- Email: [email protected]
CRIMINALITY AND LENGTH OF THE Y CHROMOSOME
626 PREVENTION OF HEART-DISEASE
SIR,-Professor Morris (Dec. 22, p. 1435) faults the medical profession for its vague stand on fitness and the prevention of coronary heart-disease (C.H.D.). He shares that guilt. His advice "Find some exercise you enjoy and take enough of it" adds little to the controversy. One level of vigorous exercise which appears to be "enough" is the marathon run. The American Medical Joggers Association has been unable to document a single death among marathon finishers of any age’; and rehabilitation centres in Honolulu and Toronto have begun using long-distance running for their patients who have recovered from one or more myocardial infarctions.2 Five such patients finished the Honolulu Marathon and were awarded trophies by Dr Alfred Morris of the Hawaii Heart Association (Dec. 16). Since marathon runners appear to be immune from C.H.D. this race has become the logical "graduation ceremony" from a cardiac rehabilitation programme.s Only time will tell whether these marathoning cardiac patients will share the C.H.D. protection of Olympic runners, but the results have been encouraging so far, and this definition of "enough exercise" is certainly not vague (i.e., a 42 kilometre run) ! C.H.D. now
Department of Pathology, Centinela Valley Community Hospital, Inglewood, California 90307, U.S.A. 1. 2. 3.
THOMAS
J.
BASSLER.
Bassler, J. T. Lancet, 1972, ii, 711. Kavanagh, T. J. Am. med. Ass. 1973, 224, 1580. Bassler, T. J. ibid. 1973, 226, 790.
IMMUNOENZYMATIC ASSAY FOR ALPHA-FETOPROTEIN
SIR,-The detection of alpha-fetoprotein (A.F.P.) in the sera of adults is a useful marker of primary liver carcinoma or embryonal teratoblastoma.’-’ Quantitative estimations of A.F.P. have been found to be helpful in evaluating prognosis after therapy.A.F.P. has been shown to be raised in trace amounts in maternal sera in the presence of fetal distress,5s and increases have been reported in amniotic fluid in the presence of certain specific congenital abnormalities.’ The clinical significance of these increases in sera and amniotic fluid has stimulated much interest in rapid and sensitive methods for its detection and quantitative estimation. We describe here a quantitative doubleantibody immunoenzymatic assay for A..F.P. in serum. Horseradish peroxidase (H.R.P.) was conjugated to sheep anti-rabbit gamma-globulin.8 The conjugated immunoglobulin was separated from free H.R.P. by gel filtration.8 Electroimmunodiffusion was performed in agarose gels impregnated by rabbit anti-A.F.P. antibody, as described by Laurel1.9 The plates were washed with phosphate-buffered saline and overlaid with a thin layer of diluted H.R.p.-conjugated sheep anti-rabbit gamma-globulin. The plates were incubated overnight in a moisture chamber at room temperature and washed with O.1R "tris" HCI buffer, pH 7.6. The plates were developed by immersing in a solution containing 0.5 mg. per ml. of diaminobenzidine in O.lM tris HCI buffer, pH 7.6, for 10-20 minutes before washing once more in the O.1M tris HC1 buffer. The immunoprecipitates stained a deep brown in the gel and were easily measured either directly or after drying. A standard curve was generated by the measurement of serial dilutions of calibrated A.F.P.containing serum used as a primary standard.1O Electroimmunodiffusion in agarose with routine protein staining could identify and quantitate A.F.P. in sera containing as little as 200 to 400 ng. per ml." Further dilution of the antisera results in immunoprecipitates too faint to
visualise after protein stains. These invisible precipitin peaks can be visualised by a modified form of double-antibody radioimmunoassay and radioautography using 1-anti-IgG. This method can measure A.F.P. in sera containing as little as 50 ng. per ml’1 However, several days of washing and several more days to develop the radioautograph are required. Background radioactivity frequently made visualisation and measurement of some samples difficult. In contrast, H.R.p.-labelled goat anti-rabbit immunoglobulin is stable for long periods of time and the reaction takes minutes instead of days. Electroimmunodiffusion in very dilute antibody allows migration of trace amounts of A.F.P., forming invisible precipitates which can be visualised by immunoenzymatic incubation with H.R.p.-conjugated sheep anti-rabbit immunoglobulin. Incubation with the conjugate diluted 1 in 50 gave as good results as incubation with more concentrated conjugate. As little as 50 ng. per ml. of A.F.P. could be visualised and quantitated with distinct im-
munoprecipitin peaks. The method is rapid, quantitative, and specific, and can be used to quantitate any antigen in trace amounts. Reagents are readily available, and the method is easily adaptable to any clinical laboratory able to perform electroimmunodiffusion. Antigen, which is difficult to isolate with sufficient purity for competitive-inhihition radioimmunoassay, is not required, obviating the need for radioisotopes. The method approaches the sensitivity of classical forms of radioimmunossay for A.F.P.12-14 but is not able to detect A.F.P. in normal human sera. However, levels of A.F.P. over 50 ng. per ml., which are of clinical significance in cancer and prenatal diagnosis, can be detected and quantitated. This work was supported by grants from the American Cancer Society (IM 14A), the National Institutes of Health (CA012389-03), and a grant from the National Ileitis and Colitis Foundation.
