957 overdosage; and they point out that the rapid heart- nte may prompt the physician to give more digitalis. with fatal results. They have found that 5 g. potassium chloride by mouth will often remove the symptoms of intoxication and stop digitalis-induced arrhyth- miss.19 20 procainamide (05-1 g. by mouth four-hourly of six-hourly) may also control the arrhythmias.21 22 LOWN and LEVINE have sought to solve the problem of whether patients have had too much or too little italis by a tolerance test in which a rapidly acting coside with a short-lived effect (acetyl strophan- thidin) is injected intravenously. The degree of diritalisation is assessed by the amount of the drug required to produce E.C.G. evidence of digitalis moxication.19 This test may prove of particular in determining the digitalis requirements of patients previously given digitalis who develop cardiac failure or an arrhythmia after operation on the heart. berg, C. D., Simmons, H. G., Mintz, A. A. Amer. Heart J. 39, 713. K., Garlett, E. L., Bellet, S., Getter, W. I. Amer. J. 1951, 11, 431. ord, M. C., Taguchi, J. T. Circulation, 1951, 4, 387. Pharmaceutical Codex 1954. London: Pharmaceutical Pp. 1340. 63s. Annotations THE CODEX THE British Pharmaceutical Codex is almost as old as the century in which we live. The sixth edition, 23 published the week, fulfils even more successfully than its prede- the intention of the Pharmaceutical Society of Britain : to produce a book of reference for those gaged in prescribing or dispensing medicines." A good deal of what appears in the Codex is necessarily predetermined by the contents of the Briti8h Pharma- paia. But for twenty years the Codex has published andards for many drugs not contained in the B.P. Comprehensiveness is desirable, but the Codex Revision fommittee is obliged to bar the way to inclusion when hut is less evident than fantasy. No doubt the com- muttee’s sense of responsibility has increased with the palisation that the B.P.C. (and the National F’orrn2cltary) New rank with the B.P. itself in guiding the Joint Com- mittee on Prescribing in its herculean task of classifying proprietary medicinal preparations. Another outstanding frature of the B.P.C., as compared with the B.P., is the mclusion of paragraphs on actions and uses ; thus, in effeet, the Codex incorporates a handbook of clinical pnarmacology. The new edition is notable for a more attitude towards the reputed therapeutic value of old and new alike. The moulding of policy and the of developments in particular directions may - seem to come within the committee’s terms of refer- . Even so, such is the status and the scope of this that the work of the experts who revise it inevitably the outlook of teachers of pharmacy and of thera- to this extent the B.P.C. exercises an important on the shape of things to come. The revision ttee, however, is obliged to bear in mind that its to meet the needs of contemporary doctors and in their professional work. Thus grave about the value of a drug do not necessarily mention of it to be excluded. In the words of the uction: in some instances many medical practitioners have drugs and preparations with confidence in their aithough convincing clinical evidence of their value is Such drugs and preparations have not been excluded there is acceptable evidence that they are ineffective have fallen into virtual disuse." This statement is noteworthy for its implication that a drug receives " official " sanction unless it can be proved that it has no therapeutic value—which reflects an attitude that is radically different from one that ia voiced in other quarters (and especially by some teachers in our medical school;-) that the onus of proof that a drug has therapeutic value rests on those who make the claim. Nevertheless some diserimination is exercised ; for if the book were simply a cumulative furmulary of all official and non-official remedies, its publication would long ago have proved impracticable. The additions include nearly a hundred general and special monographs. The potency of the new drugs is another remarkable sign of the times—when the syn- thetic chemist is virtually the keeper of the doctor’s arrnoury. These drugs include dyflos (D.F.P.), hexa* methonium tartrate. phenylbutazone, procainamide sulpliate, suxamethonium chloride, and tolazoline hydro- chloride. Among antiriera, vaccines, and related substances interesting additions are B.C.G. vaccien, diph- theria whooping-cough prophylactic, and immune human