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CURRENT DIGEST Powered By Docstoc
					         CURRENT DIGEST
           of Scientific Papers Relating to Tobacco Use
         (Compi ed and Described for Informational Purposes Only for The Council for Tobacco
         Resean :h-U .S .A . The Summaries Are Not Intended to be Complete Scientific Abstracts .)

Vol . XI, No . : 10                                                                            October 1966

                                           Contents                                    Page

                                1 . Lung Function Studies                                  1
                                2 . Statistical                                            5
                                3 . Tobacco Chemistry                                     10
                                )+ .   Polonium-210 and Lead-210                          11
                                5.     Human and Animal Tests                             13
                                6.     Heart and Circulation '                            18
                                7.     Other Systemic Conditions                          21
                                8.     Smoking Habits and Psychology                      23
                               9 . Medical Opinions                                       25
                              10 . The Netherlands' Controversy                           33
                                              - o 0 o -

                                1 . LtJNG FUNCTION STUDIES

BATES, D . V .- MD, MRCP, FRCP(C), GORDON, C . A ., MD, PAUL, G . I ., BSC,
   MSc, PhD, PLACE, R . E . G ., MD, CM, FRCP(C), SNIDAL, D . P ., MD, and
   WOOLF, C . R ., MD, MRCP, FRCP(C), participants, Co-Ordinated Study
   of Chronic Bronchitis in the Department of Veterans Affairs, Canada

"Chronic broi .chitis ." (Medical Services Journal -- Canada 22/1 :1-59,
   January 1 ;,66)

             This report of the third and fourth stages of the study relates
to 216 male tronchitis patients at four centers -- Toronto, Winnipeg, Montreal
and Halifax - average age 48 .4 years, of whom 4 .7 per cent are still in the
Armed Services . The highest proportion of men (18%) are in clerical work,
and the next highest (17 .1%) in servicing trades .

          Replies to questionnaire data relating to smoking habits showed
"a remarkable constancy between the men in all four cities in their replies
to the question about the age at which they started cigarette smoking," the
authors say . "Only two of the 216 men in the study were non-smokers, and a
further ten had smoked only pipes throughout their adult life . . . . There is
also a remarkable similarity in the average age at which these men say their
cough began ." These data are shown in Table IV (Adapted) :

                           CONFIDENTIAL :

                                                                                               TIMN 0230970

                          Smoking                       Cough              Hemoptysis
Center        No .    Started     C'ettes/week     Started Sputum Vol .    *Q   % in
                      at age                       at age     oz ./day         Center

    1958/60   44       18 .5           99           30 .5      3 .9        13      29 .6
    1960/62   26       17 .5          120           30 .2      2 .4         9      34 .6
    1960/62    67      18 .5          105           30 .0      2 .0        20      29 .8
    1960/62    39      18 .5          115           29 .0      2 .2        17      43 .5
    1960/62   40       18 .0          110           31 .0      2 .1        18      45 .0
TOTAL         216                                                          77
%             100                                                          35 .6
* Has your sputum e7er been streaked with blood?

          After revLewing the results of pulmonary function tests on the men,
the,authors say, "A detailed comparison of the smoking habits of the normal
subjects will have ~o'be undertaken before possible differences in smoking can
be eliminated as a~ause of these findings Lsuch as data suggesting individual
or regional differe ;ices between the menJ ."

CURTIS, John K ., MD, LISKA, Ashley P ., RASMUSSEN, Howard K . and CREE, Edna M .,
   MD, University o° Wisconsin Medical School and Veterans Administration,

"The bronchospastic component in patients with chronic bronchitis and emphysema ."
   (Journal of the :~merican Medical Association 197/9 :693-696, August 29, 1966)

           The autho_^s conducted respiratory studies on 100 patients with
moderate to severe , .hronic bronchitis and emphysema over a 5-year period --
an average of 34 moaths per patient -- and determined that a bronchospastic
component exists in most patients, whether or not a history of asthma is
elicited .

           "This st??dy gives no clue as to the cause of bronchospasm," they
say . "Most of the : .)atients had given up smoking and were not subjected to
air pollution in th= :ir environment ."

EDELMAN, Norman H ., MITTMAN, Charles, NORRIS, Arthur H ., COHEN, Bernice H .
   and SHOCK, Nathaa.W ., National Heart Institute, Bethesda, Md .,
   Baltimore City Hospitals, and Johns Hopkins University School of Hygiene
   and Public Healt%, Baltimore, Md .

"The effects of cigarette smoking upon spirometric performance of community
   dwelling men ." American Review of Respiratory Diseases 94/3 :421-429,
   September 1966)

                               CONFIDENTIAL :
                MIl`(NESOTA TOBACCO LITIGATION                         TIMN U2309i71 .-

          Lung function tests were made on 410 healthy community dwelling
men aged 20 : ;o 103 years -- mean age 52 years -- divided into four groups :
non-smokers, current cigarette smokers, former cigarette smokers, and pipe
and cigar smokers . They included 360 men involved in a population survey
of aging and 50 medical and laboratory personnel .

           "The evidence that cigarette smoking impairs ventilatory function
was twofold," they say : "(1) Current cigarette smokers had significantly
lower vital ~sapacities (VC), one second timed vital capacities (FEV1) and
maximal voluntary ventilations than non-smokers . (2) Partial regression
analysis of 1 ;he data of the current cigarette smokers indicated that the
greater the r :onsumption of cigarettes the lower were the observed VC, FEV0,5
and FEV1 .

            "Si .milar analysis of the data of former cigarette smokers indicated
that the gre-- .ter the number of years of smoking the lower were the FEV0,5
and FEV1 . I_TL addition, after correcting differences in age, height, and
total cigarel ;te exposure, a significant positive relationship was found in
this group bi_!tween smoking-free intervals and VC, FEV0 .5 and FEV1 .

           "It ; was concluded therefore, within the limits of a retrospective
cross-sectio-,ial study, these findings constituted evidence that : (1)
Cigarette s_m__t_)king impairs ventilatory function in subjects who appear healthy
upon clinical evaluation ; (2) this effect is related to the amount of cigarettes
consumed ; ant . (3) this effect is reversible upon cessation of smoking . . . .

          "Comparison of former cigarette smokers to non-smokers and current
cigarette smukers in the present study does not provide clear evidence for
or against rrversibility of ventilatory impairment ."

HOLLAND, W . W . *, ASHFORD, J . R .%#, COLLEY, J . R . T . *, MORGAN, D . C rooke ~,
   and PEARSUN, N . J . #, *St . Thomas's Hospital Medical School, London ;
   % Pneumocuniosis Field Research, British National Coal Board ; and # University
   of Exeter, England

"A comparisor, of two respiratory symptom questionnaires ." (British Journal
   of PrevenTive and Social Medicine 20/2 :76-96, April 1966)

          Th- authors tested the relative merits of a short version of the
British Medical Research Council's Respiratory Symptoms Questionnaire (MRC)
and the Pneu«,oconiosis Field Research Questionnaire (PFR), among men at
a Welsh colliery; the latter survey is similar in form to the MRC's but
more concise .

           "In all a total of 357 men came forward for examination at the
first stage cf the trial and 286 of this group were re-examined at the second
stage," the authors say . "As far as smoking habits are concerned, the
proportion of smokers assessed on the basis of the replies given to the PFR
Questionnaire amongst the men to whom the MRC questionnaire was applied first
is similar tc that amongst the men to whom the PFR Questionnaire as applied
first . On the other hand, the proportion of non-smokers in the former group
is slightly higher and the proportion of ex-smokers is slightly lower than
in the latter . . . .

                     CONFIDENTIAL :
         MIl`fNESOTA TOBACCO LITIGATION                        TIMN 02309 7 2        _

           "The oveo-all proportion of smokers amongst the men examined
(68 per cent) was - .bout 10 per cent lower than the average figure for the
colliery and the over-all proportions of non-smokers and ex-smokers were
correspondingly hill ;her . . . . In view of the generally high level of
reproducibility of the replies to the questions about smoking habits, it is
considered that thz! minor differences between different observers and the
two orders of exam ;,nation are probably a fair reflection of real variations
between the groups examined ."

KOURILSKY, Raoul,   ;1RILLE, Denise, and HATTE, J ., H8pital Saint Antoine,
   Paris, France

"Etude statistique de la relation entre le tabac et la bronchite chronique ."
   (Bulletin de 1' : .cademie Nationale de Medecine 150/17-18 :318-329, May 1966 :
   Translated in p~- .rt)

          In condu~_ :ting a study of chronic bronchitis among males in various
industries in the varis area, the authors divided the subjects into three
10-year age groups and into four categories of smokers : there were 833 non-smokers,
474 ex-smokers who had not smoked for three months or more, 1769 medium smokers
(up to 15 grams of tobacco daily), and 1786 heavy smokers (more than 15 g daily) .
Cough, sputum and :respiratory studies were made . For all age groups, the
frequence and degr~~e of symptoms rose regularly with the amount of tobacco smoked,
they say .

WILHELNbEN, Lars, - .nd TIBBLIN, Gosta, Sahlgrenska Sjukhuset, University of
   Goteborg, SwederL

"Tobacco smoking iiL fifty-year-old men ." (Scandinavian Journal of Respiratory
   Disease 47/2 :127 .-130, 1966)

           The authc)rs analyzed the effects of tobacco smoking on respiratory
symptoms and venti? .atory function in 339 fifty-year-?ld men as part of a
population study o0 973 men born in 1913 living in Goteborg, centered on the
early manifestatio=Ls of chronic disease . There were 84 non-smokers (24 .8%),
73 ex-smokers ( 21 . . ;%) , 106 smokers of 1 to 14 grams of tobacco daily ( 31 . 3%) ,
58 smokers of 15-2'- g/day (18 .1%) and 18 smokers of 25 g/day or more (5 .3%) .

          There wa= ; no significant difference of symptom frequency between
those who smoked ci .garettes or other forms of tobacco with the same weight
of consumption, th-=~y say ; peak flow, but not other tests, showed significantly
lower values for ci .garette smokers than for pipe and/or cigar smokers .

          The commora trend in the various measurements of ventilatory function
"was a decrease in mean values of lung function with increasing tobacco
consumption," the ; .uthors say . "Peak flow was significantly higher in ex-smokers
than in non-smoker : : and the two groups of smokers . In all other tests there
were no significani ; differences between non-smokers and ex-smokers . The
outstanding result : ; were found in the group of men smoking more than 15 g/day .
They showed signifi .cant differences in all tests, save FEV% Lforced expiratory
volume in one second divided by vital_capacityJ compared with non-smokers and
for vital capacity. FEV1 .0 and MMEF Lmaximum mid-expiratory flowJ also against
the other groups . ., .

                             CONFIDENTIAL :             TIMN             0230973

          "The most common respiratory symptom, viz, morning cough, was
somewhat more frequent in this material (36 .3 per cent) than in those from
Denmark and the United Kingdom (17 .3 per cent and 30 .0 per cent, respectively) . . . .
The ventilatory function tests did not show clearcut differences between non-
smokers and ex-smokers, except for the peak-flow test which gave higher results
in the ex-smoker group . This and the low frequency of symptoms in the ex-smoker
group means that the ex-smokers are comparable with non-smokers, at least if
the period of non-smoking has been more"than five years .

          "According to our observation the smokers' cough and sputum often
cease within a week when smoking is discontinued . The increased frequency of
cough, sputum, and, at least partly, wheezing in smokers indicate an inflammatory
reaction in the bronchi to the tobacco smoke . This reaction may differ with
individual differences in susceptibility ."

                               2 . STATISTICAL

ABELIN, Theodor, Assistant Professor of Epidemiology, Harvard University
   School of Public Health, Boston) Mass .

"Smoking habits and survival of lung cancer patients . Application of the
   temporary expectation of life as a measure of survival ." (American Journa].
   of Epidemiology 84/1 :110-119, July 1966)

          This paper reports on a follow-up of 262 men with primary cancer of
the lung "who, during hospitalization for their cancer, had been carefully
interviewed as to their smoking histories," the author says . "Originally,
this information was obtained from a group of 500 patients LLombard &
Snegireff, Ci?rrent Digest, April 1959, page 77 . . . The hypothesis is tested
that smoking habits earlier in life are associated with the survival of
lung cancer patients . . . . Except for a statistically insignificant trend
among localized cases, no association could be found between smoking habits
and survival experience . If an association exists, it must be small and can
be detected cnly by using much larger study populations ."

          Table 2, showing accumulated survival rates according to lifetime
cigarette smcking, shows no detectable trend with increasing amounts smoked ;
table 3, showing temporary expectation of life through fifth year after
diagnosis, according to lifetime cigarette smoking, shows no significant
difference between smoking categories, the author says . "Survival rates by
total and maximum amount smoked were standardized for age and socio-economic
status of the subjects as determined at the time of the initial interview .
Neither afferted the outcome,,and the results of these computations are not
presented heie ."

                    CONFIDENTIAL :

                                                                TIMN 0230974

ALLEN, Albert R ., MD, FCCP, and ALLEN, Loxi Marian, BS, Selah, Washington

"The appearance of carcinoma of the lung in pulmonary tuberculosis patients ."
   (South Dakota Journal of Medicine 19/7 :13-20, July 1966)

          This is a review of 14 cases of carcinoma of the lung occurring
among 919 patients with proved pulmonary tuberculosis admitted to the Central
Washington Tuberculosis Hospital from its opening Jan . 20, 1950, to its
closing on Dec . 31, 1957 ; eleven were males, and there were 13 smokers of 1
or more packs of cigarettes daily, they say . On the basis of their review,
the authors believe that isoniazid is the main factor in the increased
incidence of bronchogenic carcinomaa in patients with pulmonary tuberculosis .

