Archives of Internal Medicine

Childs, Barton

doi: 10.1001/archinte.1961.03620020001001pmid: 13693095

Abstract The recent surge of interest in genetics has been associated with the remarkable development of biochemical techniques. These methods have enabled us to comprehend the action of the genes in terms of their relationship to protein specificity and ultimately of their control over rates of metabolic reactions. The genetic analytical method, on the other hand, brings homogeneity out of confusion, circumscribes and delineates problems, and poses the questions which biochemistry must answer. An illustration is the recent discovery of a unitary basis for a number of apparently unrelated drug-induced hemolytic anemias.1,2 First to see these problems as one were the group at the University of Chicago working under the direction of A. S. Alving. Their investigations revealed that a number of drugs could cause hemolysis of the erythrocytes of some Negroes, while those of white persons were spared. They also described certain biochemical characteristics of the sensitive erythrocytes, of References 1. Beutler, E.: The Hemolytic Effect of Primaquine and Related Compounds: A Review , Blood 14:103, 1959. 2. Childs, B., and Zinkham, W. H.: The Genetics of Primaquine Sensitivity of the Erythrocytes , in Wolstenholme, G. E. W., and O'Connor, C. M., Editors: Biochemistry of Human Genetics , London, J. & A. Churchill, Ltd., 1959, p. 76. 3. Marks, P. A.; Johnson, A. B., and Hirshberg, E.: Effect of Age on the Enzyme Activity in Erythrocytes , Proc. Nat. Acad. Sc. 44:529, 1958.Crossref 4. Childs, B.; Zinkham, W. H.; Browne, E. A.; Kimbro, E. L., and Torbert, J. U.: A Genetic Study of a Defect in Glutathione Metabolism of the Erythrocyte , Bull. Johns Hopkins Hosp . 102:21, 1958. 5. Gross, R. T.; Hurwitz, R. E., and Marks, P. A.: An Hereditary Enzymatic Defect in Erythrocyte Metabolism: Glucose-6-Phosphate Dehydrogenase Deficiency , J. Clin. Invest. 37: 1176, 1958.Crossref 6. Marks, P. A., and Gross, R. T.: Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency: Evidence of Differences Between Negroes and Caucasians with Respect to This Genetically Determined Trait , J. Clin. Invest. 38:2253, 1959.Crossref 7. Zinkham, W. H., and Lenhard, R. E., Jr.: Metabolic Abnormalities of Erythrocytes from Patients with Congenital Nonspherocytic Hemolytic Anemia , J. Pediat. 55:319, 1959.Crossref 8. Rimon, A.; Askenazi, I.; Ramot, B., and Sheba, C.: Activation of Glucose-6-Phosphate Dehydrogenase of Enzyme Deficient Subjects , Biochem. & Biophys. Res. Comm. 2:138, 1960. 9. Kirkman, H. N.; Riley, H. D., and Crowell, B. B.: Different Enzyme Expressions of Mutants of Human Glucose-6-Phosphate Dehydrogenase , Proc. Nat. Acad. Sc. 46:938, 1960. 10. Ramot, B.; Fisher, S.; Szeinberg, A.; Adam, A.; Sheba, C., and Gafni, D.: A Study of Subjects with Erythrocyte Glucose-6-Phosphate Dehydrogenase Deficiency: II. Investigation of Leucocyte Enzymes , J. Clin. Invest. 38:2234, 1959. 11. Marks, P. A.; Gross, R. T., and Hurwitz, R. E.: Gene Action in Erythrocyte Deficiency of Glucose-6-Phosphate Dehydrogenase: Tissue Enzyme Levels , Nature, London 183: 1266, 1959. 12. Zinkham, W. H.: Enzyme Studies on Lenses from Persons with Primaquine-Sensitive Erythrocytes , in Transactions of the Society for Pediatric Research, 1960, p. 33. 13. Motulsky, A. G.: Metabolic Polymorphisms and the Role of Infectious Diseases in Human Evolution , Human Biology 32:28, 1960.

WAYS, PETER;HUFF, JOHN W.;KOSMALER, CHARLES H.;YOUNG, LAWRENCE E.

