The uptake of ingested vitamin B12 and its total body balance: a mathematical model suggests the optimal supplementation strategy.

Excerpt The differential diagnosis of various types of macrocytic anemia often presents difficult clinical problems. Many cases of dietary folic acid or B12deficiency and sprue cannot be distinguis...

Excerpt The common denominator of the clinical entities variously known as non-tropical sprue, tropical sprue, celiac disease and idiopathic steatorrhea is impaired intestinal absorption of various...

Article1 August 1957STUDIES OF B12 Co60 ABSORPTION IN MALABSORPTION SYNDROME: RESULTS BEFORE AND DURING SPECIFIC THERAPYJOHN W. FROST, M.D., F.A.C.P., MANFRED I. GOLDWEIN, M.D., BARRE D. KAUFMAN, M.D.JOHN W. FROST, M.D., F.A.C.P.Search for more papers by this author, MANFRED I. GOLDWEIN, M.D.Search for more papers by this author, BARRE D. KAUFMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-47-2-293 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMalabsorption syndrome can be defined as a disorder resulting from a defect in the intestinal absorption of various substances, including protein, fat, vitamins and minerals. The syndrome is a manifestation of various gastrointestinal disorders, such as sprue, regional enteritis, intestinal strictures and anastomoses, hypogammaglobulinemia and pancreatic dysfunction. In patients with this disorder, variability in the extent of the absorptive defect is often encountered. Relapses and remissions are common.Since there are multiple absorptive defects in the syndrome, numerous tests have been utilized to measure defects in the absorption of fat, protein, carbohydrate and vitamins. The relative simplicity of the technics...Bibliography1. HeinleWelchScharfMeachamPrusoff RWADVGCWH: Studies of excretion (and absorption) of Co60 labelled vitamin B12 in pernicious anemia, Tr. A. Am. Physicians 65: 214, 1952. MedlineGoogle Scholar2. GlassBoydGellinStephanson GBLJGAL: Uptake of radioactive vitamin B12 by the liver in humans: tests for measurement of intestinal absorption of vitamin B12 and intrinsic factor activity, Arch. Biochem. 51: 251, 1954. CrossrefMedlineGoogle Scholar3. Schilling RF: A new test for intrinsic factor activity, J. Lab. and Clin. Med. 42: 946, 1953. Google Scholar4. BestWhiteLouisLemarzi WVWFJLR: Experiences with the Schilling test using Co60 labelled vitamin B12 in pernicious anemia, sprue, and other conditions, J. Lab. and Clin. Med. 44: 767, 1954. Google Scholar5. Glass GB: Intestinal absorption and hepatic uptake of vitamin B12 in diseases of the gastrointestinal tract, Gastroenterology 30: 37, 1956. CrossrefMedlineGoogle Scholar6. HalstedSwendseidLewisGasster JAMAPMM: Mechanisms involved in the development of vitamin B12 deficiency, Gastroenterology 30: 20, 1956. CrossrefGoogle Scholar7. DoscherholmenHagen APS: Absorption of Co60 labelled vitamin B12 in intestinal blind loop megaloblastic anemia, J. Lab. and Clin. Med. 44: 790, 1954. Google Scholar8. Glass GB: Differentiation of macrocytic anemias and detection of pernicious anemia and sprue in remission by accelerated measurement of hepatic uptake of radioactive Co60 B12 , International Society of Hematology, VI Congress, p. 251, 1956. Google Scholar9. Turnbull A: Experiences with labelled vitamin B12 , Proc. Roy. Soc. Med. 47: 42, 1954. Google Scholar10. HalstedLewisGasster JAPMM: Absorption of radioactive B12 in the syndrome of megaloblastic anemia associated with intestinal stricture or anastomosis, Am. J. Med. 20: 42, 1956. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania*From the Symposium on Diseases of Intestinal Absorption, presented at the Thirty-eighth Annual Session of The American College of Physicians, Boston, Massachusetts, April 9, 1957.From the Hematology Clinic, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.†Fellow American Cancer Society.‡Captain (MC) U.S.A.F.Aided by a grant from Eli Lilly & Company, Indianapolis, Indiana.Requests for reprints should be addressed to John W. Frost, M.D., 3400 Spruce St., Philadelphia 4, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byVitamin B12 Absorption in Cystic FibrosisDie megaloblastischen AnämienCorticotrofina e cortiomdes em neurologia: avaliação critica dos resultados em 518 pacientes hospitalizadosCoeliac DiseaseEfeito da corticotropina sobre a absorção de vitamina B12 na mielose funicularPyridoxine-Responsive Anemia with NeuropathyEUGENE M. BEAUPRE, M.D., PATRICK M. GROWNEY, M.D.The Malabsorption Syndrome, with Special Reference to The Effects of Wheat GlutenMegaloblastic Anaemias of Gastrointestinal OriginRadio-Vitamin B12 in der klinischen DiagnostikVitamin B12 Absorption in Pyridoxine-Deficient RatsPathogenesis of Anemia in a Case of Nontropical SprueObservations on Vitamin B12 Absorption in Primary Pernicious Anemia during Administration of Adrenocortical SteroidsSymposium on problems of intestinal absorption 1 August 1957Volume 47, Issue 2Page: 293-299KeywordsCystic fibrosisEnteritisExcretionFatsHematology and oncologyHospitalsPancreasProteinsSteroid therapyVitamins ePublished: 1 December 2008 Issue Published: 1 August 1957 PDF downloadLoading ...

