Tobacco Documents Online

COAR6SPOHDf3NC6 arms, illegal drugs, and narcotim. Further, it is very commendable that itdluential medical journals like 77. Lmtcer contribute to the disclosure of the agenda of organisations that will not contribute to stop such trade. However, I do not understand why your editorial indicates that an advocacy for increased effort against infectious and other poverry-related diseases should be in conflict with a stand against trade of harmful commodities and other imponam threats to health. It is a well documented fact that infectious diseases represent the greatest disease burden for the poor of the world, and that we in the more-developed world have the most cost-effective interventions. As shawn among orhers by Gwatkin and colleagues, the effect of intervention among The poor will also be largest if morc resources are made available for the "unfinished agenda" of prevention and treatment of these diseases. This is also the policy of WHO, as expressed in the World Health Report 1999: °First and furemast, drere is a need to reduce the burden of excess mortality and motbidity suffered by the poor ... it will mean focusing more on interventions that we know can achieve the greatest health gain possible within prevailing resource limits".4 The report goes' to mention that renewed attention is necessary for diseases like mberculosis, malaria, HN/AIDS, and immunisation programmes, in addition to the diseases of mothers and children. A well accepted ethical criterion for resource allocation in the health sector is first to attend to those with the greatest needs. On the global scale, it is clear that those with the largest deficiencies in terms of access to prevention and care are the poor, and that their greatest and most immediate threats to heahh cnme from infectious diseases. I hope The Loncer will not obfuscate this fact by indicating that those who present arguments to this effect serve to create "a manipulated dichotomy in global health policy." Gunnar Kv31e Centre for Intemadonal Hexlth, tlniwrshY ol Bergen, 5021 tiergen. Nonaay (email: gunnar.lei&e®tih.uo.no) I Muorul.AmaofplWetNdichotomyin BIobJ hohb pofiry_ fmv<r 2000; 355: 1923. 2 GwatGn DN, Guiar M, Hcuvdine P. The bnNen of d;sease amung the global poer. lanm 1999; 354: 586-89. 3 geddy KS. ITe burden nf discasc amnng tbe global poor. tausr 1999; 354: 14T1. 4 WHO.lLe World Health F<port 1999- Malung a difkrence. Geoevs: WHO, 1999. Space flight related anorexia Sir-Laurence Vico and colleagues (May 6, p 1607)' described effects of long-term microgmviry exposure on can¢llous and conical weight bearing bones ufcosmonauta. They interpreted their results to be the adaptive effect related solely to the micrograviry environment of space. Corrdation of bone loss with diet and leptin (adipocyte food intake hormone) was not done. However, it is a critical hormone to measure, because it is now known that leprin has a global influence on bone metabolism, particularly calcium loss from bone. If leptin concentrations were found to be raised, this would significantly contribute to the bone demineralisa- tion chat occurs in space, because leptin stimulates osteoblast activity directly and influences calcium homeostasis via a central mechanism,' and also contributes to space flight related anorexia. Also, an alteration in leptin concentrations can be induced by a continuous light environment, as in space flights. We are studying central and peripheral mechanisms responsible for space flight related anorexia. Daily food intake (FI) is a product of meal size (MZ) and meal number (MN)- ie, FI=MNxMZ. Evidence indicates that normally meal number and size are independently and reciprocally regulated in the hypothalamus. Daily or circadian rhythms are seen in feeding behaviour. Circadian rhythms in food intake are disrupted by hypothalamic lesions, gonadectomy, and The complete absence of a dark period within 24 h. The temporal organisation and rhythmicity of feeding may be associated-with the diurnal fluctuations of various neuro- transmitters and hormones (eg, adrenaline, norepinephriny dopamine, seroconin, GABA, and certain peptides such as cyto6nes, glucose, insulin, glucagon, oestrogen (growth hormone and corticosteroids). Disruption in the normal circadian rhythm, such as by increasing the light period, induced metabolic,' hormonal,' and neuro- chemical changes,' which