C-(
`
`VOLUME 317
`
`OCTOBER 22, 1987
`
`NUMBER 17
`
`Case Records of the
`Massachusetts General Hospital
`A 6 1-Year-Old Man with Abdominal Pain
`and a Mass in the Right Side of the
`Abdomen . .. ..... .. .. .... ... ......... 1076
`JAMES M . R1cn·Tf,R AND EowARO J . G!JtMANS-
`
`Editori al
`Sodium Chloride and Blood P ressu re ... . . .
`MYRON H . \VEJN8ERC£1l
`
`1084
`
`Sounding Board
`An End to Patch work Reform of Health Care
`ROBf.RT L. DICKMAN, AlrL\SA B. FORD,
`Jt:R.OMt LIU.MAN, SHARON i\hLUO~ ... ,
`AND At.VIN L . ScnoRR
`The Medical Clerkship .................. .
`S u r.RMAN M. Mut.1st-0FP
`
`1086
`
`1089
`
`109 1
`
`1093
`
`1094
`
`Correspondence
`Adrenal Cra.fu for Parkinson's Disease ...•.•••
`H uman lmmunode6ciency Virus Viremia as a
`Prognostic Indicator in H omosexual Men
`with Lymphadcnopathy Syndrome , .. . ...•
`Meno pause and the Risk or Corona.ry Heart Dis•
`ease i n \Vomen ••••... .. •.•.•.... , •••.•
`Medic,] and Surgical Treatment for Unstable
`Angina . . . . . . . . . . . . . . . . . . . . . , .. . . . . . . .
`Fetal Hemoglobin in SIDS . , .• , •.. . ..•.... . .•
`Prenatal Diagnosis of Duchenne', Muscular
`Dystrophy ...... , •...... , ...... •• •• .. .
`Simplified Calculation of Body-Surface Area • ••.
`Book Reviews.... ... .... ... .... ... .. ... 1098
`Notices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`1100
`
`1095
`1096
`
`1097
`1098
`
`Orig inal Articles
`Pluma Glycocalic in: An Aid in the Clas(cid:173)
`sification of T h rom bocytopenic
`Disorders . ..... . . • ... . ... . . . ...•.••. ,
`MARK H . STD:..-BERO, joHs G. K ELTOs.
`AND BARRY s. COLLER
`
`"Salt-Sens itive' ' Essen tial Hypertens ion in
`Men: Is the Sodiu m ·Ion Alone
`I mportant? . . .. ... .. . . . ...... . . . . . ... .
`Tutooou ,v. KuRn.,
`HA,.IOUOI A. AL•BAN0£R,
`A.SD R. CURTIS MORRIS, J R.
`
`Use of Cytomega.lovirus I m mune Globu(cid:173)
`lin to Prevent Cytomegalovirus
`Disease in Renal-Transplant
`Recipients . .... . . . , .. .. ..... . .•. , .. . ,
`DAVID R. SsvoMAN AND OTuE..RS
`
`Inte rmittent Coronary Occlusion in Acute
`Myocardial Infarction: Value of Com(cid:173)
`bined Tbrom bolytic and Vasodilator
`Therapy,., .,, •••• , .... ,.,•,•••••• · ··
`DAVJD HACK.ETT, GR.A.HAM DAVIES,
`StRc10 C111E.RCt11A,
`ANO ATTILIO MASf.RI
`
`1037
`
`1043
`
`1049
`
`1055
`
`Medical Progress
`Aortic Dissection .. . •..•... . . .•. . . , , •.. . . ,
`ROMAN \\I. D£5AN"CT15, Ron£RT M. OoROCHAl.l,
`\V. Gta.Al,.D Ausrt.s, AND MORTIMER. J. 8UCKL£Y
`
`1060
`
`Seminars in Medicine of the
`Beth Israel Hospital, Boston
`Regula tio n o f lnsuHn-Gene Expression:
`Implication s for Gene Therap y . . . ..... 1067
`RICHARD F SELDEN', MAREK J. 5KcdKl£\VJCZ,
`PAULS. Russf!LL, AND H OWARD M . C ooo:w:AN
`
`Correction
`Changing Aspects or the Natural History or
`Valvular Aortic Stenosis ••... . ..••. . ... ,
`
`1100
`
`Owned, Publbhed, and C Copyr-lghted, 1987, by 1he Mu11chuu1t1 Medical Society
`l"ur. Nt\\" E!'foU..'fDjOU~AL or Mu»aJft; (ISSN 0028--4793) it published weekly from edi1orial offices ,H 10 Shattuck S1rcet, Sos1on, MA 02l l>-609t.
