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Biomedical subjects

J E Fletcher

Publications and source records attributed to J E Fletcher.

At least 127 records · Page 7Linked to original sources
PubMed1986

In vitro muscle contractures induced by halothane and suxamethonium. II: Human skeletal muscle from normal and malignant hyperthermia susceptible patients.

The role of lipolysis in halothane-induced contractures of human skeletal muscle was examined using three inhibitors of phospholipase A2 (PLA2) activity (quinacrine, spermine and indomethacin) and exogenously administered PLA2. In addition, we examined the effects of the same PLA2 inhibitors on contractures induced by halothane in combination with suxamethonium. The studies were conducted on directly stimulated muscle strips isolated from biopsies from patients diagnosed as MH susceptible, or not susceptible, by the halothane contracture test. The liberation of fatty acids from skeletal muscle homogenates was examined to determine whether PLA2 activity might be increased in MH susceptible patients. The three PLA2 inhibitors antagonized halothane-induced contractures of muscle from MH susceptible patients as well as induction of contractures by suxamethonium and halothane. Pre-exposing preparations that were previously unresponsive to halothane to bee venom PLA2 caused the muscle strips to respond with contractures upon subsequent challenge with halothane, but not with suxamethonium. Free fatty acid production during an in vitro incubation of skeletal muscle homogenates was greater in preparations from MH susceptible patients than in those from patients who were not susceptible. These results suggest that excess liberation of fatty acids may be involved in halothane-induced contractures of muscle from MH susceptible individuals, in the synergism observed between halothane and suxamethonium, and in human MH.

Disease Susceptibility↗
PubMed1986

Masseter muscle rigidity and malignant hyperthermia susceptibility.

Seventy-seven patients who developed masseter muscle rigidity (MMR) after receiving succinylcholine to facilitate tracheal intubation were evaluated for malignant hyperthermia (MH) susceptibility by in vitro halothane and caffeine contracture tests. Thirty-nine patients were diagnosed as MH-susceptible. Neither age, sex, nor type of surgery or anesthesia distinguished MH-susceptible from nonsusceptible patients. Two susceptible and two nonsusceptible patients had evidence of a myopathy. Fifty-two patients had serum creatine phosphokinase (CPK) levels measured in the perioperative period. Although all values were above normal, CPK values equal to or greater than 20,000 IU within 24 hr of trismus (in the absence of myopathy) were observed in six of 30 patients diagnosed as MH-susceptible, but were found in none of the nonsusceptible patients. Considering the high percentage of patients exhibiting MMR that are indeed susceptible to MH (approximately 50%) compared to estimates of MH in the population as a whole (approximately 0.005%), MMR should be considered a presumptive sign of MH. Perioperative CPK values greater than 20,000 IU are highly suggestive of MH susceptibility. Patients exhibiting MMR should be evaluated for MH susceptibility and myopathies. Succinylcholine should be avoided for subsequent anesthetics in patients with a history of MMR.

Caffeine↗
PubMed1985

In vitro interaction between halothane and succinylcholine in human skeletal muscle: implications for malignant hyperthermia and masseter muscle rigidity.

This study examines in vitro the contractures induced by halothane and succinylcholine in skeletal muscle taken as biopsy specimens from 42 patients referred to the authors' laboratory for diagnosis of malignant hyperthermia (MH) susceptibility. In addition, possible differences between the response of preparations from these same patients with and without a history of masseter muscle rigidity following succinylcholine (SCh) administration were determined to investigate the in vitro relationship of masseter muscle rigidity to MH. Halothane 3%-induced contractures in preparations from MH susceptibles were similar, whether the group had a history of masseter muscle rigidity (1.15 +/- 0.18 g; n = 10) or not (1.02 +/- 0.21 g; n = 14). Halothane did not induce significant contractures in those diagnosed as normals. Succinylcholine alone did not elicit contractures from preparations derived from MH susceptibles or nonsusceptibles. Succinylcholine induced significant contractures in all preparations preexposed to halothane. Preparations from MH-negative patients with a history of masseter muscle rigidity were rendered sensitive to halothane (contractures of 1.17 +/- 0.30 g; n = 4) when SCh was present. In contrast, halothane added in the presence of SCh did not induce contractures to the same extent in preparations from MH-negative patients without a history of masseter muscle rigidity. This is the first reported in vitro method by which to examine the clinically troublesome interaction between SCh and halothane. This approach also may prove to be important in further investigations of the relationship between masseter muscle rigidity and MH.

