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* V Vol. -O' No. 7 CORRESPONDENCE 443 1 Gallagher K. krp4ak CM. lac WSS. Jahaaoa KA. Brian HP. Rigp IL. Aammurm rf l.23-4i*rWo)fvxanmO|icpoBneiQimpBammippemri umuyumru mart- md leng-tarm rites m teat aad calcium aauoatna. tec Sal Acad So USA. la preml. 3. Jowwy I. Riggs BL. Kelly PI. Hoffman DL. Eftei at rnmhaml gonpy auk mlnuii Suondt. naiu 0. aid cricaa a raio'irnmia. Aa 1 Mad. 1471. JJ 4.V9. litti IL. Hodgson SF. Marinas DC. Kelly W. fahaaaa KA. Tmi D. Traanaa ri primary Miacpcrwu axh Suondt aad atoms dmcal atarancc sad fraoat oonoimct. JAMA. I9S0-. 24J446-9. FAMILIAL LOWER ESOPHAGEAL RINGS 7 tkr Editor- I would like to report the occurrence ofa symptomat ic lower esophageal nng in identical twins and two mother-son pairs. A 68-vear-old man had intermittent dysphagia without gastro esophageal-reflux svmptoms for 13 yean before a hiatal hernia and a lower esophageal nng were found on an esophagogram. Etutrocopy revealed a thin ring, and bougienage relieved his dysphagia. His identical twin reported having had similar dvsphagta fm five years. Endoscopy revealed a hiatal hernia and a lower esophageal ring like his brother's, and bougienage was successful. No other relatives were known to have dvsphagia. / TOLERANCE TO HYDRALAZINE IN CONGESTIVE A 33-year-old woman had intermincat dyfphagia without reflux HEART FAILURE / symptoms for 30 years before the radiondphic demonstration of a hiatal hemu and a lower esophageal nng"^Endoscopy was confirma T* ;*r Editor The artide by Packer et al.1 ia ihe Jaauyy 14 naue tory. and bougienage eliminated her ddsphagia. Her 20-vear-old son provided valuable information on Lht development o^raierance to had episodic dvsphagia without gratis symptoms for seven years lone-term hvdralaxinr therapy- in tome patients with coneotive before presenting to the tmir;tpp- room with a meat impaction in heart failure. I believe, however, that the potenbu role of fluctu- his lower esophagus. After thc/bolus was removed, endoscopy dem anoia in the effects ofdigoxin was not adequate)?considered. Pack onstrated a hiatal hernia tnp i lower esophageal ring, and bougien er n al. did not indicate the senim digoxin edneentrabons of their age stopped his dysphand: One of his five siblings had dysphagia patients, nor did they indicate that am dirofon dotafe xdjustmenu but had not sought medical attention. were made after the initiation of vxaodiUuog agents. Although the authors acknowledged that hemodvnatrite alterations may produce A 64-year-old woman had episodic dysphagia without reflux svmptoms for five/eart before her hiatal hernia and lower esopha chances in the absorption of orally administered drop (including dieovin-. thev did not address the effect ofvasodilators on the renal geal nng were forfnd by esophagography. Endoscopy confirmed the diagnosis, ancr bougienage was curative. Her 41-vear-oid son had clearance of dituxto. Cocan rtrecently found that the use of intermittenpaysphagia without reflux symptoms for five years before either hvdralaainr or mtroprusiidr in patienu with congestive heart an esophagogram showed a hiatal hernia and a lower esophageal lailure produced an increueof 30 per cent ia the mean renal clear ance of digoxin (from approximately 100 ml per minute to approxi ring. Emoscopy was confirmatory, and bougienage was successful. A foriuly history revealed no more dysphagia. mately 130 ml per mindtci. This increase in the renal clearance of dicoxin. which was accompanied by an increase in renal blood flow without a