influence behaviouml outcomes including food intake. Food consumption during spaceflight is reduced to 70% the required and recommended intake. We propose that this reduction is a result of continuous light environment. Using a rat eater meter, with 24-h continuous light exposure for 7 days, we measured food intake and meal number and size and examined the changes in dopamine: seromnin ratio in hypothalamus related to food intake. We also measured plasma cortisol, leptin, insulin oestradiol, testosteronq and mmour necrosis factor a(TNFa). Controls continued in the 12 h light- dark cycle. After I week mu were killed and blood and brain samples were collected. Tissue from lateral and medial hypothalamus, aloag with suptachiasmatic nucleus and cortez were homogenised and high performance liquid chromatography was done to measure dopamine and seroronin. Data showed that during the 12 h light-dark period both groups had similar intakes, but during continuous light, food intake decreased significantly via a decrease in meal number. Dopamine and serutonin concentrations in the ventromedial nucleus (VMN) and lateral hypothalamic area increased. Plasma cortisol and leptinincreased, while a decrease was seen in insulin, TNF-u, oestradinl, and testosterone. These data suggest continuous light stimulus via direct effect on the suprachissmatic nucleus and indirect effect on the VMN induces endacrine and neurochemical changes in these rats. The observed changes in food intake, hypothalamic monoamines, and peripheral hormonessuggest that besides microgravity, continuous light environment in space shuttles contributes to observed anorexia, and its metabolic sequelae including bone loss. Madhu Varma, Tomoi Satn, Lihua Zhang, •Michael M Meguid Newosdenoe Pmgam, Surgirsl Mefebalism and Nutrition labaratory, nelanment of Surgery, Universay Hospital, SUNY Upstate Medical Univer5lty. NewYork. NY ]321U. USA (e-maio meguidm@upstateedu) I Vm L, Collet P, Cndpundon A, c W. Effette af bug-term micmgraviw eaposure aocenom arrd corucal we;8ht-bearing boncsofcosmunams.Laaw2808:355: 16/l7-Il. 2 Dury P, Amling M, Takeda S, er ai. f<ytin hdtibits bone formadon through a hypothalamic rcl.y: a crntral cmtrol of bone man. Cd1200q 1U8: 197-207. 3 fukin tM, Moore gl. BHecn or photoperiod on body weieht and faod intake ofabese and leen Zncker Raa 1ifi, .Tnn¢e.1991; 49: 735-15. 4 Cvijie G, )anic-Sibslic V, Dcmajo M, Kankaecvic A, Peuuvic VM. Tbe dfccu of wntinuoua light and darkneas on the acdviry of manoemine avdase A aod B in The hypothalamus, ovaries and vteus of nts. Aue PAycid Himg t99ff; 85: 269-76. 5 Ivanlaevic Mitovenovik K, Stevenovk-Wncar 0, Demajo 0, Kankasevic M, Pmtic A. 7Le eflect of mnm Ugbt In The con<cntntion of caad:olamirc of The hypothalamus aud adreuW glandi eircWatory ACTN and prognterone. J EMonimlInuerr 1995; IS: 378-03. THfi L1NChT- Vol 356 - August 19, 2000 681

COBftSSPONDENCE Foree on Tobacco Control which is chaired by WHO. Global generalisations about the relative importance of the com- municable and non-communicable disease only go so far, a point that is made in the Gwatkin and Guillot analysis referred to in your editorial. The burden of disease in Eastertt Europe, for example, diBers greatly from the burden in sub-Saharan Africa. The Bank's work at the country level responds to country conditiom and the country context. You bizarrely suggest that the Bank had a hand in some wrong-minded recust editadals in the WaR Sneu 9oumul and the Times of London. You allege that the Bank has convetted "tobacco into an issue of individual choice rather than one of cWlective responsibility for public health". Yet in 1999, the World Bank published Curbing iha apidemic' gouernmenn and rhe a'.unonavs nJ tobacco conna[,' which argued strongly that tobacco control is a severe pubhc-health problem for which thero arc clear justifications for govemmenml intervention. The Bank urges governments to carry out measures that are highly inimicable to international business interests. One indicator of the importance we give to tobacco control is that Curbing the epidemic is being published in 12 languages with help from the US Centers for Disease Control and Prevention, WHO, the Pan-American Health Office, and other parmers-an all-time record for any World Bank publication. Mamphela Ramphele, one of the Bank's Managing Directors, will represent the Bank at the forthcoming World Con(erence on Tobacco or Health, in Chicago, USA, where the policy recommendations in Curbing the epidearic and some of the analytic work supported by the Bank in cnuntdes around the world will be discussed. Contrary -to your unsubstantiated allegations, the World Bank strongly supports the health agenda set out by WHO. You refer to a "deepening rift among intemational agencies", but in fact the partnership between WHO and the World Bank is stronger than ever before-and especially in tobacco contml. Eduardo A Ooryan, 'lames Chnstopher Losa?