THROMBO‐ANGIITIS OBLITERANS

of hypoglycmmia in these cases may indicate that the blood sugar concentration is not a true index of the glucose concentration in the general body tissues. Although there have been adverse reports upon the stability of protamine zinc insulin, the authors here cited maintain that its activity will remain unchanged even if it be kept for six months at room temperature. They admit, however, that the contradictory opinions of other workers are an argument in favour of the standardization of the product. Several precautions must be taken when insulin in this form is used. It is a protein mixture and must therefore not be shaken violently to secure uniform suspension, nor must alcohol be used for purposes of sterilization unless removed from both syringe and needle before injections are given. Moreover, the mixture depends for its efficiency upon an accurately adjusted pH, which means that separate instruments and separate sites of injection must be employed to prevent the possible contamination of protamine zinc insulin with the unmodified form. Again, the sterilization of syringes in common tap-water leads to the deposition in them of alkaline carbonates, which are active solvents of protein and protein precipitates, so that the periodical use of dilute hydrochloric acid is necessary. As the benefit of protamine zinc insulin is believed, with good reason, to reside in its capacity to liberate insulin at a slow rate, a state of grave acidosis would appear to be a contraindication to its use; that this is not necessarily so is shown by a rapid decrease in blood sugar after the injection of a large initial dose. Strangely enough, however, 100 units of the product have no greater effect in lowering the blood sugar than have fifty, though there is a difference in the speed with which the figures reach normal levels in the two cases. If the dose is sufficiently great, the blood sugar may sink below the normal level, to remain at that level for the space of thirty-six hours or more. Patients given gradually increasing amounts of food, on the so-called "ladder diet" plan, have responded very satisfactorily to the use of protamine zinc insulin. Judging from their blood sugar readings, their response was not only better than that to unmodified insulin, but the improvement was generally brought about by the employment of only one injection per day. Rabinowitch and his co-workers do not view favourably the practice of frequent estimation of the blood sugar during treatment with this form of insulin. They consider that it complicates treatment and may unnecessarily irritate the patient. They are content to believe that, with few easily detected exceptions, a twenty-four hour sample of urine free of sugar is an excellent indication that the blood sugar during that twenty-four hours has been at the normal level. In general, the authors state, moderately severe diabetes may be controlled by single large doses of protamine zinc insulin given at twenty-four hour intervals, and its action not infrequently continues for at least thirty-six hours. This statement is the fruit of their observations of adult and juvenile patients with diabetes of all grades of severity. Amongst 132 cases of diabetes, eight failures are cited. In these, the control of the glycosuria in diabetics with normal renal thresholds was not achieved, or the blood sugar could not be brought to normal in the fasting state when hyperglycremia existed in the absence of glycosuria. Excluding these eight patients, there were but three to whom it was found necessary to administer more than one injection per day. The excellence of these results is attributed to the uniform potency of the product used by the authors, to the precautions, previously outlined, which were employed to prevent its deterioration, to the selection of patients who would cooperate in treatment, and to the fact that all patients were kept under observation in hospital. In a forthcoming study these three workers hope to announce the results of their work with this variety of insulin upon diabetics suffering from surgical complications. A preliminary report from with one exception, the same group of investigator~ lends colour to the belief that an improvement had been made in the treatment of diabetics. It is likely that protamine zinc insulin will shortly be made available for general use, when the advantages claimed for it-lasting effects, small dosage and need for fewer injections-can be corroborated. So far, the use of the product seems to require very careful supe.rvision of the diet and the dosage, as, well as hospital control of patients.