          "Of the patients receiving isoniazid, there have been only three
carcinomas other than those of the lung reported as causes of death since
discharge from the hospital," they say ; "one of the stomach within one year
of discharge, one cf the pancreas six years after discharge and one of the
ovary eight years ?fter drug therapy was stopped ."

AUBRY, Francine, CCLLINS, Jean-Pierre, and DUFOUR, Bernadette, summer workers ;
   DAVIGNON, Lise, NID, MPH, and St .-PIERRE, J ., PhD, University of Montreal,

"Etude de l'habitud,e de fumer en relation avec 1'occupation ." (Canadian
   Journal of Public Health 57/8 :335-342, August 1966)

           "Thissur-aey was conducted to establish the different ratio of
smoking habits, esi_ecially cigarette smoking, between two different groups of
workers ; a first &L-oup exposed to industrial dusts and another group, not
exposed," the authi-irs' English summary says . "A total of 2165 persons of 50
years of age and over, belonging to the two groups, was interviewed .

           "The resi_1ts of the inquiries indicate that the first group showed
a definite occurreuce of higher smoking habits, both in the percentage of
smokers and the qur,ntity of cigarettes smoked daily and also in the length
of time since the :,moking habit was begun . Based on similar kinds of duties
or responsibilitie :_ ;, the difference is not influenced by the age of the smoker
but rather by the -~!nvironment in which he works .

          "It wolul,_ . be desirable to repeat the survey on a greater number of
individuals in the=~e specific groups to obtain additional relevant data ."

          The heavi .est cigarette smoking occurred in males with jobs entailing
responsibilities, : ;o that a socio-economic factor may be attributed to the
differences in smo?ang habits, the French text says . Among the tables presented,
which vary in tota° . numbers of persons utilized, are the following (adapted
translations) :

                            CONFIDENTIAL :

                                                                       TIMN 0230975

Table III . S :ioking habits as a function of the environment

Type of occup.Ltion :                    Exposed                  Non-exposed              Total
                                         . 1~                     No .                     T37 ___T

Never smoked                             103      7 .3            49         10 .9         152 8 .2
Former smoker :> *                       218     15 .5            82         18 .2         300 16 .2
Present cigar or pipe users              128      9 .1            55        12 .2          183 9 .9
Present cigar or pipe users
  plus cigare-:te smoking                181     12 . 9           53         11 .7         234 12 .6
Present cigar- :tte smokers              776     55 .2           211        47 .0          987 53 .1
 *stopped smo't .ing at least two years before

Table VIII .         _nfluence of type of occupation on present cigarette habits
                                     in exposed environment

      Group :                        I                    II                III                  IV              V

Daily smoking (No .)          No .               No .                  No           T     No .                No.__T

 1-14 Ctettes                   19       26 .7   17            27 .4   39         22 .3   68          34•5     98 25 .2
15-24           11              19       26 .7   31            50 .0   75         42 .8   63          31 .8   162 41 .6
25+             tt              33       46 .6   14            22 .6   61         34 .9   66          33 .7   129 33 .2
Groups : I -- 1+lanagers, etc . ; II -- Painters, store-keepers, etc . ; III -- Carpenters,
   machinists, truck drivers, electricians, etc . ; IV -- Tinsmiths, train
   conductors, mechanics, crane operators, etc . ; V -- Stokers, blacksmiths,
   boilermake^s, day laborers, etc .

          0thl :r tables show that persons in exposed occupations began to smoke
at an earlier age than the other group, and that a larger proportion of women
than men smois~ up to 24 cigarettes daily, while a much larger proportion of men
smoke 25 or more daily .

HAYBITTLE, J . L ., MA, Radiotherapeutic Center, Addenbrooke's Hospital, Cambridge,

"Cigarette smoking and life expectancy ." (British Journal of Preventive and
   Social Medicine 20/2 :101-104, April 1966)

          The author calculated life expectancies at age 40 for men in various
smoking categories -- nil, 1-9 cigarettes daily, 10-20, 21-39 and 40 + -- using
data from six prospective studies -- British doctors, Doll & Hill 1956 ; men in
9 states, Hamnond & Horn 1958 ; U .S . veterans, Dorn 1958 ; California occupations,
Dunn et al, 1960 ; California legion, Dunn et al 1963 ; and men in 25 states,
Hammond 1963 .

          "It is shown that the life expectancy of non-smokers is about 6 years
greater-than that of heavy cigarette smokers (more than 21 cigarettes per day),"
he says .

                          CONFIDENTIAL :
           MINI`fESOTA TOBACCO LITIGATION                                            TIMN 023097 6

          " . . .The results from the 5 American studies were very similar except
for the light smokers (1-9 cigarettes per day) . . . . The British :doctors' study
leads to smaller reductions in life expectancy for the lighter smoking categories,
but for very heavy bnokers (40+ cigarettes per day*) it agrees with the two
American studies in which this category was also analyzed ."
(~ "I am informed by Dr . Doll that the data for his study are slightly
misrepresented in 'S noking and Health' (1964) and that his two heaviest smoking
categories were in fact 20-34 a day and 35 or more cigarettes a day .")

Table II . Reduction in years of life expectancy at age 40 associated with
                              cigarette smoking (Adaptedl

Ceettes per day    Brit .Drs .   9 U .S .st .   U .S .Vets   Cal .occ .   Cal .leg .   25 U .S .st .

 1-9                  0 .7           2 .6         0 .7         1 .7         2 .5         3 .6
10-20                 1 .9           4 .7         4 .1         5 .1         4 .5         5 .2
21-39                 3 .3           5•9          6 .5         7 .2         5•6          5•7
40+                   7 .1           7 .1         --            --          --           6 .5

          If all of the reduction in life expectancy is caused by smoking, it
might be asked whether the average figure may be applied to the individual smoker ;
and no account has been taken of the possibility that some of the differences
in life expectancy between smokers and non-smokers may be due to constitutional
and genetic differen .ces, he says . "We may summarize therefore by saying that,
unless smokers, quite irrespective of their smoking, are shorter-lived than
non-smokers, the loss of life expectancy beyond age 40 due to smoking 21 cigarettes
or more per day is likely to be about 6 years . But for an individual with a
constitutional tendency to be short-lived, or who is particularly susceptible
to the deleterious effect of smoking, the loss of life expectancy may be greater,
and could be as hie as 12 years . . . .

          "I am greP .tly indebted to Prof . J . Ipsen for letting me see a copy of his
detailed report to the Surgeon General's Advisory Committee and to Dr . D . Kissen
for sending me a prr--publication copy of his most recent article on the significance
of personality in ling cancer in men . Dr . R . Doll kindly read an early draft of
my paper, and I am ~xateful to him for some very helpful comments . My thanks
are also due to Proi' . J . S . Mitchell for his interest and encouragement and a
number of useful di=cussions ."

RUEHN, Paul G ., MD, BECIO ;TT, Ronald, MD, and REED, John F ., bID, Surgical and
   Pathology Departments, Hartford Hospital, Conn .

"Tissue specificity in multiple primary malignancies . A study of 460 cases ."
   (American Journai . of Surgery 111/2 :164-167, February 1966 . Abstract :
   Modern Medicine ~ ;4/17 :110-111, August 15, 1966)

                           CONFIDENTIAL :

                                                                             TIMN 0230977

           "Ii ; is our opinion that there is a definite tissue specificity in
the developm= .nt of multiple primary malignancies and that anatomic locations
can be predi,sted if a patient lives long enough and has the host susceptibility
to develop a second primary malignancy," the authors say . "It is also suggested
not only tha : ; smoking predisposes to the development of oral, lung, and esophageal
cancer, and ?oossibly cancer of the bladder, but also that in patients in whom
multiple prifzary malignancies develop, all of these organ systems can be affected ."

            Th= :re were 278 female and 162 male patients with multiple primary
cancers ; 37 uere triple primary cases, and two quadruple primary malignancies .
The average Lnterval between onset of the first and second primary lesion was
4 .5 years . only three patients in whom multiple primaries of the oral cavity,
larynx, lung, esophagus or urinary tract developed were non-smokers, they say .
"The remaini ;lg patients were all heavy smokers of cigarettes, pipes, or cigars ."

MITCHELL, Ro :3er S ., MD, FACP, University of Colorado School of Medicine,

"The clinicaL versus morphological findings in chronic bronchitis ."
   (Author's abstract : Postgraduate Course #9, American College of Physicians :
   Alabama J :)urnal of Medical Science 3/2 :168-169, April 1966)

            Between September 1959 and September 1964, 380 single lungs were
obtained frc--:n consecutive routine autopsies at Colorado General Hospital and
Veterans Administration Hospital, Denver . . . . At the outset the severity and
extent of emphysematous destruction was the principal interest . Finding some
cases with little emphysemaa but a severe clinical picture of obstructive
disease led us to pay greater attention to morphologic chronic bronchitis .
Since June of 1962, we have had 175 consecutive cases . . . .

          Our outgoing studies have provided us so far with the following . . . .
Morphologic ::hronic bronchitis has been found in four persons who smoked
cigarettes oaly slightly and in one who was a lifetime habitual non-smoker . . . . "

0'DONNELL, Wa .rd M ., MD, MANN, Richard H ., MD, and GROSH, John L ., MD,
   Departments of Pathology and Medicine, Lancaster (Pa .) General Hospital

"Asbestos, aa extrinsic factor in the pathogenesis of bronchogenic carcinoma
   and mesothelioma ." (Cancer 19/8 :1143-1148, August 1966)

          The authors report finding 23 bronchogenic carcinomas and 5 mesotheliomas
of the peritoneum or pleura in 55 asbestos textile workers who had pathologically
proven asbestosis . The medium total occupational exposure to asbestos of the 28
cancer patients was 20 years ; the interval from initial exposure until recognition
of the cancer varied from 20 to 40 years . There were 25 male and 3 female workers .
"In 5 of the patients a definite history was recorded of smoking more than one
pack of cigarettes daily," they say . "Unfortunately, detailed smoking histories
were not av?ilable from the clinical records for the remaining individuals ."

                 CONFIDENTIAL :
                                                                  TIMN 0230978
10 .

   ZAJIC, F . and V:NRIK, M ., Institute for Cardiovascular Research, Prague,

"A contribution to the epidemiology of chronic bronchitis ." (Acta Medica
   Scandinavica 179/6 :737-746, 1966 . Same data : "Prispevek k epidemiologii
   chronicke broncliitidy," Casopis Lekaru Ceskych 105/26 :689-695, June 24, 1966)

          The prevalence of chronic bronchitis was investigated in men aged
60 to 64 years in the city district of Prague 2, where electoral rolls show
2837 living men of these ages . A response rate of 93 .7% (443 men) was obtained
from a one-sixth population sample (473 men), the authors say . "Chronic
bronchitis was diagnosed in 27 .6 per cent of cases," they say . "The occurrence
of chronic bronchitis was significantly correlated with cigarette consumption .
Increased frequenc y of chronic bronchitis in the lowest income group and in
heavy laborers was also related to higher daily cigarette consumption ."

          Smoking sabits are tabulated for 443 men, without breakdown for
bronchitics : there were 59 never smoked,135 former smokers of cigarettes and
4 of cigars and/or pipes ; 233 cigarette smokers (91 of 15-24, 57 of 25+ daily) ;
11 pipe and cigar smokers ; and one cigarette and pipe smoker . An association
of cigarette smoking and bronchitis is shown on figure 1 . "Owing to the
evident influence Df cigarette smoking, the search for the other etiological
factors must be focused only on light smokers and non-smokers," the authors
say .

                           3 . TOBACCO CHEMISTRY

HOLLAND, Robert H ., NID, and ACEVEDO, A . R ., BS, Veterans Administration Hospital,
   and University of Texas Southwestern Medical School, Dallas

 "Current status of arsenic in American cigarettes ." (Cancer 19/9 :1248-1250,
    September 1966)

           The arsenic content of American cigarettes had declined from 45
to 9 parts per million in the past 8 years, a comprehensive analysis of
eight brands of non-filter cigarettes made in 1957, 1961 and again in 1965
shows . "The safe level of inhaled arsenic is not known," the authors say ;
"however, there is an accumulative effect in the bronchial mucosa so that a
heavy smoker (2 pAcks a day) may still concentrate enough arsenic to initiate
a carcinoma . . . .

           "The de« .onstration that inorganic arsenic is partially pyrolyzed
 into the phenol fraction of cigarette smoke condensate may prove to be important
 in the light of recent experiments in our laboratory that show a definite
 carcinogenic activity of triphenyl arsine on mouse skin . These studies are
 still in progress and will be reported at a later date ."

                          CONFIDENTIAL :
                                                                         TIMN 0230979
                                                                                11 .

                        4 . POLONIUM-210 and LEAD-210

HOLTZMAN, Richard B . and ILCEWICZ, Frank H ., Radiological Physics Division,
   Argonne NaUonal Laboratory, Argonne, Illinois

"Lead-210 and polonium-210 in tissues of cigarette smokers ." (Science 153 :
   1259-1260, September 9, 1966)

           TMCoacentrations of lead-210 and polonium-210 in rib bones taken
from 13 cigar= :tte smokers were about twice those in six non-smokers, the
polonium-210 being close to radioactive equilibrium with the lead-210," the
authors say . "In alveolar lung tissue the concentration of lead-210 in
smokers was aloout twice that in non-smokers . These differences are attributed
to additional intake by inhalation of lead-210 . . . .

           "Lel- .d-210 is also shown to be present in the smoke, an association
not unexpecterL since stable lead is known to occur in smoke1 Cogbill & Hobbs,
Tobacco Scieni :e 1 :68-73, May 10, 1957,•J and Nusbaum et al L Arch . Environ .
Health 10 :227 ; 1965J have shown correlation between concentrations of lead
in bone and cl .garette smoking . Our measurements were made on rib bones and
alveolar lung tissue taken at autopsy (or surgery) from subjects of known
smoking habit,~ . Individuals smoking more than ten cigarettes daily were
classed as s_m_c_ikers, but in our group only one member consumed less than 20 . . . .