change, the glomerular filtration rate, was apparently I am not aware ofany other reports ofthe oDocofdanee in twins or 6the familial occurrence of a symptomatic lower esophageal ring. Although an asymptomatic lower esophageal ring may be found ia due to an inernde in the renal tubular secretion ofdigoxin. Vasodi lo 14 per cent of the population,1'1 a lower esophageal ring produc lator thcrapymay therefore improve the patient's hemodynamics tive ofdysphagia is mudt less common. Although its pathogenesis is initially, hunhr increased renal clearance ofdigoxin may precipitate problematic, anatomic data suggest a developmental origin.* These l decompofsated failure over the ensuing days by reducing the serum dieoxity concentration. This information certainly does not chal cases suggest a hereditary factor ia the genesis of the symptomatic lower esophageal ring. lenge the findings of Packer et al., but it is presented as another imp--riant factor to consider when one ia evaluating the recurrence of Gcoaet F. Loucxramt, M.D. coti.-.titve bean failure in a patient who has recently responded to Southern California va* dilator therapy-. San Diego. CA 93130 Permanente Medical Group San Antonio. TX 78384 Htnay I. Burner, Pmaxm.D. University of Trxas Health Science Center I Packer M. Mcller J. Mediae N. Yuvhak M. Gorfia > Hosaodyaamm chtntensauen of loieraoct is len{-vmt nydnlaaias Hmtpj * ximdrome heart failure. X EagJ J Med 1913: J06 37-43. 3 Cogaa II. Humphreys MH. Carbon Cl. BeBound NL. Rxpoport C. Area tbodiUier mcrapy iam-H > itiu ttanact of digpam in paorod wnh cam festive Dean failure. Cat luasa. .Ml: 64.973-4. 1. Kumar P Frequency of the ssjnapmmade lower tsophagari caamcois nag. N Enpl I Mad 1934: 334:692-4. 2. Kcyunf WX. Baker CM. McCsner RR. al. The loner napfiigus. Am J Roentgen* 19*0; *4:1070-3 3. Coyal RK. Bluer IL. Spue HM Thrnaaro and locaoea riloaar amphagari nag. N Enpl J Mad. 1971: 2*4:1173-10. 4. Coyal RK. Glaacy U. Span HM. Learn easpha<aai nag. M Eaal 1 Mad. 1970: 2*2:l29*-)03. HLA-B37 AND COLORECTAL CANCER Thr above letter was referred to the^dutbon of the arbetr in qurstmn. two of whom offer the foUojprag reply: To tkr Editaf We thank Dr. kder for his interesting comments. Tli* doses of digoxin in our patents were not altered during long term t! rapy with hydrafodne, but we did not measure acrur. dipos:r i<inccntraturns iiMnder to confirm that a constant digitalis eflret was maintained: We should point out, however, that the hrmods namic varywrs after the development oftolerance to hydraUeuir did not differ from the values seen before the initiation of thrrapv: this firming suggeita that thr adequacy ofdigitaliaation was not changed. Although increased renal clearance of digoxin may result in subthrrapeutic dnic levels in some patients receiving hvdralasine, it is likek that tolerance to this effect mav also develop in the same paurnts who have tolerance to hydralatinc's hetnodyssflix actions. New York, NY 10029 , MtkTon Pacsaa, M.D. Jost Mtuu. M.D. Mi. Sinai School of Medicine Tt tht Editor- The high familial incidence of colorectal cancer1 suggests the possibility of a linkaer or an association of this with htstocompanbility anngens brvak et al. have reported a family study compatible with thr linkage of adenocarcinoma of the colon with the major histocompatibility complex.1 On the other hand, previous studies have failed to show such aa association, parncuiariy with HLA-A and B antigens.1 We studied 81 patients (43 men and 38 women. 