83 differ from their peer group who did not use oral contraceptives. We conclude that single massive doses have no permanent effect on blood-ascorbic-acid levels, but the effect of oral contraceptives on ascorbic-acid levels can be obliterated by conscious use of fresh food, since an apple, an orange, and a salad will add 100-200 mg. extra ascorbic acid a day. Department of Food Sciences, Polytechnic of North London, London N7 8DB
A. B. HARRIS MARY PILLAY S. HUSSEIN.
increases in concentration
are
followed
by
an
augmented
response.
Because we live in an area of moderate iodine lack we carried out in our laboratory a small experiment which seems relevant to this point. Twelve goitrous (euthyroid) patients with high thyroid-accumulation rates of radioiodine were subjected to the iodine repletion test of Burrell and Frazer.9 In this test, iodine repletion has the effect of raising the level of plasma-inorganic-iodide to the optiTABLE I-DAILY IODINE INTAKE IN SOME IODINE-DEFICIENT AREAS OF THE WORLD
SIDE-EFFECTS OF PERPHENAZINE SiR,—Dr Forrester (June 21, p. 1383) reminds us how severe the side-effects of phenothiazines can be; yet these drugs are routinely given for nausea, and it is now scarcely possible for a patient to be sick in hospital without being injected with one of them. In the treatment of postoperative nausea, the effectiveness of atropine does not seem to be recognised. If nausea is accompanied by signs of cholinergic overactivity, such as salivation, sweating, and bradycardia, then atropine is logical. But it can be effective in the absence of such signs. In a dose of 1-2 mg. intravenously it is safe, works at once, and has no serious side-effects. The dry mouth, which is common when atropine is given intramuscularly in the fasting patient, does not seem to occur postoperatively. Postoperative nausea is often brief. This makes it difficult to evaluate treatment and important to exercise caution in the use of powerful drugs. Farthings, Langford Lane, Norton Fitzwarren, Taunton, Somerset TA2 6NZ.
T. A. BOLISTON.
TABLE II-RADIOIODINE-ACCUMULATION RATES AND T4 CONCENTRATIONS IN 12 PATIENTS WHO IODIDE-REPLETION TEST (MEAN±S.E.M.)
T.S.H.
AND UNDERWENT
Estimated by the method of Utinger 13 as presented by CEA-IRESORIN, Italy. Amounts in the range 0-02-1-6 ng./ml. can be measured with good precision. t Estimated by the method of Kennedy and Abelson 14 as presented by the Radiochemical Centre, Amersham, England. °
THYROID-STIMULATING HORMONE AND ENDEMIC GOITRE
SIR,-In an editorial on March 15 (p. 619) you state that " The goitre [of iodine lack] probably results from the effects of thyroid-stimulating hormone (T.S.H.), which is secreted by the pituitary in increased amounts because of the decreased thyroidal output of thyroxine secondary to iodine deficiency." If this implies that the plasma concentration of T.S.H. in goitrous subjects in these areas is higher than that in non-goitrous subjects or those living in welliodised areas of the world, then it is open to question. The reasons are that on the one hand raised T.S.H. concentrations have been found in the sub-Himalayan goitre belt,l the islands of New Guinea,2and the Idjwi island in Central Africa,3 but, on the other hand, there has been no T.S.H. elevation in the iodine-deficient areas of Apostoles4 and Neuquen5 in Argentina, Uganda in East Africa,6 or in Sarawak on Beneo Island.7 Studies of iodine intake in all these areas reveal that the degree of lack is very severe where the T.s.H. concentration was found raised (and the P.B.I. or T were often subnormal), whereas the deficiency was moderate in those where it was not (table I). This puzzling finding may be explained by Bray’s8 observation that iodine lack makes the thyroid cell more sensitive to the effects of T.S.H., so that normal or minimal 1.