sera. The surgeon’s needs are well catered for : among the new dressing-; listed are delustred regenerated cellulose and animal wool for chiropody. About eighty new items appear in the formulary. but many of these refer to preparations which became ofncial in the B.P. 1953. Dead wood has been cut away mercilessly : upwards of two hundred and fifty monographs have been deleted from the old volume, and no fewer than four hundred items have vanished from the formulary. As usual there are many appendices ; these have proved invaluable in hospitals and laboratories of many kinds. It is refreshing to find the main titles of drugs and preparations given in English at the top of each mono- graph. The Latin title in full and in its abbreviated form is retained but relegated to a lower place. This is an appropriate gesture from the revision committee, whose members have evidently felt the need for plain words and clear thinking ; and what language is more expressive than English ? 1. Morton, A. M., Jaffe, H. L., Pordy, L. Ann. intern. Med. 1954, 41, 315. 2. Harrison, T. R. Amer. J. med. Sci. 1944, 207, 561. 3. Parkinson, J. Ann. intern. Med. 1951, 35, 499. CHEST PAIN THE diagnosis of ischaemic heart-disease often resta on the history alone ; but Morton et al.1 point out that the six classical features of cardiac pain (onset related to effort or emotion ; substernal position, commonly with radiation to the left arm ; short duration ; constricting in character ; rapidly relieved by nitroglycerin) are by no means pathognomonic. Harrison found that the pain was substernal in only half of his patients with angina pectoris. Parkinson pointed out that pain radiating to the left arm may be a symptom of hiatus hernia, pleural disease, or spinal disease. Morton ot al. have investi- gated the chest pain of 100 patients with proven ischæmic heart-disease and 100 with " functional " heart-disease. They found that the two conditions could not be differen- tiated by the character or site of the pain alone ; tightness in the chest and dull aching pain occurred in functional as well as in ischaemic heart-disease. In a quarter of the functional cases the pain was substernal, and associated with effort ; and in 36% of those who took nitroglycerin repeatedly, this relieved the pain. Un the other hand, among the patients with ischæmic heart-disease, the pain was precordial or in the left chest in 30% ; it came on at rest in the same proportion ; and it was not relieved by nitroglycerin in 10—15%. Morton et al. point out that none of the six classical features should be relied on alone in differentiating between cardiac and non- cardiac pain, but suggest that if three or more of these features are present, ischæmie heart-disease can be more or less definitely diagnosed.
Transcript
957
overdosage; and they point out that the rapid heart-nte may prompt the physician to give more digitalis.with fatal results. They have found that 5 g. potassiumchloride by mouth will often remove the symptomsof intoxication and stop digitalis-induced arrhyth-miss.19 20 procainamide (05-1 g. by mouth four-hourlyof six-hourly) may also control the arrhythmias.21 22
LOWN and LEVINE have sought to solve the problemof whether patients have had too much or too littleitalis by a tolerance test in which a rapidly actingcoside with a short-lived effect (acetyl strophan-thidin) is injected intravenously. The degree ofdiritalisation is assessed by the amount of the drugrequired to produce E.C.G. evidence of digitalismoxication.19 This test may prove of particularin determining the digitalis requirements ofpatients previously given digitalis who develop cardiacfailure or an arrhythmia after operation on the heart.
berg, C. D., Simmons, H. G., Mintz, A. A. Amer. Heart J. 39, 713. K., Garlett, E. L., Bellet, S., Getter, W. I. Amer. J. 1951, 11, 431. ord, M. C., Taguchi, J. T. Circulation, 1951, 4, 387. Pharmaceutical Codex 1954. London: Pharmaceutical Pp. 1340. 63s.
Annotations
THE CODEX
THE British Pharmaceutical Codex is almost as old as thecentury in which we live. The sixth edition, 23 publishedthe week, fulfils even more successfully than its prede-
the intention of the Pharmaceutical Society ofBritain : to produce a book of reference for those
gaged in prescribing or dispensing medicines."A good deal of what appears in the Codex is necessarily
predetermined by the contents of the Briti8h Pharma-paia. But for twenty years the Codex has publishedandards for many drugs not contained in the B.P.
