Document pp4LRbZ5rn03x23ejJznRJZX7

\ 658 THE NEW ENGLAND JOURNAL OF MEDICINE March 18. 1976 CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL Weekly Clinkopftthological Exercises KOKBtD BT BXCKABD C. CABOT Robert E. Scully, M.D., Editor James J. Galdabini, M.D., Associate Editor Bmv U. McNeely, Assistant Editor Continued preparation of these Case Records has been made possible by agenerous grant from Pfizer Pharmaceuticals to the Massachusetts General . Hospital. CASE 12-1976 Presentation of Case First admission. A 35-year-old man was admitted to the hospital because of acute myelcblMtic leukemia. He was well until four weeks previously, when an upperrespiratory-traet infection developed and persisted. On the day ofentry he came to the clinic, where an abnormal blood count was found, and was admitted to the hospital. The temperature was 37.2"C, the pulse 90, and the respi rations 18. The blood pressure was 100/70 nun Hg. On examination the patient appeared robust. Enlarged lymph nodes were found in the cervical, supraclavicularand inguinal regions bilaterally. The lungs were dear, and the heart normal. The liver was not felt, and its vertical span was 8 cm; the splenic tip was barely palpable on inspiration. The urine was normal. The hematocrit was 38 per cent; the white-cell count was 23,200, with 5 per cent neutro phils, 2 per cent band forms, 18 per cent lymphocytes, 2 per cent metamyelocytes and 73 per cent blasts; occasional Auer rods were noted. The platelet count was 49,000. The patient was given cytosine arabinoside daily (or one week and a three-day course of daunorubicin. The platelet count fell to 2000, the white-cell count to 300, and the he matocrit to 21.7 per cent; numerous ecchymoses appeared. T/nfusions of platelets and of red cells were adminis tered. Oral and esophageal moniliasis developed and did not respond to mycostatin; amphotericin B was instituted. On the 21st hospital day the hematocrit was 32 per cent, the white-cell count 3000, and the platelet count 170,000. A bone-marrow aspiration disclosed evidence of complete re mission. He was discharged on the 22d hospital day to be followed in the clinic. Sromd admission (three and a half months later). The pa tient returned periodically to the clinic, where maintenance doses of cytosine arabinoside and 6-thioguanine were ad ministered. Bone-marrow relapse developed, and 10 days before admission he began to have a headache and fever. He returned to the hospital. The temperature was 38.4*C, the puke 100, and the res pirations 16. The blood pressure was 100/70 nun Hg. On examination he appeared pale. Conjunctive! hemor rhages were observed in the right eye. Small cervical and in guinal lymph nodes were palpable. The lungs and heart remained normal. The edge of the liver descended 6 cm, with a vertical span of 16 cm; the spleen'was 6 era below the left costal margin. . The urine was normal. The hematocrit was 31 per cent; the white-cell count was 184,750, with 2 per cent neutro phils, 1 per cent basophils and 97 per oent blasts. The plate letcount was 35,000. The glutarnie oxalacetic transaminase (SGOT) was 127 U, the lactic dehydrogenase (LDH) 580 U, the amylase 7 U, and the alkaline phosphatase 13.6 BodamIcy U. An x-ray film ofthe chest was normal. A lumbar puncture showed no abnormality, and multiple cultures yielded no bacterial growth. The patient was given further doses of cytosine arabino side, with vincristine, daunorubicin, eephalothin, gentami cin and orally administered mycostatin; platelets and fro zen, washed red cells were transfused. On the sixth hospital day the hematocrit was 23.2 per cent, the white-cell count 13,600, and the platelet count 15,000. Three days later a bone-marrow aspiration revealed a large number of blast cells. On the 12th hospital day bilateral retinal hemor rhages were found. Monllial Infection recurred and was treated with further doses of mycostatin and flucytosine (5- ftuorocytosine). On die 30th hospital day, after preparation with four zublethal doses of cyclophosphamide, the patient received approximately 700 ml ofbone marrow from a sister who was Identical by HL-A and mixed lymphocyte culture (MLC) methods. Prophylactic treatment with methotrexate was be