Harold L. Dobson

RENAL GLOMERULAR AND VASCULAR LESIONS IN PREDIABETES AND IN DIABETES MELLITUS: A STUDY BASED ON RENAL BIOPSIES

Excerpt It has long been suspected that the vascular disease seen in patients with diabetes mellitus might not be directly related to the control, severity, or duration of the carbohydrate defect.1...

Properties and structure of lipoproteins.

Summary 1. Extraction of serum lipoproteins of density less than 1.063 g ml with ether produces 2 distinct ultracentrifugal components. One is associated with higher density lipoproteins and the other with lower density lipoproteins in the density group less than 1.063. In a case of essential hyperlipemia and with hyperlipemic rabbit serum only the moiety associated with lowest density lipoproteins was present. It would appear that both components are necessary in transformation of lower density lipoproteins to higher ones. Absence of the higher density moiety might result in an accumulation of lipid in lower density lipoproteins as occurred in the case of essential hyperlipemia and lipemic rabbit serum. 2. Also, it was demonstrated that both alpha and beta lipoproteins bind cholesterol in vitro. This finding suggests the possibility that serum cholesterol levels may partially depend upon this mechanism of combination.

Accuracy of Urine Testing for Sugar and Acetone by Hospital Ward Personnel

1. The determination of urinary sugar and acetone by ward nursing service personnel is often inaccurate. In 12 per cent of the tests reported in this study the level of inaccuracy could lead to significant errors in management. 2. Lack of familiarity with the test procedures and personal bias were two major factors associated with these inaccuracies. Both may be reduced by better training and supervision. 3. Limitations in the test procedures are also a major factor. These cannot be eliminated completely but the twodrop Clinitest method for urine sugar offers several advantages and should be used in preference to the five-drop method.

Absorption of 131-I labeled modified insulin

Abstract The absorption T 1 2 following subcutaneous injection of a modified preparation resembling isophane insulin into the anterior thigh is a higly variable process. This same variability was observed with human serum albumin injections. In spite of the variability individual patients consistently absorbed insulin at a rate faster or slower than the mean. More rapid absorption was observed with a smaller injection volume and after intramuscular injection. Limited data suggest that patients receiving combination insulin-oral hypoglycemic therapy and those with dermatologic abnormalities at the sites of injection also absorb more rapidly. Absorption did not correlate with type of diabetes, duration of diabetes degree of control or age. Significant doses of insulin (in the range of 40 units) should be used in studying the dynamics of the absorption of therapeutically injected insulin.

Cytochrome oxidase and reductase in muscle from vitamin E-deficient rabbits

Abstract 1. 1. One member of a pair of male litter mate New Zealand rabbits was placed on a vitamin E-deficient diet, and the other member was pair-fed the same diet supplemented with vitamin E. 2. 2. Cytochrome c reductase and oxidase enzyme determinations were carried out on biopsy material obtained at weekly intervals. 3. 3. Cytochrome c reductase was elevated in deficient animals in the terminal stages of deficiency. This elevation was apparent when the enzyme activity was expressed in units of activity per milligram of nondialyzable nitrogen, enzyme activity per milligram dry weight, or units of enzyme activity per milligram of wet weight. 4. 4. Cytochrome c oxidase tended to decrease in the first week and then returned to normal levels. 5. 5. These results strongly suggest that disruption of the cytochrome system may be a part of the biochemical metabolic defect in nutritional muscular dystrophy.

Socioeconomic status and diabetes mellitus.

Abstract The diabetic patient attending a charity clinic presents a multitude of social, economic, and medical factors that tend to make him a much different problem from the diabetic under private care. These charity patients are faced with extremely limited financial resources, are on the average in a lower intelligence group, and are often given rather superficial medical care. All too often, there is more interest in the urine or blood sugar than in the patient. Some of the measures employed to correct the more serious problems arediscussed briefly.

