- Email: [email protected]
IMPROVED SURVIVAL IN WILMS' TUMOUR
1290
Incidentally,
as
neither
severe
infantile
gastroenteritis
croup are notifiable diseases, we should be interested to know how Dr Easton arrives at the figures which he uses in support of his arguments. nor severe
Infectious Diseases Unit,
City Hospital, Edinburgh EH10 5SB.
J. A. GRAY J. McC. MURDOCH G. SANGSTER S. PICKENS.
THYMUS TRANSPLANTATION IN ADVANCED CANCER SiR,-We have read with interest the letter from Rzepecki et al.1 For our part, we have carried out the fetal thymus transplant with a double transplant on three patients. These three patients had, respectively, a neoplasm of the pancreas, cancer of the oesophagus, and a malignant lymphoma. The thymuses were aseptically removed, preserved at 4°C, and transplanted, at maximum, one hour later. All were implanted under the aponeurosis of the rectus abdominis, except one thymus, which was implanted in contact with the quadriceps muscle. All the recipients were followed up from an immunological point of view by the following tests: dosage of total complement of beta 1C and of the immunoglobulins IgG, IgA, IgM (Hyland plates), epicutaneous tests with 2,4-dinitrochlorobenzene, intradermal reactions to tuberculin (10 i.u.) and candidin (1/10,000), the natural rosettes test, and lymphoblast stimulation with phytohaemagglutinin. All tests were carried out before and then once a week after the trans-
introduction of new prophylactic agents such as methysergide and propranolol, the mechanism of action of which are still uncertain, has not resolved this problem. During the past 18 months I have treated 20 patients with longstanding classical migraine with a sustainedrelease preparation of papaverine. None of them had been able to achieve adequate control of their migraines with a wide variety of drugs, including a number of ergotamine preparations. They were selected on the following basis: th<. migraine attacks had a frequency greater than one a week; they were most often present on awakening; and the time between the aura and the onset of headache was too short to cQnsider the use of ergotamine. Any one of these criteria caused the patient to be placed on papaverine (150 mg. twice daily). The results have been extremely good, with 18 of the 20 patients reporting complete freedom from migraine headaches, and striking reduction in both frequency and severity in the other 2. No side-effects of any kind have been reported. 2 patients in the group had so-called hemiplegic migraines which responded completely to this
prophylactic
treatment.
Because of the well-established vasodilator effect of papaverine, these admittedly preliminary and uncontrolled results suggest that the initial vasoconstrictive phase of Wolff’s postulated mechanism is indeed obligatory. Department of Neurology, Degoesbriand Unit, Medical Center Hospital of Vermont, Burlington, Vermont 05401, U.S.A.
CHARLES M. POSER.
plantations. All the transplants were well tolerated. From the clinical point of view we observed no improvement. The complement and immunoglobulin levels were not noticeably modified. Only the level of the natural rosettes and the response of the lymphocytes to P.H.A. showed a significant change in the days after this implantation; but the
remained negative. Because of these results, we do not believe that thymus transplants are a reasonable solution or an essential contribution to the treatment of cancer. However, considering the fundamental role played by this organ in the defence mechanisms, we think that the acquisition of purified thymic factora could be of great interest. It is with this in mind that we are pursuing our work.33 cutaneous tests
Department of Clinical and Experimental Immunology, Centre Paul Lamarque, Hôpital St-Eloi, 34059 Montpellier, France.
B. SERROU.
PAPAVERINE IN PROPHYLACTIC TREATMENT OF MIGRAINE
SIR,—The mechanism for the pathogenesis of migraine (vascular headache) proposed by Wolff4 remains the most plausible even though details of the exact mechanism are understood. In his postulation, the initial event to be vasoconstriction, possibly generalised, followed by vasodilatation. The latter coincides with the onset of the head pain, while the former has been found to explain best some of the prodromal phenomena. Wolff never made clear whether he believed that the initial vasoconstriction was an obligatory part of the mechanism. The still
not
appears
et al. Lancet, 1973, ii, 508. Bach, J. F., Dardenne, M., Bach, M. A. Nouv. Presse méd. 1974, 3, 575. 3. Serrou, B., Reme, T., Souche, J. M., Dubois, J. B., Senelar, R., Romieu, Cl. Eur. Surg. Res. 1973, 5 (suppl. 2), 43. 4. Wolff, H. G. Headache and Other Head Pain. New York, 1948.
