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TOBACCO A WEEKLY LITERATURE SELECTION ) BY PETERS TECHNOLOGY TRANSFER SWARTHMORE ~ PEHNA. i.a,

Vol. l No. 18 ( DECEMBER 16, 1983 TOBACCO A WEEKLY LITERATURE SELECTION (: (_ FOR Brown & Williamson Tobacco Corporation Louisville, Kentucky BY PETERS TECHNOLOGY TRANSFER SWARTHMORE, PENNA. ==

c LUNG CANCER ([ C ~.~

• ~ c:,

L o Introdu~ion So far most of the hterea~ed cancer ~:lsks and of the Urban-rural difference in lung cancer rates ha~e been attributed to smoking. Occupational expo- sures and life-styla factors other than smoking are thought to play minor roles in the lung cancer risk ba i~dustrlalised countries. The combustion pred~ ucin of fossil fuels in industry mad in heating and the exhaust products of motor vehicles have been intensively studied for their possible role in the epfdemfelogy of cancer among urban populations. To date the o~erwheindng impact of smoking has made it difficult to find associations between cancer rates and the combustion of fuel. The detection of of fuels, however, may be prevention of cancer among both tally determined lung cancer is zo study oeeups- ~ e~ timmlly exposed populations, even though ~xpesed -' [ groups may comprise only a sinai] pr~portlo~ of the k== total population Both exposure and outcome can be more precisely recorded in occupational settings .~ than in studies of general populations. Also, in most % cases, the exposure eve s are of higher ma~tude . _._ than in the urban air; therefore a clearer effect earl be found among the occupationally exposed than anmng the general population. In th~ present paper Finch studies on lung cancer are reviewed as a background for discussions of difficulties in the : studies of en~ronmentally determined cancer. ~d~ Community studies " '' :~¢ Urban-r tu, al differences in the incidence rates for smokers and non-smokers residing in urban areas. a--roan~pp n to research into environmen- lung cancer have been well documented in several Another .: ~ ~ ~. ~ _ .7•~ = : .... • • industrialized eountles (1), but not all of the cau~-¸¸ atlve factors contributing to this difference have• ,• *In~tltute of Occupatlona] Health, H~ar~m~ni~k~tu l, 00290 been detected, As earl~" as 1~3~, Stocks and " "k'~mP- lIel~inki 29, Finland. bell (2) discussed an ab.~olute urban exces~ ill a= =.5 : ':" ~ .... " ;: ):

000824 Will an increase A,tho.gh ma. haveshow,a relationship between high-" : er-lnan-average intake of beta carotene fSolatene} and slightly in my inkake of beta carotene reduce my ri& ofsctbnscanccr. ~y Departments Edilor MiGh~e L Rose lower-than-average incidence of cancer; the eviderlce ]@ insuffi- cient to demonstrate any cause-and-effect relationship. For this ~eason Chades H. Hennekens. MD. associate professor of medi- cine at Harvard Medical Scnoo~ who is conducting research on beta carotene does not recommend ]ngeshon of the substance as a way of protecl~ng oneself agalnsl the possible develop- ment of cancer. "Peo~ e should forget about the idea of dosing themselves with ~3eta carotene:• Dr. HennekeRs saj,s. "Its health benefits are unproven." Reports of retrospeofive st ud~es have ¢3omted out that the inverse association between cancer incidence and t3eta carotene intake maz be due to an association of the latter with some other, truly protective dietary component with a nondietary aspect of life style, or w~tn avoidance of some harmful dietary comDor~enl A team of researchers under the direction of Dr. Hennekens has undedaken the first u~aceDo-controlied double-blind study Io as- sess the benefits and risks oIincreased beta carotene intake. The team will study 22,000 physicians, ages 40-84. for five years. About a quarter of them will lake a 325-mg asp nn tablet every "- other da~ and a gO-rag capsule of beta carotene on alternate days• The other three fourths will either take aspirin alternating with a p~aceno capsule beta carotene alternating with a placebo tablet, or two alaoebos Unlikeanirna sourcesofvitaminA betacaroteneappearstobe relative / safe to take chronica y Few side effects have 13een reported from its ingestion; even at oosages aoove those reoom- i mended P~ manufaclurers of supplements, the only significant . ~ repone(3 side effect has been sR~n o~scolorahon. None of the reported side effects have been serious or irreversible. Dr. Hen- neKens sa/s. But he adds "That it won't hurt does not mean it ought to be taken:' " - - Dr. Hennekens and other betacarotene inveshgators do have'~- ~.~ some advice for these who want to lower their odds of getting A~ cancer:Stopsmoking.Andifyoudon'tsmoke.don'tstart."Evenif ~. beta carotene groves to De as promising as we would like it to be, "-- Dr. Hennekens says, "if you are a regular c~garette smoker, your r~SK O~ gethng lung cancer wilisti~l be 10-15timeslarger than that of nonsmokers, other th~ngs being equal:' [3 ~GO 221 J

Lung cancer Jnstdence [earn they have cancen More than 444,000 will die of it. TheSe statistics, aIDng with th~ facl that more aTld more Americans are facing cancer in their lifetimes, suggest a frightening epidemic. and Health (ACSHI, using the most re- rnor tailty rates, explores the pasaibmty of a cancer epidemic in its beoaiet en~ There an Epidemic?" : The data indicate a gradual decline in the age-adiusted cancer dest h rates for both sexes under the age of 65 from 1933 to 1977, but show lung cancer on the upsurge. The American Cancer SO- ~ety estimates that Iung cancer will kill about f 14,000 men and women in 1983 alone, Even with new fechnstogy and cancer remain Jew. Currently the most lethat form of cancer among men, lung cancer is in- creasing in women• The American Cancer Society estimates that by 1984, lung cancer will replace breast cancer as the leading cause of cancer deaths among women. For example, among ',~hlt e temaTes, lung cancer incidence increased from 7 per 100,000 popula- tion in 1947 to 24 per 100,000 in f 976. Among nonwhite females, iriaidence rose from 5 per 100.000 to 26 per 100.000 in ~1976, This delayed increase in tomafe lung cancer i:teath rates in females e~ln t~e explained by the differing smoking hab- ifs beiween men and we m ell. Women didn't begin smoking in i~g~ numbers until aher WWII. whereas men took jp the habit en masse after WWI. almost 30 years eadien With th~ usual fstency period |or lung can~er being 20 to 30 years, womE~ll are just now experi~,Rc- ling the results of years of cigarstte smoking. Research shows the incidence of lung cancer among men also is ELSc~IIa~ ing. In 1947, the ~n cTdenCe amon~l white men was estimated at 39 per 1 D0,000 -. population. By ~g76, this rate had risen to 78 per 100,0D0 population, repre- sengng a 160% increase. • Even though aigare~e smoking re- mains one st the most biearly suspect causes of cancer, scie stiste are expler- i.g the linkaijes of many olher factors, including culfuraJ and personal habits such as diet, sexual and repreduct ale palter ns, alcohol Consumptlon, sun- bathing, and other aspects of lifestyle. The above stabst ai~ and ether inter- esting info;mstion on cancer and its causes, can he found in ACSH% 32- page booklet. A complimentary copy is available by sending a stamped self addressed envefepe, along with 37 cents postage, to The Am~dcan Coun- bit on Science and Health, 47 Maple St, Summit, NJ 07901. Bulk rates are also available. For more Information, carl 201-277-0024. 0008=5 t I.I, MEDICINE m

( RESPIRATORY CONDITIONS (Other than lung cancer) (

OPEN FORUM ABSTRACTS RESPIRATORY CARE • OCTOBER '83 Vol 28 No 10. @ Loose Cough as an Indicator of Ob- structi~'e Lung Disease. Teresa Chlunl BS RRT, Kathleen Fogar~y RN, Kathleen LaFond RN, Aram Tomasian MD. Mount Auburn Hospi- tal, Carahddgn MA. ( Prevalence of obstructlvc lung disease ¢OLD) was determined by spiromctry in 174 Carnbfi~ fu~t3ghters, Forced e:¢piratory volume in on~ second (F£V~) exptcssad as per cent of forced vital capacity (FEV1/FVC) of 75 or less ~va~ ¢ol3~idcred di~tgnost]¢ for OLD. Assesgments we~ made more tha~ 24 hours after the most ~ee~nl fi~eEgh~ng smoke exposure, ~o elimi- nate aCU~ effects. A startda~'d ques~ tfonaaite was used to cliagnos¢ Chronic bronchitis. End-tidal carbon monoxide expressed as earboxyhe- moglobln ~COHb) was m~asu~d to ~onf~rm smoking history and its in- tenst~y Obstrdct~v~ ]~ng ~i~ea~ as ~[etermined by sp~ometr~ was coI~° J~ed with firefighting smoke e×po- sure. tobacco smoking htstot)') pros- cn¢¢ of ]oo~e or d~ ~ough on fe.quesl, and chronic bronchitis. Twenty-seve~ f~t3ghiets had OLD by spiro~netry. Sixty-one were smokers. Fifteen had kiose cough, Sixteen had chronic b~onchigs. Presence of OLD was un- relatad ~o ~l~efightix3g smoke expo- sure,Th~een of gl smokers (21%), 4 of 16 bronch~tics t25%), and 7 of 15 with loose cough ~47%~ had OLD. ~C~s~nce of foo;~e cough is an ~aslly aequlrad sign, which has a higher corr~latlon to OLD than ~ chronic bronchitis, smoking, or firefightmg. As a result of these observations spi- romeu3' is now limlt~d to smokers, bronehitics and those with loose 0OOg 6 f~ cough in our screenings for prev- flowrale as determinad by a l~ak-flow me~er is ~ons]dered adeq~ale for oth- ¢[5 i~ S~l~ng program~,

~ ,, __tartar__ • ii ~ __ -- _ • Pulmonary dysfunction surgical risk How to assess and minimize the hazards 000827 .G~m~. C. Ok~on, MD Preview - l~t:le~ts with pulmonary" dlsesse face added risks when under- . going surgical treatment. In fact, postoperat/ve respiratory com- pIicaflons are almost a certs~ty. V~lu~t ~,ctors incre~¢ a pa- Uent's risks? Which tests are reliable indicators ofr/sk? How c~n • risks be decreased Intmoperaflvely and postoporafively? I)r " Okeson presents a rational approach to asse~ment of risk based on specific preoperative findings. Providing an accurate assess- merit of oporatlve and postopera- tive risks to the patient with pulmonary dlsease and hls or her surgeon can be a major challenge for the prima~y care physietsn. While there are few absofu~es to guide d~isions, a ratlon~ assessment of risk can usually be based on the type of - ' surgery to he performed, chracal findings, and measurements of the patieat's cunent pulxao nary function. major cause of thls change in Vital c~pacity Is temporary we~cness and d3~functtsn of the diaphragm. Residual volume and functional residual capacity of the lung usually decline o, er the first three to four postopera tlve days. accompanied by a de- Crease In the orptratory rese~,~ volume and an increase in the amount of functional airway closure [closing volume} of the lung.I This combination of events results in increased puimon ary function can be dramatic, profound, and some- times unexpected (figure~ 1}. After abdominal s d ~-g~r y~he patient's vital capacity may de- crease 25% to 50~ usually = reaching a maximum decrease during the first two pestopcra- t[~ days' and not returning to palmona~f physialogie shunt- ing and hypoxemi& Unless periodic hyperlnflatkin of the . lung is assured, these physic- fog~c events can decrease lung compliance, thereby increasing the work of breathln~ * Postopexath~ atelectasls, re- ¸ suiting from these changes in pulmonary function, is also fos-" tered by muscle splinting due to • postoperatJ~ pal n as weU as by narcotic anaJgeaics used for for file patient's comfort, but they commouly lmpair the nor- real mechanisms of stgh and cough. Aballtion of the normal periodic hyperinflation that is necessary for the rene~-al of surfactont leads to aIvealaz in- stability mad collapse. Increased insplratory concentrations al" oxTgen may also promote atel- ect~sI& Cllnl e.~ ~waluatlon Preoperative evaluation of the patient with pulmonazy dys rune tion begins with careful history taking and physical exaraina- " tJoru The physician should pay special attention to the patient's age, presence or absence of obesity, smoking histois~, exact type of surgical procedure to be performed, type of anestheaia required, and pr~ence or absence o f complicating diseas~ "[he risk ofpostoperath~" . ' , palmonary complications has , ;. been shown to be proportional ._ to the age of the patient after . age 60. Thls fact is probably duc to the natural effects of aging~ .' on the respiratory system, ie. t~ progressive Increase in func- tional residu~I capaai~y, loss of " lung elastielty. Increased prev- alence of functional air,dry closure, pragresslve decline in ~ normal for one to t~yo weeks. A pain teller Narcotics and seda- Pao~. gradual decrease in rate of recent study~ showed that a tlves are frequendy necessmy maximum expiratory flou~ and . • continued ~: :: • , ~ ~ . :. ,i¸

,..= Preoperative evalua- tion of the patient with pulmonary dysfunction begins with careful history taking and physical examination. 'i;abfe 1. ~urgical procadure; in ruder of Incr~aslng pulmorm,-/dsk NOna~ominal nonthoracic ~-:. ~ Lower abdominal • Llpper abdominal ~ -" 'J'ho~clc w~]lout re~cUo~ of funo~ox',~ Iun{} 1"hor~ciG w~il removal of [~nGt Jor-~T lung •"~1" xnonm-y ]~fl~, resulting In an --:: ncreascd incidence of aspira- tion and upper airway obstrue- as the risk of postoperative pulmona~ complications, with degree of risk proportkinal to degree of obeslty. One of the major ph~iolag[c consequences of obeslty is a decrea~ in exo plrato~a~ reserve volumc Obesity a/so Incre~es the lungs dosing volume, a measure o~ the magni- tude of functlonal air,ray clo- sure. In add[tloru ~bese p emson~ ~ave been noted to move about less and to slgh less than non- obese persons. The combination of these factors promotes ateleco h~sis and intravasctflar pul- - LIoTL monary shunting, re~uI/ing in . Obesity ~ncreases the risk of hypoxemJs, The Incidence• ofpostopera- ~a~y surgical procedure ~ we~l tivc pulmonm~ compllcatkil~s also increases In direct prop~- tlon to total cigarette consu~np tlon abo~c a threshdd of about 8 to I0 pack-years ( a~erage daily cigarette consumption in packs times number of years srnokedL Chronic c~garette smoking produces a variety of pathophyslologic changes In the lung, a~ of which predispose to postoperative atelectasis and pneumonltl~ J The rlsk of postoperative pulmonmy compUcations is also depe~dem upon the area of . the body Involved, Usually. sur- gical procedures of the head. nec~ and extremlties have the [ow~st risk of cornpllcatlonS, while thoracic surgery has the highest risk (table 1 ]. The com- plication rate with thoracic surgea~ is primartty dependent upon the severity of chronic ".] obstructh,e pulmonary diseaa~ the degree to which the beI]ov~ function of the lung ~s affected by the surgical procedure, and whether the procedure involves the removal of functional or noofuncOonaI lung tJ~su~ The more functional the lung tissue to be removed surgica~y, the ~eater the risk of postoperative complications. The incidence of complica- tions is ~lso affected by the type of a~es~het Jc agent or anesthe- ,,~

ml tlonal to the percentage of lung tisslle removed. (2} Ktl~e part of the lung to be r~seeted is found to ha~ no appreciable ventila- tion or perfusion, then the pa- tient shotfid have no permanent loss of pulmonary function postoperatively, (3] If the part of the lung to be reseaied con- rains the majority of function- ing lung tissue and the remain- der of the lung has poor venti]a- tlon-perfuslon functio11, then an exaggerated loss of pulmo- nary function can be antici- pated postoperatively, over and above the loss of function that would be calculated by consider- Ing the percentage of lung tis- sue removed. [4} If the king tis- sue to be removed Is the site of an extremely abnornlal ven til~ lion-perfusion relationship, while the remainder of the lung has a reasonably good ventfla- tion-perfusion relationship, then resection of dis~a~d lung tissue can be antidpated [o ira- prow postoperative pulmonary function. Risk modification High risk o f postopc~tive p~- monary complications can often be decreased through a pro- gram of p~monary therapy In the immediate preoperative pe- riod.~ Reassessment of risk may be indicated after severaJ days of a therapeutic progran~ con- sisting of cessation of smoking, bronchodilator therapy, mea- sures to control secretions and infection, and weight reduclion when feasible. Risk of post opera- live pulmonary complications can also be decreased through in~raoperative control of Secre- tioris, irlea~ures to pl~Venl as- piralion, intraoperattve maln- tenance ofbroncbedilalor ther- apy, intermittent hyperinflalion of the l~mgs, and minimization of the period of general anes- thesia. In addition, risk can be decreased postoperatively through continuation ofpr~ operative measures and empha- sis on periodic coughin~ inci sion spIinting procedureS, early ambulation, appropriate pain control, and frequent hyperin- flation of the lungs with an th- spirometer. Postoperative deterioration of throu~ a number ofpreopera- pulmonary foneflon ~m be considerable, resulting in hy- poxemtia z~ud atelectssls, if such effects are not anticipated and eifo ris made tD prevent ~r~e them. The risk postoperative pulmonary oom- pti~fio~ depends on the pa- llent's age. degree of obesity, aad cigarette consmption~ the type of surgery to be per. formed; and the anestheitc agent used. ~essment of ~Isk Is based p,~mA,-ily on elirdcal and laboratory ~aiuations. ~e tests performed may vary ~om patie~ to patlant,'and spedallaed studies of regional pulmonary function aze ~e- quently required. Even though a patient may be identified as having a hl~ rlsk of post~pera- five pulmons~ eompUe~tions, risk can often be decreased dye ~nd [n~zaoperadve m~- therapeutic prog~'am~ Address n'prillt reqI~t~ to CgnT~an C. 0keson MD. S~ott and %~ t e Cllni~. 2401 S 31~t Sl. Temple. TX 76508, Rl&..m~ DJaphragm [u n~un ~ter ~r abc~r~r~J ~rge:y t i~oO~v,~ l~u. l~s I V¢4 u~¢~ ,r ~Jl~r~ c~/~e~. ~r ~b~ ~.~l~t lun ~[ l~l~e~i~ ~h p~n~om~9 dl,~-~, ==

THE LUNG SOUNDS PHASE ANGLE TEST FOR DETECTION OF SMALL AIRWAY DISEASE YONGYUDH PLOYSONGSANG " Breath sounds are generated ~n the Iung and transmltted through the lung paren- chyma and tho:acic cage to the chest wall surface. The sound intensi~y recorded on the chest wall is dependent on the sound gen~ration aT~d tral~smLe.sion anal was ~ermed the uncompensated breath sound (PIoysongsang et aL, 1977]. After corr~tlon for the transmlsslo~ characteristics of the lung pare~chyma and thoracic cage. tim breath sound intensity was named the compensated breath sound intensity (PIoy- songsang et aL, 197~). The compensated breath sound intensity has been shown to correlate with regional ventilation [P]oysongsan~ et aL. 1977), with distribution of regional ventilation (PIoysongsang eta/.. 19781. and with sequences of regional ventilation (Ploysong~ang ez aL, 1979). In this stud~ the ~equcnceg of ventilation ,~ccepled for publication 25 May 1983 ~O34-5697t g3/$03.00 ~ 1983 El~vler Sele~ce PubTishers B.V*

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ma vent is used_ Thus, the supervisor should know what the solvent can do to the body, how e~iiy it vaFor- izes into the a/r, and the conditions o~ its use in ~mbinatlon with other ~bstzmc~.

