Robert G. Taylor

The Schwartz-Jampel syndrome

Abstract Patients with the Schwartz-Jampel syndrome represent an example of continuous muscle fiber activity at rest. Abolition of the continuous repetitive discharges with curare showed that this was not myotonia as previously reported. The likelihood that the abnormal discharges originated from the muscle component of the neuromuscular junction rather than the nerve was suggested by the observation that spontaneous electrical activity persisted long after peripheral nerve injury in 1 of the cases. Electron-microscopic examination of biopsy specimens showed marked dilatation of the endoplasmic reticulum of skin fibroblasts and moderate dilatation of the sarcoplasmic reticulum of muscle fibres. Tissue culture studies of the fibroblasts revealed a low level of lipid label incorporation representing a non-specific depression of the synthetic machinery of these cells. These studies failed to demonstrate any mucopolysaccharide abnormality, even though the radiologic findings in 1 of the cases were consistent with those found in the Morquio-Brailsford syndrome. Histochemical evaluation showed hypertrophy of both Type I and II fibers with SDH activity uniformly high in both fiber types. AChE staining revealed marked diffuse activity throughout the sarcoplasm of the muscle similar to that reported in embryonic muscle. These findings suggest the possibility that the abnormality in this syndrome occurs during fetal development.

Effect of hind-limb suspension on young and adult skeletal muscle: I. Normal mice

The purpose of this study was to determine the effect of hind-limb suspension (HS) on morphometric, histologic, and contractile characteristics of fast extensor digitorum longus (EDL) and slow soleus (SOL) twitch muscles in adult and immature mice. Hind-limb suspension for 2 weeks was used to produce atrophy in two groups of mice, ages 4 and 12 weeks, with nonsuspended animals serving as controls. Young HS mice exhibited marked decreases in SOL weight, length, cross-sectional area (CSA), twitch and tetanic tensions, and rates of tension development and relaxation, with increases in fatigue resistance. HS reduced the diameter of both type I and IIA fibers, increased the percentage of type I fibers, and decreased the percentage of type IIA fibers in both young and adult SOL. Muscle weight, length, CSA, IIA and IIB fiber areas, and maximum rate of tetanic tension development were decreased in EDL of young HS mice; fatigue resistance and EDL half-relaxation times were increased. For most parameters evaluated, slow twitch muscle was more affected than fast twitch. HS affected contractile characteristics less than morphometric or histologic parameters. Rates of tension development and relaxation were the contractile parameters most affected by HS, and the time parameters of contraction were least affected. For all measurements young mice were more affected than adult mice.

Continuous muscle fiber activity in the Schwartz-Jampel syndrome ☆

Abstract The Schwartz-Jampel syndrome is an hereditary disease characterized by shortness of stature, muscular hypertrophy, and persistent muscular contraction at rest. The electromyographic (EMG) findings have been referred to by all authors as myotonia. In the two cases described in this article, the EMG findings were quite different from ordinary myotonia. There was continuous electrical activity at rest which did not wax and wane and accounted for the persistent muscular contraction observed clinically. This activity was not abolished by deep general anesthesia. The technique of regional neuromuscular block with curare was used to determine the origin of these discharges. In contrast to classical myotonia, the discharges were abolished by curare, and muscular relaxation was achieved. However, the likelihood that they do originate from the muscle component of the neuromuscular junction rather than the peripheral nerve was suggested by the observation that spontaneous electrical activity persisted long after inadvertent nerve injury during a surgical procedure. We suggest that the term myotonia is not appropriate for the high frequency discharges observed in this syndrome. Regional intravenous perfusion with curare is a relatively simple technique which can assist in localizing the site of origin of abnormal EMG discharges. The application of this anesthetic technique to physiological studies of the motor unit is described.

Effect of pentobarbital on contractility of mouse skeletal muscle.

