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~t A t1 1967 a e. ugus , . Name of Investigator(s): (incfud. Title and Degrees) Oswald R. Jones, M.B. - Director of Research Ptoject 2. InslBution & Addresse gt, Luke rs, Hospital -Irest 113th Street, New lork City ,_ =; 3 Short Tide of Project; Cabbon monozide uptake and diCfusion capacity in children. This• test together with others will be used to evaluate puLnonary function in children starting at the earliest age of cooperation. This evaluation of 4. Proposed5tartingDote: pulmonary function will be applied to normal children, those with asthma bronehitis, or chronic pneumonia which conditions were subse7tuent to S Mti ' t~Qgr~tign etthjp~egfjhS,yt j}•~az.{d~arlq those caused by knovrn viral agents. Octotier 1, 967• - 3-5 years. 6. Erief Descripton of Objedives or Specific Aims:. Measurements of carbon monoxide (CO), uptake and diffusion capacity (i) have been modified to obviate painful arterial puncture by the use of end tidal PC0 at reat (2, 3, jtr S) and during graded hyperventilation (6). Application o8 these methods in the dog, and in. normal humans an& patients :with chronic chest diseases have established the reJ.ationship between~CO uptake and diffusion as graded. hyperventilation- in, normal and diseased ; a~dults (7, 10 'supporting 8,9) `'•. Normal children will be grouped according to age and size and normal values for CO uptake and. diffusion established as controls. Children with asthma bronchitis and post viral pneumonitis will be studied and the results. compared. ~ 7. Givea Brief Statemenlofyovr Working Hypothesis: The objectives of the study are: (1) to establ'ish normal values:for CO untake ¢Dd diffusion capacitv at rest and during hynerventilation in children. (2). To study the relationship of asthrcay bronchitis and viral pneumonitis on diffusion capacitv 3n d}rtdron as a background for the development of chronic pulnonary insuff iei-enc;; 4-- desm `=

9. Physical Facilties Available (Where Other than Administering Organization4ndicate Geographical tocation) The cardiopulnonary laboratory of St. Lukets Hosoital is a recognized research- • laboratory in pulmonar,-T diseases with four full time physicians, three blood gas technicians and all equipment and facilities to perform the studies outlined. New CO measurement and recording equipment is requested for . specific application to small children and;infants. r>>~t#d~nxa7s ~ . The pedicatric department of St. Luke's Hospital is headed by a full time director and operates an active inpatient service of fifty-four beds with ~ 1500'patients per one:year, as well as an outnatient depart-nent with more than, 30000 vi.sits per one year. A full time pediatric carcli ologist will devote part time ( 1/3) to this project. Antibody titre for viruses. F7.uorescent antibody search in tissues obtained by biopsy or at post•mortem, also cultures of the above tissues for oresence of bacteria and viruses. As mentioned CO nptslce and diffusion capacity techniques have been developed in this laboratory which,have been validated; in adults and which are specifically a)bplicable in children as.described. 11. Biographical sketches of all principal and professional personnell(append)' 12. List of pubGcmions: (Five most recent as pertinent) (oppend),

1 -liaterial and Method Z~+renty healthy boys, age 9 to 14 years,. from, the Cathedral School,, • . . . • . . . ~_r=~ u and that multiple results on- one person were obtazned using graded hyperventilation. - modified in such a way that correction for CO back pressure was introduced ;" helium-dilntion method, diffusion studies using carbon monoxide method of extensive spirometric measurements, lung.volume evaluation using and 11 patients from the Pediatric Department of St. Luke's Hospital of a similar age group were studied, for their lung function. Studies consisted .. tt.t _i~__~ _ .3 _1 : _1 ~ . . . . . " ~:~.: ..: L3151~Uj'y CSLLCL Ci.L1111(:cl.L CAGL111L1d"Vi1 nGI-G J.JGi'1:V.WlllGll ULL -L1+3. 110u1.4L1y UVya• clinical impressions, and the results were then compared. patients were categorized; as 1) normal~ 2) those with•min5.mal lung damage, if any~ 3) those with mild.lung damage,$ and A) those with moderate lung damage. Evaluation of the physiologic studies was done independently, without knowledge of the A1l hospital patients were examined and evaluated by a pediatrician. Hospital 'Observations Normal boys: Spirmnetric and volumetric studies have shown increase in lung volun es related to the growthr of the person studies, as expected. The ratios of the subdivisions of the lung volumes did not show any significant difference in this particular span of years. Diffusion studies have shown an lanexpected decline in efficiency of the alveolocapillary membrane when. exnressed per unit of lung,volume for more : mature boys. The findings indicate that the size of alveoli chanees with. age, so that actual alveolocapillary membrane reduces per•unit of volume. This, •' can be explained by increase of the size of the alveoli. This is, to our knowledge, the first time that this has been sho:m physiologically, although t.his. was to be expected because the growth of the lungS by prol!3f eration of the alveolar units stops. approximate.Ly at tne age or tien ana arter tinati tine lung volume increases essentially by expansion of the alveolar space. Sick persons: It vras found that the majority of the sick individuals have shown a distorted ratio of lung subdivisions (residual volume:total lung volume), although a discrimination toward normal persons "qas impossible because of the wide span of.normal values. Diffusion studies were able to differentiate sick persons from their healthy age-mates. Even mildly sick persons had. their diffusion values at the lower limit of normal or below that limit. In conclusion$ it is possible to showv that we have reliable tools for measuring lunj functions. The means are so sensitive that they can show the physiological changes related to the body growth in this age group. In addition, the results can discrininately show pathologic reduction in functions caused by chronic lung disease in:children.. 3fore studies will be needed to establish definite soan of normal values for each, age and size group, as well as to evaluate damage induced by different noxious agents. 1003546708 Added to our investigative facilities, will be a new diagnostic viral laboratory at St. Lukets ti•rere we can- identify the causative agent of pulmonary .damage in childhood. ..:.s.a:.,..,.::: ._,:_ ... •. : _.. .. ...v .. . ~ . .. _. ,.. ....... . .~