doi: 10.1001/archinte.1961.03620020004002pmid: 13783510

Abstract Introduction The propensity for chronic renal disease, particularly pyelonephritis, glomerulonephritis, and carcinoma, to be accompanied by anemia is well known in clinical medicine. More striking, though less frequently seen, is the association of renal disease, usually carcinoma of the kidney, with polycythemia. This coincidence was mentioned incidentally by Bliss,1 in 1929, and since then has been documented by numerous others.2-28 At the present time we are aware of 60 cases associating renal disease with polycythemia which have been either mentioned or described in detail in the literature. Fortyseven of these record the coincidence of primary carcinoma and polycythemia,* 3 report patients with hydronephrosis and polycythemia,20,22,26 5 patients are described in whom polycythemia and "polycystic disease" coexisted.9,25 There is one report in each instance associating polycythemia with benign adenoma of the kidney,12 sarcoma of the kidney,26 tuberculosis of the kidney,23 secondary renal carcinoma,3 References 1. References 1-8, 10, 11, 13-19, 21, 25-28. 2. Bliss, T. L.: Basal Metabolism in Polycythemia Vera , Ann. Int. Med. 2:1155-1161, 1929.Crossref 3. Medvei, C. V.: Über ein bemerkenswertes Zusammentreffen von Arthritis urica, Erythrämie Typ Vaquez und Hypernephroma malignum , Wein. Arch. inn. Med. 24:417-426, 1934. 4. Fairley, K. D.: Two Cases of Gaisboeck's Disease (Polycythemia Hypertonica) Associated with Carcinoma of the Kidney , Roy. Melbourne Hosp. Clin. Rep. 16:47-55, 1945. 5. Forssell, J.: Polycytemi vid hypernefrom , Nord. med. 30:1415-1418, 1946. 6. Forssell, J.: Polycytemi vid hypernefrom , Nord. med. 35:1479, 1947. 7. Videbaek, A.: Polycythemia Vera: Course and Prognosis , Acta med. scandinav. 138:179-187, 1950.Crossref 8. Videbaek, A.: Polycythemia Vera Coexisting with Malignant Tumors (Particularly Hypernephroma) , Acta med. scandinav. 138:239-245, 1950.Crossref 9. Forssell, J.: Polycythemia and Hypernephroma , Acta med. scandinav. 150:155-161, 1954.Crossref 10. Kurrle, G. R.: A Case of Gaisböck's Disease (Polycythemia Hypertonica) , M.J. Australia 1:777-780, 1954. 11. Lawrence, J. H.: Polycythemia: Physiology, Diagnosis, and Treatment Based on 303 Cases , New York, Grune & Stratton, Inc., 1955. 12. Gros, H.: Hypernephrom und Polyglobulie, Medizinische, pp. 706-708, 1955. 13. DeMarsh, Q. B., and Warmington, W. J.: Polycythemia Associated with a Renal Tumor , Northwest Med. 54:976-979, 1955. 14. Moe, E.: Polycytaemi og hypernefrom , Nord. med. 56:1164-1165, 1956. 15. Herbeuval, R.; Cuny, G., and Larcan, A.: Maladie de Vaquez et hypernéphrome , Presse méd. 65:132-134, 1957. 16. Berger, L., and Sinkoff, M. W.: Systemic Manifestations of Hypernephroma: A Review of 273 Cases , Am. J. Med. 22:791-796, 1957.Crossref 17. Conley, C. L.; Kowal, J., and D'Antonio, J.: Polycythemia Associated with Renal Tumors , Bull. Johns Hopkins Hosp. 101:63-73, 1957. 18. Clinico-Pathologic Conference, Cleveland Clinic Foundation, Ascites, Azotemia and Epigastric Mass , edited by J. B. Hazard, New Physician (J. Student A.M.A.) 6:44-50 ( (Nov.) ) 1957. 19. Campbell, J. H.; Pasquier, C. M.; St. Martin, E. C., and Worley, P. C.: Hypernephroma Associated with Polycythemia and Eczematoid Dermatitis , J. Urol. 79:12-15, 1958. 20. Frey, W. G., III: Polycythemia and Hypernephroma: Review and Report of a Case with Apparent Surgical Cure , New England J. Med. 258:842-844, 1958.Crossref 21. Gardner, F. H., and Freymann, J. G.: Erythrocythemia (Polycythemia) and Hydronephrosis: Report of a Case with Radio-Iron Studies, with Recovery After Nephrectomy , New England J. Med. 259:323-327, 1958.Crossref 22. Damon, A.; Holub, D. A.; Melicow, M. M., and Uson, A. C.: Polycythemia and Renal Carcinoma , Am. J. Med. 25:182-197, 1958.Crossref 23. Cooper, W. M., and Tuttle, W. B.: Polycythemia Associated with a Benign Kidney Lesion: Report of a Case of Erythrocytosis with Hydronephrosis, with Remission of Polycythemia Following Nephrectomy , Ann. Int. Med. 47:1008-1015, 1957.Crossref 24. Damon, A., and Holub, D. A.: Host Factors in Polycythemia Vera , Ann. Int. Med. 49:43-60, 1958.Crossref 25. Cramer, F., and Kimsey, W.: The Cerebellar Hemangioblastomas: Review of 53 Cases, with Special Reference to Cerebellar Cysts and the Association of Polycythemia , A.M.A. Arch. Neurol. & Psychiat. 67:237-252, 1952. 26. Forssell, J.: Nephrogenous Polycythemia , Acta med. scandinav. 161:169-179, 1958. 27. Lawrence, J. H., and Donald, W. G., Jr.: Polycythemia and Hydronephrosis or Renal Tumors , Ann. Int. Med. 50:959-969, 1959. 28. Chwalla, R.: Endokrine Erscheinungen beim Hypernephrom der Niere und ihre Bedeutung , Ztschr. Urol. 45:521-542, 1952. 29. Sjöberg, J.: Polycytaemi og hypernephrom , Nord. med. 57:294, 1957. 30. Reissmann, K. R.: Studies on the Mechanism of Erythropoietic Stimulation in Parabiotic Rats During Hypoxia , Blood 5:372-380, 1950. 31. Root, W. S.: The Stimulus for Erythropoiesis , J. Mt. Sinai Hosp. New York 20:331-338, 1954. 32. Erslev, A. J.: Physiologic Control of Red Cell Production , Blood 10:954-961, 1955. 33. Gordon, A. S.; Piliero, S. J.; Kleinberg, W., and Freedman, H. H.: A Plasma Extract with Erythropoietic Activity , Proc. Soc. Exper. Biol. & Med. 86:255-258, 1954. 34. Erslev, A. J.: Erythropoietic Function in Dilution Anemia , Blood 10:616-622, 1955. 35. Jacobson, L. O.; Plzak, L.; Fried, W., and Goldwasser, E.: Plasma Factor(s) Influencing Red Cell Production , Nature, London 177:1240, 1956. 36. Gray, D. F., and Erslev, A. J.: Reticulocytosis Induced by Serum From Hypoxic Animals , Proc. Soc. Exper. Biol. & Med. 94:283-286, 1957. 37. Erslev, A. J.: Observations on the Nature of the Erythropoietic Serum Factor: II. Erythropoietic Activity of Serum and Bone Marrow After Time Limited Exposure to Anemic and Hypoxic Anoxia , J. Lab. & Clin. Med. 50:543-549, 1957. 38. Bethell, F. H.; Linman, J. W., and Korst, D. R.: Erythropoietic Activity of Anemic and Polycythemic Plasmas , Tr. A. Am. Physicians 70: 297-304, 1957. 39. Gurney, C. W.; Goldwasser, E., and Pan, C.: Studies on Erythropoiesis: VI. Erythropoietin in Human Plasma , J. Lab. & Clin. Med. 50:534-542, 1957. 40. Gurney, C. W.: The Dynamic Equilibrium of Erythropoiesis: Studies of Its Theoretical and Clinical Significance , Proc. Inst. Med., Chicago 22:58-65, 1958. 41. Jacobson, L. O.; Goldwasser, E.; Fried, W., and Plzak, L.: Role of the Kidney in Erythropoiesis , Nature, London 179:633-634, 1957. 42. Jacobson, L. O.; Goldwasser, E.; Fried, W., and Plzak, L. F.: Studies on Erythropoiesis: VII. The Role of the Kidney in the Production of Erythropoietin , Tr. A. Am. Physicians 70:305-317, 1957. 43. Goldwasser, E.; Fried, W., and Jacobson, L. O.: Studies on Erythropoiesis: VIII. The Effect of Nephrectomy on Response to Hypoxic Anoxia , J. Lab. & Clin. Med. 52:375-378, 1958. 44. Erslev, A. J.: Erythropoietic Function in Uremic Rabbits , A.M.A. Arch. Int. Med. 101: 407-417, 1958.Crossref 45. Erslev, A. J.: Erythropoietic Factor in the Control of Red Cell Production, in Hematopoietic Mechanisms , Ann. New York Acad. Sc. 77:627-637, 1959.Crossref 46. Erslev, A. J.: Erythropoietic Function in Nephrectomized Rabbits , Clin. Res. Proc. 7:201-202, 1959. 47. Lucké, B., and Schlumberger, H. G.: Tumors of the Kidney, Renal Pelvis, and Ureter, Atlas of Tumor Pathology , U.S. Armed Forces Institute of Pathology, 1957.

RANDALL, RUSSELL E.;STRAUSS, MAURICE B.;McNEELY, WILLIAM F.