OTHER CANCERS (

7. Hi dre h. E. A.: B re. C. E*; Mc- C~eary, T. A. t'er~lslen¢¢ uf tile "h)dralazine syr;drome." A follo~-- up ~tudy of eleven cases. J. Am. 2qed, As~0c, 17~: 657-6( ); 19G0. 2~ 8. Jacobs. M. E4 Steinherff A. D.; Gor- don, J. K.: TaIaL N. Adjux~nt e~- frets of poly 1 - Doly C in New Zea- • "--. lard m~ce. Arthrltix Rheum. 15:201 207: 1972. 9. Keller. D4 Schur. P. H.: KunkeI, H, G. Immunologlcal sludlcs con- eernmg the nephrhls of sgasemlc lu- pus erythematosus j. E~:p. M~d. 125: 607-623: 1967. I 0. Litwin~ A*; Adams, L E.; Zimmer. H.: Fond, B.; Loggle, H. H.; Hess, E. V. Prospective study of ill]niu- nologk effects of hydrala~ine in hy- " t penenslve patients. C.tin. PharmacoL • TheL 29: 447-455. 1981. Morrow, J. D.: Sehroeder~ H. A.; ~I Perry H.M. Jr. Studtesoncontrol , of hypevtensmn by Hyphe×: toxic ' " " " reactions and slde-e greets. Circulation • . • cr ;- ~ 8:829--839 1955 12. Perry. H. M.. Jr. Late toxicity to hy- dr~]~z~n~ reh~lnl~hng Sx]s[~I1]lt Inplls crythematosus or rheumatoid ar- thrlus, Am.j. Med 54: 58-72: 1973. 13. Perry, H. M., Jr.: Tan. E. M.: Car- randy. S.; Sakamolo. H. Relation- . shipofacetyl transferase activity to amlnudear amlhodles and toxic ~wapmms in hvr~rlenglvepanems tremed with hydrahzine, j. Lab. Clga Med, 76; 114-t24 1970. com~3onllds, it follows that varlatioti~ 000830 - . ........ .~,, ~, "~l~tena for the das: sification of systemic lupus erythe- matostts proposed 1982 revisionl Arlhritk Rheum. 25(Suppl.l:S$: 1982 lab~tr,L 24. Tanaka. K4 Shozaburo, J.; Kajiyama~ K,: Nishlgoari~ S,; Kameda~ Sq To- shiyukL Y.: Yamaguehb M.; Mat- suy~ama, K.: Iguchi, S. Inueased hydrazlne excretion a~soclated with s~xtem[c lupus erythemarosus ella. lmmunol, lmmum,pathoL 22: 55-59: 1982 25. Uelrecht, J. P4 Wooslcy~ R. L. Ace- tylator phenotype and lupus erRhe- nlatosus. Clin, phar~a~okin~t 6:118- 134: 1981. 2ft. Vansant, J.; Woo~ley," IL L; John, J. T.; Sergen9 J. S. Normal diswi- buuon of acet}lat~r phenotypes in $ystemlc lupus erythematosus. A~- thrltls Rheum• ~1: 192-195: I978. 27. Winchester. R. J.; Nunez-Roldan. H. Some genetic aspects of systemic lu- pus erythematosus. Arthriti~ Rheum ~5: 835-837. 1~82. 28. Wcosley, R. Lg Drayer. D. E.: Rel- in individtml ¢ apacities for demxicafton of arvlamhws by N-acct~laiiorl may in part a£counl for vari,qdmts hi ~u$cep. tibillty to arylandne-indutcd toxicide, and dlsease. Thls would cer talnlv seem to be the i case. and al pFesent d]c lltel.~[urc Coil rains a nun]her of entries indicating a role for N-acctyltransferasc pbenot}~ as a partial determinant of ~usceptibfl~ ity to the dose-related toxieides of var- ious nit rogcn compounds 12. 131, From the perspective of oneology, this is of _ some interest because il is increasingly apparent that acet)IataiJIe arylamines may lmve sig]fi titan'( involvement in the ¢ausanon of human urinary bladder cancer (6). Human urinary bladder cancer In industdallzed nauons arylamines nave hcen implicated in bladder cancer causality since 1895 about 30 }.ears (a typical latent pcrlod~ after the emer- gence of the ~1q thetir chemical dye in- dustry tit Germany. The epidemlofogy of contemporary occupational bladder ~ncer has been considered to be syn- onymous witb the epldemfologp ofar- y[amine induced bladder cancel (181. Orcupatfon-related bladder cancer presently accounts for perhaps 15-30% . I~1 Reldenherg. M. M. The chem;~al in. denberg M. M.; Nies. A. S.; Carr, • due(lea of s 'stemir lupus erylhe- K.; nares, J. A. Effect of aeetylator • maousand upus- ke ¢sse At- phenoypeon heraea whchpro- thrdI~,~he~m, 24:1004 1008; 198I. camamlde Induces anunuclear ant~- r • 15. Reldenberg, M. M.; Le'~. M.; Dcayer, bodlc~ and the lupus syndrome. N. " D. E4 Zylber-Katz. E.; Robblns, Engl.J. Med.~98:1157 1159;1978. . W. C~ Acetylator pheaotvpe in id ~9. Yamanchi, Y4 Litwln, A4 Adams, ' . • input hic systemic lugars erythemato- L. E•; Zlmmer, H.; Hess, E. V. In- • • • ,' Sus. Arlgaitis Rheum. 2-~: 569 573; ductiorlofantibadi~to nuclear an "~ " ~ 1£80. *~ ' tigens in rabbits by immunization q 16. Reidenberg, M. M.; Martin, J.H. with hydralazlar-human serum al- ,~e,~,~.~. : Aoetvla~orphenotypcofgatlentswith bumin conjugates Clin, Invest 56' g~ "Sga em c lupus erp hema o u Drug - "" 958-909 975 "f " " ~ .¢ ~ ~ Metab. Dupas. 9: 71-7~ 1974. • ~ 17. Ruhln~R. L4Joslln, F.G. Tan, E.M. "~'~ • Spedficilpofanti-hlstoneant]bodles MOLECULAR EPID~MIOLOGY .* ~. ":, insl~temiclupuserythematosu~ Ar_ OF ARYLAMINE-INDUOED thfft~ Rheum. 25:779 782; 1982. URINARY BLADDER CANCER: of cases in certain urban areas (6). Cou- pled with the known al~d significant in- [ volvement of cigarette smoking in the eausat~on of bI~dde~ ca~ce~ ~19~ and ~be known presence of ca~¢ino8en~¢ / arylamines (e.g., 2 amlnonaphthalene)| in cigarl'ttc smoke, it E reasonable to / suggest that in some geographical areas | of the United States a maior portion of human bladder cancer may be at- tributed to occupational and cu]tu~l s~a~ions ~n~ob~g ~po~nre~ ~o ary~ ~ amines (8). -' " From experimental pa{hofogical studies, the ukbnate carcinogenic me- ". tabolltes of arylamines involved in " bladder carelnogenesls are evidenced • l& Sheikh, T. K4 Charran, R. C4 Kalz, SOME THEORETICAL . to be nonacet "laled metabolites (7),: ::~ • A. Renal manifestations of drugin- CONSIDERATIONS a ~ and N-acetyladon is consklered to be . : ~ q; dueedsgatemlclupuser)qhematosus, Gerald M. Low~:~ J£. ?~: : Ar~.~ C n. Paho 75" 755-762" adetoxicationprocess(8.Thus, lndi- '~" '~ 198 " " ' _ . .. . ~ . "vduas0f hcsowace "a rp ent~ t~ • 2 , • . ~ . ~ 7 . • t~ nolcateQ Dy l.ne lac~ Dt S m 11 • • • ~ 9 Sonnhag C Karsson E Hed J .... type~,oudbeexpecedtohemoresus- ~| . . syfllpo um ere s ncrea fig r~u ,~ ~ Procanamde-nduced upuserythe- ~ ..... cep be oaryam ae-nduced badder ~'[ • . . o $c p Ilaf • n cr~ n I~e re ~ ons ps . : ma ~su .hkc spndro e n rela on o . ~ . , Ca ccr, and one m ,a- bvt3o hes ze that aeel lalor pbenolypc and plasma .... a DOl3U a on of bladder cancer patlenI$ ~1 ~ ; le~eb of procaina lide. Acta Meal. typeandtncoccurrenceottox;cltyano (p~rovidedtbat smnebavearvlamlne-ln-. ~&a,d 206: 245-25I 1~79. ~ • disease after ~xposures to acetylatable • = " ~ £:C:-~ ~,~TX=~(L "Stollar, 15. D. 'NutqeE acid am~geli ? nitrogen compounds, including arll . .. _ _: . : _ :f -, Sel;,.M. ed, Theantlgem, voLI. Neg arnines. Becauseofthecenlralroleac- 'S plmred ) he n ucfnrEmi~onnff'ig .... . : Yud< AcT~dendc; 1973: 1-85. . colded N-a¢ctyladon ;Is a mecbanlsm tal st,Jdic~ Univer~iw of 'Wi.~nmlu *.i~dlr~m.•~': .~ ~l. ~;tolhr. ]~. I). The alu;ge,~ ~wntkd ~or the detoxlcahon o[ many mlrogen Wi~.~asl,. • : : • .~ . ~r ~.~ • ~ ~ ..; ~. 5 .L ~ ;., t~ ~.eF: ; . ~a~ ~..~ .., h.~.~ ~ ~- .g~ ~* ,~.,~*~r9."8094 -~.t'~ '~ ' " FEDE~at, T~O~PROCEEOING~V~L•42 NO. 14 - NOVEMBERI~t*3

duce.d dise,~ se) would display a greater Su lfamedlazine phenot) phag was again employed, and a p~pulalion of bladder c'dncer patie~lls wilh known arylatn~ne exposures displayed an ~nsigniflcant 14~ excess o f individuals with the tio~; acet ,lator phenot'¢pe t 3/" 18 = 72.2% when compared with an indust rlal non- exposed control Population (11/19 = 57•9%) (unpublished observations). Unfortunately, these studies were ter- minated after examination of only 18 ca~es, artd no conein~ions could be drawn from chem. More rceendy, however, Car twright and co-workers (I) have extended these approaches to a bladder cancer popu- lation from Huddersfield, England. Their bladder cancer population dis- played an insignificant 10% excess of individuals with "the slow acetylator phenotype (74/1] 1 = fi6.7%) when compared with Huddersfield control population (54/95 -- 56.8%). Of grea[er in~erest, this bladder cancer populatinn contained a subset of 23 in- dividuals with documemable benzidfac exposures resulting from employment ~ chemical dye workers. This subpep- percentage of slow sect)later pheno- types lh~m ,,¢ullid i~ cotllrol, c-ante r free popuhdon. Fom~ulathtg a h~ potbesis, by hs, er y ' nature, ]S iiior~ or less a~} individual acdvity. Proxlding an emgirical b;~sls for hylJ~thetis evaination in human ' i~)pulatlons, Imwever, is clearly a mul- tldisciplinary activity. Despite consld- erabla effort, it was not possible to ob- tain adequate clinical evidencye in the !: Unlted St ~tes, and the first human data • were genel-ated in Scandinavia in col- laboration with H. Wolf in Denmark : and T. Nfi~on in Sweden. Sulfamethazlne phenotyping meth- odologies developed by Weber and • Brenner(21 showed that apopulation ' of urhatl urinary bladder capeer pa- tients from Copenhagen, Denmark. displayed a 13% excess (P = 0.065) of individuals with the slow ~cetylator phenotype (46/71 = 64.8~) wheo con pared wfih a Danish control pop- ulation (38/74 = 51,4%). These data ' are consistent with the possibilit) that • arylamines may play an etioingic role they me (4), but whether they mlgbt under certain conditions be sufficiently rate limiting in arylamlnednduced car- cinogenesis to have an effect on human outcome. The available human data do indicate a slight but insignificant excess of the slow acetyhtor phenotylm among urban bladder cancer populations and inbladdercancerln thislocaleandthat uLatlon displayed a nearly 40% excess ( slow aeetylator individuals may be (P ~ 0•00005) of ~dlviduals with thc ~lightly more susceptible¸ (odds ratio slow aeetylator phenotype (22/23 • = 1.74) than ~apid ~cetylator indirid-t = 96~A) when compared with Hud "~ nuts• foasmudt as g5% of patients re-| dersfield controls (i), a finding consis- . ported blstorles of smoking, it was not~ tent with slgnlficantly increased suscep- ~ possible to examine for smoking fac-~ tibility (udds ratio = 10.7) of the z]o~ ~ ~tors. ~ acetylator phenot)~e to arylamine-ln- !: In contrast, for a'popuhtlon of rural duced bladder cancer• [ urinary bladder cancer patients from The question, then, is not whether Lund, Sweden, where bladder cancer human N-acetybeanfferaseenzyme sys- ; foddence (20/100,000) (197 ] ) is less tenA are involved in the metabollsm of i if.~ than half arthur inCopenhafien (43.8/ carcinogenic arylamines, for certalnb, ? t00,000} (1968-1972), no difference 7 in slow acetylator distribution was ob- ~" served between bladder cancer (80/ ~.115 = {ig.fi%) and Swedish control ~ (79/118 66.9% ) popalafions, which may be consistent with a relati'~e lack % of involvement of arylamines in the ~ ctioingT of rural bladder cancer. In ' summary, the data were inconclusive perhaps alarger and significant excess but sugiciemly suggestive to warrant among specific arytamlne-exposed l'urhersud)( 3 " baddercancerpopua o ~( aswould Populations with bladder cancer be expected (IB). Although this latter i Causally unrelated to arylamine expo- conclusion needs confirmation, there ~! smes would be much less likely to dis- is now a clear argument for the further ously (6113). It is perhap to discuss these approaches from the larger perspective of epidenfiological- pathological theory. Within the eonflne~ of dem olog ca -pathological theory the involvement of a .specific carcino- ! gen or c~rcinogen class in bladder can- cer eausalit implies that for the oc- i~ currence o~Ycach case of bladder can2 cer two conditions must be fulfilled; ~! 1) that humans are exposed to¸ the car~ i~ cinogen, and 2) that the response that ,~ constitutes tile disease must follow. As a result, tbe distribution of bladder" cancer in a population will be detcr~ mined by two sets of conditions, those ~' governmg the frequency and dlstnbu- ~ion of effective exposures r~o bladder ~: cardnogens, and those governing the ~! frequency" with which bladder cancer ?: follows this exposure. !t can be de- : duced, therefore, that any ~co~ditlon ~i positively associated with the oecu~ fence of disease must operate e~ther to ~ increase risk (be., exposures) or to in- :" crease susceptibility, or must do ~ both (3). ,; • • In other words, the distribution of .i bladder cancer is the result of the dlf- ,? faremial involvement of risk factors !!i (i.e., cultural-environmex~Lal deferral ~. hunts of relative c xposure~) and of su~ , ceptibifity factors (e.g., immunologic-¸ metabolic determinants of relative ho~t response)• As with most epithelial can7 ccrs, there is fittla support for immu- ~;. nosur'~eglance as a significan~ deter- ~, minant of susceptibifity (14), and host i~ metabolic defense mechanisms "(e.g.,i~ metabolic activafion/detoxicadon and ~ genomic reparation) and nutritional i~ modifiers of response (e.g., dietary pro- ~: maters) may play the more rate-limit-¸ ~ng role (9, 12). The identification Of !! determinants of ~usceptibigty in chem~'~ • ica]l -) induced disease, requires intcr-~ ~ dependent e ffori~ m molecular pat hal-. ogy, cellular patho ogy, me eeu ar pharmacology, genetics~ nutritional : toxicology,, and analytical cpidemiol-, ogy, and has become an approach rer~ ~dl ferred to as molecular epldeminlogy, the conceptual foundations of which i have been presented elsewhere (10). !i ~B "~play a relattonthtp to tile slow acety- application of these approaches to As originally employed, the term later pbcnotype than wou[d an indus~ chemically induccd human dlse~se in molacular epldemiology "#as utilized ; _~ ' trial population whh documentable general (1O). with reference to restriction endonu-, " arylamine ex }nsures• With an addi- clease fingerpriming of viral nucleic ~1~ ~ional 2 years'of effort it became ~s- 7,Tbe°retIes1 conslderattons , : acid (20). More recently the teml has "slbfe to extt'nd these slttdi~s in coliah- Discussitm of die detailed experimental been utilized with reference to the de- o a o ~ "~ N "t' ] ~ }d lit• pathological aFtd clinical pharmacoJog- ec lOFt a d c ara~erlt~tloll of'CillClrl- ~ [ Medical I)is~Shm nf DuP~all s Cbam t(~d bas~s and raltonale foI these ap osen DNA adducts (19). Taken to" ;: [ ..hers Wm'ksln Deeifu'ater, N~-wjersey. proadws has been presented previ- gether, this aspect Of molecular :¢p!~: co~raOv~asv u P~^nMaeouoGv " ~ ~ .... ._ " ~ - ~Og5

L ORIGINAL ARTICLES Scaud 3 ~rk enc£~ml healt~ 9 (t983) 315-326 ' • 000831 Nasal and sinonasal cancer Connection with occupational exposures in Denmark, Finland and Sweden by SVeD Hernberg, MD,~ Peter Wes~erhn)ra, MD 2 KksteD Schultz-Larsen MD,-~ Ritva Degerth. MSc) Eeva Kuosma. MSc? Anders Englund, MD,4 UIf Engze}l, MD,s Hanne Sand Hansen. MD.6 Pertti Mutaner~ MSC1 j~ I~ERNBERG S WESTERHOLM P S CHULTZ-LARSEN K DEGERTH R. K~JOSMA E ENGLUND A- ENGZELL l" SAND HANSEN H. MUTANEN P. Nasal and sinormsal ~ncer: Connection with occupational exposzh'e$ in Denrn~ck, FiIR]an~ ~nd Sxvedeo. Sc~d j wc~k e~iron heuI~z 9 (1983) 315-326, A joint Danish-Finnish-Swedish case- referent inves~gailon was JRitialed lli 1977 it* order to study the connecti¢m between nasal and sinonass/ cancer and various occupaflonRI exposures. All new c~se$ Of z%Rsa] and slnonas~/cancer were collected from the national cancer registers {Finland ~nd Sweden) or ~rorn the hospit~Js (Denmark). ~nose still ailve who agreed m an interview IN = 187) were indivld~all~ matched for age and sex w~th paLJents w~th co]onlc Or recta] cancer¸ A det~led telephone interview ~ made according to standardized forms. Both cases and r~ferents th~ugb~ that their concililon Was ~he one Rnder study. The exposdres were coded bl/ndly by an indust ri~] hygienlst ~fhe results sh?wed as soci~tions between na~tl and sino~a~al ca~.cer aP.d ex!3osLtr e to (il hardwood or mlXe~ wood dust (dlscord ~nt pairs 14: 2). (ii) s~ftwood dust alone (13: 4). (iii) chromium f16: 6:. (iv) nickel (12: 5. not sign)fJcanD, (v) weldlng, fiche ~ul~dng and soldering (17: 6) and Ivi) lacquers end p~dnts ~14:0). The last fi~ding w~s probably due to eonfoundlng from wood dust exposure. ~ardw oocl didst ~xpos~e w~s associated with adenoearalnorna. Softwood dust expost~'e alone w~s a~ocJa~d with epiderm o~d and aqaplast~c car Ci~ oynas, NO as$~¢ia~ons were found for a number of e~po$~re$, inelu din g agyic ultural chen~¢a~, textile dust. ¢sbesto~. quartz dusL, orgRn)e solvents Rnd leather work. Possible expos t~r¢ to formaldehyde W¢~ eveD/y ¢list ributed between the cages ~nd r~fel~nts. Ke~ zerm~: chromium epidemiology, f~miture industry, nickel sawmill *ndus~cy, weld/rig, wood dust. Nasal and alnen~sal caners have been associated with several occupatinnal expo- Sures, among them dust from hardwood (f, 2. 3. 4, 5, I0, 11.12. 15. 19. 22. 25). nlckal production (3, 9, 13, 14, 24, 28, 29), cutting .~-,rz % +., • • Instigate of Occupational HeMth Helsinki. Finland. Swed~h Confederation of ~de Uinons Sto~kholrn, Sweden Depar~nent of Mediei~P~ Copenhagen CO~* tY Hespit~l. St Z]is~th Denmsrk. The Foundation for Indu~t~] Safety and Health in the Const~uc~don Industry, Stock- holm, Sweden. • Huddinge Hospital, Stockholm, Sweden. • Radium Center, F/,lscn Institute, Copenha. germ, D~tr~rk. Reprint ~ecz,~,sts to: Prof S Hernberg, Inst/t~te of Occupational Health. ~aarh~a~irzP~tu 1 S'1-00290 HelsL~I¢/29, Finland. oils (26 phenoxyaalds and chlorophenols (18), and unspecified exposures in the boot and shoe industxy (1, 4). Qmte recently, experimental data have indicated that ex- posure ~o formaldehyde causes nasal can- cer in rats (30). Especia11~ nasal adenocarcinoma. 8 rare tumor with an incide1~ce of about I case per 1,000,000 person~ye~rs, has shown a very strong connection with occupational exposure ~c hardwood dust in the furni- tureindus~ (i, 2. 3. 4. 5. 6.10,11,19.22.25). In addition some other r~loes of nasal c~ncer mEcy OCCIIF m eXCeSS ~£f~O~'i~ ~!r~ ~ure workers, but ~,he assoc~atlor* is no~ (~ ye~ quite clear (4. 22), It is also unclear whether exposure T/j softwood dust~ eg, pine and spruce dust. can cause nasal cancer (19). In order to elucidate these

g for Table 11. Conn~tlon between nasal and sioonasal cancers ac:d exposure 10 wo¢cl du~ls by smoking s~atus 10 years before the diagnosis {unmatohed data}. Nor~okerS Smokers Total Type el exposure Odd~ 95 % cenf~nc¢ Odds 95 % c~nfldence Odds g5 % confidence ra~i@ limits Patio limits ratio ~lmits Hardwood ~ust onty 2.0 O3-15~7 0~ 0.02-42.5 1.7 ~.3- 99 Softwood dust ~niy 12 C~- 61 93 ~2 ~ 741 3A 11-~03 Hardwoc¢~ + soltwood dust 50 05 457 B.2 ~.0 --665 6,7 18-25~5 matching broken, which expIaias why the odds ratios for the whole material shown in table 11 differ from thos~ in table 8. The total series of cases also inchided some types of CanOe~ with a ins$ likely connecfion to dust exposures. In order to shacpen the analysis, the i g cases ofadeno- earctooma on one hand, and the 112 cases of eDidermoid and anap]astic carcinoma on the other, were s~rutlnieed separately. As can be seen from table 12, exposure to hardwood dust, either alone or in combixa- don with sofiwood dust, was found to be associated with adenocar~inoma. How~ ever~ the pesu~ts also su~st all a~soc~- lion between exposure to mixed wood dust and ri~k for epidermold and anaplas- tic carcinoma. Exposuie to softwood dust only showed no ~sociatlon at all with adel]o car cinoma. All 13 eases occuITing in ~is exposure category were of o~hor types, t0 of them being epidernloltl or anaplastic carcino- mas. Although this finding did not reach statistical s~gnificance~ it suggest~ that softwood d~st exposure may also have , carctoogenie properties hut that it causes other types of cancer than ~enocarci* no~a. Table 13 shows the a~sociatinn between nasal carcinomas and exposure to ~ome metals. The category "welding, flame- cuttmg a~d soldering," which represents mL~ed ex]~ostlre, was ~ignL~oa~tly asso- Table 12. Exposure to wood dusts accordin~l to histopathologica] type of canGer -- Distribution of discoTdant pair@. Expidermoid . Type of exposure and Adenc¢ ar~- anaplaSti0 nom~ carcinom~ Hardwood du~l only ~1 2:0 ~ottwoc~ dust only 10:4 0;0 $oftwoa~ + h~tdWO~d ~ust 5;0 7;0" • p < 0.05 (MC Nemar). elated with nasal and sil~onasal cancers. The same is true for exposure to chro- mium. Exposure to nickel also showed an excess nearly achieving statistical signi- ficance at the 5 % hiveL (Many of these cases fall into two or more categories*l Chromium and nickel exposure often con- alsted of the welding of stainless steel, which contams up to 30 % chromium ar=d some nickel These exposures mostly oc- curred together and can therefore not be separated statistically. Smokers and non- smokers had roughly the same odds ra- tios. The most c~mmon types of c~meer were epJdermo~d and anap]~stie carci- noma, It is of interest to note that only one case had been engaged in the production of niekel. None had worked in the produc- tion of chromates. The results hence indi- cate that also other types of t~ickal and Table 13, Exposure to some met a(s -- D~t ribugon of d[scorda0t pairs. "(he categories a~e nc)t e);olusiv@. Type of exposure DIscordant pai~ Odds ralio ~5 % confidence limits ~ " V ~n(~ @oldOring 17:6 ~J~ I~.--69 W~[ding. flam~-cu~ing S3me~ bzJt onPy I~lose wifh expesuf~ to r~ Chromium and/or r~ickeJ 13:4 3.3 1.1 --94 EleclropJali~g 9:6 15 0.5--42 Ghromium 16:6 ~7 1.1 --66 ~.~ Nickel 1~:5 2.4 0.~ ~66 321

