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USES AND DANGERS OF CHLORPROMAZINE
806 treated with sulphadiazine from admission. The response to the streptococcal infection was about the same in all the groups ; but in the penicillin group the incidence of subsequent rheumatic fever was much lower than in the untreated and sulphadiazineor were
antistreptolysin
treated groups. If the antistreptolysin response indicates the response to other streptococcal antigens it may be concluded, as Cantazaro et al. point out, " that the prevention of rheumatic fever by penicillin treatment of streptococcal disease is not related to the suppression of the immune response ordinarily seen." On the other hand, the results suggest that the living streptococcus must be present for rheumatic fever to develop although this organism has rarely been detected in the joints, blood, nodules, or heart-valves of rheumatic patients. These workers suggest, too, that their results make the " auto-antibody hypothesis regarding the aetiology of rheumatic fever less tenable ; but knowledge of the biological mechanisms of antigenicity and tissue-antibody response is at present so fragmentary that it is difficult to substantiate either this argument or the alternative hypothesis of hyper"
sensitivity analysis of
to
"
streptococcal products."
Nevertheless,
the effects of antibiotic treatment of streptococcal infections may yield further information on the pathogenesis of rheumatic fever.
ATYPICAL TUBERCULOSIS OF THE LIVER IN patients with tuberculosis the liver may be affected in many ways, either directly as a result of the spread of infection to the liver or indirectly as a result of the metabolic disturbance. Amyloid degeneration and severe fatty infiltration are the two outstanding types of hepatic disease due to such metabolic disturbance. But, apart from these severe changes, impaired liver function can commonly be revealed in tuberculous patients by function tests. Involvement of the liver owing to bacterial dissemination is also by no means uncommon, especially in the late stages of tuberculosis when the incidence may rise to 80%. Jaundice is rare ; there was only a single case in Cruice’sseries of 570 necropsies on patients who had died of chronic pulmonary tuberculosis, and only 7 in his 1748 clinical cases of tuberculosis. Tuberculosis of the liver is therefore easily overlooked in the diagnosis of chronic jaundice, especially because the clinical picture closely resembles that of infective hepatitis. Since the prognosis of hepatic tuberculosis has been vastly improved by antibiotics and chemotherapy the recognition of such cases is important. Cleve et al.2 have now described 4 cases under the title " atypical tuberculosis of the liver with jaundice." This is defined as a condition " where the liver is principally or exclusively involved in tuberculous infection and where there are signs and/or symptoms of hepatic involvement." All 4 patients were Filipino men of military age. The commonest clinical features were mild to moderate persistent obstructive jaundice, low-grade pyrexia often accompanied by chills, hepatomegaly, and Liverupper abdominal pain unrelated to meals. function tests suggested parenchymal hepatic injury ; there was increased thymol turbidity and bromsulphalein retention. In only 1 case was there evidence of active pulmonary tuberculosis ; in 2 others there was radiographic evidence of quiescent pulmonary disease. It is not surprising that the correct diagnosis was made only with the aid of laparotomy ; even then in the 1st case the raised white hepatic nodules were mistaken for metastatic neoplasms until histological examination revealed the characteristic changes and acid-fast bacilli. Laparotomy is apparently the only certain method of confirming the diagnosis, which cannot be reliably excluded by a ’
1. Cruice, J. M. Amer. J. med. Sci. 1914, 147, 720. 2. Cleve, E. A., Gibson, J. R., Webb, W. M. Ann. intern. Med. 1954, 41, 251.
negative Mantoux needle-biopsies.
reaction
or
by repeatedly negative
Treatment with streptomycin 1 g. daily has produced dramatic results. Of the 4 patients treated in this way by Cleve et al. 2 apparently recovered completely, seven and twelve months after the end of treatment. An equally satisfactory result has been reported in 2 other cases.34 Atypical tuberculosis of the liver with jaundice is undoubtedly a rare condition in this country, where the resistance of the viscera, excluding the lungs, is high. In other communities visceral susceptibility may be much greater, and Cleve’s series of 4 cases in Filipinos suggests that racial factors may be important. some
USES AND DANGERS OF CHLORPROMAZINE Two further uses for that versatile compound, chlorpromazine, have been described. Tilley and Barry5, claim that in 3 cases of neurodermatitis it considerably relieved pruritus and motor overactivity. Friedgood and Ripstein 6 gave chlorpromazine to 8 drug addicts during abrupt withdrawal of their drug (morphine in 5 instances, pethidine in 2, and pentobarbitone in 1). No patient experienced withdrawal symptoms, and the craving for the drug of addiction was abolished. It is not surprising that chlorpromazine, which has a wide range of activity, should exert toxic effects. Acute hypotension is not uncommon, especially when the patient is allowed to remain on his feet during the initial stages of treatment with large doses ; and deaths have resulted from this complication.7 Several cases of jaundice have also been reported,8-10 and this complication too has been fatal. The jaundice is peculiar in usually appearing to the clinician to be obstructive ; biopsy specimens have shown intrahepatic biliary stasis 9 or periportal cellular infiltration.1O Blood occasionally arisenotably eosinophilia,9 though agranulocytosis has been recorded 11 12 and in 1 case this was fatal.li These and other possible hazards of chlorpromazine therapy should prompt the clinician to examine critically in every case the indications for administering the drug. Repeated exposure has led to severe dermatitis in nurses 13
changes
Sir RUSSELL BRAIN has been re-elected president of the of Physicians of London for the coming
Royal College year.