           "Th==~ correlations between cigarette smoking and the concentrations of
nuclides in t1ke lungs and skeletons . . . indicate that smoke is a significant
source of intl~,ke of these nuclides . However, if we assume that our measurements
represent the whole body, the known levels of 210Po in smoke cannot account for the
higher skeletaL concentrations of this nuclide in smokers . . . . LBased on Kelley's
data -- Scient_ :e 149 :537, 1965J a one-pack-a-day smoker accumulates at equilibrium
only about 10 pc of total-body 210Po from cigarettes -- only a small fraction
of the 600 pc (approximately) in an average man ; even 100 per cent retention of
the 210po in the smoke from the daily smoking of one pack of cigarettes would
lead to a max-i .mum body content of 140 pc .

           "On the other hand, measurements on five sets of cigarettes smoked
by the method of Kelley, 2 cigarettes per samplej show (Table 3) that the
210Pb activityaverages about two-thirds that of the 21Opo in the smoke . . . .
LAlthoughJcor .centration of 210Po in tissue is important because it produces
the actual do=e, very little is acquired directly from food, water, and air --
an amount aboi .t equal to our estimate from cigarettes ."

LITTLE, J . B ., and McGANDY, R . B ., Departments of Physiology and Nutrition,
   Harvard Sc= .ool of Public Health, Boston, Mass .

"Measurement cf polonium-210 in human blood ." (Nature 211 :842-843, August 20, 1966)

           "As tobacco smoke has been shown to contain trace amounts of
polonium-210, we have related blood concentrations to smoking habits in a group
of middle-aged, men," the authors say . The study group included 31 cigarette
smokers, 14 pipe and/or cigar smokers, 30 past smokers, and 25 non-smokers,
aged 45 to 54 years . "The average polonium-210 concentration in smokers was
1 .72 pc/kg blcod, compared with 0 .76 pc/kg in non-smokers," they say .

12 .

           "Although a significant difference existed between blood concentrations
in cigarette smoker- and non-smokers (Pz-0 .001), a two to three-fold variation
among individuals w=,s present in each group . Such variation has also been
observed among polo-ILium-210 concentrations in pulmonary tissues of different
individuals . In ad'_Lition, we have examined other body tissues including liver,
spleen, kidney, urinary bladder and bone obtained at autopsy from ten cigarette
smokers and four noLL-smokers . Average concentrations were very similar to
those recently reported by Hill LCurrent Digest, December 1965, page 3J, but
up to a three-fold •rariation in concentrations in each organ was observed among
individuals .

          "The variation in blood concentrations may in part result from
dietary factors . A :3 Hill has pointed out, polonium-210 concentrations differ
widely in various foodstuffs . . . . In a preliminary study of possible dietary
effects, several blood samples were drawn from an 85 kg subject before and
after a meal contai-aing about 100 pc of polonium-210 . . . . Blood polonium-210
concentrations were 0 .98 pc/kg before the meal and rose to a maximum of 1 .56
pc/kg after the meaL, which suggests that a significant fraction of the isotope
present in food is absorbed into the blood .

          "In separite experiments in four heavy cigarette smokers, blood
samples were obtained before and at regular intervals after sudden complete
cessation of smoking . Blood polonium-210 concentrations fell an average of
27 per cent during the first week after smoking was stopped, but thereafter
changed very little during the next 4-8 weeks ."

TSO, T . C ., Agricultural Research Service, U .S . Department of Agriculture ;
   HARLEY, Naomi, , ;ealth and Safety Laboratory, U .S . Atomic Energy Commission ;
   and ALEXANDER, 7, . T ., Soil Conservation Service, U .S . Department of
   Agriculture, Beltsville, Md .

"Source of lead-210 and polonium-210 in tobacco ." (Science 153 :880-882,
   August 19, 1966 ;

          Test tob;=o plants were grown within a chamber enriched with
radon-222 in the ai ;mosphere, in tobacco fields with different sources of phosphate-
containing fertili-ser, and in culture containing lead-210 in the nutrient solution,
the authors say .  :he harvested leaves were subjected to three standard curing
conditions : quick-oven drying, air-curing, and flue-curing .

           "Our resizlts seem to indicate that the principal source of Pb210~
and thus of Po210Y in tobacco is the soil and that its nuclides are absorbed
by the plant roots," they say . "However, other factors may also contribute to
the final concentr~~tion of Po210 in tobacco ."

          The activity of polonium-210 in quick-oven dried and air-cured leaves
was similar, but wzen the samples were flue-cured a small increase in Po210 content
was apparent . "Th-a combustion products from the fuel used for flue-curing may
lead to this increise," they say . "Polonium-210 from the fuel is volatile at
the temperature of combustion and readily attached to the leaf surface ."

                          CONFIDENTIAL :                   TIMN 02309 8 1
                                                                            13 .

TSO, T . C ., HARLEY, N . and ALEXANDER, L . T .

"Radium-226 and polonium-210 in Burley and cigar wrapper tobacco ." (Tobacco
   Science 10 :105-106, August 19, 1966)

          ",the level of Ra-226 and Po-210 activity in Burley and cigar
wrapper tob?ccos is within the same range as those found in cigar filler,
Maryland anti,flue-cured tobaccos," the authors say . "Results obtained
from sample= of these tobacco types show a lower Po-210 content in
United Stat=s tobaccos than that of Rhodesia tobacco, and a higher content
than that oi' New Zealand tobaccos ."

                        5 . HUMAN AND ANIMAL TESTS

BECISBTT, Ari .old H ., PhD, FRIC, FPS, Chelsea College of Science and Technology,
    London, Kngland

"Drug distribution and metabolism ." (Dansk Tidsskrift for Farmaci 40/7 :197-223,
   July 19616)

          Whereas in animal experiments it is possible to give large doses
so that rea=,onable concentrations of drugs and metabolites in the biological
fluids are = .vailable for analysis, this is not generally possible in man, and
it is imporl ;ant that increased attention be given to sensitive and specific
analytical ~,iethods, the author says . As an example of the problems arising
from the fal .lure to use specific analytical techniques for work in man, he
presents a i'igure showing the apparent amphetamine and nicotine excretions
in the urin=r of a smoker as determined by gas-liquid chromatography and by
the methyl orange complexing procedure ; the latter "gives values which are
far too hien, " he says .

          "''he sum of the amphetamine content and the nicotine content, both
determined by gas chromatography, gave values comparable to the apparent
amphetamine content determined by the methyl orange technique . These dye -
complexing iaethods of analysis of bases in urine in man are inapplicable if
smokers are used as subjects . Despite this obvious conclusion, papers dealing
with excretLon of amines in man do not indicate whether smokers or non-smokers
have been u: ;ed in the trial, even when non-specific dye-complexing analytical
methods of analysis are used ."

CHESEER, G . B ., and JAMES, Barbara, Department of Pharmacology, University of
   Sydney, Wstralia

 "The InicotLnic'andfmuscarinic' receptors of the urinary bladder of the
    guinea-pig ." (Journal of Pharmacy and Pharmacology 18/7 :417-423,
    July 1966 ))

          '11e authors examined the effects of acetylcholine and nicotine on the
urinary bla3der of the guinea-pig, using three techniques of physiological
denervation .

                                   : TIMN
            P 4INNESOTA TOBAC C O LITIGATION                    02309 8 2
14 .

           Nicotine -as neurogenic (acting through the nerves) and equiactive
concentrations of ac- ;etylcholine were myogenic (acting through muscle tissues) .
Since no response to nicotine could be elicited in two experiments, despite
almost complete den= :rvation, the authors say that the experiments indicate
that the response oi' the bladder to nicotine is indirect and was due to the
stimulation of auto-nomic ganglion cells, which occur in the bladder of
guinea-pigs and som=-~ other species .

           "Apart from the receptors of the intramural ganglion cells, there
was no evidence for the presence of nicotinic receptors in the bladder
musculature of the ; ;uinea-pig," they say . "Should such receptors exist, and
assuming them to be resistant to the effects of denervation (as were the
muscarinic receptor :>), one would expect that a response to nicotine could
still be elicited a ;'ter denervation . As we found that this was not so, we
conclude that the n .cotinic receptors in the guinea-pig bladder are confined
to the ganglion cel-_s ."

CHOWDHURY, Jayasree Roy, Chittaranjan National Cancer Research Center,
   Calcutta, India

"Tumor formation in Swiss mice with human cancer filtrate ." (Annals of the
   New York Academy of Sciences 136/11 :259-274, August 17, 1966)

           "Differen~ malignant tumors from human patients were collected from
operating rooms," tae author says . "Benign tumors and normal tissues were
taken for control s-,udy . The third group of specimens included histologically
non-metastatic tissues near the cancer area ." After preparation of filtrates,
inbred Swiss Webste_^ mice less than 24 hours old were inoculated intra-
peritoneally with 0 .2 ml of the filtrate .

              "Significant tumorigenic activity of cancer filtrates was 12 .9
per cent as compared to 2 .27 per cent in the controls," he says . "The apparently
non-metastatic tisszes of cancer patients gave an appreciably tumorigenic effect
of 11 .54 per cent t-mor formation in the mice ., thus supporting the presence of a
hypothetical agent and necessitating further investigation ."

DAUTREBANDE, L . and WALIENHORST, W ., Silicosis Research Institute, Bochum,
   Western Germany

 "New studies on aer :)sols XXIV . Deposition rate of various microaerosols in
    human lung with special reference to the hygroscopicity of the material
    inhaled and to cLgarette smoke ." (Archives Internationales de Pharmacodynamie
       162/1 :194-218) July 1966)

                              CONFIDENTIAL :

                                                                       TIMN 0230983
                                                                             15 .

           "A nethod is described for estimating, in man, the degree of
deposition of fine particles at various levels of the lungs," the authors
say . "It avoLds many of the artifacts observed when dealing with animals .
Submicronic Farticles are dispersed for 1-2 min into a 0 .5 m3 chamber,
from which weLl trained subjects inhale the aerosol for 2 min . . . . /AtJ
the end of th=a second minutel a forced expiration is collected . . . . 'L]"i-n
such manner taatJ the air collected from different levels of the lungs
can be compar=ad with the inspired air to determine, by particle counting
and sizing, tae deposition characteristics of the inhaled particles . . . .

          "If made exclusively of submicronic particles, aerosols from
hygroscopic salt solutions or of hygroscopic cigarette smoke offer the
same depositi :)n curves as insoluble particles . Similarly, the density
of the submicronic particles does not appear to influence their deposition
(at any level of the lungs) as studied by the present method . Under an
electron micr-oscope, the size most frequently observed for particles
sampled from deep alveolar air lies between 0 .05 and 0 .4)Um ; their maximum
size has neve r been found to exceed l/&m . None of these findings appear
to be influenaed by the number of particles present in the inspired air
(from 4,000 to 900,000 per ml) ."

           The authors say that "the smoke produced by the burning endd of
a cigarette c- :)ntains an extremely high number of particles per ml of air
and that the maximum size of these particles has never been found to be
above 0 .2/dm . On the contrary, the smoke as issuing from the smoker's end
of the cigarette contains much less particles than the burning end ; they
are also of a larger diameter when observed on electron microscope screens . . . ."

GREEN, Gareth M ., and CAROLIN, Diana, Boston, Mass .

"Inhibition oe the bactericidal activity of alveolar macrophages by cigarette
   smoke ." (Authors' abstract : 58th Annual Meeting, American Society
   for Clinical Investigation, May 2, 1966 fCurrent Digest, July 1966, page 8_7 :
   Journal of Clinical Investigation 45/6 :1017, June 1966)

           Rec; :nt evidence has demonstrated that alveolar macrophages are
primarily res :)onsible for the clearance of inhaled bacteria . When alveolar
macrophages w~~re obtained by tracheobronchial lavage of rabbits' lungs and
layered on th- : surface of tissue culture flasks, 90% of an added bacterial
culture of Staphylococcus albus was killed in 3 hours . Introduction of
cigarette smo ke depressed this in vitro killing activity in a dose-related
fashion .

           Fiv-w ml of smoke in the culture flask produced about 50% inhibition,
and 10 ml cam .?lete suppression of bacterial killing with resultant bacterial
multiplicatio- :L . Several standard length, king size, and filtered brands of
cigarettes produced virtually identical results . One brand with a charcoal
filter had a toxicity of one-third to one-half that of other brands .

       . The toxic action of cigarette smoke was not removed by filtration of
the visible particles . However, after a single bubbling through an aqueous
bu3fer, the siaoke became non-toxic for the cells . Furthermore, aqueous
extraction of the smoke showed virtually a quantitative transfer of the toxic
action to the aqueous phase . . . .

                    CONFIDENTIAL :                               TIMN 0230 98 4
16 .

KERSHBAUM, A ., Philadelphia (Pa .) General Hospital

"A comparative study of cigarette, cigar and pipe smoking effects on blood
   lipids, catechola:n,ine excretion and nicotine content of the urine ."
   (Author9s abstrac ;_ ; 9th International Congress of Internal Medicine)
   Amsterdam, The NeTherlands, September 1966 : Excerpta Medica International
   Congress Series 1~1 :54, 1966)

           This study was undertaken to determine if different forms of
smoking vary in theit effect on certain biological processes associated
with atherogenesis aiLd to ascertain the influence of inhaling and of the
degree of nicotine a16sorption . In studies of the effect of smoking on
lipid metabolism, sul>jects showed greater free fatty acid (FFA) mobilization
with cigarettes than cigars, which was reversed when cigars were inhaled
and cigarettes not i_iihaled . In dogs, with the inhalation factor constant,
there was no differe!ice in FFA or triglyceride response to cigarette, cigar
or pipe smoke ; lipid effects of nicotine were similar to tobacco smoke .

