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Biomedical subjects

R Hughes

Publications and source records attributed to R Hughes.

At least 163 records · Page 9Linked to original sources
PubMed1983

Histological study of motor innervation to long nuclear chain intrafusal fibers in the muscle spindle of the cat.

Several muscle spindles of the cat tenuissimus muscle were cut in serial, 1-micron thick transverse sections and stained with toluidine blue in search for long nuclear chain intrafusal muscle fibers. Five complete poles of the long chain fibers were located. Each fiber pole displayed one plate-type motor ending situated in the extracapsular fiber region. The endings were supplied by myelinated motor axons that originated from intramuscular nerve fascicles containing motor axons to extrafusal muscle fibers. One of the endings was innervated by a collateral from a motor axon that supplied an extrafusal end-plate. Ultrastructurally, the long chain endings resembled extrafusal end-plates. They were more complex, in terms of prominence of sole-plate and degree of post-junctional folding, than any other intrafusal ending present in the spindles. The motor endings of the long chain fibers were assumed to be the terminals of static (fast) skeletofusimotor axons, which preferentially innervate the longest nuclear chain fibers of cat muscle spindles.

Animals↗
PubMed1983

Arterial lesions and blood lipids in rhesus monkeys fed human diets.

The results of three consecutive experiments are reported in which atherosclerotic lesions of adult male rhesus monkeys produced by a ration relatively rich in calories, cholesterol, and saturated fats and resembling the "average American" table-prepared fare were compared with the atherosclerotic lesions in similar monkeys fed a low-fat, low-cholesterol, and low-calorie, so-called "prudent" table-prepared ration. Each experiment lasted 2 years. The frequency and severity of gross and microscopic aortic atheromatous disease and microscopic coronary artery disease were compared. In addition, the qualitative features of the lesions, several types of analyses of blood lipids, and the reactions of aortic cells to in vivo deposited interstitial aortic deposits of lipoprotein fractions prepared from these animals are described. In general, the animals fed the average American ration had serum cholesterols that were consistently higher (383 +/- 35 mg%) than animals fed the prudent ration (199 +/- 13 mg%). The contrasts in lesion involvement varied from about 6:1 in severity for both aortic and coronary lesions to approximately 3:1 or 4:1 in frequency. The aortic gross surface area involvement at autopsy was 46% for monkeys fed the average American ration compared to 7% for the prudent diet group. In lesions of animals fed the average American ration much of the lipid was extracellular and both cell proliferation and fiber protein deposition were prominent. The small lesions in the animals fed the prudent ration were much more likely to be composed mostly of "foam cell" intimal thickenings. The lesions seen in the animals fed the average American ration resemble those seen in autopsies of many young Americans whose lesions have been studied recently and who demonstrate raised lesions in their coronary arteries and aortas in the third decade.

Animals↗
PubMed1983

Effects of 4-nitroestrone 3-methyl ether on dimethylbenz(a)anthracene-induced mammary tumors.

4-Nitroestrone 3-methyl ether has been shown to be an effective growth inhibitor of certain dimethylbenz(a)anthracene-induced rat mammary tumors in intact or ovariectomized rats. When administered at optimum levels (24 mg/kg daily), this A-ring-substituted estrone displayed no toxicity, slight estrogenicity, and an antitumor activity which was comparable to that of tamoxifen and nafoxidine and was surpassed only by ovariectomy or pharmacological doses of 17 beta-estradiol 3-benzoate. In addition, the appearance of mammary tumors was prevented when this estrogen derivative was administered to rats just prior to or after dimethylbenz(a)anthracene intubation. Unique to the action of the methyl ether of 4-nitroestrone on mammary tumors was the destruction of adenocarcinomas while permitting the appearance of fibroadenomas. Systemically, 4-nitroestrone 3-methyl ether brought about focal atrophy within the pituitary and ovaries while causing moderate hypertrophy of the uterus. Plasma prolactin was unaffected.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Use of atracurium infusions for general surgical procedures including cardiac surgery with induced hypothermia.

Atracurium was administered by infusion to four patients undergoing general surgical procedures. A mean infusion rate of 0.0068 +/- 0.0007 mgkg-1 min-1 provided adequate surgical relaxation and recovery from neuromuscular blockade was similar to that following the use of bolus injections. The effect of hypothermia on the duration of action of atracurium was studied in six patients undergoing cardiopulmonary bypass. During the phase of induced hypothermia, significantly slower infusion rates provided satisfactory surgical conditions. Atracurium appears to be eminently suitable for administration by infusion in both general and cardiac surgery.

