Creatine Tolerance Research Articles

Williams Textbook of Endocrinology

The first edition of this famous textbook, published in 1950, was written by Robert H. Williams and 11 contributors. Williams stated then that authors chosen to collaborate in writing this book are men who have maintained intimate contact with progress in both basic and clinical investigations, and who have had great experience in the practical application of this information. [In 1950] the main clinical tests for the evaluation of thyroid function were listed as basal metabolic rate, protein bound iodine, radioiodine studies, creatine tolerance, and blood cholesterol. The main object of the text, in Williams' words, was to provide condensed and authoritative discussion of the management of clinical endocrinopathies, based on the application of fundamental information obtained from chemical and physiologic investigations. In short, this text was to serve as a bridge between basic science and clinical endocrinology. It is informative for the modern clinician to peruse that

MECHANISM OF THYROID-INDUCED CREATINURIA IN RAT, WITH SPECIAL REFERENCE TO CREATINE SYNTHESIS IN LIVER AND CREATINE LOSS FROM SKELETAL MUSCLE

Mechanism of thyroid-induced creatinuria was investigated in rats. The rats were injected with triiodothyronine (T3) (100 mug/100g, sc) at 9.00 hr. Oxygen consumption increased 12 hr after T3 injection, reaching peak value 48 hr after the injection and decreasing to the pre-injection level at 96 hr. Urinary creatine excretion also increased during the first 10 hr after the injection, approaching maximal value 34-48 hr after the injection, and decreasing to the pre-injection level 72-82 hr after the injection. Throughout the experimental period, urinary creatinine decreased with time after the injection, although the difference between the groups was not significant. A decreased creatine tolerance was also observed after T3 injection. Beta-Guanidinopropionic acid (beta-GPA), a competitive inhibitor of creatine transport into skeletal muscle, as well as partial hepatectomy, caasing inhibition of creatine synthesis, were without effect on the difference in urinary creatine excretion between T3-treated and control animals. T3 increased the plasma creatine level both in bilateral nephrectomized and in bilateral nephrectomized plus beta-GPA administrated groups. These results suggest that increased creatine loss from skeletal muscle in addition to decreased creatine uptake of skeletal muscle rather than increased hepatic synthesis of creatine play an important role in T3-induced creatinuria.

A mechanism for increased creatine tolerance in myxedema

A mechanism for increased creatine tolerance in myxedema

Muscular dystrophy. IV. Endocrine studies.

Despite early opinion to the contrary, it is now agreed that in muscular dystrophy there are no gross endocrinologic abnormalities. Evaluation of a group of children with muscular dystrophy undertaken in this clinic * provided us with an opportunity to determine the endocrine status of such children by means of some of the newer indices. MATERIAL AND METHODS Data based on observations in some but not all the members of a group of 31 children with muscular dystrophy are available. The clinical status of each child, the findings on biopsy of muscles, and the results of roentgenographic, hematologic, blood, serum, urine, and liver studies have been reported in the studies cited earlier †; relative hypercreatinemia was present prior to and at the 145-minute point of creatine tolerance tests. The particular endocrine studies, the techniques employed, and the findings are presented in the section which follows. RESULTS A. Pituitary Gonadotropins.—The output

Muscular dystrophy. III. Serum and blood solutes and other laboratory indices.

It is the general impression that in muscular dystrophy there are no regularly demonstrable abnormalities apart from the oftendescribed changes in creatine and creatinine.* On the other hand, none of the reported observations excluded the possibility of significant mean deviations detectable only upon comparison with suitable control groups. That this is indeed so is evident from studies presented in this paper. MATERIAL AND METHODS The following observations were made in a group of 31 children with history, physical examination, muscle biopsy, spinal fluid findings, and radiologic features compatible with the childhood type of muscular dystrophy.† A. Creatine Tolerance Tests .—Serum levels of creatine and creatinine were determined prior to and following the oral administration of creatine ‡ to children with muscular dystrophy and to healthy controls on the per-kilogram-of-body-weight dosage schedule indicated in Figure 2. B. Blood and Serum Solutes .—Fasting levels of blood sugar and nonprotein nitrogen and of serum

Role of female genital function in creatine metabolism as revealed by the serum creatine tolerance test

Role of female genital function in creatine metabolism as revealed by the serum creatine tolerance test

Creatine metabolism in paralyses due to various causes, especially injuries to the spinal cord.

