Overview. Clinical types of MS.MS is a chronic recurrent inflammatory disorder of the CNS. The disease results in injury to the myelin sheaths, the oligodendrocytes, and, to a lesser extent, the axons and nerve cells themselves. [1][2][3][4][5] The symptoms of MS vary, depending in part on the location of plaques within the CNS. Common symptoms include sensory disturbances in the limbs, optic nerve dysfunction, pyramidal tract dysfunction, bladder or bowel dysfunction, sexual dysfunction, ataxia, and diplopia. 5Four different clinical courses of MS have been defined. 6 The first, relapsing-remitting MS (RRMS), is characterized by self-limited attacks of neurologic dysfunction. These attacks develop acutely, evolving over days to weeks. Over the next several weeks to months, most patients experience a recovery of function that is often (but not always) complete. Between attacks the patient is neurologically and symptomatically stable. The second clinical course, secondary progressive MS (SPMS), begins as RRMS, but at some point the attack rate is reduced and the course becomes characterized by a steady deterioration in function unrelated to acute attacks. The third clinical type, primary progressive MS (PPMS), is characterized by a steady decline in function from the beginning without acute attacks. The fourth type, progressive-relapsing MS (PRMS), also begins with a progressive course although these patients also experience occasional attacks. Outcome measures in MS clinical trials.Evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy. Clearly, the most important therapeutic aim of any disease-modifying treatment of MS is to prevent or postpone long-term disability. However, long-term disability in MS often evolves slowly over many years.1-3 Clinical trials, by contrast, study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy. As a result, it is important to validate any short-term measure by its correlation with the actual patient outcome many years later. For a discussion of these issues, interested readers should consult the full-length assessment on the Neurology Web site at www.neurology.org.Scope of this guideline. The purpose of this assessment is to consider the clinical utility of these disease-modifying agents including the anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are currently available.

Though twelve years have now passed since the first prefrontal leucotomy was performed, the status of this form of therapy is still far from settled. There are some who would never perform the operation at all; and some who would reserve it for the chronic sick; while others (Fleming, 1944) would advise its use at an early stage in the illness in cases where there were reasonable grounds for believing that recovery would not otherwise occur. With opposition of a purely emotional kind, the profession as a whole need hardly concern itself; for appeals that the integrity of the nervous system be maintained at all costs are unlikely to impress those whose daily work brings them into contact with the personality degradation of chronic mental illness. It is difficult to see why interference with the brain in order to save sight or to save life in the case of tumour should be regarded as either more or less wicked than interference designed to save human reason.

was a marked increase in the absolute amount and percentage of nitrogen retained. The increase in food intake and in body weight is apparent. The changes in the percentage of nitrogen retained were due to changes in the proportion of ingested nitrogen excreted in the urine (Table II), whereas the percentage of the ingested nitrogen that was excreted in the faeces remained relatively constant.It is apparent (Chart) that nitrogen equilibrium was restored when the insulin injections were stopped. This latter change in nitrogen balance was accompanied by a fall in body weight. The loss of weight was due to the loss of fat or water or of both. No appreciable amount of protein was lost, since the animals did not exhibit a significantly negative nitrogen balance. Discussion The hypophysectomized insulin-treated rats were not maintained on a restricted diet, since this preparation is extremely sensitive to the hypoglycaemic action of insulin. The effect of the increased caloric intake has therefore not been defined. MacKay et ad.8 have shown that insulin enhances nitrogen retention in intact rats maintained on a restricted diet.Our data suggest that a linear relationship may exist between insulin dosage and nitrogen retention. This relationship might have been more apparent if it had been possible to prevent compensatory decreases in pancreatic beta-cell activity which undoubtedly occurred. Chaikoff and Forker' have shown that in depancreatized dogs the amount of insulin administered is linearly related to the amount of nitrogen retained.Since Banting, Campbell, and Fletcher' first showed that insulin decreases the nitrogen excreted by diabetic patients, abundant evidence has accumulated to indicate that insulin is intimately associated with protein synthesis. It has been shown in vivo and in vitro that the antidiabetic hormone stimulates the utilization of amino-acids and the synthesis of proteins and inhibits protein catabolism.6-T he results of our experiments are in accord with this evidence and they confirm and extend our previous reports. SummaryThe effect of insulin on nitrogen balance in the hypophysectomized rat has been studied. It has been found that under the conditions of this investigation hypophysectomized rats treated with insulin show a marked increase in the absolute amount and in the percentage of nitrogen retained. Over the range studied the percentage of ingested nitrogen retained bore an approximately linear relationship to the amount of insulin given.The results of these experiments confirm and extend the earlier reports from this laboratory that insulin can function as a growth hormone in the absence of pituitary factors.

Anxiety is an abnormal emotion which resembles fear subjectively but differs from it in its persistence when the cause of the emotion is no longer apparent to the patient or appears inadequate to account for the symptoms experienced. It is abnormal by the criteria we apply to illness generally-namely, that the patient is called to bear an unreasonable amount of discomfort and is disabled to a varying degree in his work and in his capacity to maintain satisfactory social relationships. Thus the definition of the term excludes the normal or

ON CHEMICAL TRANQUILLIZERS BRITISH 943 MEDICAIL JOURNAL~i However, I can only say that as a result of our recent experiences I would be sorry indeed to be without this drug again at the present time. And if frenquel, used alone or combined with E.C.T., helps only a small limited group of cases of depressions and early schizophrenics, and we can learn to pick out these groups clinically, it will still be very much worth while. Conclusion