Kochupillai, N., Deo, M. G., Karmarkar, M. G., McKendrick, M., Weightiman, D., Evered, D. C., Hall, R., Ramalingaswami, V. Lancet, 1973, i, 1021. 2. Buttfield, I. H., Black, M. L., Hoffman, J. J., Mason, E., Welby, M. L., Good, B. F. J. clin. Endocr. 1966, 26, 1201. 3. Delange, F. M., Hershman, J. M., Ermans, A. M. ibid. 1971, 33, 261. 4. Soto, R. J., Codeville, A. H., Wenistein, M., Rosados, I., Rabinovich, L., Goldberg, D. Metabolism, 1968, 17, 326. 5. Pisarev, M. A., Utinger, R. D., Salvaneschi, J. P., Altshuler, N., De Groot, L. J. J. clin. Endocr. 1970, 30, 680. 6. Kajubi, S. K. E. Afr. med. J. 1974, 51, 856. 7. Ogihara, T., J. clin. Endocr. 1972, 35, 711. 8. Bray, G. A. J. clin. Invest. 1968, 47, 1640.
and thus lowering the previously raised accumulationwhen this is repeated six weeks later. T.S.H., serumthyroxine, and radioiodine-accumulation rates were measured before and after the repletion procedure. Table II shows that, while the mean accumulation-rate was significantly lowered, T.S.H. and 1B concentrations remained unaltered. These observations are consistent with the existence of increased sensitiveness to T.s.H. by the thyroid cells when there is low plasma-iodide. We were also interested to note that the T.S.H. concentrations in our goitrous patients were similar to those in our patients with thyrotoxicosis.6 It appears reasonable, therefore, to take it that (apart from autoregulation7(among the compensatory mechanisms to iodine lack increased sensitiveness to the effects of T.S.H. is adequate in moderate degrees of deficiency. Increased T.S.H. concentration and the synthesis of T in favour of T will follow when the degree of iodine lack is very severe-so severe as to result in subnormal levels of
mum
rate
plasma-thyroxine. You also say that " The size of the goitre shows a relation with the serum-T.S.H. level and is inversely related to the level of serum-thyroxine ". This likewise is not supported by published work from areas where the deficiency is moderate (vide supra). Goitres of all sizes are seen in these areas and yet the concentrations of T.S.H. have not been higher in those with large goitres and vice versa. 9. 10. 11. 12. 13. 14. 15.
Burrell, C. D., Frazer, R. Q. Jl Med. 1957, 26, 559. Follis, R. H., Vanprapa, K., Damrongsaksi, D. J. Nutr. 1962, 76, 159. Ramalingaswami, V., Subramanian, T. A. V., Deo, M. G. Lancet, 1961, i, 791. Delange, F., Tilly, C., Ermans, A. M. J. clin. Endocr. Metab. 1968, 28, 114. Utinger, R. D. J. clin. Invest. 1965, 44, 1277. Kennedy, J. A., Abelson, D. M. J. clin. Path. 1967, 20, 89. Follis, R. H., Connor, D. H. E. Afr. med. J. 1966, 43, 114.
84
Similarly, the blood concentrations of thyroxine have not varied with the size of the goitre. The statement can only be applicable to those areas where the deficiency is severe. Additional possibilities which may serve to contradict this statement further have been suggested ’*: (a) portions of the goitre may become autonomous and therefore independent of the influence of T.S.H. ; (b) some portions of the goitre may become replaced by non-functional tissue which, however, continues to contribute to the goitre. Makerere University Medical School, P.O. Box 7072, Kampala, Uganda.
long way to the centre, we try to provide a rapid and personal service to compensate for the journey. Our patients have their blood-counts done immediately on arrival, they -are examined and given treatment, and leave within
one to two
hours.
Bone-marrow and other
un-
pleasant examinations are done under anaesthetic,2 and the results are available by lunch-time: the children can leave within three hours. In our experience, patients may spend as long at normal outpatient clinics, and few local hospitals can provide as rapid a service for children with leukaemia.