`Subtniplion price-: S6G.OO per yur. Stcond-dus postage paid at Bos1on and ll additional mailing offices.
`POSTMASTER: S.nd addrm chang<t 10 P.O. Bo, 803, Wahham, MA 02'1)1-0803,
`
`Miltenyi Ex. 1034 Page 1
`
`

`

`1098
`
`THE NEW ENGLAND JOURNAL OF MEDICINE
`
`OcL 22, 198) 1
`r
`j
`
`Thus, che cDNA method al.lows direct detection of the mutation .
`DNA, eliminating the need for linkage testing that is mostly a pU ln
`hie to large fa~ilies a;nd has inhcrc,nt problems due to rcco:m::
`tion. Most patients with Duchcnne s muscular dystrophy arc fi
`families with a single proband, and in 50 pc.rcent of these, diagoo,s~
`of potential carriers and unborn fetuses can now be made accu et
`(Darras BT, ct al.: unpubli,hed data).
`ra, Y
`UTA F"""""'· M.o
`. e_,..,L T. DAaRAs, M.o·
`Yale Umversuy School or Mcdicio;
`
`New H aven, CT 06510
`
`r i
`
`Du~hcnnc's mu:scular dystrophy. We suspect that several of our
`paucnts have an autosomal disease with the same phenotype as
`Duchcnnc's muscular dystrophy but with a different genetic defect ...
`Whatever the cause. recombination is an imporlant source of
`error in the use of DNA probes for genetic counseling of families
`with X-linkcd dys trophy. As with a.ny diagnostic test, it is important
`to ha ve reliable data on the accuracy of these probc.s if they arc to~
`used clinically. On the basis of our information, 1hc error rate with
`even the best probes is at lea.st 7 percent.
`
`Philadelphia, PA 19104
`
`.
`
`KENNETH H. Fisc11BE.CK, M .D.
`Aut:.RT W. RrnER
`Hospital or the
`Uni\lcrsity of Pcnn.sylvania
`
`I. Goodfellow PN, Davies KE, Ropers H-H. Rcpon of I.he committee on the
`geoclic ooastit11tion of the X and Y chrcm<>,omes, Cytog<net Cell Genet
`1985; 40:296-352.
`2. FlSChbcck KH, Riner AW, TmchwcJI DL, ct al. Rerombination with
`pERT87 (DXS164) in families wilh X-linked musc,ilar dystrophy. uncel
`1986; 2:104.
`3. On J, Estimation of the recombination fraction in human pedigrees: efficient
`a,mpuwion of the likelihood fot human linkqe $1\.N:lie$. Am J Hum Genet
`1974; 26:588-97.
`4. F'ascbbcck KH, tuner A, Kunkel LM, ct al. Cicnetic heleqeneity in Ou(cid:173)
`chenno dystrophy. Neurology 1987: 37:Suppl 1:116.
`
`The above letters were referred to the authors of the article in
`question, who offer the following reply:
`
`To tlu Edi/JJ,: Although we agree with Dove and colleaguco that
`the normal distribution of crcatine .ldna.se levels has to be carefully
`considered when scrum crcatine kinase determinations are used to
`assign carrier status, we disagree with their opening statement that
`"the use of DNA probes for prenatal diagnosis of carrier status
`. . . relied, in the absence of a.n affected male, on measurement of
`serum creatine kinase activity." This is not true of the famUies
`presented in our paper. In both ramilies that fell into th.is category,
`Families A a nd B, the maternal grandmothers of the male fetu.scs at
`risk were obligate carriers. One had two affected sons, and the other
`had a'n affected brother and an affected son. The task at hand was to
`determine by DNA analysis whether the pregnant woman had
`pas.scd on her maternally derived, po.uibly mutant, or her paternal•
`ly derived, normal Xp2l region to her fetus. The crcatine kinase
`rcsuJu were irrelevant to the diagnosis in both eases, especially since
`values in the normal range do not exclude carrier status.
`Fi,chbcck and Ritter provide additional data on the frequency or
`recombination between the phenotype for Duchenne's muscular
`dystrophy and polymorphi,ms detected by intragenic probes, which
`agree with our conclusions that recombination within the gene is an
`important source of error. Their 7 percent error rate, however,
`appcan to be based on the use of a single intragcnic marker. As we
`pointed out in our paper and documented in the families in our
`study, this type or error can be avoided by using Ranking DNA
`markers outside the gene in addition to intragenic markers. If the
`entire Xp21 haplotype is transmitted without apparent recombina(cid:173)
`tion, the risk of error is much lower than 7 percent. On the other
`hand, if haplotype anaJy1is reveala a crossover event, the study is
`uninfonnative if the site of the mutation with respect to the site of
`the crossover r~int is unknown.