/ace Hunan Development Netwark, The World Bank, Washingnn. OC 20433, u5A I FAUorial.AmanipWareddshoromyinglobal heahh pnliryv fm:u.2000; 35$: 1923. 2 Wwld gank. Cu,big the epidemic: govemmeors aod the emmmiie of rnhacco control. Hemdoo: World gank, 1999. Sir-In your editorial on global health pohcy' you made two implicit or explicit obsetvations about the World Trade Organization (WTO) both of which .eveal gross misundetatandings about the WTO and the international trade rules that it establishes. The first is to suggest that the WTO, through its mandate to promote open markets, is ettcouraging "the exchange of harmful commodities-firearms, landmines, psychoactive substances, tutsafe pharmaceuticals, contaminated food, and hazardous waste", apparently on the basis that the WTO's position on free markets requires all these matters be left to "individual choice rather than one of collective responsibility for public health". You go on to say that "free trade has health consequences, and these should be faced, nor shouted down". The notion, being presented, therefore, is that the WTO equates with a total absence of govcmment intervention. This is completely false. No country would accept international tmde rules which restrict its ability to regulate the marketing and importation of the products which the editorial mentions. The WTO's rules make it extremely clear that WTO member countries have an absolute right to ban or restrict the sale and importation of goods when doing so u necessary to protect public health at the level that they choose. This has never been called into doubt and all the products which are mentioned would typically be subject to such restrictions in most if not all WTO membets. To take another example, most WTO members restrict the sale of alcohol in some measure, whether on health, public-order, or public mortality grounds. This causes no probletn vis-a- vis WTO rules, if the restrictions apply equally to domestically-produced and hnportedalcohol. - In more general terms, the WTO rules allow for the fact that govemments may need to intervene to deal with market imperfections and further, that where markets are nor the most suitable means of ineeting social needs, they can be superseded entirely. Far from being incompatible with strong government and appropriate government intervention in markets, the market economy is predicated on such governance-including ensuring the provision of basic services, the protection of property rights, and the role of law- Although the market is a remarkable mechanism for hamessing the energies of individuals in the social interest, government intervention will always be necessary to stmcture markets in such a way that they serve this purpose and to prevent actions that would be harmful to others. Indeed, the WTO system of consensus-based multilateral trade mles, aimed, as they are, at ensuring the rule of multilateral Iaw in trade relations, can itself be seen as an expression of rhe importance of good governance, this time at the international level. The second allegation made is that the WTO is "opposing the health agenda set out by WHO". I have no idea where you obtained this notion. To start with, it is no[ the job of the WTO to have a view about the health agenda set out by the WHO. In the WTO, we respea fully the competettce of the WHO as the body through which the international commuruty expresses its will in regard to health issues and the WTO has no mechanism for taking a view on such matters. However, to the extent that tmde and health do interact, we work closely with the WHO in helping it carry out the mandate that its member governments (which are essentially the same govemments as make up the membership of rhe WTO) have given it. For example, the WTO seQe®tiat participates actively in the WHOIFAO's Ad Hoc Inter-Agency