S. K. KAJUBI.
Royal Manchester Children’s Hospital, Pendlebury, near
MEDICAL CARE OF CHILDHOOD LEUKÆMIA SiR,-Dr McCarthy (May 17, p. 1128) is wrong to suggest from a narrow experience in London that local hospitals throughout the country could provide the same facilities as special centres. The hospitals he chose for his study are hardly representative. One of his special centres treated few children and provided no primary care. At the same time seven of his local hospitals were undergraduate teaching hospitals. This is not the case with leukaemia centres and local hospitals elsewhere. Furthermore, in the Metropolitan regions, the ratio of staff to population is nearly twice the national average in haematology and 20% higher in pxdiatrics.l In the North-West Region, over the years 1954-68, we found that survival-rates for children treated in the two main children’s hospitals of Manchester were consistently better than those for children treated in the paediatric units of general hospitals. As late as 1964-68, results from the regional units were still worse than those achieved in the children’s hospitals five years earlier, between 1959 and 1963 (see accompanying figure). As a result, we
Manchester M27 1HA.
D. I. K. EVANS PATRICIA MORRIS J. K. STEWARD.*
JONES
THYROTOXICOSIS DUE TO " SILENT " THYROIDITIS SiR,—The paper by Dr Papapetrou and Dr Jackson (Feb. 15, p. 361) was of particular interest to me, since I published similar data on four occasions 3-8 between 1971 and 1975. I had chosen to label this entity " occult subacute thyroiditis ".’ In a recent analysis of 100 consecutive patients with subacute thyroiditis, 6 presented with clinical features of thyrotoxicosis without the characteristic pain and tenderness.8 This entity deserves emphasis. The authors might have been more searching in their review of the literature. Northland Thyroid Laboratory, P.C., ’
Northland Medical Building,
20905 Greenfield, Southfield, Michigan 48075, U.S.A.
JOEL I. HAMBURGER.
PIPED MEDICAL-GAS SYSTEMS
SIR,-We congratulate Dr Feeley and his colleagues (June 28, p. 1416) on identifying some omissions from the U.K. guidance document (Hospital Technical Memorandum no. 22). We would however point out that their criticisms are applicable to some extent to nitrous oxide, Entonox’, and medical compressed-air systems as well as to oxygen systems. "
Testing of a high-pressure alarm is described as nearly impossible ". This need not be the case. If the highpressure alarm were connected upstream of the main shut-off valve (see figure in original paper) and an emergency supply-point fitted downstream of this valve (as is the practice in the U.K.) then the alarm could be tested while the main shut-off valve was closed and the gas supply maintained at constant pressure through the emergency
Survival-rates for children with acute leukaemia (all types) treated in psediatric units of regional hospitals (dotted lines) compared with those for children treated in the two main Manchester children’s hospitals (solid lines). at this hospital by 1971 and thus such results, since over 90% of longer compare The results cases from the region are now treated here. have continued to improve, showing that the poor results achieved in the peripheral units was not due to selection of cases. Of the 21 cases of acute lymphoblastic leukaemia presenting in 1970 and treated here, 11 (52%) are still alive and 10 (48%) are in initial remission and off treatment. Although parents may have to bring their children a
centralised the treatment
can no
1. From Hospital Medical Staff Regional W/T Equivalent Tables, as at Sept. 30, 1973. Department of Health and Social Security.
supply-point. This procedure can_also be used to test the pressurerelief valve and the low-pressure alarm which in the U.K. is normally sited upstream of the main shut-off valve. The fact that the gas pressure is not monitored by the alarm system when the emergency supply is in use is not considered to be a dangerous situation because the system will be under manual supervision. The main purpose of the alarms is to monitor an unattended system. Building Services Research Unit, 3 Lilybank Gardens, Glasgow W2.
W. CARSON E. GIBSON.
* Dr Steward died on Tune 20. 2. Evans, D. I. K., Morris Jones, P., Morris, P., Shaw, E. A. Lancet, 1971, i, 751. 3. Hamburger, J. I. Mich. Med. 1971, 70, 1125. 4. Hamburger, J. I. Nontoxic Goiter: Concept and Controversy; p. 94. Springfield, Illinois, 1973. 5. Hamburger, J. I. J. nucl. Med. 1974, 15, 81. 6. Hamburger, J. I. Clinical Thyroidology; p. 174. Southfield, 1974.