doi: 10.1001/archinte.1961.03620020013003pmid: 13739449

Abstract I. The Diversity of Clinical Manifestations Eleven years ago Burnett and his associates1 described a syndrome occurring in patients who had ingested milk and absorbable alkali for prolonged periods of time. The characteristic features were hypercalcemia without hypercalciuria or hypophosphatemia, mild alkalosis, a normal serum alkaline phosphatase, severe renal insufficiency with azotemia, and calcinosis manifested chiefly by the presence of band keratopathy. Improvement followed restriction of the intake of milk and absorbable alkali. In the intervening decade it has become apparent that there are many variants in the "milk-alkali syndrome," as it has now come to be known.2-20 It is the purpose of this paper to present 4 cases illustrating the variability of manifestations which may result from excessive intake of milk and to stress 3 facts: 1. Hypercalcemia may continue for many months after cessation of a large calcium intake; 2. Moderate impairment in renal function with References 1. Kindly performed by Dr. William H. Baker, Massachusetts General Hospital, Boston. 2. The alkaline phosphatase values in normal adults lie between 0.8 and 2.3 Sigma units, comparable to 1 to 4.5 Bodansky units. 3. In dogs, experimentally produced hypercalcemia of 24 hours' duration (range 12.3 to 16.0 mg/100 ml.) not only led to marked impairment of urinary concentration, but in most instances to reduced inulin clearance (an index of filtration rate) and moderate elevation of blood urea nitrogen content.61,62 In several animals studied weeks later, one or more of these parameters of renal function remained abnormal. Animals autopsied within a few days as well as weeks after the episode of hypercalcemia showed extensive lesions involving the ascending limb of Henle, the distal convolution, and the collecting system.62,88 Intratubular calcific casts led early to dilation proximally and in some instances to later atrophy of proximal convolutions. To this intratubular obstruction the diminished filtration rate and nitrogen retention may be ascribed. 4. Coray: Traite d'Hippocrate des airs, des eauxet des lieux, Paris, Baudelot et Eberhart, 1800, Chap. III, Paragraphs XXVII-LVII. 5. Burnett, C. H.; Commons, R. R.; Albright, F., and Howard, J. E.: Hypercalcemia Without Hypercalcuria or Hypophosphatemia, Calcinosis and Renal Insufficiency: A Syndrome Following Prolonged Intake of Milk and Alkali , New England J. Med. 240:787-794, 1949.Crossref 6. McQueen, E. G.: "Milk Poisoning" and "Calcium Gout," Lancet 2:67-69, 1952.Crossref 7. Miller, J. M.; Freeman, I., and Heath, W. H.: Calcinosis Due to Treatment of Duodenal Ulcer , J.A.M.A. 148:198-199, 1952.Crossref 8. Wermer, P.; Kuschner, M., and Riley, E. A.; Reversible Metastatic Calcification Associated with Excessive Milk and Alkali Intake , Am. J. Med. 14:108-115, 1953.Crossref 9. DuFault, F. X., Jr., and Tobias, G. J.: Potentially Reversible Renal Failure Following Excessive Calcium and Alkali Intake in Peptic Ulcer Therapy , Am. J. Med. 16:231-236, 1954.Crossref 10. Dworetzky, M.: Reversible Metastatic Calcification (Milk-Drinker's Syndrome) , J.A.M.A. 155: 830-832, 1954.Crossref 11. Kyle, L. H.: Differentiation of Hyperparathyroidism and the Milk-Alkali (Burnett) Syndrome , New England J. Med. 251:1035-1040, 1954.Crossref 12. Rodnan, G., and Johnson, H.: Chronic Renal Failure in Association with the Excessive Intake of Calcium and Alkali: Report of Case and Review of Pathogenesis , Gastroenterology 27:584-597, 1954. 13. Snapper, I.; Bradley, W. G., and Wilson, V. E.: Metastatic Calcification and Nephrocalcinosis from Medical Treatment of Peptic Ulcer , A.M.A. Arch. Int. Med. 93:807-817, 1954.Crossref 14. Holten, C., and Lundbaek, K.: Renal Insufficiency and Severe Calcinosis Due to Excessive Alkali-Intake , Acta med. scandinav. 151:177-183, 1955.Crossref 15. Kessler, E.: Hypercalcemia and Renal Insufficiency Secondary to Excessive Milk and Alkali Intake , Ann. Int. Med. 42:324-338, 1955.Crossref 16. Ogle, J. C., and Harvey, C. M., Jr.: Hypercalcemia and Renal Impairment Following Milk and Alkali Therapy for Peptic Ulcer , South. M.J. 48:126-129, 1955.Crossref 17. Schneider, R. W.: Problems in the Differentiation of the Milk-Alkali (Burnett's) Syndrome and Hyperparathyroidism, Illustrated by 2 Case Reports , Cleveland Clin. Quart. 22:184-189, 1955.Crossref 18. Scholz, D. A., and Keating, F. R., Jr.: Milk-Alkali Syndrome: Review of 8 Cases , A.M.A. Arch. Int. Med. 95:460-468, 1955.Crossref 19. Atlas, D. H.; Gaberman, P., and Eisenberg, H. L.: Syndrome of Masked Hyperparathyroidism , Ann. Int. Med. 44:1195-1210, 1956.Crossref 20. Case Records of the Massachusetts General Hospital: Case No. 42441 , New England J. Med. 255:863-870, 1956.Crossref 21. Epstein, F. H.: Reversible Uremic States , J.A.M.A. 161:494-499, 1956.Crossref 22. Wenger, J.; Kirsner, J. B., and Palmer, W. L.: The Milk-Alkali Syndrome: Hypercalcemia, Alkalosis and Azotemia Following Calcium Carbonate and Milk Therapy of Peptic Ulcer , Gastroenterology 33:745-769, 1957. 23. Frank, A., and Greenspan, G.: Milk-Alkali Syndrome Complicated by Salt-Losing Nephritis , New England J. Med. 260:210-213, 1959.Crossref 24. Rifkind, B. M.; Chazan, B. I., and Aitchison, J. D.: Chronic Milk-Alkali Syndrome with Generalized Osteosclerosis after Prolonged Excessive Intake of "Rennie's" Tablets , Brit. M.J. 1:317-320, 1960.Crossref 25. Fiske, C. H., and Logan, M. A.: The Determination of Calcium by Alkalimetric Titration: II. The Precipitation of Calcium in the Presence of Magnesium, Phosphate, and Sulfate, with Applications to the Analysis of Urine , J. Biol. Chem. 93:211-226, 1931. 26. Elliott, W. E.: Volumetric Determination of Calcium in Blood Serum , J. Biol. Chem. 197: 641-644, 1952. 27. Fiske, C. H., and Subbarow, Y.: The Colorimetric Determination of Phosphorus , J. Biol. Chem. 66:375-400, 1925. 28. Bodansky, A.: Phosphatase Studies: II. Determination of Serum Phosphatase: Factors Influencing the Accuracy of the Determination , J. Biol. Chem. 101:93-104, 1933. 29. Garner, R. J.: Colorimetric Determination of Magnesium in Plasma or Serum by Means of Titan Yellow , Biochem. J. 40:828-831, 1946. 30. Gornall, A. G.; Bardawill, C. J., and David, M. M.: Determination of Serum Proteins by Means of the Biuret Reaction , J. Biol. Chem. 177: 751-766, 1949. 31. Young, M. K., Jr., and Raisz, L. G.: An Anthrone Procedure for Determination of Inulin in Biological Fluids , Proc. Soc. Exper. Biol. & Med. 80:771-774, 1952. 32. Goldring, W., and Chasis, H.: Hypertension and Hypertensive Disease , Cambridge, Mass., The Commonwealth Fund, Harvard University Press, 1944, p. 203. 33. Howard, J. E.; Hopkins, T. R., and Connor, T. B.: On Certain Physiologic Responses to Intravenous Injection of Calcium Salts into Normal, Hyperparathyroid and Hypoparathyroid Persons , J. Clin. Endocrinol. 13:1-19, 1953. 34. Henneman, P. H.; Carroll, E. L., and Albright, F.: The Suppression of Urinary Calcium and Magnesium by Oral Sodium Phytate: A Preliminary Report , Ann. New York Acad. Sc. 64: 343-350,. 1956. 35. Henneman, P. H.; Dempsey, E. F.; Carroll, E. L., and Albright, F.: The Cause of Hypercalcuria in Sarcoid and Its Treatment with Cortisone and Sodium Phytate , J. Clin. Invest. 35: 1229-1242, 1956. 36. Serum Acid and Alkaline Phosphatase and "Prostatic" Acid Phosphatase Using "Sigma 104 Phosphate Substrate," Tech. Bull. No. 104, Sigma Chemical Corporation, St. Louis, Mo., 1958. 37. Raisz, L. G.; McNeely, W. F., and Saxon, L.: Studies on the Renal Concentrating Mechanism: I. Role of Vasopressin , J. Lab. & Clin. Med. 52:437-445, 1958. 38. Gutman, A. B., and Yu, T. F.: Renal Function in Gout: With a Commentary on the Renal Regulation of Urate Excretion and the Role of the Kidney in the Pathogenesis of Gout , Am. J. Med. 23:600-622, 1957. 39. Cope, C. L.: Base Changes in the Alkalosis Produced by the Treatment of Gastric Ulcer with Alkalies , Clin. Sc. 2:287-300, 1936. 