Pentobarbital is a hypnotic drug commonly used as anesthesia for in vivo studies in various animals. A direct effect of pentobarbital on the central nervous system and skeletal neuromuscular junction has been known for at least 30 years. A recent study using single fiber preparations from amphibian muscles indicated a significant acute and direct effect on muscle contractility at drug concentrations within the anesthetic range. The present study using whole muscles from mice demonstrated a similar augmentation of twitch tension and rate of tension development whereas tetanic tension was reduced by this drug at similar concentrations. In addition, most time parameters of contraction were prolonged. It is of interest that the slow (oxidative) muscles were considerably more sensitive to pentobarbital than the fast (primarily anaerobic) muscles. We suggest that pentobarbital should not be used as the anesthetic agent for in vivo studies of other interventions when conclusions are based on changes in muscle contractility.

Incidence of acetylcholinesterase in the sarcoplasm of human and chicken muscles

Fifty-nine biopsies of human muscle, 53 of them abnormal, 6 normal, were studied for the histochemical localization of acetylcholinesterase (AChE) using frozen sections and light microscopy. In addition to AChE which was found at the myoneural and myotendon junction, specific staining was found around the periphery of many fibers from normal and abnormal muscles. Moreover, AChE activity was found to be high in the sarcoplasm of more than 10% of the fibers from 28 biopsies of abnormal muscle including cases of hemiplegia, spinal cord injury, denervation and neuropathy, infantile spinal muscle atrophy, Duchenne, limb-girdle and facioscapulohumeral dystrophies, Schwartz-Jampel syndrome and a myasthenic syndrome. Of the muscles from experimental animals examined, only the Rhesus monkey exhibited AChE around the periphery of the fibers, and only the dystrophic chicken and not the dystrophic mouse or hamster, showed extensive sarcoplasmic AChE. Histograms of muscle fiber diameters indicated that AChE in the sarcoplasm was associated with fibers of all sizes, depending on the nature of the disorder examined. Fibers containing AChE were smaller than unstained fibers in dystrophic chicken muscle. The results suggest that in the human, sarcoplasmic AChE is reversibly repressed during muscle maturation and that its mode of regulation by motor neurons is similar to that found in the chicken.

Fast and slow skeletal muscles: Effect of ethanol on contractility of muscles from mice

We examined in vitro the effect of ethanol at four concentrations (0g%, 0.1g%, 0.2g%, and 0.4g%) on contractile parameters of 40 fast extensor digitorum longus (EDL) and 40 slow soleus muscles from healthy mice at 35C. Preparations were curarized to avoid the possible effect of ethanol on the terminal axons or skeletal neuromuscular junction. Contractile parameters measured included: (1) twitch and tetanic tension; (2) rate of tension development; (3) time to peak tension and half relaxation for twitch; (4) time to first evidence of relaxation in the tetanus; and (5) maximum rate of relaxation. The three lower concentrations of ethanol had no significant effect on muscle contractility; however, the 0.4g% dose reduced EDL twitch tension by 9%. High doses of ethanol (2.5g%) reduced the tetanic tension produced by the EDL and soleus muscles 31% and 26%, respectively. Ethanol at 2.5g% also reduced the twitch tension of the EDL and soleus by 50% and 38%, respectively. The data suggested that the 0.4g% is the highest dose of ethanol that should be used to dilute drugs in a solution that will bathe directly stimulated curarized muscle without confounding effects. In addition, it is highly unlikely that a direct effect of ethanol on muscle contractility in humans is related to an impairment in driving.