Task Force on Tobaa.ro Control and coropetates with activity on food safety mattets and access to drugs. In fact, the working relationa between the two organisations have neverbeen closer. Mike Moore World T2de Organiration,1211 Geneva 21, Swinenznd 1 FditonaLAmu,ipWstddkhutomym170bil hcalth poliry. fa.ra 2000; 355: 1923. Sir-In your June 3 editorial' and with reference to a report by Gwatkin and colleagues' you question the appropriateness of putting com- municable diseases on the top of the global health agenda. It seems that TAe Lancer fears that focusing on infectious diseases among the global poor will divert attention from the fight against the tobacco industry and the hatmful effects of free trade of hstmful commodities. In support of this view, the editorial quotes a statement in a leaer to 77m Lancet by the cardiologist K S Reddy that the calculation by Gwa[kin and colleagues "subverts the efforts of leas-developed countries to address imponantpolicy issues related to global detenninants of non-communirable diseases".' The editorial further argues that "the World Bank is now buttressing a beleaguered World Trade Otganisation, and that both institutions ate opposing the health agenda set out by WHO". It is important that the health profession and others stand up against the tobaco industry and the harmful health eflect of fiee tmdq in particular of 680 THE lANC6l'- Vo1336 • Augua. 19, 2000

(.,JI-ICD ommnoicable diseasa in subSalman Africa: the essmeal NCD health imervention proiecr lLNic XmW 19t; 113- 141-/6. . 4 stamler L 3'lamler. R, Neamn J, et al. low risk-fasur prufde W Imgterm cerdiovescWar and noranrdiovazculur mottalrty and IiPe eapectanry. je3hfA 1999; 281:2012-IB. 5 Pobeel. Csrd'nvasculsrreacarch:.luxuryin trnp¢s1.Aln'ca} SmrAfr MeM91997; 6C: 396-d10 Parity and breast cancer in BRCA1,/8RCA2 carriers Sir-H J Meijers-Heijboer and colleagues (June 10, p 2015)' describe factors that predict a woman's decision to undergo genetic testing for breast cancer susceptibility. The investigators found that parenthood was a strong predictor of testing in unaffected women. This implies that the parity of the sampled population is not representative of pariry in the underlying population; this finding has important implications for epidemiological studies. Women with breast cancer may seek testing for other reasons-ie, parity may not influence their decision. We would then observe mean parity to be greater in the unaffected women than in the affected women in the sampled (tested) population. Parity would, therefore, seem protective against breast cancer. In the study by Meijers-Heijboer and colleagues, 24% of the tested population were nulliparous, compared with 40% of women who declined testing. In a casa control study based on this sample, a spurious risk ratio of 15 for the risk of breast cancer associated with nullipariry would be observed. We have reported that nulliparity is protective against breast cancer in young women who are BRCAI and BRCA2 carriers.' It is important to be aware of the implications of potential ascertainment biases due to sel4sdection for genetic testing, when interpreting epidemio- logical studies of gene carriers. SYeven Narod Cenare for Research on Women's Health. UnNersity of Toronto, Torontu. M5G 1N8. Camaa (e-mail: Steven.naro"sewhsc.on.ca) I Meyera-Heiiboer EJ, Vchoog LC, BreRelmans CCM, et al. Prerymptomatic DNA «stmg vnd prophyl.aic surgsry'n, families wirh a BRC51 or BRCA2 mutetion. l, 2000; 355: 2015-20. 2 Jemstrom H, t<rrnan C, Gbedvien P, et el. Pregnancy and rhe rhk nf enly nnset brevt cancer in orriers of BRCAI and BRCA2 munoons. (m,r r 1999; 354: 1846-50. Thyroid FNA and benign thyroid disease Sir-We fully accept the point made by Armando Banolxzzi in his May 13 commentary' that the predictive value of thyroid fine-needle aspiration (FNA) for thyroid cancer is poor. There ate several reasons for this situation. The accumte distinction of adenoma or well differentiamd fo0icular caminoma from hyperplastic nodules is not possible on FNA cyrology, and the separauon of follicular adenomas from hyperplastic or adenomatoid thyroid nodules is aleo not easy on cytology. Although it should be possible to separate papillary carcinomxs from benign or admomatous Iraions nn cytology, this is often impossible because the nuclear featutrs of papillary carcinoma may be seen focally in adenomatoid