Resting membrane potential and ionic distribution in fast- and slow-twitch mammalian muscle.

The resting membrane potential and intracellular potassium and sodium concentration of three guinea pig hind limb muscles were studied. These properties are related to the gross color, the speed of contraction, and the biochemically defined fiber type composing the muscle. The resting membrane potential and intracellular content were: white vastus (grossly white, fast-twitch glycolytic) -85.3 mV. potassium 171.9 meq/liter; soleus (grossly red, slow-twitch oxidative) -69.7 mV, potassium 137.5 meq/liter; and red vastus lateralis (grossly red, fast-twitch oxidative glycolytic) -71.7 mV, potassium 139.6 meq/liter. In soleus and red vastus lateralis, the relative permeability of sodium to potassium was 0.041 and 0.036, while in white vastus it was 0.015. These results give us the first exception to the hypothesis that fast-twitch fibers have higher intracellular potassium and higher resting membrane potential than slow-twitch fibers.

Uric acid. Characterization of its interaction with human serum albumin.

Binding of sodium urate to human serum albumin (HSA) was measured by continuous ultrafiltration at pH 7.4 and ionic strength 0.16 over the concentration range 1-13 mg/100 ml. The percent sodium urate bound to 5 g/100 ml HSA was constant over this concentration range: 30.3 (SE+/-0.6)% being bound at 4 degrees C, 22.6+/-0.3% at 22.5 degrees C, and 19.6+/-0.3% at 37 degrees C. Derived association constants, assuming one binding site were 6.0 x 10(2) M(-1) (4 degrees C), 4.47 x 10(2) M(-1) (22.5 degrees C), and 3.88 x 10(2) M(-1) (37 degrees C).

Measurement of intracellular pH of skeletal muscle with pH-sensitive glass microelectrodes.

We used three methods to examine the relationship among intracellular pH, transmembrane potential, and extracellular pH. Single-barreled electrodes permitted the determination of resting potential and intracellular pH with a minimum of cellular injury. Double-barreled electrodes, which incorporated a reference as well as a pH-sensitive electrode in a single tip, facilitated the direct measurement of intracellular pH without the interposition of the transmembrane potential. Triple-barreled electrodes permitted measurement of intracellular pH during the controlled hyperpolarization or depolarization of the cell membrane. The results of all three methods were in close agreement and disclosed that the H(+) activity of intracellular and extracellular fluid is in electrochemical equilibrium at any given transmembrane potential. This implies that the determinants of intracellular pH are the transmembrane potential and the blood pH. The actual pH of the normal resting muscle cell is 5.99, as estimated from the normal transmembrane potential and blood pH, or as determined by direct measurements of intracellular pH.

Serum pyruvate-kinase (PK) and creatine-phosphokinase (CPK) in progressive muscular dystrophies.

PK and CPK have been determined in the serum from 208 individuals including 70 normal controls (61 adults and 9 children) and 138 patients with a variety of neuromuscular disorders. In adult controls the mean activity (+/- SE) for PK is 1.2 +/- 0.05 mumol/ml/h. In normal children PK activity was about twice as high as in normal adults and decreases with increasing age. In 26 patients with Duchenne dystrophy the range of serum PK was 4.0-150.4 and in 17 individuals with the Becker type, 3.0 to 148.7. All had elevated PK and CPK levels. Eighteen of 20 patients with the facio-scapulo-humeral (FSH) from of muscular dystrophy had increased PK while only 9 had elevated CPK. Regression analyses have shown an inverse correlation between PK levels and age (or degree of disability in DMD). Kinetic and electrophoretic studies indicate that the PK isozyme found in the serum from affected patients and from heterozygotes for the DMD gene is mainly the M1 type PK, which is the only PK isozyme found in skeletal muscle and brain and the major component from myocardium.

Serum pyruvate-kinase (PK) and creatine-phosphokinase (CPK) in female relatives and patients with X-linked muscular dystrophies (Duchenne and Becker).

Determination of serum creatine phosphokinase (CPK) activity is often used in efforts to detect carriers of X-linked muscular dystrophies. We have recently demonstrated that another serum enzyme, pyruvate-kinase (PK) may also be of use in the diagnosis of patients affected with a variety of neuromuscular disorders. To evaluate the usefulness of this assay for carrier detection, a comparative study of serum PK and CPK activity was performed in 74 female relatives of patients affected with Duchenne (DMD) and Becker (BMD) muscular dystrophies. For obligate carriers of the DMD gene, 10 of 14 had elevated CPK's, 11 of 14 had elevated PK's and 12 of 14 had abnormal results for either of the two enzymes. Three of 16 mothers of isolated cases had increased serum CPK activity and 6 of 16 had increased PK activity (7 had elevation of at least one enzyme). These preliminary data suggest that the use of PK may enhance the capability to discriminate carriers for these X-linked recessive genes.

Modified in situ decompression of the ulnar nerve at the elbow.

