11 



Vol. 330 No. 34 



EDITORIALS 



From the perspective of public health, however, the 

 movement toward low-yield cigarettes makes sense. 

 There has been considerable progress in reducing the 

 prevalence of smoking in the United States, Canada, 

 and many European countries, but smoking rates are 

 much higher in other parts of the world, and the ciga- 

 rettes smoked in many other countries have a much 

 higher yield than their American counterparts. A 

 worldwide attempt should be made to reduce the 

 yields of toxic substances and to make the yield of all 

 cigarettes as low as possible. Public health policy 

 should encourage smokers who have not yet quit to 

 smoke cigarettes with the lowest possible yield. The 

 yields of American cigarettes should not be allowed to 

 drift higher as research finds that low-yield cigarettes 

 are not less hazardous. Mandated ceilings for tar, car- 

 bon monoxide, and other toxic components of tobacco 

 smoke that could be lowered gradually over the years, 

 or a progressive tax on higher-yield cigarettes, are 

 logical ways to implement such goals. 



Sao Francisco Genera] Hospiu] 

 Saa Francisco, CA 94410 



Neal L. Benowttz, M.D. 

 Refxrences 



Palmer JR. Rosenberg L, Shapiro S. "Low yieid~ cigarenes and the risk of 

 nonUtaJ myocardja] infarroon in women. N Engl J Med 1989-. 320: 1 569-73. 

 Kaufinan DW. Helmricli SP. Rosenbeij L. Miemnen OS. Shapiro S. Nico- 

 tine and caiboQ monoxide conlsol of cigarette smoke and the nsk of myocar- 

 dial infamon in young men. N Engl J Med 1983; 308:409-13. 

 Benowici ML. Hall SM. Henimg Rl. Jacob P m. Jones RT. Osman A-L. 

 Smoken of low-yietd cigarettes do not consume less nicotine. N Engl J Med 

 1983; 309:139-12. 



Beoowia ML. Pharmacologic aspects of cigarene smoking aitd nicotine 

 addiction. N Engl J Med 1988; 319:1318-30. 



Beaowitz ML. Jacob P m. Yg L. Talcoo R. HaO S. Jones RT. Reduced tar. 

 nicotine, and carbon tnoncutk exposure while smoking uitralow but not 

 low-yield agamies. JAMA 1986; 25«;24l-6. 



Gori Gfi. Lynch CJ. Analytical cigirctle yields as ptrdicton of smoke 

 bioavailability. Regul Toxicol Pharmactil 1985; 5:314-26. 

 Russell M.A. Jarvis MJ. rey cjib end C. Saloojcc Y. Reduction of tar. nico- 

 tine, and carton monoxide iiTtake m low tar smoken. J Epidemiol Cooimu- 

 mty Health 1986; 40-80-3. 



Maron DJ, Foflmaiio SP. Nicottne yield and UKasum of cigarette smoke 

 expocure in a large population: are lower-yield cigamiea safer** Am J Public 

 Health 1987; T7:546-9 



Kozlowski LT. EvideiKe for limits oo the acceptability of lowest-tar ciga- 

 rette Am J Public Health 1989. 79: 198-9 



Department of Health aad Human Scrvkca. The health cottsct)uenc«s of 

 ww^*'if- the cbaapag dprdk; a report of the Surgeon (jencnJ. Washing- 

 ton. D.C; OMWlHiuui t Prtatisg Oflke, 1981. (Publication no. DHHS 

 (PHS) 81-jaUt.) 



PamcipaflO vMnPonrA Scarbtmngh CoBfcreiice oo Pievenbve Medicine. 

 Is there a IMi* igr loMMvykld cigarelKa? Lsncxt 1985: 2:1111-4. 

 Kauftnaa DW, MaarlR. Koaeaberj L, SMley P. Wirshmer E. Shapiro 

 S. Tar oo^Httofeigauaaiotclaioa to Inag cancer. Am J Epidemiol 1989; 

 129:703-11. 



Sparrow D, Saefea T. 3caat R. Webs ST. The Rialiooship of tar content ui 

 decline in pulmonary hmctioa in cigarette smoken. Am Rev Respir Dts 

 1983; 127J6-3 



Augustine A. Harris RE. Wynder EL. Compensation as a risk factor for lung 

 cancer in smoken who switch from aoofiltrr to filter cigarettes. Am J Public 

 Health 1989;79:188-91. 



PREDNISONE THERAPY FOR DUCHENNE'S 

 MUSCULAR DYSTROPHY 



In the past five years, progress in understanding the 

 molecular basis of Duchenne's muscular dystrophy 

 hn^ hern tiibstaniini The .ifTecled grnr in this disease 



has been cloned, <ind ns protein product, dystrophin, 

 characterized.' The importance of dystrophin in the 

 pathogenesis of this disorder has been defined: dystro- 

 phin is absent from muscle in Duchenne's muscular 

 dystrophy and is usually present but of abnormal size 

 in Becker's muscular dystrophy, a milder variant." 

 Unfortunately, these dramatic advances have not yet 

 had an effect on the clinical management of muscular 

 dystrophy. Duchenne's muscular dystrophy remains 

 invariably fatal. The disease is common, occurring in 

 approximately I in 3000 male infants. A third of the 

 cases result from new mutations in the dystrophin 

 gene. It is therefore essential to develop effective treat- 

 ment for this disorder. 



In this issue of thejourrml, Mendell and colleagues 

 report that the administration of prednisone in sin- 

 gle doses each day over a six-month period improved 

 the strength of patients with Duchenne's muscular 

 dystrophy.' This confirms the results of three pre- 

 vious unrandomized, unblinded studies. '"'' In an ear- 

 lier study, these investigators found prednisone effec- 

 tive in such patients as compared with historical 

 controls who were only observed.* They now report 

 similar results of a randomized, blinded trial. Sev- 

 eral factors were evaluated to gauge muscle status, 

 including strength in several muscles, joint contrac- 

 tures, timed functional tests (e.g., the time needed 

 to climb four stairs), overall functional grading of 

 the limbs, and pulmonary-function tests. In all catego- 

 ries except joint contractures, progressive improve- 

 ment was detected at one, two, and three months; the 

 improvement in muscle function was maintained for 

 three to six months. 



Several points commend this report. It demon- 

 strates benefit from a therapy for Duchenne's muscu- 

 lar dystrophy in a double-blind, controlled trial. It 

 exemplifies the value of well-executed multicenter col- 

 laboration for rapid, statistically accurate drug trials. 

 It is also a tribute to the Muscular Dystrophy Associ- 

 ation, which has been a dominant force promoting 

 research into the pathogenesis and treatment of the 

 disease. 



These points notwithstanding, the paper raises sev- 

 eral questions. Perhaps most important, can any trial 

 of steroids at these doses remain truly blinded and free 

 of a placebo effect.' The answer is not clear. Certainly, 

 it is unlikely that observer bias explains the significant 

 clinical improvement at one month in this study, since 

 the cushingoid appearance induced by steroids had 

 not developed in most of the prednisone-treated pa- 

 tients by that time. Although the results of many 

 of the functional tests might have been influenced by 

 a placebo effect, it is doubtful that this alone would 

 have accounted for the overall pattern of improve- 

 ment in the prednisone groups. Twenty-four-hour uri- 

 nary creatinine levels, which reflect total muscle 

 mass, increased during prednisone treatment. This 

 observation is objective and presumably independent 

 of any placebo effect. Furthermore, some trials of 

 drugs have not benefited patients with Duchenne's 

 mtisnilar dystrophy,' intliraiing iliai placebo rllrrts 