Anesthesia, General↗
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↗
PubMed1983

Clinical assessment of atracurium using the single twitch and tetanic responses of the adductor pollicis muscles.

Atracurium has been evaluated in anaesthetized patients using the single twitch and tetanic responses of the adductor pollicis muscles. I.v. doses of 0.3-0.9 mg kg-1 produced complete neuromuscular block. In the dose range used mean arterial pressure was only decreased by about 20% of control for a few minutes after 0.9 mg kg-1 which was three times the standard dose. Changes in heart rate were minimal. The onset of maximum block of the tetanic response was faster and the subsequent block was greater and more prolonged than that of the single twitch. Intubation of the trachea could be accomplished when blockade of the tetanic response was complete and at a time when the single twitch was only slightly depressed. It was concluded that the tetanic response provided a more accurate assessment of the time-course of neuromuscular blockade than the single twitch. Infusion studies demonstrated that recovery from full neuromuscular blockade after a 30- or 60-min infusion was as rapid as that after bolus doses of atracurium 0.3-0.9 mg kg-1 and this could be regarded as further evidence of the lack of cumulative effects.

Adult↗
PubMed1983

Assessment of tetanic fade following atracurium.

The records of the recovery pattern of 30 patients given atracurium 0.2-0.9 mg kg-1 were studied. Recovery of the sustained tetanic contraction did not follow an exponential curve as had previously been assumed. However, it did fit a logistic curve so that the plot of logit blockade against time was linear between 99% and 5% blockade. The results support the previous claim that the rate of recovery is independent of dose and that the effects of atracurium are not cumulative in the clinical dose range. The use of the logit transformation may also prove helpful in the analysis of the single twitch contraction during recovery from neuromuscular blockade by atracurium.

Atracurium↗
PubMed1983

Muscle in chronic uremia--a histochemical and morphometric study of human quadriceps muscle biopsies.

This report describes qualitative and quantitative studies performed on ten muscle biopsies from chronic uremic patients on renal dialysis at light and electron microscopic (EM) levels. The muscle biopsies showed myopathic changes (variation in fiber size, central nuclei, and fiber splitting). Histochemical studies showed type II fiber atrophy and lipid deposits. The ultrastructural study showed disruption of myofibrillary architecture and subsarcolemmal deposits of glycogen, mitochondria, and lipids. Quantitative estimations of the subcellular organelles revealed a statistically significant increase in lipid and glycogen contents of the muscle. The myopathic changes, type II atrophy, and lipid and glycogen deposits in chronic uremic patients raise the question of the effects of uremia and/or chronic dialysis on muscle metabolism.

Adult↗
PubMed1982

Tachyphylaxis after repeated dosage of decamethonium in anaesthetized man.

1 The tetanic and single twitch responses to the adductor pollicis muscle were used to study the neuromuscular effects of repeated dosage of decamethonium in nine anaesthetized patients. 2 In two of three patients who received the same total dose of decamethonium in three separate series of injections, blockade of the tetanic response was less after the third administration. In the third patient tachyphylaxis was evident after the second series of injections. 3 In three other patients, tachyphylaxis occurred after the second series of injections when the total dose of decamethonium administered was at least twice that given on the first occasion. 4 In terms of tachyphylaxis the single twitch response followed a similar pattern to that of the tetanic response. 5 Once tachyphylaxis had developed, neuromuscular block of the tetanic response by decamethonium was antagonised by neostigmine (2.5 mg) and enhanced by 2% halothane. 6 In contrast, in three patients who were not exposed to more than one series of injections of decamethonium, and presumably therefore before tachyphylaxis had developed, neuromuscular block of the tetanic response was potentiated by neostigmine. Under these circumstances recovery was unaffected by halothane. 7 Thus, when tachyphylaxis occurs with decamethonium the characteristics of the block change to resemble those of the competitive neuromuscular blocking agents; these findings could be of importance in clinical anaesthesia.

Anesthesia↗
PubMed1981

The pharmacology of atracurium: a new competitive neuromuscular blocking agent.

