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MYOCARDIAL CARNITINE DEFICIENCY IN ACUTE MYOCARDIAL INFARCTION

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    of system involvement and with presentation either in childhood orin adulthood, treatment would generally be in conjunction withother specialists. Seeing patients together in combined clinicswould seem to be the best way of achieving this.There is an air of defeatism related to many lethal or seriously

    handicapping genetic disorders. Clinical geneticists must notencourage this by being satisfied to limit their involvement todiagnosis and genetic counselling.

    Royal Manchester Childrens Hospital,Manchester M27 1FG M. SUPER

    PHENYLPROPANOLAMINE AND BLOOD PRESSURE

    SIR,-Although phenylpropanolamine (PPA) has been safely usedin the U.S.A. for over forty years as a nasal decongestant, your April10 editorial raised the possibility that PPA in weight controlpreparations could produce increased blood pressure.In the past two years, I have done three large studies in our obesity

    clinic in San Francisco of the effects of three dosage forms of PPA.More than 400 obese patients were studied. The results will bepublished elsewhere.Data were gathered on a twelve-week, double-blind,

    placebo controlled study of 50 mg PPA three times daily(twice the recommended dose for weight loss); a double-blind,placebo controlled study of 50 mg PPA combined with 200 mgcaffeine in controlled-release form; and a single-blind trial of 75 mgPPA in controlled-release form.

    All three dosages caused no significant increase in blood pressurein more than 400 patients. 2 patients experienced noteworthy risesin blood pressure after treatment with 75 mg PPA, but theseincreases were felt not to be drug related.The mean pooled systolic and diastolic blood pressure in the 50

    mg x 3 PPA/placebo study are shown in the figure.Our results confirm that PPA does not cause a significant increase

    in blood pressure even when the amount ingested (150 mg/day) issubstantially higher than the recommended 75 mg dose. There was,on the contrary, a reduction in blood pressure as the studies

    progressed.Cathedral Hill Obesity Clinic,San Francisco, California 94103, U.S.A. RUDOLF E. NOBLE

    Mean systolic and diastolic blood pressure.

    CEFTAZIDIME AND SALMONELLA

    SiR,-Dr Gozzard and colleagues (May 22, p. 1152) listed aSalmonella newport septicaemia treated with ceftazidime 1 g threetimes daily as a failure. The minimum inhibitory concentration forthat strain was 0 - 2 5 lAg/ml. Probably the dosage was too low. Wehave treated a 33-year-old African man, who had sickle cell anaemiaand an osteomyelitis with S. typhimurium (MIC 0-25 J.lg/ml),successfully with, at first, 2 g twice daily for 17 days and, after anoperation, 3 g twice daily for 25 days. The bone marrow sampletaken during operation was sterile. A higher dosage is probablyrequired in Salmonella (and, possibly, Shigella) infections. Ofinterest would be information on susceptibility of the isolatedorganisms to other currently available antibiotics and successfultreatment of the infections by ceftazidime, where prior antibiotictherapy had failed.Infection Laboratory,Johann Wolfgang GoetheUniversity Clinic,

    6000 Frankfurt-am-Main 70,West Germany

    PRAMOD M. SHAHWOLFGANG STILLE

    MYOCARDIAL CARNITINE DEFICIENCY IN ACUTEMYOCARDIAL INFARCTION

    SIR,-Dr Suzuki and colleagues (Jan. 9, p. 116) reported decreasedlevels of free L-carnitine in the myocardium of chronic heart failurepatients and a concomitant rise in acylcarnitine. These changes arerelated to a removal of accumulated free fatty acid (FFA) and long-chain acyl-CoA esters secondary to chronic hypoxia which in turninhibits adenine nucleotide translocase. This metabolic device,also observed in dog hearts during the reversible phase ofischaemia2 seems to act as a servo mechanism tending to relievemyocardial injury. Suzuki et al. suggested the administration ofexogenous L-carnitine during acute and chronic cardiac ischaemia.In acute experimental ischaemia, however, progressively more totalL-carnitine is lost the longer the ischaemia lasts.2 The two findingsstrongly suggest that the maintenance of physiological levels ofL-carnitine and the acylcarnitine to free carnitine ratio play animportant role in the control of the metabolism of the injuredmyocardium.We measured3,4 heart L-carnitine levels at necropsy in seven

    patients who had had acute myocardial infarctions and in four whohad died from causes other than heart disease. In the first group thetissue samples were removed from the necrotic area, from the borderzone, and from the healthy myocardium; whereas in the controlsL-carnitine levels were separately determined in specimens takenfrom the left ventricular wells. The necrotic myocardial areas hadlower L-carnitine levels, while the border zone tissue showedintermediate values between necrotic and healthy surroundingtissue levels. There was no discrepancy between the myocardialL-carnitine values in the controls and those found in the healthysurrounding tissue of those who had died from myocardialinfarction.We did not observe short and long chain carnitine esters in the

    tissue fragments of either group, presumably because in specimensremoved 24 h after death all the L-carnitine content is present in thefree isomer form, as a result of hydrolysis during the period sincedeath and during storage at -25C for 10-15 days. Therefore, inour experimental model free L-carnitine corresponds to totalcarnitine. This statement is supported by the fact that the tissueL-carnitine levels we found in the healthy myocardium wereidentical to the total L-carnitine levels mesured by Cederblad in themyocardium of heart surgery patients. 5

    1. Shug AL, Shrago E, Bittar N, Folts JD, Koke JR. Acyl-CoA inhibition of adeninenucleotide translocation in ischemic myocardium. Am J Physiol 1975; 228: 689.

