- Email: [email protected]
GERIATRICS IS MEDICINE
107
603% ±9.3 (difference from control P < 001). Results with the lower concentration were highly variable, possibly because ovine prolactin is a foreign protein for human lymphocytes and may have had some stimulating effect, but the higher concentration produced consistently lowered counts. We therefore suggest that prolactin may play a part in the suppression of lymphocyte transformation observed in the situations mentioned. 15 ng. per ml. is a normal plasma-prolactin concentration, while 75 ng. per ml. is a pathological one. We have also tested the effect of the prolactin-suppressing drug, bromoergokryptine, on thymus growth in neonatal mice. We used four litters of Swiss mice adjusted at birth to a litter size of six pups. Half the animals were injected daily with saline and half with 25 µ.g. bromoergokryptine (kindly supplied by Sandoz). They were killed after three weeks. The mean weight of the controls was 13-08 g. ± 069 (S.E.M.) and of the treated animals 10-62 g.064 (P < 0-025). In the treated group, organ size was lowered in proportion to body-weight, except for the thymus, which was actually slightly larger in absolute terms than in the controls. In the treated animals the thymus/body-weight ratio was 68 1 °0 x 10-3, and in the controls it was 46 5 5 x 10-3 (r < 001). It is necessary to eliminate the possibility that the changes may be due to the drug itself rather than to its suppression of prolactin secretion, but the results are at least compatible with the lymphocyte work. These results offer the possibility of a new approach to both the inhibition and the enhancement of the immune response and may throw new light on the exceptionally high levels of prolactin found in amniotic fluid. 28 was
Departments of Physiology and Pathology, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU.
RASHIDA A. KARMALI I. LAUDER D. F. HORROBIN.
GERIATRICS IS MEDICINE SiR,-When 80% of the work that 80% of our doctors are called upon to do is in geriatrics, and when 80% of the work in younger age-groups is psychosocial or psychiatric, what are we going to do with all those doctors who see this sort of work as extremely mundane and lacking in intellectual stimulation? 29 Are they going to continue pushing up investigatory demands by 10% each year when increasingly the only practical way ahead is already clear without further investigation? Are they going to continue to identify more and more structural disease with very little notion of meaningful explanation as far as the practical living of the patient is concerned, and retreat into naive paternalism which is understandably resented? Are we going to continue getting the main work of the Health Service done regretfully and reluctantly, sometimes and not infrequently resentfully, or are we going do it willingly and with intelligence and imagination? Our system is still based on custody for technology, and when that fails, as it does more and more frequently, custody for a nihilistic existence, sentimentalised care, when " life style " is the all-important therapeutic issue. Ivan Illich deals with this, amongst other things, in Medical Nemesis. 30
ruefully, to
Oakleigh, Mildred Avenue, Boreham Wood, Herts WD6 2DH.
F. ALLEN BINKS.
LARGER DOSES OF IMMUNOSUPPRESSIVE
DRUGS
SIR,-It is of concern to me that clinicians are discarding
immunosuppressive drugs in disappointing results arising
of inadequate dosage. In the treatment of ulcerative colitis, Crohn’s disease, and rheumatoid arthritis, I have advocated a dose of 5 mg. per kg. daily initially, reducing to 6 or 5 days per week if there is depression of the white-cell count. I have rarely used more than 350 mg. per day, even when the subjects were 12 stone (168 lb., Recently, however,
Friesen, H., Hwang, P., Guyda, H., Tolis, G., Tyson, J., Myers, R. in Prolactin and Carcinogenesis. 4th Tenovus Workshop (edited by A. R. Boyns and K. Griffiths). Cardiff, 1972. 29. Crockett, G. S. Lancet, 1974, i, 804. 30. Illich, I. ibid. p. 918.
76
kg.). heavily-built patients whose colitis failed to go into remission with azathioprine, responded with complete healing when the dose was increased to 400 mg. per day (6 mg. per kg.) in one case, and in the other to 600 mg. per day (5’25 mg. per kg.). Incidentally, both these patients had responded in a previous attack to a
over
two
lower dose. I do not wish to maintain that 5 mg. per kg. is always safe. Some patients respond adequately to half this dose and a few can only tolerate 2-5 mg. per kg. without getting bonemarrow depression. Nevertheless, there are many patients who will remit completely (as in these 2 cases) only if given heroic doses. Newmarket General
Hospital,
Newmarket, Suffolk CB8 7JG.
R. ARDEN
JONES.
