1360 fall into disrepute. The decision to drain should not be taken lightly, and should be carefully weighed against the alternative of early surgery. We have not had to resort to drainage in any of our cases to date but have continued gentamicin cover up to the time of surgery, which should be undertaken within 48 h, in all cases of gallstone obstruction where the risk of to
ascending cholangitis is highest. Llandough Hospital, Penarth, Glamorgan CF6
1XX
G. DE B. HINDE P. M. SMITH
SEPTIC SHOCK
SIR,-The extensive experience of Dr Ledingham and Mr McArdle (June 3, p. 1194) is of great interest. However, they cannot be said to be "treating" septic shock: their skill lies in supporting the lungs and circulation in patients with sepsis. Indeed, as their mortality figures show, the patients still die of multiorgan damage, and this is known to be induced by endotoxin. The mortality of septic shock remains near 50% because most people do not have protective anti-lipid-A antibodies in any appreciable titre. Until immunisation or immediate serum therapy become the accepted mode of raising antibody titres, there will be no real progress. In Britain there are about 2000 deaths a year because of this.
cal
improvement, and the steroid dose was subsequently tapered without adverse effects. Perhaps methylprednisone and/or its hemisuccinate is preferable in patients with brain tumours who are also on anticonvulsants. One fact we must not forget is that the treatment of brain tumours with large doses of corticosteroids may prolong the survival of such patients in a functional and productive fashion, Munson Medical Center, Traverse City, Michigan 49684, U.S.A.
FREDERICK M. VINCENT
D.A.T. (DAUNORUBICIN, CYTARABINE, 6-THIOGUANINE) IN ACUTE MYELOID LEUKÆMIA SIR,-In 1977 we reported’ a remission-rate of 85% in twenty consecutive patients with acute myeloid leukaemia treated with the D.A.T. regimen-a combination of daunorubicin 50 mg/m2 on day 1, cytarabine 100 mg/m2 12-hourly by intravenous push and 6-thioguanine 100 mg/m2 12-hourly on days 1-5. Many inquirers have asked whether this remissionrate is being maintained. We have now treated forty consecutive patients with the D.A.T. regimen, of whom thirty-four (85%) entered complete remission. Figs 1 and 2 show that the median duration of survival is 104 weeks and the median duration of remission is 61 weeks. A second remission following a relapse was obtained in 45%.
Department of Therapeutics, Sheffield Royal Sheffield
Infirmary,
E. N. WARDLE
1.
Rees, J.
K.
H., Sandler,
R.
M., Challener, J. Hayhoe, F. G. J. Br. J. Cancer,
1977, 36, 770.
PHENYTOIN/DEXAMETHASONE INTERACTION SiR,-The interaction noted by Dr McLelland and Dr Jack (May 20, p. 1096) has serious implications for the "successful" treatment of patients with brain tumours. There is a dose dependency of dexamethasone and other steroids in patients with brain tumours,’-3 and if patients deteriorate on conven16 mg dexamethasone daily), the sitube considered hopeless. Thus, some patients may require as much as 96 mg dexamethasone a day to control their symptoms; the same is true for equivalent doses of methylprednisolone. Several reportsl-3 have cited patients who had progressively deteriorated on conventional doses of dexamethasone but who became symptom-free when dosages were increased. Although steroid side-effects were not uncommon, the quality of life for these patients was quite good and survival was prolonged. In part this dose dependency may depend on the concomitant administration of drugs (usually anticonvulsants) which accelerate the metabolism of the steroid preparation. Although dexamethasone is the most common steroid used in patients with brain tumours, there is evidence which suggests that methylprednisolone and its hemisuccinate salt are as effective and that they do produce significant clinical improvement and reduce both periventricular elastance and intra!cranial pressure.3 They also undergo less metabolic clearance than dexamethasone in patients who are concurrently receiving phenobarbitone or phentoin, a fact which is both experimentally and clinically proven. 3,4 I have treated two patients, both with glioblastoma multiforme of the parietal lobes, who were receiving dexamethasone and, phenytoin. Symptoms improved on this regimen, but returned in 6-8 weeks. The switch from dexamethasone to equivalent doses of methylprednisone resulted in prompt clini-
tional doses ation should
(usually not
Renaudm, J., Fewer, D., Wilson, C. B., Boldrey, E. B., Calogero, J., Enot, K. J. J. Neurosurg 1973, 39, 302. 2. Lieberman, A., LeBrun, Y., Glass, P., Goodgold, A., Lux, W., Wise, A., Ransohoff, J. J. Neurol. Neurosurg. Psychiat. 1977, 40, 678. 3. Miller, J. D., Sakalas, R., Ward, J. D., Young, H. F., Adams, W E., Vries, J. K., Becker, D. P. Neurosurgery, 1977, 1, 114. 4. Stjernholm, M. R., Katz, F. H. J. clin. Endocr. Metab. 1975, 41, 887. 1
Fig. 2-Actuarial curve: remission (34 patients).
