Brennan, Michael J.

Monto, Raymond W.

Rebuck, John W.

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical JournalVolume 1 | Number 1 Article 53-1953Inhalation And Nasal Instillation Of CrystallineB12 Therapy In Pernicious AnemiaRaymond W. MontoJohn W. RebuckMichael J. BrennanFollow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournalPart of the Life Sciences Commons, Medical Specialties Commons, and the Public HealthCommonsThis Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in HenryFord Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. For more information, please contactacabrer4@hfhs.org.Recommended CitationMonto, Raymond W.; Rebuck, John W.; and Brennan, Michael J. (1953) "Inhalation And Nasal Instillation Of Crystalline B12 TherapyIn Pernicious Anemia," Henry Ford Hospital Medical Bulletin : Vol. 1 : No. 1 , 15-20.Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol1/iss1/5INHALATION AND NASAL INSTILLATION OF CRYSTALLINE B12 THERAPY IN PERNICIOUS ANEMIA R A Y M O N D W . M O N T O , M . D . * J O H N W . R E B U C K , M . D . , Ph.D.** M I C H A E L J. B R E N N A N , M . D . * * * Parenteral therapy of pernicious anemia with vitamin B12 has been established as the treatment of choice while oral administration of the drug has been Ineffective except in massive doses or In combination with "Intrinsic factor."1,2,3 In view of the demonstration that pharmacologic agents may be absorbed from the respira-tory tract mucosa4, this report Is a summary of one year's experience with crystalline B12 inhalation and nasal Instillation In the treatment of pernicious anemia. METHODS AND MATERIALS Six cases of pernicious anemia in relapse were treated with vitamin B12 by in-halation or nasal instillation. Three of these patients received crystalline B12 in physiological saline without a preservative by vaponephrin nebulizer. B12 lactose powder was administered to one patient by dust inhalator (aerohalor—Abbott). Nasal instillation of vitamin B12 In saline was utilized in the last two cases. Twenty patients with pernicious anemia in remission were given Inhalation B12 therapv at comparable intervals to maintenance parenteral treatment. CASE REPORTS Case 1. F.Z., a white male, aged 56 years, presented classical clinical and hematological findings of pernicious anemia with an initial ervthrocyte count of 1,360,000. On the 8th day of B 12 aerosol therapy a maximum reticulocyte response of 44.2% was obtained. The subsequent treatment and course of the patient are shown In Chart 1. The bone marrow and peripheral blood smears before and three weeks after therapy are illustrated in Figure 1. Case 2. L . H . , a white female, aged 71 years, was studied for mild manifesta-tions of pernicious anemia and minimal peripheral neuritis. Her response to therapy is depicted In Chart 2. Case 3. S.G., a white female, aged 51 years, demonstrated typical mani-festations of pernicious anemia with an Initial erythrocyte count of 1,640,000. *Chief of Division of Hematology. **Associate in Department of Laboratories. ***Formerly Associate in Division of Hematology. Now serving in U. S. .A. M . C. 15 Treatment consisted of Inhalation of B12 lactose powder which resulted In the production of over 400,000 erythrocytes a week In the first twenty-one days of therapy. Chart 3. Case 4. C.C., a white male, aged 66 years, with usual findings of pernicious anemia did not respond to oral administration of B12 (15 meg. daily) for 10 days, but demonstrated a satisfactory course on inhalation at the same dose. Chart 4. Case 5. J.P., aged 82 years, white male with severe pernicious anemia in relapse was given a single Inhalation of 100 meg. crystalline B12 followed by a reticulocytosis of 17%, on the 5th day. Three weeks after his Initial therapy nasal Instillations were administered daily with the hematological Improvement shown in Chart 5. Case 6. J.A., white male, aged 69 years, with classical findings of pernicious anemia of a moderate degree (erythrocytes 2,880,0(X)) was treated by a single nasal instillation of 100 meg. of B12 in 1 ml. saline. On the 8th day a reticulocy-tosis of 37%, was recorded. Three weeks later relnstltution of nasal therapy resulted In continued satisfactory Improvement, Chart 6. The twenty patients on maintenance inhalation therapy for one year have had no evidence of relapse and appear to be adequately treated. DISCUSSION The six cases presented In this paper demonstrate the efficacy of the treatment of pernicious anemia by inhalation and nasal Instillation of crystalline vitamin B12. Further, the maintenance of pernicious anemia In remission by Inhalation B12 therapy has proved feasible. Inhalation and nasal Instillation of crystalline vitamin B12 In saline and lactose powder has thus far produced no Irritating or