Atracurium besylate, 2,2'-(3,11-dioxo-4,10-dioxatridecylene)-bis-[6,7-dimethoxy-1-(3,4-dimethoxy-benzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolinium] dibenzenesulphonate, is one of a new series of competitive neuromuscular blocking agents. An i.v. dose of 0.25 mg kg-1 produced complete paralysis in anaesthetized cats, dogs and rhesus monkeys; paralysis was of medium duration and was readily antagonized by neostigmine. Vagal blockade occurred only after doses 8--16 times greater than the full neuromuscular paralysing dose and effects on sympathetic mechanisms were minimal. Hypotension and bradycardia were evident after supramaximal doses of 4 mg kg-1 i.v. and these effects, together with circulatory depression, were probably attributable to histamine release. In vitro studies have shown that the non-enzymic decomposition of atracurium by "Hofmann Elimination" was enhanced by increasing pH. In vivo neuromuscular paralysis was significantly reduced when the arterial pH was increased. There were indications that neither the liver nor the kidney plays a major role in the metabolism and elimination of unchanged drug. These results are of sufficient interest to merit the evaluation of atracurium in anaesthetized man.

Acid-Base Equilibrium↗
PubMed1981

Evaluation of atracurium in anaesthetized man.

Atracurium is a potent competitive neuromuscular blocking agent in anesthetized man with no cardiovascular effects at doses required for paralysis. Endotracheal intubation can be accomplished after i.v. doses of 0.6 and 0.3 mg kg-1, within 1 and 2 min respectively. Paralysis is readily antagonized by neostigmine and is enhanced by halothane. The consistent response in terms of block and recovery which emerged when the drug was given as increments of 0.05 or 0.1 mg kg-1 indicates the absence of cumulative effects. The course of action of atracurium was appreciably shorter than that of other recognized competitive blocking agents. Doses of 0.3--0.6 mg kg-1 i.v. provided adequate relaxation during surgical intervention for 15--45 min; spontaneous recovery without the use of neostigmine was observed in some patients. In addition to the non-enzymic decomposition by "Hofmann Elimination", atracurium may also undergo an enzymic ester hydrolysis but, unlike suxamethonium, it may not be destroyed by pseudocholinesterase.

Adult↗
PubMed1981

A preliminary assessment of atracurium, a new competitive neuromuscular blocking agent.

Atracurium besylate, 2,2'-(3,11-dioxo-4,10-dioxatridecylene)-bis-[6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl 1,2,3,4-tetrahydroisoquinolinium] dibenzenesulphonate is a potent non-depolarising (competitive) neuromuscular blocking agent in the cat, monkey, dog and anaesthetized man. In man, it caused complete paralysis of the tetanic response of the adductor pollicis muscles at doses of 0.2 mg/kg. Blockade was of medium duration with rapid spontaneous recovery, and was readily reversed by neostigmine. The electrocardiogram, heart rate, arterial blood pressure and central venous pressure were virtually unchanged following doses of 0.2-0.4 mg/kg. Intubation was readily accomplished in 1.5-2 min after administration of 0.25-0.3 mg/kg.

Animals↗
PubMed1981

Synthesis and assay for activity of a proposed anorexogenic agent, L-pyroglutamyl-L-histidyl-glycine.

L-Pyroglutamyl-L-histidyl-glycine has been reported to be an anorexogenic agent in female mice. In this report the synthesis of this tripeptide is described. The synthetic material was injected into female and male mice and into male rats. In no instance did the animals decrease their food intake. Further, the weights of peptide-treated animals were the same as those of control (saline-treated) animals. The results suggest that L-pyroglutamyl-L-histidyl-glycine is not an anorexogenic agent.

Animals↗
PubMed1980

Neuromuscular blockade by neostigmine in anaesthetized man.

The tetanic and single twitch responses of the adductor pollicis muscle were used to study the neuromuscular effects of neostigmine in 26 patients anaesthetized with thiopentone and nitrous oxide. Neostigmine 2.5 mg i.v. given 5 min after exposure to halothane antagonized non-depolarizing neuromuscular block, whereas a second dose give 2-5 min later depressed the peak tetanic contraction and re-established tetanic fade. In the absence of halothane the second dose of neostigmine had less effect. Recovery of the single twitch was not impaired by the second dose. A single dose of neostigmine 5 mg rapidly antagonized the competitive block of the tetanic response but the subsequent slight depression of the peak contraction and the brief reappearance of fade were less than after 5 mg given in two doses of 2.5 mg. In patients who were not given neuromuscular blocking drugs, one or two injections of neostigmine 2.5 mg caused a substantial reduction in the peak tetanic contraction and severe tetanic fade which persisted for about 20 min; the single twitch was slightly potentiated. The neostigmine block of the tetanic response could be antagonized by gallamine and potentiated by suxamethonium. These findings indicate that neostigmine in clinical doses can produce an acetylcholine-induced block which be a potential hazard in anaesthetic practice.

Anesthesia, General↗