Departments of Medicine, Harvard Medical School and Massachusetts General Hospital (Gastrointestinal Unit), Boston, Massachusetts 02114, U.S.A.
E. ALPERT R. COSTON
J.
PERROTTO.
1. 2.
Abelev, G. I., et al. Int. J. Cancer, 1967, 2, 551. Alpert, E., Uriel, J., deNechaud, B. New Engl. J. Med. 1968, 278, 984. 3. O’Conor, G. T. et al. Cancer, 1970, 25, 1091. 4. Alpert, E., Starzl, T. E., Schur, P. H., Isselbacher, K. J. Gastroenterology, 1971, 51, 144. 5. Seppälä, M., Ruoslahti, E. Am. J. Obstet. Gynec. 1973, 115, 40. 6. Cohen, H., Graham, H., Lau, H. L. ibid. 1973, 115, 881. 7. Brock, D. U. H., Sutcliffe, R. G. Lancet, 1972, i, 197. 8. Avrameas, S., Ternynk, T. Immunochemistry, 1971, 8, 1175. 9. Laurell, C. B. Analyt. Biochem. 1966, 15, 45. 10. Alpert, E., Hershberg, R., Schur, P. H., Isselbacher, K. J. Gastroenterology, 1973, 51, 137. 11. Alpert, E. Natn Cancer Inst. Monogr. 1972, 35, 415. 12. Ruoslahti, E., Seppala, M. Int. J. Cancer, 1971, 8, 374. 13. Purves, L. R., Purves, M. S. Afr. Med. J. 1972, 46, 1290. 14. Hirai, H., Nishi, S., Watabe, H. Protides biol. Fluids, 1973, 20, 579.
CRIMINALITY AND LENGTH OF THE Y CHROMOSOME
SIR,-In men an additional Y chromosome often results in an abnormal personality and pronounced antisocial behaviour. Large Y chromosomes are reported to have a similar effect.1-3 We have investigated 45 male criminals in a psychiatric security hospital and a control group of 26 schoolboys, using cultured leucocytes and the quinacrine fluorescence method. With this technique, the distal part of the long arm of the Y chromosome (Yf), which causes the individual variation in the length of the Y,4,5 has bright]: fluorescent segments with weakly fluorescing bands in
627 we have investigated the role of phosphate in calcitonin secretion in man.
1’-CHROBfOSOhiE VALUES FOR CRIMINALS AND CONTROLS
reason
Hourly blood-samples were taken from a healthy young for 24 hours, during which she fasted in order to minimise the effect of gastrointestinal peptides, which are known to influence calcitonin secretion.3 Serum calcium, phosphate,4 parathyroid hormone, and calcitonin were measured, and highly significant correlations were found only between calcium and parathyroid hormone (r = 0.531, p < 0.01) and between calcitonin and phosphate (r = 0.718, p < 0.001). Since then, we have looked for a correlation between calcitonin (c.T.) and phosphate (p) in 43 fasting healthy subjects with normal serum calcium and phosphate concentrations, and we have found the following result: log c.T. (in pg. per ml.) = 2.5951 log P (in mg. per 10 ml.) -9.484 r = 0.574 p < 0.005
woman
1 etBB’een.6 About 90% of Y chromosomes have two segments in Yf. The loss or addition of one segment produces one-segmented and three-segmented Y chromosomes in approximately 5% of males. The rarest Y chromosome types have no segments (absence of Yf) or four cements. The best measurement for relative length of the Y chromosome is Yr/Y (YI being the length of the long arm of Y). We found a close correlation between the value of Yf/Yt and the number of segments. There was no significant difference between the Yf/Yi1 vaiues for criminals and controls (see accompanying table), but there was a remarkable difference in the number of cases with one and three segments between the two groups. So far no differences in psychiatric background, violence, and brutality have been found between those men with short Y (one segment) chromosomes and those with large Y (three segments) chromo-
Furthermore,
does not suggest that long Y chromosomes in criminals. So far it seems that the genetic material in Yf is inert, and that the YY condition may be due to the genetic material in the short arm of the Y, which determines male sex.7
study
are more common
Norsk Hydro’s Institute for Cancer Research,
Montebello, Oslo 3, Norway.
increase of 3000 pg. of calcitonin was a patient with hyper-
phosphate infusion in
University of Liège, Radioimmunoassay Laboratory, Boulevard Piercot 23, B-4000 Liège, Belgium.
