Grace Medes

Solubility of Calcium Oxalate and Uric Acid in Solutions of Urea

Conclusions The peptizing action of urea may be an important factor in increasing the solubility of these sparingly soluble compounds which are normally present in urine at about their saturation limit.

An Unknown Reducing Urinary Substance in Myasthenia Gravis.

In the course of the determination of urinary inorganic phosphate by the method of Fiske and Subbarow 1 in a case of myasthenia gravis it was observed that the phosphomolybdic acid became reduced and an intense blue color developed before the reducing agent, aminonaphtholsulfonic acid, was added. The same immediate reduction of the phosphomolybdic acid did not take place after the acid digestion in the course of the total phosphorus determination. It was also observed that occasionally in this particular urine the inorganic phosphate figures slightly exceeded the values for total phosphorus. Attempts to elucidate this phenomenon have led to our present conception that we deal with a hitherto unknown reducing urinary substance. We have obtained the same color reaction from the urines of two other cases of myasthenia gravis, but have failed to demonstrate the same in one case of muscular dystrophy and in one case of muscular atrophy, diseases in which as in myasthenia gravis a creatinuria is or may be present. Of our second and third cases of myasthenia gravis, which at the present show a milder clinical picture than our first case and from which only random samples of urine were obtained, none developed as deep a color as our first case. In one we designate the color as weak but definite, in the other as of moderate intensity. In normal urines we have never observed this reaction, which also must be in accordance with the experiences of Fiske and Subbarow. The only other condition in which we have observed a similar behavior is alkaptonuria.

Blood Flow to the Kidney and Creatinine Clearance.

In a series of experiments carried out at the University Hospital, Minneapolis, by one of us (Medes) in collaboration with Dr. Hilding Berglund, it was demonstrated that creatinine clearance may be elevated in hyperthyroidism. In 20 cases of hyperthyroidism the clearance averages 196 ± 8.6 cc. per minute, as compared with a normal average of 173 ± 2.9 cc. per minute. In the former group the range extended from 111 to 338 cc. per minute, whereas in the latter group the highest value found in 60 tests was 296 cc. per minute. That increased blood flow through the kidneys might be one factor responsible for the increased creatinine clearance seemed probable, and the present investigation, undertaken at the suggestion of Dr. Berglund, is an attempt to evaluate this factor. The thermo-stromuhr method of Rein 1 for measuring blood flow was used because it permits observations to be made under more nearly normal physiologic conditions. 2 , 3 All observations were made on dogs and limited to one kidney, the other having been removed 3 or more weeks prior to the measurement of blood flow. The unit was applied to the renal artery, employing the usual ether anesthesia and sterile technic. After the recovery of the animal observations were begun. The observations were made at intervals of about 15 minutes, and the average value throughout the period was estimated. Creatinine clearance was measured by the method of Rehberg. 4 Creatinine (1.5 to 2 gm., depending on the weight of the animal) was administered intravenously one hour before readings were started, and 150 to 250 cc. of water was given by stomach tube. All urine was removed by catheter, the bladder was flushed with several washings of physiologic sodium chloride solution and the washings were added to the urine. Summary and Conclusions. A series of experiments was undertaken to study the relation between creatinine clearance and blood flow. The thermo-stromuhr method of measuring blood flow was used because it permits such observations without the complicating factor of anesthesia. All observations were made on unilateral nephrectomized dogs. A general parallelism but not a direct proportinality between the blood flow to the kidney and the creatinine clearance was observed.

Germinal epithelium of guinea pigs during early stages of scurvy.

Guinea pigs were fed a scorbutic diet of alfalfa meal and wheat flour, equal parts by weight, oats ad libitum, and powdered whole milk (Klim) corresponding to 50 cc. fresh milk daily. The increase in weight for about 10 to 15 days was approximately at the same rate as control rats which received, in addition, 2 cc. of orange juice daily. They showed no symptoms of scurvy. At this time, however, histological changes characteristic of scurvy have already set in. Observations made on the testes of guinea pigs, fed on a scorbutic diet and killed after ten days, show engorgement of the blood vessels with degeneration of seminal epithelium in some of the tubules. Cells in early stages of spermatogenesis were especially affected. Other tubules were normal and contained all stages of developing spermatozoa. Guinea pigs kept for 30 to 40 days in a state of severe chronic scurvy show almost complete recovery of germinal epithelium after 17 days on an antiscorbutic diet.

