NYSA TI Single-Page 4
f_or (a mm_ si_ _Ung a fall). t_m_ of t_ _vid_
Abstract
Em~an co,tries in the Scv~ ~mrics" Study (G Farchi and A N~enotti, unpublish~ ~ta, 1978). At entry ~se ove~II sco~s ~ alm~ i~t~d in hi~-risk men bnt averaged 5".
Fields
- Named Organization
- Agriculture Department (USDA)
- American Cancer Society
- American College of Chest Physicians
- American Farm Bureau
- American Heart Association (Voluntary health organization that focuses on cardiac health)Voluntary health organization that focuses on cardiac health and stroke. AHA occasionally teams with tobacco retailers to engage in promotions/fund-raisers (see http://www.smokefree.net/doc-alert/messages/247136.html and http://www.rawbw.com/~jpk/stand/Pictures.html).
- American Lung AssociationVoluntary health organization concerned with fighting lung disease, promoting lung health and advocating clean air, indoors and out.
- American Medical Association House of Delegates
- Appropriations Committee
- Association for Cancer Research
- British Medical Association
- CBS (Columbia Broadcasting System)
- Chapel Hill
- Columbia University
- Committee on Agriculture
- Commodity Credit Corporation (Lender to tobacco farmers, part of U.S. Dept. of Agriculture)Lends money to tobacco farmers cooperatives, is part of the U.S. Dept. of Agriculture.
- Davidson College
- Department of Agriculture (USDA)
- *Department of Health, Education, and Welfare (HEW) (use United States Departmen (use @hew_dept)
- DuPont
- East Carolina University
- Environmental Protection Agency (EPA)
- Farm Bureau
- Federal Aviation Administration (FAA)
- Federal Communications Commission (FCC)
- Fortune
- General Accounting Office
- GPO (government printing office)
- House of Representatives
- Imperial Tobacco Co. (Determined optimum nicotine levels for cigarettes)Did testing pre-1972? of U.K. smokers and concluded that the optimum nicotine delivery for the cigarette, and that stepwise reductions in delivery caused progressive rejection by consumers (see Project Wheat)
- Indiana University (Located in Bloomington, Indiana)
- Lancet
- London School of Hygiene and Tropical Medicine
- Mason Research Institute (Evaluated smoking machines for animal inhalation studies)Evaluated smoking machines for animal inhalation studies and did toxicity tests on rodents.
- Merck (pharmaceutical company)
- Middle Tennessee State University
- NASA
- National Institute of General Medical Sciences (part of NIH est. 1962)
- New York University
- Plenum Press
- R.J. Reynolds Corporation (second tier subsidiary of RJR Industries)
- R.J. Reynolds Industries, Inc.
- Reader's Digest
- Research Council
- Reuters (News organization)
- Rockefeller Foundation
- Roswell Park Memorial Institute
- Royal College of Physicians (Monitors the quality of Canadian/U.K. medical education)
- Rural Development
- Senate
- State Department
- Tobacco and Health Research Institute (University of Kentucky)
- Tobacco Associates Inc.
- Tobacco Institute (Industry Trade Association)The purpose of the Institute was to defeat legislation unfavorable to the industry, put a positive spin on the tobacco industry, bolster the industry's credibility with legislators and the public, and help maintain the controversy over "the primary issue" (the health issue).
- Tobacco Warehouse Association
- U.S. Department of Agriculture
- United States Senate
- University of Athens
- *University of California (use specific branch)
- University of Kentucky
- University of Leeds
- University of Mississippi
- University of North Carolina
- Wall Street Journal
- Wayne State University
- White House
- World Health Organization (Concerned with global public health)International organization concered with public health worldwide
- Named Person
- Ames, Bruce N.
- Aronow, Wilbert S.
- Barnes, Michael
- Barr, Laura
- Beach, Myrtle
- Becker, Carl
- Bergland, Bob
- Block, John (United States Department of Agriculture)
- Block, John R.
- Boggs, Hal
- Breaux, John
- Bridges, Byrn A., Ph.D. (Microbiologist, U. of Sussex, Cell Mutation Unit)Carcinogenesis & Mutagenesis researcher
- Bro, Susan L.
- Bryant, Frank
- Butz, Earl (U.S. Department of Agriculture Secretary, 1972.)
- Byron, Beverly B.
- Califano, Joseph A.
- Califano, Joseph A., III
- Califano, Joseph Anthony, Jr. (Sec. of U.S. Dept. of Health, Education, and Welfare)Joseph Califano Jr. is the former secretary of Health, Education and Welfare (1977-1979), in Carter's administration (A 5/17/94; WP 4/3/85). He spoke against the tobacco industry on ABC's "Day One" program. He testified before the Waxman subcommittee on 5/17/94. He was an adviser to President Lyndon B. Johnson (AP 5/17/94). He was President of Columbia University's Center on Addiction and Substance Abuse, circa 1994 (AP 5/17/94).
- Cart, Edward A.
- Christensen, Rob
- Christopher, F. Hundall, Jr. (RJR Director (1982-85, 87-89))Defense
- Cook, Marlow Webster (TI Attorney, Shook Hardy & Bacon, Senator (R-Kentucky) 1968)
- Cooley, Harold
- Cooley, Harold D.
- Cunningham, Donald J.
- Cyrus, John
- Danes, Shannon
- Day, Sandra
- Dole, Robert (U.S. Vice President, Senator (R-KS))Defense
- Doll, Richard
- Dunlop, George
- Dupont, Robert
- East, John
- Edmondson, Spencer S., Jr.
- English, Glenn
- Faulk, Page
- Frick, Kenneth
- Gaskins, Cecil
- Glasson, Vernie
- Godfrey, Horace
- Graham, Jim
- Harden, Blaine
- Harkin, Tom
- Helms, Jesse (U.S. Senator, (R-North Carolina))Strongly pro-tobacco
- Helms, Jesse A.
- Hickey, Andrew J.
- Hooks, Billy
- Hopkins, Larry J.
- Huber, Gary L., M.D. (Harvard University: Conducted Smoke Inhalation Studies)Testified for industry
- Humphries, Bill
- Hunt, James B., Jr.
- Hunt, Jim
- Ill, G. Rose
- Inouye, Daniel
- Jenrette, John W., Jr.
- *Johnson, James W. (use Johnston, James W.) (RJR Executive VP, resigned in 1984, 1989-1996)Returned to RJR in 1989, resigned in 1996
- Jones, Walter (leader of Tobacco Caucus)
- Jones, Walter B.
- Kahn, Donald R.
- Kennedy, Edward
- Kennedy, Edward M.
- Kornegay, Horace A.
- Kornegay, Horace R. (TI President and Exec. Director)VP Leaf Ops (RJR), TI Chairman (1985)
- Krieger, Barry
- Lair, Richard
- Lawther, Patrick J.
- Lennon, Alton A.
- Lesher, William G.
- Levin, Steve
- Long, Clarence D.
- Louise, Sarah
- Marr, Jean
- McBride, Virgil L. (RJR public affairs)
- Mcdonough, Robert
- Merrit, John
- Mikulski, Barbara
- Miller, George
- Mira, Joe
- Morgan, Robert A. (Philip Morris, Inc. Scientist)Robert A. Morgan was a Philip Morris, Inc. scientist.
- Nahas, Gabriel
- Natcher, William H.
- Neas, Ivan
- O'Neill, Tip
- Osgood, Charles
- Part, Gary
- Patton, Bob
- Peterson, J. R. (Pres., RJR Board of Directors '76-80, Exec. VP '76-81)Served on R.J. Reynolds Board of Directors, 1976-80, and as Executive Vice President from 1976-81. Formerly president of Pillsbury.
- Peyser, Peter
- Pinney, John M.
- Poole, Bob
- Powers, Sue
- Preyer, L. Richardson
- Price, Season
- Pyle, Howard, III
- Rather, Dan (T.V. News Anchor)
- Reid, Donald
- Richardson, Oscar
- Richardson, Sarah Louise
- Richmond, Fred
- Richmond, Frederick W.
