Rosevear, John W.

Familial metaphysial dysostosis has been described as it occurred among 18 members of a family in seven generations. The roentgenologic changes were very similar to those seen in vitamin D resistant rickets. No biochemical defect could be detected. Studies of renal function with special reference to tubular reabsorption of phosphorus gave normal values. The treatment of choice is osteotomy, after epiphysial closure has occurred, to correct the pronounced bowing of the legs. Administration of vitamin D in high doses has no effect on the course of this disease.

Abstract A chromatographic system for organic acids has been developed, with improved stability, resolution, and sensitivity for measuring organic anions in biological samples. A calibration mixture containing 100 nEq each of 18 organic anions was clearly resolved, with a signal-to-noise ratio greater than 100:1. The baseline was essentially flat throughout the chromatogram. With scale expansion, the sensitivity limit was about 0.2 nEq per constituent. The width of each peak at half its height was 1 to 2% of its retention time. The system could thus resolve 50 or more constituents. In chromatograms of whole blood and urine more than 40 compounds are resolved. The system is basically a liquid-liquid partition between an acidified aqueous phase on silicic acid and a gradient of nonpolar and polar solvents. Eluted organic acids are detected photometrically by mixing the column effluent with a miscible solvent containing a suitable indicator. Samples require about 6 h for complete chromatography at present.

Abstract A glucose oxidase-peroxidase method for continuous automated monitoring of blood glucose has been developed. The response is linear over the range 0-800 mg/100 ml. Sensitivity can be maintained for 24 hr or longer and can be restored by rinsing the analytic system with sulfuric acid to permit studies of longer than 48 hr in duration. A precision of ± 1% can be maintained between rinses for samples containing 100-600 mg of glucose per 100 ml. This method is satisfactorily specific for glucose: The response with other sugars is less than 1% of the response obtained with the same concentration of glucose. Ascorbic acid causes no significant inhibition of the response to glucose. The inhibition by uric acid has been reduced fifty-fold compared to that in other methods. Transit through the sampling catheter and analytic system requires 15 min. Timed from the first detectable response to a change in concentration, 25% of total response is achieved in 30 sec and 90% in 80 sec. Fifty percent of an oscillation with a half-period of 45 sec can be detected; no oscillations this short were observed in records of human blood glucose. Applicability and feasibility of this method have been demonstrated in over 2000 hr of repeated blood glucose recordings in 12 diabetic and 6 normal subjects.

Eighteen diabetic patients representing a spectrum from hyperlabile to stable forms of this disease were investigated under metabolic ward conditions. Hyperlabile patients had the greatest daily and hourly variation in glycosuria and the most marked ketonuria. In our hyperlabile patients, multiple daily injections of short-acting insulin proved to be the only therapeutic measure that provided significant improvement in diabetic regulation when dietary and general health measures were already optimal. In more stable patients, longer acting insulin injected less frequently was found to be satisfactory therapy if careful adjustments to individual needs were made. Blood glucose and serum ketone-body and free fatty acid concentrations as well as qualitative estimates of glucose and ketone bodies in small samples of freshly voided urine were found to be suitable indicators of the immediate state of metabolic regulation. These parameters correlated with one another to a satisfactory degree, but they proved to be poorly correlated with measurements of urinary glucose and ketone bodies during periods of five to twenty-four hours. Quantitative analysis of individual blood samples or qualitative estimates of glucose or ketone bodies in freshly voided urine specimens proved to be unreliable indices of the patients' long-term metabolic compensation except in the most stable patients. Quantitations of urinary glucose and ketone bodiesin five, nine, and twenty-four-hour collections of urine, on the other hand, give satisfactory data to assess diabetic regulation, both as to accuracy of compensation and stability.

Three normal, three stable diabetic, and eight unstable diabetic subjects were investigated, with continuous automated blood glucose analysis for forty-eight-hour periods, during metabolic balance studies of six days' duration under near normal conditions (fed and ambulatory) after the attainment of clinically optimal diabetic regulation. The studies on unstable diabetics were performed during constant dietary intake, with one or two daily injections of intermediate-acting insulin and then repeated with four daily injections of short-acting insulin. A characteristic of blood glucose behavior, the mean amplitude of glycemic excursion (MAGE), was measured. MAGE was small for normals (range, 22 to 60 mg./100 ml.), larger for stable diabetics (67 to 82 mg./100 ml.), and largest for unstable diabetics (119 to 200 mg./100 ml.). Associated with a significant decrease (p = 0.004) in the mean diurnal glycemic level (from 146 to 244 mg,/100 ml. to 101 to 152 mg./100 ml.) achieved through the use of four daily doses of short-acting insulin there was a significant increase (p = 0.006) in hypoglycemic episodes (from 0 to 4/48 hr. to 3 to 6/48 hr.) without significant change in MAGE. The persistently large value of MAGE despite therapy with multiple injections of short-acting insulin appears to be a characteristic of unstable diabetes.

A study has been made at the Mayo Clinic of the results of treatment in 28 hypertensive patients receiving thiazide diuretics. The use of these agents produced a significant but very temporary reduction in plasma volume in most patients. The plasma volume reverted to or toward normal after the first week of treatment; therefore, hypovolemia could not explain the prolonged hypotensive effect of these drugs. Administration of thiazide diuretics did not deplete the body of its sodium stores, as measured by isotope studies in five patients on an unrestricted diet. Therapy with thiazides did not produce a persistent increase in urinary aldosterone excretion in the nine patients studied for this possibility.