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Biomedical subjects

R Hughes

Publications and source records attributed to R Hughes.

At least 199 records · Page 11Linked to original sources
PubMed1976

Studies on fazadinium bromide (ah 8165): a new non-depolarizing neuromuscular blocking agent.

Intravenous dose-response relationships were used to correlate neuromuscular paralysis with the effects of fazadinium (AH 8165) on autonomic mechanisms in anaesthetized cats and rhesus monkeys and with cardiovascular effects in man. In cats and monkeys neuromuscular paralysis of the twitch responses of the gastrocnemius muscle by fazadinium was accompanied by impairment of the vagally induced bradycardia, but cardiovascular disturbances were small. Blockade of sympathetic mechanisms and hypotension were only evident with supra-maximal doses. In man tachycardia was a common occurrence and in some patients hypertension occurred with doses of the drug needed for complete neuromuscular paralysis. Fazadinium was three to four times more potent in rhesus monkeys than in cats and its course of action was considerably longer. The potency of the drug in man corresponded more closely to that in cats than in rhesus monkeys but its course of action in patients was similar to that in monkeys. In man, dose-response curves were constructed for the contractions of the adductor pollicis muscles elicited by tetanic and single twitch stimuli applied to the corresponding ulnar nerves. The onset of paralysis of the tetanic contractions after the intravenous injection of fazadinium (0.4 mg/kg) occurred within two minutes, but recovery was slow and about 50 minutes were needed for its completion. Depression of the simultaneously recorded twitch responses was less marked, slower in onset and recovery was slightly more rapid. These effects were similar to those obtained with tubocurarine (0.2 mg/kg) but the action of fazadinium was slightly shorter. Tetanic-tension ratios were computed after 30 and 50 per cent recovery from neruomuscular blockade in man. These ratios were lower with fazadinium than with tubocurarine and indicated taht tetanic fade was greater and more persistent after fazadinium than after tubocurarine.

Animals↗
PubMed1976

Studies on dimethyl tubocurarine in anaesthetized man.

Intravenous doses of 0.3 mg/kg dimethyl tubocurarine were required for consistent and adequate surgical relaxation in patients during nitrous oxide anaesthesia and produced virtually complete neuromuscular paralysis (96-100%) of the tetanic and twitch responses of the adductor pollicis muscle. The duration of action of the drug was prolonged--more than 3 h was required to attain 50% recovery from full neuromuscular paralysis. At this degree of recovery neostigmine was an effective antagonist. Determination of the tetanic tension ratios showed that tetanic fade developed during onset of paralysis and remained maximal until about 25% recovery of the tetanic contractions, when it disappeared raidly as recovery progressed. These doses caused no significant changes in arterial pressure and heart rate and this absence of cardiovascular side-effects is a desirable property of dimethyl tubocurarine. However, for many surgical procedures, an agent with a similar pharmacological profile but with a shorter action is desirable.

Anesthesia↗
PubMed1976

Effects on non-depolarizing neuromuscular blocking agents on peripheral autonomic mechanisms in cats.

Intravenous dose-response relationships were used to correlate neuromuscular paralysis with effects on autonomic mechanisms in anaesthetized cats. Whereas autonomic blockade with tubocurarine occurred at parasympathetic and sympathetic ganglia, neuromuscular paralysing doses of gallamine, alcuronium, pancuronium and fazadinium caused blockade at vagal postganglionic sites in the heart. The vagolytic (atropinic) activity of these compounds in cats relative to their neuromuscular blocking activity appeared to correlate well with their known liability to cause undesirable hypertension and tachycardia in man. The absence of cardiovascular effects after the administration of neuromuscular blocking doses of dimethyl tubocurarine would support its more extensive clinical use, but the need remains for a short-acting muscle relaxant with properties similar to those of dimethyl tubocurarine.

Acetylcholine↗
PubMed1976

Sequential changes in the fade of tetanic tension after the administration of tubocurarine in anaesthetized man.

Tetanic and single twitch contractions of the adductor pollicis muscle in anaesthetized man were measured continuously following the i.v. injection of tubocurarine 0.2 mg/kg. Tetanic contractions were depressed earlier by tubocurarine and to a greater extent compared with the single twitch. Recovery was also slower for the tetanic contractions. The fade of tetanic tension was also measured throughout the blockade produced by tubocurarine. Fade was expressed in terms of the tetanic tension ratio: the ratio of the magnitude of the muscle tension at the end of 1 s of tetanic contraction compared with its peak height at the beginning of that contraction. Tetanic tension was well maintained during the onset of the neuromuscular block but was less well maintained during the recovery phase. It is suggested that the assessment of tetanic tension fade shoudl be carried out throughout the various stages of curarization.

Aged↗
PubMed1976

Cardiovascular and neuromuscular effects of dimethyl tubocurarine in anaesthetized cats and rhesus monkeys.

Intravenous dose-response relationships for dimethyl tubocurarine showed that vagal blockade only became appreciable (50-83%) at doses 8-16 times those sufficient for full neuromuscular paralysis in anaesthetized cats (0.0625 mg/kg) and rhesus monkeys (0.125 mg/kg); heart rate was unchanged. Sympathetic function was unimpaired by supramaximal paralysing doses of 0.5 and 1 mg/kg in cats, but was reduced (20-41%) by comparable neuromuscular paralysing doses of 1 and 2 mg/kg in rhesus monkeys; these doses decreased carotid arterial pressure by 22-36%. The duration of action of dimethyl tubocurarine was prolonged; more than 60 min was required for recovery from full neuromuscular paralysis; the drug was even more persistent in rhesus monkeys than in cats. Thus the need remains for a drug resembling dimethyl tubocurarine in its highly specific action at the neuromuscular junction, but with a much shorter duration of action.