The effect of age on the nucleic acid content of slow- and fast-twitch muscle in normal and dystrophic mice and their litter mates☆

RNA, DNA, and NCP content were measured in fast- and slow-twitch skeletal muscle of normal and dystrophic mice (HDM) and their littermates at ages 4 through 29 weeks. In normal and litter mate mice RNA and DNA content were far greater in the soleus than in the gastrocnemius while the RNA/DNA ratio and NCP content were greater in the gastrocnemius. In dystrophic mice, however, the differences between nuleic acid content of the 2 muscles were far less, apparently due to a proportionately higher content in the dystrophic gastrocnemius. Due to a proportionately lower ratio in the gastrocnemius, dystrophic RNA/DNA ratios for the 2 muscles were essentially the same. Age had a marked effect on the nucleic acid content of both muscles in all 3 mice types but to varying degrees. In the soleus, RNA and DNA content rapidly decreased until 9 to 10 weeks of age followed by a gradual decline. Soleus RNA/DNA ratios showed little change with age except in the HDM mice in which there was a significant overall decline. In the gastrocnemius, RNA content followed the same pattern but with a smaller decline in the younger ages. Age had no affect on DNA content in the normal gastrocnemius, but there was significant decline in the HDM gastrocnemius. RNA/DNA gastrocnemius ratios showed marked fluctuations in both normal and dystrophic mice but did not appear to be affected by age.

Effect of hind-limb suspension on young and adult skeletal muscle. II. Dystrophic mice.

Disuse atrophy induced by limb immobilization reportedly protects dystrophic mouse muscle from histopathological changes. This study was conducted to determine whether disuse atrophy induced by hind-limb suspension (HS) limits the histopathology and contractile abnormalities typically observed in the dystrophic mouse. Two weeks of hind-limb suspension were applied to dystrophic mice (line 129B6F1) at two ages, 4 weeks (6 mice) and 12 weeks (8 mice). Thirty-one untreated dystrophics served as controls. In general, HS exaggerated the dystrophic signs, especially in the younger mice; it reduced animal weight, muscle weight, maximum tetanic and twitch tensions, and rates of tetanic and twitch tension development. HS further slowed the contractile properties of soleus (SOL) and extensor digitorum longus (EDL) muscles, and increased their fatigue resistance. HS reduced the size of type I and IIA fibers in the 6-week SOL and EDL, but not in the 14-week muscles. HS produced a preferential atrophy of SOL type I fibers, with a parallel increase in type IIA fibers. However, it did not alleviate the fiber size variability, degree of necrosis, central nucleation, inflammation, or muscle fibrosis in dystrophic muscles. These data demonstrate that disuse by hind-limb suspension does not prevent the histopathological deterioration or loss of muscle function in 6- and 14-week dystrophic mice.

Serum creatine phosphokinase variations in dystrophic mice

Abstract Prior studies reported increased serum or plasma creatine phosphokinase (CPK) activity in dystrophic mice from strains C57BL 6J and 129 B6F1, but technique may have been a factor. In strain 129 REJ there are conflicting data with respect to CPK activities in the dystrophic mice and also with respect to any age effect on CPK activity. We compared serum CPK activity in all three dystrophic mouse strains and in a nondystrophic strain using a technique designed to eliminate or minimize muscle trauma. No significant difference in CPK activity with increasing age was noted in 129 B6F1 dystrophic or normal mice or in mice from the nondystrophic strain. Strains C57BL 6J and 129 B6F1 showed no difference in CPK activity between dystrophic and normal mice of the same strain. In strain 129 REJ, dystrophic mice had a significantly lower CPK activity than normal mice from the same strain. Significant interstrain differences in CPK activities for both normal and dystrophic mice were also observed among the three dystrophic strains as well as compared with the nondystrophic strain. Serum CPK activities are not elevated in mouse muscular dystrophy and, therefore, this disorder differs significantly from human dystrophy. Because of interstrain differences in CPK activities, studies using CPK activity as a dependent variable should use strain-specific controls.

Ulnar compression neuropathy: an uncommon complication in surgical repair of pressure ulcers.

Four patients with paraplegia at levels T3 or below were required to remain in the prone position for periods of 3 to 5 weeks following plastic surgical repair of their pressure ulcers. Serial nerve conduction studies permitted early identification of compromise of ulnar nerve function prior to onset of symptoms. These objective findings are helpful in encouraging patients to protect the nerve, thus preventing palsy.