563

narrowed renal artery was similarly dealt with at a secondsuccessful operation. Postoperative aortography showedboth renal arteries to be functioning normally withoutconstriction or impairment of renal flow. The blood-pressure gradually fell and the diastolic six weeks laterwas about 30 mm. Hg below the preoperative level ;renal function tests were unimpaired. The boy hasremained well.Poutasse et al. suggest that the hypertension in all 3

patients was caused by stenosis of the renal arteries due, a developmental flaw. Their report suggests twothings: narrowing of the renal arteries must be con-sidered as a cause of juvenile hypertension, which can bedetected only by aortography ; and the indications forarterial grafting are now even wider and call for theclosest cooperation between physician and surgeon.

1. Savage, D. Brit. J. Anœsth. 1955, 27, 346.2. Norton, H. I., Weingarten, M., McDonough, E. T. Amer. J.

Obstet. Gynec. 1956, 71, 1251.3. Anz, U. E., Smith, L. J. Ibid, p. 1242.

4. Schaffer, A. L. Ibid, p. 1247.

CHLORPROMAZINE IN OBSTETRICS

TiiE diversity of the pharmacological actions of chlor-promazine has suggested to many people that this anti-histamine may be of value in obstetrics. First, it mayhave a central " tranquillising " action secondly, it maypotentiate and prolong the action of analgesic drugs sothat smaller doses are effective ; and, thirdly, it mayprevent vomiting of pregnancy.The sedative action of chlorpromazine during labour is

good, though once a total dosage of 75 mg. is approachedthe mother is likely to become indifferent to her sur-roundings and less cooperative than is normally desirable.Effective analgesia can be produced by a mixture of25 mg. of chlorpromazine and 50 mg. of pethidine (abouthalf the usual dose of pethidine), and this combinationcan be repeated when necessary. It should be given bydeep intramuscular injection. A small dose of scopol-amine (gr. 1/200) will then produce amnesia if that iswhat is wanted, since this action is also potentiated bychlorpromazine.There is no doubt that the mixture is effective in

producing analgesia, but when compared with the moreusual means of doing so in labour, such as pethidine;dune. pethidine and a barbiturate, or similar combi-nations with scopolamine, there is little or no differencein the result so far as the mother is concerned.l 2 Anyadvantage must be sought in the effect on the baby.Here results are conflicting, though all workers agree’hat chlorpromazine does no harm to the child. Asignificant decrease in the incidence of neonatal asphyxiahas been attributed to the reduced dosage of analgesics 3 4;’u’ others disagree.2 Nausea and vomiting, however,both in early pregnancy and during labour, can beeffectively treated with chlorpromazine.Among the possible disadvantages, the action of chlor-

promazine on uterine contraction is of considerableimportance. Provided the dose is kept below 75 mg.,about is not prolonged, though in the second stage theactive expulsive efforts of the mother may be poor, andthe number of forceps deliveries may increase in con-sequence.1 The third stage of labour is not affected.The hypotension caused by chlorpromazine is slight inthe ’tcumbent position and does not matter provided thepatient is warned not to sit up. It may, however, be atr to the use of the drug for patients with essential

hypertension or hypertension due to toxaemia of preg-: i:.’ v. The total dose given in labour is so small that thedanger of jaundice from liver damage can be disregarded ;

- ’ the same cannot be said when treating hyperemesis’

°

. ;- periods.Through it seems promising, chlorpromazine must be.;..: investigated before its use in obstetrics can be

accepted without reserve. It seems likely to be of

particular value for certain types of patient, especiallywhen there are reasons for avoiding narcotic or analgesicdrugs or for giving them only in very small doses.

1. Antibiotics Annual, 1955-1956. New York, 1956; pp. 909, 918,924.

2. Gause, G. F. Brit. med. J. 1955, ii, 1177.3. Correspondence correcting our own mistake over the relation of

novobiocin to albomycin appeared in our issues of March 17(p. 330) and April 14 (p. 450).

4. Welch, H., Wright, W. W. Antibiot. Chemother. 1955, 5, 670.5. Simon, H. J., McCune, R. M., Dineen, P. A. P., Rogers, D. E.

Antibiot. Med. 1956, 11, 205.6. Lin, F. K., Coriell, L. L. Ibid, p. 268.7. Martin, W. J., Heilman, F. R., Nichol, D. R., Wellman, W. E.,

Geraci, J. E. Ibid, p. 258.8. Nichols, R. L., Finland, M. Ibid, p. 241.

NOVOBIOCIN

SINCE the announcement of the discovery of novo-biocin at the third annual antibiotic symposium in

Washington last November,’- bacteriological and clinicalinvestigations have confirmed that it is a relatively non-toxic antibiotic which promises to be of particular valuein staphylococcal infections. It has also been calledstreptonivicin, ’ ‘ Cathomycin,’ Albamycin,’ and ’ Cardel-mycin.’ It has no connection with the apparently dis-similar Russian antibiotic, albomycin.23 s The confusionin terminology arose because streptonivicin and catho-mycin were independently isolated from cultures oftwo actinomycetes, Streptomyces niveus and Strep.spheroides. Their ultra-violet and infra-red absorptionspectra, and some of their other physical properties,have since established that they are the same 4 ;and the generic name, novobiocin, has now been

adopted.Novobiocin can be given by mouth in doses of 500 mg.