500001~13 H E~ H 0 U U r/? m 0

The Lancet • Saturday 15 October 1983 00083=

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Gastroesophageal reflux Simple measures often suffice 000833 Preview duodenat contents. Regurff:ta- Regnargithflon of the gastric contonts into the esophagMs is o~m- tton refers to the reflux of gas- moat and af~ i1~oflced. When s3~mptotD~ maeh as heatthu.m, tt troduoder~al contents beyond sour or bitter taste in the mouth, or even cheat pain .~;,~;~t~ d the upperesophageal sphlncte~ tmgina pecinrls or myocardial Isalaemia prompt a patient to seek Water brash is the acid or bitter /~elp. the faCtOr or factors responalbl e for reflt~ za v.st be soviet, taste ~xperlenced ,vhen reflux The po~thle underIying eatme$ mm numero~, e.s Dr Barhm~n 0ccurs totc the mout]x ~" points out in this discussion of the pathophyalology, diagnosis, " mad h~ttment ofgastro~opltageal reflm~ The desired end point Symptoms ~ ~ m,,, .$ement ,u~.s wall sthu.~l i~ ~,e aeca o~ 2.000 !~e&r$ ag° CltoleeJly. the chief s3,mpinm of ~ u ~ g~d°h~ored sth~ch.N e~phageal reflux is hero, burn (pyrosl s). cisssieally described . as re~r~ternal bumtng dt~m- O~tr~sophageal reflux is one m outin" re'~aled that 7% expe- fort With ~ional upwa~ of the most common gastmin- risneed s~nmptoms dally while radiation. ~d~ae. bfliar~, and t~ttoal e~mplalnts in dintcal 36% had them at least mont2fly, gastraduedenal disease must be practice. Even In antiquity, the .~rnong pregnant ~en fn a considered to the differen~ lmI~rtance ofa "go~t digestion" r~uune obstetric dtole. 25% of diagnosis. Chest path may was recognized in prose and those po~ed had daily ~'mp- mtmtc m~gina peetorts or my~- t:~r~etr~ In 850 Bc. Homer wrote toms of hero, bum. cardAal lschemi~u particuIarly If to the O~ysset~ esophag~ml spasm occur& £aln - _ .There ~ nothtog to the WOrM D~"~nfttoats of esophageal reflux may be mcn~ shame~ than this The definition ofgostroesopha- atypies1, leading to diagnostic ~ ~dbel~uJ1~forcesamanto ~ea~re~qu~orasitisc~mmonly confustsn.Anunusualcom- rernem~r lt. in sptte ~fd~re ealle~, esoph~:g~eal r eJl ux. may plaint experienced by some ~; sorrow of heart differ depending on whether the es~phagltis patients is ear i~n " i " 'Today, the p ethora of media ~dewpotot is tl~at of the pr~ma~ referred ~'la the aurlcular ~ ~ , . adve~ttsements and the 8150 care ph~.~aie~ ran. path~oglsL ~f/~no~cL~ million price tag of over-the, radio]og'lst or endos~plst. The Water brash 15 a frequerd ~tmter znt~ld prepm~tlons recognition Of asymp tomatlc ~ncomtiant s~'mpcom. ~ In- sold to the United States an- thdi'dduals with ~hys[ol~ cre~tog number o[reports In- nually attest to the frequency of esophageal reflux due to tram- dlcate a slglllflcant tale of heartburn or reflux-related slent sphincter relaxation iden- esophageal reflux In some per- ~ • ymptorn s. A random poll~ of tifies a population to which sons With resplra~ory com~ '- ~58 "normal" persons to deter- esophageal reflux is not nece~ plaints of nocturnal choking or mine the frequency of "burning, t~r~y pathaloglc.~ A broad def- aspiration, paroxysms of wheez- substemal pa~n that usually oc- Intitsn of cltoica]]y r~cagnizable ing or dyspnea, recurrent eurred after eating or upon lying esophageal reflux is an esopha- pneumonitis, or nonseasonal gea~ response, e~ther subjective asthma.*~ OccaslonaL*y, mucosaf ~"~ "" ~ not hav~ been ~ssociated with or objecrI~, due to tnjunj erosions or ulceration may lead • an acid or bltter taste th the eausedbymjluxofthe~astro- to chronic blood isss, resultthg • ~L 74, NO $ ,tl~ZEMBER 1~ ;pOSTG~D(jATE UEO~¢~, GA|TRO[~pHA G[Ak R £~Ux "~ 1~ ~.~ !

Documentation of the physiologic occurrence of reflux may require esophagography, esophageal pH monitoring, or gastroesophageal scintiscanning. the patients with hernia did not have evidence of esophagtils. Problems with the definitions of the~e entities and the technical dlfferenc~ between studies make the exact role of hiatal hernia thconclusi~ at presenL Recent studies report evl- dence that normal individuals have periods of sponla.neous LES ralaxatlon, with resultant reflux. How~'en in the majority of persons, a peristaltic wave rapidly removes the offending gastroduodenal fluid~~ In pe~- sons with d ecrea~ed (or absent} peristalsis or d~d effec- tlveness of clearance, ¢~ntact of the acid fluid may be pro- longed,n Studies document that patients with symptomatic re- flux require a greater number of swallc~vs than a~Tnpt omatic persons for adequate esophageal clearance. Ape~stalsis due to scleroderma, for e~xample, may lead to severe reflu~ The Integri~ of the esopha- geal mucc~a maybe an Impor- tant variable in reflux injury in some Individuals. Pllor esopha- geal irradiation may predispose to both mucesal and motor changes, leading io decreased l'e~Istance to Inju~. Both gas- trlc acid and pepsin induce esophageal damage with pro- longed contact. Duodenal con- tents, part(ctl[ar]y in persons with prior subtotal gastrecto- • roles, may cause significant alkaline reflux esophagitis.~= In lane 2. Inl~u~c~ on lower ssophageal sphircte¢ tone Iri~u~ce Incr~ase~ lone DietaryHigh protein Gastric pH Alkaline (~n~cids) Hormonal Gas&~r~ Phacmaceugcal MetooIepramide Cho[inergic agerC~s hath anlmals and humans, the bile salts In concentrations found in gastric contours will cause permeability changes in e~ophageal mucosa. Not only is the type of rcfluxed material I ml~ri~mt but the ~l- ume may be criticak Altered gastric emptying {gasteoparesls or outlet obstruction) may in- crease gastrle contents, Increa~ Ing the likelihood of reflux. Although some foods produce symptoms of heartburn doe to either a direct irritant effect on the esophagus or a decrease in LES pressure, studies surest that paln develops in some in- dividuals after ingestion of foods With high osmolalltyJ~ Hypertonie solutions of saline a~nd sucrose ~ith the same osmolaliry as commercial erange Fally foods Tobaaao • Alcohol Chc~olat~ C~ffee . Acid ." Chol~yaok~nin Se~re~in G]uoago~ O~al co~t~aceplives Proge~te¢one ~ An~cholinergic agenI~ .%ipi~a-ad rener~ic antagonist~ juice cause pain in some per- sons with all acfd~sensftlve esophagus. Spicy f~ads, which are generally prepared with salt may also be hyperosmolar. This may represent an additional mechanism of food Intalmance in some persons. Dh~.als The diagnosis of uncomplicated esophageal reflux may often be suspected from the patient's history of sulisternal burning discomfort associated with re- cumbency and/or food inges- tion, with prompt relief after in- gestion of antacids. In many pa- tients with mild symptoms, di- agnostic tests may not be neces- sary. For patients with complicated reflux problems or those who continued

Offen~ simple life-style changes may lead to significant symptom- atic improvement of uncomplicated esophageal reflux. leukocytes and eosinophfs in the lamina proprl~.~ Esophageal matflity studies consist of passage of snm[l per- fused catheters or transducers to measure esophageal pcriatal- sis and LES pressur~ AS noted previously, the overlap between LES pressure in normal sub- Jects and in symptomatic pa- tients limits the usefulness of thts measurement. In persons with an LES pressure of less than 10 mm Hg, the potential for significant reflux increases. Determination of the adequacy of esophageal contractions may allow the identification of a subset of reflux patients with a motility disorde~ Also, when fundopfeation to create a high- • pressure zone for prevention of reflux is being consldereci manometric studies are impor- tant to determine whether weak peristalsis will increase the llke- li]]ood of postoperative dy~ phag%~ "/he Bernatein test employs the infusion of saline alternated with [klN hydrochloric acid Into the midesophagus~L A positive test is denoted by reproduction of the patient's discomfort on acid infusion. CorreIattsn of positive test results with fnd- ings on gaatroesophageal scin- tiscan has not been impres- sive,~ although some studies have reported good correlation ~th reflux symptoms~ - . • ..... ~t~ • ~2,¸ :,~ ~t Table 3. l~e~py for es(~phageal reflux :: Mechanlca~ measures ": ~ "' Avoid recumbency (nocturne, postprandMl) Reduce abdominal pressure (weight loss, avoidance of t~ht garments and strai~in g at stoo~) i Reduce gastric contents (decrease Jn meaP si~, avoidance of f~tty foods} ; Pharmacolog(¢ measures : Avoid antidholidergic agents, antihistamines Neutralize gastric secretion (msiacids) - " ! Create gastrlc acid harder (alglnid ac4d] Enhance 9a$1rlc emptying (urechoTine, metocloplamide) Reduce gastric ~ecrefior~ (cimefidlne} Dieta~ measures Avoid tobacco, fatty foods,'c ho¢ola~, co~ee, alCOhol ¢ • Surg~I me~ sures ~ - _ . : Relieve ga~-ic ou~et ob~ructic~, ~f present Improve gastroesophage~ (~ompetency {fun dopl;C~on, AngeTch~k prosthesis) ?. : Placement ofa pH electrode approximately 5 cm above the gastroesaphageal Junction al- lows the measurement of esoph- ageul pPL Acid is instilled In the stomach, fallowed by maneuvers to increase lntraabdoratnai pres- sures and provoke reflu~ The pH monitoring test is sensitive. and results show good eorrela tten with cl~ nica~ symptoms. Recently, 24-hour pH nlonltor- Ing has alJowed for prectse quantitatlon of the duration of rethuc Correlation of results wlth symptoms and with his- tologtc findings appears good. Measurement of the pH of re- fluxed gasiric juice afo~s the assessment of both LES Jncom- petency and e~aphageal dear- , ance.=* The technique of 24~ hour pH monitoring has been adapted for outpatient us~ Thus, the patient may be mobile and abM to pursue normal ac- tivit tes during quantitative e~al- uation of reflux.~ Gastroesaphageal scintiscan- ning employs admln~atrat tsn of technetium Tc 99m sulfur col- loid and scintillation counting over the gastroesophageal Junc- tton, The teelYnique Is reported to be highly sensitive and spe- cific¸z~ Among its adwantage~ are that it measures reflux di- recdy, does not require Jntub~ tlon, and has a high degree of sensitivity, continued g g

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J Ttmaac C,xRDfox ss~ Sine 86:616-620, 1983 6oo s Coronary revascularization in septuagenarians Despite a 15 year experien~" with the aorta~ercJlam, bypass olx,mtion, indleatlolt~ j'or its use remain utL~euled, esmciaIlr in rke elder r Ben*wen Janttary. 1974 and June. 1980. 2.667 .~atients utnfer~nt ~oroptaO' tarter)- relx~cularization ~th an ol~rall tnvrlallly of 3.8% [10112.6671. During the lasl 12 nlomt~ the nmrmlio" has d&'rcased ta 1%. Them g~re 2 562 I~tte,ts below lhe age of 70. ~4th a nrortali(r of 3.5% ~90/2_~62 hl contra~t to /OS patients o~r the age of 70. w#k a mortalit¥ of lO.5% fl l]105J (p = 0,002/. In patlenrs le~s than 70 years of age there was a sign~ficam difference bet~n the martalltl, of men. 3.12~ 16712.146L arm ihar of "az~men. 553% f23/416) rp = 0.01.51. This dispaffO' of ol~erati*~ r~k ~as for mor~ pronounced in Jatiems over 70 ~ears of age: teen 6% (5/~"t and women 2,¥.6 % f6/2D Ip ~ O.fJO2h The olerMI operatA~" mortality of "~mea. 6.6 ~ (29/437). was alg~iftetrnlly different from the o~'ra?l monaho, of men 3.2% (72/2.230) fp - 0001)..'In i,~ depth o,ah.sis of past ntedk~l h~tory, rBk factors, and cathclerizatfon data is presemed in these patiems over the age of 70. The awmge nuo her oJ x~sel$ btTas~ed "a~rs 2.40. men 2 47 and ~;'on ea 209 (p = A'S) The ages ~rled J~ 70 to 81 years with ~ mean of 72.5 S,ttoMng IP = 0.012 and diabetes fp - ~I078] were s?grdfie~m tqsk faeto~s for ¢oronart" disease. Smoking Ip "* 0 032 J end abnormal pldmonor), after3 pressures IP = 0.0429) "~re .qg;dficam xariables effeetlng mortMity. .4 97.1% follox'up ~os obtained up to 78 ntotrths. CoronaO. arterr rel.aseldarfzat~n can be perforated in men below the age of 70 ~th a~eptable tuor~ahl~ bul there is a g~v.aeold ~llereo$¢ abot,e the ~ge of TO. Womei~ ct~n ltndergo re~7$ctdarizatlon bdrm. the age of 70 t~th a sigt : k'am! " kigher risk than mates. 77 vse abv~ the age of 70 are u stmere eL~ aad shouId undereo re~eMarira!l ~n onll after careful selegllolt Richard S. Faro. M.D.: Mar~hMl D. Golden. M.D., Ht~hang Javld, M.D., C~rus Serry. M.D.. GLacomo A+ Delarla. M.D.. IYavid Monson. M.D.¸ Milton Weinberg. M.D.. James A. Hnnter. M.D. and Hassan Na.iafi. M.D- Chicago. IlL Th .. . . e number of coronary artery revascularlzations has We have analyzed our experience with pure o~maai3. ~ incrcasfgl in the past I5 years with a decrease in artery revaseularization in 105 patlenls over the age of ;7 mortality and mo~bidky. Revascafarization has been 70y~arsandhaveobse~edadisparitybetweenmenand ") showntoprofangllfei~lcertainpatients.~Parallelinglhls :, women. A thorough analysis with late follow*up resuk~ ine/-ease in the number of revascular~zatlon procedures " follows. ' being performed, there has been an exter~ion of this .:'" "~:" " : "' procedure into the extreme~ pf age. Numerous authors ~ I~}~ttents and methods .: . • ~ v "haveadvcc.atedcardiacoperhticns.lntheddei'ly,'~ndthe !-'" Casehislorlesofallpahentsoverthaageof70~,~ars resulting mortality and morbidit~ have been accept- able.z' Large series of cases ha~'e been repartcd in which the risk factors, preoperative variaNes, and postopara- tive results have been reviewed.~ Prom tile Delmnmem of Cardio~awalar-Thoracic SurgeD, Rush pr~.~b3~crl,m.S L**k¢" ,M~'d ca Con Chcago* I11 Rc~eltred for l~Nieation Oct 14. ISSZ A~x.'eptcd for F~bli~ation Feb 4 t983 .~=z=~ . ,, Addm~ ftwr~ptint~, MarsbMI O Golden, MD. Dexxartmea/ of Cardhwagz~lar Th~mclc Nurgeo. R~h I~b~crlan St. Luke's M~XlkM CenlCX. Chs¢~u. IlL 60612. who underwent coronary artery revaseularlzation from Jan, 1. 1974. through June 30. 1980. were reviewed *(Table I). Patients with Concomitant valve replacement resection of left ventricnlar aneurysm were excluded ~/~i oy " from thls'revlew. A total of 2,667 patients operated upon. Tlaere were 105 patienIs over the age of 70, with 84 men ~80%) and 21 women [20%1. 3[laeir age~ ranged from 70 "to 81 years with an average of 72.5 years (Table 11). Patients were reviewed by age, sex. history of angina, hypertension, arrh~¢hmla% congenital heart fail- - - * pt~Nettl ,,ddr tx,, R kh,lrd S. fa to. M O.. ,.tss ~ m al pw f~or, DeN ri are, prior myoeardM infarction, smoklng, and diahele, ,. - mentofSur~cr3.Univur.it~ dFk~nd,~.Guin~l;lle. F~a. 32610+ CatheterlT~tlOn dala were thoroughly re~q~ewed x~th J [ g+ + • •-? 0+~+': . + + "1 + " + + ~+ ~__:'+ " + + ,~ £', ~ . " " ' " + ' # ~ :', "+ --", L~+q " " "+. J .... '~ 1+ ~"

~.~ ~,, ~e~',:. ~ ~,, ~ - , ~,:" ~-~-, ~ ~'' ..... -~'~ ~ ~ " ~ :~i~i'i~-~ , '' 111-160 ABSTRACTS CIRCULATION, VOL 68, SuPe IIl, OCTOBER,•1983 " • " " " : L , TRARSITIOR OF CARDIOVASCULAR RISK FACTORS FROM ADOLESCENCE IO YOUNG ADULTHOOD: T~E BOCALVSA POST H[GH SCROOL STUDY , ~, , kS Webber, JG Baugh, dL Cresanta, GS Berenso., • , Specialized Center of Research--After 0 eleros S, " . CV risk factors change over time with ecergence . ," ~f clinically abnormal levels in post hlgh school , , years• A cohort of 29) young adu)ts (ages 17-21) ~ e . was examined for CV risk factors III 1973.74 and • ~ . again in IgTg.~O• M~_an systolic BP increased 8~ • ~ , • 4 m ~g, whi e d asto io Increased B-12 m Hg. "r ~ r Mean total cholesterol (TC) did not chBnge in .... the original I0-13 year olds however those 14-15 ' ~. ' Ine~ )O-~l) had an increase of 10 mg/dl in TC ," • with a 16 lag/dl rise in ~-lipoproteln cholesterol • . " ~ (6-LP-C) and 7 mgldl drop in o-LP°C, pramatic ~±", . increases were seen in sc~e individuals with dia- • stollc BP • 85 eln Hg in 6.2%, TC • 200 n~g/dl in ~." . • I5.BZ and triglycerIdes > 140 IB /dl in 6.2~. Ten or n~re clgarettes/day were smoked by 26% ~thite Inales 22% white females 1~% black males and7~ • " black females. Seven or more alcoholic drinks/ , week were ~nsuned by 46g whi~e ~ales and ~1% • ~ black m~les* Lifestyles deleterlo~s for opti~l health become ao~arent in oost high school years. -~ ~egular cigarette smoking, gradually decreasing physical actlvlty, )nd Increased CV risk as sho~q b~' ObeSity, ~yper~ension and hyperlipoproteinemia well zredict dave" )ment of CV ~o~bidi~'~. : 000B36 / ,ill ), 'I

ABSTRACTS OF THE 56TH SCIENTIFIC SESSIONS 000037 EIrF~CT OF ClC4~RET~ ~IOKING ~ ELEUfRICAL A ~¥ OS~NG p~OGpdd~D VE~/TRICUtAK $Tl)~r.~ ~T~ILI~T ~ V~NTRICIJI.~R ~OC~.RDI~M 1~ M~.~. ~T~/ ~ ~Ep~TITIV~ VF~VFRICUL/~R iLESPONSE Jkn~o~y N. BeMaria. ~ a~d UK fl~d~l C~nters. ~¢zicuI~ myo~lxl~l I~. Th~fo~e~ %min~ His ~t~l&ti~ IpVS] ~e evll~lt~l ~ 22 c]~c • IO~er$ ~h )~|io~raphically px~ ¢~nax~ at- ttl~ dis¢~ th~ ag~l~ effects of ~okin~ ~ ~tte ~ ~tl~ ~a~ricu~r r~s~onse CKVR). • ~,lge~ted ~rker o~ ~. ~d e~f~ctiw ~E} a~d N~t~r~nt~ w~zm ma~ be£o~ ~d ~i~h~n 15 ~i~ ~terC Sin. ~WR was ~I)~e~ed /ul 2 pa~l~n~ {pt~] b~f~r~ ~d 7 pr~ ~¢e~ C Sin. T~e ER~ ~250 * 6 W |D ~¢. p~0.O51 d~cl~d $f~niFi¢~tl~r fx~ c~trol. Biood ~%ao0~ ~noxi~e l~ve~ ~Memx ~ $D] 5.2 . ~.5 VoW% be~o~ ~d 5.9 ~ ~.5 x~l~ &~ ~c~dcn~e ~ RVR. 2~ C $m $ig~aifi~Iy de~ ~d ~he ~RP and FR~ O£ ~. ~ Higher i,¢l- l~Y~o~e~l~ effect ~ C Sm J~el~¢n~en~ ~ ~h~ -? kk~ ~56A CLINICAL RESEARCH VOL 31. NO" 4 I983

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The pattern and severity of coronary artery disease in Asians and whites living in Birmingham PATRICIA J. LOWRY M.B. Ch.B., M.R.C,P. D. R. GLOVER M.B_ M.R.C,P. P. J. l~ M-ACE M.B.. M.R.C.P, W. A. Ltt ILER M.D., F.R.C.P. SRtnlnary Thlrty.four Asian patSents with eorona~ artetT disease (CAD] ~ere each matched foz age, sex. blood pressttre and duration of symptoms ~th 2 white patients with CAD. Blind assessment of coronary Ilr~eriogr ares demonstrated aignifie~tl) more Severe disease in Asians hut dis~rlhution of disease was similar in beth groups, Assessment of risk factors showed that the Asian group had s[golfieamty more non-smokers, lower cholesterol levels and ~eighed less sh~m whites. WOPO~: ~mru~y art~r3 dise ~.~e. r~k fl¢~o~.. Asi~. [utrcducflor The inuldenee of eorona~ ane~ disease (CAD) led defit:aaoa of risk factors have been well docu- mented in while populations, bet recent reports {Gflhim. 1952= Gillum mad Grant. 1982) showing maial differences tn beth haeidence and risk factors ~, . have received little attention even though they are ~own tO O¢O1L Differel~ee$ in risk faclors compared with whites, have been noted before (Beevers and Crolekshank, 1981; Eisenberg et aL, 198 I). We set out to confirm or refute our imprt~sinn that Asian patients with CAD investlgaled by coronaw an#o- gr~phy irJ our Departmer t had more ~vere CAD in Im"t eular, mo~¢ severe distal CAD than whlt~ (important in considering suitability for o~rona~ artery bypass ~). Patients Jmd methods --= Out of a Consecutive series of 36 Asian patients ~dth CAD studied in our Department since 1976, 2 =~_. xvere excluded as their coronary angingrams were Results lost. Each of the remaining 34 were matched with 2 The 2 observer scores were compared with each ~ ~- ,~,~ :,,~.. ...... CO32 5473/83/100~34 $0200 ~ [ ~$3 The Fellowship of potlgradutl~ M~dkine white patients with CAD for age. sex. blood pressure i a~ad dl~r~tlo~ Of Syl~ptoms. Eac'h eorollal~ ~,t~lo- • gram was vlewed blindly by 2 independem observers: ~ the 3 ¢eronaD arteries were examined for CAD and ': ~ separately from 0-5 for proximal disease and i• :j scored sirailar13, for distal disease. The s~r¢ was an assess- ~-. merit of narrowing oftbe vessels (normal vessel 0: .p ti'; to 25% narrowing, h up to 50%. 2; up to 75%. 3: sub- l ~. total leaion. 4: total occlusion 5"t. In the ~fight coronary ane~ (KCA). proximal was defiv, od as the RCA xlp to the o~gln of the poste~or descending uricW and ol] other branches of the RCA were ~, defined as distal. The left math artery was s~ored separately; the left anterior descending artery w~s ~ proximal for the fast Iwo-t~ddrds of ilS eo~arse: the distal third and all other branches were deimcd aa distal. The eh'~¢x arlery was proximal to the origin of'he obtuse marshal branch: all the rest was classified as disud. Left vemriesinr (LV~ funetinn was ~,sessed from ulrteangiogr urns noting the ptes¢~e or absence of a left veatrioalar aneu~sm and mitral regurgqtatio~ and th~ culcn/ation of ejection fracrion by volumes. Tha leR vemrleular e, nd-thastolie pre~- the left vet~trie~l~r angiogram. Risk factors other - than those for which the patients were matched were also noted---zmoking, diabetes, and fasting chules- lerol and triglyceftde levels taken oa the morning of , Results ~ver¢ expressed as the m~ =hs.d. alld shTferen~s between groups assessed by paired and • . unpaired Student's t-test.

