129 weeks. Using this regimen, response characteristically occurred within two courses of therapy and was dramatic in 5 (19%), and was objectively good in 12 (44%): the remaining 10 (37%) either failed to respond or had only slight objective change. Side-effects were very mild and, significantly, myelotoxicity was not a limiting factor. The schedule was very acceptable to patients, but 8 of the 17 patients (47%) who responded well relapsed within three months. The addition of 500 mg. per sq.m. of cyclophosphamide to the regimen at this stage resulted in remission again being achieved in these patients. We conclude that VP 16-213 is effective in diffuse histiocytic lymphoma but of limited value when used on its own. Prospective studies are now in progress role in combination therapy.
to
evaluate its
We thank Sandoz for the VP 16-213.
7.0 S
1 U
am.
1
7.45
pm. p.m. lymphocyte-antigen (purified
Departments of Haematology and Radiotherapy, University of Cape Town and Groote Schuur Hospital, Observatory 7900, South Africa.
Effect of naudicelle capsules on protein derivative of tubercle) interaction as measured by slowing of macrophage electrophoretic mobility.e’s
Arrows indicate 2 capsules taken. Normal subject fasting (except for black coffee) until third set of capsules. L.A.L.A.= linoleic-acid-like activity. Ether-soluble fraction is that extracted from serum by ether, leaving the unaltered protein moiety.
animals appeared healthy. All animals on a vitamin-rich Oxoid breeders’ diet. In 6 control
were
maintained
(oleic acid) animals tail-graft survival averaged
12-5 ±1-87 days (range 10-15 days). In the experimental group (9 mice) mean tail-graft survival was 14°9 2°02 days (range 12-18 days). p= 0-05-0-025—a level of significance we are reluctant to accept. In a second experiment, skin was grafted on to CBA mice, and in both control and experimental groups all animals showed rejection between the llth and 13th days. We would treat the result of both naudicelle series with caution, since clearly the oleic acid did produce much more local reaction (and therefore perhaps more stress) than did naudicelle itself.
We agree with Mertin that there is a need for " extended in vitro and in vivo investigations into the role of PUFAs in immunity " but would caution against the too-ready acceptance of the results of inadequately controlled animal studies in formulating policies and dosage regimens for clinical trials in human subjects.
Newcastle University Hospitals, Newcastle upon Tyne.
P. R. ULDALL R. WILKINSON M. I. MCHUGH E. J. FIELD B. K. SHENTON K. BAXBY R. M. R. TAYLOR.
CHEMOTHERAPY OF ADVANCED HISTIOCYTIC LYMPHOMAS SIR,-We read with interest the letter by Dr Sweet and his colleagues (May 17, p. 1136) on this subject. We have also found M.o.p.p. and c.o.p.p. of limited value in stage III and IV disease, and one year ago we began an evaluation of the epipodophyllotoxin VP 16-213. Early results 10 in 27 patients are encouraging. Of these 27 patients, 20 had previously failed to respond to all other forms of chemotherapy and radiotherapy. Induction of remission was attempted by intravenous administration of 60 mg. per sq.m. VP 16-213 daily for five consecutive days every two 8. 9. 10.
Field, E. J., Caspary, E. A. Lancet, 1970, ii, 1137. Caspary, E. A., Field, E. J. Br. med. J. 1971, i, 612. Jacobs, P., King, H. S., Sealy, G. R. H. S. Afr. med. J. 1975, 49, 483.
PETER JACOBS HELEN S. KING.
N.B.T. TEST AND S.L.E.
SiR,—Your periodical has given attention
to the evaluatest.1-3 We have used this test4 in two groups of patients with systemic lupus erythematosus (S.L.E. with fever, cough, and radiological evidence of pulmonary involvement) in order to distinguish S.L.E. exacerbation (lupus pulmonary infiltration) from bacterial pneumonia. In a group of ten patients with lupus pulmonary infiltration the N.B.T. test was negative (5%, range [normal 6%, range 2-10%]), and further treatment with immunodepressants and glucocorticoids sufficed. In another group of ten s.L.E. patients with bacterial pneumonia (confirmed bacteriologically) the N.B.T. test was positive (28%, range 20-40%). Additional antibiotic treatment appeared to be effective in these cases. Thus the N.B.T. test can be applied to the differential diagnosis of lupus pulmonary infiltration from the bacterial pneumonia which often complicates s.L.E.
tion of the
N.B.T.