19 to 83 yean aid) with histologicallv proved colorectal licbcrkuhnian epithelioma. Six teen of them 130 per cent) had a dose relative affected by the same disease. HLA-A and B antigens were compared with those of 319 controls. B37 antigen was found in 16 patients 119.9 per cent) and in 37 controls 18.3 per cent:. Tue relative risk was 3.67 (P<0.0l). No other sntigen wss found with s significant difference in frequency between the two fr&uos. The frequency of the B37 antigen was comparable among thr patienu with affected relatives Ithree of 16) and in the whole sample 16 of 81.. Abdominal films in sll patienu showed definite sacroiiiitts in three, all of whom were B37-posiiive and none of whom had clinical evidence of ankvlosing spondviitu. Thus, provided that rsT00(J5309 DOW 06661 * THE NEW ENGLAND JOURNAL OF MEDICINE Aug. 13, 19*2 colorectal cancer may join the group of diseases associated with Table 1. Piasme Levels of Growth Hormone and Prolactin HL4-B27. The increase in the frequency of thii tustocompitibiliiy before and after Exercise. Performed in Subjects Given a antigen m not higher in femiliai forms of colorectal cancer; the Saline or Pyridoxine infusion. frequency of radiologic signs ofankylosing tpondyiibs anwog B27- potitirr patienu with colonic cancer (three of 16) was comparable to Tm Gei that bund bv some of us among B27-peeidvc healthy blood donors (16 of40).* suggesting that the existence ofcolorectal cancer in B27posmve people has no influence on the incidence ofradiologic signs wm MM MTI of sacroiliins. These results raise the question of a possible causal rate of B27 antigen in colonic caranoma and ankylosing spondylitis. Since some microbial spades (e.g.. klcbsieUa) are thought to have s responsibil- itv in the genesis of ankylosing spondylitis.* and since some others (Stnpuacmjutahi and destndia I arc thought to be colonic cardno- gens.*-; it is conceivable that B27 antigen Isvon some intesonal dys- microbisms that would lead to different spedfle diseases. Finally, it is notrworthv that another potential colonic carcinogen, asbestos.* ?can give rise to another B2?-associated disease. * Before taercue 20 min before At nan (basal) Altai ettreus J min I5nua 30 nua 43 IMS *0 ana m-t 22*0.9 1.9*0.! 1.1*4.4 25.5*7.4 20.1 *6.1 12.4*42 *.11*12 4**0J 42*1.4 22*5.1 1.**20.* 41.9*42 27.4*5J 17.0*421 86021 Poitiers. Trance M. Alcalat; D. Bootocx; N, Maui; Cl. MATuotA.v*xr; D. Alcalar, assj. Tamils Hdpital Jean Bernard 1. DuasioneGH. KnsgpTWL. Fimilitl cenow of ds solan sod isceen-JMed Oenst. I>73; *JM. 2. Si*ek MV. ~i ......... limn Sivak 0. Bm WA. Sallivas >H. A heksfe 27*41. ). Tcnsab H. Pertae ST. Mickey MB. HLA hsqesacass is chow: a sseoad udy. b: Mulvmin JJ. MOkr RW. Pnuami JT Jr. ad. Gmtncsaf hsaas oncer. New YartL' Itswe Pros. 1977221-1. 4 AJcsls> M. AmorB. HsMwf.asl. Ankylosmi ^aatjlioi red rkleesi till m/areen a sppanaly Malay HLA 827 Wood Cocas. J Btmmmat 1*7*; HN-Ji. 3. Eknaga RW. CsMwag OR. Coadag P. Ebriafa A. Seqatanal abas a aCtvlocal tpocdyhns: sssodtnoe of rjrbn lit pefosas w* sense CM cate. AM RMua Du. 1*7*; 37:146.31. i. Hill MJ. TM role of colon anaerobes b be amaholimt at Mb acids and acmes, and as nrlaocn a colon cancer. Carer. 1973: 3423*7-400. 7. Repen boa the Imrramnail Agency tar Imart oe Casa beaaonal Microncoloo Grab. Dicury SMe. cams hiss. Isncal Means aoiasts and eoioo caneer in two Scxodmmaa populanoa Lmcsl I>77; 2207- II. t LsmbenR. Epirleminlnp atmloncul tsiciootmcaa. SrMX*Moe colon ic camnofcnesis -- May 27-21. Tioaas. Gnasy. 1X1. 