Comprehensiveness is desirable, but the Codex Revisionfommittee is obliged to bar the way to inclusion whenhut is less evident than fantasy. No doubt the com-muttee’s sense of responsibility has increased with thepalisation that the B.P.C. (and the National F’orrn2cltary)New rank with the B.P. itself in guiding the Joint Com-mittee on Prescribing in its herculean task of classifyingproprietary medicinal preparations. Another outstandingfrature of the B.P.C., as compared with the B.P., is themclusion of paragraphs on actions and uses ; thus, ineffeet, the Codex incorporates a handbook of clinicalpnarmacology. The new edition is notable for a more
attitude towards the reputed therapeutic value ofold and new alike. The moulding of policy and the
of developments in particular directions may- seem to come within the committee’s terms of refer-. Even so, such is the status and the scope of this
that the work of the experts who revise it inevitablythe outlook of teachers of pharmacy and of thera-
to this extent the B.P.C. exercises an importanton the shape of things to come. The revision
ttee, however, is obliged to bear in mind that itsto meet the needs of contemporary doctors and
in their professional work. Thus graveabout the value of a drug do not necessarily
mention of it to be excluded. In the words of theuction:
in some instances many medical practitioners havedrugs and preparations with confidence in their
aithough convincing clinical evidence of their value isSuch drugs and preparations have not been excluded
there is acceptable evidence that they are ineffectivehave fallen into virtual disuse."
This statement is noteworthy for its implication that adrug receives
" official " sanction unless it can be provedthat it has no therapeutic value—which reflects anattitude that is radically different from one that ia voicedin other quarters (and especially by some teachers in ourmedical school;-) that the onus of proof that a drug hastherapeutic value rests on those who make the claim.Nevertheless some diserimination is exercised ; for ifthe book were simply a cumulative furmulary of allofficial and non-official remedies, its publication wouldlong ago have proved impracticable.The additions include nearly a hundred general and
special monographs. The potency of the new drugs isanother remarkable sign of the times—when the syn-thetic chemist is virtually the keeper of the doctor’s
arrnoury. These drugs include dyflos (D.F.P.), hexa*methonium tartrate. phenylbutazone, procainamidesulpliate, suxamethonium chloride, and tolazoline hydro-chloride. Among antiriera, vaccines, and relatedsubstances interesting additions are B.C.G. vaccien, diph-theria whooping-cough prophylactic, and immune humansera. The surgeon’s needs are well catered for : among thenew dressing-; listed are delustred regenerated celluloseand animal wool for chiropody. About eighty new itemsappear in the formulary. but many of these refer to
preparations which became ofncial in the B.P. 1953.Dead wood has been cut away mercilessly : upwards oftwo hundred and fifty monographs have been deletedfrom the old volume, and no fewer than four hundreditems have vanished from the formulary. As usual thereare many appendices ; these have proved invaluable inhospitals and laboratories of many kinds.
It is refreshing to find the main titles of drugs andpreparations given in English at the top of each mono-graph. The Latin title in full and in its abbreviated formis retained but relegated to a lower place. This is anappropriate gesture from the revision committee, whosemembers have evidently felt the need for plain words andclear thinking ; and what language is more expressivethan English ?
1. Morton, A. M., Jaffe, H. L., Pordy, L. Ann. intern. Med. 1954,41, 315.
2. Harrison, T. R. Amer. J. med. Sci. 1944, 207, 561.3. Parkinson, J. Ann. intern. Med. 1951, 35, 499.
CHEST PAIN
THE diagnosis of ischaemic heart-disease often resta onthe history alone ; but Morton et al.1 point out that thesix classical features of cardiac pain (onset related toeffort or emotion ; substernal position, commonly withradiation to the left arm ; short duration ; constrictingin character ; rapidly relieved by nitroglycerin) are byno means pathognomonic. Harrison found that the painwas substernal in only half of his patients with anginapectoris. Parkinson pointed out that pain radiating tothe left arm may be a symptom of hiatus hernia, pleuraldisease, or spinal disease. Morton ot al. have investi-
gated the chest pain of 100 patients with proven ischæmicheart-disease and 100 with " functional " heart-disease.They found that the two conditions could not be differen-tiated by the character or site of the pain alone ; tightnessin the chest and dull aching pain occurred in functionalas well as in ischaemic heart-disease. In a quarter of thefunctional cases the pain was substernal, and associatedwith effort ; and in 36% of those who took nitroglycerinrepeatedly, this relieved the pain. Un the other hand,among the patients with ischæmic heart-disease, thepain was precordial or in the left chest in 30% ; it cameon at rest in the same proportion ; and it was not relievedby nitroglycerin in 10—15%. Morton et al. point outthat none of the six classical features should be reliedon alone in differentiating between cardiac and non-cardiac pain, but suggest that if three or more of thesefeatures are present, ischæmie heart-disease can be moreor less definitely diagnosed.