2-8%
Hospital Therapy Department, Medical Institute, Novosibirsk 630091, U.S.S.R.
ALEK A. DEMIN.
MEDICAL AID TO DEVELOPING COUNTRIES
SIR,-Mr Dass’s point of view (June 21,
interesting reading.
I
p. 1373) makes gather he is writing mostly about
India. He suggests that the " economic lure of the West " is the only reason for the migration of the technically expert. If this were entirely true, Britain would find it very hard indeed to get any doctors from the Subcontinent. Corruption, nepotism, and gross political interference in almost every walk of life are but a few of the other motivating factors. I graduated from a first-class medical college (Roman Catholic and hence not under State aegis) in Bangalore in South India and returned to my home State of Madras to apply for a post in the Government service seeking to work anywhere, even in the remotest primary health centre. After months of delay, I was told that, as I had graduated from outside the State of Madras, I was ineligible for service there. Local graduates had to be accommodated first. I returned to the State of Mysore, only to be told that, as I was a Tamil Madrasi and not a 1. Lancet, 1974, i, 664. 2. Nathan, G. ibid. 1975, i, 225. 3. Freeman, R., King, B. ibid. p. 104. 4. Gordon, A., Rowan, R., Brown, T., 1973, 26, 52.
Carson, H. G. J. clin. Path.
130 native-born Mysorean, I had no chances there. Jobless and literally Stateless I had to leave the country. Mine is not an isolated example. There are many more who have returned from abroad (having resisted all economic lures) and languished for months in scientific pools, been at the mercy of non-technical administrators, and fruitlessly tramped the corridors of power, only to return to where they could at least be assured of a living and perhaps even only the barest minimum recognition of their technical worth. Again, Mr Dass’s wholesale condemnation of aid seems a bit sweeping. Donor and recipient are both to blame for the type of aid that is given. My alma mater (to which I owe a great deal) is a shining example. The St. John’s Medical College was started by the Roman Catholic bishops of India with massive aid from the Church in the affluent countries of Western Europe and the U.S.A. It turns out a medical graduate of high quality, equal to any in the West-unfortunately just another costly and well-trained addition to the ever-increasing number of medical graduates churned out in every State of the Union. There is a 90% emigration-rate among its products. Would it not have been better instead to have opened or helped to finance more primary health centres and rural clinics-basic medicine ? In a similar vein, misdirected aid is being pumped into building citadels of cardiology, neurology, and nephrology in a country where sanitation is non-existent, cholera still rages, the hookworm flourishes, and starvation, ignorance, and malnutrition reign supreme. The Bangladesh catastrophe was ably handled by indigenous personnel. But one must still gratefully acknowledge the blankets, medicines, and materials that came in as aid. In conclusion, Mr Dass speaks glibly of a medical curriculum " built around our own needs ". Do he, the health administrators, or the men at the helm of medical affairs in India know exactly what these needs are ? In all these years of independence they have been too busy dreaming about and chasing Western technical advancement and methods, high-flown research and abstruse papers, airconditioned intensive-care units (catering mostly to the rich atherosclerosed businessman), and complicated
gadgetry. The poor, the ignorant, the maimed, the halt, and the lame of India still wait. Royal Bath Hospital, Harrogate HG1 2PS.
D. RAMAN.
present). The subjects lived in a rural area with intense year-round sunlight and little atmospheric pollution, making an ultraviolet-radiation deficiency highly unlikely. We have also recorded a striking loss of cortical bone in slender postmenopausal women smokers compared with nonsmokers or obese smokers. These studies will be published shortly. that the fracture-rates are increasin women than in men, at a time when the mass of " liberated women " who began to smoke in the 1930s and 1940s are beginning to enter the ranks of senior citizens. It is of interest
ing much
Burton, J. L., Ensell, F. J., Leach, J. F., Hall, K. A. Lancet, April 5, 1975, p. 795. 2. Eddy, T. P. ibid. June 21, 1975, p. 1388. 3. Daniell, H. W. J. Am. med. Ass. 1972, 221, 509.
to note
rapidly
2020 Court
Street, Redding, California 96001, U.S.A.
