The purpose of this study was to compare the effects of various regimens of pyridostigmine administration on the contractile strength of skeletal muscle. Rats were exposed to pyridostigmine according to 3 dosing schedules: 2 mg/kg ip daily, 5 mg/kg X d by sc infusion, and 25 mg/kg X d by sc infusion. After 1, 4, 10, and 20 d of exposure, measurements were made of muscle tension during tetanic stimulation, and of muscle mass, erythrocyte acetylcholinesterase activity, and body weight. Pyridostigmine produced a dose-dependent decrement in the contracture generated during tetanic stimulation. Peak effect was observed after 4 d of exposure but remained depressed after 20 d. The magnitude of the decrement correlated with the frequency of the tetanic stimulation (from 20 to 100 Hz). Muscle tension at the end of the tetanic stimulus was affected to a greater extent than the initial tension. The 25-mg/kg infusion of pyridostigmine significantly depressed erythrocyte acetylcholinesterase activity throughout the study and also decreased body weight on d 1-4. No change in muscle mass was observed in any treatment group. These results show that pyridostigmine exposure results in decrements in skeletal muscle contracture that are dose-dependent, frequency-dependent, and time-dependent. The effect is probably not the result of muscle wasting and does not correlate well with erythrocyte acetylcholinesterase inhibition. The results are consistent with effects of pyridostigmine, both presynaptically and postsynaptically, at the neuromuscular junction that affect neurotransmitter release and receptor responsiveness.

NPH Insulin-Retard Leo has an even action spread over about 20 hours. Despite this long duration of action, single daily injections proved to be adequate in only 9-12% of diabetic patients. Twice daily injection provided a highly favourable fasting blood sugar level in all instances. Because of the small initial effect, the addition of regular insulin proved necessary in some of the patients. 50:50 mixture of regular and NPH Insulin-Retard Leo is available as Insulin Initard Leo, a 30:70 mixture as Insulin Semitard Leo. There remains a group of diabetics who should mix them to their own individual requirements. There were no local reactions when using highly purified components, as long as it was the first time that the patients used such insulin or were changed over from other reaction-free preparations. Diabetics with cutaneous allergies due to other forms of insulin had the same response to NPH preparations as to highly purified insulins of other forms.

Cocaine use is reaching epidemic proportions in the UK and the consequences are a number of debilitating effects. Strokes may result from a number of mechanisms related to cocaine use. This report describes a case of cocaine induced stroke in an apparently healthy young man with unusual patterns of radiological findings on his brain MRI.

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