gun. Esophagitis recurred, and additional doses of ampho tericin B were given. On the 36th hospital day a purpuric eruption appeared. A skin biopsy revealed a nonspecific re action that included slight vacuolization in the region ofthe basement membrane and a sparse, superficial perivascular lymphohistiocytlc infiltrate.' Antibiotic therapy was discon tinued. On the 44th hospital day a bone-marrow-aspiration smear was normal except for a shift to the left; a cytogenetic study revealed a female karyotype. On the 45th hospital day grand-mal seizures developed; a lumbar puncture yielded grossly bloody cerebrospinal flu id under a normal pressure; stained smears disclosed no micro-organisms,,and cultures gave no bacterial growth. A computed axial tomographic study (CAT-acan) of the brain and an electroencephalogram showed no abnormality. Phenytoin (diphenylhydantoin) sodium and phenobarbital were instituted, and seizures did not recur. On the 48th hos pital day the hematoerit was 28.6 per cent, the white-cell count 2900, the platelet count 90,000, and the reticulocyte count 6.1 per cent. Methotrexate was continued. On the 52d hospital day the patient was discharged on a regimen of prednisone, mycostatin, phenytoin sodium and phenobar bital. Final admission (10 days later). He felt well until two days /* AP000204I2 A OB*M: V. Kayo Smith a/UChmieaA- AUWTOWH FA. 28 Hay 1976 cc: A. Ross Adams W. L. Ball J. T. Barr T. L. Carey/H.L.Watson/J.C.Novak E. Donley Richard Fleming Hantell B. Tepper, M.D. RECEIVED JUN i 1976 . S MEDICAL 0fL' . -1 i . X AP000204I3 \ V Manufacturing chemists Association Minutes of Meeting M 1016 V*. w: SMITH VINYL CHLORIDE RESEARCH COORDINATORS Crystal City Marriott Hotel Arlington, va. April 27, 1976 Chairman Torkelson convened the meeting at 9:00 p.m. The record of attendance is: MEMBERS PRESENT: T. R. Toxkelson Z. G. Bell, Jr. W. D. Harris M. N. Johnson H. L. Kusnetz W. M. Smith R. N. wheeler M. Freifeld Chairman GUESTS PRESENT: w. R. Gaffey R. V. Johnston M. w. Palshaw B. A. Schwetz P. G. Watanabe *** ** The Dow Chemical Company PPG Industries, Inc. UNIROYAL, Inc. B. F. Goodrich Chemical Company Shell Oil company Air Products & Chemicals, Inc. Union Carbide Corporation MCA Staff Equitable Environmental Health, The Dow Chemical Company Stauffer Chemical Company The Dow Chemical company The Dow Chemical Company Inc. ******* 1. Birth Defects The article on "Genetic Risks of Vinyl Chloride", by P. F. Infante et al., which appeared in Lancet recently, (report edly identical to the article distributed to the panel on March 17, 1976), attempts to implicate VC but its data base is very weak. Currently, The Center for Disease Control (CDC) is conducting a study on this subject in Kanawha county. West Virginia, in the discussion of whether this group should rec ommend undertaking a study in this area, the conclusion was r AP00020414 VC/RC - 2 reached that no feasible way of conducting it could be found. Hence, it was suggested that the matter be held in abeyance until the results of the CDC project are known. Dr. Schwetz felt there was no need for additional animal testing with relation to birth defects. However, he thought other test should be considered. He pointed out that the Ames test is marginally positive with VC but dominant lethal and cytogenetic tests are negative. Therefore an approach such as heritable genetic translocation studies of the type conducted by Russel at Oak Ridge might be suitable. The birth defects surveillance program of CDC was scheduled to be a major topic at a meeting April 21, chaired by Dr. E. Landau of The American Public Health Association and attended by Dr. Ken Johnson of the MCA staff, in the absence of Dr. John Herbert of CDC, who was to speak on this program, the discussion centered on a presentation by Dr. Theriault whose work is described in a paper, "Distribution of Primary Cancers of the Liver in the Province of Quebec", in CNA Journal, February 8, 1975, pages 305 to 307. Dr. Theriault sought additional funds to pursue his investigations and indicated a written proposal would be forthcoming. The Research Coordinators felt'they would probably not be interested in supporting Dr. Theriault's work at this time, particularly since he did not plan to investigate birth defects. The group decided to defer any recommendations on mutagenesis/birth defects until the results of the CDC study are known. 