CREATINE intolerance is characteristic of the various types of muscular dystrophies.* However, it has been described in many other conditions. Among the neurological diseases it has been noted chiefly in progressive muscular atrophy † and anterior poliomyelitis.‡ Of great importance is its occurrence both in acute anterior poliomyelitis and in the severe residuals. It has been reported in many non-neurological disorders but from few observations, as in immobilization 11 and amputation. 12 Among the patients with injuries to the spinal cord were many with disturbances in metabolism of heat, water, sugar, etc. As a part of the studies of disturbances in metabolism there was included one on creatine tolerance. The clinical material consisted of 14 patients with severe hemiplegia and 3 with crural paraplegia of cerebral origin, 9 patients who had been submitted to an anterior rhizotomy, and 6 patients with severe residuals of anterior poliomyelitis. This portion of the

Modification of the effects of immobilization upon metabolic and physiologic functions of normal men by the use of an oscillating bed

A study was made of the influence of an oscillating bed on the metabolic and physiologic disturbances associated with immobilization. The subjects were three normal healthy young men. The investigation was carried out on a metabolism ward during control (four to five weeks), immobilization (five weeks) and recovery (five to six weeks) periods. The dietary intake was constant. During the immobilization periods the subjects were in bivalved plaster casts extending from umbilicus to toes. One year previously the three subjects studied had participated in an experiment identical with the present study except that they had been immobilized in standard (fixed) hospital beds. During immobilization in the oscillating bed: 1. 1. Nitrogen excretion increased in the same general pattern as in the fixed bed experiment; but in two of the subjects nitrogen loss was approximately half as great as during an equal period of immobilization in the fixed bed. 2. 2. The loss of calcium, chiefly in the urine, was, on the average, half as great as during the same period in the fixed bed. 3. 3. The loss of phosphorus was significantly less in two of the subjects than during the same period in the fixed bed. 4. 4. Although urinary citric acid, pH and urine volume did not appreciably change, the significant reduction in urinary calcium and phosphorus losses would render the precipitation of calcium phosphate in the urinary tract less likely than during immobilization in a fixed bed. 5. 5. There was good correlation between the excretion of urinary total sulfur and nitrogen on the basis of the ratio in which they exist in muscle. The correlation between nitrogen and phosphorus on the same basis was less good, between nitrogen and potassium poor. 6. 6. Creatine tolerance tests indicated that creatine metabolism was significantly less impaired than during immobilization in the fixed bed. The decrease in muscle mass and strength of the immobilized limbs was also less than during an equal period in the fixed bed. 7. 7. Changes in basal oxygen consumption were not significant. 8. 8. The deterioration produced by fixed bed immobilization in the mechanisms essential for adequate circulation in the erect position (as measured by tilt table tests) was largely prevented. 9. 9. Measurements of venous pressure in the foot veins during oscillation revealed an average change in pressure of 140 mm. of water with each change in position of the bed. A rhythmical shift was observed in the average level of the diaphragm with each change in position of the bed, without significant alteration in the pulmonary minute ventilation. 10. 10. Changes in urinary 17-ketosteroid excretion and in serum calcium levels were not significant. 11. 11. As in the fixed bed experiment, there were no significant alterations in blood coagulation studies, circulation time, heart size or electrocardiograms. During the recovery phase most metabolic and physiologic functions returned to control levels or became re-stabilized more rapidly than following immobilization in the fixed bed. Following recovery from the oscillating bed experiment, one subject was re-immobilized in a fixed bed for two weeks. The results duplicated closely the changes observed during the first two weeks of his first immobilization in a fixed bed a year previously.

