Warren F. McGuckin

A Mathematical Model of the Glucose-tolerance test

A complete description of the response of man to large doses of glucose involves the use of more than sixteen rate constants, each varying from one person to the next. It is demonstrated here that the response of blood-glucose concentration (G) as a function of time (t) can be represented adequately by an equation involving only four constants in the equation: G=G0+A e−αt sin ωt. The values of these four constants are defined by the four measurements usually made in an ordinary glucose-tolerance test. The natural frequency ω0=r(ω2 + α2) is shown to represent the product of the rate constants for insulin production due to added glucose and for glucose utilization due to insulin action. On the basis of measurements on over 750 persons, it is suggested that the value of ω0 can be used to distinguish normal from diabetic persons more closely than any other parameter.

Serum α1-Acid Glycoprotein in Chronic Ulcerative Colitis

Serum α1-acid glycoprotein was studied in 31 controls and 130 patients with chronic ulcerative colitis (no liver disease) judged clinically to be either quiescent (25 cases), mildly (38 cases), moderately (34 cases), and severely (33 cases) active. This serum glycoprotein is increased in ulcerative colitis when the disease process is active. For example, the highest observed value in the 31 controls was 111 mg per 100 ml, the lowest value in the 34 moderately active cases was 149, and the lowest value in the severely active cases was 290. After colectomy and proctectomy for chronic ulcerative colitis, serum values declined to normal range (25 cases). In the presence of hepatic disease (cholestasis and chronic hepatitis, both with and without cirrhosis), serum glycoprotein values tended to reflect the degree of activity of the ulcerative colitis (17 cases). The serum value for α1-acid glycoprotein is a more reliable index to the degree of activity of the inflammatory process in ulcerative colitis than is the sedimentation rate. It might serve as a guide to the efficacy of controllable therapeutic procedures for chronic ulcerative colitis, since it has been shown that surgical removal of actively diseased colon and rectum produces glycoprotein values within the normal range and that the receding of severely active chronic ulcerative colitis to the quiescent phase induces glycoprotein values within or slightly above the normal range.

Treatment of Wilson's disease (hepatolenticular degeneration) with DL‐penicillamine

SINCE IT HAS BEEN THOUGHT that the abnormal accumulation of copper in the liver, brain, and kidneys might account for the symptoms and clinical findings in Wilson’s disease, it was only logical that treatment was designed with the aim of increasing the excretion of copper from the body. McCance and Widdowson,’ in 1946, and Mandelbrote and associates,” in 1948, had demonstrated that the administration of dimercaprol (BAL) could produce an increased urinary excretion of copper. This led Cumings? to report the use of BAL in the treatment of Wilson’s disease. Denny-Brown and Porter‘ also reported their experience with the use of BAL in the treatment of this condition. Because of several disadvantages of BAL, a search has been made for other preparations that might increase the urinary excretion of copper and have the advantages of oral administration and little or no toxicity. In 1956, Walshes reported the use of p, p-dimethylcysteine ( penicillamine) in hepatolenticular degeneration, demonstrating that it appeared to be superior to BAL in promoting the urinary excretion of copper. In 1958, Fister, Boulding, and Bakers reported the results of treatment with penicillamine over a period of nine months. Seven, Kliman, and Peterson,’ in 1959, recorded their experience in the treatment of 2 patients with penicillamine for ten months. Osbom and Walshea compared the effect of penicillamine and BAL on the turnover of copper in hepatolenticular degeneration. Walshe# recently reviewed the experience of 16 medical centers involving the treatment of 22 patients with penicillamine over periods ranging from four weeks to three years. In most of these patients, penicillamine proved better than BAL in promoting the urinary excretion of copper and in producing clinical improvement. However, 3 patients showed either no improvement or actual worsening of the clinical state despite a satisfactory increase in the urinary excretion of copper. Lange and Hagerlo reported on the treatment of 3 patients, plus 1 patient in whom the condition was “preclinical,” but their patients