LEUKÆMIA AND LOWER-MOTOR-NEURON DISEASE
SIR,-Gardner and others1 have reported a high incidence of spontaneous lower-limb paralysis in a population of wild mice with electron-microscopic evidence of infection of the neurons of the spinal cord by type-C oncornavirus. These mice also had a high incidence of malignant lymphoma, and 99% of them had serological evidence of type-C oncornavirus antigens in extracts of spleens. In transmission experiments, both the neurological disease and the malignant lymphomas seemed to be caused by the oncornavirus. These observations prompted us to review the cases of two sisters studied at the Clinical Center of the N.I.H., one of whom died of granulocytic leukaemia while the other died of a rapidly progressive anterior-hom-motor-neuron degenerative disease. Case 1._A 20-year-old woman presented in August, 1970, with malaise, night sweats, and increased bruisability. Laboratory examination showed pancytopenia with circulating myeloblasts and myelofibrosis. An enlarged spleen was removed in September, 1970, and was found to contain myeloid infiltrates. She was first thought to have a myeloproliferative disease, but subsequently the diagnosis was changed to granulocytic leukaemia and she was treated with prednisone, 6-mercaptopurine, vincristine, cytoxan, and cytosine arabinoside. She died in July, 1971, with evidence of granulocytic leukaemia at necropsy. Case 2.-A 17-year-old girl, the sister of case 1, complained of weakness of her upper extremities and difficulty in walking in October, 1970. These symptoms progressed to quadriplegia and involvement of cranial motor nerves except those for eye movement.. After complete study her disease was classified as a rapidly progressing form of lower-motor-neuron degeneration (progressive muscular atrophy). She died in December, 1971, of respiratory failure due to involvement of respiratory muscles. Pathological examination of the spinal cord showed extensive loss of anterior motor neurons with little reactive gliosis. Electron microscopy was attempted with the formalin fixed tissue removed from the paraffin blocks. No conclusive evidence as to the presence or absence of viral particles could be gathered, owing to the poor preservation of the tissue. -
The 28.
many diseases because of out
1.
development of leukaemia and a lowerdegenerative disease in two sisters, when
concurrent
motor-neuron
Gardner, M. B., Henderson, B. E., Officer, J. E., Rongey, R. W., Parker, J. C., Oliver, C., Estes, J. D., Huebner, R. J. J. natn. Cancer Inst. 1973, 51, 1243.
603% ±9.3 (difference from control P < 001). Results with the lower concentration were highly variable, possibly because ovine prolactin is a foreign protein for human lymphocytes and may have had some stimulating effect, but the higher concentration produced consistently lowered counts. We therefore suggest that prolactin may play a part in the suppression of lymphocyte transformation observed in the situations mentioned. 15 ng. per ml. is a normal plasma-prolactin concentration, while 75 ng. per ml. is a pathological one. We have also tested the effect of the prolactin-suppressing drug, bromoergokryptine, on thymus growth in neonatal mice. We used four litters of Swiss mice adjusted at birth to a litter size of six pups. Half the animals were injected daily with saline and half with 25 µ.g. bromoergokryptine (kindly supplied by Sandoz). They were killed after three weeks. The mean weight of the controls was 13-08 g. ± 069 (S.E.M.) and of the treated animals 10-62 g.064 (P < 0-025). In the treated group, organ size was lowered in proportion to body-weight, except for the thymus, which was actually slightly larger in absolute terms than in the controls. In the treated animals the thymus/body-weight ratio was 68 1 °0 x 10-3, and in the controls it was 46 5 5 x 10-3 (r < 001). It is necessary to eliminate the possibility that the changes may be due to the drug itself rather than to its suppression of prolactin secretion, but the results are at least compatible with the lymphocyte work. These results offer the possibility of a new approach to both the inhibition and the enhancement of the immune response and may throw new light on the exceptionally high levels of prolactin found in amniotic fluid. 28 was
Departments of Physiology and Pathology, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU.
RASHIDA A. KARMALI I. LAUDER D. F. HORROBIN.
GERIATRICS IS MEDICINE SiR,-When 80% of the work that 80% of our doctors are called upon to do is in geriatrics, and when 80% of the work in younger age-groups is psychosocial or psychiatric, what are we going to do with all those doctors who see this sort of work as extremely mundane and lacking in intellectual stimulation? 29 Are they going to continue pushing up investigatory demands by 10% each year when increasingly the only practical way ahead is already clear without further investigation? Are they going to continue to identify more and more structural disease with very little notion of meaningful explanation as far as the practical living of the patient is concerned, and retreat into naive paternalism which is understandably resented? Are we going to continue getting the main work of the Health Service done regretfully and reluctantly, sometimes and not infrequently resentfully, or are we going do it willingly and with intelligence and imagination? Our system is still based on custody for technology, and when that fails, as it does more and more frequently, custody for a nihilistic existence, sentimentalised care, when " life style " is the all-important therapeutic issue. Ivan Illich deals with this, amongst other things, in Medical Nemesis. 30
ruefully, to
Oakleigh, Mildred Avenue, Boreham Wood, Herts WD6 2DH.