40. Kirsner, J. B., and Palmer, W. L.: The Role of Chlorides in Alkalosis: Following the Administration of Calcium Carbonate , J.A.M.A. 116:384-390, 1941. 41. Telfer, S. V.: Studies in Calcium and Phosphorus Metabolism: Part III. The Absorption of Calcium and Phosphorus and Their Fixation in the Skeleton , Quart. J. Med. 17:245-259, 1923-1924. 42. McGowan, J. P.: Some Considerations Regarding and Investigations into Calcium and Phosphorus Metabolism , Biochem. J. 27:934-942, 1933. 43. Schmidt, C. L. A., and Greenburg, D. M.: Occurrence, Transport and Regulation of Calcium, Magnesium and Phosphorus in the Animal Organism , Physiol. Rev. 15:297-434, 1935. 44. Albright, F., and Reifenstein, E. C., Jr.: The Parathyroid Glands and Metabolic Bone Disease: Selected Studies , Baltimore, The Williams & Wilkins Company, 1948. 45. Kempster, E.; Breiter, H.; Mills, R.; McKey, B.; Bernds, M., and Outhouse, J.: The Utilization of the Calcium of Di-Calcium Phosphate by Children , J. Nutrition 20:279-287, 1940. 46. Howard, J. E.; Parson, W., and Bigham, R. S., Jr.: Studies on Patients Convalescent from Fracture: III. The Urinary Excretion of Calcium and Phosphorus , Bull. Johns Hopkins Hosp. 77: 291-313, 1945. 47. Knapp, E. L.: Factors Influencing the Urinary Excretion of Calcium: I. In Normal Persons , J. Clin. Invest. 26:182-202, 1947. 48. Hegsted, D. M.; Moscoso, I., and Collazos, C. C.: A Study of the Minimum Calcium Requirements of Adult Man , J. Nutrition 46:181-201, 1952. 49. Patton, M. B., and Sutton, T. S.: The Utilization of Calcium from Lactate, Gluconate, Sulfate and Carbonate Salts by Young College Women , J. Nutrition 48:443-452, 1952. 50. Nicolaysen, R.; Eeg-Larsen, N., and Malm, O. J.: Physiology of Calcium Metabolism , Physiol. Rev. 33:424-444, 1953. 51. Rubin, M.; Thomas, R. D.; Litovitz, T. A., and Geschickter, C. F.: Dynamics of Calcium Metabolism , in Metabolic Interrelations with Special Reference to Calcium, Transactions of the 5th Conference , edited by E. C. Reifenstein, Jr., New York, Josiah Macy, Jr. Foundation Publications, 1953, pp. 53-71. 52. Brine, C. L., and Johnston, F. A.: Endogenous Calcium in the Feces of Adult Man and the Amount of Calcium Absorbed from Food , Am. J. Clin. Nutrition 3:418-420, 1955. 53. Kerr, C.; Loken, H. F.; Page, E. W., and Gordan, G.: Calcium and Phosphate Dynamics in Pregnancy: Effects of Oral Calcium Preparations, work in preparation. 54. Henneman, P. H., and Baker, W. H.: Two Mechanisms of Sustained Hypercalcemia Following Hypervitaminosis D and the Milk-Alkali Syndrome , abstract, J. Clin. Invest. 36:899, 1957. 55. Heaney, R. P., and Whedon, G. D.: Radio-calcium Studies of Bone Formation Rate in Human Metabolic Bone Disease , J. Clin. Endocrinol. 18:1246-1267, 1958.Crossref 56. Neuman, W. F., and Neuman, M. W.: The Chemical Dynamics of Bone Mineral , Chicago, University of Chicago Press, 1958. 57. Rich, C.: The Distribution of Calcium Given to Human Subjects by Sustained Intravenous Infusion , J. Clin. Endocrinol. 20:147-156, 1960.Crossref 58. Thomas, W. C., Jr.; Connor, T. B., and Morgan, H. G.: Diagnostic Considerations in Hypercalcemia, with a Discussion of the Various Means by Which Such a State May Develop , New England J. Med. 260:591-596, 1959.Crossref 59. Thomas, W. C., Jr.; Morgan, H. G.; Connor, T. B.; Haddock, L.; Bills, C. E., and Howard, J. E.: Studies of Antiricketic Activity in Sera from Patients with Disorders of Calcium Metabolism and Preliminary Observations on the Mode of Transport of Vitamin D in Human Serum , J. Clin. Invest. 38:1078-1085, 1959.Crossref 60. Carpenter, H. M., and Pautler, E. E.: Hyperparathyroidism with Renal Insufficiency: Report of a Case Confused with the "Burnett Syndrome," New England J. Med. 250:453-456, 1954.Crossref 61. Dorhout Mees, E. J.: Disturbed Water-Reabsorption by the Renal Tubules in 2 Patients with Hypercalcaemia , Acta med. scandinav. 157: 199-204, 1957.Crossref 62. Cohen, S. I.; Fitzgerald, M. G.; Fourman, P.; Griffiths, W. J., and de Wardener, H. E.: Polyuria in Hyperparathyroidism , Quart. J. Med. 26:423-431, 1957. 63. Edvall, C. A.: Renal Function in Hyperparathyroidism: A Clinical Study of 30 Cases with Special Reference to Selective Renal Clearance and Renal Vein Catheterization , Acta chir. scandinav. , (Suppl. 229) , 1958. 64. Epstein, F. H.; Rivera, M. J., and Carone, F. A.: The Effect of Hypercalcemia Induced by Calciferol upon Renal Concentrating Ability , J. Clin. Invest. 37:1702-1709, 1958.Crossref 65. Epstein, F. H.; Beck, D.; Carone, F. A.; Levitin, H., and Manitius, A.: Changes in Renal Concentrating Ability Produced by Parathyroid Extract , J. Clin. Invest. 38:1214-1221, 1959.Crossref 66. Epstein, F. H.: Calcium and the Kidney , J. Chron. Dis. 11:255-277, 1960.Crossref 67. Relman, A. S., and Schwartz, W. B.: The Kidney in Potassium Depletion , Am. J. Med. 24: 764-773, 1958.Crossref 68. Welt, L. G.; Hollander, W., Jr., and Blythe, W. B.: The Consequences of Potassium Depletion , J. Chron. Dis. 11:213-254, 1960.Crossref 69. Cooke, R. E.; Segar, W. E.; Reed, C.; Etzwiler, D. D.; Vita, M.; Brusilow, S., and Darrow, D. C.: The Role of Potassium in the Prevention of Alkalosis , Am. J. Med. 17:180-195, 1954.Crossref 70. Evans, B. M.; Macintyre, I.; MacPherson, C. R., and Milne, M. D.: Alkalosis in Sodium and Potassium Depletion (with Especial Reference to Organic Acid Excretion) , Clin. Sc. 16:53-65, 1957. 71. Huth, E. J.; Squires, R. D., and Elkinton, J. R.: Experimental Potassium Depletion in Normal Human Subjects: II. Renal and Hormonal Factors in the Development of Extracellular Alkalosis During Depletion , J. Clin. Invest. 38:1149-1165, 1959.Crossref 72. Albright, F.; Bauer, W.; Ropes, M., and Aub, J. C.: Studies of Calcium and Phosphorus Metabolism: IV. The Effect of the Parathyroid Hormone , J. Clin. Invest. 7:139-181, 1929.Crossref 73. Farquharson, R. F.; Salter, W. T.; Tibbetts, D. M., and Aub, J. C.: Studies of Calcium and Phosphorus Metabolism: XII. The Effect of the Ingestion of Acid-Producing Substances , J. Clin. Invest. 10:221-249, 1931.Crossref 74. Albright, F.; Burnett, C. H.; Parson, W.; Reifenstein, E. C., Jr., and Roos, A.: Osteomalacia and Late Rickets: The Various Etiologies Met in the United States with Emphasis on That Resulting from a Specific Form of Renal Acidosis, Therapeutic Indications for Each Etiological Subgroup and the Relationship Between Osteomalacia and Milkman's Syndrome , Medicine 25:399-479, 1946.Crossref 75. Brown, G. E.; Eusterman, G. B.; Hartman, H. R., and Rowntree, L. G.: Toxic Nephritis in Pyloric and Duodenal Obstruction: Renal Insufficiency Complicating Gastric Tetany , Arch. Int. Med. 32:425-455, 1923.Crossref 76. Zeman, F. D.; Friedman, W., and Mann, L. T.: Kidney Changes in Pyloric Obstruction , Proc. New York Path. Soc. 24:41-46, 1924. 77. Cooke, A. M.: Calcification of the Kidneys in Pyloric Stenosis , Quart. J. Med. 2:539-548, 1933. 78. Martz, H.: Renal Calcification Accompanying Pyloric and High Intestinal Obstruction , Arch. Int. Med. 65:375-389, 1940.Crossref 79. Kirsner, J. B.: Effect of Prolonged Administration of Large Quantities of Sodium Bicarbonate on the Kidney of the Dog , Arch. Path. 32: 76-84, 1941. 80. Kirsner, J. B., and Knowlton, K.: Acid-Base Balance, Renal Function, and Gastric Secretion During Hypochloremia in the Dog , J. Clin. Invest. 20:303-312, 1941.Crossref 81. Kirsner, J. B.; Palmer, W. L., and Humphreys, E.: Morphologic Changes in the Human Kidney Following Prolonged Administration of Alkali , Arch. Path. 35:207-225, 1943. 82. Lowenhaupt, E., and Greenberg, D. M.: Renal Changes Associated with a Chloride-Deficient Diet in the Rat , Arch. Path. 42:49-55, 1946. 83. Berger, E. H., and Binger, M. W.: The Status of the Kidneys in Alkalosis , J.A.M.A. 104: 1383-1387, 1935.Crossref 84. Jeghers, H., and Lerner, H. H.: The Syndrome of Alkalosis Complicating the Treatment of Peptic Ulcer: Report of Cases with a Review of the Pathogenesis, Clinical Aspects and Treatment , New England J. Med. 214:1236-1244, 1936.Crossref 85. McCance, R. 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MANLEY, KEITH A.;SKYRING, ALAN P.