R: REDACTED MATERIAL 1- - Sub-Total r 2, 800>.00 2,900.00 28,9~i2.00 7 r$(>.30 Totd Salaries Consumable Suppl. Other Expenses Permanent Equip. Itis understood;thatthe applicant and institutional officers In applying for a, grant have read and found acceptable the Council's "Statement of Policy Containing Conditions and Terms Under Whieh Project Grants Are Made" 2~.h . .30 Overhea& Total None = Same 26 728 i0 26,728 30 ' /. Signatur// oK d f.n.i.N ~•jelephone ' W~inar Offfoe..f thL Ihnirvfi°e Telephone dc~ am=

tJrt finandol wpport for r.soarch from all roure+r, includiny own institution, for this and/or rolat.d r.s.arch projmctr. Sourca Stqny Yro1d Corporation Amount $90000 1 ear Duration \

0. R: REDACTED MATERIAL CI~; RICUT,tT.'.t VITAP: OS:'iALD R. JO'i :S3, LA.D. 1?- 9, •,";aterbury' Conn-. B.fi.p 1919 Yale College, V.D. COI:t1T'1yJiII 1923- St. ?.ul;© ts I'd~ital., N.Y. med. 192j-?_5, Be1.Iqvue . IiosII.j, 2I.Y. chest oerv. 1925-26, asslt Dath. St. I,ukels flosp.' 1926 27. Inst. in '.'•ed. Col. Univ. 1927 32. Assoc. in ?'ed. 1932 37. Asst. Clin. - Prof. of Med. 1937-62. F.A,C.P. Dipl. Tnt. `zed., Ac. t'ed.t Dir. .Car~a.o Respiratory Lab. St. Lukels. Cons. nhy. St. Lukols., Cons. Phy. _ Chest dis. S out.~:aepton Hosp., Cons. nhy. chest serviea- B©Ilevue ITosp. "Rc~ferences: 1. Jones, 0.q.s ?3easles - A Cause of Emhyse^.as An Hyoot'l:esis Ccncerning Chronic ~b.lr.onary ?:z?hysena, a Poss3.ble Cause end its Prevmtion, Am. Pzv. P.esF. I'rls. S'ol. $7# Lcr A.pr..1963 . Jones, 0.a., Platt, "7.D., and Amill, L.A. -'jiliary ":ht•erculosis Caused b~ Intravenous Self-In3ection of ;'u'-erc1Q- Pa:ci111., Treated .`alccessfulZ;l'•Tiah Strente*.xycin 'i'hcrauy.p ~n. PevR of T.II., Vol. 60, tlo. h Oct. 19h9 ' _ 3. Jonas, O.R. nnd Cournand A. - The Shsmikea FuLmns.r3* I:o1ae •rriih Chronic Bronciiiecvasis., Am. I?ev. of T.B. Vol. 2% ho. 3 Sept. 1933 Mler, J.A.# s.nd Jonos, 0.R.. - Primary Carcinosa of the Lung. Am. Rev. of T.B. Vol. 21, Flo. 1, Jan. 1930 Jones, O.p. and Burfor*3, G.R. - has;rive Atelect<isis following Cyclcp:ropane I!nEsth"sia - Jour. A: t.A. vo11 11% Apr. 2, i93~-.