Surface Scintillation Measurements in Humans of the Uptake of Parenterally Administered Radioactive Vitamin B12

Article1 January 1960ABSORPTION OF RADIOACTIVE B12 IN PATIENTS WITH PERNICIOUS ANEMIA AFTER LONG-TERM ORAL AND PARENTERAL THERAPYP. J. FOUTS, M.D., F.A.C.P., O. M. HELMER, Ph.D., S. M. CHERNISH, M.D.P. J. FOUTS, M.D., F.A.C.P.Search for more papers by this author, O. M. HELMER, Ph.D.Search for more papers by this author, S. M. CHERNISH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-52-1-29 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptINTRODUCTIONThe Hematology Research Clinic at the Marion County General Hospital in Indianapolis has been in continuous operation since the days when raw liver was used in the treatment of pernicious anemia. During this time more than 400 patients have been treated with oral and parenteral liver extracts, intrinsic factor preparations, and injectable B12 solutions. Some of the patients who have been followed continuously and are still reporting to the clinic have been on oral therapy for 29 years; others, on intrinsic factor preparations, parenteral liver or B12 solutions for as long as 26 to 27 years.During the last...Bibliography1. SchwartzLousMeulengracht MPE: Reduced effect of heterologous intrinsic factor, after prolonged oral treatment in pernicious anemia, Lancet 1: 751, 1957. CrossrefGoogle Scholar2. KristensenLundOhlsenPedersen HPJASJ: Maintenance therapy in pernicious anemia, controlled by determining vitamin B12 level in plasma, Lancet 1: 1266, 1957. Google Scholar3. Killander A: Oral treatment of pernicious anaemia with vitamin B12 and purified intrinsic factor. I. The value of serial estimation of the vitamin B12 levels of serum, Acta med. Scandinav. 160: 339, 1958. CrossrefMedlineGoogle Scholar4. BerlinBerlinBranteSjoberg RHGS: Failures in long-term oral treatment of pernicious anemia with B12-intrinsic factor preparations, Acta med. Scandinav. 161: 143, 1958. CrossrefMedlineGoogle Scholar5. LowensteinBruntonShapirode LeeuwDufresne LLLNM: Maintenance therapy of pernicious anaemia with oral administration of intrinsic factor and vitamin B12 , Canad. M. A. J. 77: 923, 1957. MedlineGoogle Scholar6. Schilling RF: Intrinsic factor studies. II. The effect of gastric juice on the urinary excretion of radioactivity after the oral administration of radioactive vitamin B12 , J. Lab. and Clin. Med. 42: 860, 1953. MedlineGoogle Scholar7. FoutsZerfas PJLG: Maintenance dosage of liver extract in the treatment of pernicious anemia, Ann. Int. Med. 6: 1298, 1933. LinkGoogle Scholar8. WillMuellerBrodineKielyFriedmanHawkinsDutraVilter JJJFCCEBVRJRW: Folic acid and vitamin B12 in pernicious anemia. Studies on patients treated with these substances over a ten-year period, J. Lab. and Clin. Med. 53: 22, 1959. MedlineGoogle Scholar9. BerlinBerlinBranteSjoberg RHGS: Refractoriness to intrinsic factor-B12 preparations abolished by massive doses of intrinsic factor, Acta med. Scandinav. 162: 317, 1958. CrossrefMedlineGoogle Scholar10. ShayKomarovBerk HSAJE: Some fallacies in the clinical measurement of gastric acidity with special reference to the histamine test, Gastroenterology 15: 110, 1950. CrossrefMedlineGoogle Scholar11. Helmer OM: The relation of the secretion of mucus to the acidity of the gastric juice, Am. J. Physiol. 110: 28, 1934. CrossrefGoogle Scholar12. Goldhamer SM: The presence of the intrinsic factor of Castle in the gastric juice of patients with pernicious anemia, Am. J. M. Sc. 191: 405, 1936. CrossrefGoogle Scholar13. Goldhamer SM: The gastric juice in patients with pernicious anemia in induced remission, Am. J. M. Sc. 193: 23, 1937. CrossrefGoogle Scholar14. KeuningArendsMandemaNieweg FJAEHO: Observations on the site of production of Castle's intrinsic factor in the rat, J. Lab. and Clin. Med. 53: 127, 1959. MedlineGoogle Scholar15. SchwartzLousMeulengracht MPE: Absorption of vitamin B12 in pernicious anemia. Defective absorption induced by prolonged oral treatment, Lancet 2: 1200, 1958. CrossrefMedlineGoogle Scholar16. BerlinBerlinBranteSjoberg HRGS: Studies on intrinsic factor and pernicious anemia. I. Oral uptake of vitamin B12 in pernicious anemia with increasing doses of an intrinsic factor concentrate, Scandinav. J. Clin. and Lab. Invest. 10: 278, 1958. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Indianapolis, Indiana*Received for publication May 16, 1959.Presented at the Fortieth Annual Session of The American College of Physicians, Chicago, Illinois, April 22, 1959.From the Lilly Laboratory for Clinical Research and the Marion County General Hospital, Indianapolis, Indiana. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByIntrinsic FactorVitamin B12 and Intrinsic Factor 1 January 1960Volume 52, Issue 1Page: 29-43KeywordsAnemiaClinical laboratoriesHematology and oncologyHospitalsLiverMucous membranesPatientsPernicious anemiaResearch laboratoriesUrine Issue Published: 1 January 1960 PDF DownloadLoading ...