- Rimm, Alfred
- Roach, Eugene
- Rose, Charles
- Rose, Charles G.
- Rose, Charles G., III
- Rose, Charlie (U.S. Rep. (D-NC) 1986-1994)Tobacco grower political ally.
- Rose, Frances Duckworth
- Rose, Geoffrey
- Rosenkranz, Herbert S.
- Said, Rose
- Sanford, Terry
- Scott, Bob
- Senkus, Murray (RJR Director of Research c. 1968-early 1980s)
- Shuman, Michael
- Simmon, Vincent F.
- Sledge, John
- Smith, G. Dee (RJR Director 1970-86; Pres.&CEO RJRI 1976-80)G. D. Smith was Director for RJR Tobacco Co. 1970-1986 and Executive Vice President & Assistant to the President in 1985. (Source: R. J. Reynolds Summary - RJR Liability Notebook). G. D. Smith worked for RJR Tobacco International Inc. as President & CEO 1976-1980; Accounting Positions in 1955; Manager of Cost Accounting in 1963; Assistant Comptroller in 1968; Comptroller in 1970; Vice President in 1972, Senior Vice President in 1973, Executive Vice President in 1973, and on the Board of Directors in 1983. (Source: RJR Who's Who NMLRP)
- Start, Robert I.
- Stokes, Colin H. (RJR Chairman & CEO 1973-78)Defense
- Tashkin, Donald, M.D. (Pulmonologist, U of CA, Los Angeles, Industry Expert)
- Taylor, Ron
- Terry, Luther Leonidas, M.D. (Surgeon General, 61-65, U of Pennsylvania, Anti-Tobacco Expe)Luther Terry was former Surgeon General of the United States Public Health Service from 1961 to 1965. Terry was emeritus professor of Research Medicine at the University of Pennsylvania School of Medicine in 1984 (E. Whelan 1984).
- Thompson, Daniel
- Turner, Carlton
- Vashon, Louis
- Watson, George B.
- Wehr, Elizabeth
- Whit, Charlie
- White, Paul C., Jr.
- Whitley, Charles O. (TI Spokesman, U.S. Representative (D-NC))
- Whitley, Charlie O.
- Wicker, Tom
- Wingerson, Lois
- Wright, Richard
- Zahn, Hilda
- Zahn, Leonard S. (CTR Public Relations consultant)Leonard Zahn & Associates, Public Relations consultant to the tobacco industry
- Zeiger, Errol
- Master ID
- TI09781644-3113
- TI09781644 DHEW Publication No. (NIH) 74-544 DEPARTMENT OF HEALTH, EDUCATION AND WELFARE Public Health Service
- TI09781828 Indermight
- TI09782012
- TI09782196
- TI09782564 4- Reading an A_erican magazine recently, I cane across a state=ent about what is happening in
- TI09782748 the )nehostion of fl find- many ueh as invade Fig, 7. Roentgen film of the chest showing a
- TI09782932 0 I_f. B. Rosenblat'r
Related Documents:
Document Images
on all examined subjects). Table II preterits a mo~t ret-med aml.vm.
• m~ at ~ to ~ ~ to ~t~te hit ~fi~ ~ f~ th~
f~or (a mm~ si~ ~Ung a fall). ~ t~m~ of t~ ~vid~
c~n~ ~ ~ c~rc~ by sub~t~ f~ it ~e
val~ for t~ control ~p to allow ~ for ~y drift L~t mi~t
have ~u~cd indc~ndcmt of our inte~cntion and for rcgress~n
towardg the n~n. ~i~lly thi~ corr~ed e,ti~te of ~ ~ect of
inte~enti~ ~s exp~ as a ~rc~m~ of ~c initial ~an ~he
for t~ intc~'~tion group at a whole. S~t~tical ~i~nce
call,ted by a r te~t on the diffcr~e b~n the ~
for intervention and c~trol ~amp~.
~e ri~ factor le~h at ~ry gene~l~ ~ ~m ~tc~
bet~cn the intervcntion and control g~upL The ~st dis~ri~
10
S
140
130
5-9
E
5.5
80
o ...... o Cmtrol group
~ Intervention group
Plasma cholesterol
b~ 2~ . . .
0 I 2 3 4 F
Yec~r
~IG 2--T~stimated mean risk levels for men in random
samples.
w~ for body w~tght m the-high-risk racn (~ l). ~ich
c~mbm~ ]l~ to o~I1 ~. ~'~O ~ ~
m~t~le ~tm ~+ ~i~ to mdivid~ls" val~s f~
c~ ~ed ~ ~y, ~t~ b~ p~ssu~, ph~ c~l~t~l
c~t~, ~d ~y ~s ~d~. T~ wcigh~ ~c~ts)
appli~ to ~ch factor were ~o~ derived fr~ t~ ~per~cc of t~
Em~an co,tries in the Scv~ ~mrics" Study (G Farchi and
A N~enotti, unpublish~ ~ta, 1978). At entry ~se ove~II
sco~s ~ alm~ i~t~d in hi~-risk men bnt averaged 5".
hi~er in inte~¢nt~ ~n
1SIGH-RISK MEN
High-risk men showed the largest changes in risk factor levels.
They reported a decline in mean daily cigarette consumption of
29% at the end of the first year, and this effect was sustained. Thc
controls changcd little, so that the corrected c~tlnmte for the effect
of intervention at the final examination was again -29".. (table II);
by then 12% of those who were smokcrs at entry had stopped
completely.
Blood pressure showed a large regression to thc mean in both
groups, but throughout the trial the systolic pressure averaged
about 3 mm Hg lower in the intervention group. Systolic prcssurcs
of 160 mm Hg or more were recorded in 38", of the high-risk men
in the intervention group initially and in 16% at final examination.
An almost identical fall occurred in the control group.
Advice on cholesteroI-towering diets was more concentrated in
the early months of the trial. After one year the plasma cholesterol
concentration in men in the intervention group fell by an average of
8~.~, and 75~. claimed to have changed their eating habits. Judging
by the two-year results in the control group, about half this fall
represented the effects of intervention. Little dietary advice was
given in the second year, and the gain was lost entirely. After renewed
efforts in the next two years the estimated effect of intervention was a
fall of 6.9°,t~ at four years (table II). During the final stages of the
trial the nurses were fully occupied with examinations, and once again
most of the ground was lost.
Individual advice on weight loss was given to those high-risk men
who were I5% or more overweight. By the two-year examination the
high-rlsk group as a whole had lost t.4 kg more than their controls.
The whole of this advantage was later lost.
The estimates of overall changes in risk suggested that the benefit
at the end of year ] of about 20% had all been lost by a year later.
But during the final three and a half years the net effect of intervention
in these high-risk men averaged - 12%, or - 11% over the whole trial.
REMAIND~ OF STUDY POPULATION
Results for r~ndom samples of both intervention and control
grow~ are give~x i~ fig 2 and table II. Reported cigarette consumption
was substantially ~du~l by int*rvention throughout the trial: at the
final examinations the corrected estimate of change was - 19% for the
whole intervention g~ap, or -16% when hig.b,-risk men w,re ex-
cluded. About 9~ ~ of smoker~ lad by then been persuaded to stop (7%
excluding high-risk men). Special measures to reduce blood pre~ure
TN]LE tl--Pereemage me,at ¢~ar~ in riA faaor .Car i~iduab in interoentian group, corr*c2ed for
~r~ol~adi~*~ clmr~es in ce.,~trol F~u~
High-ri=k inert Random sample
T109782380

Ietter~, bookkts, and po~ers. Conversations whh ~ ~ su~d
that t~e ~ a ~c ~, ~ at ~h of ~c ~ ~
" " a~ ~¢'~, of ~ose ~' ~amined (e~l~mg
high-ri~ men) r~ ~at they ~d c~ged their ~ting ~bi~.