    2. Shug AL. Changes in tissue levels of carnitine and other metabolites during myocardialischemia and anoxia. Arch Biochem Biophys 1978; 187: 25.

    3. Pearson DJ, Tubbs PK, Chase JFA. Carnitine and acetyl carnitine. In BergmeyerMU, ed. Methods of enzymatic analysis: Vol IV New York: Academic Press, 1974:1758.

    4. Seccombe DW, Dodek P, Frolich J, Hahn P, Skala JP, Campell DJ. Automated methodfor 1-carnitine determination Clin Chem 1976; 22: 1589

    5. Cederblad G, Lindstedt S, Lundholm K. Concentration of carnitine in human muscletissue. Clin Chim Acta 1974; 53: 311.

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    LEVELS OF L-CARNITINE IN HUMAN MYOCARDIUM OF THE LEFT

    VENTRICLE

    Our data confirm L-carnitine depletion in necrotic areas ofmyocardium and suggest that the intermediate L-carnitine values(see table) found in the infarct border zones reflect an area ofreversible metabolic injury for which restoration of adequateL-carnitine levels could protect the myocardium from damagecaused by accumulation of FFA and long-chain acyl-CoA esters.

    Institute of Anatomyand Pathological Histology II,

    Department of Ultrastructural Pathology,University of Rome,

    Rome, Italy 00161

    LUIGI GIUSTO SPAGNOLIMARCO CORSISERGIO VILLASCHIGIAMPIERO PALMIERIFRANCO MACCARI

    MEASLES VACCINE VERSUS INOSIPLEX

    SIR,-Your editorial (May 8, p. 1052) on inosiplex, particularly inrelation to treatment ofsubacute sclerosing panencephalitis (SSPE),forcefully illustrates that we are, sadly, still preoccupied withtreatment rather than prevention. The most contentious commentis: "... meanwhile patients continue to fall sick with what is ahorrible and usually seriously progressive disease". Moreover, youthen go on to suggest that what is needed is "a mode of treatmentthat will deal rapidly with... the disease". Nowhere is it mentionedthat measles vaccination is a far more efficient weapon againstSSPE, although there is now good evidence 1,2 that, by controllingmeasles, the subsequent development of SSPE is prevented. Thesmall number of cases in vaccinated children may well beattributable to a natural attack of measles before vaccination,2 and inthe U.S.A., where considerable progress has been made towards theeradication of measles, cases of SSPE have declined in number. 3

    There is now no excuse for patients to "continue to fall sick".The benefit-cost ratio for measles vaccine in Western countries is

    about 10 to 1.4,5 El06 has estimated that control or eradication ofSSPE will increase the benefit by at least 10%. While inosiplex maybe useful for other slow virus infections, a drug that produces "ahighly statistically significant" improvement in survival of 21 Iyears in a disease showing such wide variations in its natural courseis less than impressive. Our priorities should lie in improving thepoor measles vaccine acceptance rate in the U.K., rather than inseeking a drug for treatment of a preventable infection.

    P.H.L.S. Communicable DiseaseSurveillance Centre,

    London NW9 5EQ

    P.H.L.S. Epidemiological Research Laboratory,Central Public Health Laboratory,London NW9

    NORMAN D. NOAH

    CHRISTINE L. MILLER

    1. Modlin JF, Jabbour JT, Witte JJ, Halsey NA. Epidemiological studies of measles,measles vaccine and SSPE. Pediatrics 1977; 59: 505-12.

    2. Centers for Disease Control Subacute sclerosing panencephalitis and measles.MMWR 1977; 26: 309-10.

    3. Centers for Disease Control. Measles prevention. MMWR 1982, 31: 217-31.4. Witte JJ, Axnick NW. The benefits from 10 years of measles immunisation in the

    United States. Publ Hlth Rep (Wash) 1975; 90: 205-07.5. Creese AL, Henderson RH. Cost-benefit analaysis and immunisation programmes in

    developing countries. Bull WHO 1980; 58: 491-97.6. Elo O. Cost-benefit studies of vaccinations in Finland. Devel Biol Standard 1979; 43:

    419-28.

    POSTSPLENECTOMY INFECTIONS

    SIR,-Polyvalent pneumococcal-polysaccharide vaccines toprotect children who are splenectomised or for whom a splen-ectomy is planned has reduced the risk of infection by Strepto-coccus pneumoniae. Immunisation