1. Rzepecki, W. M.,
2.
IMPROVED SURVIVAL IN WILMS’ TUMOUR SIR,-Mortality from Wilms’ tumour in the U.S. fell by a third between 1940 and zIn seeking an explanation for this trend, we examined staging, treatment, and survival patterns for 644 children aged 0-14 with Wilms’ tumour reported to the End Results Group of the National Cancer Institute, a series including over a hundred hospitals of various types and sizes in different parts of the U.S.3,4 Between 1940 and 1969 there was little change in the mean age or the stage at diagnosis for Whites and nonWhites (see table). An increasing percentage of patients received surgery and/or radiotherapy within four months of diagnosis, but the change was slight compared with the use of chemotherapeutic agents. Chemotherapy, little used before 1960, was administered to 83% of cases by 1965-69. Survival-rates more than doubled between 1940-49 and 1965-69, rising from 26% to 61%. Improvement in survival was noted at all stages for children over one year of age at diagnosis. Survival was unchanged for infants, who in earlier periods may have had renal hamartomas, a more benign condition only lately distinguished from Wilms’ tumour.5 Racial differences were slight and not statistically significant, but, compared with Whites, non-Whites showed less decline in mortality,2 tended to be older at diagnosis, had more extensive disease, and had poorer survival-rates. Use of chemotherapy did not vary by race, but non-Whites received significantly more radiotherapy than Whites (;==4-6, P < 005). Since there seems to be no change in the incidence of .
1. 2.
3. 4.
5.
Fraumeni, J. F., Jr., Everson, R. B., Dalager, N. A. Lancet, 1972, ii, 48. Everson, R. B., Fraumeni, J. F., Jr. Med. pediat. Oncol. (in the press). Cutler, S. J., Latourette, H. B. J. natn. Cancer Inst. 1959, 22, 633. Biometry Branch, National Cancer Institute. End Results in Cancer: report no. 4. U.S. Department of Health, Education, and Welfare publication no. (NIH) 73-272, 1972. Bolande, R. P., Brough, A. J., Izant, R. J., Jr. Pediatrics, 1967, 40, 272.
1291 DATA FOR 644 CHILDREN WITH WILMS’ TUMOUR REPORTED TO THE END RESULTS GROUP, 1940-69
DOMICILIARY PHYSIOTHERAPY SERVICES
SIR,—We were interested to read the article by Dr Waters and others (May 25, p. 1033) on their experiences of the domiciliary physiotherapy services. Others may be interested to know that we also started a very similar service two years ago. Through the very active help of our local Ladies Circle and local charities E1500 was raised and our running costs were about E628 last year. This was balanced by incoming covenants and charges made by those patients who felt they could afford it up to a maximum of 50p. Our area covers roughly 18,000 patients and our part-time physiotherapist last year saw 68 patients in 438 treatment sessions (in 1972-73 the figures were 71 patients in 307 treatment sessions). The physiotherapist finds the work interesting and rewarding and the cases are similar to those treated by the Sheffield group. All the local G.P.S have used the services, although some use it more than others. Wilms’ tumour over timethe decline in mortality can be attributed to improved survival. We could not find support for Constable’s suggestion6 that earlier diagnosis contributed to the better survival, since the mean age at diagnosis and percentage of patients with localised tumours remained constant. The trend toward improved survival seems closely related to more effective treatment, especially the use of chemotherapeutic agents. Recent survival-rates for Wilms’ tumour patients in this group of varied hospitals are not as high as those reported from certain specialised centres,7,but they do suggest that improved therapy has reached great numbers of patients with Wilms’ tumour in the U.S. Epidemiology and Biometry Branches, RICHARD B. EVERSON National Cancer Institute, JOSEPH F. FRAUMENI, JR. Bethesda, Maryland 20014, MAX H. MYERS. U.S.A. VARICOSE VEINS IN TROPICAL AFRICA
SIR,-Iwas very interested in the letter by Dr Rouge(May 4, p. 870). I have always maintained that while generalisations on the relative absence of a number of conditions, of which varicose veins is one, in tropical Africa are possible, there are bound to be exceptions, and these exceptions should be followed up in detail because they may reveal new clues to aetiology. I have worked in the West Nile district of Uganda for mont
33 years and in that time have seen well over 100,000 different patients, whose records I have filed. The West Nile district covers an area of approximately 4000 square miles and has a population which has grown from 20,000 to over 600,000 in my time. I have not seen more than 50 cases of varicose veins in the whole of my time here. Like certain other conditions such as diabetes mellitus, hypertension, and peptic ulcer it appears to be becoming slowly more common. Last year I saw 2 cases of varicose veins, and this year have seen 1. This last was a huge varicosity of one saphenous vein with a typical varicose ulcer, which I have never seen before. I feel, therefore, that Burkitt’s contention is certainly true for the West Nile district of Uganda. My feeling is that if attention could be paid to possible ethnic, environmental, or dietetic differences in the areas which Dr Rougemont describes, some new light might be shed on the aaiology of varicose veins and possibly other conditions as well. Kuluva Hospital, P.O. Box 28,
Arua, Uganda. 6. 7. 8.