O~ecfive ~ of c~nge ~, ~r, n~ligib]e. In t~ m~d~
3~a~ of t~ tr~l ~e ~ ~s ~ to advise thc~ men individual~,
the c~t~ c$t~te at four y~r$ x~$ of a fall averages 4%
(ruble ]I). ~i$ ~t di~ in t~ final st~ ~ ~e trY, w~
the int~ntion effo~ ~d to be relaxed. No eff~ts on b~y ~i~t
~ ~t at any ~, ~ o~i~t ~ ~d ~i~
postal advice in the firs~ year.
Overall there wcrc no clear differences bctw~n ~e intervention
and control ~u~ in total ri~ estimates. Over ~e whoie per~d of
the trial, the net eff~t of ~nte~ention on ove~ll risk averaged
u~er 4~.
Resulm o~ physical activhy have not been presented,
there *~s no adequate m~surc of ~sponsc, though some indivi~a]s
~e~ised energetically and persistemly. Annual quemionnaires
su~ested a persis~ modest advantage to ~e ime~enfion group.
Thus at gout years, for example, vigorous exercise was repor~ by
35% of the intervention g~up compared with 22% of co~trols. This
estimate of response could ~ll be exaggerated.
EFFECT OF SCREENING IN CONTROL MEN"
We did not know what effects screening might have on behaviour
or use of medical care in the control group, and the assessment of
changes in incidence will therefore be based on the 90°., of control
men who had no contact with the trial until the final examination.
A comparison of risk-factor levels at the final examination berc,'ecn
this 90% and the remaining 10% of men who had been examined
before showed almost identical results for smoking~ cholesterol, and
weight, but a significant difference in blood pressure. The average
was 4.1!2.0 mm Hg lower in the men who had been screened before.
Since few had been referred for treatment, this presumably resulted
from habituation to medical examinations.
Discussion
The control of coronary heart disease necessarily depends on
prevention, since treatment so often comes too late. Mass
medication is potentially dangerous~s and it would be better if
risk factors could be controlled by changing habits. To be
effective in middle age this would require that the risk factors
did cause the disease, that the progress of the disease could be
altered, ~nd thin those advised c~uld c1~age tl~ir habk~. This
report deals with the last of these issues. The answers to the
first .~nd second depend on showing dumges i~ the k~cideace of
disease and will form the subject of a subsequent report from
the WHO European Co|labo~at~vc Trial.
Screening ~nd health education require t~e same rigorou~
evaluation as a new treaunent, but this has to be organised at
community level, which makes it difficult to obtain a suitable
control group. The North Karelia project in Finland" and the
Th~e Communities study in California' each u~ed a sLugle
community as control, but this gives no estimate of
bility of results, and it is impo~ible to assess statistical
significance* We therefore inck~cd many o~mmunitie~ in the
study and then randomised these, rather u~n individuals, to
intervention or control status. This produced two
group~, and the conu'ols remained free from contamination by
the intervention programme proceeding elsewhere.
T~ne meab-~ selected for evak~ion were b~ed on the
choice today. /v~re debatable was the level of remurcc~
appropriate to implementing Lhe programme. It could be
argued that a marc hazard to public health m~it~ a ma~or
inve~.mcnt in its ~xol, bu~: we had to make do lm'gely w~Ja
what wa~ available. A bigger eff~'t might have achieved bigger
r~uhs. Periodic examinatio~ of .~all random ~.'-aples, cxmpled
~ Mk"D[CAL JOL'I~*gAL
15 xu, dto~ 19~t
with good respoose rates, pr~-/ded an excellent m-ml
memas of ~itor~g p~s. ~itc ~pl~g c~
oval ~e~ ~ clear. ~ results s~w the n~ity ~ a
c~t~ group to i~ntify ~d allow for rcgr~sion to the mean
(b~ pressure and ch~esteml), habi~uati~ ,o ~minauon
procures (bl~d ~), ~d ~x~ ch~s
out thc t~ thc wholc stay ~pulation x~s cx~'d to con-
flicting prcssurcs f~m advcrti~ ~d health cdu~tion).
It p~cd rclativcly casy to disscminatc information ~d
men's rcs~scs to q~fi~ing~f~ ~mplc, by thc end of
first year 75' ,, of high-risk men and 30".. of the remainder
claimed ro ~ve ch~d thor caring habits in r~ to
advlce~but their claims were nor paralleled by ~rcspunding
~anges in plasma ~olesterol concentrations and ~dy weight.
This was particularly evident in the men who were m~ at high-
risk and who, during the e~ly stages of the trial, received
letters and ~n~al p~p~anda. ~opaganda seemed ~cctive
a me~s of spreading informatk~, but a substantial c~ngc
habits seemed to require some personal
The screening ex~inations proved to be a two-edged weapon.
In gener~ ~ey stimulated interest in the aims of the project,
and enhanced the receptiveness to advice of the high-risk men
re, led for personal consultation. The remaining men, however,
tended to regard a satisfactory report as tantamount to some
sort of ~arantee of health, even though their letter warned that
heart attacks could still happen. Only after four years, when
many had re~ntly been recalled for personal dietary advice,
was there any evidence of an effect on dietary habits in the
inte~ention group as a whole. When the interv~mion effort was
later relaxed this benefit was soon lost.
The only strong and maintained effect of mass advice was
on the number of cigarettes reported as smoked, which was
persistently reduced in the intervention group. If this reduction
was real this could be an important benefit, but the claims are
unvalidated. Other centres in the WHO ~llaborative Trial
are examining the use of plasma thiocyanate levels as a means
of validation.
The high-risk men responded better to advice. ~heir reported
fall in cigarette coasumption was larger, and the percentage of
smokers appeared to be reduced. Average blood pressure levels
were lowered by a few millimetres. The measures of the effc~ of
dietary c~ge on pl~ma cholesterol levels reflected the
amour of recent personal advice~ being greatest in the first
year (about 3% allowing for estimated regression to the mean)
and the fourth year (6-9%). Even these modest responses were
q~ckly lost when re~lar personal ~ntact c~ld not be main-
tained. The same was true of weight loss. Perhaps dietary
advice needs to be ~ded in ~e sa~ way as l~-term d~g
~eatm~t, ~i~ sustained ~ns~tations and en~u~gement
over ~e
T~e ~ial has sh~a that ~na~ risk factors ~n be ch~d
ia the w~kiag popularly, Wen p~pcr org~i~i~ ~d some
sapplemen~i~ ~ ~isting res~s. But cha~¢s were not
large, ~d we ~ave not shown ~at they can be su~ined. The
pa~icipativ~ oc~tlon~ physicim~s concluded that on p~sent
evidence ~ would not ~mmend the gene~ introduction
of ~s ~ of sc~ni~ ~d ~eal~ education s~vi~. At the
same time ~ reprised ~eidenml ben~ts h ~e form of
cl~er ~n~ wi~ em~oyees, ~d ~'~1 individual
were d~ted ~ m~ n~ng ~tm~.
If a r~acti~ ~ risk fa~o~ ~ to be a~cd by a
~s~ate f~l ~ risk then the ove~l ~ x~k of the
hi~-fi~ men was r~u~d by an estimated a~ of 11%
~d of the inte~emi~ ~up as a whole by ~ ave~e of 4%.
~ ~ ~ b~ ~t a r~ ofcv~ IIOL ~
~t ~ ~ ~th w~ ~ cqui~[e~t f~ m~ny other
w~t • rare ~e~ive ~ ~u~mi~d cffor~ m~t achieve.
We thank the medical staff, rnanagcrm.'nts, track- tmions, and em-
ployees, all of whom co-operated Wlcndidly; Prof~so~ V H T Jam~
TI09782381

~d Mrs P Hopgood for =holc~crol ettirtmtitms; oor c~ ~
A G~, ~ M~ K O~. ~ ~u~ ~ ~ ~ ~
~lpful thro~t. ~N~-K ~ re~ m~ ~
prov~cd by Glaxo Ltd.