Tho~ 19fig;38:785~7fi7 Packed cell Volume, haemoglobin, and oxygen saturation changes in healthy smokers and non:smokers 000840 , VGTIRLAPUR, KIMAN|GICHERU, BMCltARALAMBOUS, PJEVAN$,MAMIR From the Department of Med cine, University Hospital of Wales, Cardiff ..... : A~S'mAcr We have investigated the relationship between cigarette smoking, packed ceil volume, haemoginbin concentration, and arterial oxygen saturation (Suez) in 114 non-smokers, 66 llght smokers (1-20 cigarettes a day), and 50 heavy smokers (over 20 cigarettes a day) aged 20-75 years. Packed cell volume was grealer in female heavy smokers (p < 0-001) over 40 years of age and in all female smokers over 60 gears (p < 0.001) than in non-smoking contemporaries. Haemoglobin concentrations were higher in 40-$9 year old female heavy smokers (p < 0-05) and . in male and female light (p < 0,05) and heavy smokers (p < 0.001 ) over 60 years of age than in non-smoking contemporaries. Saca was lower in 20-39 year old male heavy smokers (p < 0.02) and female (p < 0.05) light smokers and also in 40-59 year old male light and heavy smokers : (p < 0-001) and female tight smokers (p < 0-02) than in non-smoking contemporaries. It was also inwer in female light (p < 0.05) and heavy (p < 0-02 smokers over 60 years, whereas it was higher in male light smokers over 60 (p < 0.001). Cha~ges in Sac2 were seen at a younger age than changes in haemoglob!n concentration and packed cell volume. Increase in packed ceil volume in healthy smokers is were light smokers (I-20 cigarettes per day), and 50 caused by increase in erythrocyte mass.~-~ ~h/le were heavy smokers (> 20 cigarettes per day); the attorial oxygen saturation (Sao~) appears to be she table shows the age dlstribntion of each group• All most important determinant of the eryshropoled¢ smokers inhaled the tobacco smoke regularly but response.4 Cigarette smoking has been shown to she frequency- and duration of inhalation was not determine the degree¢ of secondary polycythaemia assessed, Subjects were studied between 09.00 and in patients with hypox cshron c obstrdctive puimo- 12.00 a8er 60 minutes' abe~inon¢¢ from smoking. mtrythsease,Sbuttherelafionshipbctweencigar¢tte Venous blood was sampled for measurement of smoking, Saozandhaemaoogea ndiees nhealhy haemogloginandpackedcellvol~me, Haemoglobin subjects has not been studied. We designed this Was measured by Cyan-Mot (model S) and the study toinvesflgate the interactions betl~eea stuck- packed cog volume was calculated by a CouIter = ing habits, age, sex, haemoglobin concentration, ¢ountercomputcr after tbe~edccgconntandmean , packed ceil volume and Sacz in healthy subjects ¢orpusozlar voZu~¢ had been obtained. Sac: was measured by an ear oximeter ~qew]ett-Paekard, Methods Two hundred and thirty healthy hospital employees, L medical students, and nurses aged 20-75 )ears were stadiud after we had obtained their informed con- sent and approval of the local ethleal committee. One btandrud and four/con were laol~-smohers, 6g ACidt~s for reprint requests: Dr VG Tirlapa~ Department of . Medicine, Ll~iversity Flospit~l of Wales, Heat~ park. Cardiff CF44XW Acoepled 16 May 1983 47201A). Results were anaIySed by Stud©nts's unpaired t test. ': " --an ResaRs • The results of haemoglobin, packed ccH volume, and Sact measurements are summarisud in the figure. whore light a~d heavy smokers are compared with ~ ' non-smokers of the same age and sex- Mean haemoglobin concentration was inen:~sed in female heavy smokers aged 40-59 yeat~ (p < h.# 0.05) and in male and femate light (p < o'og) and 785 .

L d . %., ~ Compliance Characteristics of 291 Hypertensive Patients From a Rural Midwest Area 001)841 Reuben B. Widmer, MD, Remi J. Cadoreh MD. and Edward TroUghton own City, Iowa Patient compliance with treatment regimens has been ~ concern "~" of both researchers and cliniclans. Research st~Idies on compli- ance have generally originated in large city clln~es and teaching institution~ The results paint a dismal picture. The question is, are the compliance percentages found in the literature appliet~ble to the hypertensive population in the semirural Midwest who receive long4err~ care from their family physician? This study was carried out in the practices of seven mid- ~• western family physicians. The 29I patients in the study b, ad a . . mean compliance percentage of 87 percent. By-product data indicate that omcome results were good. Research on compliance traditionally has conceived of the problem in large part as one of defective behavior by both the patient and the health care system. The physician-patient rela- tionship in a family practice should contribute to better medica- tion compliance. In this study semirural l~atientg with hylxrteu- sion who receive continuing care from their family physician had better qomplianc¢ than national figures suggest it should , . have been• " ' ::- ""~'~ "' One fund*.mentaI component of medical prae- . aompha~ce flgtlres In the literature apply to pa- ~- tree ls *.he patient's cooperation with the treatment dents irt some other clinic• No one likes Io admit : regimen proposed b~ his or her physician. Physi- there is a lack of patient esteem for his ma~ag~- -,. - • clans assttme their patients are compliant, and few riae nt ptan. But the truth is. there are patients who tikatdadmittohavlngpatientgflherence~roblems " display li[tle lxspect for that quintessence of • in thelr-own practi~es. Most physicians .fed the iaealth eaTe aetfvlty, the prescription. According to ~2 • ~ . . ~.. " " , . ' ~tudles in metropollt~n centers, approximately a?%:., ........ " ' ."" . )" i . ; . .. 6he third of patients do not have their antlhYper- ~;ii"~ " tension prescriptions filled, and only one half of :" he rest take the medlca on as dkeeted.''~ In the~. ~" F om he Oepirtmen o Fam y Practice and th~ EleDat~- • V ~ttjelltL me~ of Psychiatry, U~livers~ty o owa, owa (2 y ow~- ~xpel"leIlef~ of O~e Of th~ ~,~t[~3~'S~ hOW£: el', [3 ..... ' Reque~s for redrinlsshould be ~ddressedt°Dr' Reube~lB" ¢omp ance observed ~n an essen a y rural mid- , ~ Widmer, Departmen o Faro y P ael ce Llmvers~ v of I~wa Western' dM" agree wl" h he "*r :~ Iowa City, 'A 5E242. practice ,Ot Seerd tO ~k~ ~" .... 1~3 Apple,on-C.ntury-Cro.s :i::'C ~ o . : : • . , : •

COMPUAtVCE IN HYFERTENSION Table 1. Demographic Informatian of Participating Practices Prescription Percentage of Number of Writer Patlettts w~tb Town Physici~$ Or Town Years in Patlent5 Third party Number in Practice Dispe=lser Size Practice ~n Study Payer 1 1 Dispenser 700 35 . 114 35 2 1 Dispenser t,008 8 55 g 3 2 Dispenser 1,000 18 34 10 g 4 1 Dispenser 900 21 38 10 5 2 Writer 8,500 13 82 5 3 Table 2~ Demographic Data of Sample Table 3 Compgance Percentage by Study Factors Mean age (yr) 63.2 Mean diastolic bloGd pressure (mmHg) 83.7 Mean number of times medication 5.1 purchased Mean number of days w~th adequate 234.3 m edlc~'tlon Mean number of days medication was 272.3 required Male median weight (Tb) 186.0 Female median weight (Ib} 160.0 less. Weight and smoking significantly affected treatment outcome (Figure I). When compliance is ~elated to outcome, the re- suits tend to agree with Sackett etal,9 who state , that a compliance of at least 80 percent should acheveapos veoueomefromanan hypertens- re'medea ell reanentregmen tlt s sudy. 75 percen of the pauen s had ~i eomp ance of-a ~!. least 80 percent (Table 4). Table 5 looks at out- come in relationship to compliance, where gener- ally the compliant patients had a betier outcome. Statlslical anaIysls using the chi-square gives a p vague of .0506. Seventy-elght percent of the 219 patients who achieved goal hlood pressure were at least 811 percent •compliant. TWO hundred twelve patients had an 80 percent c6mpliailce rate, and 80 percent of these •achieved goal blood pressure, whereas 68 percent of the 72 patients with a lower compliance achieved goal blood pressure. Even though there was no significant difference in compliance I?etweed the sexes, significantly more 6ZZ Compliance Factor NO. Percentage Male 109 88.7 Female 182 87.1 Dispense 939 86.3 Write prescription 52 87.9 Below median weight 123 87.4 Above median weight 181 ggA No complications 251 86.9 At least 1 complicat~o~ 40 84,6 Medication taken daily or 262 g7.5" twice daily Medication taken |hree or 29 78.0 four times a day Nonsmokers. 260 87.0 Smokers' 31 B2.9 *Indicates ~ignifieant difference women than men had diastolic blood pressure under 90 mmftg. Discussion ~J1 " ". Determining the compliance of pallen~s to anti- hypertension regimens in a family practke was the primary purpose of this study. Outcome results,~ were recozded as the stale of the art in practices of seven different physicians. The results are 0~ THE JOURNAL OF FAMILY PRACTICE, VOk. 17, NO. 4, 1983

COMPLIANCE IN HYPERTENSION Table 4. Cumulative Table of Patient Compliance Complignce • Percentage Number of Percentage Cu mulat Jve Interval • Indi~i~luals Sample Percentage 95-100 126 • • 43 43 , 80-94,9 .. 43 : . 15 58 88~9.9 . 25 8 67 g0~4.9 23 '" ~ 8 75 78-79.9 • 18" , • 4 79 70-74.9¸ ~ • 16 4 6,: ; 85 • ~ 15 100 69.9 ~'~ ~" 45 resented with the reaI~zatfon that ~he design for future prospective studies of blood pressure out- come would need the followlng changes: (1) iu- cfude" only newly diagnosed hyperlenslon patients, (2) give criteria used for diagnosis of hypertension, (3) slandardlze the method of blood.pressure measurement, (4) control for age of palient, (5) follow up on paricnts who drop out of treatment; and (6) determine goals of treatment for physicians collecting the data. The mean diastolic blood pressure of 83.7 mr~{g for this sample (n=284) indicates good COtltFOI compargd with pretreatment blood pres- sures of 8~ater than 90 mmHg. A compliance per- ¸ centage beuer than 80 percent produced a better o~t cortlc ~ban the results of the study noted abov~ by Sackett et ah9 A~ shown i£ previous sludles, a complicated regimen resulted in significantly poorer cortlp]iance and outcome. This effect on compli~nce supports the pracliee of prescribing medicatlon that can be takeo ol~ce or twice a day. more complicated dosage schedule would imply THE JOURNAL OF FAMILY PRACTICE, VOL 17, NO 4, 1983 623

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OrlginaI Articlp on Economy and Health 00 {}~ 4 2 • = ' ~ , " " MORTALITY AND ECONOMIC INSTABILITY:

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(c~ ¢o~j PAPERS AND SHORT REPORTS ( _J' 7 1. 2.. 7t.~-v. _ ,~ 000843 Carbon monoxide yield of cigarettes and its relation to • eardJoresp~'atory disease COI.I~BOF.~VD~ ~A~DREWCHAMBERIAIN~ TIMHIGENBOTTAM~ ~TIN~H~PLEY~ GEOFFRey ROSE Ab~tea~ Est]mate~ o f z~e ~bon m~n~x~de y~cld o f theie cdga~e~t~s ~een obtained for ~J0 ~o~er s (~8% of aU smokers) ~ Wh/teh~ irad~ of za¢~ a~ed ~10 to E4. ~ the J0 Bf~er e~a~at~.n ~ ~¢n died. ~ea men smv~ c~gar~tte~ ~.A~h high caeSon ~o~d¢ yield were ¢~p~red w~h ~ose s~k~g ~a~ettes w~ a tow ~e~d. anti a~cr udjg~flng for age. employment geade~ amn~nt ~m~ed. ~md ~,r yle~o, the z~ of d~tl~ w~ :t~ lowee for ©oro:~t~ heart d~ea~e, 4~% ~gher for Im~g ~mcer. mad 10% lower foe to~al mort~ thes~ d~ffcr~ were ~ot sta~I~cl~Uy ~i~fi~t. Among men who ~=~d t~at th~ IntOJ~d tl~ risk zf fatal ¢oro~¢~ heart ~e~e w~ 51% lower ~a the hLgh ~rbon mono~de Weoup (p <0"01X wl~te the ~ af I~ag ~¢er w~m 7~% h~gl~cr~ ~. "I~ese relu~s l~rOv~ ~o evtde~uce that a s~cok~ ~du©e ~ rl~ of dtmh by ~uok~g ~ br~ud w~gh ~ io~ g~rboz~ ~ouo~ide ~l©~d~ he n~ght ~ven ~¢rease it* Xhe cz~pIex ~terac~ionm ~tween ~racte~sO~ of the ~o~¢e. ~mo~u~ be~a~our~ co~fltue~ts oF tobacco Imoke. ~md heo/th are agah~ demo~xated. ~L[~ BOUND, ~r, r~eh fellow ~l~lm~ ~ B~IdCminlogV. Lct~d4~ s~al ¢~f ]~lI~n© ~d Iat~ott tmt:im~ q~e ~h for ~ I~ ~dou~ d~et*~ k~ dcp~de~l ~a jdeufif~j~g ~spe~eel I~t rmfld com/m~e~t~ of t~b~eeo smoke a~d r~ea r~d~,¢i~ ~ti~ cou~nt~fio~ I~Md~] mt~t c~tr~d ~r, and ~n ~e t~nlred xan~dom ~t,x~ I~69 and ~9~0 t~ ~11~ w~t~d avc~a~¢ ~eid for ~ in ~ufactu~ dg~m~tes £~1 f~om ~t to 16 ~l; t~ d~I~¢ i~ te~d~8 to ~l~tcn ot~t. ~ i~ mow moving t~ ~'0on monoxide. ~usc ~ it~ ~a~ected Ida~on to cavd~¢~v~og~r ~isea~ it~ yi~ ~d[ tufty ftma ~l to 16~$ m~,Th¢~ i~ Iceo~g p¢~ both o~ ~n~nu f~rex~ ~ redtme the average ~o~ monmdAe yie2d ~d c~t the pubffc ~ ~t~e~ law~ yield bt~d~. ~evttt.~ Such a pMi~. ~Le e~x~eri~e~t o f t2~ W~t eha~ lt*adyls rde¢~z~L* l In 1¢~d3 t]a~ '~i~¢~alt study Cx~raJ~ed t8405 a~] sm~t~ tg¢~ 40 (o ~. ~ac~¢ r~m]~eted • qa~, ~mch i~clu~ed[ ~tm]$ of ~,~Tctlt ~gr t~¢ o~mm~lff~tt m~ mxw/ d~et~e m~O tmdct~et~ t ~r~tm~ ~dt~ ~ dt~ wedge spltamct~+Ttm p~ew]~ of czr amu~ h~rt ~$¢ at Ir~l et.~xLoa ,os a~tmed by ~e X~e ~ aad mc0~c ~-I~ af d~[ene b~0* wet ~awn from ~vera~eat C~e~d~t I~s ma~v~ old ~ d Cigarette, ~td from raked bF ~Sm ~ of t M ~gar~t~e t t ~ke~ m th~ stogF.* ~ht tct0g~¢I~ • m~ed h&ad roIle~ dgaret~ at le*¢ FO~ b~¢. C~met a~tmy et eett~t = ,~r:¢laUon ~ =O.9O fe~ m, ~O 08~ for m~flae; n=~2) tad t~e ~ a~ff.r :a~ (r~mt~ o~ r~t ~e~mt ~,~l mmm ~t o~ ......... ...................... ~:'~ C~r~e~dt~r~:patr~Ge~. • ~rnor~on ia ~lu~ ~w~ .e~ti~le. ~o ~h v~dad~n .~a~ •

~'J~"=~ "~ d~ . ~ * ~ .,.~1=r -r . 4 ,*, .j '~1~ ~ ~ 00084( Biological half-time of cadmium in the blood of workers after cessation of exposure by Lars J~rup, MB Artur RogsnfeR. MD.= CarbGustaf Elinder. MD: Koji Nogawa, MD.= Tord KjellstrSrn, MD4 " ~ ~':~ "- JAF.UP L ROGEN~T~T A. ELINDER C-G. NOGAWA K. KJ~LI~TROM T. hJoIogi- ca] ha]Prime of cadmiuxn in the Edood of workers after cessation of exposure. Seand j tooek en~i~a health 9 (1983 ~27-331. T~ biological b~lf.fime of cadmium in the blood of prevlotts]y exposed worker~ was estimated aller the cessation of e:¢~, Five men were fonowecl for a period of 10 to 18 yeats. One<ompat *,n~ent and two-com- partmen,, exponential elunlna~on models were used to describe the decrease £a blood Cadmium le~eis over tirae- The bes= fit to the observed data was obtained with a tw, c- compartment model "Foe haIPtimes estimated from this mode] ranged from 75 to 128 d for the f~st component and from 7.4 to 16.0 years for the slow c0raPonent The restflts eonV~rm that there is a very long whole.body bioloi1ical half-time for cadrmurx.. ~d ~': " the estimated half-times are similar to those obtained w~th different methods " K¢~ ~e~ms: metabolic model. • ne decline in the blood cadmium of single ~xponentist functions• The biologi- workers after the cessation 0f exposure c~ half-times ranged from 25 to 146 d. the tO cadmium has been studied to a limlted median "value being 41 d. The authors extent only. concluded thai a one-compartme~ ex- Most estimations of the biological half- ponemial elimination model is too simple time in the blood of human beings shortly to describe the blood cadmftmq curves after the cessation of exposure are made and that the rapid decline in blood cad- accordingzoa one-exponemtist eliminatio~ mium after the cessation of exposura did model. In an earlier study (I0). 25 sol- not reflect the total body bioiogical half- derers were foUowed for t5 months after tm~e. the cessation of exposure. The periods Based on the accumulation of cad- of exposure varied from 8 months to 17 mium in kJdney with age, it has been estz- i. ,~ ' years (average values for two groups of mat~i that the total body biological -:.:~ workers). For 11 solderers it was possible half-thne for cadmium is very. loni1, ploh- - ~ ' to analyze the decay kinetics more closely, ably I0 to 30 years (2), • " ' ~ ~ ~ The decay curves of these workers fitted Data on the accumulation of cadre urn ' " !='- ~.~t~ = ~ -.~•~ :.~ ~ ~ ~" : " m b ood after a sl2dden ncrease m expo- ' f , ~ t Department of Environmental Hygiene of sure can also be t~sed for esLL~atmi1 the , .~- ~. ~: - • : : the Karolinska Institute and the National half-tlme of the fast component•Based on . Institute of Envlroz~mental MedicL~e, Stock- data from 17 workers, an average of 77 d ; - • -" ' - holm, Sweden, i : ' • Granges Aluminium, Finspang. Sweden• was suggested, and this estimate was a Department of Hygiene, Kanazawa MedicaI used in developing an eight-compartment :. = ~ ' UtdversJty, Uchinada-machL Ishikawa-ken, kinetic.model for the metabolism of cad- ! • " Japan. • :~ : " • Department of Community Health, Medical minm (i1). SO fax, it has not been possible to ca]- __~ | School, Un Jverslty of Auckland. New Zea- ~;~" " • and " culate, with any accuracy, the slow cam- "~ ~ | ~;=" .... '~:"~,~"' "~''~' " ponent of the biological half-tlme of cad- • ' • ~ " t{eprlnt requests to: Dr L Jhrtlp, Department miur/~ in the blood of human beings, The --, ~. of Enviroamentat Hygiene. Karo]inska InstL present study was carried out in inves- , lute. PO Box 60400. S-I0401 Stockholm, tigale this particular problem. ,~ Sweden. t • i:-