HARRY W. DANIELL.
TWIN GLOMERULI
SIR,-Normally, each renal afferent arteriole supplies a single glomerulus,l but very occasionally one afferent arteriole has been reported to supply two glomeruli.2 I have observed this in sections of kidney from biopsy and
Section from kidney post mortem, showing 2 glomeruli by a single afferent arteriole.
(Haematoxylin and
eosin.
Reduced
supplied
by half from x 100.)
material, as well as in microdissection. It is my impression that this is a relatively common anatomical variation, which should be illustrated (see figure). necropsy
Department of Pathology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, U.S.A.
INCREASE IN FRACTURE OF THE FEMUR IN THE ELDERLY
SiR,—Two letters in your columns 1,2report striking increases in the frequency of femoral fractures among the elderly. Burton and his colleagues1 proposed that this increase might be related to cholecalciferol deficiency secondary to decreased ultraviolet radiation resulting from recent increases in atmospheric ozone, and urged appropriate investigations. Eddy2 also related the fractures to decreased ultraviolet radiation, but proposed domestic coal smoke as the likely offending pollutant. Our own studies3 suggest that an atmospheric contaminant responsible for this increasing fracture-rate may be none We other than the ubiquitous villain-tobacco smoke. reported that spontaneous compression fractures of the vertebral bodies in women younger than 65 years occur almost exclusively in women who have smoked heavily during their postmenopausal years (unless rheumatoid arthritis or other causes of secondary osteoporosis are
more
DAIRTON MIRANDA.
BREAST CANCER
SIR,-Your excellent editorial on carcinoma of the breast (May 24, p. 1171) and the equally good assessment of needle biopsy by Mr Preece and others (May 24, p. 1184) prompted me to write to you. We have found that since we adopted a conservative approach to breast cancer with reconstruction of the breast by prostheses we have seen cancer of the breast more and more frequently at a very early stage, and diagnosis has become more and more difficult owing to the small size of the lesion. Some years ago, therefore, we adopted a needle biopsy technique using a punch-type prostatic needle, and the results were excellent. In the same way as the surgeons at Cardiff, we felt we had
1.
1. 2.
Heptinstall, R. H. Pathology of the Kidney; vol. I. Boston, 1974. Trump, B. F., Bulger, R. E. in Structural Basis of Renal Disease (edited by E. L. Becker). New York, 1968.
to
evaluate its
We thank Sandoz for the VP 16-213.
7.0 S
1 U
am.
1
7.45
pm. p.m. lymphocyte-antigen (purified
Departments of Haematology and Radiotherapy, University of Cape Town and Groote Schuur Hospital, Observatory 7900, South Africa.
Effect of naudicelle capsules on protein derivative of tubercle) interaction as measured by slowing of macrophage electrophoretic mobility.e’s
Arrows indicate 2 capsules taken. Normal subject fasting (except for black coffee) until third set of capsules. L.A.L.A.= linoleic-acid-like activity. Ether-soluble fraction is that extracted from serum by ether, leaving the unaltered protein moiety.
animals appeared healthy. All animals on a vitamin-rich Oxoid breeders’ diet. In 6 control
were
maintained
(oleic acid) animals tail-graft survival averaged
12-5 ±1-87 days (range 10-15 days). In the experimental group (9 mice) mean tail-graft survival was 14°9 2°02 days (range 12-18 days). p= 0-05-0-025—a level of significance we are reluctant to accept. In a second experiment, skin was grafted on to CBA mice, and in both control and experimental groups all animals showed rejection between the llth and 13th days. We would treat the result of both naudicelle series with caution, since clearly the oleic acid did produce much more local reaction (and therefore perhaps more stress) than did naudicelle itself.
We agree with Mertin that there is a need for " extended in vitro and in vivo investigations into the role of PUFAs in immunity " but would caution against the too-ready acceptance of the results of inadequately controlled animal studies in formulating policies and dosage regimens for clinical trials in human subjects.
Newcastle University Hospitals, Newcastle upon Tyne.