958
A careful history and thorough physical examination,combined with electrocardiography, will usually resultin correct diagnosis. In doubtful cases the possibility ofspinal, gall-bladder. or œsophageal disease, or of hiatushernia, must be considered. Hiatus hernia should besuspected if the pain is worse when the patient stoopsor lies flat, or if flatulence is particularly prominent.Anæmia caused by bleeding from an associated pepticor œsophageal ulcer may also suggest this diagnosis.Gall-stones and hiatus hernia may, of course, be symp-tomless accompaniments of ischæmic heart-disease; theyare not necessarily the cause of the pain. In difficultcases electrocardiography before and after effort is oftenhelpful ; in cardiac ischæmia induced by effort the STsegment is depressed and the T wave flattened or inverted.This test should be carried out only when the restingcardiogram is normal or equivocal.
1. See Lancet, 1953, i, 278.2. See Ibid, p. 285.3. Szabo, J. L., Edwards, C. D., Bruce, W. F. Antibiot. Chemother.
1951. 1, 499.4. Fletcher, A. P., Knappett, C. R. Brit. med. J. 1953, i 188.
Stollerman, G. H., Rusoff. J. H. J. Amer. med. Ass. 1952,150, 1571.
5. Perry, C. B., Gillespie, W. A. Brit. med. J. Sept. 25, 1954, p. 729.6. Diehl, A. M., Hamilton, T. R., Keeling, I. C., May, J. S. J. Amer.
med. Ass. 1954, 155, 1466.7. Chamovitz, R., Catanzaro, F. J., Stetson, C. A., Rammelkamp,
C. H. New Engl. J. Med. 1954, 251, 466.8. Denny, F. W., Wannamaker. L. W. Brink, W. R., Rammelkamp.
C. H., Custer. E. A. J. Amer. med. Ass. 1950. 143, 151.
GROUP-A STREPTOCOCCI AND BENZATHINE
PENICILLIN
THERE is little doubt that rheumatic fever is initiatedand perpetuated by infection of the respiratory tractwith group-A streptococci. Prophylaxis, to be effective,must be continuous.’ For this purpose daily administra-tioia of sulphacdiazine over long periods has provedeffective, simple, and cheap ; but because of occasionaltoxic effects and the increasing emergence of resistantstrains, it is not fully satisfactory. Penicillin is superiorin both these respects, and it. too, may be given orally 2 ;but oral penicillin is expensive and patients dislikehaving to take tablets daily for many months. Theintroduction by Szabo et al.3 of a really long-acting paren-teral preparation (benzathine penicillin G) was an
important advance; subsequent work 4 has shown thata single intramuscular injection of this sparingly solublecompound gives a detectable blood-level for two to fourweeks, depending on the dosage. Perry and Gillespie5have now administered this substance to a group ofchildren recovering from rheumatic fever or chorea, whoincluded many persistent carriers of group-A streptococci.Monthly injections of 1.5 mega units of benzathine peni-cillin quickly eliminated streptococci from the throatsof carriers and almost completely prevented new infec-tions. The consequent fall in the incidence of infectionin the community led to a rapid reduction in the numberof carriers in a
" control " group of untreated cases.