Animals↗
PubMed1976

The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs.

1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg digoxin were used in a randomized sequence allowing at least ten days between each dose. 3 Digoxin reduced the amount of acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin. 5 These results suggest that there is little or no increased risk of cardiotoxicity during periods of transient increase in plasma levels of digoxin.

Animals↗
PubMed1975

A case of polytetrafluoroethylene poisoning in cockatiels accompanied by polymer fume fever in the owner.

Five cocatiels (Nymphicus hollandicus) died within 30 minutes following exposure to fumes from a frying pan coated with the "non-stick" plastic polytetrafluoroethylene (PTFE) that had accidentally overheated. Within an hour the owner developed symptoms of "polymer fume fever" but recovered in the next 24 hours. Clinical signs and post mortem lesions of the cockatiels are described and reference is made to the unusual susceptibility of parakeets to the pyrolysis products of frying pans coated with PTFE.

Animals↗
PubMed1975

Maximum compliance and the symptom of fullness in Meniere disease.

The symptom of fullness in Meniere disease was investigated in relation to measurements of maximum compliance (Cm) at the eardrum. The symptom of fullness is considered to be related to an increase in inner ear fluid pressure in Meniere disease. The Cms between ears were measured and compared for 36 patients with Meniere disease and the symptom of fullness in only one ear (full ear). A comparison of the Cm between the full ear and nonfull ear showed that the Cm was reduced for 32 of the patients. The data were interpreted as indicating that the Cm can be affected by pathological mechanical changes in the inner ear.

Compliance↗
PubMed1975

A new method for determination of postmortem left ventricular volumes: clinico-pathologic correlations.

A description is presented of a new and simple procedure for ventricular volume determination by means of pressure fixation of the heart and preparation of plastic molds of the ventricles which can be used to displace water in a graduated cylinder to determine the volume of the mold. Correlations between postmortem ventricular volume as measured by this method and antemortem stroke volume or clinical cardiac status indicate that a large left ventricular volume is often correlated with a low cardiac output and cardiogenic shock.

Autopsy↗
PubMed1975

The effect of suxamethonium alone and its interaction with gallamine on the indirectly elicited tetanic and single twitch contractions of skeletal muscle in man during anaesthesia.

Simultaneous measurements of tetanic and single twitch contractions of the adductor politics muscle in man were made during neuromuscular blockade induced by suxamethonium (0.2 mg/kg) under nitrous oxide, oxygen and pentazocine anaesthesia. 2. After a suitable control period, suxamethonium (0.2 mg/kg) was given intravenously and the same dose was repeated 15 min later. After a further 15 min gallamine (0.2 mg/kg) was administered intravenously. When recovery from gallamine reached a plateau on the tetanic contraction recording a third injection of suxamethonium was given. 3. In most patients, suxamethonium (0.2 mg/kg) caused a partial blockade of the single twitch and complete blockade of the tetanic contraction. In every instance, the tetanic contraction was more depressed and recovered more slowly than the single twitch which not only recovered promptly but also showed overshoot. 4. After gallamine marked antagonism to suxamethonium block developed and this was greater with the single twitch than with the tetanic contractions. 5. Tetanic-tension fade was observed after every injection of suxamethonium and the degree of fade was dependent on the frequency of the tetanic stimulation.

Adolescent↗
PubMed1975

The skeletal muscle response to the repeated administration of suxamethonium and its interaction with edrophonium in anaesthetised man.

Tetanic and single twitch contractions of the adductor pollicis muscle in man were recorded during repeated injections of suxamethonium (0.2 mg/kg or 0.1 mg/kg) every 15 minutes. 2 Tachyphylaxis to suxamethonium developed rapidly in every patient studied when single twitch contractions were observed but tetanic contractions later showed an increasingly prolonged recovery with repeated injections. 3 Edrophonium administered at the point of 50% recovery of the tetanic contractions in patients given suxamethonium (0.2 mg/kg) repeatedly first potentiated the blockade but when the tachyphylaxis had developed fully on the single twitch, usually after the third or fourth injection, the blockade of the tetanic contractions was reversed. 4 These findings indicate that the tachyphylaxis and the change in the nature of the blockade produced by suxamethonium in man take place at the same time and might be part of the same phenomenon.

Aged↗
PubMed1975

Swine dysentery: pathogenicity of Treponema hyodysenteriae.

When pure cultures of Treponema hyodysenteriae were orally inoculated into pigs, severe disease characteristic of swine dysentery developed. Less severe lesions were produced by oral inoculation of infective minced colon. Noninoculated pigs were used as controls. Inoculations of surgically isolated porcine colonic loops with either pure cultures or infective minced colon produced lesions only in the injected loop; the adjacent noninjected colon remained normal. Pigs and other experimental animals, including rabbits, guinea pigs, and mice, inoculated with washed cultures by various parenteral routes remained normal.

Administration, Oral↗