TRYGVE URDAL ANTON BRØGGER. 1.
Deftos,
L.
G. HEYNEN P. FRANCHIMONT.
J., Powell, D., Parthemore, J. G., Potts, J. T., Jr.,
J. clin. Invest. 1973, 52, 3109.
1. Nordland, E. Nord. Tidskr. kriminalvidenskab, 1969, 57, 74. 2. Harvey, P. W., Muldal, S., Wauchob, D. Lancet, 1970, i, 887. 3. Nielsen, J., Friedrich, U. Clin. Genet. 1972, 3, 281. 4 Bobrow, M., Pearson, P. L., Pike, M. C., El-Alfi, O. S. Cytology, 1971, 10, 190. 5. Schnedl, W. Humangenetik, 1972, 12, 188. 6 Wahlström, J. Hereditas, 1971, 69, 125. 7. Krmpotic, E., Szego, K., Modestas, R., Molabola, G. B. Clin. Genet. 1972, 3, 381.
2.
Heymen, C., Franchimont, P. in Rapports et communications du XVe Colloque Médecine Nucléaire (Louvain, June 1-2, 1973).
3.
Swaminathan, R., Bates, R. F. L., Bloom, S. R., Ganguli, P. C., Care, A D. J. Endocr. 1973, 59, 217. Kessler, G., Wolfman, M. Clin. Chem. 1964, 10, 686. Kennedy, J. W , III, Talmage, R. V. in Calcium, Parathyroid Hormone and the Calcitonins (edited by R. Y. Talmage and
(in the press.) 4. 5.
P. L.
Munson);
p. 407.
Amsterdam, 1972.
TRANSFER FACTOR IN JUVENILE RHEUMATOID ARTHRITIS
HUMAN CALCITONIN AND SERUM-PHOSPHATE
SIR,-Following the paper by Deftos et al.’ about secretion of calcitonin in hypocalcaemic states in man, we should like to draw attention to a point which has probably been overlooked by most investigators. We have developed a very sensitive radioimmunoassay of human "dkitonin which can detect as little as 10 pg. per ml. of Serum.2 In chronic renal failure we found raised serumr;,1citonin levels, but could not conclusively demonstrate Lypersecretion or reduced metabolism or excretion of ,;:1citonin. In patients with hyperparathyroidism, however, , were surprised to find a significant rise (P < 0.01) :erum-calcitonin levels during the 24-42 hours after removal of the hyperfunctioning gland(s). Moreover, ":.1citonin was raised in two patients who had hypocal’,(-rJ1ia and hyperphosphataemia without impaired renal :’:).ct)on (500-1000 pg. per ml. in a case of idiopathic : :. [1(Jparathyroidism and 600-800 pg. per ml. in a case of : ,r:urlohypoparathyroidism). In these two cases, a calcium;rrru’ion test produced a large rise (500-1000 pg.) in levels, as Deftos found.’ The rise in serumlevels in association with both lowered and =F-i calcium levels suggests that some factor other than ";’:m-c?dcium controls calcitonin levels, and for this
a
Kennedy and Talmagé have postulated that the influence of calcitonin on phosphate transport could be a primary effect, preceding the well-known modification of calcium transport. Our results show both that phosphate and calcitonin levels are closely related in the basal state in normal man and that high calcitonin levels may be found in states where there is a tendency to hyperphosphataemia. It is suggested that a new concept of the physiopathological role of calcitonin secretion is required.
somes.
Our
an
observed after calcaemia.