2. Continuation of Dow Metabolism studies The results of a letter ballot on this effort reported on by the Project Manager indicated the Panel was overwhelmingly in favor of continuing these studies. Only two of the ballots received indicated any reluctance on this score. Dr. watanabe outlined the next step of proposed studies as following the binding of VC to macromolecules including those containing sulfhydryl. Concurrently, in vitro investigations are planned to determine what happens to tissues of exposed animals. Ho specific recommendations were felt necessary from this group in the light of the ballot results. AP00020415 VC/RC - 3 3* . University of Louisville proposal In a letter, of.April 20, to Dr. Torkelson, Dr. Tamburro outlined studies on immunological systems and electron micro scopic evaluation of liver tissues. This was a further descrip tion of areas the Panel previously found to be of interest. An important aim of this proposed work is to develop new diagnostic tools, (mainly based on enzyme testing), for anticipating diseases due to VC exposure. This will complement Dr. Tamburro's major effort, supported by The National Cancer Institute, for applying known, accepted methods for diagnosis and treatment. The support level requested was at about $235,000 per year but an alternate funding suggestion was at the rate of about $200,000 per year. Dr. Torkelson transmitted a sense of urgency, if indeed the group wanted to support this effort, so that Dr. Tamburro could keep his staff intact. On motion made and duly seconded to support this program at the rate of $200,000 per year for three years, the vote was five in favor and two opposed. 4. Selection of Vice Chairman Dr. W. Mayo Smith was unanimously elected as this group's recommendation to the Panel for Vice Chairman. The vacancy was created when Dr. Rinehart left Ethyl corporation. The meeting was adjourned at lls30 p.m. MFsec Minutes Subject to Approval May 25, 1976 Milton Freifeld 0 AP00020416 f. AP000204I7 CHEMICAL MARKETING REPORTER MARCH 8, 1976 Disease Control Center Seeks Link With VCM in W.Va. Birth Defects The National Center for Disease Control is doinf an epidemiological study in the area of Charleston, W. Va., near where Union Carbide Corpo ration has one of its vinyl chloride po lymerization plants. The purpose of the study is to determine whether the higher than average rate of birth defects in the Charleston 8. Charles ton area may be related to exposure to vinyl chloride monomer. Between 1970 and 1953. fifty-three chil dren with central nervous defeets were bore in this region. Bated on the national average, thirty-one such births might have bees expected. National Center epidemiologists hope te interview the parents of ail childrent ta the region with eentrel nervous system defects in order to find out where the parents werk and how far away from the PVC plant they lived, especially during the early stages at pregnancy. Their experiences will be com pared with those of a control group of parcats with normal childreo. This study is a follow-up of an earlier study done by the center in an area la Ohio near a PVC plant. That study, which was inconclusive, was prompted by eariier find ings by a National Institute for Occupation nl Safety 4 Health epidemiologist wee Ascovered an unusually high rate of birth detecta* especially nervous system delects tang children bore In three eitteeb* Obie where VCM polymerization plants are lo cated. The epidemiologist. Dr. Peter F. Infest*, has also repeated twe- te thmefo* in crease in the eec efstiUbixthe. wad mteear riages among die wive* of vfcqri chloride polyieerttnrt-- workers unfit with wives af PVC fabrication and rebhar work ers. (Cmx rent, pg. m>. It was also reported last week that Envi ronmental Protection Agency, in conjunc tion with American Public Health Associa tion. is planning to study the rates of can cer. stillbirths, miscarriages, birth defects and ether diseases that might be related to VCM. 'WJ'- n~ J VCM 5 I cji><5?t+- -i--. T*\* fatUAsdis In 1 tic-iu-X v i-'- c kTr-vi ^ flQA 31 AP00020418