doi: 10.1001/archinte.1961.03620020032004pmid: 13766193

Abstract Introduction There is increasing awareness of the importance of heritable diseases in medical practice. Individually, most of the diseases with a clearly defined pattern of inheritance are rare, but as a group they make up an appreciable proportion of the cases with which we have to deal. Some of them affect the alimentary tract, and an awareness by the doctor of their manifestations and genetic implications is of importance in the management of the patient and his family. In other gastrointestinal diseases environmental factors are of major importance, and although genetic factors contribute, no clear pattern of inheritance is evident. Peptic ulceration22 and gastric cancer39 may be mentioned as examples of the latter group.The patient suffering from recurrent gastrointestinal bleeding of uncertain origin presents a perplexing problem, and the cases to be described will illustrate some of the distinctive features which may assist the internist when confronted References 1. There is a further affected Negro family attending the Moore Clinic, and in fact there is no reason to suppose that telangiectasia is any less common in Negroes. 2. This case has been reported briefly by Maloney57 and recently by Haddad and Wilkins." 3. This patient has been reported in brief by Maloney.57 4. This case has been reported in detail by Cooley,18 with the exception of the autopsy. 5. Adlersberg, D., and Schein, J.: Clinical and Pathological Studies in Sprue , J.A.M.A. 134:1459-1467, 1947.Crossref 6. Albright, F.; Smith, P. H., and Fraser, R.: A Syndrome Characterized by Primary Ovarian Insufficiency and Decreased Stature: A Report of 11 Cases with a Digression on Hormone Control of Axillary and Pubic Hair , Am. J.M. Sc. 204:625-648, 1942.Crossref 7. Balzer, F.: Recherches sur les charactères anatomiques du xanthelasma , Arch. physiol. norm. et path. 4 (Series 3):65, 1884. 8. Barr, M. L.: An Interim Note on the Application of the Skin Biopsy Test of Chromosomal Sex to Hermaphrodites , Surg. Gynec. & Obst. 99:184-186, 1954. 9. Bartholomew, L. G.; Dahlin, D. C., and Saugh, J. W.: Intestinal Polyposis Associated with Mucocutaneous Melanin Pigmentation (Peutz-Jeghers Syndrome) , Proc. Staff Meet, Mayo Clin. 32:675-680, 1957. 10. Barton, A. D., and Inglis, K.: Neurofibromatosis with Both Cutaneous and Visceral Lesions , J. Coll. Surgeons, Australasia 3:397, 1931. 11. Bean, W. B.: The Cutaneous Arterial Spider: A Survey , Medicine 24:243-331, 1945. 12. Bean, W. B.: Enteric Bleeding in Rare Conditions with Diagnostic Lesions of the Skin and Mucous Membrane , Tr. Am. Clin. Climatol. A. 69:72-86, 1957. 13. Bean, W. B.: Vascular Spiders and Related Lesions of the Skin , Springfield, Ill., Charles C. Thomas, Publisher, 1958. 14. Bird, R. M.; Hammarsten, J. F.; Marshall, R. A., and Robinson, R. R.: Family Reunion: Study of Hereditary Hemorrhagic Telangiectasia , New England J. 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ROBERTS, C. EVANS;PERRY, DAVID M.;KUHARIC, HENRY A.;KIRBY, WILLIAM M. M.

doi: 10.1001/archinte.1961.03620020054005pmid: 13742131

Abstract In September, 1959, a new tetracycline compound, demethylchlortetracycline* (here-after referred to as DMCT), became available for general use. This compound is reported to be identical in structure to chlortetracycline except for the absence of a methyl group in the 6-position.1 In early studies it was found to be more resistant to acid and alkali degradation than the other tetracyclines in common use,1 and to be generally more active against bacterial pathogens than tetracycline (hereafter referred to as TC) or oxytetracycline.2-5 The amount of DMCT absorbed from the gastrointestinal tract of man following a single dose was less than with TC,6,11 but Kunin and Finland found that the serum half-life was 44% greater for DMCT than for TC, and the renal clearance of the former drug was only 43% of the latter.7 Assays of serum antibacterial activity after equal doses of the 2 drugs showed significantly References 1. The trade name of Lederle Laboratories Division, American Cyanamid Company, Pearl River, N.Y., for demethylchlortetracycline is Declomycin. 2. The trade name of Lederle Laboratories Division, American Cyanamid Company, for tetracycline is Achromycin V. 3. Kindly performed through the courtesy of A. C. Dornbush, Biochemical Research Division of Lederle Laboratories, and by Dr. Henry Welch, Director, Division of Antibiotics, Federal Food and Drug Administration. 4. Kindly performed through the courtesy of A. C. Dornbush. 5. Kindly provided by Dr. Stanton M. Hardy, Lederle Laboratories Division, American Cyanamid Company. 6. The trade name of Baltimore Biological Laboratory for optochin disks is Taxos P. 7. McCormick, J. R. D.; Sjolander, N. O.; Hirsch, U.; Jensen, E. R., and Doerschuk, A. P.: A New Family of Antibiotics: The Demethylchlortetracyclines , J. Am. Chem. Soc. 79:4561-4563 ( (Aug.) ) 1957.Crossref 8. Roberts, M. S.; Seneca, H., and Lattimer, J. K.: Demethylchlortetracycline in Genitourinary Infections , Antibiotics Ann. 1959-1960, p. 424. 9. Finland, M.; Hirsch, H. A., and Kunin, C. M.: Observations on Demethylchlortetracycline , Antibiotics Ann. 1959-1960, p. 375. 10. Vineyard, J. P.; Hogan, J., and Sanford, J. P.: Clinical and Laboratory Evaluation of Demethylchlortetracycline , Antibiotics Ann. 1959-1960, p. 401. 11. Garrod, L. P., and Waterworth, P. M.: The Relative Merits of the Four Tetracyclines , Antibiotics Ann. 1959-1960, p. 440. 12. Sweeney, W. M.; Hardy, S. M.; Dornbush, A. C., and Ruegsegger, J. M.: Demethylchlortetracycline: A Clinical Comparison of a New Antibiotic Compound with Chlortetracycline and Tetracycline , Antibiotics & Chemotherap. 9:13-22 ( (Jan.) ) 1959. 13. Kunin, C. M., and Finland, M.: Demethylchlortetracycline: A New Tetracycline Antibiotic That Yields Greater and More Sustained Antibacterial Activity , New England J. Med. 259:999 ( (Nov.) ) 1958. 14. Ross, S.; Puig, J. R., and Zaremba, E. A.: Absorption of Demethylchlortetracycline in Children: Some Preliminary Observations , Antibiotics Ann. 1959-1960, p. 388. 15. Perry, D. M.; Hall, G. A., and Kirby, W. M. M.: Demethylchlortetracycline: A Clinical and Laboratory Appraisal , Antibiotics Ann. 1959-1960, p. 409. 16. Advertising literature 1960 , Lederle Laboratories Division, American Cyanamid Company, Pearl River, N.Y. 17. Hirsch, H. A., and Finland, M.: Antibacterial Activity of Serum of Normal Subjects after Oral Doses of Demethylchlortetracycline, Chlortetracycline and Oxytetracycline , New England J. Med. 260:1099-1104 ( (May) ) 1959. 18. Tompsett, R.; Shultz, S., and McDermott, W.: The Relation of Protein Binding to the Pharmacology and Antibacterial Activity of Penicillins X, G, Dihydro, F, and K , J. Bact. 53: 581-595 ( (May) ) 1947. 19. Arnold, R. C.; Boak, R. A.; Carpenter, C. M.; Chesney, A. M.; Flemming, W. L.; Gueft, B.; Mahoney, J. F., and Rosahn, P. D.: A Joint Report on a Cooperative Investigation of the Efficacy of Species of Penicillin on Treatment of Experimental Syphilis , Am. J. Syph. 31:469-475 ( (Sept.) ) 1947. 20. Reynolds, F. W.: Nationwide Results in the Treatment of Early Syphilis with Penicillin , Am. J. Med. 5:679 ( (Nov.) ) 1948. 21. Kunin, C. M.; Dornbush, A. C., and Finland, M.: Distribution and Excretion of 4 Tetracycline Analogues in Normal Young Men , J. Clin. Invest. 38:1950-1963 ( (Nov.) ) 1959. 22. Lichter, E. A., and Sobel, S.: The Distribution of Oral Demethylchlortetracycline in Healthy Volunteers and in Patients under Treatment for Various Infections , Antibiotic Med. 7:165-170 ( (March) ) 1960.