9 Mate; H. Lsnfe A. Srooiik R. HLA ano|ea a setomsm Alt* taaansl Tber Eap. 1977; 23:419-*!. PYRIDOXINE IB6) SUPPRESSES THE RISE IN PROLACTIN AND INCREASES THE RISE IN GROWTH HORMONE INDUCED BY EXERCISE Tt tor *-.* The role ofmonoamincs in control ofthescernioo of antenor piimu-v hormones hss been widely studied in the post few vein. ' The hypothalamic dopaminergic pothwayt have been shown to be involved in the regulation of protocan, growth hormone, ACTH. and gonadotropins.1 Pvridounc (vitamin Be) is one of the natural pseennort of pvri- doxal-i'-phoephate coenxvme in the deesrbarytobon and trans amination of amino adds. As s coctuyme of dope decarboxylase, this vitamin can induct the transfcrmabeo of dopt to dopamine, thus sharing the endocrine effects ofthis ammo. In feet, this drag has been reported to reduce prolactin levels sod raise gravth hormone levels,* although this action has not been confirmed.' We conducted a study to evaluate the effect of pyridoxine on prolactin and growth hormone levels during exercise, since eserdae provides a good model fee the physiologic release ofthe sdenohypnphi-seal hormones.*4 Six healthy subjects 2Ss3 years old volun teered to enter the study. Informed consent was obtained from all subjects. Each volunteer was tested at two different times separated bv a tvcn-dav interval (once with drug and once with placebo). Phvncal exercise, performed on a bicydc ergomeicr, was moni tored by an open-circuit gas analyser. A spirometer included in the fiBi imr * wm MM rm B/mi Baton nerase 20 mm Mfere At sun (basal) After citrate 3 nun 13 BUS 30 mm 43 mm *0 BUS 72*l.t 3.4* 1.4 1 *.9*2.1 23.0*4.1 12.1*1.* .4*0.4 t.l*l.4 32*0.9 42*0.1 42*0.9 32*02* 32*021 41*0.9 4.0*12 Mm tU. aa M|M fcfXifiMBUr Si/toMi ham star vox uM mtm l (KS.OOI. system was used to evaluate the tube and dynamic lung volumes.* The bicycle workload was adjusted so that the heart rate, moni tored from a V, lead, was constant at s value corresponding to 80 per cent of the maximum heart rate ofeach subject (about 170 beats per minute), during the eight minutes ofmaximum workload. The am ase phase was preceded by a 20-minutc rest period and followed by a 45-minute recovery phase. Saline or 600 mg ofpyridoxine in 250 ml of i-lrne was given by infusion for the duration of the test (res', exercise, and recovery phases). The subjects were not told which infusion was given. A catheter was introduced into s forearm vein to collect Mood at the beginning ofthe 20-minute rest period, immediately before the sun ofexercise, and then five, 15. SO, 45, and 60 minute! after the end ofthe cxerase period. After blood collection the test tuba were placed on ice; the plasma was immediately separated and fresco at -70"C. Levels of growth hormone and pratoebn were measured by means ofsensitive and spedfle tadioinununoiaaayi.1 The results, analysed with Student's i-tat, are shown in Table I. A significant increase in growth hormone and prolactin occurred in response ao maximal effort during the test performed after the saline infusion. The hormonal response to physical cxerase performed alia the pyridoxine infusion showed that prolactin response was suppressed (P<0.00l) whereas the growth hormone response was enhanced (P<0.00l). The present data indicate the efficacy ofvitamin B in stimulating growth hormone and suppressing the rise in prolactin induced by cxerase. This phenomenon is probably due to the increase ofdopa minergic activity by pyridoxine.* 00100 Rome, luly Coctamxo Mosxrn, M.D ; A. Fasixi; L Gnuai; V. Bomraao; and F. Faajou University of Rome 03100 Sssuri, Italy A. Isreow University of Sasseri 1 1 OResnnois DOW