The fo]~wing com~nie~ a~ ~pati~al ph~ician~ ~ipat~ :
British Airwa}~ (Dr~ D M B~t~, I M ~n, C C O ~fl);
British Steel ~rmion (Drs J A E Ricb~ds, G B D~m, A
Si~ir, C F R~, the ~t¢ C R T~mas, J B ~¢~t~); ~db~-
~hw~s Ltd (Dr C ~¢); ~I M~ Indu~h~! Hcahh
S~'~e (the late Dr G E Ff~h); G~t Ke~ Nettlefold Ltd (Drs P L
~I~ar: ] A R~', L E Tyler); Guin~ Ltd (Dr B M ~am~);
Ilford L~d (Drs V O S~ew~, D ~ul]) ; Ko~k Ltd (D~ M Falconer,
G Hughes, K W Harbord, T Kelly); May and Baker Ltd (Dr J
Cmhbcrt); Phili~ Ind~tricz (Dr D J Terry); Royal Ordnance
Factor" (~he late Dr Tyrer, Dr C Edward~); Shell Chemical~ UK L~
(Dr C M S ~pp~); Tare and Lyle Refinerie~ Ltd (Dr G L ~c~d).
751
Referem=es =
l J~nt Worl~g Party o~ the Ro~I Co'ego ~ Ph~mc~ ~ ~ ~
~ R Call P~uoa~ ~ 1~76;10~!3-75.
~ ~ G. A ~d t~ of h~ di~ ~cnt~n in md~t~'. Try,
~ Ot~p Aicd 1970~:1~-1 !.
in t~ multff~t~ml ~tion o[ coma~ ~rt dts~. Intff &pidtmwl
1074~:219-24.
t Waik~ SH, Dun~n DB. Estimati~ of the probability of an event as a
fun~ ~ s~c~ in,pendent vafia~s. Biomnrtka 1967#4:167-70.
t ~tt~ ~ Pri~i~l Instate. A c~rati~ tml in the ~m~"
p~*cnt~n of i~h~mic heart di~asc using clofib~tc. Br Heart ~
1978;40:10~-118.
t ~s~ P. N~h Ka~lia ~t, a pr~ for ~uni~ c~tml of
~rdiovascular diseases. Publications of the Univcrsi~ of Kuopio.
~mmunity Health 1974; Series A:I.
7 F~qu~r JW, ~c~by N, W~ PD, a al. Community ~cation for
~rdiovas~lar health. Lancet 19~7 ;i : 1192-5.
Vitamin D supplements in pregnant Asian women:
effects on calcium status and fetal growth
GBROOKE, IRFBROWN, CDMBONE, NDCARTER, HJWCLEEVE,
MAXWELL, V P ROBINSON, S M WINDER
Summary and conclusions
In a double-blind trial of vitamin D supplements in
pregnant Asian worsen calciferol (ergocalciferol, 1000
IU/day) was administered to 59 women and placebo to
67 controls during the last trimester. The two groups
had similar distributions of maternal age, height, parity,
number of vegetarians, countries of origin, and sex and
gestation of the infants.
At entry to the trial maternal serum 25-hydroxy
vitamin D (25-OHD) concentrations were low in both
treatment and control groups and significantly lower in
vegetarians than non-vegetarians. Mothers in the treat-
ment group gained weight faster in the last trimester
than those in the control group~ and at term they and
their infants all had adequate plasma 25-OHD con-
centrations..~others a~ infants in the control group,
however, had low plasma concentrations of 2fi-OH~D
St George's Hosp|tal. London SWI? ORE
Department of Child Hem|th
0 G BROOKE, ~n, ~ar.l% senior l~turer
N D CA~TER, ~nD, ~ni~ lectu~r
Dew.meat ~ ~e~ Pathology
1 R F BROWN, P~ ~a~Ar~, l~tu~r
H ~ W CLEEVE, ~p~, senior l~t~r
De~me~ of O~tet~ a~ Gyaa~gy
V P RO~NSO~, u~ ~n~r ~tmr
and calcium and raised plasma alkaline phosphatase
(bone isoenzyme) activity. Five of these infants developed
symptomatic hypocalcaemia. Almost twice as many
infants in the control group were small for gestatlonal
age (29% v 15%), but there were no significant differences
between the two groups of infants in anthropometric
measurements. Infants in the control group, however,
had larger fontanelles, suggesting impaired ossification
of the skull.
Because of the benefits to mothers and infants in the
treatment group and the absence of side effects, vitamin
D supplements should be given to all pregnant Asian
women in the United Kingdom.
Introduction
Despite improved living standards there is continuing clinical
and biochemical evidence of vitamin D deficiency in As/an
immigrants, both among children and adults? This problem is
not confmed to Scotland and the north of England, where
winter sunlight hours are short, and Turton er al recently
showed that vitamin D deficiency occurred in pregnant
Asian women in the south Londo~ di~ict of Tooting, which
contains a relatively affluent Asian community.:
Osteomaiacia is a wcll-recogniscd complication of pregnancy
in Asians living in the United Kingdom." Asian women appear
to be particularly at risk of vitamin D deficiency during
pregnancy, since low co~ccntraticaas of 25-h.xxtVOgT vitamin D
(25-OHD) are fuund at this time.: *-' Possible nemaatal con-
sequences of this deficiency include hypocalcacmia,: craniot abes ,'
and frank z4~ckz,~s.' Since the ~ to the fetus of subcl/nieal
maternal vitamin D deficiency axe not ck~arly defined and since
birth size of Indian Asians in Britain is le~s than that of north
Europeans and Negroes," ~° we have undertaken a trial, using
cakifel~l (crgocakZderol) supplements, to investigate the
effects of the vitamin tm maternal and infant oJ~_-ittm honx~-
costasis and fetal growth.
T109782382

14
were seen with the leanmorgeat rel IUD with eke greater daily
rdease ra~e, w~ ~nar~ occu~ ~ a ~ with
an iml~ix~d release r~e well bdow the amount normally
measured for this model,js
The daily amotmt ofprogcstagen released can be reduced
by using a potent c~,apound like levonorgcstrcl, and thus the
lifelime of r~ach a medicated device can be prolonged by
• several years. This could make the need for medical interven-
tion more infrequent and the increase in the number ofdays
of intermenstmal spotting usually occurring immediately
after insertion ofa r/ew IUD can therefore be avoided. The
levonorgestrd IUDs of the present study have been
calculated m have a life,an of~t least seven years.)+
No case of pelvic infection was noted daring the present
study. A predisposing factor for ascending i~fecrions is an in-
creased number of d~ys of bleeding, and the fewer days of
bleeding associated with the levonorgestrel IUDs thus pro-
tect against pelvic inflammatory disease.
Although the differences were not statistically significant,
the rates of pregnancy ~nd expulsion were numerically lower
with the levonorgestrel IUDs than with the control IUD.
Amenorrhoea as a reason for removal of the device was found
only with the levonorgestrel tUDg experimental studies;3'1(
suggest that it was not associated with a deterioration in the
hormonat function of the subjects. Levonorgestrel-rdeasing
IUDs significantly reduce menstrual blood loss: the total
number of days of bleeding, except during the first 2-3
months, is less than with the nova-T device and continues to
fail with time. There seems to be no problem of infection with
levonorgestrel IUD% and the pregnancy rates are very low
and do not seem to be affected by the skill of the inserter.
initial spotting was not the reason for many removals and was
neither a health problem nor an inconvenience. In view of.
these findings the use of the potent progestagen,
levonorgestrel, for intrauterine release seems to be a most
promising new approach to achieving a long-lasting
intrauterine contraceptive device equally suitable for both
developing and developed countries.
This work was undertaken as part of the contraceptive development
programme sl~raored and coordinated by the International Committee for
Contr~ceptlon Re.arch of the Pop~laHon Cooncil, Inc., l~¢wYork. We thank
the staffofthe ¢linles for their eoopera lion and the Intemationa! Devdopm ent
Resea~ca C~nrte of C.annda, the U.S. Agency for Internalion:l Development
(gram A|Dtpha,.~ l ] 16)~ the Fe~d Fo~andalJoa~ the Rockefeller Foundation,
and the (3ooJ. Hecht Fund for fmanchlsupl~ort. Thceontcnt ofth~s work does
not necessarily reflect the policy ofany of the Funding murves.
gc~uots lot rcpdms should h¢ ~dr~.*ed tO C. G. H.