Hematologic responses in pernicious anemia to orotic acid

Hematologic Responses in Pernicious Anemia to Orotic Acid

Article1 March 1956THE URINARY EXCRETION TEST IN THE DIAGNOSIS OF ADDISONIAN PERNICIOUS ANEMIAS. FRED RABINER, M.D., HERBERT C. LICHTMAN, M.D., JACQUELINE MESSITE, M.D., R. JANET WATSON, M.D., F.A.C.P., VICTOR GINSBERG, M.D., F.A.C.P., LEON ELLENBOGEN, Ph.D., WILLIAM L. WILLIAMS, Ph.D.S. FRED RABINER, M.D.Search for more papers by this author, HERBERT C. LICHTMAN, M.D.Search for more papers by this author, JACQUELINE MESSITE, M.D.Search for more papers by this author, R. JANET WATSON, M.D., F.A.C.P.Search for more papers by this author, VICTOR GINSBERG, M.D., F.A.C.P.Search for more papers by this author, LEON ELLENBOGEN, Ph.D.Search for more papers by this author, WILLIAM L. WILLIAMS, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-44-3-437 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAddisonian pernicious anemia is a deficiency disease resulting from the lack of a specific gastric secretion which is essential for the optimal absorption in the intestine of orally ingested vitamin B12. Probably a mucoprotein,1, 2 this gastric enzyme, commonly referred to as intrinsic factor,3, 4 is produced by the mucosal cells of the stomach of man and other animals. It has not yet been fully characterized chemically, nor is there available a direct method for detecting its presence in the stomach secretions.In hematologic relapse the diagnosis of pernicious anemia is readily established by the findings of megaloblastic erythropoiesis, macrocytic...Bibliography1. WilliamsEllenbogenEsposito WWLRG: Preparation of highly purified intrinsic factor, Proc. Soc. Exper. Biol. and Med. 7: 400, 1954. CrossrefGoogle Scholar2. GlassBoydRubinsteinSvigals GBLJMACS: Relationship of glandular mucoprotein from human gastric juice to Castle's intrinsic antianemic factor, Science 115: 101, 1952. CrossrefMedlineGoogle Scholar3. CastleTownsend WBWC: Observations on etiologic relationship of achylia gastrica to pernicious anemia. II. Effect of administration to patients with pernicious anemia of beef muscle after incubation with normal human gastric juice, Am. J. M. Sc. 178: 764, 1929. CrossrefGoogle Scholar4. CastleTownsendHeath WBWCCW: Observations on etiologic relationship of achylia gastrica to pernicious anemia. III. Nature of reaction between normal human gastric juice and beef muscle leading to clinical improvement and increased blood formation similar to effect of liver feeding, Am. J. M. Sc. 180: 305, 1930. CrossrefGoogle Scholar5. Schilling RF: Intrinsic factor studies. II. The effect of gastric juice on the urinary excretion of radioactivity after oral administration of vitamin B12 Co60 , J. Lab. and Clin. Med. 42: 860, 1953. MedlineGoogle Scholar6. RabinerEllenbogenLichtmanWilliamsKabakowWatson SFLHCWLBRJ: Urinary excretion of vitamin B12 Co60 as a method of assay for intrinsic factor, Clin. Res. Proc. 3: 28, 1955. Google Scholar7. EllenbogenWilliamsRabinerLichtman LWLSFHC: An improved urinary excretion test as an assay for intrinsic factor, Proc. Soc. Exper. Biol. and Med. 89: 357, 1955. CrossrefMedlineGoogle Scholar8. GlassBoydGellinStephanson GBLJGAL: Uptake of radioactive vitamin B12 by the liver in humans: test for measurement of intestinal absorption of vitamin B12 and intrinsic factor activity, Arch. Biochem. and Biophys. 51: 251, 1954. CrossrefMedlineGoogle Scholar9. HeinleWelchScharfMeachamPrusoff RWADVGCWM: Studies of excretion (and absorption) of Co60 labelled B12 in pernicious anemia, Tr. A. Am. Physicians 65: 214, 1952. MedlineGoogle Scholar10. CallanderTurnbullWakisaka STAG: Estimation of intrinsic factor by the use of radioactive B12 , Brit. M. J. 1: 10, 1954. CrossrefMedlineGoogle Scholar11. Meyer L: Oral administration of Co60 B12 in pernicious anemia, Proc. Soc. Exper. Biol. and Med. 82: 490, 1953. CrossrefMedlineGoogle Scholar12. Castle WB: Development of knowledge concerning the gastric intrinsic factor and its relation to pernicious anemia, New England J. Med. 249: 603, 1953. CrossrefMedlineGoogle Scholar13. WallersteinHarrisSchillingCastle ROJWRFWB: Observations on etiologic relationship of achylia gastrica to pernicious anemia. XV. Hematopoietic effects of simultaneous intravenous and of simultaneous or serial oral administrations of intrinsic factor and vitamin B12 , J. Lab. and Clin. Med. 41: 363, 1953. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pearl River, New York*Received for publication August 8, 1955.From the Division of Hematology, Department of Medicine, State University of New York College of Medicine at New York City, Brooklyn, N. Y., Kings County Hospital, and the Nutrition and Physiology Section of American Cyanamid Company, Research Division, Lederle Laboratories, Pearl River, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUse of radioisotope techniques in the clinical evaluation of patients with megaloblastic anemiaVitamin B 12 Malabsorption in Chronic Pancreatic InsufficiencyIntrinsic FactorVitamin B12 and Intrinsic FactorRadio-Vitamin B12 in der klinischen DiagnostikUntersuchungen mit radioaktivem Vitamin B12Effect of Renal Disease on the Schilling Test 1 March 1956Volume 44, Issue 3Page: 437-445KeywordsExcretionHematology and oncologyHospital medicineMegaloblastic anemiaNutritionOral administrationPernicious anemiaResearch laboratoriesRiversStomach ePublished: 1 December 2008 Issue Published: 1 March 1956 Copyright & PermissionsCopyright ©, 1956, by The American College of PhysiciansPDF downloadLoading ...

Excerpt Vitamin B12, originally isolated by Rickes and associates1in the United States and by Lester Smith2in England, is now known to be but one of a group of related compounds for which the gener...