A. B. HARRIS MARY PILLAY S. HUSSEIN.
increases in concentration
are
followed
by
an
augmented
response.
Because we live in an area of moderate iodine lack we carried out in our laboratory a small experiment which seems relevant to this point. Twelve goitrous (euthyroid) patients with high thyroid-accumulation rates of radioiodine were subjected to the iodine repletion test of Burrell and Frazer.9 In this test, iodine repletion has the effect of raising the level of plasma-inorganic-iodide to the optiTABLE I-DAILY IODINE INTAKE IN SOME IODINE-DEFICIENT AREAS OF THE WORLD
SIDE-EFFECTS OF PERPHENAZINE SiR,—Dr Forrester (June 21, p. 1383) reminds us how severe the side-effects of phenothiazines can be; yet these drugs are routinely given for nausea, and it is now scarcely possible for a patient to be sick in hospital without being injected with one of them. In the treatment of postoperative nausea, the effectiveness of atropine does not seem to be recognised. If nausea is accompanied by signs of cholinergic overactivity, such as salivation, sweating, and bradycardia, then atropine is logical. But it can be effective in the absence of such signs. In a dose of 1-2 mg. intravenously it is safe, works at once, and has no serious side-effects. The dry mouth, which is common when atropine is given intramuscularly in the fasting patient, does not seem to occur postoperatively. Postoperative nausea is often brief. This makes it difficult to evaluate treatment and important to exercise caution in the use of powerful drugs. Farthings, Langford Lane, Norton Fitzwarren, Taunton, Somerset TA2 6NZ.
T. A. BOLISTON.
TABLE II-RADIOIODINE-ACCUMULATION RATES AND T4 CONCENTRATIONS IN 12 PATIENTS WHO IODIDE-REPLETION TEST (MEAN±S.E.M.)
T.S.H.
AND UNDERWENT
Estimated by the method of Utinger 13 as presented by CEA-IRESORIN, Italy. Amounts in the range 0-02-1-6 ng./ml. can be measured with good precision. t Estimated by the method of Kennedy and Abelson 14 as presented by the Radiochemical Centre, Amersham, England. °
THYROID-STIMULATING HORMONE AND ENDEMIC GOITRE
SIR,-In an editorial on March 15 (p. 619) you state that " The goitre [of iodine lack] probably results from the effects of thyroid-stimulating hormone (T.S.H.), which is secreted by the pituitary in increased amounts because of the decreased thyroidal output of thyroxine secondary to iodine deficiency." If this implies that the plasma concentration of T.S.H. in goitrous subjects in these areas is higher than that in non-goitrous subjects or those living in welliodised areas of the world, then it is open to question. The reasons are that on the one hand raised T.S.H. concentrations have been found in the sub-Himalayan goitre belt,l the islands of New Guinea,2and the Idjwi island in Central Africa,3 but, on the other hand, there has been no T.S.H. elevation in the iodine-deficient areas of Apostoles4 and Neuquen5 in Argentina, Uganda in East Africa,6 or in Sarawak on Beneo Island.7 Studies of iodine intake in all these areas reveal that the degree of lack is very severe where the T.s.H. concentration was found raised (and the P.B.I. or T were often subnormal), whereas the deficiency was moderate in those where it was not (table I). This puzzling finding may be explained by Bray’s8 observation that iodine lack makes the thyroid cell more sensitive to the effects of T.S.H., so that normal or minimal 1.