M. J. SHIPLEY BRIOHY J. TBO~S
Iummar3, Inn longitudinal study of civil servant%
1422 men were classified according to their
average daily alcohol lotto:Over 10 years of follow-up, the
mortality rate was lower in men reporting moderate alcohol
intake tha~n in either non-drinkers or heavier drinkers (>34 g
alcohol per day). Cardiovascular mort alley was greater in non-
drinkers and non-cardiovascular mortality was greater in the
heavier drinkers. The heavier drinkers had higher mean
blood pressures and contained- a greater proportion of
smokers.~ multivariate analysis showed this U-shaped
relationship between reported alcohol consumption and
subsequent mortality to be largely independent of differences
in ~blood pressure, plasma cholesterol, and grade of
cmploym~
Introduction
THE question of a safe limit o falcohot consumption has not
been resolved. Alcoholics have a higher mortality rate than
the average,~ but this tells us little of the risks of more
moderate drinking. There have been few studies on non-
institutionalised popuJations of the relation between alcohol
consumption and mortality. There are reports that moderate
drinkers have a lower mortality rate than either heavy
drinkers or abstainers~'~ and that moderate drinking may
DR HLI._SSON AND OTHER'S: REF'EXENCE~--conI~nu~d
9. Nilnon CG. A d-notges.d-rdeaging IUD. M.D. t hesit, Univer~iv/ofHdsi~, 1977.
10. Nilsson CG, Luuk~in~ T, Arko H. Endomeu~l mowholo~ in women using
! I. ~il~ ~. ~m~ndve quancks~i~ of m~ns~al bl~ ~s with a ~n~gcstreb
~d~fing IUD and * ~ev~T~p~r d~. ~nua~r ~a 19771 ! ~:
12. ~ ~ Lu.~ T. lm~o~m~t of t 6norg~t~el.rcl~ng IUD.
~ntra~t~a I977; t3:
TI09782383

We have invesdg~ed the rdation between estimated
akehoi comumtxkm and mort-Airy over the subsequent ]0
yearn of follow-up in a longltud|n#l study ofa sarn~ td'mcn
ha active employment, the Whltchall Srody ofclvil ~crva~ts?
The analysis takes into account smokJatg and o~er risk
Methods
In 1967-69) a screening examination was carried out on 18 403
male civil ae-rvant~ al~ed 40-64, wocking in several departments in
and around London" The ~xamlnati~ included a questionnaire,
determination of Mood pre~ure, and mcgstlrcmc~t Of
chol~ co~emWa~i~a. A I -i~10 sample of~he f'~rst I~ 000 men
screened Were asked to return by mail a completed dietary record
that listed everything eaten or d.r~nk ~ a 3-day period (Sm~hy,
Monday, Tuesday).
The response rate to this request was 89% and 1422 completed
dietary records were received. The food items consumed were coded
according to type and amount. Nutrlcnt intake was calculat~ by
means ofcomputcriscd analysis based ou food tables made available
by Misa Jean Marr and UlXlated by us. The mc~ure of alcohol
Latake comes from this 3~day record of dietary intake.
For over 99% of the men, ~ccords in the N.H.S. Cer~tfa| Registry
were idemL6¢d and flagged. A copy ofthc death certificate ha~ beta
provided for each man who died, in the LLK., during the 10 years
from examination. Dcatlx certificates wcrc coded by the O~cc of
Population Ccususcs and Surveys.
Age-standardlsation was by the direct method using the total
population zs standard. Rdativc risks (strictly, relative betting odds)
and t~ts of significance w-re calculated by fitting multiple iogisdc
regressions to the data using the statistical package G.L.I.M.~° This
allowed the significancc and size of the alcohol-mortality
relationship to be assessed after taking into account the ctTects of
age, cigarette smoking, blood pressure, plasma choIcsv'rol c-oncen-
trafion~ and grade of employment. It also aliowed us to test for a
linear or quadratic U-shaped relationship ofalcuhoi with morxality.
Results
The nutrient analysis of the dietary record produced
figures for alcoholconsumption in g/day~ here cazcgoris~l as
0~ >0-9~ ~9-34~ >34 g/day. The General Household
Survey~ referred to "onc drink" (8-10 g alcohol) as being
halfa p'mt of beer (2~t mt), one mcasureo~'spirits(23-25 ml),
on~ 2 oz gl~ss of port or sherry (56 ml), or one 4 oz glass of
wine (1|2 ml). Our highest alcohol category therefore is
roughly equivalent.to four or more &inks consumccl per day.
Table ~ shows the per ~nt of men who died in 10 y~rs of
f~Row-u!b according to age and ~h¢ amount of alcohol tb.cy
reported having consumed at entry into the study. Among
men aged 50-59 and 60-64, the albcau~e mortality ha those
who consumed no alcohoI on the days ofdictary recording is
~er than in those whose reported alcohol intake corr~-
spond~ m 0" 1-34 g/day. The "heavy'* ~rir~s C~.34 g/day)
haw a Mghe.r mortally than Llte mod¢~ dfird~ers. ~he
overaR rdativc risk~ adiusdng for age, is shown arbitrarily
~ the men ha ~e 0-1-9 g/day ca ~t~ory m have a r~lativc
risk of 1-0.
To ~est f~r sig:aificance of the U-shaped relatioashi~ a
qna&-afic carve was fi~ed m the data. Th~s was significant
(p=0-021), The axal variation ia ~clativc risks, as estimamd
by X~ was mahaly ac~oumed for by Lhc wdafion du~ m the
This U-shaped relat~ of alcohol m total atonality
4O-49
5O-59
6O-64
0 0-1-9
2.9 5.2
12-~ 4.7
po~ 072)
20-0 15-9
1 "$
9-1-34 >~4
4.9 5-0
(!~4) (~)
7-3 !1-4
(177)
$-7 21-7
1"! I-~
*Fitting a quadratic (U-sha~) curve |o ~bcs¢ tel=five fi=~ ~e~ Z; =5.29
U-shaped relationship is largely the result of a higher cardio-
vascular mortality in the "non-drinkers" and a higher non-
cardiovascular mortality in the "heavy" drinkers. Of the 63
cardiovascular deaths, 49 were due to coronary heart disease.
Restricting the analysis to those who died from coronary
heart disease did not change the pattern of a higher mortality
among the "non-drinkers" and little difference in mortality
between the other drinking groups.
The mortality from non-cardiovascular causes is shown for
cancer and other causes in table II. For both these categories
there is the suggestion of a U-shaped relationship (not sig-
n~cant) with the highest mortality in the men reporting the
heaviest drinking. The 7 deaths due to "other" causes in the
heaviest drinking category were from pneumonia (2), chronic
bronchitis (1), disease of the larynx (1), hiatus hernia (1), and
suicide (2). Only 1 of the total of 21 "other" deaths was due to
cirrhosis and 2 to motor vehicle accidents.
The high mortality among "abstainers" could be the result
of people who were already sick at the time of examination,
having given up alcohol and subsequently having a higher
than average mortality rate. If this were so the higher mor-
tality in the abstainers would be most marked in the first years
of follow-up and become less marked the longer the follow-up
period. HowcveG when we examined the mortality rates after
excluding deaths in the first 2 y~ars of the I0 years follow-up,
~e U-shaped relation between alcohol intake and mortality
was scea a~ strongly as shown above.
The possibi~ty must be coo-sidereal that the observed rela-
tionship b~tweca alcohol and mortality may be the result of
10'
8.
%6"
Z-
ALcohol, (giddy}
T100782384

582
Othe~
TABLE |H-- BLOOD PRE.SSURI~, SMOK LI¢O, AND PIM~MA CHOLI~'~EROL
LEVEI~ I~ ALCOHOL C~NS~MPTION: ~E.AD~USTI~D ME.~aM$ (AND
STAI~ RD ERROP~J
*rnrno~1= m~dl+ 38-7. °
0
136"9
(0-96)
85.0
(o-e5)
42- !