sensitizing action at the local sites. Oral administration of vitamin B12 in amounts of 10,000 meg. results In urinary excrerion of less than 0.05 mlllimicrograms per ml. On the other hand. Inhalation of 200 meg. of B12 in saline produced an urinary excretion of 0.26 mlllimicrograms per ml. Direct Instillation of 100 meg. of B12 into the pulmonary tree by means ot a bronchoscope gave an urinary excretion level of 9.76 mlllimicrograms per ml. Nasal instillation of 200 meg. B12 in saline resulted in a concentration of 1.36 mlllimicrograms per ml. SUMMARY Inhalation and nasal Instillation of crystalline vitamin B12 In saline and lactose powder has produced satisfactory clinical and hematologic responses In six parients with pernicious anemia In relapse. Twenty parients with pernicious anemia In remission have been maintained by Inhalarion B12 techniques for over a period of one year. 16 Ht) R B.C Retic Gms, 10^ V . r l 5 -r ^ 1 - 5 0 - | - 1 4 - - 4 5 -- 1 3 - - 4 -- 4 0 -- 1 2 - - 3 5 -- I I - • 3 • - 3 0 -- 1 0 - - 2 5 -- 9 -- 2 -- 2 0 -- B - - 1 5 -- 7 - - 1 -- 1 0 -- 6 - • 5 -- 5 L 0 • 0 -B-12 Aerosol Treatment in Pernicious Anennia. F.Z , H.F.H, ^674802. Aged 56 yrs., <S' R B C. Normocy l ic 18 20 22 24 26 26 30 6 A P R I L , MAY 1 9 5 2 Therapy: is/igm. -12 Aerosol 3 t imes a week by Hond Atomizer I iOO^gm Once o week by I B~I2 Hand Alomzer .Aerosol Hb RBCRe ' i c Gms 10= V „ CHART 1 B-12 Aerosol Treatment in Pernicious Anemia. L K , H F H , 4 2 5 1 4 9 A g e d 71 / ^ s ., ? 2 3 A P R I L , 1952 1 5 u g m T h e r a p y by B - 1 2 P r e s s u r e T a n k CHART 2 Charts 1, 2, 3 and Figure 1 witfi kind permission, from Monto, R. W., Rebuck, J. W., and Brennan, M . J.: Crystalline B12 Inhalation Therapy in Pernicious Anemia, .^M. J. M. SC. Feb. 1953. 17 B-12 Dust Inhalation Treatment in Pernicious Anemia. Hb. R.B.C.Retic. Gms. l o ' * / . 5. G.,H.F.H.. ^686563. Aged 61 yrs., d". 2 5 --15 - • 4 -20-•11 - - 3 - 5 -- 9 • - 2 -C -- 7 - • 1 -5-Megaloblasts I 39 6 V, Therapy: 8 10 12 14 16 18 20 22 24 26 28 30 2 4 6 8 10 12 14 16 IB 20 22 24 26 28 30 AUG. SEPT. 1952 1952 - 1 2 Dust I n h a l a t i o n 5 C y c l e , „ I I I I I I P L A T E L E T S 1 0 0 , 0 0 0 _ I 0 0 0 >igm»._ (1 c a p s u l e ) P L A T E L E T S 3 7 5 , 0 0 0 CHART 3 B-12 AEROSOL TREATMENT IN PERNICIOUS ANEMIA. Hb RBC Relic Gms lO^ CC . H F H , 221155 Aged 66 yrs , a" M e g a i o b i o s f s 2 9 "/» 15 17 19 21 23 25 27 29 I 3 5 7 9 I I 1 3 ^ 1 8 23 28 2 7 12 NOV. 1952 OEC JAN. 1953 1 5 >igm B-12 Aeroso l A e r o s o l Aerosol A e r o s o l ORAL \^ _ugm D o i l y 3 X a WE E K 1 X WEEK 1 X EVERT OTHER WK CHART 4 18 Gms 10^ V . 15 - r 5 B-12 AEROSOL a NASAL INSTILLATION TREATMENT OF PERNICIOUS ANEMIA. I L J P,H F H, 366JZ6 AGED 82 YRS , <f. M e g a l o b l a s t s 2 5 Vo -o 24 26 28 30 i 5 MOV I 9 5 2 | DEC lOO / i .gm B-12 AEROSOL 7 9 - » l 3 17 21 Z5 29 1 5 9 13 — * 26 JAN 1953 Nose Drops 10 MS'" EVERyOAY Hb R B C Relic Gms 10^ % CHART 5 B-12 NASAL INSTILLATION TREATMENT OF PERNICIOUS ANEMIA J*? J. A., H.F H., ^ 699 081 Aged 69 yrs., 10 12 14 16 16 2 0 22 2 4 2 6 2B 3 0 2 4 DEC 1952 J JAN 1 9 5 ^ T h e r a p y N o s e D r o p s I 0 0 _ ^ g m in I m l . 10 12 —»- 26 Nose Drops 5 >iqrn B - 12 Da i l CHART 6 10 •h i t •Hi' Figure 1 Fig. 1. Case 1. Representative megaloblasts and a giant neutrophilic metamyelecyte in the marrow aspirate prior to treatment. X12!)0. Fig. 2. Case 1. Normoblasts and unaffected members of the neutrophilic series in the marrow aspirate after crystalline B;; aerosol treatment. X12(K). Fig. 3. Case 1. Megalocytes and poikilocytes in the peripheral blood prior to treatment. X12l)0. Fig. 4. Case 1. Normocytes w i th only an occasional macrocyte in the peripheral blood after crystalline Bj2 aerosol treatment. XI200 . ACKNOWLEDGMENT The authors wish to express appreciation to H . W. Schoenlein, Director of Bacteriological Laboratories, Difco Laboratories Incorporated, for supplying the crystalline Bi2-lactose powder and the urinar}' B12 determinations. B f B L I O G R . A P H Y 1. Conley, C. T.., Kreyans, J. R., Chow, B. F., Barrows, C , and Lang, C. A. , Observations on the absorption, utilization and excretion of vi tamin B12, J. L.'^B. & C L I N . M E D . ,38:84, 195L 2. Dautrebande, L . , Physiological and pharmacological characteristics ot liquid aerosols, P H \ SIOL. REV. 32:214, 1952. 3. Meyer, L . M . , Sawitsky, .A., Cohen, B. S., K r i m , M . , and Fadem, R., Oral treatment of pernicious anemia with vi tamin 812, A.M. J. M . SC. 220:604, 1950. 4. Ungley, C. C , Absorption of vitamin B12 in pernicious anemia. I . Oral administration without a source of intrinsic factor, B R I T . M . J. 2:905, 1950. 2! I 

Inhalation And Nasal Instillation Of Crystalline B12 Therapy In Pernicious Anemia

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