Disclosure: A.E. De Rosairo: None. D. Patel, MD: None. D.H. Sacoto, MD: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None. Introduction: Polyglandular autoimmune syndromes (PAS) are rare polyendocrinopathies which are caused by an immune-mediated destruction of endocrine tissues, characterized by the failure of several endocrine glands and nonendocrine organs. PAS Type 3 is defined as the combination of thyroid autoimmune disease (TAD) and other autoimmune disorders (other than Addison disease), and is divided into 4 subtypes. PAS type 3B (thyrogastric syndrome) is combination of TAD and pernicious anemia. This case highlights an interesting presentation of an individual with Graves’ disease (GD) who developed pancytopenia with symptomatic anemia secondary to severe vitamin B12 deficiency due to pernicious anemia. Case: A 44-year-old Hispanic male with medical history of GD (diagnosed 3 years ago controlled with methimazole 20mg daily) and hypertension presented to the ED with symptomatic anemia with worsening fatigue, dizziness, dyspnea, nausea, vomiting and non-bloody diarrhea for 3 weeks. Laboratory findings remarkable for pancytopenia, including leukopenia (white blood cell 2.44 K/uL), thrombocytopenia (platelets 138 K/uL), macrocytic anemia (hemoglobin 4.9g/dL, hematocrit 14.4%, MCV 117.1fl), LDH 3231 U/L, reticulocytes count 3.231%. Other lab values were within normal limits. Peripheral blood smear noted teardrop cells, fragmented cells, polychromasia, poikilocytosis, and hypersegmented polymorphonuclear leukocytes. Patient received 4 units packed red blood cell with noted improvement in symptoms. Thyroid function tests were within normal limits hence methimazole was held to rule out methimazole induced pancytopenia. Bone marrow biopsy showed hypercelluar marrow with marked erythroid hyperplasia with left shift, no evidence of acute leukemia. Normal serum folate levels but vitamin B12 levels significantly low <150 pg/ml (232 - 1245 pg/mL) and intrinsic factor antibody positive (227.9AU/mL). Patient was started on vitamin B12 injections; thereafter, symptomatic anemia and pancytopenia resolved. Repeat TSH low (0.02 ulU/mL), free T4 1.9 ng/dL and thyroid stimulating Immunoglobulin 0.14 hence, patient was restarted on methimazole. Patient was clinically stable in subsequent follow up visits. Discussion: The patient with known TAD suddenly developed pancytopenia, with symptomatic megaloblastic anemia. Severe vitamin B12 deficiency and intrinsic factor antibody positive confirmed diagnosis of pernicious anemia which respond to cobalamin treatment and noticed resolution of pancytopenia. PAS type 3B was first described in the early 1960s and refers to the presence of thyroid autoantibodies in patients with pernicious anemia and it is inherited with a polygenic inheritance pattern. This case emphasizes that there can be coexistence of other autoimmune disorders and it is important to screen for other autoimmune disorders when suspected. Presentation: 6/3/2024

