curves recorded in patients with congenital heart defects. Results are presented comparing shunt fractions obtained from thermodilution curve analyses with oximetrically determined values in 20 patients. Comparing left-to-right shunts measured by the two methods, the mean systematic difference was 0.7% of pulmonary flow and the standard deviation was 7.6% of pulmonary flow. Statistical validation of the bidirectional shunt method will require acquisition and analysis of more data; however, reasonable shunt fractions were computed in five cases studied and good agreement with oximetric determinations was obtained in two cases where complete oximetric data were available.

Adolescent↗