was fitted to the data with both elimina- tion models. The biological half-times were : then calctdated and found to be 7•7 years for the one-~xponential model. Results • obtained using the two-axponential model " were 91 d for the fast component and 9.3 : ~ i "i years for the slow corn ponent. Discussion m i dioacdve isotopes have" also been made. ~arnagata et al l1 II, as cited by Takabatake fgh studied the retention of cadmium in the body of an experimental subject who had ingested rice oantaining nScad- mium. Using the retention curve~ they ex- trapolated the absorption rate to he ap- proximately 7 (range 5-10) cA. They as: sumed that the total body burden of cad- ::In this study the exposed workers were minm for the experimentalperson wa~ 30to ! followed for an unusually long period of time ll0 to 13 years) aRer the cessation : ~ • " of exposure to cadmium. Four of the • :! .workers numbers I-4 had a constant aa which was largex than a, (table 2). Thus , !; ~ • a m~jer part of the blood cadmium in these workers was reLRfod to the slow COl- ¸ ~ portent For one of the workers lnumber 5. table I), a~ was larger than as• This • " man was exposed to relatively high con- eentrations of cadmium between 1964 and i ¸¸ ¸1968 and it is therefore reasonable to as- • sume that the iaxger proportion of hls hiood eadrninra sboald be related to the 40 mg and that the daily ingestion of figurP~s and a two-exponential c lnodel, they calculated the biological¸ half-time of the slow component to be 20 years or more. me period of obsPJ~ation was rather short~ hov:ever, and the accu- ~ racy of the obtained values is therefore lira- • ited. Nevertheless their estimate agrees ¸well with the biological half-thnes of the slow component found in the present study• • Shalkh & Smith (g) studied teers~ who ingested beef kidney containth fast component, retention was monitored in the subjects Aceordlngtothemetaboliomodel(3)the for 56 to 808 d. The best fit to the data constant a, can be assumed to represent was obtained with three expo~ntials. recent exposure, whereas the constant a~ The three components of the curve had should he proportionalto the body burder~ biological half-times of 1.58, 33.7, a~d of cadmium• 9.605 d (26.3 years), respec~vely. The range of the fast component in This study agrees with earIieresfimations the two-exponential elimination model of the biological half*time of cadmium, was 75 to 128 d, which is within the limits even though the other estimations were of the vaines obtained in the earliPr study obtained with methods differing from (I0). The range in that particular study was the one used in the present study. The 25 to 146 d. The estimated slow component slew component of the biological hal£- of the hio~ogioal half4ime for ~he three lime of cadmium in blood after *.he cos- . workers without tubular damage ranged sation of exposure and the whole*body from 11 to 16 years, which is in accordance half-time of cadminm are in the range 10 ~ith the model proposed by Kje]letrgm & to 20 gears. Nordberg 3 and eariier estimat'ons of the ' • ~ ~ [~ ,~ total body and k dney b o og ca half- ~ : tlene(2). .... .: ~ .... Acknowledgment ~' | , Thelevelsofbinedeadmiumthatwere . ~ ~." @~,~ ~ J .zeaebedsubsequentthbetweenlOand13 Wewant ta thankMrRSk erwall the :!~'~:%" "" " years of fallow up, after the cessatmn of Karobnska Institute. Department of f~ exposure, ranged from 8 to 15 ~g Cd/] Statistics. for his helpful assistance in i,~~'z ! (71.2 to 133.5 nrnol/l). Which is significantly using the mathematical modeling tools higher than normal blood cadmium levels, required for the nonlinear curve fitting. A recen~ Study on Swedish men not sub- ject to occupational exposure showed r" that the median blood cadmium level for References . • : ~: nonsmokers is 0.g ~g Cd/1 (1.8 nmol[Ih and for smokers 1.6 [~g Cdl1114.2 nmol/l) (l/. L Elinder C4~. Friberg L. Lind B. dawaid M. : Lead and cadmium levels in blood samples Attempts to estimate the biological from the genera] population of Sweden. halLtime of cadmium in humans with ra- Environ res (in press}.

¢-" ,, t .I, ~8000

500001237 0 0 ~9 0 H m ~4 0

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• "):'i%~ ~ • Ii k . 000847 Special Communication AN INTEGRATED PROGRAMME FOR THE PREVENTION AND CONTROL OF NONCOMMUNICABLE DISEASES A KALNAS REPORT RcpoIl oft 3.~eetmg. 16 20 Novcmher 19,ql L S. GI As~ x'ox~ V. GKAI~AUSKAS. W. W. HOLLAND* ~nd F. H. E~S-ItiN ion behalf of lhc participants, listed p. 7I 17qTRODUCTION AS ~'ARX of its overall policy to attain "health for ag by the year 2000" [I] the WHO ~s ¢xp[orin3 [he concept of an integrated approach to the pr~vcnllon and control of non- communicable diseases. Disease prevention and control has mainly been directed at single diseases rather than clusters of diseases or health problems with common aego]o- gicai fi~ctors. Several of the more prevalent noncommunicable diseases have the same or close]s related £~tlSe~r. It is logical therefore to take common actions igainst them• Even % when a sttateg~ is concerned specificall2, with ~one disease other conditions must be eoitsidered in the planning and e~aluadon of the programme since actions directed " against one disease may ]nadvertentl~ increase the incidence of another, An integrated 2 programme for/]1~ prevention and eo~tr.o] of ooneot~mllnleah]e diseases combines. In an " - operationally feasible manner, resources and approaches currently being devoted to the prexenilon and control of selected ~oneommunicable diseases and related conditions. It permits the managerial unification of a set of pre~entive and other control activities that should lead to tile prevention and control of major tt oneommurdcahle diseases and to the promotion of health in total comrtlnnltles• Following preparatory consultations in Dublin.'Geneva [2] and Zuricl! [3], WHO convened a n~eeting m Kat3t~as. Litbuanlan SSR. USSR in November 1981 [4] to pro- mole tile concept of an integrated.approach IO ~aoncommunicable diseases and to de- ~'[ veloF a suitable programme of collaboration with Memner States. There were 26 pat lici- pants from t3 eounlries and the meeting was'also attended by nine WHO staff members ~ " and 30 local observers. This report presents ideas and i[tformation emerging "ram tile deliberations of dlat meeting, which are pertinent to this important WHO programme. It indicates in broad terms how strategies of prevention and control of nonconlmlmicable r"- diseases m:t~ be de~ised Io provide a framex~ork for new concepts and future action. ~.O • *ell ~liieSl~nlll~¢ll~¢ ,he/t[d be :lddlc~ed i~1 Profei~or ~" W Holt,rod. [Oeparllnenl Of Comlmnl~t~ Mtxh'allle. , ...-~ S a ~, p ta ~x X ¢ Scho Gu. dg Than Hop • o~ SE g .

I -.7 !: __ P~l¢lluon ;iNd ('Onlrol O~ ~ llcolfll11u r~{¢:l [I I~ D [seils~s 42] c:,ir( og~ [)1 l~, T[R ~'~ "~] ]I )% A'~II L[~ • or I'R~VI 'dTIO%~ L~'cl of L¢~ai~l~tl~ c Provision of Ch.ln~ine ind1~dt~a] L¢~1 I T~llon on clg;tlelteS ~ea]t]l ~'d~¢,11iOl1 of Social "h~haviour~] faclor~- f ar~d alc~ho[. ~li[ic~l $ -i Heahh ~.ir~i gs on --smoklng pr tadu~s itLtl~[i]0n • ,*. ~ C]¢an.alr ¢~l~li~liotl. ~xerc~s~ - .~ Re~lrlct~ns On adl erlls[~B --alcohol 2 L~l~I:itl0n Ot~ for I~ro~,~o~ of high blo~d ~re~e~re ?rcscrihed ~'~[mC'll~ ;I rlc:ice ~hi[]~ ci~nce[ RellablI~latlt~n C~tr~ ill I[1¢ eId:rI~ (c Care shotlld be taken to avoid selecflng a particular popuhtdoll hc~x~ause of pressure from all illteresIed group, since the populatien thus chosen may not meel the criteria [or inclusion in an integrated pro~amme. CATEGORIES OF DISEASE PREVENTION AND CONTROL The pre~enflon of diseases can conveniently be classified as: Level I rgmoving the causes of a disease and it5 precursors. Level 2--reducing the number or the Ie~] of disease precursors at a stage when the condition is ~till re~ ersible. Level 3--treating chn~eal disease [latent or m~nifest) to prolong life or limit disabditg. There is ~till some debate about this terminology. Many'include the first two levels under "primar~ prevention~ and define the lhird as "sfi'condary prevention ' while others refer to the three levels a~ primary, ~eoondar'~ at/~t ce~'ffary prevention respectively. ~,['PRO'tCHES TO INTERVENTION AND FEASIBLE TYPES OF ACTION Intcrvenflons can take the form of legislative action health services, an~ ~etions designed to change individual behaviour. Table I gii'es examples of preventive measures classified according to the three levels define~l above. Responsibility for these measures can he assigned IO society in general, to governments, t¢ public health bodies, and to indlxiduals. While Ihis classification' is useful for identifying the mare :areas of responsl- • • ~ • . ~bs~11¢¢ of svn3piollis. ~-;~'~- ~," ~..:~,.g~..; ~.;~. ~,~,~.-, ';~: ,. 7~'~'~':: ., .~:~" '-'~,-:~.~":.z*~,., ¢dl billty these categories overlap. For example, legisla tire or governmental measures such as cigarette taxation, health warnings on cigareile packets, and the reslriclion of tobacco advertising ~,ill colour sociaI attitudes to smoking, which in turn will influence individ- uals when exercising their o~vn choice• Sin~garly il~ the detecIion and treatment of high blood pressttre, it is necessary to haveheabh ~erviees x~ith responsibilit) for Ihe measure- rllent tllld control of blood pre~ure, and a sgstelill]llc medlod of identifying those who should be scleencd. Prevention then depends on Ihe individual's choice-whether In accepl sc~eel~l~g ~nd ~hether to comply wflh a Iong-lcrm drug re~imen, usually in the

table 2 summarlses proven prevennte strmegies, classified according to various target groups, ill rc,pcet of which nllegraled acllon 15 lu~dfitiffie. The main {arge|~ for aclion fag u.der "personal habits and behavmur". Avoidance of smoking is at present 'tthe slngie most important action thal "aould prevent lhe main dlseases that cause premature death and disabifity in many couiitries, vlz. coronar3 heart disease, lung cancer, and chronic obstruclivc lung disease. In those countries where these diseases are relatively less com- mon. their rising incidence fofiov, ins the introduction of smoking is slgr~aIling the begin- ning of an epidemic which has alreadx affected tile economically developed countries. Cettain larget groups can be design ated on the basis of age and sex rather than specific diseases. Women attending a centre for cervical screening for example could haw their blood pressure measured ("incidental screening') and during pregnanW several disorders can be prevented incJuding the important congenital disorders, spina bifida and Do~vn's sbrndromg,'as wefi as rhesus haemolyric diseases of the newborn and phenylketonuria. • ,~ A number of occupations are associaled with an increased risk of certain diseases, and occupational hyglene standards have Io be applied to prevent them. Many substances cause occ pa ona caheers bu he r eontribu on ti~ the occurrence of e~neels in a total ~opll]gttiorl IS re!a.tlvel~ small, m conh'ast to•smoking, vdllch is estimated to accollnt for at least one-s~:~d~ of the'~unual iotal mortality in countrles where it has been common for many years. Nevertheles% the workplace is a useful base for preventive programme~, for "example. in respect of cigarette smoking or hypertension. The remaining targets mentioned in Table 2 cover a wide range of actions such as improving the quality of water, air, foo& and housing, and promoting traffic safety. They " are c ose y assocja ed w h socioeconomic deveropment. - &ltlloua[~. at first sight, file integration of'varlous preventive measures appears difficult on accounl of the wide variety of diseases and methods involved, it is practicable and effective for a number of common diseases. Examples of possible specific actions in respect of reducing tobacco smoking and higb blood pressure are given in Tables 3 arid 4 respeclively. DJfferetlt countries of course will ha~e different prlorifies for the condhions to be tackled and some framework is needed m define these priorities. Silnple mcdlods include estfinati>lg the frequency of different conditions in a parlieular community, assessed in lernl~ of morlalily or morbldh3 or bodl, and identlfging the affeeled age-groups. The burden of disease among file newbora and relatlve[) ~oung for example wig be greater in deve]oplng countries than ill the more dexcloped Other imporlant conslderation~ are lhe

Pr~ventlon ~d Contr~q or Non¢oln mu glu;lblc Di~eas~ TAm I ] /~.PPROAf I IF$ TO lIMITATION OR ~S~A~ION T~ IOBACCO ~MUKIN(I 423 GO~etl] menl legMatil'e aelions tlan. or reslrlc~ IlXe omductiom ~tle and use [n ¢er taln ]neatlon~ olin on ~o~It~t s )1¢IdJn~ I~tlaJn ~el~ ¢~f a s~b$1an¢~; --de~ ¢loomcnt or le~ hazar dolls inalenal~ Io O¢ II~a a~ smox~ng a~lllS: --mo~ ~ pl'l'~ bI I~l~liolll ¢~¢lude ~obao2o ~r relall price maex- . dlffcrcntial¢ tax¢~ b~r t)!~¢ of Ioba¢¢o product. Mas~ m~ia Ot olher in,irma1 ~ means . ~leelive re~lriclion or b;In o1~ ~d~er~'.i~: -,~rlCtlOn or ~rOlUOtJon of ¢~enl~ b2 iooa~¢o companies: l~01tll ~d~¢.lliOn of I~e public, pressure ~ro~. campaigns; regroup or lndi~ idual an I i-~meking cnnlcs healLh edl~CallOl~ or ~n[luellltal gtoup~ ~llch as pohl~¢lan~, allfl~tes, t¢.lcher~ and aclor~. ~pecillc or~tan[elll[ona[ $1ru¢lure~ lind ~er ~onnel I~a~ on ~1 ~illh~hlllly and u~¢ Of tob~lcc~ in l~ealIh ~¢~lillCe, --~ducdlJoll dlr~ct¢~l at healtll per~u,ne d¢~,/[Oplll¢lll ~lnd u~ of ~p~¢ific lobac¢o-rcla~¢d di;~noMi¢ dJ~d ~resq~lmlol~ Dro~cl~/Ires [n S~rcel~i g ~11o c,~u~llon ,¢h~.o1~ Io dt~u-du eh~dr~ from ~tlr~ing hc haI, l~: t L~.'F~liCd I $llpl~r t :1110 ont'ot~rag~men~ to ~n ll-~IllOkln~ ~lm[~t~gn: self help. smoking ce s~alion group~ . illffuencmg reef pressure ~gMnsl ci~arell¢ smok[n~ habil~; expected cost of any suggested preventive at[ion ~hether the eomrmlnity or cot~lllry Call ~flbrd it. and the cost-effecth.ene~$ and cost-benefit of particular actio~£ PROFESSIONAl. TRAINING AND MANPOWER ORGANISATION The implementation of the programme within each participating country will depend on the coordination of the acti~'itles of health care worker., including those in the prmmry health care sector, l~on-health professionals st/oh as educationists and those concerned with socioeconomm development_ and community representatives such as leachers and trade un!on representatives, Health care workers will need to be skilled in identifying risk factor~ the early diagnosls of disease, health educatlon and counselling. Edueation[sts and community representatives will be concerned both with obtaining the active parucipation of the whole community iu the programme, and with the community bealtb educatmn elements of the programme. They wilI also need some training ~o provide tbem )~/ith,~.n ~j~erstandipg °f th~ ¢o] cet~{s of an inlegrated approach to pre- vention, and with ba~ic elements of ed{acational techniques, and aspecls of psycbolog) and sociology relevant to the response of the eommumty to the programme. Guidelines should be provided for the manpower org,anisagon and lraining necessary to implement the progzamme within the framework ~f different countries" primary health care systems. ~i'~ItLE 4. AppRt~ACII~S lO Tiff. (ONTRgL OF R*~ISF O BIJ.;OD IIRI~URE Go~crnnll21~Gll I.eMalive aclmus • --~ompLl[~Or~ m0asurem~n~ of bl~d -ressnr0 ",v hen a p]nl~ ling ~r or r en,/wlng driving I[¢¢11¢u ~'~ g /~lu~a or in furlnatlon mean~ i~ro~ld¢ cog ~i~t ~l~l inter in;glen oll importance of blood -r~,ure control and of ~,~m ph a nee wln~ i~r¢,~rlt~ He.dr h-~l ~ ic¢ ~lnd *~lh~r o[gl ll:at~onal aetl~lll¢~ ~2~%~/~ m~.[ire blood pr ¢~11r¢ of popohllion ~ollp~ through ~p~¢lal ~llr ~ ~ and tuk~ ~ll]oll..u i acunn: ~ ~ measule blood pressure o~ emp[o ~ ~n ~.'1¢~ dl~ t ;IL,~ ~¢x-occ~.l[{onal gloup< .l~d tdke folh ~,.i ~ ~¢f~oll; ! plolnote rned~lT¢lll~llt Of biolld ~T¢~le o[ poplllalitm ill p~lb~Jc pla~¢~ ~rl¢l1,1~ m~rkel,~ clnell i. ihuatle~ I~ - g - and lake rolln~ s ~ action --~• -; • • ~i ~ , 1.~ • , ~ ,t ~~¸ , , • . ~ ~ _ ~ . • • , ~ ,

ABSTRACTS ORCULATJON, VOL 68, SGPP Ill, OCTOBER, 19~3 000B48 .....

t 000840 PERSONALITY AND IQ SCORE VARIATION IN A CAMBRIDGE UNDERGRADUATE SAMPLE C. G. N. MASCIETAYLOIL A. M. MACLARNON AND P. M. LANIGAN Department of Pfiy3ica! Anthropl logu, University of Cambridge Summary, This study, using an undergraduate sample, examines the relationship between len independent ~¢ariab'cs and their iineractlons, on two IQ components and sixteev persont llty ~aetcrs. There was a highly significant relationship between hcth IQ components and subject studied al " university, and between the verbal IQ component and birth order. A mintlonship b~ tween smoking habit a/ad personality was also found. lntroduetlon Individual differences in psychometric abgity scores have been shown to be related to social, personal, and family varlab'es 02errlon, 1979). TPis study examines ten independent variables mad their interactive effects on the variances of two IQ components azd sixteen personality ~'actors hi a Cambridge undergraduate sample. The ten variables comprise sex, year of study, type of school attended, subject studied at unlversky, season of birth, handednes~ birth order, smoking habit, pbenSyeltxhid°i~r::bamisd; (EfTC~tlnntgy a~F~nY ::tdadABObbol°h°IdQgr°~'personaI~ty vacan scores. Generally Females score higher on tasks involving verbal skills and males higher on v'suo-~patlal tasks (Mtecoby & 3aek9n, 1975; McManu~, & M~scie-Taylor, 1993); fem*Ies also ..core sagnificanfly higher than males on - neurotic/sin se~les (Muscle-Taylor & Gibson, 19791. Attention has also been given to the possible effects of type ofsehool attended and subjects studied on school performance (Steedman, 1980), TbJs study examines whether there are IQ and personality differences between students attending grammar, comprehen',ive~ direct grant and independent schools and between students studying sciences, arts or "mixed" subjects at unlverHty. Ccnflieting evidence ~xists as to be reintic nAa~ between intq liger, ee test sccre and season of birth. Some studies (Orme, 1962, 196~1 based on subnormal and retarded subj0cts have reported that the summer and autumn born (May-Octuber) subjee's scored significantly higher on IQ-tests than the winter and spring born .~:~ -- . ~ .M .artlndali endivldu~l~ [November-Apr9)~ However~oma essoeiation either for general IQ or for pelsonality (Crookeg s,ener~ SlackP°pulati°l n970).s Aarnpl:ore receh ntaVoelresults from a retarded group and frOfal ml:tldytOshowLmOn~rata eseasonal effect f19 or63~ Davies, 196a 4;slgnfeant . i~i,!"~ 7Z~Z~m

= Longevity of Women Apropos Constance Holden's ar*dcle "Can smoking explaln ultimate gender gap?" (News and Comment. 9 Sept.. p. i034L it is easy to hefiev¢ that tradition- ally heavier smoking by men contributes greatly to the relatively greater longevity of women. But he~Jer drinking, too, must be considered. Next in line of ctfiprit s, I propose the ~er-dinner nap. Think of the good cooks now enjoying sprightly later years who treditionafiy 3umped up from the dinner table and spent up to 2 hours seooilng around the kitchen cleaning up while habby halsted himseffto his feet, lumbered into the living room, sank into his eas~ ghmr "&ith his newspaper, or stretched out on the couch for an hour of shut-eye. No weeder Kannel finds that -women maintai~ the advantage" as re~ ~fd$ c.~ dloVas~u ]By mortality. This. too. shall change! As ~vomen's smoking and dtinkmg habits come to mote closely resemble those of miles, even the good cook will be piling the dishes hastily into the automauc dish- washer and dashing into the living room to join hubby in front of the television set whiie the cholesteroI accumulates equally in the sedentary vessels JULIA ~, ~ORTOI'I Morton (]ollecfa,tea • University of MiamL Coral Gables, Flurida ~3124 SCIENCE, VOL. 222 000850 ....... tl :.~ ~ /q, Ifg} ~a y/,2-O - C:I