Effects of immobilization upon various metabolic and physiologic functions of normal men

A study of the effects of immobilization upon various metabolic and physiologic functions of four normal, healthy, young men was carried out on a metabolism ward during control (five to seven weeks), immobilization (six to seven weeks) and recovery (four to six weeks) periods. Throughout the study, dietary intake was kept constant. During the immobilization period the subjects were placed in bi-valved plaster casts extending from the umbilicus to the toes. 1. 1. Nitrogen excretion began to increase on the fifth to sixth day of immobilization and reached its peak during the first half of the second week. Total nitrogen losses ranged from 29.8 to 83.6 Gm., and averaged 53.6 Gm. 2. 2. Both urinary and fecal calcium excretion increased during immobilization, maximum excretion being reached by the fourth to fifth week. Total calcium losses ranged from 9 to 23.9 Cm. The calcium content of the urine was doubled during immobilization. The absence of appreciable increase in urine volume, the slight rise in urinary pH and the failure of urinary citric acid to rise parallel with the increase in calcium would all favor the precipitation of calcium phosphate in the urinary tract. A slight elevation in serum calcium levels occurred at the end of the immobilization period. 3. 3. During immobilization there was an increase in the excretion of phosphorus, total sulfur, sodium and potassium. Total sulfur was excreted in the urine in close correlation from week to week with urinary nitrogen in the ratio in which these elements exist in muscle protoplasm. The changes in phosphorus excretion showed moderately good correlation with the changes in nitrogen and calcium excretion. 4. 4. During recovery there was retention of nitrogen, calcium, phosphorus, sulfur and potassium. The recovery or return to control levels of metabolic functions was slow, retention of nitrogen and phosphorus continuing for six weeks. Re-stabilization of calcium metabolism appeared to require more than six weeks. 5. 5. Although creatine and creatinine excretion remained fairly constant, there was a definite lowering of creatine tolerance during immobilization. This impairment in creatine metabolism was accompanied by a significant decrease in muscle mass and muscle strength in the immobilized limbs. 6. 6. In only one subject was there a significant lowering of 17-ketosteroid excretion during immobilization; this subject also experienced the largest nitrogen losses. 7. 7. The decline in basal metabolic rate during immobilization averaged 6.9 per cent among the four subjects. 8. 8. Immobilization brought about a deterioration in the mechanisms essential for adequate circulation in the erect position as indicated by an increased tendency to faint in tilt table tests. Experiments indicated that the legs were the principal site of changes responsible for this deterioration and suggested that increased venous engorgement, increased extravascular fluid, capillary fragility and impaired venous or muscle tone play a r&e. 9. 9. Other circulaotry changes brought about by immobilization were a decline in total blood volume averaging 5.4 per cent, marked decreases in exercise tolerance as measured by Master and Schneider tests and an increase in the resting pulse rate of 3.8 beats per minute during immobilization, followed by an additional increase of 4.7 beats per minute during the first three weeks of recovery. 10. 10. The recovery or return to control levels of most physiologic functions required three to four weeks; exercise tolerance and leg girth required four to six weeks and the reclining pulse rate more than six weeks. 11. 11. Changes in body weight during immobilization were small, probably as a result of the simultaneous loss of muscle protoplasm and storage of fat or carbohydrate. 12. 12. There were no significant changes due to immobilization in blood coagulation studies, blood circulation time, heart size, electrocardiograms, resting arterial blood pressure, hematocrits, blood counts, vital capacity, maximum ventilation capacity or breath-holding.