(2 capsules) every six hours, intravenously in a similardose every twelve hours, or intramuscularly 250 mg. everyeight hours. It is rapidly absorbed and peak serum con-centrations are reached in two hours if it has been takenon an empty stomach. The antibiotic is largely bound toprotein in the blood, principally to serum-albumin ; butthis is presumably a loose linkage since high urinaryconcentrations appear within eight hours of absorption.In-vitro studies show that, in the presence of 10% ofhuman serum, 50-95% of antibacterial activity is lost :but since the antibiotic can be recovered unimpaired byextraction of the serum, it does not seem to be altered ordestroyed by this contact.5 It diffuses into pleural andperitoneal cavities but it does not apparently cross theblood-brain barrier. Part of a dose is excreted inthe bile.The bacteriostatic range is chiefly against gram-positive

cocci ; it is ineffective against gram-negative organisms,with the possible exception of species of proteus, whichmay be moderately sensitive in vitro. Although novobiocinhas cured anthrax 6 and has subdued pneumococcal andstreptococcal infections, its chief value is in the controlof staphylococci. Since it shows no cross-resistance with

penicillin, streptomycin, chloramphenicol, the tetra-

cycline drugs, neomycin, bacitracin, or erythromycin, 7its chief indication will probably be for staphylococcalinfections which cannot be controlled by other anti-biotics. Clinical trials are being conducted to see whetherits use in combination with other antibiotics, notablyerythromycin, may hamper the emergence of resistantstaphylococci. 8

Novobiocin has had mild toxic effects, of which thecommonest and most troublesome are rashes and drugfever. There may be gastro-intestinal upsets, but it isunlikely that it will cause staphylococcal enterocolitisbecause the fæcal flora is unchanged in its content of

gram-negative bacilli, yeasts, and clostridia. Indeed,novobiocin has been effective in the treatment of staphylo-coccal enterocolitis. 7 There has been no evidence of

564

damage to the blood, kidneys, or liver. A raised ictericindex has been noted diiring treatment, but this may bedue to a yellow pigment metabolite of novobiocin.

1. Cohen, P. P., Hekhuis, G. L. J. biol. Chem. 1941, 140, 711.2. LaDue, J. S., Wróblewski, F., Karmen, A. Science, 1954,

120, 497.3. Karmen, A., Wróblewski, F., LaDue, J. S. J. clin. Invest. 1955,

34, 126.4. Agress, C. M., Jacobs, H. I., Glassner, H. F., Lederer, M. A.,

Clark, W. G., Wróblewski, F., Karmen, A., LaDue, J. S.Circulation, 1955, 11, 711.

5. LaDue, J. S., Wróblewski. F. Ibid. p. 871.6. Nydick, I., Wróblewski, F., LaDue, J. S. Ibid, 1955, 12, 161.7. Chinsky, M., Shmagranoff, G. L., Sherry, S. J. Lab. clin. Med.

1956, 47, 108.8. Denney, J. L., McAuley, C. B., Martin, H. E., Ware, A. G.,

Segalove, M. J. Amer. med. Ass. 1956, 161, 614.9. Kattus, A. A. jun., Watanabe, R.. Semenson, C., Drell, W.,

Agress, C. Ibid, 1956, 160, 16.10. Merrill, J. M., Lemley-Stone, J., Grace, J. T. jun., Meneeley,

G. R. Ibid, p. 1454.11. Wróblewski, F., LaDue. J. S. Ibid. p. 1130.12. Ruskin, A., Mahaffey, W. C., Ruskin, B. Clin. res. Proc. 1956,

4, 30.13. Agress, C. M., Glassner, H. F., Jacobs, H. I. Circ. Res. 1956,

4, 220.

TRANSAMINASE IN ISCHÆMIC HEART-DISEASE

WHILE studying transamination in intermediarymetabolism, Cohen and Hekhuis noted that transami-nase activity was greater in heart-muscle than in othertissues. Some years later LaDue at al.2 investigated theactivity of serum glutamic-oxalacetic transaminase invarious human diseases, using a spectrophotometricmethod.3 They found that the serum-transaminase

activity was much above normal about twenty-four hoursafter cardiac infarction ; it returned to normal within afew days. Important questions were whether otherconditions, especially those which might clinically beconfused with cardiac infarction, were accompanied bycomparable elevation of the serum-transaminase level,and whether the raised level reflected the amount of

