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Biomedical subjects

T E Nelson

Publications and source records attributed to T E Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1983

Prolonged electromechanical coupling time intervals in skeletal muscle of pigs susceptible to malignant hyperthermia.

Electromechanical properties of skeletal muscle were compared between malignant hyperthermia (MH)-susceptible and control pigs. These muscle properties were studied both in vivo and in vitro. The in vivo time interval from nerve stimulation to onset of mechanical tension was longer in muscle of pigs susceptible to MH. Kinetics of formation of the in vivo compound muscle action potential did not differ between pig groups, whereas the time from peak of the muscle action potential to tension onset was longer for MH muscle. In vitro the time from direct stimulation to tension onset was also longer for MH muscle. These results suggest that the mechanism causing longer electromechanical time intervals in MH skeletal muscle is distal to the myoneural junction. Data comparing contraction kinetics between muscle from MH and control pigs indicates that the mechanism contributing to the longer time interval involves the transfer of signal from the transverse tubule to the sarcoplasmic reticulum in the pigs studied.

Animals↗
PubMed1983

Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia.

Two fractions of sarcoplasmic reticulum, one light (LSR) and one heavy (HSR), were isolated from gracilis muscle of control and malignant hyperthermia (MH)-susceptible pigs. Part of the gracilis muscle biopsy was used to compare the contracture sensitivity of the muscle to the calcium-releasing effects of caffeine on isolated SR membranes. Gracilis muscle of MH pigs was more sensitive to the contracture-producing effects of caffeine than control pig muscle. The caffeine dose-cumulative contracture response curve for MH muscle was shifted left of that for controls. The amount of caffeine-induced calcium released from SR is a function of the amount of calcium preload and this did not differ between LSR of MH and control muscle. When LSR fractions were optimally loaded with calcium for caffeine-induced calcium release, no difference in calcium-releasing effects of varying caffeine doses was observed between MH and control LSR. At calcium preloads below optimal, the MH-LSR appeared to be more sensitive to caffeine-induced calcium release. The HSR fractions could not be loaded with calcium in a manner similar to the LSR fractions because of an apparent calcium-induced calcium release phenomenon. Therefore, calcium threshold for calcium-induced calcium release was compared between MH and control HSR fraction. The effect of caffeine on the calcium-induced calcium release was also studied. The average calcium concentration threshold for calcium-induced calcium release was markedly lower for MH vs. control HSR; 20 vs. 63 nmol Ca2+/mg, respectively. Caffeine decreased the threshold for calcium-induced calcium release more in the MH than in control HSR. Under all conditions studied, the amount of calcium released did not differ between the two groups. Ruthenium red increased the threshold calcium concentration for calcium-induced calcium release while it reduced the amount of calcium released. Increasing concentrations of Mg2+ increased the Ca2+ threshold for release and the amount of Ca2+ released but did not significantly affect rate of Ca2+ release. Results of the study suggest a defect in the mechanisms causing calcium release from SR in MH-affected muscle.

Animals↗
PubMed1983

Spectrum of susceptibility to malignant hyperthermia--diagnostic dilemma.

Utilizing established in vitro muscle contracture tests, we have identified three diagnostic contracture phenotypes for malignant hyperthermia susceptibility (MHS) among 103 patients. Phenotype H is an unequivocal diagnostic result for MHS, as is the nonsusceptible phenotype N. The third diagnostic group, phenotype K, represents an equivocal diagnostic response. To provide a basis for understanding relationships between contracture phenotypes and MHS, pigs with phenotypes H, K, and N were exposed to a standardized anesthetic protocol for assessing MHS. During the anesthetic challenge, phenotype H pigs developed a more severe form of the MH syndrome than did phenotype K pigs. Comparing phenotype H v K average responses, VO2 increased four- v twofold; lactate increased 13- v 9-fold; and temperature increased 41.7 degrees C v 39.2 degrees C, respectively. These values either had no change or decreased in the phenotype N pigs. Results of this study suggest that a spectrum of MHS exists among the human population.

Animals↗
PubMed1982

Masseter spasm induced by succinylcholine in children: contracture testing for malignant hyperthermia: report of six cases.

We evaluated six boys who had developed isolated masseter muscle spasm following intravenous succinylcholine. All were receiving halothane by inhalation.l In vitro muscle contracture tests utilizing halothane and caffeine were performed. Four of the six boys had contracture response similar to those of malignant hyperthermia susceptible patients. Rigidity following succinylcholine should prompt the clinician to consider malignant hyperthermia but has been associated with other myopathic conditions as discussed.

Anesthesia↗
PubMed1982

Malignant hyperthermia: a disease of specific myofiber type?

The present study attempts to determine if malignant hyperthermia susceptibility (MHS) is limited to muscles composed predominantly of a single major fiber type. The MHS trapezius muscle (49 per cent type 1 and 51 per cent type 2 fibers) has greater abnormal contracture response to halothane or to caffeine than does MHS gracilis (11 per cent type 1 and 80 per cent type 2 fibers). The dynamic properties (contraction and relaxation times) of MHS trapezius and MHS gracilis are similar, suggesting that the greater contracture response of MHS trapezius to halothane or to caffeine is more biochemical than physiological in origin. The results of this study are discussed in relevance to the diagnosis and to aetiologic investigation of malignant hyperthermia.

Animals↗
PubMed1982

Neurobehavioral effects of neonatal hypermagnesemia.

