Upon careful examination, 23 of 24 patients with progressive systemic sclerosis (PSS) were found to have abnormalities of muscle. Nineteen patients presented a homogeneous 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.

Summary. We used three methods to examine the relationship among intracellular pH, transmembrane potential, and extracellular pH. Singlebarreled 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.

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.

Gastric haemorrhage was produced regularly in mice within 6 hours of the subcutaneous injection of a large dose (2 to 10 mg./kg.) of reserpine or of deserpidine. Rescinnamine,, and tetrabenazine (Ro 1-9569) were less active. Gastric haemorrhage was also produced within 6 hours when 5-hydroxytryptamine (10 mg./kg.) was injected every half-hour. Neither reserpine nor 5-hydroxytryptamine produced gastric haemorrbage in mice which had been vagotomized by tying the oesophagus at the cardio-oesophageal junction or which had been pre-treated with iproniazid. Amphetamine was less effective than iproniazid in preventing gastric haemorrhage after reserpine, and the following drugs were ineffective: cocaine, methyl phenidate (Ritalin), amarin, caffeine, nikethamide, lysergic acid diethylamide and its 2-bromo derivative (BOL148). Gastric haemorrhage was not observed in mice which had been given substantial doses of atropine or of hexamethonium before reserpine. The incidence of haemorrhage was substantially reduced by treatment with an antacid mixture. It is concluded that reserpine-like drugs cause gastric haemorrhage by a mechanism which has an important central component and which involves the liberation of 5-hydroxytryptamine.Haverback and have shown that gastric erosion was produced in rats within 18 hr. of the injection of large doses of 5-hydroxytryptophan. Reserpine in large doses had a similar effect (Benditt and Wong, 1957;Haverback and Bogdanski, 1957;Blackman, Campion, and Fastier, 1958). Some of the pharmacological actions of both these drugs appear to be mediated by 5-hydroxytryptamine. Reserpine liberates 5-hydroxytryptamine from platelets and certain other parts of the body, and interferes with the uptake of 5-hydroxytryptamine, while 5-hydroxytryptophan is the natural precursor to 5-hydroxytryptamine (Pletscher, Shore, and Brodie, 1955; Page, 1958). Therefore, when we observed in experiments on mice that large doses of reserpine produced gastric haemorrhage and melaena within a few hours (Blackman et al., 1958), we supposed at first that this was a peripheral effect brought about by an increase in " free " 5-hydroxytryptamine. The possibility that it was a central effect was raised by our observation that reserpine did not produce gastric haemorrhage in mice which had been vagotomized at the cardio-oesophageal junction. Another observation at variance with our original hypothesis was that reserpine did not produce gastric haemorrhage in mice which had been previously treated with iproniazid (Blackman et al., 1958). Since iproniazid is a powerful inhibitor of mono-amine oxidase and is believed to delay the destruction of 5-hydroxytryptamine in the body (Page, 1958), it would be expected to enhance rather than antagonize the harmful effect of reserpine on the gastric mucosa, were the erosion brought about by the local action of 5-hydroxytryptamine. These anomalous findings induced us to carry out the experiments reported here. METHODS Male mice weighing 30 to 40 g. were used. During the 24 hr. period precedi...

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