myocardium destroyed.Agress et awl. 5 observed the effect of experimental

myocardial infarction on serum-transaminase. The con-centration rose rapidly in dogs ; and the changessuggested a linear relationship between the peak leveland the amount of infarcted myocardium at necropsy.This work was confirmed,6 and the infarcted muscle wasfound to contain less transaminase than adjacenthealthy muscle.Many workers have reported increased serum-trans-

aminase in the presence of liver disease 7-11 and in

pancreatitis.’ 8 12 If the level of serum-transaminase isto be used clinically to supplement the electrocardiogramin the qualitative diagnosis of cardiac infarction, thismatters less than the finding of a raised serum-trans-aminase after pulmonary embolism, although this hasnot been found in experimental pulmonary infarction. 13Further investigation of this important point is needed.Myocardial infarction may take place and yet no diag-nostic change in serum-transaminase is found 8 9 ; one

such patient died before the peak level of transaminasewas likely to have been reached, and it could be missedin others. Significant elevation has been found after veryrapid cardiac arrhythmias and after saddle embolus ofthe aorta.10 Merrill and his colleagues 1° concluded thatincreases in serum-transaminase might be associated withcellular injury in various tissues.The view that estimation of serum-transaminase may

be a useful guide in excluding, as opposed to diagnosing,myocardial necrosis is sound, if the test is done at the

right time. Ultimately it may prove more helpful as aquantitative estimate of cardiac infarction than as a

qualitative aid to existing methods of diagnosis. A recentreport 12 showed that there was some overlap in thetransaminase levels between patients with cardiac infarc-tion and acute coronary insufficiency, and between thosewith acute coronary insufficiency and angina pectoris.Clinical details are lacking but presumably the angina

pectoris was related to exertion-: Some of those wangina pectoris had had past cardiac infaretion and othhad not. It may- be that some of the patients considereto have acute coronary insufficiency, or angina pectiomay have had undiagnosed subendocardial infanAlternatively, there is the possibility of myocnecrosis with prolonged or severe angina pectoris.At present the transaminase test seems to offer littl

a supplement to the electrocardiogram in the diagnostcardiac infarction, particularly in differentiating _endocardial infarction from acute coronary insufficientlFurther studies on humans, with necropsy control. necessary before the place of serum-transaminase. eitas a qualitative diagnostic procedure or as a quantity’measure of cardiac infarction, can be accurately judgQuantitatively it could prove valuable both intclinical management of the patient and in prognosis.

1. Silverton, M. I. Med. Offr, 1956, 96, 76.2. Bradley, W. H., Richmond, A. E. Mon. Bull. Minist. Hlth Lab.

Serv. 1953, 12, 2.3. Lawrence, E. N. Met. Mag. 1956, 85, 164.

POLIOMYELITIS AND THE WEATHER

KNOWING what it does of the habits of whooping-couand measles, the public at large finds it hard to undstand the natural history of a disease, such as cerebspinal fever, few of whose victims give any overt evidenof infection. To this characteristic poliomyelitis arelative novelty, an apparent predilection for the younand sometimes a fatal end. It is not surprising, thereiuthat it is commonly thought of as a mysterious diseawhose incidence and effects are to be explainedprocesses outside the common experience of doctor; well as laymen. Suggestions in this direction have rangfrom the helpful to the hopeless, but no-one would wto suppress them. Outside our profession the miasmattheory of disease is by no means dead, and the seasare credited with powers for good and evil which not entirely supported by vital statistics. Few epidemdiseases in fact show an incidence unchanged throughothe year-a remarkable fact in itself-and a good dhas been made of the observation that the maximincidence of poliomyelitis coincides with that of intestinal infections in the late summer. (Hypothesbased on this may have been premature, for there is doubt that Sonne dysentery is now commonest in spring.) It is in the late summer that counters barrows are piled with Victorias and Worcester: asince fruit-pickers are sometimes none too strict abo

personal hygiene, it may be that raw fruit plays sopart in the spread of infection.1Attempts to associate epidemic poliomyelitis w

meteorological phenomena such as temperature and huidity have been unproductive,2 but recently Lawrenhas shown that the odds against the association of weekand annual notifications with " accumulated degweeks from a base of 60°F" being due to chance abetween 20 and 50 to 1. It is a pity that he doeexplain in simpler terms what this phrase means : we tit to mean that poliomyelitis is commoner in a

summer. That is a very interesting observation, buimportance is doubtful. No-one yet knows whether mfcations bear a constant ratio to infections, and until point is settled the high proportion of symptomle;;, r::&l

tions detracts from the value of notifications as a tneof poliomyelitis. As far as is known, the Tiru’- i’

obligatory parasite of homoiothermic animals and to jufrom experience with bacteria the physical conditithe outside air concerns these very Jittle. Before too f:.effort is expended on pursuing this line of inquirmight be of value to examine the correlation of " accumulated degree weeks for a base 60 F’ w

the sales of soft drinks, the flowering of dahlias, a.: : averages of the leadin-- fast bowlers.