KAPLAN, NORMAN M.

doi: 10.1001/archinte.1961.03620020062006pmid: 13751318

Abstract An elevated glucose tolerance curve is widely accepted as indicative of the presence of diabetes mellitus.1,2 Caution has been advised, however, in assuming that an elevated response to a glucose load is, in itself, proof of the existence of this disease in patients with fasting normoglycemia.3,4 Uncertainty has arisen primarily because the oral tolerance test lacks specificity. Almost always abnormal in patients with diabetes, the test is frequently abnormal in nondiabetics as well. Thus, the incidence of a "diabetic" response to oral glucose in a random population sample was 15 times the estimated frequency of diabetes in the general population.5 Only between 20% and 30% of subjects with normal fasting levels but elevated curves developed overt diabetes or fasting hyperglycemia during 5- to 30-year follow-up studies.6-9 Just as many reverted to normal as became diabetic.9 The diagnostic unreliability of the oral test has been attributed, References 1. Generously supplied by Dr. C. J. O'Donovan, The Upjohn Company, Kalamazoo, Mich. 2. American Diabetes Association: Diabetes Guide Book for the Physician , Ed. 2, New York, American Diabetes Association, 1956, 95 pp. 3. Colwell, A. R.: Types of Diabetes Mellitus and Their Treatment , Springfield, Ill., Charles C Thomas, Publisher, 1950, 97 pp. 4. Peters, J. P., and Van Slyke, D. D.: Quantitative Clinical Chemistry , Vol. 1, Ed. 2, Baltimore, The Williams & Wilkins Company, 1946, 1041 pp. 5. Duncan, G. G.: Diseases of Metabolism , Ed. 4, Philadelphia, W. B. Saunders Company, 1959, 1104 pp. 6. Unger, R. H.: The Standard 2-Hour Oral Glucose Tolerance Test in the Diagnosis of Diabetes Mellitus in Subjects Without Fasting Hyperglycemia , Ann. Int. Med. 47:1138-1153, 1957.Crossref 7. Rabinowitch, I. M.: Diabetes Mellitus , Am. J. Digest. Dis. 16:95-111, 1949.Crossref 8. McCullagh, E. P.; Fawell, W. N., and Lane, F. J.: Significance of Hyperglycemia Without Glycosuria , J.A.M.A. 156:925-929, 1954.Crossref 9. Wilkerson, H. L. C.; Krall, L. P., and Butler, F. K.: Diabetes in a New England Town: III. A Comprehensive Baseline Study in Oxford, Mass. , J.A.M.A. 169:910-914, 1959.Crossref 10. Unger, R. H.; Madison, L. L., and Adair, R. M.: The Significance of "Normal" and "Abnormal" Oral Glucose Tolerance Curves as Determined by 5 to 10 Year Follow-Up in 200 Subjects , in Proceedings of the 19th American Diabetes Association Meeting, 1959 , p. 41. 11. Soskin, S.: Use and Abuse of the Dextrose Tolerance Test , Postgrad. Med. 10:108-116, 1951. 12. Burns, T. W.; Engel, F. L.; Viau, A.; Scott, J. L., Jr.; Hollingsworth, D. R., and Werk, E.: Studies on the Interdependent Effects of Stress and the Adrenal Cortex on Carbohydrate Metabolism in Man , J. Clin. Invest. 32:781-791, 1953.Crossref 13. Lozner, E. L.; Winkler, A. W.; Taylor, F. H. L., and Peters, J. P.: The Intravenous Glucose Tolerance Test , J. Clin. Invest. 20:507-515, 1941.Crossref 14. Unger, R. H., and Madison, L. L.: A New Diagnostic Procedure for Mild Diabetes Mellitus , Diabetes 7:455-461, 1958. 15. Pfeiffer, E. F.; Pfeiffer, M.; Ditschuneit, H., and Ahn, C-S.: Clinical and Experimental Studies of Insulin Secretion Following Tolbutamide and Metahexamide Administration , Ann. New York Acad. Sc. 82:479-495, 1959.Crossref 16. Vallance-Owen, J.; Joplin, G. F., and Frazer, R.: Tolbutamide Control of Diabetes Mellitus , Lancet 2:584-586, 1959.Crossref 17. Amatuzio, D. S.; Rames, E. D., and Nesbitt, S.: The Practical Application of the Rapid Intravenous Glucose Tolerance Test in Various Disease States Affecting Glucose Metabolism , J. Lab. & Clin. Med. 48:714-720, 1956. 18. Fajans, S. S., and Conn, J. W.: An Approach to the Prediction of Diabetes Mellitus by Modification of the Glucose Tolerance Test with Cortisone , Diabetes 3:296-304, 1954. 19. Johnson, J.: Protein Free Filtrate or Dialysate: Some Experiences with Automation in a Clinical Chemistry Laboratory with Special Reference to the Routine Blood Glucose Determinations , Am. J.M. Tech. 24:271-280, 1958. 20. Somogyi, M.: Notes on Sugar Determination , J. Biol. Chem. 195:19-23, 1952. 21. Himsworth, H. P.: The Syndrome of Diabetes Mellitus and Its Causes , Lancet 1:465-473, 1949. 22. Zarowitz, H., and Eis, B.: The Role of a Tolbutamide Tolerance Test in the Detection of the Mild Diabetic State: A Preliminary Report , Ann. New York Acad. Sc. 74:662-666, 1959. 23. Barros-Barreto, H. P., and Recant, L.: Tolbutamide Studies in Prediabetes , Ann. New York Acad. Sc. 82:560-569, 1959. 24. Seltzer, H. S., and Smith, W. L.: Insulin Activity in Pancreatic Venous Blood: Enhancement by Glucose and Some Hypoglycemic Agents , Clin. Res. 8:85, 1960. 25. Bogoch, A.; Davis, T. W.; Jow, E., and Wrenshall, G. A.: The Clinical Response and the Amount of Insulin Extractable from the Pancreas in Diabetic Patients Treated with Oral Hypoglycemic Drugs , Canadian M.A.J. 81:347-356, 1959. 26. Seltzer, H. S., and Smith, W. L.: Plasma Insulin Activity after Glucose , Diabetes 8:417-424, 1959. 27. Camerini-Davalos, R.; Marble, A.; White, P.; Belmonte, M., and Sargeant, L.: Effect of Sulfonylurea Compounds in Diabetic Children , New England J. Med. 256:817-822, 1957.Crossref 28. Silverstone, F. A.; Brandfonbrener, M.; Shock, N. W., and Yiengst, M. J.: Age Differences in the Intravenous Glucose Tolerance Tests and the Response to Insulin , J. Clin. Invest. 36:504-514, 1957.Crossref 29. Wrenshall, G. A.; Bogoch, A., and Ritchie, R. C.: Extractable Insulin of Pancreas , Diabetes 1:87-107, 1952. 30. Newburgh, L. H., and Conn, J. W.: A New Interpretation of Hyperglycemia in Obese Middle-Aged Persons , J.A.M.A. 112:7-10, 1939.Crossref 31. Arendt, E. C., and Pattee, C. J.: Studies on Obesity: I. The Insulin-Glucose Tolerance Curve , J. Clin. Endocrinol. 16:367-374, 1956.Crossref 32. Hurwitz, D., and Jensen, D.: Carbohydrate Metabolism in Normal Pregnancy , New England J. Med. 234:327-329, 1946.Crossref 33. Burt, R. L.: Peripheral Utilization of Glucose in Pregnancy and the Puerperium , Obst. & Gynec. 4:58-66, 1954. 34. Burt, R. L.: Peripheral Utilization of Glucose in Pregnancy: III. Insulin Tolerance , Obst. & Gynec. 7:658-664, 1956. 35. Bondy, P. K.: Some Metabolic Abnormalities in Liver Disease , Am. J. Med. 24:428-436, 1958. 36. Witten, T.: Insulin Sensitivity in Cirrhosis , Am. J. Physiol. 179:685, 1954. 37. Long, C. N. H.: Influence of the Adrenal Cortex on Carbohydrate Metabolism , in Ciba Foundation Colloquia on Endocrinology , Vol. 6, edited by G. E. W. Wolstenholme, Boston, Little, Brown & Company, 1953, p. 136. 38. Conn, J. W., and Fajans, S. S.: Symposium on Diabetes: Influence of Adrenal Cortical Steroids on Carbohydrate Metabolism in Man , Metabolism 5:114-127, 1956. 39. Soskin, S., and Levine, R.: Carbohydrate Metabolism , Ed. 2, Chicago, University of Chicago Press, 1952, 346 pp. 40. Woldman, E. E.; Fishman, D., and Segal, A. J.: Relation of Fibrosis of the Pancreas to Fatty Liver and/or Cirrhosis , J.A.M.A. 169:1281-1283, 1959. 41. Goodner, C. J., and Freinkel, N.: Carbohydrate Metabolism in Pregnancy: The Degradation of Insulin by Extracts of Maternal and Fetal Structures in the Pregnant Rat , Endocrinology 65:957-967, 1959. 42. Johnson, D. G., and Bonsnes, R. W.: The Intravenous Glucose Tolerance Test in Pregnancy , J. Clin. Invest. 27:745-748, 1948.