Potassium-Sparing Effects of Triamterene in the Treatment of Hypertension

Triamterene (2,4,7-triamino-6-phenylpteridine) was employed alone and in combination with hydrochlorothiazide in the treatment of patients with group 1 and 2 hypertension. In 21 patients, triamterene alone had an inconsistent antihypertensive effect on the systolic blood pressure, which was minimal in most patients. In 16 patients the combination of triamterene and hydrochlorothiazide (2:1 by weight) reduced the systolic blood pressure slightly more than did hydrochlorothiazide alone. Triamterene alone or in combination with hydrochlorothiazide produced an increase in the concentration of potassium in serum. Side effects due to triamterene were similar to those noted with thiazide diuretics. In addition, five patients had a decreasein blood hemoglobin concentration, and two patients had reversible alterations in liver function during triamterene therapy. Triamterene may be a useful adjunct for thiazidetreated hypertensive patients by decreasing the likelihood of complicating hypokalemia.

A STUDY OF CEREBRAL PROTEIN AND POLYSACCHARIDE IN THE DOG. III. "ALBUMIN" CHANGES IN EXPERIMENTAL CEREBRAL EDEMA.

I N PREVIOUS COMMUNICATIONS1.2 we reported on the normal cerebral protein and polysaccharide in dog brain. An increase in the relative concentration of albumin in cerebral edema was first noted by Kaps% in 1954. Sperl and associates4 developed a technic, using intracerebral implantation of psyllium seed, for consistentlv producing cerebral edema in the dog. Utilizing this technic, we have confirmed the finding of Kaps in experimental cerebral edema and are reporting an extension of this as a quantitative measure of cerebral edema.

Cerebrospinal fluid total polysaccharide in diseases of the nervous system

THIS INVESTIGATION was undertaken to determine (1) whether changes in concentration of cerebrospinal fluid polysaccharides accompany neurological disorders and (2) if so, in which disorders they occur. Detailed biochemical analyses of the various polysaccharide constituents of cerebrospinal fluid have been made by other investigators.lA The constituent polysaccharides are conjugated with protein molecules to form glycoproteins which can be separated by electrophoresis into fractions, as follows : albumin glycoprotein, alpha1 glycoprotein, alpha-2 glycoprotein, beta glycoprotein, and gamma glycoprotein. Values for total glycoprotein (total polysaccharide) and for the fractionated constituents in cerebrospinal fluid of healthy individuals were determined by Apostol and Roboz and their co-workers,l~5 Bauer,2 and Hill and co-workers.6 Although several investigatorsl+-5 have indicated that determinations of polysaccharides in cerebrospinal fluid might be helpful in the diagnosis of neurological disease, reports based on studies of a significant number of cases are lacking. In a detailed investigation of 129 patients with neurological diseases, Apostol and co-workers1 found increased values for total polysaccharide in cerebrospinal fluids of almost all patients studied. Included were those who had brain tumors, multiple sclerosis, cerebral thrombosis, infectious polyneuritis, convulsive disorders, central nervous system infections, and miscellaneous disorders. The authors stressed the significance of the ratio of total polysaccharide to total protein, pointing out that in some diseases low ratios accompanying increased values for polysaccharide could be explained by the occurrence of a selective increase in the protein fractions rich in bound carbohydrates. The present study represents primarily a survey of values for total polysaccharide as found associated with various neurological diseases. Total polysaccharide as we determine it refers to all protein-bound hexoses, excluding protein-bound hexosamine. As such, the study was not geared for specificity but rather to serve as a groundwork upon which more elaborate investigations may be carried out.

Effect of adrenocortical steroids on the hypercalciuria of Wilson's disease (hepatolenticular degeneration)☆

Abstract The effect of adrenocortical steroids on the urinary and fecal excretion of calcium was studied in 2 cases of Wilsons disease: one patient had hypercalciuria; the other did not. Both patients had an increase in urinary excretion and a decrease in fecal excretion of calcium while receiving orally 45 mg. of prednisone a day. The patient without hypercalciuria later exhibited similar changes when given orally 45 mg. of cortisone acetate a day. Although these findings shed no light on the cause of hypercalciuria seen in some cases of Wilsons disease, they do show that the urinary excretion of calcium by patients with Wilsons disease can be altered by the administration of adrenocortical steroids.