Article1 September 1944THE DIETARY FACTOR IN THE ETIOLOGY OF PERNICIOUS ANEMIAJOHN MARTIN ASKEY, M.D., F.A.C.P.JOHN MARTIN ASKEY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-21-3-402 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAddisonian pernicious anemia is known to develop in accordance with genetic, racial, climatic and geographic determinants. The hypothesis that the disease is of dietary origin has been advanced. If dietary deficiencies cause Addisonian pernicious anemia, they must explain the natural distribution and the natural history of the typical form of the disease.The Natural Distribution of the Disease. Pernicious anemia is geographically distributed. It is rare in Asia, common in Northern Europe, Canada and the Northern United States. It is less common in the Mediterranean and Southern European areas, in South America and Southern United States.Racially, it is extremely...Bibliography1. FRIEDLANDER RD: Racial factor in pernicious anemia; study of 500 cases, Am. Jr. Med. Sci., 1934, clxxxvii, 634-642. CrossrefGoogle Scholar2. PETERSEN WF(a) : The patient and the weather, vol. 1, part 1, 1935, Edwards Brothers, Inc., Ann Arbor, Michigan, page 75. MILLS C. A.: Geographic or climatic variations in death rate from pernicious anemia, exophthalmic goitre, Addison's disease and angina pectoris, Arch. Int. Med., 1930, xlvi, 741-751. (b) SMITH J. H.: Relation between deficiency of solar radiation and mortality due to pernicious anemia in the United States, Am. Jr. Med. Sci., 1934, clxxxviii, 200. Google Scholar3. MANSON-BAHR PH: Glossitis and vitamin B2 complex in pellagra, sprue, and allied states, Lancet, 1940, ii, 317, 356. MANSON-BAHR P. H.: Treatment of sprue with vitamin B2 and its bearing upon the aetiology of this disease, Trans. Roy. Soc. Trop. Med. and Hyg., 1941, xxxiv, 347-372. RHOADS C. P. CASTLE W. B.: Pathology of bone marrow in sprue anemia, Am. Jr. Path., (supp), 1933, ix, 813-826. WOLTMAN H. W. HECK F. J.: Funicular degeneration of the spinal cord without pernicious anemia; neurologic aspects of sprue, non-tropical sprue and idiopathic steatorrhea, Arch. Int. Med., 1937, lx, 272-300. CrossrefGoogle Scholar4. GOLDHAMER SM: Macrocytic anemia in cancer of the stomach, apparently due to lack of intrinsic factor, Am. Jr. Med. Sci., 1938, cxcv, 17-20. CrossrefGoogle Scholar5. STURGISGOLDHAMER CCSM: Macrocytic anemia, other than pernicious anemia, associated with lesions of the gastro-intestinal tract, ANN. INT. MED., 1939, xii, 1245-1262. Google Scholar6. CASTLERHOADSLAWSONPAYNE WBCPHAGC: Etiology and treatment of sprue, Arch. Int. Med., 1935, lvi, 627-699. CrossrefGoogle Scholar7. CASTLETOWNSENDHEATH WBWCCW: Further observations on the aetiological relationship of achylia gastrica to pernicious anaemia, Lancet, 1930, i, 1062-1063. CrossrefGoogle Scholar8. BARKERHUMMEL WHLE: Macrocytic anemia in association with intestinal strictures and anastomoses; review of the literature and report of two new cases, Bull. Johns Hopkins Hosp., 1939, lxiv, 215-256. Google Scholar9. Year Book of General Medicine, 1933, Editorial note, page 341. Google Scholar10. STRAUSSCASTLE MBWB: Studies of anemia in pregnancy; the etiologic relationship of gastric secretory defects and dietary deficiency to the hypochromic and macrocytic (pernicious) anemias of pregnancy and the treatment of these conditions, Am. Jr. Med. Sci., 1933, clxxxv, 539-551. Google Scholar11. SCHENKENSTASNEYHALL JRJWK: Antianemic principle in human liver in carcinomas of stomach and cecum, Am. Jr. Med. Sci., 1940, cc, 11-17. CrossrefGoogle Scholar12. BLOOMFIELDPOLLAND ALWS: Fate of people with unexplained gastric anacidity; follow-up studies, Jr. Clin. Invest., 1935, xiv, 321-324. CrossrefGoogle Scholar13. ASKEY JM: Prevention of pernicious anemia; recognition of latent stage in relatives, ANN. INT. MED., 1940, xiv, 593-607. Google Scholar14. YANGKEEFER CSCS: Pernicious anemia in Chinese patients; report of case, Nat. Med. Jr. China, 1931, xvii, 218-223. Google Scholar15. SNAPPER I: Chinese lessons to western medicine, 1941, Interscience Publishers, Inc. New