16-6
(0-56)
5-19
(o-o63)
]37-8 134-2 139-7
0"~) (l.It) (I-~)
85-3 ~,~ 87.3
(o-~ (o.~) (o-9~)
36-5 37.5 52.8
(0-62) (0-75) (0-98)
5-27 5-22 5-26
(o-~e) (o.~4) (o-oe4)
other factors. Table III shows mean systolic and diastolic
blood pressures to be highest in the heaviest drinkers. Both
the per cent of men who were smokers and the mean number
of cigarettes consumed per day per smoker show a U-shaped
relationship to alcohol consumption, higher in the non-
drinkers and higher in the heavy drinkers. There was no asso-
ciation between alcohol consumption and plasma cholesterol
concentration.
L~able IX.' shows the all-cause mortality (~ge-standardlsed)
according to alcohol consumption and smoking. The
moderate drinkers (0-1-34 g/day) have a lower mortality rate
than the non-drinkers, regardless of smoking status. Only
among the ex-smokers do the moderate drinkers not also have
a lower mortality tha~ the heavy drinker~
This analysis was done separately for eardiovasoalar and
non-cardiovascular mortality~,.~..mong smokers the previous
pattern was seen--higher ¢ardiovasoalar mortality in non-
drinkers, higher non-cardiovascular mortality in heavy
drinkers. It w~ less clearly seen in the non-smokers, bat there
were Few dea~
To take into account not }use smoking but also the number
of'clgarettes smoked, a multivariate analysis was done which
0"1-9 9-1-34 >M
3"6 3-4 7-I
~-4 6-2 4.2
7-) 7-9 13-8
~=0-~5) and ~ overa~ ~ ~tween ~lcohol c~tegofi~ ~c~
75-{.e., the qua~adc rehfiomMp =~nts f~ m~t ~e diffe~c~
~lween ~legoriet.
adjusted for age, smoking habit (non-smoker, ex-smoker, and
1-9, 10-19, or >20 cigarettes/day), systolic blood pressure,
plasma cholesterol, and grade of.employment. The results are
summarised in table V as relative risks, the group reporting
0.1-9 g alcohol/day being assigned a relative risk of 1- 0. The
magnitude oftbe relative risks shown in table I are reduced
slightly (p = 0- 065) but the overall pattern is the same. Thus,
to a major extent, the association between alcohol and
mortality is independent of" the factors included in this
analysis.
Discussion
In this study, alcohol intake was assessed by analysing the
report of 3 days' dietary intake. This dietary method has been
studied for other nutrients and has been shown to result in
substantial errors in classifying indlvlduals,t2 It is unlikely
that random errors could account for the lCmttem ofmortality
observed. A serious bias would arise h'heavy drinkers failed
to report their use of alcohol and were wrongly classified as
non.drinkers. This could east doubt on the high mortality of
the non-drlnkers, although not of the heavy drinkers.
A spuriously high mortality among non-drinkers could al~o
occur if men who were already sick and at high risk of dying
gave up the use ofalcohol. When we confined our analysis to
the last 8 years of Follow-up the association did not weaken.
We have no information on past drinking histories. However,
Room and Day examined this poss~ility in a study ofsamples
6ftbe U.S. popu.lation.~ They similarly found a higher mor-
tality in abstainers than in moderate drinkers. Removing
from the analysis people who reported their health to be poor
did not change this. Amoa~g tt~e *'healthy", moderate drini~ra
e~periet~eed a lo~.r mortality than a~stalners.)
Other studies rapport the f'mding of an apparem|y pro-
tectlve effect of moderate alcohol consumption in cardio-
vasoalar disease?n Dyer et 81., reviewing the relation of
alcohol to cardiovascolar disease, point out that some studiea
show a harmful effect of atcohoL4 In general the poskive
smdi¢~ have shown the at-risk category to consist o~problem
drinker~ of'wh0m there were likely to be t"ew in our group
with the highest alcohol im~ke of >34 g/day. A protective
effect of alcohol o~ ¢ardio,caseular di$c~-'e could be medimed
by the eft .e.~t ofa|ooh~t ~ fairing HDL cholesterolI~ ]-~te~,
Keys has sugge~ttml that ~ HDL Ievek predi*ixxse to
higher ratea off" non-cardiova~oahr mort~ty.~ Ifconfirmed
th~ ~ld be a mediator of the adverse effect~ ¢ff~ghet ~
of alcohol emmampdoaL
It lm~ been suggested that the protecdv~ effect ofalenhol i,
confirmd ~o wine.~ Our ara~,~is did not di~tlngu~ the form
of~ drunk, k k po~s~l~ ~t it is not the ethanol itseff
T109782385

sumcd more alcohol than men in the lower grades; inclmion
of grade of empkffmem ha the multivariate analysis made
lit-de d'~K'reu~ te the resuks. Hence, k is untigdy that the
higher mortality among heavy drinkers ob, er~ed in this
pop,orion was the reault of general social ch~ differences.
Similarly, the association between smoking and drinking
appeared to account for llttle of the higher mortality. The
most likdy conclusion is that men who consume more than 34
g of alo~hol (4 or more 6riffles) pox day incur an Lnc~eascd
mortality risk. The size of the study does not permit us to
estimate mortality for subgroups of this >34 g alcohol
categmy.
There is historical precedent for this limit. Anstie in 1864
proposed that an amount of drink equivalent to about 35 g of
alcohoI W..r day was the safe limit,ts The public health
message is not a slmlSte one. Our data on alcohol suggest that
moderation is associated with longevity, but that small
increases above that are associated with a shortening of life.
Before recommending that everyone take one or two drinks
per day, we must bear in mind that a higher mean level of
alcohol intake in a population is usually associated with a
higher proportionofpeople suffering from alcohol-associated
problems--not only mortality but also social and biological
disability,t6
We thank the civil servants who gave their time to participate in this study;
the Civll Service Medical Advisory DeFaixment (in particular, the late Sir
Daniel Thompson, DrA. Blair Harlngton, and Dr Adrian Semmence) for their
hdp; and Miss Lind:~ Colwell who processed the death certiiicales. M. G. M. is
supported in part by a grant from the British Heart Fou ndadon, arid the ~tudy
was supported by a g~am from the Tobacco Research Council.
Requests for reprints should be addressed to M. G. M., Department of
Medical $lali*tles and Epidemiology, London School of Hygiene and Trolfical
Medicine, Keppel Streth London WCIE 7HT.
I. Surglby P. Ak'otm|ixm am~ moiety. ~ Univ~tsltc~sforlagct, 1967.
2. Pearl ~ ~koh~l a~ I~gcvhy. New Y~ Alfred & Kno~, 1926.
~. R~m ~ Day ~. ~hol t~ ~ality. In: alcohol ~d health: ~¢w k~wled[e ""
(~ t~l ~n m the U.~ ~te~ Wu~n~ D~ U.~ Govtr~
P~ti~ 0~, 1~4.79-~.
M3
Prelimimry Communications
VI SEROLOGY I1~ THE DETECTIO~ OF
TYPHOID CARRIERS
C~ZLES M. NOL~
Departmem ~f M~dio'~% U,f~ersity ~
PAUL C. WHITE, JR
Ar~as ~ate D~runem of Hmlt~ Li~tk R~ Ar~ns~
JOHN ~ FEEL~ ED~H A. HAM~IE
SUSAN L. BRO%~ KwEI-HAY Wo~
~t~ for Dixmu Cont~ At~nm, G~
Summa~ A new haemagglutination assay for Vi
antibodies was evaluated in searches for
symptom-free carriers of Salmonella typhi associated with
sporadic cases of typhoid fever. The assay differs from pre-
vious ones in that a purified (instead o fcrude)Vi antigen from
Girrobacter was used to sensitise the red blood cells. In ten
sporadic outbre~s of typhoid stool c~lmre identified seven
enteric carriers orS. typhi among the patients' families or
other close contacts. All seven carriers had Vi antibodies in
titres ranging from 1:40 to 1:256.0. Moreover, among thirty-
seven stool-culture-negative contacts of patients, only one
had Vi antibodies, in a titre ofl: 10. Thus, the new assay for Vi
antibodies was as sensitive and as specific as faecal culture in
detecting symptom-free typhoid carriers. It could become a
convenient screening test.