Zone Electrophoretic Studies of Proteins and Glycoproteins of Bovine Serum and Synovial Fluid

Summary 1) Zone electrophoresis of 13 bovine sera yielded a mean concentration of 3.37 ± .29 g (42%) albumin, 1.19 ± .10 g (15%) alpha globulin, 1.23 ± .15 g (15%) beta globulin and 2.28 ± .49 g (28%) gamma globulin/100 ml. Serum protein-bound hexose was 124 mg/100 ml or 1.53 ± .12% of the mean serum protein concentration of 8.08 g/100 ml. Zone electrophoretic separation showed albumin to contain 7 ± 4%, alpha globulins 51 ± 6%, beta globulins 23 ± 4% and gamma globulins 20 ± 5% of the protein-bound polysaccharide. 2) Twenty-one synovial fluids from the same animals had a mean concentration of .90 ± .27 g (50%) albumin, .24 ± .08 g (14%) alpha globulins, .29 ± .10 g (16%) beta globulins and .37 ± .11 g (21%) gamma globulin/100 ml. Synovial fluid protein-bound hexose was 36 ± 11 mg/100 ml or 1.98 ± .46% of the mean synovial fluid protein of 1.80 g/100 ml. Zone electrophoretic separation showed albumin to contain 10 ± 5%, alpha globulins 49 ± 8%, beta globulins 28 ± 5%, and gamma globulins 14 ± 4% of the protein-bound polysaccharide. 3) The synovial fluid had relatively more albumin (50%) and relatively less gamma globulin (21%) than serum (albumin 42%, gamma globulin 28%) and a higher hexose/protein (PR) ratio indicating preferential permeability of albumin and one or more glycoproteins. Alpha globulins were not separated into alpha 1 and alpha 2 zones.

Picric acid staining of serum paraproteins

Abstract The picric acid stainability of globulins on paper electrophoretic strips was investigated in serum from 196 patients. In 5 of the 22 with multiple myeloma the globulins did not stain. But all of the 10 samples from patients with macroglobulinemia, 12 of the 40 from patients with liver disease, five of the 18 from patients with rheumatoid arthritis, three of the 11 from patients with lupus erythematosus, and 25 of the 95 from patients with miscellaneous diseases were strongly positive for globulin staining by picric acid. The degree of staining seemed to correlate with the concentration of γ-globulins more closely than with the type of disease.

EFFECTS OF TRIPARANOL ON THE HYPERLIPEMIA OF EXPERIMENTAL NEPHROSIS.

Summary Since triparanol (MER-29) has been shown to arrest synthesis of cholesterol at the desmosterol stage and prevent an increase of serum cholesterol, we investigated whether this drug would decrease hypercholesteremia and hyperlipemia and reveal a relationship between increase of serum cholesterol and decrease of serum proteins in nephrosis. Experimental nephrosis was produced in dogs by intravenous administration of serum from rabbits sensitized to dog kidney (NTS). Triparanol was given orally in doses of 25 mg/kg of body weight per day before, during, and for 2 weeks after administration of NTS. Total serum lipids, serum cholesterol, and serum and urinary proteins were determined before, during, and for several weeks after injection of NTS. Triparanol decreased serum cholesterol markedly and serum lipids slightly, but it had no influence on hypoproteinemia and proteinuria. The histologic changes in the kidneys were the same in the dogs receiving NTS plus triparanol as in the dogs receiving NTS alone, namely endothelial proliferation in glomerular tufts, adhesion of tuft to capsule at several points, focal fibrosis of glomeruli, hyalinization of tufts with periglomerular fibrosis, irregular thickening of basement membrane, and fusion of foot processes. The tubular epithelium showed hydropic degeneration. Triparanol aggravated the course of the disease.