          Catecholam- .ne excretion during 4-hour periods of smoking was
greater with cigaret ; ;es than cigars . In dogs there was no difference in
catecholamine output with cigarette, cigar or pipe smoke when similarly
administered by traclaeal inhalation . The nicotine content of urine
collected during 4-hour periods of smoking was greater with cigarettes than
cigars or pipes . ThLs was reversed when cigars and pipes were inhaled and
cigarettes not inhal= :d . In dogs, with inhalation constant, there was no
difference in nicoti~ie excretion . Blood specific activity measurements after
smoking radioactive tobacco showed greater absorption of pyrolysis products
with cigarettes .

          The findi?? ; ;s demonstrate that the greater lipid and catecholamine
response to cigarettz : smoking is due to the tendency to inhale cigarettes
with resultant great=ar nicotine absorption . This is substantiated by the
higher level of nicotine excretion with cigarette smoking which is equalized
by cigars and pipes ahen they are inhaled .

PALECEK, Frank, and WIADO, Domingo M ., Department of Pharmacology, University
   of Pennsylvania School of Medicine, Philadelphia

"Importance of histamine in mediating bronchoconstriction by cigarette smoke ."
   (Authors' abstract : Fall Meeting, American Physiological Society,
       August 29-Sept . 2, 1966 : Physiologist 9/3 :260, August 1966)

          The increase in lung resistance and fall in compliance following
the inhalation of cigarette smoke are mediated by the release of histamine, as
suggested by the following sets of observations : (a) In the anesthetized dog,
the lung compliance and resistance were measured by the method of Mead and
Whittenberger (1953) . The inhalation of cigarette smoke, histamine solution
in aerosol form and the intravenous injection of nicotine caused an increase
in pulmonary resistrnce, which is blocked by atropine . The three forms of
stimuli induce bronc:hoconstriction partly by stimulation of the vagus .

                            CONFIDENTIAL :
                      M [NNESOTA TOBACCO LITIGATION TIMN 0230985
                                                                            17 .

           (b) Blockade of histamine synthesis by administration of a-hydrazino-
histidine abolished the bronchoconstrictor response to cigarette smoke in the
dog . (c) In the anesthetized cat cigarette smoke, nicotine and histamine
aerosol were followed by the same type of response as in the dog, though to
a less extent . Pretreatment with a-hydrazino-histidine abolished not only
the bronchoconstrictor response to smoke, but also to nicotine and intra-
venous histamine . (d) The anesthetized rabbit did not respond to all forms
of stimuli . A pulmonary mechanism reactive to histamine, nicotine and
cigarette smcke is absent in the rabbit . (Supported by a grant from The
Council for i,obacco Research-U .S .A .)

WALIKER, Ted i- ., and KIEFER, John E ., Research Laboratories, Tennessee
    Eastman Company, Division of Eastman Kodak Company, Kingsport, Tenn .

"Ciliastatic components in the gas phase of cigarette smoke ."   (Science
   153 :1248-1 .250, September 9, 1966)

            "The work presented here deals only with the gas phase of cigarette
smoke which -.s separated from the particulate phase by a glass-fiber filter,"
the authors aay . "The Lamellibranch, Anodonta cataracta, which is a fresh-
water mussel, was chosen as test specimen . For exposure to smoke, 4 mm by
20 imn sectio-as of the reflected lamellae of the inner gill plates were placed
in . . .solutions . . . . A stroboscope was synchronized with the metachronic
wave of in vLtro mussel cilia permitting quantitative measurement of any
change in ci Liary frequency ."

           A :)uffing machine drew a 35 ml puff of tobacco smoke in 2 seconds
at the rate :)f 1 puff per minute, automatically diluted the puff with air to
100 ml, and pushed it across the specimen . Eight puffs were taken on each
cigarette . The gas phase was seps .rated into condensable and permanent gases
by means of a. cold trap, and the permanent gases were passed across the specimen
in the same way as the total gas phase, and at the same rate .

          "By this method the permanent gases showed little or no ciliastatic
activity," they say . "This would appear to eliminate such compounds as 1,3-
butadiene, NO, and CO as major contributors to ciliastasis, since they appear
in the permanent gases ."

          Since it was impossible to determine the activity of condensable
gases on a ruff by-puff basis, the authors say, a gas chromatographic
technique wp-s devised : after passing through a chromatographic column, fractions
of the cond=nsable gases were carried across the ciliated . specimen ; several
fractions w=re found to be active, and . hydrogen cyanide appeared to be the
important ctintributor to the ciliastatic activity of smoke .

WILSON, J ., and MATrHEWS, D . M ., Medical Research Council Clinical Genetics
   Research Unit, Institute of Child Health and Institute of Neurology,
   The National Hospital, London, England

"Metabolic Lnter-relationships between cyanide, thiocyanate and vitamin B~
   in smoke--s and non-smokers ." (Clinical Science 31/1 :1-7, August 1966)

                   CONFIDENTIAL :
        MIrTNESOTA TOBACCO LITIGATION                         TIMN 023t)986
18 .

          Plasma cyariide, thiocyanate and serum Bip concentrations were
estimated in 27 heah ;hy subjects of both sexes, including 17 smokers of
cigarettes or pipes ;Lnd 10 non-smokers . "The proportion of serum B12
extractable in the alosence of added cyanide was higher in smokers than
in non-smokers," the authors say . "Taking both smokers and non-smokers
together, there was ZL positive correlation between cyanide and thiocyanate
concentrations . . . . ~ ;xtrapolation of the data suggests that at low serum
B12 levels, plasma cyanide concentration might be sufficiently elevated
to produce chronic n- :uropathological effects . . . .

           "Plasma th_ .ocyanate concentrations were much higher in smokers than
in non-smokers ; cya_n_ : .de concentrations tended to be higher but the difference
was not statistically significant . . . . Total serum B12 concentrations were
very similar in smok~ :rs and non-smokers . However, tFe difference between
non-CN-extracted B12 and total B12 . . . was significantly smaller in smokers
than in non-smokers ~Lnd non-CN-extracted B as a percentage of total B 2
was significantly hi~ ;her . . . but did not ap~r2roach 100°~ even in the heavi~st
smokers . °t

                         6 . HEART AND CIRCULATION

EISEN, Milton E ., MD, Mount Sinai Hospital, New York City

"Coexistence of throciboangiitis obliterans and arteriosclerosis : Relationship
   to smoking ." (JoiLrnal of the American Geriatrics Society 14/8 :846-858,
   August 1966)

          This reporl ; is based on a study of 2500 cases of thromboangiitis
obliterans (TAO) for the years 1941-1947, which revealed 473 associated cases
of coronary occlusioa and 150 cases of angina pectoris, the author says .
The data were obtain~ :d from the records of Mount Sinai Hospital and from
private practice records, "constituting the largest amount of such material
available in the wor'_d . . . .

           "Among the 2500 cases studied, there was not a single record of
TAO occurring in a non-smoker," he says . "At present (1965) cases of TAO
have practically dis ;Lppeared from the Peripheral Vascular Clinic of the
Metropolitan HospitaL, although about 2000 cases of peripheral vascular
disease are seen the ;7e yearly . . . . In this large series, intimal atherosclerosis
appeared to be preci~,)itated by a toxic factor -- carbon monoxide . . . . Evidence
is presented to show that thromboangiitis obliterans (TAO) and atherosclerosis
are essentially the aame disease, and that TAO may be the acute inflammatory
phase of atherosclerosis both in the extremities and in the heart ."

   M . R ., Toronto, Ganada, and MURPHY, E . A ., MD, ScD, Baltimore, Md .

"Cigarette smoking aad platelet aggregation ." (Canadian Medical Association
   Journal 95/11 :549-553, September 10, 1966)

                            CONFIDENTIAL :
                    M[NNESOTA TOBACCO LITIGATION                           TIMN 0230987
                                                                                  19 .

           The authors studied the influence of cigarette smoking on'blood
platelet aggrz :gation in 37 smokers and 30 non-smokers, of whom 17 and 21
respectively T,Tere female . Smoking three cigarettes in rapid succession
(during 30 mi-lutes) after overnight fasting "had little effect on surface-
induced plateLet aggregation in habitual smokers," they say . "Non-smokers
showed similar results, though on the second of two identical tests control
values were sLgnificantly less than in smokers .

          "We think that this difference may have been masked during the
f irst test by apprehensiveness on the part of the non-smokers . Adenosine
nucleotide an3 serotonin contents were similar in smokers and non-smokers
in the control state, and neither showed significant changes on smoking .
There were significant correlations between the control concentrations of the
various nucleotides in both groups, and there were even higher correlations
between the changes in them after smoking . . . . We conclude that the long-term
effect of smcking is probably more important than the acute effect ."

JOUVE, Prof . A ., AUBERT, M . and AVRIL, P ., Faculty of Medicine, Marseille,

"Causes et ccinditions favorisantes des art4riopathies pc"riphWriques ."
   (Actualitz-s Cardiologiques et Angdiologiques Internationales 15/1 :1-8,
   1966 : Tra!Lslated in part)

           It is generally agreed that tobacco plays a toxic role in the
development of obliterative arteriopathies of the lower extremities, but this
opinion rela~ :es mainly to the disease after it is established, the authors say .
In a retrospc :ctive study which excludes patients suspected of coronary disease,
they say the :T have found evidence of an additive role of tobacco that is highly
significant zstatistically (P <10-6) . Their tabulation follows :

                             Controls                         Patients
                           No .     ~                  No .              ~

Non-smokers                31        26 .2             12                 4 .8
 1-10 cigarettes daily     32        27 .1             35                14 .1
11-20 do .                 41        34 .5             91                36 .6
21-40 do .                 14)       11 .8             96)               44 .3
41+     do .                0)                         14)

          The figures exclude four persons because of inadequate data on smoking .
The authors conclude : "Tobacco therefore appears to be a definite risk factor and
it plays a part, not only in aggravating disease in progress, but equally in
the genesis of arteriopathy ." Other factors discussed are android biotype,
arterial hyiertension, metabolic disorders, and excessive food intake .

MULCAHY, Ri :teard, M.D, MRCP, and HICKEY, Noel, MB, MRCPI, St . Vincent's
   Hospital ; and McDONALD, Marcella, BA, MSS, University College, Dublin, Eire

"A note on ~~ quantitative method of recording cigarette smoking experience ."
   (Irish Journal of Medical Science 6/487 :301-304, July 1966)

              CONFIDENTIAL :
        MIIJNESOTA TOBACCO LITIGATION TIMN                                       0230988
20 .

          In their ri :trospective study of more than 1000 patients with coronary
heart disease over tae past five years the authors have collected smoking
information, among o ;her data . "We have used a quantitative method of measuring
cigarette smoking ex.:?erience since the inception of this study which we think
has advantages . . . . A figure is arrived at by estimating the average daily
consumption of cigarc :ttes in each year of the patient's life to date . . . .
Despite the shortcomLngs attached to all methods of measurement involving recall,
it provides a reason_ably accurate method of estimating cigarette smoking experience .

          "The rest of this monograph is concerned with an examination of the
accuracy of the meth :)d and with an appraisal of factors which interfere with
accurate recall .

          "When possible the cigarette index is plotted during the course of the
first clinical interview by the physician (R .M . or N .H .) . It is best recorded
at this stage becausa the patient may, if made aware of the firm views on cigarette
smoking as a serious health hazard held by physicians in general, acquire feelings
of guilt about his s ;noking which may cause him to distort recall and minimize his
smoking experience . Also observer bias is less likely to operate at this early
stage when a definite diagnosis has in many cases not yet been arrived at .

          "The Department of Social Medicine at University College, Dublin, was
asked to do a random check on the validity of the data noted at clinical
examination . One hundred patients who were cigarette smokers or ex-smokers were
randomly chosen and independently questioned on their cigarette smoking habits by
a trained social worker (M .McD .), havin .E already had their cigarette indqxes measured
at the first clinicel examination . . . . LAJ high degree of correlation is evident . . . .
The rather higher figure noted by M .McD . for patients with a heavy smoking experiencea
can be attributed tc an initial reluctance on the part of the clinicians to accept
the history of really excessive smoking recounted by some of their patients ."

          Factors wrich interfere with recall include unreliability of older
witnesses, lack of education and intelligence (rural witnesses less reliable than
city dwellers), and inadequate or neurotic personalities, they say . The authors
"found the task of iecall to be more of an effort for women than men . Also
patients who have »r .dergone repeated interviews on the subject may eventually
show altered recall and this is particularly so in patients who acquire a feeling
of guilt about smoking . Finally, the patient who has successfully overcome the
habit may give an e : :aggerated account of his past smoking experience ."

 RAAB, W ., MD, Univeesity of Vermont, Burlington

 "Origin and prevent~ .on of so-called 'coronary' heart disease ." (Journal of the
    Tennessee Medica` . Association 59/8 :760-761+, August 1966)

           "Contrary to still widespread beliefs, hypoxic, so-called 'coronary,'
 heart disease is no ; : caused merely by coronary atherosclerosis but by a multi-
 plicity of pathogen .c factors among which myocardial oxygen-wasting sympathetic
 adrenomedullary ove--activity, probably in conjunction with an overproduction
 of potassium-deplet .ng adrenal 17-hydroxycorticosteroids, is most prominently
 involved," the author says .

                         CONFIDENTIAL :
                   MINNESOTA TOBACCO LITIGATION TIMN 0230989
                                                                                             21 .

                      "Rationa.l preventive measures consist (a) in a dietary reduction of
            atherogenic ~aturated animal fats and cholesterol and (b) in the avoidance
            of living h?:)its and environmental circumstances which elicit a detrimental,
            sustained el==vation of the cardiac sympathetic tone and excitability, i .e .,
            sedentary liTing, socio-economic tensions and anxieties, sensory annoyances
            (noise, hectLc 'entertainments'), and tobacco smoking ."