nodules or atypical adenomas, and bbatre nuclei may be seen after carbimamle therapy or after radioiodine therapy. The follicular variant of papillary carcinoma is also particularly difficult to diagnose with confidence on FNA cytology berause atypical nuclei present in smems msy not be entirely suggestive of papillary carcinoma on FNA cytology, and may show some features, particularly if colloid is present, more suggestive of a hyperplasric nodule or follicular adenoma. A specific marker of carcinoma that could be applied to the distinction of caminomas of the thyroid from follicular adenomas would be of great use, similarly a marker that could be used to separate papillary carritoma from non- malignant papillary hyperplasia would also add greatly to the cytopathologlst's arrnamenmrium. There is, however, a different approach to this challenge. In our own hospital and in other centres, FNA cytology is used as a diagnosis of exclusion. If the aspirate shows benign, small, and regular epithelial cells without nuclear and cytologiwl atypia and there is ample colloid present it is classified as benigs. Any FNA that does not show both benign epirhelial cells and is also colloid in sufficient quantity for a confident benign diagnosis would be regarded as indeterminate (the Portsmouth working formulation for diagnostic criteria for thyroid FNA is given on www.thelanceccom).' Our group and others have found that this, (or similar systems of diagnostic categotisation of FNAs of the thyroid), is most helpful for excluding benign disease, in as much as the percentage of malignanries in the benign FNA category (THY2) during the period of a retrospective 2 year audit was uro.' We think that FNA cytology should be used primarily as a means of diagnosing benignthytnid disease rather than as a means of diagnosis of malignant disease. If this simple approach is followed about a third CORRESPONDENCE (58 [37%] of 156 in our study) of patients with benign nodules can be excluded from further assessment or aeatmeny without a significant number of false negative FNAs. Inevitably thhere will be some false negative cases in a larger series of patients, either due to miadiagr.osis or for other reasons (eg, patients with microscopic papillary carcinoma with celLs aspirated fivm co- costem admoma or colloid noduks or because the aspirate taken is non- represenmtive of the nodule). This fact does not negate the value of this approach to thyroid FNA. The negative predictive value for thyroid neoplasia in our series is as good if not better than that referred to in the article of C044v6 plus galectin 3.' •0 PoNer, C Yiangou, M Llrmmings, D Hoote Ilepadmems of eHistopalholaW. Surgerr, Medclne. and Oncolng, Queen Alexand2 Hospaal, Portsmoula p0E 3LY, Ua Ie.nall:daMC®polar,oamon.cn.:kl I Bartdam A. Improving accvraty of rytul~ for nodular thyroid Iraions. (a:rer 2000; 355: 1661-62. 2 Potlv DN, m, W"nn AK, Qmm,vas MH, Mikel B, Eoore D, Perry M Fme needle asp4ation ofthe thyrvid; mrporwncc uf the "vNaenninarediaBaostircatcgory.C .r Cyrrqarh 2000; 90: 239-M. 3 Gasbarri A, Mamgaoi MP, DrA Prerc P, ct al. (iaecen 3 ard CD44v6'aafmms in the prroperarive evaluatlcn of thyro;d nMWes. ]Cb, OnW 1999; 17: 3494-502. Global health policy Sir-Yout June 3 editorial' entitled "A manipulated dichotomy in global health policy", caused surprise and dismay. It contains unfounded, incotrect statemen¢, and destmcdve insinuations. The World Bank and WHO are both strongly committed to improving health conditions among the poor, and are working closely together to do so. Both institutions have strong progmmmes to addtess communicable diseases and noncommunicable diseases. For example, WHO and the World Bank are working together to support the global Roll Back Malaria partnership because of the importance of malaria in the burden of disease in many poor countries, especially Africa. Thete ate many other examples of the dose working relationship and shared agenda of the Bank and WHO, such as in HIV/AIDS, childhood illnesses, and healrh-sysrem reform. While the Bank is scaling up efforts against infectious diseases, it is slso doing important work on non-cornmunicable diseases, especially those caused by tobacco. The Bank is a strong parmer in WHO's Tobacco Pree Initiative and a core member of the Inter-Agency United Nations Task TFIS IANC6T- Vo1356-Augun 19, 2000 679 N 0 ~ ul N m N to N Ul