E. H. WILLIAMS.
Constable, W. C. Lancet, 1972, ii, 278. Fernbach, D. J., Martyn, D. T. J. Am. med. Ass. 1966, 195, Farber, S. ibid. 1966, 198, 826.
1005.
It is our strong feeling that there is a need for such a service within the National Health Service, but at the moment it will be better if it could be linked with other voluntary schemes, such as our local Volunteer Stroke RthPmP for Tlve»hacia 28
Aylesbury End, Beaconsfield,
ANN BURTON D. W. GAU.
Bucks.
HEAVY DRINKING AND INCREASE IN
IgA
SIR,-Following research suggesting altered immunoglobulin levels with stress 1,22 and in psychiatric disorders, 4-6 we have carried out immunoglobulin determinations on the sera of 110 psychiatric inpatients. Included were 16 alcoholic patients without clinical evidence of hepatic cirrhosis. In preliminary analysis of the data we have found that mean IgA for the alcoholics was significantly (P < 0-01) raised to about twice the normal control level (482 mg. per 100 ml., S.D. 289 v. 237 mg. per 100 ml., S.D. 104; method of Fahey and McKelvey 6). Drinking history of the patients was retrospectively classified into 3 groups: normal, alcoholic, and an intermediate group operationally defined as consuming alcohol to the equivalent of 6 or more bottles of beer daily or intoxication more than once weekly. This intermediate group of 21 also had a mean IgA level higher than controls and the remainder of the patient group (383 mg. per 100 ml., S.D.
127
v.
273 mg. per 100
ml.,
S.D.
112;
p<
0-001).
Alcohol use was not found to have any effect on mean levels of IgG or IgM. There is practical importance in reporting this observation of increased IgA with heavy drinking in the absence of overt liver disease. In clinical work such elevation may be unexplained or attributed to another cause. As well, drinking history should be taken into account when a laboratory is establishing its normal range of immunoglobulins and in research such as we have been carrying out. Lamy et al.observed the return of IgA towards normal when alcoholics remain abstemious. Triger and Wrightsuggested that hepatotoxins might damage the Kupffer cells, resulting in increased release 1.
Hendrie, H. C., Paraskevas, F., Baragar, F., Adamson, J. D. J. psychosom. Res. 1971, 15, 337. 2. Hendrie, H. C., Paraskevas, F., Varsamis, J. Can. psychiat. Ass. J. 1972, 17, 93. 3. Solonon, G. F., Allansmith, M., McClennan, B., Amkraut, A. Archs. gen. Psychiat. 1969, 20, 272. 4. Strahilevitz, M., Davis, S. D. Lancet, 1970, ii, 370. 5. Amkraut, A. Solomon, G. F. Allansmith, M., McClellan, B., Rappaport, M. Archs. gen. Psychiat. 1973, 28, 673. 6. Fahey, J. L., McKelvey, E. M. J. Immunol. 1965, 94, 84. 7. Lamy, J., Aron, E., Lamy, J., Martin, J. C., Weill, J. Clin. chim. acta, 1973, 49,189. 8. Triger, D. R., Wright, R. Lancet, 1973, i, 1494.