            VILLIGER, U . and HEYDEN-STUCKY, S ., Cantonal Hospital of St . Gallen, and
               Institute of Social and Preventive Medicine, University of Zurich,

            "Das Infarktorofil . Unterschiede zwischen Infarktpatienten und Kontrollpersonen
               in der 0s'i~schweiz ." (The infarct profile . Differences between infarct
               patients and control subjects in East Switzerland) . (Schweizerische
               Medizinis~ :he Wochenschrift 96/23 :748-758, June 11, 1966 . Translated in part)

                         "C`'.garette smoking (and especially cigarette smoke inhalation) has
            a strong bea~-ing on the incidence of myocardial infarction," the authors say .
            "Table 6 s?nfi~iarizes the smoking habits of 100 infarct patients and 100 control
            subjects . . . .

            Table 6 . Smo' :ing habits (Adapted and abridged)

                                                    Men                              Women
                                         Patients          Controls       Patients            Controls

            Non-smokers                    5                    18          20                  23
            Former smokers                 3                    11                               1
            Cigarette smc)kers            48                    33           8                      4
               1-19 dail;,,                    13                    17          3                      3
               20+ daily                       35                    16          5                      1
            Cigar and/or pipe smokers     16                    10

   0      Totals                 72             72        28           28
   Q, "W= also investigated the significance of the duration and size of
    ~ the smoking T .abit, asking ourselves which group had smoked most heavily and which
   ~-+ group had smoked longest," they say . "To answer this question, we multiplied the
   ,.~ daily consLun_-tion of one pack (or more) of cigarettes by the number of years
            smoked to deTermine the so-called 'pack-year' . . . . Result : the per-patient average
~ UO for the infaict victims was 33 .7 pack-years ; in the control group, this average
            was 33 .6 pacf :-years . From this we concluded that it is neither habit duratic)n
W~ nor the numb=r of cigarettes smoked per day which are decisive in producing
~ pa infarction, ?nd that infarct morbidity and mortality are influenced by cigarette
~T+ O smoking as such ."

~             ~               7 . OTHER SYSTEMIC CONDITIONS

            DEELEY,, Thom_?-s J ., MB, ChB, FFR, DMRT, Hammersmith Hospital, Postgraduate
               Medical School of London, England

 ~ "Relationship between cancer of the bladder and smoking ." (Author's abstract,
             5th Inter=American Conference on Toxicology and Occupational Medicine,
             Miami, Fla ., Aug . 1-4, 1966 : Industrial Medicine and Surgery 35/7 :572,
               July 1966)

                                                                             TIMN 0230990
22 .

          This paper compares the smoking habits of a group of 127 patients,
presenting at a radiotherapy department with a histologically proved carcinoma
of the bladder, with a similar group of patients from the same geographical
area and of the same age group who had no symptoms of bladder cancer . For
comparison the smokiag habits of_126 patients with a proved carcinoma of the
bronchus are also given .

          The investLgation was confined to cigarette smokers only . Each
patient in the cancer group is matched with a non-cancer patient of the
same age, so that th-~ number of years in which the patient has been at risk
are the same . The ?avestigation recorded the number of cigarettes smoked
per day and the totaL duration of smoking .

          Two per ce at of the cancer of bladder group were non-smokers
compared with 7% of the controls ; the comparable percentages for cancer of
the bronchus were 1% and 9% . The average number of cigarettes smoked was
significantly higher in the cancer group than in the non-cancer group . When
comparisons are made of patients with the same smoking habits, there is
evidence to suggest that there is a higher incidence of cancer with increasing
number of cigarettes smoked .

FUSCO, Frank D ., MD, Veterans Administration Hospital, Washington, D .C ., and
   ROSEN, Saul W ., PhD, MD, National Institute of Arthritis and Metabolic
   Diseases, Bethesdi, Md .

"Gonadotropin-producing anaplastic large-cell carcinomas of the lung ."
   (New England Journal of Medicine 275/10 :507-515, September 8, 1966)

          Four male smokers of 1 or 2 packs of cigarettes daily for at least
20 years, aged 43, 42 and 77 -- Negroes -- and 46 -- Caucasian, all with
gynecomastia, had histories, physical findings, laboratory studies and clinical
courses typical of bronchogenic carcinoma . The fourth man was a heavy drinker .
All denied ever receiving hormones, digitalis, or other drugs associated with
gynecomastia .

          "The pathological diagnosis of each case was anaplastic large-cell
carcinoma of the lung," the authors say . "These cases probably represent
the first documented examples of gonadotropin production by a bronchogenic

KOVACEV, V ., and NIrODIJEVIC, 0 ., Institute of Physiology, Medical Faculty of
   Skopje, Yugoslavia

"0 dejstvu nikotina na graviditet i okot belih pacova ." (The action of nicotine
   on pregnancy and a litter of white rats) . (Godishen Sbornik na Meditsinskiot
   Fakultet vo Skopye 12/12 :221-226, 1965 : Authors' English summary)

          Subcutanecus injections of 2 .2 mg/kg of nicotine were made in two
groups of female rats 7 days after being placed in cages for fecundation, the
first receiving nicctine until delivery of offspring, the second through 15
days of lactation . A third group served as controls . The weight of newborns
was registered at birth and 15 days later ; duration of pregnancy, number of
births,- and number cf stillborn were recorded for each animal .

                         CONFIDENTIAL :                                   -MN OZ3~~~1
             MINIV : :SOTA TOBACCO LITIGATION                          ~~
                                                                            23 .

          The weight of neonates treated with nicotine showed a significant
decrease compared to untreated controls, but weights at 15 days following
birth showed no differences between offspring of treated and untreated mothers .
The number of stillborn was significantly higher in the treated rats, compared
to the controls . There was a decrease in number of deliveries in treated
compared to urtreated animals, but the decrease was not significant . There
was a slight I= .ecrease in duration of pregnancy in treated rats, but the term
was within nolmal limits .

ROSENFELD, Myi-on E ., MD, Germantown Hospital, Philadelphia, Pa .

"Disseminated necrobiosis lipoidica ." (Journal of the Germantown Hospital
   7/1 :45-1+7, April 1966)

           Dis,:ussing a case of the above skin condition, the author says it
should be "noted that this disease occurs almost exclusively in patients who
smoke . (Our oatient has smoked for more than 30 years) . The relationship of
smoking to nearobiosis lipoidica is not clearly established ."

                      8 . SMOKING HABITS AND PSYCHOLOGY


"Smoking ." (Editorial : 64/7 :165, July 1966)

           "T'f .e increase in number of deaths from carcinoma of the lungs
parallels th= increase in the use of cigarettes since World War II," the
Journal says= "Members of the nursing profession are often heavy smokers
and figures _ .re not available to show whether there is any reduction in
number which still indulges in the habit . . . . Ninety-six per cent of
Australian doctors believe the habit is a health hazard, but 25% still
remain cigari :tte smokers . . . ."

LEMIN, Brian, SRN, RMN, QIDNS, HV Officer's Certificate, Male Health Visiting
   Officer, Aberdeen, Scotland

"A study of the smoking habits on 14 year old pupils in six schools in Aberdeen ."
   (Medical Dfficer 116/6 :82-85, August 5, 1966)

           In a study of smoking habits in 482 boys and 436 girls, 47 .3°f and
52 .1% respectively had "never tried" smoking, 23 .2% and 16 .7% had "smoked in
past," and 29 .5% and 31 .2% respectively were present smokers . Roughly
two-thirds cf the boys who smoke (95 out of 142) and one-third of the girls
who smoke (53 out of 136) were classified as regular smokers, i .e . having
cigarettes d,aily . Only 42 boys and 9 girls smoked more than 1+0 cigarettes
a week, while 40 boys and 50 girls smoked less than 10 a week .

                     CONFIDENTIAL :

                                                                     TI.lVIN 0230992
24 .

            About one-tliird of the boys and one-seventh of the girls (present
and past smokers) began smoking at age 10 or younger (14 boys and 3 girls at
age 7 or younger) ; 71 .1% of present and past smokers obtained their first
cigarette from a frie,zd, 13 .7% bought it, 9 .1% got it from a relative, and
5 .9% stole it, he say :3, "the latter being appreciably commoner in boys (23)
than in girls (3) . . . . Although seven fathers and six mothers in every
10 smoke, the vast ma_jority of parents seek to discourage smoking by their
children . . . and indeed 24% of the boys and 57% of the girls smoke only in
secret . By contrast L6% -- taking the sexes together -- receive cigarettes
from parents ."

SESTAK, Zvonko, MD, b:- :dical Faculty, School of Public Health, University of
   Zagreb, Yugoslavia

"Neka zapaznja o puse aju srednjoskolske omiladne ." (Some observations on
   smoking habits in secondary schools) . (Lijecnicki Vjesnik 88/3 :263-269,
   1966 . Author's English summary)

           The author surveyed smoking habits in 22 classes of three secondary
schools, one urban ani two rural, including 593 pupils aged 15 to 19 years .
In higher classes 63 .7% of the pupils have had some smoking experience, but
only 25 .4% are current smokers . The boy/girl ratio is 72 .3%-58 .7% ; town
youth smoke more than country youth, but the difference is not significant .
Curiosity and peer influence are the reasons for taking up smoking, at ages
15 to 16 .

SWINEHART, James W . and KIRSCHT, John P ., University of Michigan, Ann Arbor

 "Smoking : A panel study of beliefs and behavior following the PHS Report ."
    (Psychological Reports 18 :519-528, March 18, 1966)

          Questionnaires were administered to a panel of 128 college students
2, 4 and 12 weeks after the Report to the Surgeon General appeared in 1964, the
author says, in a revision of a paper presented in October 1965 (Current
Digest, December 1965, page 28 : 126 students) .

           "Data were obtained on smoking behavior, recall and evaluation of
the contents of the Report, perceptions of the personal relevance of health
threats from smoking, satisfactions derived from smoking and expected benefits
from quitting . Restiictions in the data obtained prevented a test of the
prediction that a spscified combination of beliefs would lead to a given
behavioral change .

            "The data y=artially confirmed predicted belief differences between
 those who continued 11_-o smoke, those who resumed smoking, and non-smokers .
 Neither the level of, nor changes in, reported satisfactions from smoking
 and benefits expectei .from quitting seemed to be used as means for dissonance
 reduction . However, smokers, as compared with non-smokers, became less
 accurate in recallin; ; the content of the Report, and evaluated the Report
 less favorably . Smo' :ers appeared to accept the possibility of personal
 harm from smoking bul ; believed they could quit if they decided to do so .
 An intention to quit apparently helped some smokers tolerate the disturbing
 discrepancy between ! ;heir beliefs and their behavior ."

                     (:ONFIDENTIAL :             TIMN                   0230 9 93
                                                                             25 .

ZAGONA, Salvatore V ., and HARTER, M . Russell, University of Arizona

"Credibility of source and recipient's attitude : factors in the perception
   and retention of information on smoking behavior ." (Perceptual and
   Motor SkiLls 23/1 :155-168, August 1966)

          Th=° credibility of printed statements on smoking and the subjectst
smoking habits were determined in a group of 57 male and female introductory
psychology students . The high, medium, and low credibility sources selected
by the authors were, respectively, the Report to the Surgeon General, information
attributed to Life Magazine ("no known stand on issue"), and to an advertisement
by the American Tobacco Company . "Each of these sources was identified with
the smoking information both verbally and in the information content," the
authors say .

           "Statistically significant results indicated that : (1) Ss LsubjectsJ
receiving ±1t .e information attributed to sources of high and low credibility
retained more information than those receiving the information attributed to
a source of medium credibility ; (2) Ss who perceived the information as
unbiased rei,ained more than those who perceived it as biased ;'and (3) as
credibility of the source increased, the percentage of Ss who agreed with the
information and perceived it as trustworthy also increased ."

                             9 . MEDICAL OPINIONS

BEFFINGER, Or . Jan (formerly of the Tobacco Smoking Research Center, Nairobi,
   Kenya) ; ;iow at London, England

"Lung cancer ." (Letter : Medical News (London) August 12, 1966 : 10 & 17)

          R: :search at the Center in Kenya "indicates that there are fundamental
differences in the rate of incidence of deaths from lung cancer in Poland, Spain
and Portugal from those in the UK and USA, and these are bound up with the
different methods of 'curing' cigarette-tobacco leaves," the author says .
"Poland, Spain and Portugal, which show a strikingly low rate of deaths from
lung cancer, use cigarettes made from enzymatically fermented tobacco leaves
producing an alkaline smoke . Several carbon compounds are broken down in the
leaf tissue, to the tune of a loss in dry weight of up to 18 per cent depending
on the variety of tobacco .

            'In the UK, the USA and other countries showing an alarming increase
in the ratr- of deaths from lung cancer, the cigarettes produce an acid smoke .
They are m_a,de from unfermented leaves which have only been 'pasteurized' by
applying high temperatures -- well over the pasteurization temperature . This
destroys elMymes and consequently eliminates enzymatic fermentation . Such
tobacco le-- .ves lose approximately only 2 per cent in dry weight, which clearly
indicates 4hat almost all carbon compounds in the leaf tissue remain untouched . . . .

                  CONFIDENTIAL :
                                                               TIMN 0230994
26 .

          "It is si!,nificant that cigars (which do not cause lung cancer)
are exclusively made from enzymatically fermented tobacco leaf . The limits of
this letter do not ?llow me to go into details of our 12-year research on these
lines, but our findings are now confirmed by statistical investigation and
laboratory tests -- both chemical, and on mice -- and are now supported by
over 30 university research workers in several countries including the UK and the

           "Professo~• H . J . Eysenck, in his book Smoking, Health and Personality,
considers enzymatic fermentation to be the biggest challenge to the problem of
smoking and health ~,pp .133-137, 154, 159)• Our findings are vigorously opposed
by the tobacco indu,,try which obviously fears that the reintroduction of the
enzymatic fermentatLon of cigarette-tobacco leaves will deprive the industry
of many million po?lads sterling and dollars now being saved each year on about
10 per cent 'saving' in dry weight of tobacco leaves pasteurized by the redrying
process ."