THE USE OF CHLORPROPAMIDE IN BRITTLE AND POORLY CONTROLLED DIABETES MELLITUS

The debeelopment of the oral hypoglycemic agents has led to some sweeping revisions in concepts about the control of the abnormal carbohydrate metabolism in diabetes mellitus. With the compounds presently available itolbutamide in the United States and tolbutamide and carbutamide in Europe), ord therapy is available only to patients with mild, stable, adult-type diabetes.l I t i\ well known that these patients are controlled by proper diet alone or by diet with small doses of insulin. Consequeiitly use of the oral agents for these patients has been more a convenience than a necessity. Patients in urgent need of some agent that will provide more stable control are the juvenile diabetics and the adult diabetic patients \ tho are poorly (ontrolled on any dose of insulin. Included in the latter group are those patients who are brittle in the sense that there is irregular daily alternation between gross hyperglycemia and overt or occult hypoglycemia. In these patients, many factors are involved, such as poor diet, irregular habit,, subcutaneoui reactions a t the sites of insulin injection, insulin overdosage, inability to breab down complex insulin, and infectionto name only a few. A s a rule, tolbutamide and carbutamide are ineffective in such patients, although an occasional excellent response has led to the hope that some other ulfonylurea u ould be helpful in achieving significantly improved clinical Lontrol. M?th the development of chlorpropamide, which \+as thought to be a more potent agent, it was felt that an adequate trial in the brittle, unstable, mcl poorly controlled diabetic was justified. Patients were selected from the Diabetic Clinic a t Jefferson Davis Hospital and referred to a special clinic for oral therapy. The patients attending the diabetic clinic a t this hoqital have been characterized in detail in the literature.* In general they are in poor linancial circumstances, of low intelligence, and poorly etluc,itetl. Chlorpropamide was started in large doses (as much as 1.5 gm. per day) in the poorly controlled diabetic receiving large doses of insulin. In general, the patient’s insulin doiage was reduced by one half when chlorpropamide therapy wa5 instituted. This was the usual practice if the patient was receiving more than 50 U. of insulin. Those with mild, stable diabetes received 500 to 1000 mg. per day as the initial dose, and insulin was discontinued Treatment was carried out on an outpatient basis and the

EFFECT OF CHLORPROPROPAMIDE ON INTERMEDIARY METABOLISM IN HUMAN SUBJECTS

Development of the oral hypoglycemic agents has stimulated widespread investigation in an attempt to clarify their mode of action. As a consequence, the metabolic activities of insulin have been investigated more intensively. At the present time there are two general concepts about the action of the sulfonylureas. One concept is that the principal action of tolbutamide and carbutamide is to stimulate insulin release from the pancreas;’, the other is that these agents produce hypoglycemia by decreasing hepatic glucose output without increasing peripheral u t i l i~a t ion .~ -~ Almost all metabolic studies reported in human and in experimental animals have been acute experiments; that is, the metabolic effects have been studied over a period of a few hours after the administration of the initial dose of the drug. It was felt that it would be worthwhile to investigate the metabolic effects of chronic administration of chlorpropamide in diabetic patients who were being maintained on it.

In vitro Effect of Surface Active Agents on Human Serum Lipoprotein and Protein Patterns.

Summary The effects of incubation of serum with various surface active agents on serum lipids and protein patterns have been studied on electrophoresis and in the ultracentrifuge. Direction of migration of lipid in electrophoresis depends upon the charge of surface active agents. Anionic surface active agents increase migration rate of both alpha and beta lipoproteins toward the anode. Cationic agents either decrease migration rate of lipids toward the anode or cause them to move toward the cathode. Non-ionic agents cause complete loss of mobility of all lipids toward either electrode. These effects could be explained by assuming that surface active agents are bound to lipoproteins and contribute their charge in the migration of these lipoproteins. Effects of surface active agents on protein patterns are less pronounced. Surface active agents either increase or decrease density of serum lipoproteins as studied in the ultracentrifuge suggesting that these agents are bound to lipoproteins. However, prediction of effects of these agents on lipoprotein densities cannot be made from knowledge of the charge present on the agent.

Paper electrophoresis of muscle fractions from vitamin E-deficient rabbits.

Summary Three pairs of male littermate rabbits were fed a commercial vit. E deficient and a vit. E supplemented diet. When the vit. E deficient member of each pair showed typical vit. E deficient symptoms, the pair of animals was sacrificed and the water soluble muscle proteins extracted from the striated muscle. The electrophoretic pattern of the deficient animals showed a significant change in distribution of water soluble proteins as compared to the control group. This change was an increase in the fast moving peak and a decrease in the slow moving peak.