Incidentally,
as
neither
severe
infantile
gastroenteritis
croup are notifiable diseases, we should be interested to know how Dr Easton arrives at the figures which he uses in support of his arguments. nor severe
Infectious Diseases Unit,
City Hospital, Edinburgh EH10 5SB.
J. A. GRAY J. McC. MURDOCH G. SANGSTER S. PICKENS.
THYMUS TRANSPLANTATION IN ADVANCED CANCER SiR,-We have read with interest the letter from Rzepecki et al.1 For our part, we have carried out the fetal thymus transplant with a double transplant on three patients. These three patients had, respectively, a neoplasm of the pancreas, cancer of the oesophagus, and a malignant lymphoma. The thymuses were aseptically removed, preserved at 4°C, and transplanted, at maximum, one hour later. All were implanted under the aponeurosis of the rectus abdominis, except one thymus, which was implanted in contact with the quadriceps muscle. All the recipients were followed up from an immunological point of view by the following tests: dosage of total complement of beta 1C and of the immunoglobulins IgG, IgA, IgM (Hyland plates), epicutaneous tests with 2,4-dinitrochlorobenzene, intradermal reactions to tuberculin (10 i.u.) and candidin (1/10,000), the natural rosettes test, and lymphoblast stimulation with phytohaemagglutinin. All tests were carried out before and then once a week after the trans-
introduction of new prophylactic agents such as methysergide and propranolol, the mechanism of action of which are still uncertain, has not resolved this problem. During the past 18 months I have treated 20 patients with longstanding classical migraine with a sustainedrelease preparation of papaverine. None of them had been able to achieve adequate control of their migraines with a wide variety of drugs, including a number of ergotamine preparations. They were selected on the following basis: th<. migraine attacks had a frequency greater than one a week; they were most often present on awakening; and the time between the aura and the onset of headache was too short to cQnsider the use of ergotamine. Any one of these criteria caused the patient to be placed on papaverine (150 mg. twice daily). The results have been extremely good, with 18 of the 20 patients reporting complete freedom from migraine headaches, and striking reduction in both frequency and severity in the other 2. No side-effects of any kind have been reported. 2 patients in the group had so-called hemiplegic migraines which responded completely to this
prophylactic
treatment.
Because of the well-established vasodilator effect of papaverine, these admittedly preliminary and uncontrolled results suggest that the initial vasoconstrictive phase of Wolff’s postulated mechanism is indeed obligatory. Department of Neurology, Degoesbriand Unit, Medical Center Hospital of Vermont, Burlington, Vermont 05401, U.S.A.
CHARLES M. POSER.
plantations. All the transplants were well tolerated. From the clinical point of view we observed no improvement. The complement and immunoglobulin levels were not noticeably modified. Only the level of the natural rosettes and the response of the lymphocytes to P.H.A. showed a significant change in the days after this implantation; but the
remained negative. Because of these results, we do not believe that thymus transplants are a reasonable solution or an essential contribution to the treatment of cancer. However, considering the fundamental role played by this organ in the defence mechanisms, we think that the acquisition of purified thymic factora could be of great interest. It is with this in mind that we are pursuing our work.33 cutaneous tests
Department of Clinical and Experimental Immunology, Centre Paul Lamarque, Hôpital St-Eloi, 34059 Montpellier, France.
B. SERROU.
PAPAVERINE IN PROPHYLACTIC TREATMENT OF MIGRAINE
SIR,—The mechanism for the pathogenesis of migraine (vascular headache) proposed by Wolff4 remains the most plausible even though details of the exact mechanism are understood. In his postulation, the initial event to be vasoconstriction, possibly generalised, followed by vasodilatation. The latter coincides with the onset of the head pain, while the former has been found to explain best some of the prodromal phenomena. Wolff never made clear whether he believed that the initial vasoconstriction was an obligatory part of the mechanism. The still
not
appears
et al. Lancet, 1973, ii, 508. Bach, J. F., Dardenne, M., Bach, M. A. Nouv. Presse méd. 1974, 3, 575. 3. Serrou, B., Reme, T., Souche, J. M., Dubois, J. B., Senelar, R., Romieu, Cl. Eur. Surg. Res. 1973, 5 (suppl. 2), 43. 4. Wolff, H. G. Headache and Other Head Pain. New York, 1948.