Creatine Retention Capacity of Boys in Relation to Androgen Function12

It is known that prepuberal boys and girls and adult women exhibit a creatinuria though the adult male does not. Also that the tolerance for exogenous creatine is much less in the former group than in the adult male. The difference in tolerance between the sexes is, apparently, not due to a difference in sex, per se, since some muscular women exhibit a marked capacity to retain exogenous creatine (1). It is believed that a poor creatine tolerance occurs until about the age of 13 years and parallels the physiological creatinuria of adolescence (2). Castrates, eunuchoids, aged humans and those exhibiting hypogonadism also show impaired creatine retention. Thus interest is focused on the relation of hormones to the metabolism of creatine. Remen (3) found a creatinuria in elderly men (70–90 years), one eunuch and one castrate. These behaved like infants and children in that they excreted most of the injected creatine. Thus he concludes the male gonad has a definite effect on creatine excretion.

Metabolic Studies in Dermatomyositis, with a Note on the Effect of Wheat Germ.

SummaryTwo patients with dermatomyositis showed a decreased excretion of urinary calcium and an apparent impaired ability to store phosphorus. The amounts of urinary creatinine were diminished proportionally to the amounts of muscular wasting. Both patients had considerable creatinuria and an impaired creatine tolerance. Prolonged administration of large amounts of wheat germ was followed by decrease in creatinuria, increase in urinary creatinine, and definite clinical improvement.

Creatinine in Mentally Defective Patients

The influence of the endocrines on the excretion of creatine and on the urinary creatinine level has become increasingly recognized of recent years. It has, of course, long been known that hyperthyroidism is accompanied by creatine excretion. A recent investigation by Sohval, King and Reiner (1938) found that the creatine tolerance test was positive in 90% of patients with active Graves' disease, but only in 10-18% of controls. Shelton and Tager (1937) showed that four out of five slightly hypothyroid children had an increased creatine tolerance.

THE RELATIVE VALUE OF THE BASAL METABOLIC RATE, VELOCITY OF BLOOD FLOW AND CREATINE TOLERANCE TEST IN THE DIFFERENTIAL DIAGNOSIS OF GRAVES' DISEASE AND ALLIED CONDITIONS

Article1 August 1939THE RELATIVE VALUE OF THE BASAL METABOLIC RATE, VELOCITY OF BLOOD FLOW AND CREATINE TOLERANCE TEST IN THE DIFFERENTIAL DIAGNOSIS OF GRAVES' DISEASE AND ALLIED CONDITIONSFREDERICK H. KING, M.D., ARTHUR R. SOHVAL, M.D.FREDERICK H. KING, M.D.Search for more papers by this author, ARTHUR R. SOHVAL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-2-261 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe differential diagnosis of Graves' disease from a group of conditions, which occasionally simulate it in symptomatology, not infrequently presents a difficult problem. Whereas typical cases of Graves' syndrome present no difficulty, since the clinical picture is so characteristic, borderline cases in which the symptomatology is not clearly delineated are not so easy to differentiate. We refer to cases of inactive Graves' disease, autonomic imbalance, menopause with autonomic imbalance and hypertension, simple goiter and cases of essential hypertension.Because these cases are not as readily diagnosed on clinical grounds, efforts have been made by previous workers to find some objective...Bibliography1. SHORR E(a) quoted by RICHARDSON, H. B.: The relation of the thyroid gland to Graves' disease, Med. Clin. N. Am., 1934, xviii, 791. (b) RICHARDSON, H. B., and SHORR, E.: The creatine metabolism in atypical Graves' disease, Trans. Assoc. Am. Phys., 1935, l, 156. Google Scholar2. FISHBERGHITZIGKING AMWMFH: Measurement of the circulation time with saccharin, Proc. Soc. Exper. Biol. and Med., 1933, xxx, 651. CrossrefGoogle Scholar3. KESSELHYMAN LHT: Studies of Graves' syndrome and the involuntary nervous system. II. The clinical manifestations of the disturbances of the involuntary nervous system (autonomic imbalance), Am. Jr. Med. Sci., 1923, clxv, 513. CrossrefGoogle Scholar4. MOSCHCOWITZ E: The nature of Graves' disease, Arch. Int. Med., 1930, xlvi, 610. CrossrefGoogle Scholar5. BLUMGART H: The velocity of blood flow in health and disease, Medicine, 1930, x, 1. Google Scholar6. SOHVALKINGREINER ARFHM: The creatine tolerance test in the differential diagnosis of Graves' disease and allied conditions, Am. Jr. Med. Sci. 1938, cxcv, 608. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication February 12, 1938.From the Medical Service of Dr. George Baehr, The Mount Sinai Hospital, New York City. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byKrankheiten der Schilddrüse 1 August 1939Volume 13, Issue 2Page: 261-269KeywordsBlood flowCreatineHypertensionMedical servicesMenopauseMetabolic disorders ePublished: 1 December 2008 Issue Published: 1 August 1939 PDF downloadLoading ...