,
SIR,-In both juvenile and adult rheumatoid arthritis deposition of immune complexes probably contributes to the inflammatory tissue reactions.°2 These patients, however, also have deficient cell-mediated immune responses.3,4 Immunopotentiation therefore-for example, with dialysable transfer factor5-could be a therapeutic alternative to immunosuppression. We have attempted treatment with transfer factor of patients having juvenile rheumatoid arthritis. The three patients (aged 3-7 years) selected for this study all had very active juvenile rheumatoid arthritis, with pronounced general illness in addition to synovitis in multiple joints. Two of the patients had typical fluctuating high fever. All had received conventional therapy, including corticosteroids, and two of them had also received azathioprine without improvement. After withdrawal of azathioprine, administration of transfer factor was started, accompanied by corticosteroids in unchanged doses. During a treatment period varying from three to five months the three patients received from five to ten injections of transfer factor, each dose corresponding to the biological material prepared from 400-450 ml. of normal blood.6
SIR,-Professor Morris (Dec. 22, p. 1435) faults the medical profession for its vague stand on fitness and the prevention of coronary heart-disease (C.H.D.). He shares that guilt. His advice "Find some exercise you enjoy and take enough of it" adds little to the controversy. One level of vigorous exercise which appears to be "enough" is the marathon run. The American Medical Joggers Association has been unable to document a single death among marathon finishers of any age’; and rehabilitation centres in Honolulu and Toronto have begun using long-distance running for their patients who have recovered from one or more myocardial infarctions.2 Five such patients finished the Honolulu Marathon and were awarded trophies by Dr Alfred Morris of the Hawaii Heart Association (Dec. 16). Since marathon runners appear to be immune from C.H.D. this race has become the logical "graduation ceremony" from a cardiac rehabilitation programme.s Only time will tell whether these marathoning cardiac patients will share the C.H.D. protection of Olympic runners, but the results have been encouraging so far, and this definition of "enough exercise" is certainly not vague (i.e., a 42 kilometre run) ! C.H.D. now
Department of Pathology, Centinela Valley Community Hospital, Inglewood, California 90307, U.S.A. 1. 2. 3.
THOMAS
J.
BASSLER.
Bassler, J. T. Lancet, 1972, ii, 711. Kavanagh, T. J. Am. med. Ass. 1973, 224, 1580. Bassler, T. J. ibid. 1973, 226, 790.
IMMUNOENZYMATIC ASSAY FOR ALPHA-FETOPROTEIN
SIR,-The detection of alpha-fetoprotein (A.F.P.) in the sera of adults is a useful marker of primary liver carcinoma or embryonal teratoblastoma.’-’ Quantitative estimations of A.F.P. have been found to be helpful in evaluating prognosis after therapy.A.F.P. has been shown to be raised in trace amounts in maternal sera in the presence of fetal distress,5s and increases have been reported in amniotic fluid in the presence of certain specific congenital abnormalities.’ The clinical significance of these increases in sera and amniotic fluid has stimulated much interest in rapid and sensitive methods for its detection and quantitative estimation. We describe here a quantitative doubleantibody immunoenzymatic assay for A..F.P. in serum. Horseradish peroxidase (H.R.P.) was conjugated to sheep anti-rabbit gamma-globulin.8 The conjugated immunoglobulin was separated from free H.R.P. by gel filtration.8 Electroimmunodiffusion was performed in agarose gels impregnated by rabbit anti-A.F.P. antibody, as described by Laurel1.9 The plates were washed with phosphate-buffered saline and overlaid with a thin layer of diluted H.R.p.-conjugated sheep anti-rabbit gamma-globulin. The plates were incubated overnight in a moisture chamber at room temperature and washed with O.1R "tris" HCI buffer, pH 7.6. The plates were developed by immersing in a solution containing 0.5 mg. per ml. of diaminobenzidine in O.lM tris HCI buffer, pH 7.6, for 10-20 minutes before washing once more in the O.1M tris HC1 buffer. The immunoprecipitates stained a deep brown in the gel and were easily measured either directly or after drying. A standard curve was generated by the measurement of serial dilutions of calibrated A.F.P.containing serum used as a primary standard.1O Electroimmunodiffusion in agarose with routine protein staining could identify and quantitate A.F.P. in sera containing as little as 200 to 400 ng. per ml." Further dilution of the antisera results in immunoprecipitates too faint to
visualise after protein stains. These invisible precipitin peaks can be visualised by a modified form of double-antibody radioimmunoassay and radioautography using 1-anti-IgG. This method can measure A.F.P. in sera containing as little as 50 ng. per ml’1 However, several days of washing and several more days to develop the radioautograph are required. Background radioactivity frequently made visualisation and measurement of some samples difficult. In contrast, H.R.p.-labelled goat anti-rabbit immunoglobulin is stable for long periods of time and the reaction takes minutes instead of days. Electroimmunodiffusion in very dilute antibody allows migration of trace amounts of A.F.P., forming invisible precipitates which can be visualised by immunoenzymatic incubation with H.R.p.-conjugated sheep anti-rabbit immunoglobulin. Incubation with the conjugate diluted 1 in 50 gave as good results as incubation with more concentrated conjugate. As little as 50 ng. per ml. of A.F.P. could be visualised and quantitated with distinct im-
munoprecipitin peaks. The method is rapid, quantitative, and specific, and can be used to quantitate any antigen in trace amounts. Reagents are readily available, and the method is easily adaptable to any clinical laboratory able to perform electroimmunodiffusion. Antigen, which is difficult to isolate with sufficient purity for competitive-inhihition radioimmunoassay, is not required, obviating the need for radioisotopes. The method approaches the sensitivity of classical forms of radioimmunossay for A.F.P.12-14 but is not able to detect A.F.P. in normal human sera. However, levels of A.F.P. over 50 ng. per ml., which are of clinical significance in cancer and prenatal diagnosis, can be detected and quantitated. This work was supported by grants from the American Cancer Society (IM 14A), the National Institutes of Health (CA012389-03), and a grant from the National Ileitis and Colitis Foundation.
