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PROLACTIN, LEVODOPA, AND MIGRAINE
810
PROLACTIN, LEVODOPA, AND MIGRAINE SIR,-Mr Parantainen (Feb. 22, p. 467) advocated clinical trials of levodopa to test its anti-migraine properties in view of its prolactin-inhibiting effect. Whatever the role of prolactin in migraine may be, the use of levodopa for that purpose should be accepted with reluctance in view of the properties of the various known, prolactin suppressors. After a single dose of levodopa (500 mg.) the decrease is followed by a rebound at 8 hours, while after chronic administration (500 mg. four times daily) a saw-toothed effect is observed with brief falls after each dose, followed by sharp rebounds. According to Horrobin’s hypothesis,1 this variation in prolactin levels would be propitious to migraine attacks, despite the inhibitory effect induced by
levodopa. In
another
drug, bromocripine (CB-154, a more profound and sustained decrease in serum-prolactin levels after a single oral dose as well as during continued oral administration. A comparison between levodopa and bromocriptine in this regard clearly favours the latter.3 In a disease such as migraine, where assessment of therapeutic efficacy is particularly difficult, levodopa seems a rather poor contrast,
2-Br-
induces
candidate. M. ROZENCWEIG J. C. HEUSON.
LATE MORTALITY IN WILMS’ TUMOUR of mortality late in the course of Wilms’ reported by Dr Li and others (Jan. 4, p. 41) of long-term survival of 599 cases of review a prompted Wilms’ tumour in Whites diagnosed between 1935 and 1969 and reported to the End Results Group (E.R.G.) of the excess
tumour
Actuarial survival curve for 225 cases of Wilms’ tumour in patients alive 36 months after diagnosis compared with cases reported by Li et al.
National Cancer Institute.3,4 Of 225 patients alive three years after diagnosis, 12 have died. This series from a large group of U.S. hospitals presents a better prognosis for long-term survivors of Wilms’ tumour than suggested by Li et al. (see accompanying figure). The difference Horrobin, D. F. Lancet, 1973, i, 777. Rozencweig, M., Heuson, J. C., Bila, S., L’Hermite, M., Robyn, C. Eur. J. Cancer, 1973, 9, 657. 3. Cutler, S. J., Latourette, H. B. J. natn. Cancer Inst. 1959, 22, 633. 4. Everson, R. B., Fraumeni, J. F., Jr., Myers, M. H. Lancet, 1974, i, 1. 2.
1290.
I thank the Biometry Branch, National Cancer Institute, for the data used in this report. Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20014, U.S.A.
RICHARD B. EVERSON.
ENDOTOXÆMIA IN LIVER CIRRHOSIS : TREATMENT WITH POLYMYXIN B SIR,—Prompted by the survey of Dr Bradfieldof the problem of spilloverand by the letter of Dr Bjornboe and Dr Prytz (Jan. 4, p. 45), we should like to present evidence for the occurrence of endotoxaemia in cirrhosis of the liver, which has a bearing on the problems discussed. 9 consecutive patients admitted to were investigated for endotoxaemia
hospital with liver cirrhosis by means of the Limulus gelation test (L.G.T.).3 L.G.T. (’Pyrogent’, Byk-Mallinckrodt, Dietzenbach, West Germany) was performed in heparinised plasma undiluted and in dilutions of 1/10 and 1/100. All 9 patients had endotoxaemia; in 2 of them endotoxins could be detected also in the ascitic fluid. Bactersmia 3
Department of Medicine and Clinical Investigation, Institut Jules Bordet, 1000 Brussels, Belgium.
SiR,-The
probably reflects larger numbers in the E.R.G. series, patient selection, and treatment employed.
was
present in
patients.
Caridis et al. have also demonstrated the presence of endotoxaemia in 2 non-septic patients with liver cirrhosis.