IN the Cabinet changes announced last week Dr. CHARLES HILL was appointed Postmaster-General. Prof. EVELYN SPRAWSON, consulting dental surgeon to the London Hospital, died on April 6 while attending a meeting of the council of the Medical Protection Society. He was 74 years of age. Choremis, C. V., Ninios, N. Acta. pœdiat., Stockh. 1949, 37, 188. Melville, I. D. Brit. med. J. 1951, i, 1187. Tilley, R. F., Barry, H. New Engl. J. Med. 1955, 252, 229. Friedgood, C. E., Ripstein, C. B. Ibid, p. 230. 7. Rea, E. L., Shea, E. J., Fazekas, J. F. J. Amer. med. Ass. 1954, 156, 1249. 8. Boardman, R. H. Brit. med. J. 1954, ii, 578. 9. Van Ommen, R. A., Brown, C. H. J. Amer. med. Ass. 1955, 157, 3. 4. 5. 6.
321. 10. Zatuchni, J., Miller, G. New Engl. J. Med. 1954, 251, 1003. 11. Boleman, A. P. J. Amer. med. Ass. 1955, 157, 364. 12. Lomas, J. Brit. med. J. 1954, ii, 358. 13. Lewis, G. M., Sauricky, H. H. J. Amer. med. Ass. 1955, 157,
909.
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WE now print a small proportion of our weekly issue India paper for transmission to distant countries by air. The subscription rates for one year, inclusive of on
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postage,
are :
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antistreptolysin
treated groups. If the antistreptolysin response indicates the response to other streptococcal antigens it may be concluded, as Cantazaro et al. point out, " that the prevention of rheumatic fever by penicillin treatment of streptococcal disease is not related to the suppression of the immune response ordinarily seen." On the other hand, the results suggest that the living streptococcus must be present for rheumatic fever to develop although this organism has rarely been detected in the joints, blood, nodules, or heart-valves of rheumatic patients. These workers suggest, too, that their results make the " auto-antibody hypothesis regarding the aetiology of rheumatic fever less tenable ; but knowledge of the biological mechanisms of antigenicity and tissue-antibody response is at present so fragmentary that it is difficult to substantiate either this argument or the alternative hypothesis of hyper"
sensitivity analysis of
to
"
streptococcal products."
Nevertheless,
the effects of antibiotic treatment of streptococcal infections may yield further information on the pathogenesis of rheumatic fever.
ATYPICAL TUBERCULOSIS OF THE LIVER IN patients with tuberculosis the liver may be affected in many ways, either directly as a result of the spread of infection to the liver or indirectly as a result of the metabolic disturbance. Amyloid degeneration and severe fatty infiltration are the two outstanding types of hepatic disease due to such metabolic disturbance. But, apart from these severe changes, impaired liver function can commonly be revealed in tuberculous patients by function tests. Involvement of the liver owing to bacterial dissemination is also by no means uncommon, especially in the late stages of tuberculosis when the incidence may rise to 80%. Jaundice is rare ; there was only a single case in Cruice’sseries of 570 necropsies on patients who had died of chronic pulmonary tuberculosis, and only 7 in his 1748 clinical cases of tuberculosis. Tuberculosis of the liver is therefore easily overlooked in the diagnosis of chronic jaundice, especially because the clinical picture closely resembles that of infective hepatitis. Since the prognosis of hepatic tuberculosis has been vastly improved by antibiotics and chemotherapy the recognition of such cases is important. Cleve et al.2 have now described 4 cases under the title " atypical tuberculosis of the liver with jaundice." This is defined as a condition " where the liver is principally or exclusively involved in tuberculous infection and where there are signs and/or symptoms of hepatic involvement." All 4 patients were Filipino men of military age. The commonest clinical features were mild to moderate persistent obstructive jaundice, low-grade pyrexia often accompanied by chills, hepatomegaly, and Liverupper abdominal pain unrelated to meals. function tests suggested parenchymal hepatic injury ; there was increased thymol turbidity and bromsulphalein retention. In only 1 case was there evidence of active pulmonary tuberculosis ; in 2 others there was radiographic evidence of quiescent pulmonary disease. It is not surprising that the correct diagnosis was made only with the aid of laparotomy ; even then in the 1st case the raised white hepatic nodules were mistaken for metastatic neoplasms until histological examination revealed the characteristic changes and acid-fast bacilli. Laparotomy is apparently the only certain method of confirming the diagnosis, which cannot be reliably excluded by a ’
1. Cruice, J. M. Amer. J. med. Sci. 1914, 147, 720. 2. Cleve, E. A., Gibson, J. R., Webb, W. M. Ann. intern. Med. 1954, 41, 251.