Ethical Theories for Promoting Health Through Behavioral Change Janelle K. O'Conndl James H. Price , ~ " ABSTRACT - ~. r ,, ~t~r~ali~mal]dd~ln'~utiv~juM~lrcrevie'~edi~reladontoc~ngiN~p]t's Nhlviog. Fir~][~', the health ~cl[¢lI~~ ~o]e ~rl behavior change Is ~'~lmllI N a~ INTRODUCTION how best to controi indlviduals who are responsible for thcir own ili health. Health education strategles, sp~ifi- eahy, health promotion programs, are emerging as promlslng policy alternatives over other public health intervendons, These educational programs are designed to preserve and maintain good health and wall-being. Wikier suggests three major reasons why h~lth educators I~ight institute health promotion progeams to • modify unhealthy behaviors: |. to foster behavior productive of heaIth; 2. to decrease, eliminate or modlfy the burden that the salf-destruetlve person places upon ot~er m~bers ~ • ofsoalety and " . ; 3. toeurial]self-destructivebehaviorsandbenefitthe . " ' overall society? ,;.~-~ C¸ Thes~ ethically rg]evant issues are concerned with pro- :~" duelng the gr~test amount of good for the greates ~ number of md valua s. Thus, the purpo e of h s paper is to explore the ethical issues related to health promo- tion and the role of health education in changing be- ¸ haalor. ; • ETHICAL THEORIES OF BEHAVIOR CHANGE " Natural Law /~.: The theory of natural law maintains that all ~. ~ individuals have the right to select their personal health ' behavior or lifestyle. This is a fundamental right based ; Whenever possible, health educators must ensure con- 000851 : sumers' rights to Choose how they want to Eve and die. Health educators, governmental officials and medical personnel have a duty to aIIow individuals to exercise these rights, individuals have a right to decide for them- selves whether or not the health behavior is appropriate, Additionally, they have the right to choose whether or not to act on their personal decision. This type of autonomy, limited to personal choice, should be respected. However, to~ternal restraints on an iadivldu al's actions are necessary when the behavior is no longel a question of self-harm, but also includes harm to others. In other words, individuals are always free to act and make decisions relative to themselves, but not always to others. In this manner, some individual free- doms are sacrified for the welfare of society. Health educators have a duty to provide information necessary to make a rational decision regarding personal health behaviors. Thus, an individual is able to volun- tarily engage in the behavior and accept the respon- sibility for the consequences. Not all members of society will choose the most healthfuI behaviors and this is their right only when their actions do not affect others. How- ever, they must be willing to accept the consequences of their informed choice. UtitRarla nism The theory of soalal utility supports the curtailment of self-destructive behaviors resulting in an overall benefit to society. The utilitarian theory does not rely on claims that the unhealthy are at fault or violating the rights of others. Instead, this theory provides society with'an opportunity to enjoy significant economic gains • and to avoid loss. However, for the utilitarian argument to be successful, a moral principle is necessary to distin- guish between basic and nonbasic freedoms• Because no me hod ex s s for de erm nlag which bet es are basic, health educators cannot be certain that depriving people of pleasant self-destructive aetivitlas, such as smoking : 476 * JOSH • October 1983, VOI. 53, NO. 8 50000 4B :

I Behavioral change through persuasion gives the professional a claim to superior knowledge of what is good for everyone and attempts to mold everyone's ' behavior to one p0rfect image, Many people may not agree with the professionals' judgment that certaln•llfe- styles wilt lead to a longer and healthier life• A strong : belief in behavior change means that the hcakh educators would have to do everythirtg in their power to ' bring about change, with or without the individual's • . OOnSCtlt. • -. ' ' : Finally, if the objectives of health educators are behaviorally oriented, then they must accept being regarding their personal lifesJyle c£n either improve or detract from their personal well-being,t) • Health educators should prepare individuals to make . decisions that are health generating, They should pro- vide informadoh so individual hea]th behaviors can be determined based on informed choices• In this manner; ' 7each individual is responsible for their personal choices and any dictrlmentaI conseqtmnces that may result. Health edhcatdrs should intervene into personal decls[on making when the lives of others are being threatened or harmed, a condition that occurs more frequent!y than we want to admit '. ' :judged on how well they achieve such behavioral Reierenc~ • changes. •.." •~: . •" i¸~ At what point in time should the government in ter fer¢,~,~.~ ~U:~¸ I wikk, r Dh C~ve Men,ares in Heahh Promotlon: Can They ~ in the yes of lad V dun s 0 es ah sh protec ve mea ' .~bc.'Ju~tlfied? 14eatth Ed Men 6:223-241. ]978. ' • : ~ .... .) 2. Beauchamp TL: *the R~gulat[~n of Ha~rgs a0d Hazardous :i SUre$ heil~fidal to the m&iortty of the population. At ~•B~hasiors I~ea#h Ed Men 6"2'13 257 1978 : i • what point do health educators intrude into the personal ~k Benjamin M. Curtis J: Ethics in NurMng. Ntw York. Oxford • lives Of the eollsumers, infringi:qg ell their rights as¸ Unlver~ily pre~. 1981• - , ~, indivlduals? Pellegr[flo suggests that the line b~ drawn 4. Pollard MR, Brannan JT: Disease P~evendDn ~nd He,lib r !, , • for governmental a~qd public interferenice based On the Promotion Inltlafives: So~e Legal Cemsi~emtio~s. Nealth E# Men • . • 6:2] 1-223. 197g. . • =i .~ connection botween the evideDce that a speci fie behavior ~ ~. Nakam~ra R, lverson D: Pr~tige of Heahh Educators within i • does or does ilOt cause a disease. Three categories are the Health Care Delivery Sy;tera. J $ch Health 47:296.301, 197:. suggested: eettathty, suggestive and speculative. When . "': 6. B~a~champ DE: Public Heahh and Individual Liberty. Ann• the evidence is vr~ry strong or certain that the behavior • gev Pub Health 1:I21~6, 19~0, catl~es the disease, such as cigarette smoking calasfng 7. Simonds SK: Heah~ E~ucadon Today: B*ues and Chagertge~. lung cancer, then the government is justified in applying coercive measures. When the evidence linking personal hahhs to specific illnesses is only suggestive or speculative, such as the , relationship between high fat d~ets and colon cancer, in- voluntary measures would be difficult to morally defend. In such cases, methods of health education should he employed that allow the individual to decide which choice to make. .... Hochhaum would seem to suggest that in the case of ~ee~ative or suggestive disease, health educators must • be able o convince people that their goals and needs can be more easily achieved by engaging in behaviors that ..... '" h are health promoting,'~ The value of these behaviors are likely to be secondary, as most people tend to appreciate the behavlor*s health value after they have adopted the behavior and find it to their liking (i.e., brushing their teeth). 2 co ctuslo . ~ As beahh educators, it is our duty to promote protec- tion and preventive health styles. We are Iotally for ~,~:, health promotlon programs by the government in our communities and schools. These programs foster recog- nition of one s health and promote individual respon- sibility for health• The choices an individual makes J Seh Health 47:584-S92, 1977. 8. Fader, RR, Faden AI; The Ethics of FlED ~ Public Health Policy. Health Ed Men 6:181-197, 19"/8. ~. Mendc[sohn H: Which $ha[I It Be: Mas~ Education or Mas~ persuasion for ~lcal[h. Am J Pub Health 58:13~-~37, 1968• 10• pcllegrino E: Health Promotion as Public polity: The Need for Moral Groundi~gs. pt~v Med 10:371-378. 1981• II. Hoehbaum GM: Behavior Change as the Goal of FIea[th Education. Em Sigma Gamman t3:3 6, ]98L 12. Hochba~m GM: An Alternative Ap~ach to Health Education. Health V~tues: Achieving High Level Wetlnem 3:1~7-201, 1979 I~• Block ~L, Newton J: Should Health Behavior Change Be A~ Obj~etlve Of School ~Jealth PersonneI? J Sch Health 5hl89 190, 198[• danellv K. O'Connell, MA, Doctoral Student, Depart- ment of Health Education, The University of Toledo. James H. Price, PhD, MPH, Profesor and Chairman. Department of Health Education, The University of. Toledo, Toledo, Ohio 43606. I School Nurse Day ] JAN. 25, 1984 Providing Health Care for the Nation's Future A Health) C•hilg: The Key to th Basl~

~, ~ ;~ t indicate ~4mthcr th~ z)~rnug~n Js aetk'ated~3 during an aeme ~i ck of hmditar~' anglcedem~ would be an expected finding. The ~. m ¢~z~.r~ i~13 r~moved fromthecirculadon kison] .--~ utra ed E prote.e~ inhlbitors, C I inhibivor, or alph~te ! ~ tcr°gl Ul of low levels ofpr e~alliDei n a¢tiv. sn t~¢p~ ~ orpre~lllkrein anIige~ (Fig. 2 ~ r paper) k Logen a~ivatlon In Ck o.4 AI t hough ~" r r Figure2 ~at of prekallikrfin was present in . . lmt~se in r do not mean to imply, that in all X ~ ¢&c~s °r acu~ ry angloedema 50 per cent of tot~[ .~ is ~omplexcd to inhibitor. This is no indicatlon of whether those who do not di~ early co~t society -. more From ill health !Ixa/~ the oottsmoke~, and iftoj how m~eh motx. I do not kllow which way the I~alance tl¢~ b~t ~usp¢¢t t~al Lh¢ • lung e~ncer s and thromhosc~ m~.¢ sa.*e tnor~ mont'/than th~ e~st Of earing for the smoking¸ ~nd nonsmol~in~ sur.@ors. GZOX~Z T. WA'CCS Birmingham B4 6NH. England The Goaer*d Hos#tal Temple L'nlver sit~. The above [ett¢~ ".~er¢~ refer~ed to Dr. Cad¥, who. offers the foI. hwing reply: • To t~ Editor: D~s. Rosen a~d Watts false intexestlng points in polltlcal ~0d eeonomlc decision maldng rcgardlng the payment eft" medical CXFe,Ses resuhi~g from personal habiLs -- ex~en~ that the maj0r;ty of the population avoids by h~havlor r~str*dnh good he.a]th hahltsj and a~dane¢ elf excessive r~sk. l~tlra~¢~ Or the ~preading of ri~k over a large I~p~latlon Io ~id catastrophic ¢o~ ~om ~c Ic~s for the ~r~d~vldual~ was cntlce~e~d a~ protectlt~n from ~ct$ of God,. o~ ch~ce ~.~¢nLS. insurance wa~ not intendctl to Spread the c~u ofsd~induced economic ]ossc~ among ~hose wltMmt that risk. [n times ~f economic re*traint, ~pcdally ia a period of poblle ~n- ~ ~bout health ¢~s% it sects onIy fair to make the ~¢'gm¢llt o{ s~ie~' that ddlberately ircur~ ex~slv¢ Or ~ique fi~k p;ly their own ~y ~y varh6on~ of the assigned-rlsl~-pool concept. This should apply as ~¢1[ to mot or~ clisL~ who r erase to ".~ car heh~¢t~. ~at omobit~ dfi~.¢r ~ who refuse to wear se~t beits~ a]~hoIie~7 smok- ers, and the roorb~dly obese. Gra~ted that man~ Of th~c ~0eha~or ir~.~t~ arc ~txslderod *~d [~east~.~* it nevertheless s~ tx~onab]e and equitable to reward those in society who avoid ex~'sslvc health risks hy reducing their costs. This ~ili u~ate powerful incentive. ~q~cou raglug r~o~h[e h~a[th pr a¢li~. Dr ~ose~'s snggest~nr~ Or taxation at the point or c~ga~ette roman* ~act ure would ~,oi~ problerch* of illegal rnarkctlng to av oi~i last tlon and dil~eulty {~ collectlons. It .vould also pmduo~ a ~ha~ in,tease ir~ price, and ~eh an iu~r ease h~ been sho~.~ to pro~uee mar~ redt~ct ions in eonsump~. It ~s an e-xee]len t idea a~d could ~s wcJJ be applied In alcoholic be~.erag~2. I have 11o answers or economic dam ~o offer iu l~S 1:a3~ to Dr. W~tt ts' comments, attd I r eo3g~iz e th~.t th~ ~cono'm~e~ may ~lt both ways. In England~ it has beer. t~tlmat~t that the ccssatlon ofa~] sr0oki~g ~2o~ld result [r~ h(gh e-osLs to ~ov¢l~mcr t t feolll lxdtlce~ tsx irttake at~d ~ne~as~ old-age L~neflts Howe~er, our obligation gs physid ans should be to red uce health risks ~d en~urage comtmc- d'¢e h ~t biLs. '1~¢ ~ o~ i~d~vldual ~:onomlc ~n~entlv~ s~ro~ ,or only reasonable but pzobahly effective. Boston, MA 02215

• •{~ + file mi~lakef. I. 00085 MEDICAL CARE AND THE COSTS OF SMOKING T.M. Vogt Summery, rntroduezlon: Trends in Ctg~ette Consumption; Dir ~ct and Indirr~ Cost E~tlm~tes: Di~cu~ion References SUMMARY The [ncteaseM risks of morbi~[ity and mortahty associzted with dgarette smoking ere we]l ~st ablPshed Effot~ to ¢m]c~laI¢ the e XC<'.S s costs of m~[ica] care ~s~oc[ated with ~g~relte smo~clng have rafted prlmarffy on exlrapolations from the e~abl JsherI mor- bldit~ ~nd mot tality fl ~fferen~.s This arllcle presentx ~ r~Aew of vzr~ou$ esl~l]~ alg$ uf the eX~SS dir©~l and ]n~/r~t costs asfo~ated 'J:it h e)garel~e smo]I]n~ and d~$se$ why there Is a substaJltlal vattahon in those estlm~tes. Smoker~ af~ r~L'~ily dlff~rc Jlt from nonsmokers i~ ~ variety of demographic, vociaL and hehavioraI "~'ays. Sino~ the utilizat )n Of med{¢al care scrviee~ is also related to many faclcrs other that~ rite simple presence or absence ¢tf morbidity, tt is ]ike[~ that esttmating ex~s ¢ost~ of care by pro- jeetln n from morbldffy di fee renc¢s is nnt t~rrib[z ~ccurat¢. Gr~ving pressure to place +*health tax'+ on cigarette con~umoti<+n makes it critical to ~rrlv¢ at rtllai+le and repeatable estimates ofexc~s~ co,is a~sociattZL with smoking, + - Thomas M. Vogt. MD. Director of Ept demio[ogig stud~m. Health S*rvic*s Research b "~ C ~ ~ • C~nler, Kaiser Foundation Hospitals, Potlla. d, Oregon, USA. I Ma mg addre$~ Health S*r vices R~s*ar~h Ce~ter~ Kaiser Foundatiun Hosplt al~+ 46 I0 S.E, Belmont St.. portland. OR 972t S U,S.A. ' + Recei~edSeptember 13+ 1982 * , l(ecelved i. reff~ed form Feb~y 24,1983 ~ CoPrtigh~ lg~3 by Tech~osdar LId.--Intemational Scie~I~e Publicalion$ ~ I • PrnIedinl~rae ~ I • 121 ~ I / !

Medicine and the Media ( ~r~ ~k :~ .... ~ ...... ~ !i:¸

! rL L 00085S r . Higher "sin" tax favored to aid Medicare T~¢ Federation of Amerlcan Means Co~itte¢'s health ~crned about l'~slng sem- Ho~pha~ (FAH) has put its subco~lmitt~, would ~tend £~ent funds wltbout addinB to support bebi~l a bill that tbetobacco~andhwTea~ tbopa!~ollorincon~taxbur- would add some S50 b~llon |be tax on d~tiUed ~pirit~. den. sccording to WeikeL o~r the re~ 10 yBar~ ~o Calffn~bcb;]lI'tbemost~q- "V/=al~or~zethatc~er~ Medica~e's No~i~al |nsur- m~bl¢ form of ~enue en- oftoboc~oandal~boltend~ an~ t~t fundi hanc©m~ut available,1" M, util~ more medical ~c~, Kehh Welke], Pb,D.. FAll and it is onl~ fair that tboy T~e b~l. introduced by Rep. p~de~t, ~d that "bnds¢~ pay a bit more ~han .~onu~ Andy Jacob~ (D~I~), chair- ~u alone v~n not solve this ers,~ he ~aid, • W of the Ho~ Wa~ and problem," T~ FAH is con- ~7CI

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500001254 M L)

Plant Ph~,~oL (1983) 73, 228-232 0032-0889/83/73/0228/0M$00.50/0 :/~ i 000857 Shikimate Pathway Activity during Shoot Initiation in Tobacco Callus Cultures~ , ~' geceived for l~ca~ca Mmx~ 10. 1983 arid in revlged forum Ma~ 15, 19g~ • . f • ":'. Plant Physiology Research Group, Department of Biology. UrdverMty of Calgary,

"I~-~'AppIG~aetl198~. 66;233 239 © SpfingeroVeflag 1983 000858 Studies on the use of toxic precursor analogs of opines to select transformed plant cells G.A~ Dahi and LTemp~ [nstltat de ,~¢xobiologle,Unive r th~ de Parls-Sud. B~timcnt 409. I:-91405 O~ay. France Reeeivcd~pt~mber27,1982;AeeeptedFeh~uaq 19,1983 ¢.~mmuaieated by P, Mahga Snmmary. g-(2-aminoethyl-)L~=ys~eine and L-tartar- atone were less toxic for octopi~e-type crown gall tissues that ¢oatained lysopine dehydrogcnase than for other crown gall or habituated /issues. These a~a[ogs "are substrales for lysopthe dehydrogenase ia vitro and in vivo. Taus toxic anafoga of amino acid precursors of opines may be useful in selecting for cells that contain • an opine dehythoganase. Key wo~Is: Selection - Amino acid analogs - Opines ~ Lysoplne degydroganas¢ - Crown gall -A grobacWrium , Inlrodueflon • Crown gall turnouts result from the transfer and int¢- for re~iews oa the crown gall systemL lhis Iransfetred DNA codes for enzymes that ealal~ze the bm~nthesi~ of :new substances, generally called ~oplnes"~ that are . not pre~ent in uninfected plant cells. For example, • :' ly~l~ne dchydrogenas¢, which is usually present in oclopine-type tumors, catalyzes the reductlve eondensa- " • tlon of pyravate and L-arginine, L-lysine, L-histld/ne, ; or L-omJthine to yield octopine, lysopine, histoplne, or oetopinic acid, respectively (Fig. l). Nogalin¢ dehydro- ganas9 catalyzes similar types of reactions in nopaline- type tumors, resulting in reduetiv¢ condensation of alpha-ketoglmarate and ar~inlae or omithin¢ to yield nopagne or nopalinie acid. " !~ Tills paper pre~en*s out initial results on the use of toxic anafogz of the amino acid precursors of the octopine family of opines to ~leet transformed cells. Tae~e ~tudies were based on the idea that a toxic amino : :.~:~. grat~on into plan hue ear DNA of a 10-20 kilobase acid might be metabolized in vlvo to a less to,de or ;. ;' ~egmen d6dved from a q~i-p asm d of a viru en Agro- non-toxin opine analog by" lysopine dehydrogenase. 7 ;*~,': baeterlumtumefaciensstraln(seeKahlandSchell1982 Tgus, transformed cells that contain lysoplne dehydro- : a HOOC n ..... '.'~ 0~= ~0 Ly~pj~e dehydrogeral~ [ ~ ~O . :~, C O ÷ H~Xq~-H • H~C-N -H •

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0008S9 INSECTICIDE EVALUATIONS FOR TOBACCO INSECT CO~TROL Gary A. Herzc Research Entome legist Evaluation of insecticides for control of Insec~ pests of flue-cu£ed tobacco ~emalns a high research priority. This work. ~n p~r1~, a[d:~ ~eorgi~ Cooperative Agrlcultural Extension Service personnel ir makilg recommendations ~o producers on the best ~nd ~ .! most COSt effective materials for use in their insect zontrol .k~ programs. Prnducers may thus make s~und management decisions in _ k-~ choosing the ipsect control m~terials to best fit their needs Tnse ;tlcideE which were ~ested include ~terials which ~re ~urrently registered for use ~n tobacco ~s well as some co~pounds .~\~ which show some promise as effective control agents. Upon registration of these materials, we will nave data available ~, co~cernlng their spectrum of ~ctlVlty as well ~s the proper dosage rates for optimum levels of ~ontrol. Soil Applled Insecticides for the Central of Adult Tobacco Fle~ Beetles Materials ;~nd flethods: Replicated small ~]ot trials were condu't~d [~ evaluate various insecticidal compounds and ~pplic~loD ~echiLiques for the ~ontrol of early season pe~ e~ flue-cnrcd rebaci:o. Th~ tObaCCO Was transplanted on April 12. 1982. The variety used was NC ;326, a standard "old-line" variety Th6 nlots w~re arranqed in a randomized complete block deslgn witt ~ re~[ic~tlons per ~reaxment. Plot size was 1 row w~de bv 30 ft lo~3, Pl~nns were spaced on 2 ft centers in th~ row with a 36 in row spacing providing a pl~nt population o~ abo~t 7 000 p~ants/A. Narrow row spaclngs were used as since l~sect~c~nt~o] .onslderatlon. ?;ere the prlmary objective of the study tanner tha* ~gronomlc charac%eristics. ~{,cor~neDdod production practices were carried our in the culture of the ~ibaeeo. Tillam and Devrinol was applied and incorporated a[ a ~ate of 4.0 - 1.0 Ibs AI/A, respectively, ~rzor ~o transpl~nting for weed and qrass consrol. Ridomil (I qf/A) was tank mix£~ w[th the herbicide for pro~ectio~ from blue ~old. Pernospora tobacln~. Fertilizur (4~8-12) was applied at a ~ate ~. of 1,000 ibs A prlor to transplanting and sidedressed with 800 ~- ibs/A approximately 3 weeks after transplanting• ' Applications of insecticides in these studies were mg~e . ~ o either as transplant water additives or as sldedress appl~cations ~.~ ¢ollowing transplanting. O~e treatment was applied as a foliar spray which served as the control standard. There was also an --~. untreated control. The following procedures were used In making the applications: 7 J D