BOYD, William, MD, F'RCS(C), University of Toronto, Ontario, Canada

"Pathology for the Physician ." (Published 1965, by Lea & Febiger, Philadelphia, Pa . :
   Review by W .D ., Psychosomatics 7/4 :265, July August 1966)

          "Of particular interest to this reviewer is the realization that there
are still many unsclved enigmas and dilemmas in organic medicine, and that this
state of affairs iF not limited to psychiatry," the review says . "For example,
there is apparently still considerable controversy as to the relationship of
diet, particularly lipids, to arteriosclerosis . Another instance is that proof of
the relationship oT' smoking to lung cancer is as yet unsolved ."

BURGESS, Alex M ., Pm, Miriam Hospital, Providence, R . I ., and BURGESS, Samuel
   B ., MD, Glover ~[ospital, Needham, Mass .

"Chronic obstructi-ie pulmonary emphysema . A review, with special reference to
   its relation to cigarette smoking ." (Rhode Island Medical Journal 49/8 :
   461-494, August 1966)

          "We beli=~ve that it has been clearly shown that the inhalation of
cigarette smoke is the major factor in causing bronchogenic carcinoma," the
authors say . "In this communication we plan to review the relation of
obstructive pulmor3ry emphysema to the same atmospheric pollution . We shall
also add a short study of our own, the result of which stimulated us to attempt
this summary . . . . We have included all patients for whom a diagnosis of emphysema
was entered on the record Lat 3 Rhode Island hospitalsJ and a history as to the
use of tobacco was recorded .

                           CONFIDENTIAL :

                                                                        TIMN 0230995
                                                                            27 .

          "Ryyond a doubt we have included a number of patients with 'senile
emphysema,' and in several instances this diagnosis was made . The inclusion of
senile emphy3ema and the fact that a patient's statement that he does not smoke
may mean that he no longer smokes but formerly did, introduce an error which
would tend tD increase the number of people listed as non-smokers ." Of 206
patients, 97 smoked more than 1 pack daily, 79 smoked 1 pack daily, 15 smoked
less than 1 pack daily, and 15 did not smoke, they say . "A study of the
records of the 15 patients who denied having been smokers . . . indicates that
at least, two who had been 'gassed' in World War I, had a reasonable cause for
their emphysema ."


"Tobacco and pulmonary emphysema ." (Editorial : 49/8 :475, August 1966)

          Discussing the above paper, the Journal says, "Pertinent clinical
and laboratcry studies have yet been relatively few in number . But there is
a growing bcdy of evidence ." (AUERBACH et al ; DALH,AMN & RYLANDER ; SMART ;
RENZETTI et al ; SG Report, 1964 ., are cited : see Current Digests July 1966,
page 7 ; Augi=,st 1966, page 9, and Supplement, page 2 ; September 1966, page 4 .)
"The Tobaccc Institute . . . serves its supporters poorly in repeatedly and
consistentlytaking issue with studies such as the above, conducted in the
public inteiest and by scientists having no axe to grind ."

CANADIAN ME-PICAL ASSOCIATION, Annual Meeting, June 13-17, 1966, Edmonton

"Report of i ;he Committee on Cancer ." (Canadian Medical Association Journal
   95/10 :46c)-468, September 3, 1966)

             ' :^ .lthough your Committee has diversified its fields of interest to
other than oigarette smoking and its health hazards, it still feels there is
considerab_1i- : education of the public to be done in this rega .rd," the report
says . "LYoIirJ Committee has been cooperating with the Department of National
Health and Welfare to produce a pamphlet on the hazards of cigarette smoking . . . .
LItJ noted that a smoking withdrawal center to be established in Toronto is not
functioning as yet . . . LandJ felt that smoking in hospitals both by staff and
patients wa=s a worthwhile area for further discussion . . . ."

           ALso discussed in the report were various legislative measures then
before the ;iouse of Commons in Ottawa ; a plea for members of the Association not
to smoke in public ; a decision to be represented at the First International
Congress on Smoking and Health ; and sundry other matters dealing with tobacco .
Four resolu~ions implementing the Committeets report and program were adopted
by the memb=srs .

                     CONFIDENTIAL :

                                                                TINiN 0230996
28 .

COLE, Frank, MD, Edttor, Lincoln, Nebraska

"Don9t shoot the st=a.tistician ." (Editorial : Nebraska State Medical Journal
   51/9 :357-358, Se, .)tember 1966)

              "The statLsticians tell us," the author says . "They are often
wrong, but they te1L us . Their work is full of traps and pitfalls, where
we might go astray, but they do not . The queerest we know is the one
about the hundred c=a.ncer patients with 18 deaths . One statistician said
20 had low-grade ca,icer and 10% mortality rate, and 80 had high-grade
disease with 20% mo7tality rate . Another called the first 80 patients
low-grade, with a 1'i% death rate, and 20 patients high-grade, with a 30%
rate . . . . But the patients were the same, and the number of deaths was the
same . . . .

          °fWe do no~ say this to laugh at the statistician ; we mean only to
show how difficult Ls his tiask and how haxd he works . . . . He tells us that
our study was improDer and our conclusions were wrong, and he is right . For
if we are to decide if smoking is dangerous or if a drug is hepatotoxic, he
must tell us . What we believe, and what we tell our patients, and what we
give them, is often unscientifically motivated ; we may enjoy smoking . The
funniest scene is t'ze doctors at the conference table, all smoking, discussing
lung cancer . But t'Zen, we're not statisticians ."

EDINGTON, G . M ., NID, Department of Pathology, University of Ibadan, Nigeria

"Symposium on cancer of the alimentary tract in Africa ." (Medical Proceedings
   12/150347-349, Ja1y 23, 1966)

          Summariziag the conference, the author says that "smoking and drinking
were implicated in retrospective studies Lof esophageal cancerJ in Johannesburg
but they alone could not explain the sudden increase unless recent accidental
contamination had . cacurred . . . . Alcohol and smoking could not be incriminated"
in stomach cancer and were not mentioned in epidemiology of intestinal cancers .

ENDICOTT, Kenneth M ., MD, Director, National Cancer Institute, Bethesda, Md .

°fMan°s cancer rate increasing, reports Institute ." (AMA News 9/33 :6, August 15,

          Dr . Endicctt expressed the opinion that humans now are subjected to
more causes of canc-ar than they were 30 years ago, in commenting on federal
support of cancer r-°search, which now is about $164 million a year, compared
to $400,000 in 1937 when the Institute was established, the journal says .

           "In 1937, 144,774 Americans died of cancer, a crude death rate of
112 .4 per 100,000 . That year approximately 48,000 cases were cured -- a cure
rate of 25%," .the director said . "In (fiscal) 1967, 305,000 Americans will
die of cancer, a crude death rate of 153 per 100,000 . The five-year cure rate
is now better than 35% . Physicians will cure 165,000 cancer cases in 1967,
and it is safe to predict that the salvage rate will continue to rise as we
achieve wider application of our present knowledge . . . .

                    CONFIDENTIAL :
           NIINNE.~OTA TOBACCO LITIGATION                              TIMN 0230997
                                                                              29 .

          '`1iwen so, we seem to be losing ground . The cancer rate is increasing
more rapidly than the cure rate . What does this mean? Part of the answer lies
in population growth and longer life-span . More people live long enough to
get cancer . But this cannot explain the total increase . New cancer causes
must be at ~rork .

           "! : am firmly convinced that the unexplained increase in cancer must
be attribut= :d largely to an increase in man's exposure to cancer-causing agents
in his daily environment ."

HOFFSTAEDT, E . G . W ., MD, Smokers' Advisory Clinic, Newcastle-upon-Tyne,

"Letter ."   :Medical News, August 19, 1966 : 8 & 13)

          NLcotine holds so strong a grip over its victims that they tend to
behave very much like addicts, but it can be suddenly and completely withdrawn
without sertous effects, the author says . "However, the irresistible desire
of the habitual smoker to gratify the nicotine hunger . . . can have disastrous
effects on the smoker's personality and behavior . . . . The less desirable
personality traits of smokers are not the reason for, but the consequence of,
heavy habitial smoking . . . .

           "Et is time we denounced the mythical triad of extroversion, genetic
tendency to smoking heavily and constitutional liability to contract broncho-
genic carci,-zoma anyway . . . . Have men (and women) perhaps recently developed
brand new ganes on account of which they are doomed to smoke themselves to
death? The acceptance of such scientifically untenable, fatalistic theories as
that of the 'genetic triad' would spell the end of medical progress ."

HURST, Allan, NID, Department of Internal Medicine and Inhalation Therapy,
   General Rose Memorial Hospital, Denver, Colorado

"Cigarette smoking is found common to six families reporting emphysema ."
   (Medical Tribune 7/107 :24, September 7, 1966)

          In a paper presented before the 22nd annual congress of the American
College of Allergists at Chicago recently, the author said the only common
denominators found in six families with emphysema occurring in two members or
more were cigarette smoking and appearance of symptoms at a relatively early
age . Only a large twin study could clear up the question of whether a genetic
factor is _involved, he said . "In the meantime, whenever a diagnosis of chronic
obstructive airway disease is made, all family members should be encouraged to
have simple ventilatory studies . . . ." The six families are described briefly .

                 CONFIDENTIAL :

                                                                 TIMN 0230998
30 .


"ACOSH ." (Editori?l : 1/24 :1031, June 11, 1966)

          "It has teen remarked wryly that only a few years ago we called
cigarettes coffin nails and regarded it as a joke," the Journal says . "It
is no joke today . . . . LTheJ newly formed Australian Council of Smoking and
Health warrants syn .pathetic and vigorous support from all medical organizations
and individuals . . . . It has a beautifully militant name in its contracted
form -- ACOSH -- ai- .d should be able to make a real impact with enough weight
behind it ."

MEDICAL PROCEEDING`, Johannesburg, Union of South Africa

"You may smoke ." (Editorial : 12/14 :297-298, July 9, 1966)

           "As far -h~ack as 1843, when cigarette consumption was trivial,
medical journals w=_re apparently expressing concern about the increase in lung
cancer," the journ~c .l says . "Now, more than a century later, we are still
assailed by the same warnings ." The editorial then discusses the motivations
which led to the wilting of C . Harcourt Kitchin's book under the above title
(Library 33 Limite,- ., London, England, 1966), and says that his "review leads
him to conclude th~ .t a careful examination of the statistics finds little to
condemn moderate ci .garette smoking as a cause of lung cancer and that the
answer probably li~ :s in moderation -- a desirable way of life in so many
other fields as we? .1 ."


"Antismoking : Qual .fied progress ." (Editorial : 7/104 :11, August 29, 1966)

          The Roya . College of Physicians report (1962) and the Surgeon General's
report (1964) both were "followed by a dramatic decline in the sales of cigarettes,
but the decline wa=s temporary," the journal says . "Recently there has again
been a modest decl'.ne in sales" in Britain (3% in 1965) and the United States
(3•5% in fiscal l9o5-66) -- "although there are marked differences in antismoking
efforts in both colxntries ."

           In the Uaited States, the National Clearing House for Smoking and
Health has a budge° : of about $2 million, disbursed in 40 grants, and the tobacco
industry spends mo~-e than $200 million yearly in advertising, it says . In
Britain, tobacco manufacturers spent more than $30 million in advertising during
the last 12 months, a reduction by almost one-half since August 1965, when TV
advertising of cigarettes was banned .

          The editorial concludes that "the noticeable reduction in the percentage
of medical student :3 and young doctors who smoke cigarettes" perhaps "should be
regarded as the mo=st encouraging element in current observations ."

                      CONFIDENTIAL :
                                                                       TIMN 0230999
                                                                            31 .

OCHSNER, Alton, NID, Ochsner Clinic and Ochsner Foundation Hospital, New Orleans,
   La .

"Health hazards from tobacco ." (Section of "Traumatic Medicine and Surgery
   for the Attorney," published 1966 by Butterworth, Inc ., Washington, D .C . ;
   Review : 'Ll'edical Tribune 7/104 :23, August 29, 1966)

          This report "may become a definitive medicolegal reference in
litigations over diseases caused or aggravated by smoking," the review says .
The sum of all deaths from infections, accidents, suicide, homicide and
alcoholism, according to Dr . Ochsner, "equaled all deaths from tobacco
diseases in the United States during 1963 ." Among the findings in the report
are the following :

          "Cne out of every 23 heavy smokers now at the age of 35 will be dead
before reaching 45 . The death rate among cigarette smokers from 40 to 69
years old is 92% higher than that among non-smokers ."

           "Nicotine is a toxic drug that acts with a rapidity comparable to
that of cya_r:ide ."

           thlaken by mouth, the average lethal dose of nicotine is about 60 mg
in an adult, or the equivalent of smoking and inhaling a package of 20 cigarettes ."

          Also mentioned are associations of smoking with various types of
cancer, respiratory' cardiovascular and gastrointestinal diseases, diminution
of visual ability, and abortion,prematurity, and infant mortality .

SCHOR, Stanley S ., PhD, Temple University, Philadelphia, Pa .

"The misimplied normal ." ("The Mystic Statistic" : Journal of the American
   Medical Association 197/7 :556, August 15, 1966)

          "P'ine per cent of the physicians who died in 1964 failed to reach
the age of 10," the author says . "Sixty per cent of men with myocardial
infarction ?re considered overweight . Fifty pe'r cent of the manuscripts
published i~ . Journal Z have conclusions of doubtful validity .