Diehl et al.6 have administered benzathine penicillin tooutpatients with inactive rheumatic fever, taking as
controls the healthy siblings of these patients. Their
preliminary results apparently justify this prophylacticuse of the drug. Recent trials have shown that prolongedmaintenance of a low or intermittent blood-level of
penicillin does not give rise to hypersensitivity or
cause resistant strains of streptococci to develop, andthe only drawback is that most patients complain oftenderness at the site of injection for twenty-four toforty-eight hours. There seems, then, to he good evidencethat for the prophylaxis of streptococcal infections inrheumatic subjects benzathine penicillin is an effectivealternative to oral sulphadiazine or oral penicillin.For the treatment of streptococcal respiratory infec-
tions, Chamovitz et al.7 believe that benzathine penicillinG may be the drug of choice. Denny et al.8 had previously
shown that penicillin given in adequate doses andlong enough (a week or, better, ten days) will neaalways prevent an initial attack of rheumatic f
following streptococcal sore throat. But when symptsubside after a few days, both patient and doctor mayreluctant to continue injections ; while oral penicialthough prescribed, may equally be spurned hy recovering patient. Chamovitz et al. have therefturned to a single dose of benzathine penicillin in trf-streptococcal sore throat. Their results in a carefplanned trial show that among 102 young adults g600,000 units of beuzathine penicillin intramusculawithin three days of onset of sure throat, streptocwere virtually eradicated from the throat within thweeks ; the infection evoked a minimal antistreptolysresponse and no subsequent signs of rheumatic feOf an untreated group of 66 similar cases. 80% still infected at three weeks : the average antistreptolresponse was distinct ; and subsequently 2 cases of rmatic fever and 1 of acute glomerulonephritis occurAlthough penicillin reactions were commoner in treatment trial than the prophylaxis trials, it is clear benzathine penicillin is a most promising advance intreatment of streptococcal respiratory infection.
1. Lancet, Aug. 21, 1954, p. 372.2. Thorson, A.. Bjōrk. G., Bjōrkman, G., Waldenström, J.
Heart J. 1954, 47, 795.3. Dalgliesh, C. E., Toh, C. C.. Work, T. S. J. Physiol. 195
298.
4. Jepson, J. B., Stevens. B. J. Nature, Lond. 1953, 172 7725. Blaschko, H., Philpot, F. J. J. Physiol. 1953, 122, 403.6. Titus, E., Udenfriend, S. Fed Proc. 1954, 13, 411.7. Dockerty, M. B., Ashburn, F. S. Arch. Sury., Chicago, 1943, 8. Stewart, M. J., Willis, R. A., de Saram, G. S. W. J. Pat
1939, 49, 207.
ARGENTAFFINOMA AS ENDOCRINE TUMOU
WE have lately drawn attention to the interesyndrome in which transient macular cyanosis pulmonary stenosis are found in association
metastasising argentaffinomata. Thorson et al.,2 first described this syndrome, suggested that it resfrom secretion by the tumour of 5-hydroxytrypta(serotonin or enteramine), and this engaging hypothis strongly supported by the latest work of Dr. Peand Professor Waldenström described in a prelimicommunication on an earlier page of this issue. Incases- of the syndrome biological assay showed thasera contained about a hundred times the normal atnof 5-hydroxytryptamine. Their method of assay, the rat colon,3 is highly specific, but more precise chr-identification by paper chromatography4 should besible. (Experience with noradrenaline has shownnecessary it is to identify accurately substances whicpharmacologically active.) A third method of investion is suggested by the fact that 5-hydroxytryptanafter breakdown by amine-oxidase, 5 is excrete
5-hydroxy-indole-acetic acid; in health about 10 mthis is excreted daily in the urine,’ but excretion isprobably increased in patients with the syndrNo standard method of estimating 5-hydroxy-inacetic acid has been published ; but the proceunlikely to be technically difficult, and would certbe very valuable in studies of this kind.
Many investigators have been puzzled by the consable local hypertrophy of smooth muscle which accompanies argent affinoma.7 When the tumouin the ileum or even the appendix obstruction olumen might be the cause; but such hyperthas also been found with ovarian teratoma.6 the work now reported by Pernow and Waldenstrseems that the hypertrophy is due to the !wal eff5-hydroxytryptamine. Two important points from this work. First, it suggests that the secretthe normal argentaffin cells of the intestine acts