TOBACCO INSECT CONTROL - -- David Jones and Herbert Womack Extension Entomologists - Statesboro and Tifton - 1982 Highlights "'" " Insect infestations in tobacco were more severe in [982 • than in 1981. Tobacco hornworm infestations began earlier _. -~ tha~ ~ormal and persisted througnout the season, tobacco bud- worms required more insecticide applications than in ~he pre- vious year. Some ~reas reported difficulty in controlling bud- ~,~ worms and repeated insecticide applications where necessary to brin~ infestations under control. The necessity for complete coverage with insecticides was demonstrated on many farms. " ~:+~ Wireworms continue ~o be a problem beltwide and growers who use fumiqants as a nematicide should use an insecticide in transplant wa~er for wireworm control• Flea beetle and ~phid infestations were scattered and not as severe as i~ ths prevlous ~. year. Tobacco Pest Managemen~ Program The Tobacco Pest Management Program expanded into ~wo addi- tional counties in 1982. The slx counzles ~articipating i~ the proaram included Appling, Candler, Coffee, Emanuel, Montgomery, and Treutlen. A total Of 2097 acres were monitored by seven scou~s. Scouts monitored insect infestations, reported the presence of diseased plants and made observations to ~ssist growers in making decisions on toppin~ and sucker control• Soil samples for nematode assay and fertility were taken from fields . re be plantP~ to tobacco in 1983. -e '~ Field tralning and assistance was provided zo the scouts by Cooperative Extension Service personnel throughout the season. , e " i

000861 :i- IN~ODUI~ON Insect haemolymph ]s in general an unsuitable bath- mg medium for insect nerves: studies of the central lervous system (CNS of insets whose haemolymph ion levels are bl~iTe have contributed much to our understanding of how homeostasis of the neuronal mvironment is achieved ITt'eheri~e. 197~t~ The same approach should be useful for [taming how the ~europil¢ ts protected fruit potent~alIy toxtc organic compounds, be they merabolites or xenobiotles. Self. Guritrie and Hodgson (1964a) showed that the to- bacco,homworffz Can tolerate large quantltt~ ol ingested nicotine, the latwa© rapidi) excrete nlcoline in an unmetabo]isod form using, as demonstrated by Maddrell and Gardnier 1976 a powerlol blood-to- lumen transporl system in the Malpighian tubutcs. Newrthele~. excretion is not• on its own. sul~cien t to protect the CNS from the toxic effects of nicotine. Pieris bmrsicae caterpiIlar~ an~ reodtiy killed by inges- tea meotme (David and Gardiner 1953) evcrt though they excrete nicotine at impressively high rates fMad- drell and Gardloer 1976L Moreover. in spite of exertuon, the haemolymph of Manduea larvae fe~d- s [n8 on tobacco contamz about 2.3 x 10- M nicotine (Self et aL, 1964a}. Confirming the insensitivity of M~duca to nicotine is the observation that feeding behaviour in the larvae is normal 30ruth after an injection of nicotine which produces an loltial con- c~ntration of about 1.5 x 10-~ M, even though b]ood-nicotthe levels are still about 3 x 10- M aRer 60rain. Self et eL (1964a) postulated that the w~ter ,~, solubility of nicotine (ma amphiphilic molecule) at ,physiological pFI might delay its movement into epres~nt address: E~I of Biology, University ni" Ottawa. O~tad0, Ca0ada, nervous u~tms. Considering however, the Manduea larvae feed cOntlrtnola~ly over a r~L~raber of w~ks iMcFadden. 1968~ and that a fraction of the haemolymgh-nleodne would always be present in the unprotonated, lipid-saluble form. the CNS would nect~a~ly talmhbfat~ ~mth th~ haemo.falphonlco- Line In the vertebrates, excrelory organic base pumps art: found both In the ~xcretory systLm3 ~rena] tubulg$~ and in the CNS ~chorold plexus~) ffc~hino and Schanker. 1965: Wether. 1973L Since Manduea Mni- phigian lUbU[eS have alkaloid (orgamc I:es~l pumps (Maddr tel and Gaediner, 1976), it s~m~l fih¢ly that, by analogy with the vertebrates, similar pumps could be used to prot~:t the CNS. Patterns of nieudne uptake we~ studied to examthe this possibility. Earlier whole animal studies of Mauduca and other lepldoprgrous tobacco-ft:¢~lers rcve.alod no r~¢tabo- lism of nicotine, a~thoug~ oxidative metabofites were readily detected from a variety of other insects ISeli etal.• 1964a.bL ft Was thus st~rpnslng to disco v~r that the CNS of Maoduca de~ metabolise nicotine: this greatly ~0mplicates the interpretatthn of uptake data. Nevertheless. it is of inter~t both in its own right and as a point of ¢ompartson w~th the mammaIs, whose CNS do not metabofise nlcudne, or most other xenoblolies, sthe~ detogification by tissues such as the liver (Hanson. Hoffman and Schmit~rltxv, 196¢) nor. , really keeps blood-levels of ingested xenobiotics low at the niood~brain int~rth~. The chromatosraphlc characteristics of metabo- lites produced by Manduca CN5 arc unlike those of most nieot the met abolit~s deser thed in the iiteratn~, Preliminary studies wet© made to detCrlmne if the rretabdiites could be conjugates and the question of whether pruduedon of metabothes could be affgct~l 8O7

]'boor Appl Gcnet (1983} 66;203-207 000862 © Sprlnger-Vedag 1983 • " Ah pl i edbyp pl tfu i diti • efero asm c state induc roto as sion s a necessary con on for detecting rearrangements in Nicotiana mitochondrial DNA .c F. Nagy, O.Lfizfir, L. Menczel and P. Maliga • I~U ut¢ ofplant Phyfaolo~', BRC, Hungarian Academy ofSoeace~ p O. Box 52L Szeged, H~6701~ Hun~tT : Rtedved January 18. 1983 Commumcat~d by O. M~ehcrs :'.: ~unma~. Mitoebondrial DNA (mtDNAI restriction , palterfls were stuthed m muGanl, cybrtd and somatic ,:'~'~: hybrid plants regenerated ~om Nicotiana protoplasts. -: ": - I has been shown tha neither components of the • ¢mlture medLa used for protoplas cu ure and p an regeneration, nor the antibiotics streptomycin and '.: ,_ t;ncomyein used for the mutant seIection induced ~, alterations in the mtDNA. No rearrangements were • detected in the mtDNA of plants derived from homo- ' plasmth fusions where the mtONA of the parents was , , identical as judged by mtDNA restriction patterns. • . -. "I~ere wcJe rearrangements, however in the mtDNA of each of the aybtid planIs derived from • " heteroplasmic fusions. Resection patterns generated :,-,;-' by Bamiffl and Sail restriction ¢~adonueieases were somatic hybrids, rearrangements in the mtDNA were " " different from those of both parents, and were corn- confirmed by hybridizing E. colt ribosomal RNA genes f posed of parental and non-pa;-eutal fragments, to the restriction fragments. In Petunia interspecifie • .~±.. , ,. , . , , somatic hybrids, the mtDNA restriction patterns were . ~ Eey words: Nieotiana - Mit°cbondrial DNA-cybrids also non-parental (~L Hanson, personal communina- . .~@72,~. Somatic hybrids " tion; A. J. KooL personalcommunication). ' ~ ...... . It has been shown in Zenmays that extensive re- - c ~, ~" ' "'~arrangements in the mtDNA may take place during ~:" "" : .... " • - cell culture, a phenomeno~ which does not normally C:." , Intreduetlo. , oocttr in plants (Gengenbach utah 1981; Kemble etal. - ~ , 1982). Jn Nieotiana no studies have been made on the .._ L-ytoplasm~c nnxang and in-parental transmission of the mtDNA of plants regenerated from unfused proto- : " F .. ~ ¢.~toplasmle organeiles does not occur during sexual plasts. Therefore, the possibility that alterations in the -.~,~. reproduction in the genus Nicotinna, or in many other mtDNA were induced by ceil ¢uh~e conditions has ~ ':;-" flowering plant species (Sears 1980). Somatic cell fusion not been excluded. Tire effect of polyethylene glycol, • " makes it feasable Io produce ceils with mixed "bl- the chemical agent used for fusion induction, has also • . parental" cytoplasm in these cases, Mitochondrial not yet been studied. Furthermore, it has not been ,. "~ DNA (mtDNA) was studied in two types of plants excIuded whether streptomycin selection, employed in ~denved from cell fus on In somat c hybrids the ehro- one of hese studies (Nagy et aL 1981), is responsible mosomes of both parents were present as the result of "for some of the cbanges in the mtDNA. Such a study as .'~ nuclear fusion in the heterokar~ons. In the cybdds, the present one is justified by ~ports showing that ~;~ chromosomes were retained only from one of the strcplomycin induces mutations (Sa~er 1972) and re- \ par~mts as the result of the segregation of nuclei in the primar), protoplast fusion products. (Note that ha the • literature somatic hybrids may be ~efcrred to as aybrids " in order to indicate the hybrid origin of the cytoplasm, "Ibis terminology does not distinguish the clones according to the fate of nuclei in the primary fusion product. Somalic hybrids are derived from o~lls with a r mixed cyloplasmI thexefure in those eases we do not use • the term ¢ybrid.} • MtDI'~A in Nieotiana tabacum (Belliard el al. 1979) and Nieotiana sylvestris (Galun et aL 1982) ¢ybtids, arid in Nicotiana tabaeum+ Nleotlana knlghtiana somatic hybrids (Nagy et al. 1931) was non-parental, as judged by mIDNA restriction patterns. In the case of the

Sprthger-Ver]a8 1983 Regeneration of fully nitrate reductase - deficient mutants from protoplast culture of Nicotiana plumbaginifolia (Vivianl) LNen=t~tiu~ IL Dirhs and ~ Jacobs Planten~enetiea, Vnje Univerdt ell Btassel. Insthunt veor Moleeala~re Biol~gae. 65. Pnardenstraat B*I640 SL Gene~u~ Rodek Be~ium Received MayS. 1983 Communicated by G. Melehers Summaff. Pro~up]ast-dndved cidonies of haploid N.plumbaginifnila were selected for by chlorate resls- ta~ce in media supgleMented cat]] casarodno acids. Eighty resistam lines were confirmed by a second passage on a higher concentration of chlorate. Fre- qutaaey of spontaneous mutation ranged from 10-s to • Ill~. FiRy of the resistant lhaes could he regenerated into plan~, and 30 were characterized biochemically. bYme~ pereem wtre fury defidem for nltrat¢ mductase acfieiry. The Iines were th~L.hex test ed for xanthine fiehydro- 8enase actMty and subsequendy da.,cifi ed as defective in the upoenzyme (n/a type, 26 lines) or the cofactor (cnx type, 4 fines). Two groups had been identified up until now within the cnx type by growth tests on high concentrations of molybdate supplied ~ the medium. Nitrate redu'dase deficiency" was stably and con- tinously expressed in both variant ceil cultures and analysis demonstrated that hitrate was inherited as a single ~ecessive 19801, cell suspensions of ~oha¢co (Midler and Gr~fe 1978: Miifier 1981) Damra innoxla (King and Y~anna 19801, and Rosa damascena /Murphy and Imbrle 1981), or protupIast cultures of N.fflumbagfnifolla " (Marten etaL 1982a). Direc~ screening for in vivo " . NR activity (KJeinhofs etal. 19801 and a total iso- lation procedure for auxotmph selection (Strauss . et aL 19811 also enable the selection for NR deficiency n bar ev and Ild'OScyamvs mutieus respeerively. Except " for certain barley mutants reported by Bright etal. " ,. (1982). all those islated at plant level were shown to "~' " maintain residual NR activity. Fully NR defieiem Lines . - were described in cell suspension anti protup1ast eni- .. ! lure systems, but plant regeneration followed by genetic analysis was reported only in the amphitetruplold species N. labacum. The tobacco mutants were shown tO be double recessive m~a~ants for both Ma and enx types (Mailer 1981, 19821. In the ease Of N.plumbag~- nifolia, plant regeneration was achieved only in cell nuclear gene. Key words: C, enefie analysis - Inheritance - Nitrate reductase deficiency -~Lplumbaginifolia Introduction Nitrate reductase defieient mutants (NR-) have heert reported in several plant species• In most cases they • were selected for by chlorate reslstance, one of the rare .... available positive seteenlng procedures leading to'an auxotruph phenotype. In this way the NR- types were obtained using M2 seeds of Arabidopsis thaliana (Oostindier-Braaksma and Feenstra 19731, harley (gd~ht ¢tal. 19821, and pea {Feenstra and Jacobsen ! gnes with residual NR activity (Morton et ab 1982 a). In this paper we report on isolation, re and bio¢fiemlcal and genetieal characterization of ~: haploid protuplasts ofN.Flumbaginifalia, atrue diploid . :" Materials and methods Protoplast and callus cullure. Screening conditions Haploid proloplast mother plants were cultured as previously described (Negratiu 19811. Two haploid I/nes, PI and YI- AECg~ were used as a protoplast source, q[lae latter contains a • mutat]en for resistance Io the I sine analogue. S~mino- ethvI-L-c~steiae (AECR; menogenie recessive, unpublishedh : Media us'cd dudn~ the ex~efime~L~ are listed in Table 1. Ti~ey all ~ ere sterilized b~ aatoclavin8 ..... . % ;

..... .~ A Genetic Analysis of the Association Between Resistance to Meloldogyne incognito and a Necrotic Response to Infection by a Strain of Potafo Virus Y in Tobacco Reheea C Rue y, E. A. Wernsmar,. and N. T. Powell 000864[ Researeh associaleand professor• Deparlment of Crop Science. and pro[essor• Departmgnt of Plant Pat hoiog), respccatx eb'. both at No[th " Carolina State University. Raleigh 27650. Jovrnal Series Pa~:r 8632 of the Noah Carolina Agricuh ural Research Service. Raleigh 27650. Use of Irade mimes imp]tes neither endorsemem of the products named nor criticism of similar ones not mentioned• ~Aceepted for pubhcatlon 2 May [983 ABSTRAr'T ÷ Ruh~ R.C•,Werasman. E.A..andPo~e[LN•T. 19$3. Agenetieana[ s[softheassneiatlonbet~¢enresistane toMelodo . e. gnltaandanecrot]¢ - : .~sp~nset~infecIi~ya~trainofp~taI~`~[~usYi~t~bacc~Ph~I~path~i~gy73:~4l3.I4[8. (~ ~;~ ~'t~'~n~ 7 . • Thegenetmbasisfotthe isso~Jatlonbel~eenres[stancetathefoobknot ner~eto~e gefo{~gj,~ lnco~ni~, and It se~'~ ~ISCtll*~r UeCr~l$ =n ~esponse m infectinn by the M N~ stm~n of pmam virus Y tpVY*M~Xm )in '[ob8~o (N~colJa~ l~¢'Llm L,t was [fix~stl~ated. MOI'C titan I~.0~0 F: piants dcnved from roobkrcat re~i~tant ~ ronl.knol susceptlble crosses were ino~ulatedwkitbothpath~eens. At[plantsthztdk[~otde~elepnecroslsln response to the vlrus ~cr¢ roobknot susceptlbic: i¢. recor~binatlnn bet~ een root-knot feb[stance and ~he ned:rot if response to the x irus ~s not detected. E~chlraiti~eontrolledbva nge.domman $¢n¢locatedonchromosome G of tobacco b~ mona am c and nu om c ann ys The v u 4nduced tecros[s may be a p~totrop~¢ r~pon~t of lh¢ gone ¢oatro~hng root-knot 'esisI[t n ce, pin,is ~osse~s] ng both root-knot J~ p~*~y resistac, ecde~o~ tittle or no necrosi~ pVy r~s] lathe i eon~ toned by a fee* s ~'e gehe tha appear r~ to I~ epistle ic to the gent connie [onlng root-knot resistance. A search ~as made among Nicot~na ~pp. for I new $ou~e of toot-knot • r~s[stance not a~soeiatcd ~{th tb~ n~ctot[¢ n~actlon to pVy.M~a. P*~otmna iomer~t~a, ac~*~io~ ~. was highly ttslstanz to the nen~at gde , and appea~¢d to be [mmur~ to the v~r tls. An assoeiation between resistance to the root-knot nematode Meloidog we ncogn ta(Kofoldand White)Chitxsoodandase~er¢ .ecrnt]c reaclJoa to a strain of potato ~irus Y (PVY) in tobacco (A~eoduna rabacum L) was ~epor ted from Virginia by Henderson and Trout man (ld)• Later. this strain of PVY ~as report~ to be ' one of thrg~ atralns that can be classified on the basis of their reactiort on flue-cured tobacco cultlxa~ reslstant or susceptible to the root-knot nematode (]2). The MSM~ strain (PVY-M~M~} induces vein-banding and mottling symptoms on both rool-k noz- ~esistantand-suscepllbleeultivars; the MSN~ straln{pvy.MsN~) causes necrosis on root-knot-reslstant eultivars, bat t'fiild symptomsonroot-knotsusceptlblecu rostand heNSN~s an (PV y*NSN ~) induces near osis on all culti~ar$. All tobacco cuhivars that have a single gene for r~istance to the I:OOt.knot nematodede .e opse~ evascu a n~ o swhet~ nf¢c ed With PVY-M N , but ]title Is known abbot the genetic basls for this : association These ~.wo eac ons could be controlled by t~o independent genes in light linkage o by p e o op c ef ec's of a single gene. ~'$" Resistance to the root-kn0t nematode is controlled b~r a single ~:dominant factor, or a chromosome block thai behaves as a single r factor 9LTh'.~ res tahoe reported ~ or g na ed~ omT, , 706 and v.~s trat~fer ed Into floe-cured tobacco cu t vars by E• E. Clayton in the J930s (6). All modern tobacco cuhivars resistant to the : root+knot Itematod¢ derive re~istan~ from Clayton'~ original incompletely dominant (15). ~" ~t-knnt resistance in tobacco cu~inars hIvoI~ es a necrotin o¢ h~perse~siti~ reaction in the roots that pre~ent~ the nematl3d¢ from establishing a feeding relationship. This reacdon is temperature depelldeht a~d is not ¢;~p[ess~I abo~e 32 ~ Soil temperature { ] 0,21 ) The ~ ~r t/s-lad ~d necros~$ ts a]~o tempel~dur¢ - sensiI}Ve and i$ inhibited al the sRn~ gempeFetIl/r~ as rooI-knol f~sista~eei]~gTheserep~l ug~estlh~thvp~r~n$~ti~igvioroot- knot a nd PV Y-lad uced necrosis may be plelotroplc responses of a • ~ng]¢ ~ene. This iS a potential p~ob Ie Ffl in ~onh Carolina bccatlse • the incidence of PVY-MSN~ in the state has been incrc~sing in recent years (l l ) and mary popular fI1/~,~zured eull[~ps are rnot- knol re$1$tanL - Studies reported herein ~e~e conducted with the following objectives: to dete fmine the a~odc of inheritance of the necroti¢ r~ct[on induced by PVY-MS]q~; to determine whcIher the association belween ro0t-knoT resistance and the ~rus-[ndneed t~ecrosis is due to linkage or pleiotropism; to search for ~egregatio~ between the t~o reactions [fi F1 populations derived f~om root- k~Io| res[sta nl X foot .knol susceptible crosses &nd among haploid and dihaploid lines of tobacco; to locate the chromosome bearing the locus controlling the necrotic reaction induced by the virus and to confirm the location of the root-knot resistant geae on chromosome G by aneup[oid analys~s; and to search for new sources of root-knot i~sistance a tTtong ~¥coil'ana s p. that al~ ilot : : mat erial• An alterrlative hypothesis states that the source of root- associated With the necrotic reaetlon to PVY-MSN~. ~ ~ l~notreslstara:ewasrm T.I. 706 bu A omentosaacces~ion~8 (2g). Thefactorcontrollingroot-knotresistan~e hasbeenreporled MATERIALS AND METHODS . : ~:.. to be incal~'d on tobacco chromosome G {221. ..... . v ~:~,~; A teeessw=e f~aetor for resistance to th ...... tlcreaetloninduced r~e lm~hler~tI n~eer ;| ud; ~[s a H ~h~e ~:~ga~ ~ s2 'r n~sa~ s t 72 ~;~; ~2 ~; ~ ~ ~ "~='bY PVY-N N has been reported to be ocated on obacco • , P • not ~:~ eh O~O ome , . root knot suseepubl¢ g©notypes. Cult ~ar NC 744 roo -k ~'L~' E (13), On the ot her hand. the mode oflnherltane¢of susceptlblei ~as used in some crosses because it has a recessive tene .':,t it has been reported that t obacco p~ants homozygoas for root .k notthe necrotic reaction to PVY-MSN~ has not been in~ esfigated, but for resistance to PVY-NSN~, Pro chics in the F: generations were~ [nitlaIIy inoculated ~ith PVY-M~N* (type i~ola~e NC 138), and ~ r ": resistance develop severe n¢crosls n espon e o PVy-M~Na• "' ~]3ereasbeterozygousplantsde~elopamild orattenuated fotmof later inoculated with race 3 of M. incogn#a. PVY tests ~¢re J~,~e~r0sis;~'This:luggests=thaf the reaction to PVY mav be conducted at 20-28 C and root-knot tests at J0-3g C aerial ;,~" ; • . tempe~tares. S¢~dswerebroadcastonthesurfaeeofa2:lfolxtufe :!~ rhe~Jl~h~I~JO~¢¢~ii~f lhtS~nlCl4~j~eOelf4t ~¢n g~ *] OyO~ eh ¢g ~ty~ Th of steam-sterJii/ed sand and sand ,-Icutm soll covered v*ith ~t tblrt ~¢~!;~soe~o'e'¢a~n~¢=:l Approx[mate[I 50 8 of slo~-reiease fertilizer (Osmo~ole~) ~e~ [ ~1983 TP.e Ameemln Phylop~lholOg[c~t t S~¢{ety added tO the SO~I mixture ifl ¢&¢h ([at. Se¢~[t fl~S ~1~ i'll ~IIOCUla f~ [