LOURIA, DONALD B.;KAMINSKI, THERESA;BUCHMAN, JOSEPH

doi: 10.1001/archinte.1961.03620020075007pmid: 13763699

Abstract The therapy of severe staphylococcal infections caused by microorganisms resistant to penicillin is currently unsatisfactory. In 1955, a new antimicrobial agent, vancomycin, was isolated from strains of Streptomyces orientalis. This antibiotic was markedly effective in vitro against Gram-positive microorganisms, including staphylococci which were resistant to penicillin and other antistaphylococcal antimicrobials commonly in use.1,2 Studies by several authors3-7 have indicated that vancomycin is beneficial in severe staphylococcal disease in man. The effects of vancomycin therapy in 8 patients who had overwhelming staphylococcal infection are reported in the present studies. Complete clinical recovery and apparent eradication of the infection was achieved in 5 of the 8 patients. Marked improvement occurred in one patient, but the microorganism was not eradicated. Two patients were considered to be therapeutic failures. These cases are reported below in detail to permit clear evaluation of the capabilities of this new and effective antistaphylococcal agent. Special attention References 1. McCormick, M. H.; Stark, W. M.; Pittenger, G. E.; Pittenger, R. C., and McGuire, J. M.: Vancomycin, a New Antibiotic: I. Chemical and Biologic Properties , Antibiotics 1955-1956, pp. 606-611. 2. Ziegler, D. W.; Wolfe, R. N., and McGuire, J. M.: Vancomycin, a New Antibiotic: II. In Vitro Antibacterial Studies , Antibiotics Ann. 1955-1956, pp. 612-618. 3. Kirby, W. M. M.; Perry, D. M., and Bauer, A. W.: Treatment of Staphylococcal Septicemia with Vancomycin , New England J. Med. 262:49-55, 1960.Crossref 4. Kirby, W. M. M., and Divelbiss, C. L.: Vanncomycin: Clinical and Laboratory Studies , Antibiotics Ann. 1956-1957, pp. 107-117. 5. Geraci, J. E.; Heilman, F. R.; Nichols, D. R., and Wellman, W. E.: Antibiotic Therapy of Bacterial Endocarditis: VII. Vancomycin for Acute Micrococcal Endocarditis; Preliminary Report , Proc. Staff Meet. Mayo Clin. 33:172-181, 1958. 6. Dutton, A. A. C., and Elmes, P. C.: Vancomycin: Report on Treatment of Patients with Severe Staphylococcal Infections , Brit. M.J. 1: 1144-1149, 1959.Crossref 7. Ehrenkranz, N. J.: The Clinical Evaluation of Vancomycin in Treatment of Multi-Antibiotic Refractory Staphylococcal Infections , Antibiotics Ann. 1958-1959, pp. 587-594. 8. Kirby, W. M. M.; Perry, D. M., and Lane, J. L. Present Status of Vancomycin Therapy of Staphylococcal and Streptococcal Infections , Antibiotics Ann. 1958-1959, pp. 580-586. 9. Spink, W. W., and Hall, W. H.: Penicillin Therapy at University of Minnesota Hospitals: 1942-1944 , Ann. Int. Med. 22:510-525, 1945.Crossref 10. Finland, M.: Current Status of Therapy in Bacterial Endocarditis , J.A.M.A. 166:364-373, 1958.Crossref 11. Kerr, A., Jr.: Subacute Bacterial Endocarditis , Springfield, Ill., Charles C Thomas, Publisher, 1955. 12. Watson, K. C.: The in Vitro Diffusion of Antibiotics Through Fibrin Membranes , Brit. J. Exper. Path. 38:493-497, 1957. 13. Smith, M. R., and Wood, W. B., Jr.: An Experimental Analysis of the Curative Action of Penicillin in Acute Bacterial Infections: III. The Effect of Suppuration upon the Antibacterial Action of the Drug , J. Exper. Med. 103:509-521, 1956.Crossref 14. Darnell, J. E., Jr.; Pesch, B. B., and Glaser, R. J.: Effect of Penicillin on Group A Streptococci in Vivo in the Absence of Leukocytes , J. Clin. Invest. 34:1237-1241, 1955.Crossref 15. McDermott, W.: Microbial Persistence , Yale J. Biol. & Med. 30:257-291, 1958.

LOWE, ROLLAND;DE LORIMIER, ALFRED A.;GORDAN, GILBERT S.;GOLDMAN, LEON

doi: 10.1001/archinte.1961.03620020091008pmid: 13763814

Abstract Recent reports have aroused considerable interest in fluoxymesterone,* an orally effective, highly potent androgen, for the treatment of advanced breast carcinoma.1-7 Because its exact antitumor efficacy in breast carcinoma was uncertain and had not been studied with simultaneous controls, we attempted an objective comparison of the effects of fluoxymesterone with those of testosterone propionate in a random series of patients who had received no previous hormonal therapy. Fluoxymesterone differs from testosterone in having a methyl group in the 17-α position (as does methyltestosterone), a fluorine atom in the 9-α position, and a hydroxyl group in the 11-β position (Figure). Method of Study Selection and Classification of Patients.— All patients seen in the Advanced Breast Tumor Clinic with recurrent, inoperable, or metastatic carcinoma of the breast, including inflammatory carcinoma, were admitted to the study if they had had no hormonal therapy for breast cancer, were postmenopausal, and had References 1. Halotestin (Upjohn); also available as Ora-Testryl (Squibb) and Ultandren (Ciba). 2. Kennedy, B. J.: Fluoxymesterone in Treatment of Advanced Breast Cancer , Clin. Res. Proc. 5:219 ( (April) ) 1957. 3. Kennedy, B. J.: Fluoxymesterone in Treatment of Advanced Breast Cancer , Cancer 10:813-818 ( (July) -Aug.) 1957.Crossref 4. Kennedy, B. J.: Fluoxymesterone Therapy in Advanced Breast Cancer , New England J. Med. 259:673-675 ( (Oct. 2) ) 1958.Crossref 5. Segaloff, A.; Bowers, C. Y.; Rongone, E. L.; Murison, P. J., and Schlosser, J. V.: Hormonal Therapy in Cancer of the Breast: XIII. The Effect of 9α-Fluoro-17α-Methyl-Δ4-Androsten-3-One-11β, 17β-Diol (Fluoxymesterone) Therapy on Clinical Course and Hormonal Excretion , Cancer 11:1187-1189 ( (Nov.) -Dec.) 1958.Crossref 6. Stoll, B. A.: Fluoxymesterone (Halotestin) in Advanced Breast Carcinoma , M.J. Australia 1:70-74 ( (Jan. 17) ) 1959. 7. Beckett, V. L., and Brennan, M. J.: Treatment of Advanced Breast Cancer with Fluoxymesterone (Halotestin) , Surg. Gynec. & Obst. 109: 235-239 ( (Aug.) ) 1959. 8. Scheiffarth, F., and Zicha, L.: Die Therapie endokrin abhängiger Tumoren mit neuen halogenierten Steroidderivaten , Deutsche med. Wchnschr. 84:1373-1375 ( (July 31) ) 1959. 9. Gordon, D. L., and Segaloff, A.: Castration as a Palliative Therapy for Advanced Breast Cancer , in Second Louisiana Cancer Conference: Breast Cancer , edited by A. Segaloff, St. Louis, The C. V. Mosby Company, 1958. 10. Segaloff, A.: Chemotherapy of Breast Cancer: Standard Androgen Therapy; Conference on Biologic Activity of Steroids, Vergennes, Vt., Sept. 27-Oct. 2, 1959 . 11. Escher, G. C.: Current Endocrine Therapy of Advanced Mammary Carcinoma , in Gordan, G. S., Editor: Year Book of Endocrinology 1957-1958 , Chicago, The Year Book Publishers, Inc., 1958, pp. 347-352. 12. Solomon, G. F.; Dickerson, W. J., and Eisenberg, E.: Psychologic and Osteometabolic Responses to Sex Hormones in Elderly Osteoporotic Women , Geriatrics 15:46-60 ( (Jan.) ) 1960.