F. ALLEN BINKS.
LARGER DOSES OF IMMUNOSUPPRESSIVE
DRUGS
SIR,-It is of concern to me that clinicians are discarding
immunosuppressive drugs in disappointing results arising
of inadequate dosage. In the treatment of ulcerative colitis, Crohn’s disease, and rheumatoid arthritis, I have advocated a dose of 5 mg. per kg. daily initially, reducing to 6 or 5 days per week if there is depression of the white-cell count. I have rarely used more than 350 mg. per day, even when the subjects were 12 stone (168 lb., Recently, however,
Friesen, H., Hwang, P., Guyda, H., Tolis, G., Tyson, J., Myers, R. in Prolactin and Carcinogenesis. 4th Tenovus Workshop (edited by A. R. Boyns and K. Griffiths). Cardiff, 1972. 29. Crockett, G. S. Lancet, 1974, i, 804. 30. Illich, I. ibid. p. 918.
76
kg.). heavily-built patients whose colitis failed to go into remission with azathioprine, responded with complete healing when the dose was increased to 400 mg. per day (6 mg. per kg.) in one case, and in the other to 600 mg. per day (5’25 mg. per kg.). Incidentally, both these patients had responded in a previous attack to a
over
two
lower dose. I do not wish to maintain that 5 mg. per kg. is always safe. Some patients respond adequately to half this dose and a few can only tolerate 2-5 mg. per kg. without getting bonemarrow depression. Nevertheless, there are many patients who will remit completely (as in these 2 cases) only if given heroic doses. Newmarket General
Hospital,
Newmarket, Suffolk CB8 7JG.
R. ARDEN
JONES.
LEUKÆMIA AND LOWER-MOTOR-NEURON DISEASE
SIR,-Gardner and others1 have reported a high incidence of spontaneous lower-limb paralysis in a population of wild mice with electron-microscopic evidence of infection of the neurons of the spinal cord by type-C oncornavirus. These mice also had a high incidence of malignant lymphoma, and 99% of them had serological evidence of type-C oncornavirus antigens in extracts of spleens. In transmission experiments, both the neurological disease and the malignant lymphomas seemed to be caused by the oncornavirus. These observations prompted us to review the cases of two sisters studied at the Clinical Center of the N.I.H., one of whom died of granulocytic leukaemia while the other died of a rapidly progressive anterior-hom-motor-neuron degenerative disease. Case 1._A 20-year-old woman presented in August, 1970, with malaise, night sweats, and increased bruisability. Laboratory examination showed pancytopenia with circulating myeloblasts and myelofibrosis. An enlarged spleen was removed in September, 1970, and was found to contain myeloid infiltrates. She was first thought to have a myeloproliferative disease, but subsequently the diagnosis was changed to granulocytic leukaemia and she was treated with prednisone, 6-mercaptopurine, vincristine, cytoxan, and cytosine arabinoside. She died in July, 1971, with evidence of granulocytic leukaemia at necropsy. Case 2.-A 17-year-old girl, the sister of case 1, complained of weakness of her upper extremities and difficulty in walking in October, 1970. These symptoms progressed to quadriplegia and involvement of cranial motor nerves except those for eye movement.. After complete study her disease was classified as a rapidly progressing form of lower-motor-neuron degeneration (progressive muscular atrophy). She died in December, 1971, of respiratory failure due to involvement of respiratory muscles. Pathological examination of the spinal cord showed extensive loss of anterior motor neurons with little reactive gliosis. Electron microscopy was attempted with the formalin fixed tissue removed from the paraffin blocks. No conclusive evidence as to the presence or absence of viral particles could be gathered, owing to the poor preservation of the tissue. -
The 28.
many diseases because of out
1.
development of leukaemia and a lowerdegenerative disease in two sisters, when
concurrent
motor-neuron
Gardner, M. B., Henderson, B. E., Officer, J. E., Rongey, R. W., Parker, J. C., Oliver, C., Estes, J. D., Huebner, R. J. J. natn. Cancer Inst. 1973, 51, 1243.