P. R. ULDALL R. WILKINSON M. I. MCHUGH E. J. FIELD B. K. SHENTON K. BAXBY R. M. R. TAYLOR.
CHEMOTHERAPY OF ADVANCED HISTIOCYTIC LYMPHOMAS SIR,-We read with interest the letter by Dr Sweet and his colleagues (May 17, p. 1136) on this subject. We have also found M.o.p.p. and c.o.p.p. of limited value in stage III and IV disease, and one year ago we began an evaluation of the epipodophyllotoxin VP 16-213. Early results 10 in 27 patients are encouraging. Of these 27 patients, 20 had previously failed to respond to all other forms of chemotherapy and radiotherapy. Induction of remission was attempted by intravenous administration of 60 mg. per sq.m. VP 16-213 daily for five consecutive days every two 8. 9. 10.
Field, E. J., Caspary, E. A. Lancet, 1970, ii, 1137. Caspary, E. A., Field, E. J. Br. med. J. 1971, i, 612. Jacobs, P., King, H. S., Sealy, G. R. H. S. Afr. med. J. 1975, 49, 483.
PETER JACOBS HELEN S. KING.
N.B.T. TEST AND S.L.E.
SiR,—Your periodical has given attention
to the evaluatest.1-3 We have used this test4 in two groups of patients with systemic lupus erythematosus (S.L.E. with fever, cough, and radiological evidence of pulmonary involvement) in order to distinguish S.L.E. exacerbation (lupus pulmonary infiltration) from bacterial pneumonia. In a group of ten patients with lupus pulmonary infiltration the N.B.T. test was negative (5%, range [normal 6%, range 2-10%]), and further treatment with immunodepressants and glucocorticoids sufficed. In another group of ten s.L.E. patients with bacterial pneumonia (confirmed bacteriologically) the N.B.T. test was positive (28%, range 20-40%). Additional antibiotic treatment appeared to be effective in these cases. Thus the N.B.T. test can be applied to the differential diagnosis of lupus pulmonary infiltration from the bacterial pneumonia which often complicates s.L.E.
tion of the
N.B.T.
2-8%
Hospital Therapy Department, Medical Institute, Novosibirsk 630091, U.S.S.R.
ALEK A. DEMIN.
MEDICAL AID TO DEVELOPING COUNTRIES
SIR,-Mr Dass’s point of view (June 21,
interesting reading.
I
p. 1373) makes gather he is writing mostly about
India. He suggests that the " economic lure of the West " is the only reason for the migration of the technically expert. If this were entirely true, Britain would find it very hard indeed to get any doctors from the Subcontinent. Corruption, nepotism, and gross political interference in almost every walk of life are but a few of the other motivating factors. I graduated from a first-class medical college (Roman Catholic and hence not under State aegis) in Bangalore in South India and returned to my home State of Madras to apply for a post in the Government service seeking to work anywhere, even in the remotest primary health centre. After months of delay, I was told that, as I had graduated from outside the State of Madras, I was ineligible for service there. Local graduates had to be accommodated first. I returned to the State of Mysore, only to be told that, as I was a Tamil Madrasi and not a 1. Lancet, 1974, i, 664. 2. Nathan, G. ibid. 1975, i, 225. 3. Freeman, R., King, B. ibid. p. 104. 4. Gordon, A., Rowan, R., Brown, T., 1973, 26, 52.
Carson, H. G. J. clin. Path.