           "inferences drawn from these statements may vary from reader to reader .
The reason i .s simple . No number in and of itself has meaning . . . . Statements
of numbers -without appropriate comparisons with controls can . . . be very misleading .
An investig?,tor owes the reader a description of the best control available . . . ."

SCOLTEN, Adxlan H ., M .D, Portland, Me .

"Physician fumes ." (Letter : Geriatrics 21/8 :224, August 1966)

                      CONFIDENTIAL :
                                                               TIMN 0231000
32 .

              "Each day too many MDs still smoke," the author says . "As far back
as 1938, I wrote a per pointing out the probable link between cigarette smoking
and lung cancer L-~~and have been preaching this ever since . . . . I firmly
believe smoking sh :)uld be called an addiction, for it is exactly that in most
smokers . . . ."

* (Ed .note : "Why s :noke?" Article in The Church World, which had a masthead
called "Direct SelLing Channel to Mainets 275,536 Catholics," January 14, 1938,
cites Dr . D . G . Chapman, Va . Med . Mo ., November 1937 on tobacco causing
leukoplakia, unnawd authors on smoking causing oral cancer .)


"°Projects get 40 P'3S grants backing smoking research ." (Medical Tribune
   7/102 :14, August 24, 1966) Also : "Grants approved .for heart, cancer,
   stroke programs ." (Medical Tribune 7/105 :4, August 31, 1966)

           "Anti-s_m_oking research projects dealing with parents and children,
college students, ,,Zealth workers, hospital patients, educational television
broadcasters, and ~aommunities were granted 40 U .S . Public Health Service awards
and contracts totaLing nearly $2,000,000 during the fiscal year 1966," the
journal says in thzs first report . According to the second, "The new regional
programs in heart disease, cancer, and stroke are under way with eight grants
approved from amonz 35 applications by mid-July ." (Smoking is not mentioned
in the latter repo-°t)

WYNDER, Ernest L ., and HOFFMANN, Dietrich, Sloan-Kettering Institute for Cancer
   Research, New York City

°tBeziehungen zwisciien Epidemiologie und experimenteller Karzinogenese ."
   (Munchener Medi ; :inische Wochenschrif't 108/31 :1501-1512, August 5, 1966 :
   Authorst English abstract)

               Epidemio .ogical observations on the geographic distribution of
cancer, its occurr- :nce in different regions within a country, different races
and socio-economic levels, its sex distribution, and the possible change in its
incidence all prov .de clues to factors in the environment that may relate to
cancer . . . .

          The exper'imental oncologist attempts to identify external and internal
cancerigenic facto~,s and studies the mechanism by which such factors contribute
to cancer in man . There are also instances where leads from the experimental
laboratory are helr>ful to the epidemiologist . In environmental cancerigenesis,
the epidemiologist and the experimental oncologist together investigate factors
that contribute to the development of human cancer .

          (The auti-iorsi experiments with cigarette smoke condensates are among
the material .cited in this review paper .)

                         CONFIDENTIAL :
                 M[NNESOTA TOBACCO LITIGATION . TIMN 0231001
                                                                            33 .

                      10 . THE NETHERLANDS' CONTROVERSY

DROGENDIJK, A . C ., NID, Professor of Social Medicine, Free University,
   Amsterdava, The Netherlands

"Is today's anti-smoking campaigh socio-medically justified?" (Acta
   Medicina=_ : Legalis et Socialis 18/3-4 : 291-301, July-December 1965)

           TrLe difficulty of eradicating "certain smoking habits has been
underestimaY,ed," the author says in a review of the results of anti-smoking
campaigns . He believes no stone should be left unturned in educating youths,
but adults "will have to be continually hammered at to smoke wisely," meaning
a switch frcm cigarettes to pipes and cigars, and moderation in smoking the
latter . "Oj .ly in this way it may be possible -- for the experiences are as
yet not ver ;•favorable -- to bend the rising curve of cases of lung cancer . . .,"
he says .


"Smoking and lung cancer ." (Triangle (The Sandoz Journal of Medical Science)
   7/5 :166-169, 1966)
          After describing the statistical evidence supporting the cigarette•-
lung cancer causal theory (Doll & Hill, 7th Day Adventists, etc .) the author
says "a few serious objections must, all the same, be leveled against such a
view . Firstly, it must be pointed out that those who do not die from lung
cancer incl"de many moderate and even heavy smokers . . . . TM (Wynder & Graham,

           "Secondly, it might be conjectured that if lung cancer were directly
due to the carcinogenic action of tobacco smoke, heavy smokers, and especially
chain smokers, ought to die from lung cancer at an earlier age than light
smokers . However, this is not the case, for fairly generally a peak is found.
in the 50 to 60 age group, more precisely between the age of 55 and 60 years .
The only conclusion that can be drawn from this is that cigarette smoking is
not the sole and direct cause of lung cancer, but that other factors also exert
an influence .

          "Tdirdly, it has not so far proved possible to induce lung cancer in
animals (mic°) by exposing them to tobacco smoke in the air they breathe . . . .
The results Df these experiments do not, of course, mean that tobacco smoke is
innocuous to man, but they do greatly detract from the probability that smoking
might be the sole and direct cause of lung cancer .

              "Fourthly, some investigators claim that lung cancer has also increased
in dogs . . . . These observations acquire added importance in view of the fact
that accordiag to experts the canine tumors resemble those found in man in many
respects . Ab all events if this increase is confirmed by further investigations,
this would b=: a hard blow to the theory which holds one sole factor responsible
for the enormous increase in lung cancer, for dogs do not smoke .

                  CONFIDENTIAL :
      MINN: SOTA TOBACCO LITIGATION                            TIMN 0231002
                                                 CONFIDENTIAL :
3~'        MINNESOTA                     TOBACCO LITIGATION
          "Fifthly, there are a number of facts which are difficult to
explain with the aid of the hypothesis that cigarette smoking is the only
guilty factor, but which can be easily, or at any rate much better accounted
for if air pollution is assumed to be an accessory factor in the etiology of
lung cancer . . . .

          "Although the relationship between smoking and lung cancer is not so
close, in a causative sense, as some would have us believe, this should not
restrain us from actively supporting a campaign against excessive cigarette
smoking, especially since the smoking of cigarettes leads to abuse, gives
rise to various diseases and is hence the most harmful way of taking .tobacco ."

   DUMOULIN, F . V . B ., and DROGENDIJK, A . C ., The Netherlands

"De factor luchtversntreiniging in het roken-longkankervraagstuk ." (The
   air pollution faztor in the smoking-lung cancer problem) . (Letters :
   Nederlands Tijds ::hrift voor Geneeskunde 110/24 :1ll2-1118, 1966 : Abstracted
   in English)

           The exchaages that follow stem from Drogendijk's paper with the
above title in the 4ay 7 issue of the same journal (Current Digest, August 1966,
page 17) .

          1 . In repLy to Drogendijk's suggestion that it might be better to
spend more mone y on combating air pollution, in view of regional differences
in lung cancer mort;ility in The Netherlands, Meinsma says it would reflect
poor judgment to re ;)lace the Non-Smoking Action among young people by a
general public campaign to reduce air pollution . Little is known about the
influence of air poLlution, whereas the detrimental effect of smoking is a fact
which is recognized also by Prof . Drogendijk, he says .

          2 . Van Rootselaar says that if Drogendijk has figures to prove a
strong urban vs . ru7al factor in lung cancer, he will gladly believe that an
air pollution relatLonship exists, but "the non-linearity of the correlation
between cigarette consumption and frequency of lung cancer may . . . not be used
as an argument for ,.he existence of an additional factor ."

          3 . Bierst=:ker concludes from Anglo American studies "that although
air pollution mayb=s of importance as a co-factor, smoking is the main factor"
in lung cancer mort~Llity . "Abstinence from smoking is a virtually absolute
guarantee against limg cancer, regardless of the milieu one lives in ."

          4 . Bloemb= :rgen has three objections : If in a group which smokes
60% more, the incid_ :nce of lung cancer is 140% higher, it may not be concluded
that other factors Lre involved, he says . Secondly, if the lung cancer death
rate among non-smok :rs in Liverpool (where the air has 8 to 11 times as much
benzpyrene as in r1n-al areas : Stocks & Campbell, 1955) is 9 times higher than
in rural areas, it nay still not be concluded that there is a close correlation
between the benzpyrone content and the lung cancer death rates, he says .
Thirdly, he challenges Drogendijk's tabulations showing per capita increases
in cigarette use from 667 in the first half of 1963 to 675 in the first half of
1965 ; if the first Oive months are looked at, smoking decreased from 548 to
541 cigarettes, he :oays .

                                                                       TIMN 0231003
                                                                                    35 .

                5, Dumoulin says Drogendijk emphasizes .outdoors air pollution but
      fails to merition indoors air pollution through which non-smokers "are exposed
      to cigarett=~ smoke to almost the same degree as are smokers ."

                6 . In a reply to each of the foregoing, Drogendijk says (1) that
      he did not =3tate that the air pollution theory has been proven, nor that it is
      the sole ex ;?lanation of the lung cancer increase, nor that the anti-smoking
      campaign among young people should be discontinued ; (2) that he did not
      intend to pcesent mathemetical evidence ; (3) that he does not place the air
      pollution tieory in opposition to the smoking theory, but considers it an
      additional Eactor ; (4) that cigarette use in The Netherlands for all of 1965
      was 1460 pec capita, against 1362 in 1962, and that differences between
      months are to be expected ; and (5) that the literature does not mention any
      difference Ln indoor air pollution between urban and rural areas .

                 "The real difference between city and rural areas lies in the
      pollution oE' the outside air," he says . "The fact that non-smokers in the
      city are exposed to indoor air pollution to almost the same extent as are the
      smoking city dwellers, and that there is nevertheless a marked difference
      between these two categories in regard to lung cancer frequency, indicates
      clearly that indoor air pollution is of little or no importance ."

                                           - o 0 o -

                                        BOOK REVIEWS

      "Management of Chronic Obstructive Lung Diseases, Conclusions of the Eighth
         Aspen Emphysema Conference, June 10-13, 1965, U .S . Public Health Service
         publication No . 1457, May 1966 . Sundry quotations follow .

      MeCLEMENTL John H ., MD, Columbia University, New York City : "It is well
         established that severe obstructive lung disease is primarily a disease
         of cigarette smoking men, past 50, that it is more common among city
         dwellers, and that in many it is preceded by a long period in which the
         symptoms of chronic bronchitis are present . . . . Until we can do better
         than just identify the group which is at highest risk, we do not
         und.erst-?nd etiology ." (p .4)

      Committee cu Home and Clinic Care . . . (Hepper, Norman G ., chairman) : "It
         is impei-ative that the patient stop smoking . . . . Medications designed to
         aid in -.topping smoking have been of little value . If the patient cannot
         stop smr-iking he should be encouraged to perhaps try a pipe, cigars,
         snuff, ur chewing tobacco ." (p .29)

~ ~   AVIADO, Domingo M ., MD, University of Pennsylvania, Philadelphia : "The
~ ~      inhalati .on of tobacco smoke causes both b ronc hoco nstriction and broncho-
U E      dilatio«, as well as constriction of the bronchial arteries . . . . The
 0       toleranoe of . . . bronchomotor mechanisms to repeated administration of
         cigareti ;e smoke require additional investigation ." (p .59)

      S_PICER, Wi_liam S . Jr ., MD, University of Maryland, Baltimore : "Attempts to
         relate ohanges in the lung to single air pollutants fail to recognize that
         other agents are simultaneously impinging upon the respiratory tract . . . ."
          (p .60)

                                                                    TIMN 0231004
36 .                            MIlVNESOT ONFIDE1~rTIAL :
               A             TOBACCO
"Medical Advances in Cancer," Memorial Sloan-Kettering Cancer Center Number,
  Medical Clinics of North America 50/3 :611-923, May 1966 . Among papers
  were the following .

SCHOTTENFELD, Davii, MD, and HOUDE, Raymond W ., MD : "The magnitude of the
   relative risk of dying from lung cancer among heavy cigarette smokers
   has overshadowe3 the additional or alternative considerations of urban
   residence, air pollution, decreasing socio-economic class, family history,
   and occupational exposures ." (p .622)

WYNDER, Ernest L ., MD, and HOFFMANN, Dietrich, PhD : "Studies in experimental
   tobacco carcinogenesis serve as an example of collaborative epidemiological
   and laboratory efforts . . . . Inhalation experiments with mice have shown
   but few bronchial alterations independent of infection . Apparently this
   is because the nasal cavities of mice and other laboratory animals have
   intricate defensive systems that do not permit the passing of a sufficient
   amount of tobacco smoke components to produce neoplastic alterations in
   the respiratory epithelium . The effects that have been noted, particularly
   in studies with hamsters previously sensitized with diethylnitrosamine
   (DENA) are probably due to the gaseous components of tobacco smoke ." (pp .644-645)

          The authors suggest 18 ways of reducing "tumorigenic activity of
tobacco smoke condensate ." (Table 2, p .6145)

"Biochemical Pathclogy," Proceedings, First International Symposium, June 13-18,
   1965, publishea 1966, The Williams & Wilkins Co ., E . Farber and P . N . Magee,
   editors . Amonb the papers was the following .

MILLER, James A ., PhD, and MILLER, Elizabeth C ., PhD : "Man served unwittingly
   as the first sreeies in which chemical and radiation carcinogenesis were
   demonstrated, A,nd several types of each of these agents are now known to
   be carcinogenic _ for humans . It is to be expected that viruses will be found
   to play a role in the occurrence of some neoplasms in man . The role of
   radiation, virPl, and chemical carcinogens in the over-all etiology of
   human neoplasm_= is not known ." (p .217)

           "Much mure information at the molecular level in studies on carcinogenesis
will be needed bei'ore mechanistic order can be brought about in the field of
experimental carci,nogenesis ." (p .232)

"World Health StaUstics Annual, 1963," Volume I : "Vital Statistics and Causes
   of Death," published 1966, World Health Organization, Geneva, Switzerland .