DOWBEN, ROBERT M.;PERLSTEIN, MEYER A.

doi: 10.1001/archinte.1961.03620020095009pmid: 13724133

Abstract Norethandrolone (17α-ethyl-19-nortestosterone, Nilevar) is an anabolic and myotrophic steroid,1-3 which increases the rate of synthesis of endogenous creatine.4 When administered to mice afflicted with an hereditary disease resembling human muscular dystrophy, norethandrolone increased the median survival time from an average of 13 weeks in control dystrophic mice to 33 weeks at a dosage level of 5 mg/kg. body weight thrice weekly and to 22 weeks in doses of 0.5 mg/kg. body weight thrice weekly.5 Treatment of dystrophic mice with norethandrolone did not result in improved strength; it merely slowed the rate of progression of the disease. Force-feeding and administration of testosterone propionate did not prolong significantly the survival of dystrophic mice. In view of these findings, a clinical trial of norethandrolone therapy was undertaken in patients with muscular dystrophy. Materials and Methods A total of 52 patients with muscle disease were enrolled in a "double blind" study; References 1. Saunders, F. J., and Drill, V. A.: The Myotrophic and Androgenic Effects of 17-Ethyl-19-Nortestosterone and Related Compounds , Endocrinology 58:567, 1956.Crossref 2. McSwiney, R. R., and Prunty, F. T. G.: Metabolic Effects of Substances Allied to Testosterone with Special Reference to 17-Alpha-Ethyl-19-Nortestosterone , J. Endocrinol. 13:25, 1956. 3. Weston, R. E.; Isaacs, M. C.; Rosenblum, R.; Gibbons, D. M., and Grossman, J.: Metabolic Effects of an Anabolic Steroid, 17α-Ethyl-17-Hydroxy-Norandrosterone in Human Subjects , J. Clin. Invest. 35:744, 1956. 4. Dowben, R. M.: Increased Creatine and Creatinine Excretion after 17α-Ethyl-19-Nortestosterone , Proc. Soc. Exper. Biol. & Med. 98:644, 1958. 5. Dowben, R. M.: Prolonged Survival of Dystrophic Mice Treated with 17α-Ethyl-19-Nortestosterone , Nature, London 184:1966, 1959. 6. Adams, R. D.; Denny-Brown, D., and Pearson, C. M.: Diseases of Muscle , New York, Paul B. Hoeber, Inc., Medical Book Department of Harper & Brothers, 1953. 7. Swinyard, C. A.; Deaver, G. G., and Greenspan, L.: Gradients of Functional Ability of Importance in Rehabilitation of Patients with Progressive Muscular and Neuromuscular Diseases , Arch. Phys. Med. 38:574, 1957. 8. Owen, J. A.; Iggo, B.; Scandrett, F. J., and Stewart, C. P.: The Determination of Creatinine in Plasma or Serum and in Urine: Critical Examination , Biochem. J. 58:426, 1954. 9. Wroblewski, F., and LaDue, J. S.: Lactic Dehydrogenase Activity in Blood , Proc. Soc. Exper. Biol. & Med. 90:210, 1955. 10. Dounce, A. L.; Barnett, S. R., and Thannhauser-Beyer, G.: Further Studies on the Kinetics and Determination of Aldolase , J. Biol. Chem. 185: 769, 1950. 11. Milhorat, A. T.: Therapy in Muscular Dystrophy , M. Ann. District of Columbia 23:15, 1954. 12. Lilienthal, J. L., Jr., and Zierler, K. L.: Diseases of Muscle , in Biochemical Disorders in Human Disease , R. H. S. Thompson and E. J. King, Editors, New York, Academic Press, Inc., 1957, p. 483 et seq. 13. Schapira, G.; Dreyfus, J. C.; Schapira, F., and Kruh, J.: Glycogenolytic Enzymes in Human Progressive Muscular Dystrophy , Am. J. Phys. Med. 34:313, 1955. 14. White, A. A., and Hess, W. C.: Some Alterations in Serum Enzymes in Progressive Muscular Dystrophy , Proc. Soc. Exper. Biol. & Med. 94:541, 1957. 15. Thompson, R. A., and Vignos, P. J., Jr.: Serum Aldolase in Muscle Disease , A.M.A. Arch. Int. Med. 103:551, 1959. 16. Dowben, R. M.: Effect of Norethandrolone on Serum Enzyme Levels , J. Clin. Endocrinol. 18:1308, 1958. 17. Kory, R. C.; Bradley, M. H.; Watson, R. N.;; Callahan, R., and Peters, B. J.: A 6-Month Evaluation of an Anabolic Drug, Norethandrolone, in Underweight Persons: II. Bromsulfalein (BSP) Retention and Liver Function , Am. J. Med. 26: 243, 1959. 18. Schaffner, F.; Popper, H., and Chesrow, E.: Cholestasis Produced by the Administration of Norethandrolone , Am. J. Med. 26:249, 1959. 19. Steiner, M. M.: Personal communication to the authors. 20. Morrell, R. M.: Abnormal Hepatic Tests in Muscular Disease , A.M.A. Arch. Int. Med. 104:83, 1959.

CHEITLIN, MELVIN D.;KAMIN, EDWARD J.;WILKES, DANIEL J.

doi: 10.1001/archinte.1961.03620020102010pmid: 13692726

Abstract Midesophageal traction diverticula are only rarely symptomatic. Very infrequently diverticulitis1-3 and spontaneous hemorrhage3,5-7 have been observed to develop, and on rare occasions spontaneous perforation and fistulization with other mediastinal structures have been reported.8-20 It is the purpose of this paper to report an extremely unusual case of a midesophageal traction diverticulum which formed a fistula with the superior vena cava, caused multiple septic pulmonary emboli, and terminally resulted in exsanguinating esophageal hemorrhage. Report of Case A 36-year-old white male officer was admitted to the U.S. Army Hospital at Fort Gordon, Ga., complaining of a nonproductive hacking cough, mild pleuritic chest pain, and intermittent chilly sensations, which had persisted for 5 days. Physical examination revealed no abnormality of the heart or lungs and was otherwise unremarkable except for a temperature elevation of 100.8 F. Initial laboratory studies were within normal limits and included white blood cell count and References 1. Palmer, E. D.: Clinical Problems Associated with Esophageal Diverticula , Am. J.M. Sc. 229:16, 1955.Crossref 2. Webster, B. H.: Spontaneous Perforation of an Oesophageal Diverticulum: Report of a Case with Survival , Dis. Chest 31:345, 1957.Crossref 3. Schick, A., and Yesner, R.: Traction Diverticulum of Esophagus with Exsanguination: Report of a Case , Ann. Int. Med. 39:345, 1953.Crossref 4. Guillon, H.; Batisse, R., and Jacques, A.: Diverticulum of the Lower Esophagus Fistulizing into the Mediastinum , Ann. oto-laryng. 72:440, 1955. 5. Wallace, R. P.: Traction Diverticula of the Esophagus , Arch. Int. Med. 60:454, 1937.Crossref 6. Wallace, R. P.: Traction Diverticula of the Esophagus , M. Clin. North America 26:889, 1942. 7. Witter, J. A., and Lookanoff, V. A.: Massive Hemorrhage as the First Manifestation of Diverticulum of the Lower Thoracic Esophagus , Surgery 29:895, 1951. 8. Powell, M. E.: Case Report: Aorta-Esophageal Fistula , Brit. J. Surg. 45:55, 1957.Crossref 9. Grasso, M.: Case of Tuberculous Fistula of the Esophagus and Superior Vena Cava , Arch. ital. anat. e istol. pat. 24:530, 1951. 10. Stewart, W. R.; Klassen, K. P., and Horava, A. P.: Esophagobronchial Fistula Due to Esophageal Traction Diverticulum: Review of Literature and Report of Case , A.M.A. Arch. Surg. 76:317, 1958.Crossref 11. Duprez, A.; Wittek, F., and Dumont, A.: Acquired and Congenital Oesophago-Bronchial Fistulas , Thorax 11:249, 1956.Crossref 12. Coleman, F. P.: Acquired Non-Malignant Esophagorespiratory Fistula , Am. J. Surg. 93: 321, 1957.Crossref 13. McDaniel, J. R., and Knepper, P. A.: Esophagopericardial Fistula: Report of a Case and Review of the Literature , J. Thoracic Surg. 34:173, 1957. 14. Mangili, C.: Esophageal Diverticulum Producing Perforation of Aorta , Gazz. int. med. e chir. 39:583, 1931. 15. Hawes, J. B.: Broncho-Esophageal Fistula and Traction Diverticulum , Am. J.M. Sc. 161:791, 1921.Crossref 16. Mellins, R. B.: Medical Progress: Acquired Fistula Between the Esophagus and the Respiratory Tract , New England J. Med. 246:896, 1952.Crossref 17. Pape, R.: Eine chronische Oesophagus-Bronchusfistel bei Oesophagus-Divertikel , Wien. klin. Wchnschr. 47:1320, 1934. 18. Jenkinson, D. L., and Bate, L. C.: Esophagobronchial Fistula Through an Esophageal Diverticulum: Report of a Case with Treatment by Cauterization , Am. J. Roentgenol. 66:236, 1951. 19. Jaubert de Beaujeu, M.: Fistules oesophagobronchiques chez l'adulte avec diverticule oesophagien de traction , Lyon chir. 47:796, 1952. 20. Clerf, L. H.; Cooley, E. E., and O'Keefe, J. J.: Esophagobronchial Fistula , Surg. Gynec. & Obst. 77:615, 1943. 21. 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