negative Mantoux needle-biopsies.
reaction
or
by repeatedly negative
Treatment with streptomycin 1 g. daily has produced dramatic results. Of the 4 patients treated in this way by Cleve et al. 2 apparently recovered completely, seven and twelve months after the end of treatment. An equally satisfactory result has been reported in 2 other cases.34 Atypical tuberculosis of the liver with jaundice is undoubtedly a rare condition in this country, where the resistance of the viscera, excluding the lungs, is high. In other communities visceral susceptibility may be much greater, and Cleve’s series of 4 cases in Filipinos suggests that racial factors may be important. some
USES AND DANGERS OF CHLORPROMAZINE Two further uses for that versatile compound, chlorpromazine, have been described. Tilley and Barry5, claim that in 3 cases of neurodermatitis it considerably relieved pruritus and motor overactivity. Friedgood and Ripstein 6 gave chlorpromazine to 8 drug addicts during abrupt withdrawal of their drug (morphine in 5 instances, pethidine in 2, and pentobarbitone in 1). No patient experienced withdrawal symptoms, and the craving for the drug of addiction was abolished. It is not surprising that chlorpromazine, which has a wide range of activity, should exert toxic effects. Acute hypotension is not uncommon, especially when the patient is allowed to remain on his feet during the initial stages of treatment with large doses ; and deaths have resulted from this complication.7 Several cases of jaundice have also been reported,8-10 and this complication too has been fatal. The jaundice is peculiar in usually appearing to the clinician to be obstructive ; biopsy specimens have shown intrahepatic biliary stasis 9 or periportal cellular infiltration.1O Blood occasionally arisenotably eosinophilia,9 though agranulocytosis has been recorded 11 12 and in 1 case this was fatal.li These and other possible hazards of chlorpromazine therapy should prompt the clinician to examine critically in every case the indications for administering the drug. Repeated exposure has led to severe dermatitis in nurses 13
changes
Sir RUSSELL BRAIN has been re-elected president of the of Physicians of London for the coming
Royal College year.
IN the Cabinet changes announced last week Dr. CHARLES HILL was appointed Postmaster-General. Prof. EVELYN SPRAWSON, consulting dental surgeon to the London Hospital, died on April 6 while attending a meeting of the council of the Medical Protection Society. He was 74 years of age. Choremis, C. V., Ninios, N. Acta. pœdiat., Stockh. 1949, 37, 188. Melville, I. D. Brit. med. J. 1951, i, 1187. Tilley, R. F., Barry, H. New Engl. J. Med. 1955, 252, 229. Friedgood, C. E., Ripstein, C. B. Ibid, p. 230. 7. Rea, E. L., Shea, E. J., Fazekas, J. F. J. Amer. med. Ass. 1954, 156, 1249. 8. Boardman, R. H. Brit. med. J. 1954, ii, 578. 9. Van Ommen, R. A., Brown, C. H. J. Amer. med. Ass. 1955, 157, 3. 4. 5. 6.
321. 10. Zatuchni, J., Miller, G. New Engl. J. Med. 1954, 251, 1003. 11. Boleman, A. P. J. Amer. med. Ass. 1955, 157, 364. 12. Lomas, J. Brit. med. J. 1954, ii, 358. 13. Lewis, G. M., Sauricky, H. H. J. Amer. med. Ass. 1955, 157,
909.
THE LANCET AIR-MAIL EDITION
WE now print a small proportion of our weekly issue India paper for transmission to distant countries by air. The subscription rates for one year, inclusive of on
air-mail
postage,
are :
AUSTRAI.IA AND NEW ZEALAND .. &12 12 0 (sterling) UNITED STATES, CANADA, SOUTH AFRICA, AND INDIA..... P, 10 10 0 (sterling) OTHER COUNTRIES.... Quotations on request THE LANCET, 7, Adam
Street, Adelphi, London, W.C.2