INTRODUCTION
THE response ofpublic-heakh agencies to a sporadic case of
typhoid fever includes a search for a symptom-free enteric
carrier ofSalmonella ~yphi. In the United States, such carriers
have been discovered among the patients' close contacts in
30% of cases,t Full advantage should be taken ofthese oppor-
tunities to identify symptom-free typhoid carriers in order to
attempt to eradicate the infection or at least to institute sur-
veillance measures that will minimise the risk of further
spread of the organism.
Searches for typhoid carriers are often costly and tedious.
Three negative facto!cultures are traditionally required toex-
el~de each s~tspeet, ~nd many of" the~e c~ltures mast be ob-
tained from individuals who are elderly, have a poor under-
standing oFthe circumstances, and may consequently be
pieious and uncooperative.
A reliable screening test would greatly facilitate typlmid-
carrier evaluations. We have reported that 71% ofsymptom-
free chrot~ic typhoid carriers had ,emm-amibodies to a puff-
fm:i highly p.olymerised Vi antigen-' and that these antibodies
specifically correlated wkh faecal excretion of,g C~phi. The
present study was designed m assess the use~he~ of this Vi
serological test in the sea~h for undiagnoscd enteric carriers
associated with sporadic cases oftyphold fever.
MATERIA/.~ AND METHOD~
For a fottr-year period ~i~ in Jaa~, 1~6, ~h ~¢ ~
TI09782386

"I'I2TR~I~LOID F/~ROBLA~I'S ~ FAa~ILIA.L
POLYPOSIS CO~
~ract~ b7 muMpte ~t~ ~ ~ ~
~c m~li~nL F~ ~ t~ G~s ~ va~-
ant of F~ s~w ~ni~ ~ ~ in ~id~ to
~lonlc ~i~. S~nn~ ~* e( ~. ~a~* that t~trap~y
but not familial ~ly~[s wi*bom ~tra~nlc l~iom. Su~-
qu~ly ~ ~up ~ o~e v~on in the ~ of
tc~rap~ skin fi~ ~ ~h ~mff~l ~ly~ z~
Ga~ncPs synd~me and su~cst~ t~at th~s w~ duc to genetic
het~enehy,z ~e ~uH ~ke to ~ke a p~l~inary re~rt ~
our findings in thirt~n ~ly~ ~d~s, tw~ve of whom a~
on ~e ~r of St Mark*s ~i~.
Fib~b~zs~s we~ ~hu~ by stand~ ~eth~s f~m skin
samples, 3 mm squa~, no~ally taken from the in~ su~acc
of tb~ fo~arm. S~c~I p~mary ~Ru~ wc~ ~t u~ wilh
h~man or fetal c~If scr~m as m~ium supplemcnl~ but som~
times only one cuhurc p~uccd a viable line of fibmblasts.
Ch~m~ome prc~radons wc~ usua{ly made at s~nd or
third passage aRer 5-7 weeks' culture. The ~lypo~is patients
ranged in age from 13 to 66 years; the cont~]s were ten nor-
mal Peo#e s# ~tw~n I I and 56 yca~. Clinical information
Dec footnote) and Parentage of tetraploidy in cuhurcd fib~
btast~ are given in the table.
TETRAPLOID FIBROBLASTS IN FPC PATIENTS AND CONTROLS
FPC TetrapIoidy
i 6-5% 0-8
2 33.0"
3 65.0"
4 34.0"
$ 1.0% 2.7", 1.2, 5.0
6 4-5"
7 7.5", 2.0
8 I-0", 1-4"
9 4.5
I0 3.5
11 3.0", 1.4
12 1.5", 1.5, 1-3
13 8.1", 0-4, 6-0, 5.1
Contro[~ Tetraploldy
1 3.0", 10-0°, l-0
2 10,5% ii.5", 2.0
3 I-0", 5.0"
4 i7-0"
5 0-0", 4-5", 1.0, 4.0
6 1-5", 5-0", 1.0
7 8-0°, 4.0", 8.5*
8 3.5% 2.0
9 4-5
10 4-0
"Primar cultures initiated in medium with human serum. Tetra-
ploidy expressed as % of 200 dividing cells per chromosome harvest.
In FPC patient 2 only 90 cells were available. All FPC patients had
adcnomas with cancer (cases 1, 2, 4), epldermuld cysts (cases I0, 11,
? 2), ostenma (case 2), ?fibroma (case 5), and congenital retinal pig-
mentation (ease 8). All except patients 1 and 13 have a family history
of polyposis coil
There was considerable variation in levels of-tetraploidy in
independently established li~es from the same patient or con-
trot. The higher perecm~g~cs for ~ach person usually correlate
wi~h initiation o/the culture in medlu,m supplemcmcd with
human serum. Sin~ one comml wlue was as high ~ 11.5~
we wouM ~mider this only FFC lines 2, 3, and ~ show
e~ascd mtmptoldy. Shannon Danes has c~m~ that the prow
ence of cpithdlal cells is n~mry to demonstrate incr~sM
tu~s &PC 2 and 4) w~ic~ sho~ b~ tetraplo~y had no
¢pith~al out~wth in the pri~ ~lm~, hcn~ incased
~t~oidy n~ n~ ~ ~at~ to the p~ce ~ cultu~
epithe~al ~. ~r ~ ~ dam wi~ sampl~g
at later ~a~ (~n or mo~), ind~ thin tctra#oidy d~
not in~a~ wi~ ~ge level ~ ~in fib~bl~.ts f~ aff~t~
or ~m~ls. ~e ~ tkat the ~1 line with the hlg~s~ tetra-
pb~y (~ 3) ex~it~ th~ ~ ~r~ ~ ~gc t~
~me~ a: di~,d~r~'/.~a¢~ 19"/~; ~ leAS.
1365
~o.
/
Piti~ ~ 7 ~ 9 m ~ ~ ~m~ 12;
~a~s. Patinas FPC 2 a~ FPC 11 a~ a~ ~ ~d are
t~ t~ ~ticn~ d~t to ~ving h~c G~uer sy~
ph~otype. Howcv~, the lords of tctrapl~y in ~cir ~ltur~
~in fi~ m ~y ~t. ~ f~ ~m
~ ~i~ that the ~ vafiat~ ~ ~n ~mi~
tctraploidy ~vels in tither FPC or ~Mner's syndrome
sampling or cuhufing effects.
~ ~k ~ su~rt~ by the ~r R~a~
U~ty ~ ~n, Joy D. A. D~L
~n NW) 2HE MARY B. PRLTCHARD
St Mark's H~#tal, H.J.R. BUSS EY
~ndon ECt B.C. MORSON
I'~"~ LOW TAR CIGARETTE SMOKING
Sm,--ln the survey of over 18 000 male Civil Servants, Dr
Higenbottam and his colleagues (Feb. 23, p. 409) conclude
that the tar yield of cigarettes smoked influences phlegm pro-
ductlon but not the degree of airflow obstruction. Closer exam-
ination of the data, kindly provided by Prof. G. A. Rose (see
table), demonstrates not only that dccrcas~Id is associ-
ated with an increase in forced expiratory volume but also that
this association is similar in magnitude to that between dc-
crcased tar yield and decreased phlegm prevalence.
MEAN FEV (ADJUSTED FOR AGE AND HBIGHT) AND ~o PHLEGM
INCIDENCE (ADJUSTED FOR AGE) BY NUMBER OF CIGARETTES
SMOKED AND TAR LEVEL
Number of ~ FEV~
cigarettes ..............
per day" n n
1-9 I 3"2810"015 102~
$[ /2~_~ I 15801 13"31 10"055 II
1 3.1410.047 23
[ _333_ I 197 I 3"171 0.035
I0=19 [ 18-23 II096 I 3.1610-016 178
, 24-27 I lO+l 3.1slo.o52 16.