York, page 284. Google Scholar16. STURGIS CC: Diseases of the blood, in: MUSSER J. H.: Internal medicine, 4th edition, 1940, Lea and Febiger, Philadelphia, page 947. Google Scholar17. WILLSMEHTA LMM: Studies in "pernicious anaemia" of pregnancy; preliminary report, Indian Jr. Med. Res., 1930, xvii, 777-792. Google Scholar18. SPAAR EC: Pernicious anaemia in an Asiatic, Brit. Med. Jr., 1934, i, 578-579. TAYLOR G. F. CHITKARA N. L.: Report of two post-mortems and five cases of Addisonian pernicious anaemia, Indian Med. Gaz., 1940, lxxv, 16-19. CrossrefGoogle Scholar19. ERULKAR AS: Pernicious anaemia in India, Clin. Jr., 1931, lx, 237-238. Google Scholar20. DE LANGEN CD: Studies in blood diseases and blood regeneration in Java, Proc. Roy. Soc. Med., 1933, xxvi, 763-772. CrossrefGoogle Scholar21. CORNELL BS: Study of pre-disease diets of patients with pernicious anaemia, Bull. Johns Hopkins Hosp., 1927, xl, 409-421. Google Scholar22. UNGLEYJAMES CCGV: Effect of yeast and wheat embryo in anaemias; nature of haemopoietic factor in yeast effective in pernicious anaemia, Quart. Jr. Med., 1934, iii, 523-548. CrossrefGoogle Scholar23. WILLSEVANS LBD: Tropical macrocytic anaemia: its relation to pernicious anaemia, Lancet, 1938, ii, 416-421. CrossrefGoogle Scholar24. SPIESPAYNE TDW: Study of the etiological relationship between pellagra and pernicious anemia, Jr. Clin. Invest., 1933, xii, 229-234. CrossrefGoogle Scholar25. SALAH M: Demonstration of haemopoietic principle in chronic pellagric achylia, Trans. Roy. Soc. Med. and Hyg., 1935, xxix, 299-302. CrossrefGoogle Scholar26. SYDENSTRICKERSCHMIDTGEESLINWEAVER VPHLLEJW: Liver in pellagra, Am. Jr. Med. Sci., 1939, cxcvii, 755-763. CrossrefGoogle Scholar27. WILLSCLUTTERBUCKEVANS LPWBD: New factor in production and cure of certain macrocytic anaemias, Lancet, 1937, i, 311-314. CrossrefGoogle Scholar28. TROWELL HC: Liver extract in treatment of tropical macrocytic anaemia, Lancet, 1941, ii, 303-304. SPIES T. D.: Observations on the treatment of pellagra, Jr. Clin. Invest., 1934, xiii, 807-816. RHOADS C. P. MILLER D. K.: Intensive liver extract therapy of sprue, Jr. Am. Med. Assoc., 1934, ciii, 387-391. CrossrefGoogle Scholar29. HUTYRAMAREKMANNINGER FJR: Special pathology and therapeutics of the diseases of domestic animals, 4th English edition, volume 3, 1938, Alexander Eger, Chicago, page 101. Google Scholar30. GEIGERGOODMANCLAIBORN AJLSLN: Effects of gastrointestinal resections in swine on anti-anemia potency of liver, with observations on nature and sources of materials effective in pernicious anemia, Yale Jr. Biol. and Med., 1940, xiii, 259-278. Google Scholar31. FoxCASTLE HJWB: Observations on the etiologic relationship of achylia gastrica to pernicious anemia, Am. Jr. Med. Sci., 1942, cciii, 18-28. CrossrefGoogle Scholar32. MILLERRHOADS DKCP: Experimental production of loss of hematopoietic elements of gastric secretion and of liver in swine with achlorhydria and anemia, Jr. Clin. Invest., 1935, xiv, 153-172. CrossrefGoogle Scholar33. GOLDBERGERWHEELER JGA: Experimental production of pellagra in human subjects by means of diet, Hygienic Lab. Bull., U. S. P. H. S., 1920, No. 120, 7-116. Google Scholar34. WILLSBILIMORIA LHS: Studies in pernicious anaemia of pregnancy; production of macrocytic anaemia in monkeys by deficient feeding, Indian Jr. Med. Res., 1932, xx, 391-402. WILLS, L. STEWART A.: Experimental anaemia in monkeys, with special reference to macrocytic nutritional anaemia, Brit. Jr. Exper. Path., 1935, xvi, 444-453. Google Scholar35. BUSSABARGERIVYWIGODSKYGUNN RAACHSFD: Effect of gastrectomy on the monkey, ANN. INT. MED., 1939, xiii, 1028-1041. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, California*Received for publication May 21, 1943.From the Department of Medicine, University of Southern California School of Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1944Volume 21, Issue 3Page: 402-411KeywordsEtiologyGenetic determinismNatural history of diseasePernicious anemia ePublished: 1 December 2008 Issue Published: 1 September 1944 PDF downloadLoading ...