To investigate the effects on the newborn infant of maternal magnesium therapy for treatment of pre-eclampsia, we studied 36 hypermagnesemic infants born to pre-eclamptic mothers treated with MgSO4, 18 neonates born to untreated pre-eclamptic mothers, and 25 infants born to normal mothers. Impairment of neuromuscular transmission, as well as neurobehavioral differences when compared to controls, were found in hypermagnesemic infants. Awareness of the changes produced in the neonate by magnesium is important for accurate clinical assessment of the infant's condition, as well as for anticipating the postnatal interaction of magnesium with other drugs administered during labor and delivery.

Adult↗
PubMed1981

Specificity of an isolated salivary factor material to cystic fibrosis.

An oyster gill ciliostatic factor material has been isolated from the saliva of patients with cystic fibrosis (CF) by utilizing its ability to bind to alpha-amylase. It was quantitatively assayed by its ability to reversibly inhibit rabbit muscle glycogen debranching enzyme. The specificity of this CF factor material was investigated by comparing activities from the saliva of CF homozygotes (patients) varying in age, sex, and the severity of the disease; CF obligate heterozygotes (carriers); normal control subjects who had no family history of CF; non-CF asthmatic and allergic bronchitis patients; non-CF immunologically deficient patients with chronic respiratory problems; non-CF juvenile diabetic patients; non-CF pancreatic insufficiency patients; non-CF patients with obstructive liver cirrhosis; and non-CF patients with ectodermal dysplasia. The results show that the CF factor material isolated from CF saliva is specific to subjects with cystic fibrosis and is not associated with similar non-CE chronic disease states, nor is it produced as a result of an organ pathology associated with CF. There was no correlation between the amount of factor present in an individual CF homozygote sample and the severity of the disease. In the case of both the CF homozygote and heterozygote samples, there was also no correlation in either age or sex and the amount of factor present. The degree of inhibition produced by CF homozygotes compared to CF heterozygotes is characteristic of the autosomal recessive mode of inheritance of CF. This finding appears to associate the isolated CF factor material with the affected CF gene and suggests that the factor material is related in some way to the genetic lesion in CF.

Amylases↗
PubMed1980

Central core disease and malignant hyperthermia syndrome.

In a detailed investigation of a family with musculoskeletal abnormalities observed in four generations, the proband and his mother were found to have central cores and multicores on histochemical and electron microscopic studies of biopsied muscle. A male sibling experienced a malignant hyperthermic reaction during hand surgery, and although similar reactions had not been observed in other family members, unexplained ventricular dysrhythmias did occur in the proband during surgery. The proband and his mother were subsequently shown to be susceptible to malignant hyperthermia by abnormal in vitro muscle contractures in the presence of halothane or caffeine. Physicians and dentists caring for patients with central core disease should be aware of its possible association with malignant hyperthermia. Complete evaluation of patients with central core disease should include in vitro muscle contracture studies for malignant hyperthermia since many of patients require surgery for musculoskeletal defects.

Child↗
PubMed1980

Porcine malignant hyperthermia--failure of dantrolene dose response to diagnose susceptibility (halothane effect).

Dantrolene, a skeletal muscle relaxant, has been proven prophylactic and therapeutic for malignant hyperthermia (MH) in swine. This study examined the feasibility of using a dantrolene dose response as measured by indirectly evoked foretoe twitch depression as a means to safely discriminate MH susceptibility in swine. The effect of halothane on the dantrolene response was quantified. Subjects were five Poland China malignant hyperthermia susceptible (MHS) and five Hampshire malignant hyperthermia resistant (MHR) swine. Dantrolene dose response was determined twice in each anaesthetized subject, once with thiopentone and subsequently with thiopentone and halothane. Dantrolene in incremental doses, 0.15 mg.kg-1, was given to a cumulative dose of 2--3 mg.kg-1. Under thiopentone anaesthesia, the dantrolene dose responses were similar in MHS and MHR animals. The presence of halothane augmented dantrolene twitch depression in MHS but not MHR animals when compared to their response under thiopentone. Under halothane, the MHS animals had significantly augmented dantrolene response compared to MHR pigs, but three MHS animals had developed the MH syndrome prior to receiving dantrolene. We conclude that dantrolene muscle relaxant dose response cannot be used as a diagnostic test for MHS in swine. Halothane augments dantrolene twitch depression in MHS swine.

Animals↗
PubMed1980

Dantrolene dose response in malignant hyperthermia-susceptible (MHS) swine: method to obtain prophylaxis and therapeusis.

The authors examined the thesis that a dose of dantrolene producing 95 per cent of maximal muscle relaxation (ED95) would effectively prevent or treat malignant hyperthermia (MH). In one group of four pigs sensitive to malignant hyperthermia (MHS) a dose response to intravenous dantrolene was determined by quantitation of toe twitch tension. From these data, the ED95 relaxant dose (3.5 mg/kg) was derived. In a second group of four MHS pigs, the ED95 dantrolene dose was administered prior to MH challenge with succinylcholine, 2 mg/kg, and halothane, 1.5 per cent. MH was prevented in each animal, while measurements of arterial pressure, arterial blood-gas, pH and lactate values, rectal temperature, and heart rate were done. Later, MH rapidly developed in the same four animals when they were again challenged. When treated with the ED95 dose, each animal survived. Finally, each pig was challenged without dantrolene prophylaxis or therapeusis, and all succumbed from MH. Previous studies have shown the efficacious use of dantrolene in prevention or treatment of porcine MH, but doses used have varied, without rationale. The present study shows that in MHS pigs the ED95 muscle relaxant dose of dantrolene (3.5 mg/kg) successfully prevents and treats MH.

Animals↗