28-32 I 231 I 3-07 I 0-034 39:
, 33+ I 26913.0310.032
20+ tI~-23II0,~6 [ 3.05 1 0.0~5 ~08~
2~27 [ g51~.0310.055
. ~32 ] 230[ 3.011~.032
n=number of mac obse~ S~:sttnderd er~r.
A~em~ a~{~ mi~ints of 5, 15 and ~ ~tt~ ~r day
~ in reg~ssioa ana~sis.
A~m~ appellate mid~nts of 2~ 2~, 30, and 3~ mg us~ in
~es~ioa analysis.
~ phlegm
; [ 29.2s I s.so
' [ 32.03 1 2.40
'112.0112-09
' I ~.40 I ~-00
,1 44.7Z I
~4-24
My Conc|usioas were st~ggestcd by ~¢ o~mion that, ~r
~th the f~ expiratory vot~me (FE~ and phlegm datg
s~nses in the hi~est tar ~up ~r 1-9 d~rcttes a day
sm~ ~ fimi~r ~ thee h ~e b~ tar ~up for 1~19
a day smokes ~d that t~ in the hi~¢st tar ~up ~r
t~19 a ~y ~ ~re fimilar to thee h t~ lowest tar
g~p ~r ~e~ of ~ ~ mo~ ~tt~ a ~y. ~is tug-
~st~ that ~ucing tar y~ld by a~ut haff(f~m
18-23 ~ had a ~milar ~t
mm~n ~ a~ut half (f~
1~19 m 1-9 a~y) ~h f~ FEV~ #~
~dmlve ch~ m
T109782387

1366
C;garctles ~ ~r ~ a~ T ~s t~ 1~ y~ ~n
rcgr~s~ c~i~nts ~or c~[[es ~ tar y~c~ wcrc
in ~nit~ and ~th ~ndc~ntly highly significant
(p<O.001), their 95~ ~fi~nce limits ~Jn~ r~tivcly
-O.Ol~m -O.~a~ ~.Ol13m
~]e my ~vi~ c~s~s do ~ n~arily ~mo~
s~rmc an cff~t of tar ~r ~ ~ FEV ~cls~ ~n~ ~me o~h~
~ invoDcd i~stcad, they do not pro~de any a priori
sup~rtlng Higcn~ttam and ~ll~gues' su~cstion that it is
the gas~s p~ of ¢obac~ smoke rather than the tar that
to study the relationship ~[w~n FEV and smoke
yields in currem ciga~tte smokers, now thai many smogers
smoke cigarettes wkh a subs~amiatly lower tar ~ield than
smoked at ~he time ~he ~urvey was carried out.
25 Ctdar R~,
Sunon SM2 5~
PREVALENCE OF MITRAL VALVE PROLAPSE IN AN
AUSTRALIAN POPULATION
StR,--Mrs Bonella and her co-workers (April 19, p. 880)
describe an increase in crosslinked procollagen in floppy mitral
valves removed at surgery and 39~ of single-chain procollagen
in these valves with none detectable in normal valves. Mitral
vane prolapse is common in the general population and these
findings raise the question of the significance of this diagnosis.
We have assessed 200 volunteers (100 men and 100 women)
for mltral valve prolapse by M-mode echocardiography using
rigid and accepted criteria for the diagnosis' with additional
criteria to exclude false positives. The volunteers responded to
an advertisement in the hospital magazine stating that we
wished to establish normal values for our echocardiography
laboratory. This yielded a group with a wider age spectrum
(mean age +SD, 38.8+12.1 years; range 18-79) than that
reported in previous studies. There were eight subjects with
unequivocal late systolic mitral valve prolapse, 4 men and 4
women, giving a prevalence of 4%.
In 5 of these 8, systolic clicks and/or late systolic murmurs
were present on auscultation or on the phonocardiogram, but
in the other 3 mitral-valve prolapse could not be detected clini-
cally or by phonoeaediography. There were eltmtrocardio-
graphic abnormalities in 2~T-wave changes in 1 and left axis
deviation in the othea'. 1 had atypical chest l~in and I breath-
}e~nes~ for which no reason could bc identified. None
plain~ of palpitations.
A voiuntocr group may not be r~presentative of the whole
population. However, the prevalence we found was remark-
ably similar to that reported in two of the thr~e major Ameri-
can studies, one in young womena and the other in young
men.) "rh¢ one other study4 reported a much higher frequency
in young women and the possible reasons for this will be dis,
c~ssed elsewhere. Ia a series of 294 routine necropsies Hi~i
iBtr LAI~CET, JU~E 21,19g0
ai3 found ~ vaiv¢~ in 5'L (::kady mitral valvc laXla¢sc
is common in the general r, otmlation and the frequency is
approximatc~ the same in men a~d women.
The complications of mitral val~c prolapse, the most com-
mon being severe mitral regurgitation, ar~ uncommon, bow-
ever. For example, only 11~. of ari single mitrabvalve replace-
merits undertaken over the past two years in this
cardiopulmonary unit were for Sloppy mitral valves, and a
similar incidence bat bee~ roported from the U.S.~ and the
U.K.~ The disparity between these numbers and a prevalence
rate of 4'~ in the general population is striking.
There are two immediate questions. How can indlvioMals
with mitrabvalvc prolapse and a high risk of complications be
defined? Bariow and Pococks suggest that of people with
mitral-vatve prolapse those with a Marfan babitus may r~re-
sent a group at risk of having sever~ mhral ~eg~rgha,ion. But
there are as yet no data to support this. The other question is
whether the myxomatous transformation found in patients
with floppy mitral valves and scvero mhrat regurgitation is a
non-specific reaction in a congenitally malformed valve or
whether it is an expression of a specific mesoderma! abnor-
mality with the mhralvalve being the main target organ. The
interesting observation of accumulation of procollagcn in
floppy mitral valves removed at surgery for severe mitral
regnrghation reported by Bonclla ¢t aL support this possibility
but clearly does not setde the matter.
I'rmc¢ Hene.~ Hospha|, ANDREW J. HICKEY
I.mle Hay, New South Wales 2036, Australia DAVID E. L. W1LCKEN
A/'/LNION FOR LEG ULCERS
Sm,--I was delighted to read the papers by Professor Page
Faulk and colleagues (May 31) on the use of human amnlon
in the treatment of chronlc ulceration of the legs.
"l'wenty years ago, whilst a student nurse at Grey's Hospi-
tal, Pietcrmaritzburg, South Africa, a G~y's trained physician,
the late Dr R. R. McKenzie, used fresh amnion for the treat-
ment of his patients with leg ulceration. It was one of my daily
tasks to fetch fresh amnion suspended in saline from the ma-
ternity ward. As my training progressed I was permitted to do
the dressings. We were instructed to use the amnion as soon
as it arrived on the ward. It was applied directly to the wound
(which had been cleaned with normal saline), and covered by
a non-adherent dressing. The limb was firmly bandaged with
cr~pe bandages and elevated. This was standard practice for
all Dr McKenzle's patients with chronic ulceration of the legs.
We never expected the treatment to fail or the supply of
amnion to dwindle.
In 1967, as a staff nurse on a gynmcologieal wa~ at a I.on-
don teaching h~pital, I suggested the same treatment for a
patient with a chronic-varicose ulcer. My suggestion was
greeted with scorn but an adventurous registrar allowed me
one chance to prove the ~x:acy of amnioa, ~rovid~l tl~ con-
sultant was not informed. Within two w~eks ~to my great
relief) the wound granulated well and autografting was not
thought nee.essary. A ddighted patient was di,schargcd cured of
both her gynecological and varicose problems. However, I
unable to live down the reputation of rattllng bones and hav-
ing consone~ with African wkch-doctors.
Recently, having returned to nursing after a g~p of some
5. Hill l~ Oa~ M.J. ~rti~ /~V. The ~t~
6. ~y DA, Geraml S, HaBmIn G~ ~kar~ ~ Hall
1972; ~ 3~.
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