Bjornboe and Prytz mention the need for therapeutic trials with newer antibiotics. Polymyxin B, as shown in animal experiments, is thought to neutralise endotoxins.5,8 We therefore treated our patients with an infusion of polymyxin B, 1-1 mg. per kg. per 24 hours (Pfizer GmbH, Karlsruhe, West Germany), over a period of 72 hours. In 4 patients there was a positive effect on endotoxaemia, but 2 patients developed endotoxaemia during the treatment. The plasma-fibrinogen concentrations and plateletcounts, involved in the consumption coagulopathy common in liver cirrhosis,’ increased either independently or together. 5 patients significantly improved during this treatment, but 1 remained L.G.T. positive. 4 patients did not show any definite response. 1 died on the second day of treatment, still L.G.T. positive. Another became L.G.T. negative but died on the 3rd day. 1 patient, becoming L.G.T. negative, developed bleeding from oesophageal varices 2 weeks later and died. Dispite the small number of patients, we feel that the frequency of endotoxaemia in this unselected group is significant. We think that some of the clinical signs of cirrhosis should be interpreted as being due to endotoxsmia. We refer to the hyperdynamic statewith opened arteriovenous shunts in the vascular periphery and to the consumption coagulopathy 7, both of which can be induced by endotoxins in animal experiments.5,9 Furthermore, functional renal failure, as part of the picture of liver cirrhosis,lo has lately been related to endotoxxmia.11 It seems, therefore, that endotoxaemia in liver cirrhosis is not merely of pathophysiological interest but also has a clinical significance. Polymyxin B, as given here, did not Bradfield, J. W. B. Lancet, 1974, ii, 883. Triger, D. R., Alp, M. H., Wright, R. ibid. 1972, ii, 60. Levin, J., Tomasula, P. A., Oser, R. J. Lab. clin. Med. 1970, 75, 903. Caridis, D. T., Reinhold, R. B., Woodruff, P. W. H., Fine, J. Lancet, 1972, i, 1381. 5. Corrigan, J. J., Bell, B. M. J. Lab. clin. Med. 1971, 77, 802. 6. Palmer, J. D., Rifkin, D. Surgery Gynec. Obstet. 1974, 138, 735. 7. Hörder, M.-H. Thromb. Diath. hœmoorh. 1969, suppl. 36, p. 313. 8. Liehr, H., Grün, M., Thiel, H. Z. Gastroenterologie (in the press). 9. Lambert, P. B., Si Chun Ming, Ch. B., Palmerion, C. Am. J. Path. 1961, 57, 559. 10. Conn, H. O. Gastroenterology, 1973, 65, 321. 11. Wilkinson, S. P., Arroyo, V., Gazzard, B. G., Moodie, H., Williams, R. Lancet, 1974, i, 521. 1. 2. 3. 4.
PROLACTIN, LEVODOPA, AND MIGRAINE SIR,-Mr Parantainen (Feb. 22, p. 467) advocated clinical trials of levodopa to test its anti-migraine properties in view of its prolactin-inhibiting effect. Whatever the role of prolactin in migraine may be, the use of levodopa for that purpose should be accepted with reluctance in view of the properties of the various known, prolactin suppressors. After a single dose of levodopa (500 mg.) the decrease is followed by a rebound at 8 hours, while after chronic administration (500 mg. four times daily) a saw-toothed effect is observed with brief falls after each dose, followed by sharp rebounds. According to Horrobin’s hypothesis,1 this variation in prolactin levels would be propitious to migraine attacks, despite the inhibitory effect induced by
levodopa. In
another
drug, bromocripine (CB-154, a more profound and sustained decrease in serum-prolactin levels after a single oral dose as well as during continued oral administration. A comparison between levodopa and bromocriptine in this regard clearly favours the latter.3 In a disease such as migraine, where assessment of therapeutic efficacy is particularly difficult, levodopa seems a rather poor contrast,
2-Br-
induces
candidate. M. ROZENCWEIG J. C. HEUSON.
LATE MORTALITY IN WILMS’ TUMOUR of mortality late in the course of Wilms’ reported by Dr Li and others (Jan. 4, p. 41) of long-term survival of 599 cases of review a prompted Wilms’ tumour in Whites diagnosed between 1935 and 1969 and reported to the End Results Group (E.R.G.) of the excess
tumour
Actuarial survival curve for 225 cases of Wilms’ tumour in patients alive 36 months after diagnosis compared with cases reported by Li et al.
National Cancer Institute.3,4 Of 225 patients alive three years after diagnosis, 12 have died. This series from a large group of U.S. hospitals presents a better prognosis for long-term survivors of Wilms’ tumour than suggested by Li et al. (see accompanying figure). The difference Horrobin, D. F. Lancet, 1973, i, 777. Rozencweig, M., Heuson, J. C., Bila, S., L’Hermite, M., Robyn, C. Eur. J. Cancer, 1973, 9, 657. 3. Cutler, S. J., Latourette, H. B. J. natn. Cancer Inst. 1959, 22, 633. 4. Everson, R. B., Fraumeni, J. F., Jr., Myers, M. H. Lancet, 1974, i, 1. 2.