ascending cholangitis is highest. Llandough Hospital, Penarth, Glamorgan CF6
1XX
G. DE B. HINDE P. M. SMITH
SEPTIC SHOCK
SIR,-The extensive experience of Dr Ledingham and Mr McArdle (June 3, p. 1194) is of great interest. However, they cannot be said to be "treating" septic shock: their skill lies in supporting the lungs and circulation in patients with sepsis. Indeed, as their mortality figures show, the patients still die of multiorgan damage, and this is known to be induced by endotoxin. The mortality of septic shock remains near 50% because most people do not have protective anti-lipid-A antibodies in any appreciable titre. Until immunisation or immediate serum therapy become the accepted mode of raising antibody titres, there will be no real progress. In Britain there are about 2000 deaths a year because of this.
cal
improvement, and the steroid dose was subsequently tapered without adverse effects. Perhaps methylprednisone and/or its hemisuccinate is preferable in patients with brain tumours who are also on anticonvulsants. One fact we must not forget is that the treatment of brain tumours with large doses of corticosteroids may prolong the survival of such patients in a functional and productive fashion, Munson Medical Center, Traverse City, Michigan 49684, U.S.A.
FREDERICK M. VINCENT
D.A.T. (DAUNORUBICIN, CYTARABINE, 6-THIOGUANINE) IN ACUTE MYELOID LEUKÆMIA SIR,-In 1977 we reported’ a remission-rate of 85% in twenty consecutive patients with acute myeloid leukaemia treated with the D.A.T. regimen-a combination of daunorubicin 50 mg/m2 on day 1, cytarabine 100 mg/m2 12-hourly by intravenous push and 6-thioguanine 100 mg/m2 12-hourly on days 1-5. Many inquirers have asked whether this remissionrate is being maintained. We have now treated forty consecutive patients with the D.A.T. regimen, of whom thirty-four (85%) entered complete remission. Figs 1 and 2 show that the median duration of survival is 104 weeks and the median duration of remission is 61 weeks. A second remission following a relapse was obtained in 45%.
Department of Therapeutics, Sheffield Royal Sheffield
Infirmary,
E. N. WARDLE
1.
Rees, J.
K.
H., Sandler,
R.
M., Challener, J. Hayhoe, F. G. J. Br. J. Cancer,
1977, 36, 770.
PHENYTOIN/DEXAMETHASONE INTERACTION SiR,-The interaction noted by Dr McLelland and Dr Jack (May 20, p. 1096) has serious implications for the "successful" treatment of patients with brain tumours. There is a dose dependency of dexamethasone and other steroids in patients with brain tumours,’-3 and if patients deteriorate on conven16 mg dexamethasone daily), the sitube considered hopeless. Thus, some patients may require as much as 96 mg dexamethasone a day to control their symptoms; the same is true for equivalent doses of methylprednisolone. Several reportsl-3 have cited patients who had progressively deteriorated on conventional doses of dexamethasone but who became symptom-free when dosages were increased. Although steroid side-effects were not uncommon, the quality of life for these patients was quite good and survival was prolonged. In part this dose dependency may depend on the concomitant administration of drugs (usually anticonvulsants) which accelerate the metabolism of the steroid preparation. Although dexamethasone is the most common steroid used in patients with brain tumours, there is evidence which suggests that methylprednisolone and its hemisuccinate salt are as effective and that they do produce significant clinical improvement and reduce both periventricular elastance and intra!cranial pressure.3 They also undergo less metabolic clearance than dexamethasone in patients who are concurrently receiving phenobarbitone or phentoin, a fact which is both experimentally and clinically proven. 3,4 I have treated two patients, both with glioblastoma multiforme of the parietal lobes, who were receiving dexamethasone and, phenytoin. Symptoms improved on this regimen, but returned in 6-8 weeks. The switch from dexamethasone to equivalent doses of methylprednisone resulted in prompt clini-
tional doses ation should
(usually not
Renaudm, J., Fewer, D., Wilson, C. B., Boldrey, E. B., Calogero, J., Enot, K. J. J. Neurosurg 1973, 39, 302. 2. Lieberman, A., LeBrun, Y., Glass, P., Goodgold, A., Lux, W., Wise, A., Ransohoff, J. J. Neurol. Neurosurg. Psychiat. 1977, 40, 678. 3. Miller, J. D., Sakalas, R., Ward, J. D., Young, H. F., Adams, W E., Vries, J. K., Becker, D. P. Neurosurgery, 1977, 1, 114. 4. Stjernholm, M. R., Katz, F. H. J. clin. Endocr. Metab. 1975, 41, 887. 1
Fig. 2-Actuarial curve: remission (34 patients).