130 native-born Mysorean, I had no chances there. Jobless and literally Stateless I had to leave the country. Mine is not an isolated example. There are many more who have returned from abroad (having resisted all economic lures) and languished for months in scientific pools, been at the mercy of non-technical administrators, and fruitlessly tramped the corridors of power, only to return to where they could at least be assured of a living and perhaps even only the barest minimum recognition of their technical worth. Again, Mr Dass’s wholesale condemnation of aid seems a bit sweeping. Donor and recipient are both to blame for the type of aid that is given. My alma mater (to which I owe a great deal) is a shining example. The St. John’s Medical College was started by the Roman Catholic bishops of India with massive aid from the Church in the affluent countries of Western Europe and the U.S.A. It turns out a medical graduate of high quality, equal to any in the West-unfortunately just another costly and well-trained addition to the ever-increasing number of medical graduates churned out in every State of the Union. There is a 90% emigration-rate among its products. Would it not have been better instead to have opened or helped to finance more primary health centres and rural clinics-basic medicine ? In a similar vein, misdirected aid is being pumped into building citadels of cardiology, neurology, and nephrology in a country where sanitation is non-existent, cholera still rages, the hookworm flourishes, and starvation, ignorance, and malnutrition reign supreme. The Bangladesh catastrophe was ably handled by indigenous personnel. But one must still gratefully acknowledge the blankets, medicines, and materials that came in as aid. In conclusion, Mr Dass speaks glibly of a medical curriculum " built around our own needs ". Do he, the health administrators, or the men at the helm of medical affairs in India know exactly what these needs are ? In all these years of independence they have been too busy dreaming about and chasing Western technical advancement and methods, high-flown research and abstruse papers, airconditioned intensive-care units (catering mostly to the rich atherosclerosed businessman), and complicated
gadgetry. The poor, the ignorant, the maimed, the halt, and the lame of India still wait. Royal Bath Hospital, Harrogate HG1 2PS.
D. RAMAN.
present). The subjects lived in a rural area with intense year-round sunlight and little atmospheric pollution, making an ultraviolet-radiation deficiency highly unlikely. We have also recorded a striking loss of cortical bone in slender postmenopausal women smokers compared with nonsmokers or obese smokers. These studies will be published shortly. that the fracture-rates are increasin women than in men, at a time when the mass of " liberated women " who began to smoke in the 1930s and 1940s are beginning to enter the ranks of senior citizens. It is of interest
ing much
Burton, J. L., Ensell, F. J., Leach, J. F., Hall, K. A. Lancet, April 5, 1975, p. 795. 2. Eddy, T. P. ibid. June 21, 1975, p. 1388. 3. Daniell, H. W. J. Am. med. Ass. 1972, 221, 509.
to note
rapidly
2020 Court
Street, Redding, California 96001, U.S.A.
HARRY W. DANIELL.
TWIN GLOMERULI
SIR,-Normally, each renal afferent arteriole supplies a single glomerulus,l but very occasionally one afferent arteriole has been reported to supply two glomeruli.2 I have observed this in sections of kidney from biopsy and
Section from kidney post mortem, showing 2 glomeruli by a single afferent arteriole.
(Haematoxylin and
eosin.
Reduced
supplied
by half from x 100.)
material, as well as in microdissection. It is my impression that this is a relatively common anatomical variation, which should be illustrated (see figure). necropsy
Department of Pathology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, U.S.A.
INCREASE IN FRACTURE OF THE FEMUR IN THE ELDERLY
SiR,—Two letters in your columns 1,2report striking increases in the frequency of femoral fractures among the elderly. Burton and his colleagues1 proposed that this increase might be related to cholecalciferol deficiency secondary to decreased ultraviolet radiation resulting from recent increases in atmospheric ozone, and urged appropriate investigations. Eddy2 also related the fractures to decreased ultraviolet radiation, but proposed domestic coal smoke as the likely offending pollutant. Our own studies3 suggest that an atmospheric contaminant responsible for this increasing fracture-rate may be none We other than the ubiquitous villain-tobacco smoke. reported that spontaneous compression fractures of the vertebral bodies in women younger than 65 years occur almost exclusively in women who have smoked heavily during their postmenopausal years (unless rheumatoid arthritis or other causes of secondary osteoporosis are
more
DAIRTON MIRANDA.
BREAST CANCER
SIR,-Your excellent editorial on carcinoma of the breast (May 24, p. 1171) and the equally good assessment of needle biopsy by Mr Preece and others (May 24, p. 1184) prompted me to write to you. We have found that since we adopted a conservative approach to breast cancer with reconstruction of the breast by prostheses we have seen cancer of the breast more and more frequently at a very early stage, and diagnosis has become more and more difficult owing to the small size of the lesion. Some years ago, therefore, we adopted a needle biopsy technique using a punch-type prostatic needle, and the results were excellent. In the same way as the surgeons at Cardiff, we felt we had
1.
1. 2.
Heptinstall, R. H. Pathology of the Kidney; vol. I. Boston, 1974. Trump, B. F., Bulger, R. E. in Structural Basis of Renal Disease (edited by E. L. Becker). New York, 1968.