Effect of Certain Sulfur Compounds on Coagulation of Blood

The initial observation of Mueller and Sturgis 1 that cysteine inhibits the coagulation of whole blood in vitro has since been confirmed and elaborated by Carr and Foote, 2 who suggested that the delay in coagulation might be due to certain changes which they observed in the physical state of the fibrinogen. Kühnau and Morgenstern, 3 working with glutathione, also described inhibition of coagulation within a certain range of pH. Since the mechanism of the reaction has not been explained, the experiments reported here have been undertaken. Three lines of investigation have been carried out: 1. In vivo experiments in human subjects. Cysteine and methionine, ingested and injected intravenously in amounts varying from 1 to 3.5 gm., prolonged the bleeding time as indicated by the Ivy method from a 4 minute upper limit of normal to 15 minutes (methionine, 1.31 gm. intravenously) and delayed the coagulation time as shown by the 8 mm. tube method, from an 8 minute upper normal to 16 minutes (cysteine, 1 gm. intravenously and methionine, 1.31 gm. intravenously). 2. In vitro experiments with whole blood. Cysteine hydrochloride, taurocholic acid, taurine, methionine, glycine, alanine and cysteic acid, neutralized to pH 7, were added in graded amounts giving final concentration of from 4.4 × 10-5 M to 0.18 M, and the coagulation time was determined by the 8 mm. tube method. Glycine, alanine and cysteic acid did not retard coagulation. Methionine, in contrast to its behavior in vivo, also had no effect in delaying coagulation. Cysteine produced a significant effect at a 0.046 M concentration, with a coagulation time of 18 minutes. At 0.18 M concentration, the coagulation time was 53 minutes. Taurine showed a definite effect at 0.023 M concentration (16 minutes), with a 90 minute coagulation time at 0.18 M concentration. Taurocholic acid produced a significant effect at 0.011 M concentration (34 minutes), with no coagulation during 24 hours in concentrations of 0.023 to 0.18 M.

Induced Large Variations in the Urinary Proteins in Bright's Disease, Particularly in Nephrosis.

In a previous report 1 some of the factors influencing the albumin output through diseased kidneys in chronic nephrosis and in animal experiments were discussed. The present work is a continuation of this investigation, using three patients with chronic nephrosis. With two of the patients the same sudden rise under high protein diet (130 gm. daily) occurred as in the previous experiments, with immediate fall to the original level upon return to a low protein diet (30 gm. daily). The globulin to albumin ratio in the urine remained approximately constant. During a period of fever (body temperature about 38.5°) of one of the patients, the urinary proteins increased to a still higher level, and the globulin to albumin ratio also increased, indicating a greater permeability of the kidney. That the kidney was probably damaged was indicated by the slow return of the urinary proteins to their former level, as contrasted with the sudden fall after high protein feeding. The third patient was a case of myxedenra combined with nephrosis and showed a metabolic rate of −30 at the beginning of the experiment. The induced increase of urinary protein was insignificant as compared with the result in other cases. After a short period on high protein intake, the patient was given thyroid extract daily, whereupon there occurred an immediate large rise in the protein output followed by a gradual decline during the ensuing period. This sudden increased output of protein is interpreted as a confirmation of the theory of Boothby 2 that the body contains part of its protein in the form of storage protein, which, in non-nephritic cases of myxedema is being mobilized by thyroid medication and eliminated as urinary non-protein nitrogen. In the case studied by us, the whole extra nitrogen output following the thyroid medication was in the form of urinary protein.

Histological changes in the adrenal glands of guinea pigs subjected to scurvy and severe inanition.