`The issues discussed here, however, arc superseded by a recent
`breakthrough with the cloning or the entire gene for Duchenne's
`muscular dystrophy.• The 14-kb cDNA, when used u a molec(cid:173)
`ular probe, detects deletions in at least 50 percent of aU patients
`with Duchenne's or Becker's mu.1cular dynrophy• (and Darru
`BT, ct al.: unpublished data), in contrast to the detection rate
`or less than 10 percent with prcviou,ly available random DNA
`probes. These deletions represent the molecular buis of the dis•
`case and arc detectable in affected males and in carrier females,
`
`•Koenig M, Hoffman EP, Berltlion CJ, Monaco AP, Feener A, Kunkel LM.
`Coniplcl< cloning of lhe DuchcMc musc,iw dym,phy (DMD) cONA 111d pte·
`liminary acnomic orpniDlion of lhc DMD acne In normal 111d affected lndlvld•
`uals. Cell 1987; 50:509-17.
`
`SIMPLIFIED CALCULATION OF BODY-SURFACE AREA
`T" IAt Edi101: Values for ~~•surface. area are commonly used
`in the practice: of internal mcd1cme, parucular-ly to caJculate doses
`of chemotherapeutic agents and index cardiac output and Urol:c
`volume. Body-surface area (BSA) is generally calculated r"""
`height (Ht) and weight (Wt), according to equation, such as the
`) = 0.00718♦ x Ht
`classic 1916 Du Bois formula 1: BSA (m2
`(cm)•-m x Wt (kg)0
`·" '. Although many nomograms based on
`such equations have been published, some arc inaccurate,2 and one
`is not always readily available when a determination mll.!t be m:ldc.
`At our institution, we use a simple1 easy•to-remember modifica.tioQ
`of an equation by Gehan and George,' which requires the use o{ 1
`calculator with a square-,root key:
`
`') = v Ht (in) x Wt (lb)
`BSA (m•) = y Ht (cm) x Wt (kg)
`
`(
`BS
`A m
`
`or, in metric:
`
`3131
`
`3600
`
`Ir a 73-inch-tall, 175-lb patient i, used u an example, the key(cid:173)
`stroke sequence on most calculators would be:
`73 X 175 • + 3131 g V- • 2.02 m2•
`Although a slight degree of accuracy hu been lost in malting the
`above equations easy to rcmembc.r, deviations from acoepted values
`derived from other formulas'•'•• arc generally less than 2 pu=t. _
`We have made good clinical application of thC-'c equations and
`'
`believe they may be or benefit to other physicians.
`R.O. Mosn=, M.D.
`Akron City H .. piial
`
`Akron, OH 44309
`
`I. Du Bois D, Du Bois EF. A formula to cstlmlte lhe oppro.da>ale swfoce...,
`if bciaht 111d W<iJbt be known. An:h Intern Med 1916; 17:86)-71.
`2. 'l\m:olte 0. Erroneous nomognms f0< body-swfacc aru. N (;'aal l Med
`1979; 300:1339.
`3. Cld>an BA, George SL. Ea<imadon of human body swfac:e aru mim be,illl
`111d -lJbt. Can= Chcmo<hct Rep 1970; 54:225-35.
`4. ~ e SL, 00.,., BA. Methods for meoswemeat or body surface -
`l Pediatr 1979; 94:342.
`
`,
`
`BOOK REVIEWS
`NEUROANATOMY: AN ATLAS OF STlltJCTURB.S,
`SECTIONS AND SYSTEM.s
`Second edition. By Duane E. Haines. 236 pp., illustntcd. Balli(cid:173)
`morc, Urban and Schwarzenberg, 1987. S22.50.
`The second edition of this atlu hu been considerably iinprovcd
`over the first, and new material has been added. Included a,,: mor<
`th.an a dozen ~tcmal views, nine or dissections, a nd many sectio05
`with key d_rawmgs -9 coronal, 8 horizontal, 5 or the spinal cord, 15
`or the brt.1n stem'. 2 or the cerebellum, and 10 coronal views or th<
`forcbra1n, In add_mon, five horiwntal and five ,agittal ,ccti00-'.,.
`correlated on faang pages in an interesting manner. Fina.UY, rc,or
`
`Miltenyi Ex. 1034 Page 2
`
`