Pernicious anaemia (PA) is characterised by vitamin B12 deficiency due to autoimmune-mediated loss of gastric parietal cells and intrinsic factor, a specific transporter for the intestinal uptake of vitamin B12. PA is typically managed with lifelong intramuscular hydroxocobalamin injections every 2-3 months. However, this regimen lacks robust scientific validation and fails to account for varied symptomatic responses among patients, with many requiring more frequent injections(1).The Pernicious Anaemia Society (PAS) is a patient-driven charity that identified 10 research priorities for PA through a James-Lind Alliance Priority Setting Partnership(2). PAS members were surveyed to build a PA Research Repository, exploring diagnostics, treatment, family histories, and comorbidities. This project aims to better understand and manage the condition by addressing these priorities and characterising a cohort of patients.An online survey was designed using SurveyMonkey comprising 21 questions to collect data on demographics, mode and timing of PA diagnosis, diagnosed comorbidities, family history of PA or other autoimmune conditions, and management (type, regime and patient satisfaction). All questions were compulsory. The survey was sent to 3,482 PAS members (April-September 2022) via the PAS newsletter, email, and website. Chi-square tests were used to investigate associations between gender and survey responses. The study protocol and procedures received a Favourable Ethical Opinion.Completed surveys were received from 1,191 PAS members (34% response rate). Among these, 971 (81%) had a confirmed PA diagnoses, and the cohort was predominantly UK-based (92%) females (81%) aged 23-90 years, with a wide age of onset (10 to 80 years, mean 49 years). Diagnoses were typically based on low serum B12 (40%), positive intrinsic factor (31%), and/or parietal cell autoantibodies (13%), with 7% diagnosed via the now obsolete Schilling test. Diagnostic delays were common, 39% of participants reported waiting ≥3 years for a diagnosis. Over half (59%) reported other micronutrient deficiencies upon diagnosis. Half reported additional autoimmune diseases, with one-third having family with PA or other autoimmune conditions. Treatment primarily involved hydroxocobalamin intramuscular injections (77%), with 48% following the recommended guidelines and 52% injecting more frequently. Females had higher prevalence rates of Hashimoto’s disease (27% vs 7%), asthma (33% vs 20%), and iron deficiency (49% vs 35%) (all p < 0.05).This survey has established the first-ever PA research repository of over 1,000 participants offering initial insight into the complexities of PA, from varied age-of-onset and familial clustering to diagnostic challenges and treatment variability. These results support the need for improved diagnostic and treatment strategies, supporting the research recommendations made in the recent vitamin B12 deficiency NICE guidelines(3). It also highlights the potential of collaborative research with a patient-driven charity. Collaborative efforts aim to advance patient-centred PA research, improve treatment evaluation, and develop evidence-based approaches to managing this complex condition.