1. Rzepecki, W. M.,
2.
IMPROVED SURVIVAL IN WILMS’ TUMOUR SIR,-Mortality from Wilms’ tumour in the U.S. fell by a third between 1940 and zIn seeking an explanation for this trend, we examined staging, treatment, and survival patterns for 644 children aged 0-14 with Wilms’ tumour reported to the End Results Group of the National Cancer Institute, a series including over a hundred hospitals of various types and sizes in different parts of the U.S.3,4 Between 1940 and 1969 there was little change in the mean age or the stage at diagnosis for Whites and nonWhites (see table). An increasing percentage of patients received surgery and/or radiotherapy within four months of diagnosis, but the change was slight compared with the use of chemotherapeutic agents. Chemotherapy, little used before 1960, was administered to 83% of cases by 1965-69. Survival-rates more than doubled between 1940-49 and 1965-69, rising from 26% to 61%. Improvement in survival was noted at all stages for children over one year of age at diagnosis. Survival was unchanged for infants, who in earlier periods may have had renal hamartomas, a more benign condition only lately distinguished from Wilms’ tumour.5 Racial differences were slight and not statistically significant, but, compared with Whites, non-Whites showed less decline in mortality,2 tended to be older at diagnosis, had more extensive disease, and had poorer survival-rates. Use of chemotherapy did not vary by race, but non-Whites received significantly more radiotherapy than Whites (;==4-6, P < 005). Since there seems to be no change in the incidence of .
1. 2.
3. 4.
5.
Fraumeni, J. F., Jr., Everson, R. B., Dalager, N. A. Lancet, 1972, ii, 48. Everson, R. B., Fraumeni, J. F., Jr. Med. pediat. Oncol. (in the press). Cutler, S. J., Latourette, H. B. J. natn. Cancer Inst. 1959, 22, 633. Biometry Branch, National Cancer Institute. End Results in Cancer: report no. 4. U.S. Department of Health, Education, and Welfare publication no. (NIH) 73-272, 1972. Bolande, R. P., Brough, A. J., Izant, R. J., Jr. Pediatrics, 1967, 40, 272.
1291 DATA FOR 644 CHILDREN WITH WILMS’ TUMOUR REPORTED TO THE END RESULTS GROUP, 1940-69
DOMICILIARY PHYSIOTHERAPY SERVICES
SIR,—We were interested to read the article by Dr Waters and others (May 25, p. 1033) on their experiences of the domiciliary physiotherapy services. Others may be interested to know that we also started a very similar service two years ago. Through the very active help of our local Ladies Circle and local charities E1500 was raised and our running costs were about E628 last year. This was balanced by incoming covenants and charges made by those patients who felt they could afford it up to a maximum of 50p. Our area covers roughly 18,000 patients and our part-time physiotherapist last year saw 68 patients in 438 treatment sessions (in 1972-73 the figures were 71 patients in 307 treatment sessions). The physiotherapist finds the work interesting and rewarding and the cases are similar to those treated by the Sheffield group. All the local G.P.S have used the services, although some use it more than others. Wilms’ tumour over timethe decline in mortality can be attributed to improved survival. We could not find support for Constable’s suggestion6 that earlier diagnosis contributed to the better survival, since the mean age at diagnosis and percentage of patients with localised tumours remained constant. The trend toward improved survival seems closely related to more effective treatment, especially the use of chemotherapeutic agents. Recent survival-rates for Wilms’ tumour patients in this group of varied hospitals are not as high as those reported from certain specialised centres,7,but they do suggest that improved therapy has reached great numbers of patients with Wilms’ tumour in the U.S. Epidemiology and Biometry Branches, RICHARD B. EVERSON National Cancer Institute, JOSEPH F. FRAUMENI, JR. Bethesda, Maryland 20014, MAX H. MYERS. U.S.A. VARICOSE VEINS IN TROPICAL AFRICA
SIR,-Iwas very interested in the letter by Dr Rouge(May 4, p. 870). I have always maintained that while generalisations on the relative absence of a number of conditions, of which varicose veins is one, in tropical Africa are possible, there are bound to be exceptions, and these exceptions should be followed up in detail because they may reveal new clues to aetiology. I have worked in the West Nile district of Uganda for mont
33 years and in that time have seen well over 100,000 different patients, whose records I have filed. The West Nile district covers an area of approximately 4000 square miles and has a population which has grown from 20,000 to over 600,000 in my time. I have not seen more than 50 cases of varicose veins in the whole of my time here. Like certain other conditions such as diabetes mellitus, hypertension, and peptic ulcer it appears to be becoming slowly more common. Last year I saw 2 cases of varicose veins, and this year have seen 1. This last was a huge varicosity of one saphenous vein with a typical varicose ulcer, which I have never seen before. I feel, therefore, that Burkitt’s contention is certainly true for the West Nile district of Uganda. My feeling is that if attention could be paid to possible ethnic, environmental, or dietetic differences in the areas which Dr Rougemont describes, some new light might be shed on the aaiology of varicose veins and possibly other conditions as well. Kuluva Hospital, P.O. Box 28,
Arua, Uganda. 6. 7. 8.