McCarrison 1 described histological changes in the adrenal glands of guinea pigs fed a diet lacking in vitamin C. He reported hemorrhagic infiltration and degenerative changes in the cells of the cortex and medulla. The hemorrhagic areas are described as varying in size, situated in the cortex of the gland, and are circumscribed in character. The cells of the cortex are described as losing their tessellated appearance and manifesting a state of degeneration, which includes vacuolation and loss of the staining reaction of a portion of the nuclei. Findlay 2 observed congestion in both cortex and medulla, but could not corroborate McCarrisons findings in regard to other cellular changes. Hemorrhage was observed only a few times. Höjer 3 did not observe hemorrhage. The most pronounced change was simple atrophy, at first in connection with hyperemia. Twelve guinea pigs were fed a scorbutic diet of alfalfa meal and wheat flour, equal parts by weight, oats ad libitum and powdered whole milk (Klim) corresponding to 50 cc. fresh milk daily. Others were subjected to severe inanition by receiving limited amounts of the above diet with 2 cc. orange juice added daily. Histological observations upon the adrenal glands of the different animals subjected to scurvy and starvation reveal similar changes in the adrenals. These glands present varying degrees of the changes reported by McCarrison. 1 In all cases where a change has taken place, evidence of hemorrhagic infiltration is more pronounced than degeneration of the cells. The infiltration assumes a circumscribed appearance around the medulla, occurring between the columns of cells of the cortex along the connective tissue septa.

Rats on diets high in phosphorous and low in calcium.

It has been reported by a number of investigators 1 , 2 , 3 that rats become rachitic on diets high in P and low in Ca. Two rats were kept on a normal diet (A) containing 302 mg. P and 414 mg. Ca per 100 gm. diet. Another group of two were given a diet (B) low in P (124 mg. P and 372 mg. Ca per 100 gm. diet). A third group of two were given a diet (C) containing 1044 mg. P and 19 mg. Ca per 100 gm. diet. After three weeks the rats were photographed by X-rays and ashed. The ash was analyzed for Ca, P and Mg. The X-ray photograph showed that the bones of the rats on low Ca, high P were normal, except for a slight osteoporosis. In marked contrast to those on normal diet and diet low in Ca, both rats which received diet (B) became rachitic. The percentages of Ca and P in the ash of those on diet C were slightly less than in normal rats () of their own age. The P/Ca ratio in the ash of the rats was normal (0.72). The rachitic index figured by McClendons formula 4 was (A) 5.2, (B) 1.4, and (C) 2.0.

Studies on the Neutral Sulfur of Urine. Criticism of the Iodimetric Titration of Diethylsulfide.

Summary The amount of iodine taken up at a constant temperature by diethylsulfide is the function of the concentrations of iodine, iodide ion and hydrogen ion in addition to the amount of diethylsulfide added, and there is no such chemical relation under the experimental conditions as expressed by the equation : The analytical method based upon this erroneous principle is unreliable.

Observations on the Function of the Pylorus as Revealed by Duodenal Regurgitation.

The recent attention given to Boldyreffs theory 1 , 2 , 3 of the automatic regulation of the acidity of the stomach through duodenal regurgitation, has opened up an important line of clinical investigation. Two methods of determining regurgitation are being employed, the presence of bile in the stomach, and the estimation of the total chlorides of the stomach content as compared with the free or total acid. We have investigated the presence of trypsin and bile in the fasting stomach, as well as their disappearance and reappearance in the stomach in the presence of water and dilute acid and alkali. Nine examinations were made on cases as follows: 5 total achylia, giving no acid on fractional meals or after injection of histamine (pernicious anemia). 1 normal. 1 low duodenal obstruction from retroperitoneal growth. 1 duodenal ulcer. 1 pyloric resection by the Polya method. In carrying out the experiments, the contents of the fasting stomach were removed through a Rehfuss tube with the olive located in the lower part of the stomach. The stomach was then washed at 3 to 5 minute intervals with small amounts of water or of the reagent selected, and samples immediately withdrawn; or the reagent was allowed to remain in the stomach and portions fractioned out at 5 to 10 minute intervals. In testing for the presence of trypsin, the stomach content was centrifuged or filtered if opaque, the clear fluid was then shaken with permutit to remove ammonia and a solution of purified egg albumin added to each. The mixture was then brought to a pH of 8.5 (just alkaline to phenolphthalein) and allowed to incubate 48 hours at 37°, when amino acids were tested for by Folins method.