STUDIES IN DISEASES OF MUSCLE

In a previous report of this series 1 it was shown, in agreement with Findlay 2 and Rosenbloom and Cohoe, 3 that in adults with myotonia congenita the urinary output of creatinine and creatine is normal. It was shown further that the creatine tolerance 4 and the effects of aminoacetic acid on the metabolism of creatine in persons with this condition are similar to those observed in normal persons. Moreover, functional disturbances of the muscles, such as adventitious movements and increased resistance to passive stretch, were observed by us 1 to be without effect on the metabolism of creatine. Considered together, these findings suggest that there is no essential relationship between the functional defect (myotonia) in myotonia congenita and the metabolism of creatine. However, Poncher and Woodward, 5 on the basis of their studies, recently postulated such a relationship. They observed an increase in the myotonia of 2 patients with

STUDIES IN DISEASES OF MUSCLE

In a previous report 1 we discussed various factors influencing the ability of patients with progressive muscular dystrophy to retain ingested creatine. In the series of twenty cases investigated the creatine tolerance was impaired so that a large part of an administered dose of creatine was excreted unchanged in the urine. The defect in the ability to retain exogenous creatine varied with the degree of muscular disability. In adult patients in the early stages of the disease as much as 82 per cent of the ingested creatine was retained, whereas in patients showing advanced muscular wasting the creatine tolerance was impaired to the extent that all the ingested dose of creatine was excreted unchanged. The amount of creatine usually administered in performing the creatine tolerance tests in our studies was 1.32 Gm. However, other workers have used widely different amounts. Thus, Boothby and his associates 2 gave 1 Gm.; one

METABOLISM OF CREATINE AND CREATININE IN MUSCLE DISEASE

Article1 January 1936METABOLISM OF CREATINE AND CREATININE IN MUSCLE DISEASEA. T. MILHORAT, H. G. WOLFF, F.A.C.P.A. T. MILHORATSearch for more papers by this author, H. G. WOLFF, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-7-834 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Excerpt1. Patients with diseases which affect the skeletal muscle commonly have a creatinuria even when they are maintained on a creatine-free diet. Accompanying the creatinuria, there is usually a diminution in the excretion of creatinine and in the ability of the body to retain ingested creatine (a low creatine tolerance).2. In progressive muscular dystrophy, often large amounts of creatine are excreted. The level of the creatinuria and the impairment of the creatine tolerance are usually related to the amount of muscle disability. In advanced stages of the disease the creatine tolerance may be impaired to the extent that all... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Read at the Philadelphia meeting of the American College of Physicians, April 29, 1935.From the New York Hospital and the Department of Medicine, Cornell University Medical College, and the Russell Sage Institute of Pathology, New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Biochemistry of Myasthenia GravisBiochemie der progressiven MuskeldystrophieCreatinuria in Patients with palpable muscle affections (Myosis)THE EFFECT OF PARENTERAL INJECTION OF AMINO ACIDS AND RELATED SUBSTANCES UPON CREATINE FORMATION AND STORAGE IN THE RAT 1 January 1936Volume 9, Issue 7Page: 834-837KeywordsCreatineCreatinineDietDisabilitiesExcretionHospital medicineMusclesMuscular dystrophiesSkeletal muscles ePublished: 1 December 2008 Issue Published: 1 January 1936 PDF downloadLoading ...