E. H. WILLIAMS.
Constable, W. C. Lancet, 1972, ii, 278. Fernbach, D. J., Martyn, D. T. J. Am. med. Ass. 1966, 195, Farber, S. ibid. 1966, 198, 826.
1005.
It is our strong feeling that there is a need for such a service within the National Health Service, but at the moment it will be better if it could be linked with other voluntary schemes, such as our local Volunteer Stroke RthPmP for Tlve»hacia 28
Aylesbury End, Beaconsfield,
ANN BURTON D. W. GAU.
Bucks.
HEAVY DRINKING AND INCREASE IN
IgA
SIR,-Following research suggesting altered immunoglobulin levels with stress 1,22 and in psychiatric disorders, 4-6 we have carried out immunoglobulin determinations on the sera of 110 psychiatric inpatients. Included were 16 alcoholic patients without clinical evidence of hepatic cirrhosis. In preliminary analysis of the data we have found that mean IgA for the alcoholics was significantly (P < 0-01) raised to about twice the normal control level (482 mg. per 100 ml., S.D. 289 v. 237 mg. per 100 ml., S.D. 104; method of Fahey and McKelvey 6). Drinking history of the patients was retrospectively classified into 3 groups: normal, alcoholic, and an intermediate group operationally defined as consuming alcohol to the equivalent of 6 or more bottles of beer daily or intoxication more than once weekly. This intermediate group of 21 also had a mean IgA level higher than controls and the remainder of the patient group (383 mg. per 100 ml., S.D.
127
v.
273 mg. per 100
ml.,
S.D.
112;
p<
0-001).
Alcohol use was not found to have any effect on mean levels of IgG or IgM. There is practical importance in reporting this observation of increased IgA with heavy drinking in the absence of overt liver disease. In clinical work such elevation may be unexplained or attributed to another cause. As well, drinking history should be taken into account when a laboratory is establishing its normal range of immunoglobulins and in research such as we have been carrying out. Lamy et al.observed the return of IgA towards normal when alcoholics remain abstemious. Triger and Wrightsuggested that hepatotoxins might damage the Kupffer cells, resulting in increased release 1.
Hendrie, H. C., Paraskevas, F., Baragar, F., Adamson, J. D. J. psychosom. Res. 1971, 15, 337. 2. Hendrie, H. C., Paraskevas, F., Varsamis, J. Can. psychiat. Ass. J. 1972, 17, 93. 3. Solonon, G. F., Allansmith, M., McClennan, B., Amkraut, A. Archs. gen. Psychiat. 1969, 20, 272. 4. Strahilevitz, M., Davis, S. D. Lancet, 1970, ii, 370. 5. Amkraut, A. Solomon, G. F. Allansmith, M., McClellan, B., Rappaport, M. Archs. gen. Psychiat. 1973, 28, 673. 6. Fahey, J. L., McKelvey, E. M. J. Immunol. 1965, 94, 84. 7. Lamy, J., Aron, E., Lamy, J., Martin, J. C., Weill, J. Clin. chim. acta, 1973, 49,189. 8. Triger, D. R., Wright, R. Lancet, 1973, i, 1494.