Kochupillai, N., Deo, M. G., Karmarkar, M. G., McKendrick, M., Weightiman, D., Evered, D. C., Hall, R., Ramalingaswami, V. Lancet, 1973, i, 1021. 2. Buttfield, I. H., Black, M. L., Hoffman, J. J., Mason, E., Welby, M. L., Good, B. F. J. clin. Endocr. 1966, 26, 1201. 3. Delange, F. M., Hershman, J. M., Ermans, A. M. ibid. 1971, 33, 261. 4. Soto, R. J., Codeville, A. H., Wenistein, M., Rosados, I., Rabinovich, L., Goldberg, D. Metabolism, 1968, 17, 326. 5. Pisarev, M. A., Utinger, R. D., Salvaneschi, J. P., Altshuler, N., De Groot, L. J. J. clin. Endocr. 1970, 30, 680. 6. Kajubi, S. K. E. Afr. med. J. 1974, 51, 856. 7. Ogihara, T., J. clin. Endocr. 1972, 35, 711. 8. Bray, G. A. J. clin. Invest. 1968, 47, 1640.
and thus lowering the previously raised accumulationwhen this is repeated six weeks later. T.S.H., serumthyroxine, and radioiodine-accumulation rates were measured before and after the repletion procedure. Table II shows that, while the mean accumulation-rate was significantly lowered, T.S.H. and 1B concentrations remained unaltered. These observations are consistent with the existence of increased sensitiveness to T.s.H. by the thyroid cells when there is low plasma-iodide. We were also interested to note that the T.S.H. concentrations in our goitrous patients were similar to those in our patients with thyrotoxicosis.6 It appears reasonable, therefore, to take it that (apart from autoregulation7(among the compensatory mechanisms to iodine lack increased sensitiveness to the effects of T.S.H. is adequate in moderate degrees of deficiency. Increased T.S.H. concentration and the synthesis of T in favour of T will follow when the degree of iodine lack is very severe-so severe as to result in subnormal levels of
mum
rate
plasma-thyroxine. You also say that " The size of the goitre shows a relation with the serum-T.S.H. level and is inversely related to the level of serum-thyroxine ". This likewise is not supported by published work from areas where the deficiency is moderate (vide supra). Goitres of all sizes are seen in these areas and yet the concentrations of T.S.H. have not been higher in those with large goitres and vice versa. 9. 10. 11. 12. 13. 14. 15.
Burrell, C. D., Frazer, R. Q. Jl Med. 1957, 26, 559. Follis, R. H., Vanprapa, K., Damrongsaksi, D. J. Nutr. 1962, 76, 159. Ramalingaswami, V., Subramanian, T. A. V., Deo, M. G. Lancet, 1961, i, 791. Delange, F., Tilly, C., Ermans, A. M. J. clin. Endocr. Metab. 1968, 28, 114. Utinger, R. D. J. clin. Invest. 1965, 44, 1277. Kennedy, J. A., Abelson, D. M. J. clin. Path. 1967, 20, 89. Follis, R. H., Connor, D. H. E. Afr. med. J. 1966, 43, 114.
84
Similarly, the blood concentrations of thyroxine have not varied with the size of the goitre. The statement can only be applicable to those areas where the deficiency is severe. Additional possibilities which may serve to contradict this statement further have been suggested ’*: (a) portions of the goitre may become autonomous and therefore independent of the influence of T.S.H. ; (b) some portions of the goitre may become replaced by non-functional tissue which, however, continues to contribute to the goitre. Makerere University Medical School, P.O. Box 7072, Kampala, Uganda.
long way to the centre, we try to provide a rapid and personal service to compensate for the journey. Our patients have their blood-counts done immediately on arrival, they -are examined and given treatment, and leave within
one to two
hours.
Bone-marrow and other
un-
pleasant examinations are done under anaesthetic,2 and the results are available by lunch-time: the children can leave within three hours. In our experience, patients may spend as long at normal outpatient clinics, and few local hospitals can provide as rapid a service for children with leukaemia.