1290.
I thank the Biometry Branch, National Cancer Institute, for the data used in this report. Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20014, U.S.A.
RICHARD B. EVERSON.
ENDOTOXÆMIA IN LIVER CIRRHOSIS : TREATMENT WITH POLYMYXIN B SIR,—Prompted by the survey of Dr Bradfieldof the problem of spilloverand by the letter of Dr Bjornboe and Dr Prytz (Jan. 4, p. 45), we should like to present evidence for the occurrence of endotoxaemia in cirrhosis of the liver, which has a bearing on the problems discussed. 9 consecutive patients admitted to were investigated for endotoxaemia
hospital with liver cirrhosis by means of the Limulus gelation test (L.G.T.).3 L.G.T. (’Pyrogent’, Byk-Mallinckrodt, Dietzenbach, West Germany) was performed in heparinised plasma undiluted and in dilutions of 1/10 and 1/100. All 9 patients had endotoxaemia; in 2 of them endotoxins could be detected also in the ascitic fluid. Bactersmia 3
Department of Medicine and Clinical Investigation, Institut Jules Bordet, 1000 Brussels, Belgium.
SiR,-The
probably reflects larger numbers in the E.R.G. series, patient selection, and treatment employed.
was
present in
patients.
Caridis et al. have also demonstrated the presence of endotoxaemia in 2 non-septic patients with liver cirrhosis.
Bjornboe and Prytz mention the need for therapeutic trials with newer antibiotics. Polymyxin B, as shown in animal experiments, is thought to neutralise endotoxins.5,8 We therefore treated our patients with an infusion of polymyxin B, 1-1 mg. per kg. per 24 hours (Pfizer GmbH, Karlsruhe, West Germany), over a period of 72 hours. In 4 patients there was a positive effect on endotoxaemia, but 2 patients developed endotoxaemia during the treatment. The plasma-fibrinogen concentrations and plateletcounts, involved in the consumption coagulopathy common in liver cirrhosis,’ increased either independently or together. 5 patients significantly improved during this treatment, but 1 remained L.G.T. positive. 4 patients did not show any definite response. 1 died on the second day of treatment, still L.G.T. positive. Another became L.G.T. negative but died on the 3rd day. 1 patient, becoming L.G.T. negative, developed bleeding from oesophageal varices 2 weeks later and died. Dispite the small number of patients, we feel that the frequency of endotoxaemia in this unselected group is significant. We think that some of the clinical signs of cirrhosis should be interpreted as being due to endotoxsmia. We refer to the hyperdynamic statewith opened arteriovenous shunts in the vascular periphery and to the consumption coagulopathy 7, both of which can be induced by endotoxins in animal experiments.5,9 Furthermore, functional renal failure, as part of the picture of liver cirrhosis,lo has lately been related to endotoxxmia.11 It seems, therefore, that endotoxaemia in liver cirrhosis is not merely of pathophysiological interest but also has a clinical significance. Polymyxin B, as given here, did not Bradfield, J. W. B. Lancet, 1974, ii, 883. Triger, D. R., Alp, M. H., Wright, R. ibid. 1972, ii, 60. Levin, J., Tomasula, P. A., Oser, R. J. Lab. clin. Med. 1970, 75, 903. Caridis, D. T., Reinhold, R. B., Woodruff, P. W. H., Fine, J. Lancet, 1972, i, 1381. 5. Corrigan, J. J., Bell, B. M. J. Lab. clin. Med. 1971, 77, 802. 6. Palmer, J. D., Rifkin, D. Surgery Gynec. Obstet. 1974, 138, 735. 7. Hörder, M.-H. Thromb. Diath. hœmoorh. 1969, suppl. 36, p. 313. 8. Liehr, H., Grün, M., Thiel, H. Z. Gastroenterologie (in the press). 9. Lambert, P. B., Si Chun Ming, Ch. B., Palmerion, C. Am. J. Path. 1961, 57, 559. 10. Conn, H. O. Gastroenterology, 1973, 65, 321. 11. Wilkinson, S. P., Arroyo, V., Gazzard, B. G., Moodie, H., Williams, R. Lancet, 1974, i, 521. 1. 2. 3. 4.