"Sampling Methods in Morbidity Surveys and Public Health Investigations," 10th
   Report, WHO E-x-pert Committee on Health Statistics, WHO Technical Report
   Series No .336, 1966 .

                                    - o 0 o -

                                                                   TININ 0231005
                                                                                 37 .

          Also received but not excerpted were the following papers on
tobacco and related research and opinion .

AMERICAN CANCER SOCIETY, "Early detection of lung cancer," Pub . Health
   Reports 81/8 :742, Aug . 1966 . (10-year cigarette smokers in cancer
   detection project at Park Ridge, Ill .)

BALK, H . P . (Germany), "Intrazellulare Lokalisation und Funktion von
   hydrolytischen Enzymen bei Tabak," Planta 7/3 :207-236, 1966 . (Not

BELLAMY, A . R . (New Zealand), "RNA synthesis in exponentially growing
   tobacco cells subjected to a step-down nutritional shift," Biochim .
   Biophys . Acta 123/1 :102-115, 1966 : Chem . Abstr . 65/5 :7514b, Aug . 29, 1966 .

BERGEI, D . & MANKIN, G . (England), "Circulatory changes produced by chemical
   stimulation of the surface of the left ventricle in dogs," J . Physiol .
   184/2 :74P-75P, 1966 . (Nicotine acid tartrate among compounds studied)

BLAKESLEE, A ., "Pamphlet message : 'Quit smoking now, "' Med . Trib . 7/115 :27,
   Sept . 26, 1966 . (Review of Public Affairs Pamphlet #386 by Blakeslee)

BROWN, D . A . (England), "Depolarization of normal and preganglionically
   denervated superior cervical ganglia by stimulant drugs," and 2 other
   papers : Brit . J . Pharmacol . Chemotherapy 26/3 :511-520, 521-537, 528-551,
   1966 : also in Chem . Abstr . 65/1 :1247h, 1248c, 1248f, July 4, 1966 .
   (Nicotine used in series of tests)

BRUMAGEN, D . M . & HIATT, A . J . (U . of Kentucky), "The relation of oxalic
   acid to the translocation and utilization of calcium in Nicotiana tabacum,"
   Plant Soil 24/2 :239-249, 1966 : Chem . Abstr . 65/4 :5889e, Aug . 15, 19 .

CASTELLI, W . P . et al (RUI'STEIN, D . D .) (Harvard M .S .), "Serum NEFA following
   fat, carbohydrate and protein ingestion . . .," J . Atheroscler . Res . 6/4 :
   328-341, July-August 1966 . (No tobacco)

CHAPMAN, W . H . (U . of Wash .), "Effects of oral tobacco tar and a paraffin
   foreign body on the mouse bladder," Ind . Med . & Surg . 35/7 :573, July 1966 .
   (Abstract does not describe results)

CHRONIC RESP . DIS . BRANCH, USPHS, "PHS establishes clinic in fight against
   emphysema," N .Y . State J . Med . 66/16 :2080, Aug . 15, 1966 . ($131,139
   grants to Queens (NY) Hospital Center and affiliates)

FARRAR, G . E . Jr . (Phila .), "Sir Walter Raleigh," Phila . Med . 62/15 :670-672,
   Aug . 5, 1966 . (Tells "Non-Smokers' Club" history of tobacco ; approves
   S .G . Report)

GRAY, J . M . 3e HANSON, G . C . (England), "Mediastinal emphysema : etiology,
   diagnosis, and treatment," Thorax 21/4 :325-332, July 1966 . ("Mixed
   etiologica .l factors (The mode of production is not yet certain) ." -- No

                CONFIDENTIAL : TIMN                            0231006
38 .

GRUMELLI, E . & GOI, A . (Italy), "Contractile response of the tracheal muscle
   to various pharmacological agents," Boll . Chim . Farm . 105/4 :318-322,
   1966 : Chem . Abstr . 65/5 :7837b, Aug . 29, 1966 . (Nicotine etc . tested in
   cats, rats, rabbits)

HELLERSTEIN, H . K . (Western Reserve U .), "Anesthesiologists should quit
   smoking," Med . Florld News 7/32 :9, Sept . 2, 1966 . (Also should exercise
   more, give up coffee breaks)

HILDING, D . A . & HILDING, A . C . (Duluth), "Ultrastructure of tracheal cilia
   and cells during regeneration," Ann . Oto . Rhino . Lar . 75/2 :281-294,
       June 1966 . (R?bbits' ciliary injuries studied : no tobacco)

HORN, D . (USA), "Scare tactics no solution to smoking habit," Med . News
  (London) Aug . 21E, 1966 :5 . (Horn said, "There is strong agreement in the
  US that the use of fright techniques and macabre themes in anti-smoking
  programs are not effective in producing change," in describing $2 million
  US anti-smoking grants on visit to England)

INSCOE, M . N . (NaL . Bur . of Standards), "Losses due to adsorption during
  filtration of at ueous solutions of polycyclic aromatic hydrocarbons,"
  Nature 211 :1083 1085, Sept . 3, 1966 . (Sources of major discrepancies in
  results traced)

JACKANICZ, T . M . (Mich . St . U .), "The incorporation of aspartate and
   malate into the pyridine ring of nicotine," (Thesis : University Microfilms,
   Inc . 66-397)
JOHANNSEN, Z . & P:IEIBISZ, J . (Poland), "Direct effects of smoking on
  spirometric val_lLes in normal subjects and patients with pulmonary emphysema
  and chronic bro7Lchitis," Pol . Arch . Med . Wewn . 36/6 :783-786, 1966 . (No
  significant difVerences after 2 c'ettes between early and advanced emphysema
  or bronchitis aroups ; some individuals showed distinct rise in respiratory
  tract resistanci~ after smoking in both groups)

JONGKEES, L . B . W(Netherlands), "Roken en coronaria-sclerose," Ned . T
  Geneesk . 110/24=1112J . June 11, 1966 . (Quotes 0 . Auerbach's "Nugget of
  lasting value" ;Ls seen by Arch . Otolar . 83/4 :319, 1966, which refers to
  N .E .J . Med . 273_775, 1965 : 89% of heavy smokers had moderate to advanced
  coronary athero=sclerosis)

KASPERBAtER, M . J, & REINERT, R . A . (U . of Ky .), 'Biological detection of
  phytochrome in ~ ;allus tissue of Nicotiana tabacum L .," Nature 211 :714-715,
  Aug . 13, 1966 .

KOELLE, G . (Germaay), "Der Nikotin Abbau des Tabaks, ein Beitrag zur
  Wirkungsweise gLeichsinniger Gene," Z . f . Pflanzenzuchtung 55/4 :375-382,
  July 1966 . (PrLmary effects of genes in tobacco plants directly proportional
  to their number)

 KULLER, L ., LILIEiJFELD, A . & FISHER, R . (Baltimore), "Sudden and unexpected
   deaths due to ??=).tural causes in adults," Arch . Environ . Health 13/2 :236-242,
   Aug . 1966 .

                         CONFIDENTIAL : TIMN                          0231007
                                                                                39 .

LEA, A . J . (2,ngland), "Dietary factors associated with death-rates from certain
  neoplasms Ln man," Lancet 2 :332-333, Aug . 6, 1966 . (Breast, rectal cancers,

LISA, J . R . (NYC), "Metastatic vs . bronchogenic carcinoma," J .A .M .A . 197/12 :
  217, Sept . 19, 1966 . (Reply to Steele (see CD, Sept . 1966, p .3) says
  autopsies _ :xplain his results)

LOKE, Y . W . (Malaysia), "Nasopharyngeal cancer in the Malays," Brit . J .
  Cancer 20/2 :226-230, June 1966 . (Internal rather than external factors
  seen as caises)

LUNDIN, F . E . Jr . et al (NCI), "Temporal relationships of leukemia and lymphoma
  deaths in aeighborhoods," J . Nat . Cancer Inst . 37/2 :123-133, Aug . 1966 .
  (Temporal 10-year pattern in a metropolitan area suggests these diseases
  are communicable)

MATHE'WSON, H . D . (England), "The direct preparation of cigarette smoke condensate
  by high velocity impaction," Coresta 1966-2 :7-1ti .

McGOWAN, A . T . (England), "Chronic bronchitis," Roy . Inst . Pub . Health Hyg . J .
  29/2 :69-73, March-April 1966 . (Relies on U .S . SG's Report in thesis for
  Public HeaLth diploma)

McKENNIS, H . Jr . et al (USA), "The structure of dibromoticonine, a bromination
  product of nicotine," Abstract : 152nd Meet, Am . Chem . Soc ., Sept . 11-16,
  1966, NYC .

METHODIST HG3P•ITAL (Indianapolis), "A pilot project in health hazard programming,"
  J . Indiana State Med . Ass'n . 59/8 :926-928, Aug . 1966 . (Probability of death
  within 10 years weighed for 14 + diseases : if smoking stops, lung cancer and
  hypertensive heart disease risks decline)

MOORE, G . E . (Buffalo, N .Y .), "Filters give false hope," Science News 90 :173,
  Sept . 10, 1966 . "Filter tips found ineffective . . .," Med . World News 7/34 :
  39-40, Sept . 16, 1966 . (Accounts of study of "nine popular brands")

MORIYAMA, I . M . (USPHS), "The Eighth Revision of the International Classification
  of Diseases," Am . J . Pub . Health 56/8 :1277-1280, Aug . 1966 . (To be published
  in 1967)

MORRIS, J . N . et al (England), "Incidence and prediction of ischemic heart
  disease i_n_ London busmen," Lancet 2 :553-559, Sept . 10, 1966 . (1+5 of 667 men
  sampled never smoked cigarettes ; incidence of heart disease was higher in
  smokers ths.n in those not smoking c'ettes when tests began : 7 .9 vs 4 .7 per
  100 men)

MUKAI, G . et al (U . Cal ., Berkeley), "The fate of airborne benz(a)pyrene,",
  Abstract : 152nd Meet, Am . Chem . Soc ., Sept . 11-16, NYC .

MULCAHY, R . (Eirej, "Cancer of stomach," Lancet 2 :388, Aug . 13, 1966 . ("Does
  deep-freezing Lin USAJ impair hypothetical carcinogenic factors . . . in certain

                      CONFIDENTIAL :                               TIMN 0231008
                                                         CONFIDENTIAL :
40 .                                             MINNESOTA TOBACCO LITIGATION

MURMANN, W . et al (Italy), "Central Nervous system effects of four beta-
  adrenergic receptor blocking agents," J . Pharm . Pharmacol . 18/5 :317-318,
  1966 (English) : Chem . Abstr . 65/3 :4445b, Aug . 1, 1966 . (Nicotine among
  products tested in mice)

  52/7 :8-9 . July-Aug . 1966 . (Selected student views on smoking)

OCHSNER, A . (USA), "'Preventable' mortality," Med . News (London) Sept . 9, 1966 :15 .
  (Million children will die of lung cancer unless smoking is eradicated :
  AUERBACH also q>> .oted)

PASTERNAK, G . et ?1 (Germany), "Growth of diethylnitrosamine-induced lung
  tumors in syngei:,eic mice specifically pretreated with X-ray killed tumor
  tissue," Folia :iologica 12/4 :209-304, 1966 (English) . (Inconclusive

PAYNE, L . V ., "Yoi_ can kick the habit," Old Oregon (Pub . by U . of Oregon Alum .
  Assin .) 46/1•lj'-21, July-Aug . 1966 . (Only one of four methods "worked"
   on students) ~

PIERON, R . et al (France), "Les facteurs tiologiques de la bronchite ehronique,"
  Vie Me'dicale 47/'6 :789-798, June 1966 . (Tobacco among many factors cited in

QUAN, P . M . & QUIPf, L . D . (Duke U .), "1,4 ;5,6-tetrahydropyridines from
  catalytic reduc4ion of nicotinoyl derivatives and their ring opening with
  hydrazine," J . Organic Chem . 31/8 :2487-2490, Aug . 1966 .

REITYNBARG, D . I . (USSR), "Smoking and Health," Sovetskoe Zdravookhr . 24/6 :
  78-80, 1965 . (iteview without comments of SG's Report, 1964 . Not translated)

SEKIMOTO, T . (Jap~,n), "The effects of air pollution on chronic respiratory
  diseases," J . K=io Med . Soc . 43/3 :215-226, May 1966 . (Author's English
  summary says 8of 12 patients were exposed to severe air pollution, 11 had
  respiratory dis-ases, 6 smoked)

SHAMBA.UGH, G . E . t.'r . (Editor), "Cigarettes, cough, and cancer of the lung,"
  Arch . Otolaryng 84/2 :121, Aug . 1966 . (Says Boucot JAMA piece (June 13, 1966)
  shows carcinoge<<s in cpette smoke produce cancer whether or not cough is

SMITH, G . M . (Hai=vard M .S .), "Personality correlates of smoking behavior,"
  Am . Psychologis ; : 21/7 :716, July 1966 . (Author's abstract -- 74th Ann . Conv .
  Am . Psychol . As :,In . Sept . 2-6, 1966 rates behavior of student nurses,
  college, and hi,, ;h school students)

SONNENBLICK, B . P (Rutgers), "Environmental relations and the public health . . .,"
 .J . Newark Beth-! :srael Hosp . 17/2 :83-89, April 1966 . (Radiation cancer is
  main thesis : K_i)tin, Percival Pott, polonium-21o in tobacco, among citations
  in review)'

SPODNIK, M . J . Jr et al (U . of Md .) "Effects of environment on respiratory
  function," Arch Environ . Health 13/2 :243-254, Aug . 1966 . (Air pollution,
  smoking effects- studied in 100 white•male college students ; tobacco use
  information incomplete)

                                                                       TIMN 0231009

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