Caffeine↗
PubMed1984

Effects of midazolam on directly stimulated muscle biopsies from control and malignant hyperthermia positive patients.

Midazolam is a water soluble benzodiazepine of interest to the anaesthetist for use as a premedicant and for induction of anaesthesia. The effects of midazolam were observed on the resting tension of directly stimulated muscle biopsied from control and malignant hyperthermia (MH) susceptible patients. In addition, interactions between midazolam and the two most commonly used MH diagnostic agents (halothane and caffeine) were examined. Midazolam, at maximum therapeutic concentrations (ca. 0.5 microgram X ml-1), had no detectable effects on muscle contraction in preparations from control or MH positive patients. Midazolam did elicit a contracture from control and MH positive preparations when used in a concentration range of 160-1280 micrograms X ml-1. There was no significant difference between control and MH positive patients in minimum concentration of midazolam causing contracture or the strength of contracture at the respective eliciting concentration. There appears to be no interaction between midazolam and either halothane or caffeine on the resting tension of the directly stimulated muscle twitch preparation.

Anti-Anxiety Agents↗
PubMed1983

The theoretical prediction of substrate levels and their histograms in cell free perfused tissues.

The development of experimental techniques to study substrate levels in the isolated perfused heart and brain have renewed interest in the mathematical modelling of perfused capillary-tissue structures. We have reconsidered an analytic representation of the Krogh cylinder model for capillary-tissue structures and relate this mathematical model to experimental data through histograms of the oxygen (PO2) distribution. Model histograms are computed for experimental parameters of interest and changes in the histogram associated with changes in model parameters, especially diffusion constants, are demonstrated.

Brain↗
PubMed1983

An investigation into opioid systems in the pregnant rat.

The role of opioid peptides during pregnancy and parturition has not been defined. They may function as natural analgesics during parturition. Pain thresholds were tested during pregnancy but, in contrast with a previous study, were found not to change. Plasma Beta-endorphin-like-immunoreactivity (B-ELI) was measured and towards the end of pregnancy a significant increase was recorded. Peptide levels returned to the pre-gestational concentration just prior to parturition. Pituitary B-ELI was also measured and was only significantly raised on the day before expected parturition. These changes add to the evidence that opioid peptides have a physiological function during pregnancy and parturition.

Animals↗
PubMed1983

Ethoxyformylation and guanidination of snake venom phospholipases A2: effects on enzymatic activity, lethality and some pharmacological properties.

Lysine residues in the basic and relatively toxic N. nigricollis phospholipase A2 and in the acidic and relatively nontoxic N. n. atra phospholipase A2 were modified by acylation with ethoxyformic anhydride (in the presence or absence of the substrate dihexanoyl lecithin) or guanidination with O-methylisourea. Ethoxyformylation gave rise to some protein fractions in which enzymatic activity was preserved to a greater degree than intraventricular lethality. Guanidination had little effect on the isoelectric point or catalytic activity of either enzyme or on the lethal potency of the N. n. atra enzyme. However, the intraventricular lethality of the N. nigricollis enzyme was decreased much more than was its intravenous lethality, direct hemolytic potency, anticoagulant activity or cardiotoxic action on rat atrium. These results are compared to those previously obtained when the lysines in these two enzymes were carbamylated with potassium cyanate, a procedure which markedly decreased the isoelectric point of the enzymes. It is concluded that charge alone does not account for differences in toxicity. The data also indicate that there are at least two distinct active sites in both enzymes, one being primarily responsible for enzymatic activity and the other(s) associated with lethal and pharmacological effects of the protein. Modification of lysines affects the latter site(s), while having little or no effect on enzymatic activity.

Animals↗
PubMed1982

Influence of medication, pain and progress in labour on plasma beta-endorphin-like immunoreactivity.

Plasma beta-endorphin-like immunoreactivity (beta-ELI) was measured at intervals during labour in 42 patients. An increase in beta-ELI occurred during labour and increased to a maximum during the second stage. The increase in beta-ELI paralleled dilatation of the cervix. A correlation existed between the duration of labour and second stage beta-ELI in patients with labours of more than 4 h duration. Analgesic drugs were associated with changes in beta-ELI. The patients who received Entonox had greater plasma beta-ELI concentrations than those who received pethidine. A significant difference in the second stage beta-ELI existed between those who received only Entonox and those who received only pethidine. Induction and augmentation of labour were also associated with differences in beta-ELI. Patients in spontaneous labour had significantly lower beta-ELI than patients who had either artificial rupture of membranes or Syntocinon augmentation of labour.

Adolescent↗