Summary.Phytohaemagglutinin (PHA)‐transformed lymphocytes have been used as a model cell system to study the uptake of radioactive vitamin B12 by haemopoietic cells. Both mature granulocytes and PHA‐transformed lymphocytes took up more vitamin B12 than mature, non‐transformed lymphocytes. Uptake of vitamin B12 by PHA‐stimulated lymphocytes was greatest at 48–72 hr of culture, i.e. at about the time or just before the time of peak DNA synthesis.Vitamin B12 deficient lymphocytes took up significantly less vitamin B12 than normal lymphocytes. Folate deficient lymphocytes took up an average of about 50% more vitamin B12 than normal but the difference was not statistically significant for the numbers tested. Vitamin B12 uptake by PHA‐stimulated lymphocytes was related to their rate of RNA synthesis (measured by 3H‐uridine uptake) and was closely related to active cytoplasmic protein synthesis since it was rapidly inhibited by puromycin and cycloheximide.

Under physiological conditions Intrinsic Factor secreted by the cells of the gastric mucosa is required for the uptake of vitamin B12 by the small intestine. Vitamin B12 passes to the blood, reaches the liver as well as other organs, and some is re‐excreted into the bile (Grasbeck, Nyberg and Reizenstein, 1958). Whether vitamin B12 is accompanied by Intrinsic Factor on its passage into the blood and into the bile or whether Intrinsic Factor does not pass beyond the intestinal wall is uncertain.Miller and Hunter (1957) have demonstrated that not only does Intrinsic Factor enhance the vitamin B12 uptake by gut but it will also promote the attachment of vitamin B12 to serum, liver, kidney and other tissues. It has been suggested that vitamin B12 and Intrinsic Factor, but not vitamin B12 alone, is required to restore normoblastic haemopoiesis in a culture of megaloblastic marrow (Lajtha, 1950; Callender and Lajtha, 1951; Pendl, Franz and Hunkel‐Trees, 1958). Toporek (1961) has shown that Intrinsic Factor perfused through a rat liver is re‐excreted in an active form into the bile and Herbert and Kaplan (1961) have reported evidence suggesting that Intrinsic Factor, like vitamin B12 (Grasbeck et al., 1958) takes part in an entero‐hepatic circulation. Further Gulberg and Kistner (1963) have found that hog bile contains a fraction showing the same immunological behaviour as the main vitamin B12 binding component of hog Intrinsic Factor. It is likely that the haematological relapse of patients with pernicious anaemia treated with oral vitamin B12 and hog Intrinsic Factor preparations is due to the development of antibodies against hog Intrinsic Factor suggesting absorption of at least some of this material (Schwartz, 1962).On the other hand, Cooper and Castle (1960) found evidence for the release of vitamin B12 from Intrinsic Factor at the gut wall. Taylor and Medenica (1962) found that the uptake of vitamin B12 by rat tissues, particularly the liver, was independent of a source of Intrinsic Factor and others have failed to substantiate an Intrinsic Factor requirement for the maturation of a megaloblastic marrow culture (Reisner and Swan, 1954; Carrara, Taglioretti and Eridani, 1960). The large molecular weight suggested for Intrinsic Factor by some workers (Bromer and Davisson, 1961) does not favour its transport beyond the gut wall, at least in the undegraded form.The purpose of the present study was, firstly, to obtain evidence for or against transport of Intrinsic Factor into the blood and, secondly, to determine whether Intrinsic Factor, like vitamin B12, takes part in an entero‐hepatic circulation.

Comparison between Weekly Intravenous Versus Daily Oral Vitamin B12 Supplementation in Vitamin B12 Deficiency Anemia [Courage-12]: A Randomized, Open Label, Single Centre Study