Controversy continues to surround the treatment of ulnar nerve compression at the elbow in the cubital tunnel. By performing extensive segmental electrodiagnostic studies of the ulnar nerve through the cubital tunnel, accuracy of diagnosis is improved. In those patients with documented compression where the ulnar nerve enters the flexor carpi radialis, decompression of this area alone yields excellent results with rapid recovery.

Regional migratory osteoporosis. A denervation disease.

Regional migratory osteoporosis is an uncommon entity charcterized by sudden attacks of migrating lower extremity paraarticular pain, local edema, and muscle atrophy; the disease is verified by radiologic demineralization and bone scan uptake. The etiology and pathogenesis are unknown. We describe a case of regional migratory osteoporosis followed over nine years by serial electromyographic studies documenting denervation patterns coincident in time and location of each acute attack. The substantiation of denervation in regional migratory osteoporosis is of both diagnostic and pathogenetic significance.

Torque-velocity relationships and muscle fiber composition in elite female athletes.

The relationship between the predominance of fast and slow muscle fibers of the vastus lateralis and "in vivo" torque velocity properties in 22 female athletes was studied. Fiber types were classified according to the histochemical myofibrillar adenosine triphosphatase technique at a basic pH. Maximal extensor troques were recorded at 30 degrees from full extension at four selected velocities. While results confirm earlier reports on muscle fiber type and performance, an additional finding was that as knee extension velocities increased from 0 to 95 degrees/s angle specific extensor torque production did not decline as seen in in vitro muscle preparations. The difference in extensor torque between 0 and 96 degrees/s appeared far more critical than the differences observed between 96 and 288 degrees/s. Significant differences in torque were seen at 96, 192, and 288 degrees/s in thos with greater than 50% and less than 50% slow-twitch fibers. When expressed per kilogram of body weight the subjects with greater than 50% fast-twitch fiber produced the greatest torque at 192 degrees/s. These results suggest that the velocity at which torque begins to decline in vivo is related to the proportion of slow-twitch fibers in the vastus lateralismuscle.

Muscle disease in progressive systemic sclerosis: diagnostic and therapeutic considerations.

Upon careful examination, 23 of 24 patients with progressive systemic sclerosis (PSS) were found to have abnormalities of muscle. Nineteen patients presented a homogenous pattern of muscle abnormalities, which untreated was associated with a stable course ("simple myopathy"). Three patients demonstrated inflammatory muscle disease indistinguishable from polymyositis while a fourth patient developed marked weakness associated with a generalized neuropathic process. Muscle enzymes, electromyogram, and muscle biopsy permitted distinction among the different muscle disorders, a distinction that could have prognostic and therapeutic importance.

Subclinical effects of chronic increased lead absorption--a prospective study. III. Neurologic findings at follow-up examination.

Neurologic examination, nerve conduction testing and electro-oculographic testing have been performed at a baseline examination and a follow-up examination in a group of lead workers with blood lead levels predominantly between 60 and 80 micrograms/dl and in a group of control workers. A statistically significant decreased saccade accuracy measurement in the lead workers compared to the controls was found at both examinations. No other simple test or pattern of findings differentiated between the lead workers and the controls, and the biological significance of the lower saccade accuracy is not clear. Nerve conduction measurements do not appear to be a satisfactory method of detecting subclinical neurologic effects of lead exposure.

Subclinical effects of chronic increased lead absorption--a prospective study. I. Study design and analysis of symptoms.

Seventy workers exposed to lead for at least one year and 35 control workers have been enrolled in a prospective study of possible neurologic effects of chronic lead absorption at or below the current standard of 80 microgram per 100 ml whole blood. The study design is described in detail. Initial results of analysis of lead-related symptoms from baseline studies indicate few differences between the exposed and nonexposed workers. The majority of differences were for central nervous system (CNS) symptoms and muscle or joint pain. Little correlation was found between symptom reporting and indices of lead absorption. The evidence suggests that factors other than lead absorption itself may be important in symptom reporting.

Subclinical effects of chronic increased lead absorption--a prospective study. II. Results of baseline neurologic testing.

This report summarizes the results of baseline neurologic testing in a group of apparently healthy workers from a secondary lead smelter and a group of controls from nearby aluminum processing plants. The test battery included a standard neurologic examination nerve conduction measurements, quantitative oculomotor function tests and detailed audiologic studies. Lead workers and controls were intermixed so that the examiners were unaware of the status of any individual being tested. Although the lead workers reported significantly more neurologic symptoms than the controls, relatively few differences were found on quantitative neurologic testing. Decreased deep tendon reflexes occured more frequently in the lead workers than in the controls (22% vs. 11%) but the difference was of borderline significance (p=0.06) and other signs of peripheral neuropathy occurred with equal frequency in both groups. The mean motor conduction velocity and sensory latency measurements were not significantly different in the lead workers and in the controls and, of the six oculomotor function measurements, only the mean accuracy of saccadic eye movements was significantly (p less than 0.01) different in the two groups. High frequency hearing loss occurred with equal frequency and severity in both groups, consistent with the level of noise exposure in the lead and control plants.