S. K. KAJUBI.
Royal Manchester Children’s Hospital, Pendlebury, near
MEDICAL CARE OF CHILDHOOD LEUKÆMIA SiR,-Dr McCarthy (May 17, p. 1128) is wrong to suggest from a narrow experience in London that local hospitals throughout the country could provide the same facilities as special centres. The hospitals he chose for his study are hardly representative. One of his special centres treated few children and provided no primary care. At the same time seven of his local hospitals were undergraduate teaching hospitals. This is not the case with leukaemia centres and local hospitals elsewhere. Furthermore, in the Metropolitan regions, the ratio of staff to population is nearly twice the national average in haematology and 20% higher in pxdiatrics.l In the North-West Region, over the years 1954-68, we found that survival-rates for children treated in the two main children’s hospitals of Manchester were consistently better than those for children treated in the paediatric units of general hospitals. As late as 1964-68, results from the regional units were still worse than those achieved in the children’s hospitals five years earlier, between 1959 and 1963 (see accompanying figure). As a result, we
Manchester M27 1HA.
D. I. K. EVANS PATRICIA MORRIS J. K. STEWARD.*
JONES
THYROTOXICOSIS DUE TO " SILENT " THYROIDITIS SiR,—The paper by Dr Papapetrou and Dr Jackson (Feb. 15, p. 361) was of particular interest to me, since I published similar data on four occasions 3-8 between 1971 and 1975. I had chosen to label this entity " occult subacute thyroiditis ".’ In a recent analysis of 100 consecutive patients with subacute thyroiditis, 6 presented with clinical features of thyrotoxicosis without the characteristic pain and tenderness.8 This entity deserves emphasis. The authors might have been more searching in their review of the literature. Northland Thyroid Laboratory, P.C., ’
Northland Medical Building,
20905 Greenfield, Southfield, Michigan 48075, U.S.A.
JOEL I. HAMBURGER.
PIPED MEDICAL-GAS SYSTEMS
SIR,-We congratulate Dr Feeley and his colleagues (June 28, p. 1416) on identifying some omissions from the U.K. guidance document (Hospital Technical Memorandum no. 22). We would however point out that their criticisms are applicable to some extent to nitrous oxide, Entonox’, and medical compressed-air systems as well as to oxygen systems. "
Testing of a high-pressure alarm is described as nearly impossible ". This need not be the case. If the highpressure alarm were connected upstream of the main shut-off valve (see figure in original paper) and an emergency supply-point fitted downstream of this valve (as is the practice in the U.K.) then the alarm could be tested while the main shut-off valve was closed and the gas supply maintained at constant pressure through the emergency
Survival-rates for children with acute leukaemia (all types) treated in psediatric units of regional hospitals (dotted lines) compared with those for children treated in the two main Manchester children’s hospitals (solid lines). at this hospital by 1971 and thus such results, since over 90% of longer compare The results cases from the region are now treated here. have continued to improve, showing that the poor results achieved in the peripheral units was not due to selection of cases. Of the 21 cases of acute lymphoblastic leukaemia presenting in 1970 and treated here, 11 (52%) are still alive and 10 (48%) are in initial remission and off treatment. Although parents may have to bring their children a
centralised the treatment
can no
1. From Hospital Medical Staff Regional W/T Equivalent Tables, as at Sept. 30, 1973. Department of Health and Social Security.
supply-point. This procedure can_also be used to test the pressurerelief valve and the low-pressure alarm which in the U.K. is normally sited upstream of the main shut-off valve. The fact that the gas pressure is not monitored by the alarm system when the emergency supply is in use is not considered to be a dangerous situation because the system will be under manual supervision. The main purpose of the alarms is to monitor an unattended system. Building Services Research Unit, 3 Lilybank Gardens, Glasgow W2.
W. CARSON E. GIBSON.
* Dr Steward died on Tune 20. 2. Evans, D. I. K., Morris Jones, P., Morris, P., Shaw, E. A. Lancet, 1971, i, 751. 3. Hamburger, J. I. Mich. Med. 1971, 70, 1125. 4. Hamburger, J. I. Nontoxic Goiter: Concept and Controversy; p. 94. Springfield, Illinois, 1973. 5. Hamburger, J. I. J. nucl. Med. 1974, 15, 81. 6. Hamburger, J. I. Clinical Thyroidology; p. 174. Southfield, 1974.