R: REDACTED MATERIAL ~ LUCY Fi. S:711F T U.A . CttP'?.ICT1W1 "ITTAF. _ ~ P, ~ ritev York Cityp Barnarfl C.allegep tlerr York City .191t9' A.B.p Co11c .~;a of Ptysicians & SurCeons, Coluztbia ttn•iversit;r, N.Y,C. '. 11.D. 1953. Uary I=Ccne hassett Foseital, Coopersto;rn, N.Y. 1953 (Ju].y-Dec.) ;;..St. Luke'o i?osp. r~.i.C., 196C-62, clin, fe21o~ pediatric cardiolo;~ 1962- j-.•1961s, Preabyterian f?osp. I3anies F?osp. N.Y.C.,v Fes. lssoc- phem. 19514-1955 • =, 1?iv. F3p. Che:r,ollierapyp S1oan-9-otterin; rnst. 1T.Y.--:ad. Lic. ,1.Y.S. 1962p Am. Bd. of P©d. L'ipl. 1965„ Instr. Pediatrics Colu;:bia -Lni.v. 196?c-j, Asst. Att. Ped.(Cardio) St. Luko4s tTosp. 1964-, Ass&-.-Ped. Co1umbiF= res. L'.ed. Center, 4.Y.C. 1954 - 1!ssoc. Visitinv Ped., -I?zrl.cm I'osp. N.Y. 3.965 j. 1IEvd. Soc. of Co:u.tty of 21.Y.* t1.Y.State Led. Soc. Amer. ?'ed. !!ssoc.. References 1. S4iftj, L.it.$ and Giiffiths, S.P.: Cardiac 1!rrhytimias in the First Year of Life; ihe. Heart Bnllstin- 14: ]13-116, 1965 (1rov. I?©c.) I •

`.. Veljko Joseph Krstulovic, -M. D. Chronological Listing of'AII Activities Since Graduation From Professional School• I TO . Month Year Month Year Type of Activity, including Name and Address of Employer, Beginning with Date of Graduation from Professional School 1936 Baccalaureafie from Second State`s Boys Gymnasium, Zagreb. Oct. 1941 Graduation from Medical School of the University of Zagreb. Nov. 1941 May 1942 Internship in Pediatrics, Dermatology & Gynecology at ~ May 1942 Feb. 1943 The University of Zagreb. Continuation of intemship in the Chief Army Hospitaj. Zagreb. Postdocforai Training, ~ Aug. 1947 Oct. 1947 Course in Avia; ion Medicine, Zemun, Yugoslavia July 1950 Nov. 1951 While in the army, attended daily medical conf~rences, ward I ec. 951 I ec. 954 rounds, cardiac conferences and EKG reading in Medical Department of University Hospital in Zagreb. Chief, Dr. lvan Botteri, Professor of Clinical, Medicine. Residency in Internal Medicine at University"Hospital. Chief, Jan. 1955 Dec. 1956 Dr. Ivan Botteri, Professor of Clinical Medicine, succeeded by Dr. Arpad. Hahn, Professor of Clinical Medicine. Residency in Cardiology at University Hospital'. Dr. Radovcn July ' 1957 Ivancic, Associate Professor in Medicine. Board of Intemal Medicine. Croafii-a-Yugoslavia. Professional Appointments Feb. 1943 I Medical Officer in Yugoslav Army. April 1945 July 1947 Medical Officer in Air Force batta(!ion (equivalent. to flight surgeon in U,. S. Air Force). 1003546713 Jul y 1947 i Nov. 1951 Chief of Clinical Medicine in Air Force Division. IN Dec. + 1951: Jan. 1957 Insfiructor in Medicine at Medical School, University of •Zagreb. Chief, Dr. Ivan Botteri and; Dr. Arpod Hahn, Professor in, CFinical Medicine.

Veljko Joseph :;rstulovic, M. D. . ~ ~an, May FROM 1961 1965 TO Monfih ~ Year .1 ' June 1960 4 .I ' June 1960 . 9 June 196 1 'Dec. 1964 present 1966 present Type of Activity, incl uding Name and Address of Employer,'Beg inning with Date of Graduation from Professionai School Chief of Cardiopulmonary Section of Internal Medicine Polyclinic at Medical School. in Zagreb. Chief, Dr. 'k`t Vinko Vuletic, Professor of Clinical Medicine. Associate Supervisor in Charge of Physical Diagnosis Course at the Medical School in Zagreb. Chief, Dr. Vinko Vuletic, Professor of Clinical Medicine. Research Fellow at Cardiovascular Lab at Cornell Medical School. Chief, Dr. Irving S. Wright, Professor of Clinical Medicine Cornell Medical School , . Research Fellow in Cardiopulmonary Laboratory at St. Luke's Hospital Center, New York City-. Chief, Dr. A. L. Loomis Bell, Jr. '. Research Associate in Cardiopulmonary Laboratory at St. Luke's Hospital Center. - Consultant for Heart an& Lung. Diseases, Harlem Hospital.

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