000865 ~" ~ ~ Relationship Between Resistance to Meloidogyne ;ncognRa and a Necrotic Response to Infection ~'- by a Strain of Potato Virus Y in Tobacco "~" ~ ~eb¢~a C. Rufi~. N. T• Pow¢I] add G. V. Goodlng, Jr. =. :% -- . ~¢$¢~rch asscc~at c and pro f~ssoPL lesp¢ctively, J~¢pal~enl of Plant Pathologv, ~orth Ca~'oHna ~te ~nive~'~hy, R~le[g~ 276~0 Journal St ties Paper 8631 of the North Carolina Agrlcu]mral Research Serslc¢. ILale~gh 276~0• Use of trade ~mes imphes nehh¢~ ¢ndors©m=nt of the products nam=d nor erillcisro ot si~]l~ ~ ODeS no~ ff~entioned: " A~'pted faepubiicatlon 2 May 1983. ABSTRACT RufIy, R. C., poweH, N, T•jt nd Goodln£ G.V., Jr. 19~¢3. Relationship ~el.~een res~stanc~to tfe/oido~l~i~¢ognf/a and tt necrot m respot~4r toinfe~tion ~ya $Irai~ OP CUlt~ae$ of NwoHa~a labaeu~ resish~nt to the rool-~not nematode, resiszant genntypes and did not transloeale to 'root-knot Susceptible Mel°id°&~e• . hcogni:~, , de • op~ xva eu~ar n c o ~brn nfec ed b~' s m n den ~Wpes 'xhen s arious combinations of lhese gen~ypes were grafted. M N of pete o "we y pVy.M N Young 2. ol¢<mta roo-kno. Root-knolsuseeptlblep[amsde~elopedmild.veln-bandlngsymplor~sbut ~tslsz~ nt plants were m0rc susceptible to the virus than older plants end no necrosis, anti xlrus reaction gas not sigmfieanIly afgected by phmzgeor dese]oped necrosis under all aerial ~nd soil rem?erat ures rested. In eider I~mper~l~fe, T/m s;mi[arhy i~ temperature sensit i',~y invoP.~d in both plants(l?-m30~mZall).s'irus-lnducednecrosis~as'~esereat28 C, mildal toot-~not ~slslanc¢ and the neerozi: reacuon ¢liclted by PVy-MSNa • 32C. an~abseretat~-5-~C. Thes.~metemperatmev.hlchinhibilcdthe susgtsts that 1he basis foe the association oft hes¢ t we respon¢cs may b~ ¢[~¢ • expression of i~i-~not resistance else inhibited the necrotic response to to pleiotrn~ic effect 5 of a single gent. .P'dY M N *TI$e~e olclx'~clon o h ~lfg~v-lsS~Cl[~e~[oo~llflo ~ " . . n 1963, Henderson and Troutma~ d reported a severe nematode. ThegeneticbasisfortheassociatlonbelWeenroot-knot ~r~_~ ~5CUIBf I1¢¢ro$1~ in |o~¢¢o (N[coliano [a~icu~ L,) planls which xeslstance and PVY uecrosls has not been thoroughly invgst 1~8t¢~[ .: C* ~arried the gene for resistance to Ihe root-knot ~atode Iio¢ have the tv, o rea*tlons been genelieall) separated• All known [Meloldog)•~e i~¢cogrcila t Kofoid and White) Chit wood]. Necrosis was ind uc~d by a previously unreported strain of potato virus Y [PVY) (7)• Let er, Gooding and Tolin (5) characterized thre¢ st rain~ of PVY In Ihe $og~theastern United Stales based on host-speci~e rcactlo~s eliclted in t~ue-Gured tobacco cultlsar$ lcsi~t~nt Or , Susceptible to the root-knot nematode, The strain MSMn of PVY V s ~ , . [P Y-M M )causes mild, mosaic-type symploms on both root- < .: knot reslstant ~nd su~c:e~tlbIe cuhivars; str~i~ MsNR [ pvY_MSNa) = ~ produces miId symptoms on root-knot susceptible and vascular ~ ~ecro sonroooknotr¢ an eu vat and anNSNatPV'f. - Nt • • /~ . ) Is necrou¢ on both root-knot sus~¢pllh]¢ lind resistant euhivars, ~ Thebaslsoflh¢~$soclatlonhet~eenroot_knotrcslstanceandthe ~ lice rotlc ~eaCliOn io PVY- MsN k j$ nol known, The ~lssoc~a1~on ~s so • consiSt•hi that LaPra c~e and Henderson (g) screened breeding lines ~fof mot-knot resistance based o¢t t~elr reaction to ~noculation with the liras. ~h~¢h )5 simpler and quicker than inoculatlon with the foot-/cant resistant lines dcwlol~ a Severe, [l~.'i'od¢ i~act[on to - PVYoMSN~ but it is not known whether the assochtlon is due to ~ . extremelyelose[inkagtbetw¢~ntwo]oci~ortop~elotenp~ce~e©tso~ . a single gen¢. A root-knot reslstar~t cuh~var that does nut ~0 ~I¢ necrotic '~hen infected with PVY*M~Na would bent obvious value, 8h en the widespread occur fence of ~his ~rus in North Carolina (3). 7 Th~ mechanlsrn controlling rend-knot nematode i~$istan¢~ iB tobacco and tomato is temperalure ~ens~tlve (I, [ 3) The reslstance is a necrotic or hypersensitive rcactlon that diminishes as¸ 1¢mpe~1~r~ i~crea~s• The obJectlves of ~¢s~ ~[ad~s were to determine "whether 1¢raperatures Icno~n to inblblt root-knot reslstance alsolnhlbit the necrotic reacdon induced bY PVY-MsNt ~ and to detcrmine ~hether the virus-lnduccd necrosis is due to a diffusible compound or is cell-spedflc• MATERIALS AND METHODS : i Tt~e b~1ot ~n o o I ~ ST~ C • we • Oe I e~ m ~,*h ~y pac~e ¢~arg~ ~a ment ~'hJ* ~ene[al• FIue-¢u fed tobacco cuh~a fs NC 2326 tlnd Hicks both l~~4 bandm~ ssmptclms ~hcn moeutaled '~llh P~Y-M ). C ~---~¢1~ The AmeriCan Pt~O~th~lOglCll~O¢~el~ {root-knolres~Manl and de~tlops necrosis ~hen inoculated with =

Improvement of Anther Culture in Nico~ana: Media, Cultural Conditions and Flow Cytometrlc Determination of Holdy Levels D. P. S~vc~^, E. Fiaooz~, N. M. Ax, p~s and D. W. G~e~uva ~hool of Life Scismc~. Unlversjty of Nebraska-Hncoin, Linloin Nebc,~ski6~58~'O118 ~',S,A. 000866

Gene, 24 f1983 147-155" ElSev:er GENE 813 0O0867 J, Overlap and eotranscriptfon of the genes for the beta dud apsilon subunits of tahaeeu chloroplast ATPase (Recombinomt DNA; gene cloning; nucleotide sequence; overlapping genes; polycistronie mlLNA) -Z Kazuo Shinozaki, Hirnslli Deno. Akira Kato* and Masaldro Suginra ': Department orB(elegy, Nagoya Universi~. Chikusa. Nagoya 464 (Japan) Tel. 052-78]-5lll. and Department of Moleadar : ~ .... Geaetiet. National ln~tltute of Genetlcs. M'~hlnta 411 (Japan) Tel. 05.59-73.0771 %., (Received Ma~'eh 27t1~ 1983) - {Accepted April 4th. 19831 SUMMARY The nueleotide sequences of the genes for the/? and * sobuuits of tobacco chlorogIast AT~ase have been determined. The coding regions for the B and esubut~ts contain 1494bp (498 codonsl and 399bp (133 codons), respectively The 3' end of the ~-coding region overlaps by one nucleo~ide with the 5' end of the e-coding region. The overlapping termination and initiation codons ere ATGA. The ~ and ~genes cotrmasc~bed as a 2.7-kb pol.vcistr on~c mRNA. The maaoant of the fl and ~ mRNA in the ablaropiast is about nne-twenfieth that of the LS mRNA I INTRODUCTION The p~'oton-tranelecating ATPase complex of chloropinsts consists of two parts, CFo and C'FI, as do those from bacteria and mitochondria (l~elson, 1976).TheCF= s oeatedontheouter surfaceefthe thylakoid membrane and contains five different subunhs (~, ~, 2~, ~ and ~). The CFo is located in the membrane and contains three different subunits el, I1 mad III) At least three of the CF= subunits and two of'the CFo subunits ~c encoded by the ~ehloro- • present address: NatioDal l~st~tute of Agricultural Sciences. Tsukub~ Ibataki-ken 305 IJapanJ Te] 02975-6-8373. Abbre~i~l ~ns, b~, base pairs; DUCD N,~,".dieyelohex~czr. plast DNA (Westhoff etel., 1981: De~=~ and Groot. 1981) mad s2mthesiz~.d m oblorop]asts (Ellis, 1977; Nelson eta]., 1980; Doherty and Gray, 1980). The genes for the ~ and e subtmits in sevend plmats have been mapped close to and on the opposiin strand from the gene for the L$ [Westhoff etal~ 1981 ; Jelly et el., 198~ ; Howe et el., 1982). Previously, we determined the au eleofide sequence of the intercistroni¢ reglon between the .~ and LS genes from tobacco and mapped the initiation ~g¢$ . of their transcription (Shinoz~d and Sugiura, 1982ak Here we present the complete nueleotide sequence of the ending regions of the tobacco/~ ~nd ~ genes and the 3' flanking region. The Y eed ofthet~ ~-coding region was ~hown to overlap by one nueleotlde with the 5' end of the ~-coding region. v~ b~dlIm~d~:D'MSO'dlmcth!l~u~xt°e:K° ~m~°L~cs°r~l:°~a~e Cotrallscelptio~ofthesetv¢ogel3eswasa]sodemon. [taCit :~- pairs, LS. large subu~=t of rJlmlos¢-1.5-bi~pPax~pbate carboxy- strated. i~ ¢,~x.,genase ORF o~en cad n~frame:SDS, odium~o~ecyl | s*tlfi~lc: SSC, 0 15 M N~CI 0.015 M Na~ cnrale, pH 7 6, ~'~ _ . " .e " ~ (. ] ~ ' 03~-11;9/83~fl300 © 1983 Elsevier Science Publish •

f~ L ~u~ Melhoprene. an insect growth regulator, is effective against a variety of insects• including mosquitoes ~chaef~r and Wilder 19731. hunt flies on catl]e (Harris et el. 19741. and stored-prodtlet insects SIrong at~d Diekman 197~,. More recently, Manzelli ft9821 has .%ho,a n eff~etlvo control of the cigarette baede. La.llod- crma serrtc~rne ~F.). a~d the tobacco moth, EpheMiu ehitella (H~buer); additional data on control of th~ clg- arctic beetle has b~en repoaed by Long el aL (1978, 1980). This demonstrated efficacy af methopre~e for control of pests in stored tobacco ba~ ]dd If} the devel- opment of KABAT Tobacco protector b) Z~eeon Cur potation• For methoprene to be used in the control of in,eels oa stored products, including tobacco, the C]lemlCal ntu$[ exhibit sufficient stabiIity to maitaaln its effectiveness throughout the storage period. We mvesItgated the ~ta bilit}' of nledlopeene on cigarette filler tobacco and the degredadon of methoprene on bright leaf tobacco packed into slmulated.hogsheads ("mini-hogshead s" "). Materials and Methods Ti~e 15o'Clmethoprene used in the stability study on steel tray and uniformIy treated, using a micro Kontes.~-~7 sprayer with ["Clmethoprene (500 Ixg. 5.9 mCi/mmoh diluted o tim x~ hgS%ehano Aftorbelngsprayed. ~.~ he tobacc¢ wa~ icfl on ihe tray in a hood for ] h to'dr,. efo e be n~ put in a glass jar and sealed tightly. The - jar was thoroughly shaken to mix the tobacco, and four :: 01iquots were removed for total combustion analysis. Z which determhied an tpplicatkm rate of 7.5 ppm. The := jar of tobacco was stored in d',¢ dark at 24~C, 64~ relative humidity IRH}. At each time point, an aliquot (5 g) v.as rctnoved from the jar and homogenizrd wttI~ chloroform ano methanol After quantification of t adio. actwlty, the extract S were eoneelnra~ed and Ihe idenoty of radiolabel wa~ assessed by TLC. Unextractable ra- dioactivity in the restdual solids wa, determined by ¢ombnsuon. A more de~iled degradation stud)" of methoprene hi mlni-hogsheads utilized bright tobacco blend (Philip Morris. Richmond• Va.). A mixer made from a 5-gal (ca, 19-liter) can was used to tumble the tobacco (I .0O0 g). which was sprayed with [t~C]methoprene ( 12 ms) in t20 ml of ethanol: me apparatus was contained in a stainless-steel hood• The tobacco was ! cigarette filler tobacco was 99.2% 2E isomer. 0.4% 2Z in the hood overnight. The molspn'e coBle~[ of the to- isomer '58 rnCi/mmo]), whleh wa~ diluted wkh uonla- ~te~o was thea determined 1o be 13%. On t b~led ~ethopr~ne of 96% .~ur[ty For the tobacco me- ex ac on a~d aualySlS 0y LSC the api~lleation rate was =., t~boliqm study in minl hog.heads. [5:'C]methoprene .Mflt L I rag/100 g (I I ppm). Samples (100 g) were packed ~'. purtty of 91% 2E. 8% 2Z (5.0 mCi/mmol! was used. .'into nlne wooden mira-hogsheads (Fig 1) to a density Radtochemie~] purity was attaly;:ex[ by ~versed-phase"" of 0.38 g/era~ (24 Ib/fP). The boxes were mahiotained llquid obrom~togr~phy (Qumtad et.aL-,974), with quart- i4nd;°~H~ ~r oamC°~tly lit oedgnv;r~rn m:en: r~ymara.t d~ nCg ~ ~" tlflcation by liquld solar [ a on court ng (LSCI of frae- fic~s rein alnln,~ months, the buxe~ were moved outside to an ~.: Radhiaedvi~" in extracts was quantified b) LSC alone area wclI p[~tected flora ~n and sun. or in conjunCllOn with sample combustion of reslduea to At each t~me interval, one hogshead was uBpacked ~, '~COa (Qulstad et al. 1974) Radiolabeled metabolites iu extracts were a~alyz¢d by t [1hi_layer chromatography toform arid methanol Quantitative and qual~tatlve unaI- (~LC) (Quistad ct a]. 1974) with development in box- ~ses of radioaelivity were performed as in the stablhty ime.eth) I acetate (4:1): zones from the TLC plates were study scraped and radioassayed for quantificalion, i~¢sults and Discussion As an initial stud2 of slabillty of methoprene on to- bacco, a 50-g sample of filler tobacco was removed from the tobacco rods of d~e UMve~hy of Kcnlacky Research Cigarettes (2R/) The tobacco was spread on a slainIess- The stability of mcthaprene on filler tobacco for 14 ' months and bright leaf lobaceo for 4 years is sho~n in Fig, 2. There was htt[e decomposition of methoprene under the~e conditions The reduced recoveries of ra- dtoaehWty as cad}' as one and 2 weeks appeared to be : ~- 999

000869 • - Isolation and Electrophoretic Analysis of Chromatin- associated Proteins from V'was-lnfected Tobacco Leaves H.J. wa~ Tzm~ and L C. v~ LOON Department of Plant Physlcloff~ A~icnltuod University, Athoremmlzan 4, NL-5703 BE] Wageningen, The Netheclands ~¢cclved May 26.1983 " Accepted July 12~ 1983 tobacco mosaic virus (TMV) induces a characteristic light green-dark green patmra on the young developing leaves. The ligin green areas abound with vlruspartlcI~s aad physlolog/cally and blochemica~y r~sembh senescen~ leaws. On the contrary, the dark green areas are almo~ devoid of vlr0s and remain physiologlc~y young (Mat- thews, 1951L The accderazad ageth~ of light green ~r~s do,* not resuk from ~-..haustioa of the host due to its helag forced to synthe*~ze addition*/nudele ~'id aad protein for viral rcpli~ion. The ~m~shed. *train of TMV rcplic~t ¢~ ~dmost to the same extent as the common strain withou: provoking symptoms. Furthermore. after infection with the common strain, host prot*in synthesis is orgy tr~dcndy iatdblted (Fraser and Get~ witz. 1980). Symptoms a~ therefore likdy to r~mlt from intederei~¢ v~th the .,.,.r

,'4 Springcr~Vcrlag 1~83 on0870 Resistant tobacco plants from protoplast-derived calluses selected for their resistance to Pseudomonas and Alternarla toxins _~ P.Ttlanutong. I.Furusaw~. and M.Yamamoto • ~" Laborat o~' of Plant PaLhology, Facm'ly ofAgrlcultur¢, Kyolo University, Sakyo~ku, Kyoto 606, Japan L~rge ~ale screcr~ng of ¢e11 popalatlons by conventional in vitro procedures has been sac~c~sfal m producing resistant plants agan~st sofn¢ amino add del~vatlves (Carlson 1973: Ma~on and Mallga 1975: Widholm 1977L andbind~ (Umml 1979: Mafiga !t al. |975: Malign 1978b pestirdes (Painted and palacco 1977: Ch~leff and Parsons 1978~ and some patho- loxm~ (Gengeahach eta]. 1977: Mattei~ ctal. ]978: BrctteJ and lnglam 1979: "!~umas etaL 1979: Siegemu~d 198h Sacristan 1982 We have selected leaf pro~oplast-derived ca[hises from tobacco t Nicozlan~ tabacum cv. '$amsun') for their resistance to toxins from the pathoga~s of vdldli~¢ and brown spot diseases, and flare rcgaiae~-a led intact p]anLs from these calluses. The morphological characteristics and disease resistance of the ~egenerated pthnts and their progenies also have been investigated. Our results show that resistance to both pathogens is hcrisable. : Received April 24.1983 . Cumin u nicamd b v K. Tsu~ewald Sttmmal~. P~o~opthst-derived calluses of tobacco (~i¢oriana tabacum c¢. "Samslln't were selected for their resistance to tox/~s from J~$eudomona~ ~'yrsngae pv. tabacL which causes wildfire diseage al~d from Aher- naria ahemata pathotype toba~o, which causes brown spot. A number of pla~ts were ;egcn~rated .from each of the toxln-selected p~oioplast-defived calluses A larga percentage of the [alants obtained from the second ~electior, ¢'j¢1~ ca|]uses were resistant to thf~ctloit by these pathogens. Resistance to wiIdflre disease, bow- ever, stems to b~ u~re]ated to reslstal~ce ~ brown ~pot disease. Variations in the morphological char~ctetissies of the rege/aerated pIant~ were rotund." P.esnits of an assay of the ]{1 ge.qeration indicate that the ~esistanc¢ thown I~¢ R~ pla~ts against both disease is heritable. Fully expanded leaves of tobacco plants (Nicotiana tabaeum L cv, 'eoamsun') that had been grown in a greenhouse ut~der natural daylight at 25 ± 5 ~C were used for proloplast i~olzllon. Tt*e [e.a~ surface was initially sterilized "xlth 70~ ethanol for 15s and then with 0.28 mercuric chloride for Ids. Afitr rinsing the lear tb~e limes with sterile water, its lower ¢gidgrmis was removed and pieces or the leaf were floated epldermisless side downwards on a prothp]ast isolation $oth- t/on composed of 9.I~ maanito[. I~ cellulase ai~d 005~ Maeerozyme 0(akuIt Pharmaceutical thdusUy Co, Ltd. Nishlnomiya, ]ap~n), The pH of the enz)~ne solution was adjusted Io 5,8 with 0.2 N KOH prior to sterilization through a Mglex-GS filter (Mi]llpore Corporation Bedford, Mugs. USAh #ill subsequent operations were carried out aseptically in a laminar flow cabinet• Leaf materials were kept in the enzyme solution at 30 ~C for 3 h without agitation ~ntll a mcsophy)l :;~ . Kcywords:P~'eudomonassyringae-Alternarlaalfernata L~2 3~ - In vitro seleetlon - Disease zesls~ance - Heritable Materials and methods :' s~lected variation protaFlaal isolatian and culture • Introduction Several t~chniques have been used to breed crop plants • : that are disease resistant. One is the introduction of ' rcslstanc¢ from wild species, although the genetic source is z~ot niways available. Az3other means is the artificial induction ofmutatlons foa~ show resistance. "[his "a~:hnique I~s been studied intensively for many ~,ears {$imoas 19"/9), but the frequent3" of the resistant - :~ m'ztants so far produo~d has falIer~ far shor~ of early expeeta* ":~'~:~=" llo~s. The mint recent technlque in use is the ~l~'lto~ of reslslattt vafi~,nts fro~ artlficiallx cultured cells or dssues. • , Sit~ce "Dakeb~ eta] O971) reported the ability of a single , thba¢c0 |ca[p~ot0pla~l to I'e~enerate an intact plant, much : ":: attention has been placed on the screenln~ of nos'e] '-ra th~ n tS Of |h*r onomic imlmtt ime~. D

• "f : .4gnc Biol Chem 47{9) 1949 1953 1983 o 00O871 Nicotine derivatives are reqmred in the to- bacco industry and pharmacological investi- gations. "the degreAation of nicotine [1) by bacteria has been revealed in many studlcs.1~ in which two pathways were showr-, one was ~/a N-mcthylmyoswine (1I) (py~ohdin¢ path- way) and the other v/o 6-hydrox3mi¢otine (pyridine pathway). The demethyIative deg- radation pathway of nicotine r/a nornicotine (llI) (methyl pathway) was reported in to- bacco leaf3} and mammals.*'s) Nicotine d~gra- clarion.by fungi has been reported in only one .t~nt report,5) which shows Ilicotia¢ de. ~thylauon. • Tobacco pathogenic fungi are of three ~lass~. Phycomycetes, Basidiomycctes and Af~omycete$. However, nicotine de~adation by tobacco pathogens has not been investi- gated yet. We investig~tted nicotine degradation by the tobacco pathogemc fungi and some sapro- phytic fungi, Hyphomycete*. and Actinomy- L Ceres, MATERIALS AND METHODS Organb'm~ pe///cu/aria ~mento~a ]TS-205 we~t ~ from tobacco pla~0t mfect~ ~ith dampm~ effdl- ' -t~e. Other tobacco p~thosenic fungi, p~rophrhera nl- ~e vat. n/co f~m~. JTS-209. ~ ¢~fum aph~n~aerm~rma J'1~ 203. f~ de~ryJ YI~-204. ~ro~#a~a ~eterotim~m 194~

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