Departments of Medicine, Harvard Medical School and Massachusetts General Hospital (Gastrointestinal Unit), Boston, Massachusetts 02114, U.S.A.
E. ALPERT R. COSTON
J.
PERROTTO.
1. 2.
Abelev, G. I., et al. Int. J. Cancer, 1967, 2, 551. Alpert, E., Uriel, J., deNechaud, B. New Engl. J. Med. 1968, 278, 984. 3. O’Conor, G. T. et al. Cancer, 1970, 25, 1091. 4. Alpert, E., Starzl, T. E., Schur, P. H., Isselbacher, K. J. Gastroenterology, 1971, 51, 144. 5. Seppälä, M., Ruoslahti, E. Am. J. Obstet. Gynec. 1973, 115, 40. 6. Cohen, H., Graham, H., Lau, H. L. ibid. 1973, 115, 881. 7. Brock, D. U. H., Sutcliffe, R. G. Lancet, 1972, i, 197. 8. Avrameas, S., Ternynk, T. Immunochemistry, 1971, 8, 1175. 9. Laurell, C. B. Analyt. Biochem. 1966, 15, 45. 10. Alpert, E., Hershberg, R., Schur, P. H., Isselbacher, K. J. Gastroenterology, 1973, 51, 137. 11. Alpert, E. Natn Cancer Inst. Monogr. 1972, 35, 415. 12. Ruoslahti, E., Seppala, M. Int. J. Cancer, 1971, 8, 374. 13. Purves, L. R., Purves, M. S. Afr. Med. J. 1972, 46, 1290. 14. Hirai, H., Nishi, S., Watabe, H. Protides biol. Fluids, 1973, 20, 579.
CRIMINALITY AND LENGTH OF THE Y CHROMOSOME
SIR,-In men an additional Y chromosome often results in an abnormal personality and pronounced antisocial behaviour. Large Y chromosomes are reported to have a similar effect.1-3 We have investigated 45 male criminals in a psychiatric security hospital and a control group of 26 schoolboys, using cultured leucocytes and the quinacrine fluorescence method. With this technique, the distal part of the long arm of the Y chromosome (Yf), which causes the individual variation in the length of the Y,4,5 has bright]: fluorescent segments with weakly fluorescing bands in
627 we have investigated the role of phosphate in calcitonin secretion in man.
1’-CHROBfOSOhiE VALUES FOR CRIMINALS AND CONTROLS
reason
Hourly blood-samples were taken from a healthy young for 24 hours, during which she fasted in order to minimise the effect of gastrointestinal peptides, which are known to influence calcitonin secretion.3 Serum calcium, phosphate,4 parathyroid hormone, and calcitonin were measured, and highly significant correlations were found only between calcium and parathyroid hormone (r = 0.531, p < 0.01) and between calcitonin and phosphate (r = 0.718, p < 0.001). Since then, we have looked for a correlation between calcitonin (c.T.) and phosphate (p) in 43 fasting healthy subjects with normal serum calcium and phosphate concentrations, and we have found the following result: log c.T. (in pg. per ml.) = 2.5951 log P (in mg. per 10 ml.) -9.484 r = 0.574 p < 0.005
woman
1 etBB’een.6 About 90% of Y chromosomes have two segments in Yf. The loss or addition of one segment produces one-segmented and three-segmented Y chromosomes in approximately 5% of males. The rarest Y chromosome types have no segments (absence of Yf) or four cements. The best measurement for relative length of the Y chromosome is Yr/Y (YI being the length of the long arm of Y). We found a close correlation between the value of Yf/Yt and the number of segments. There was no significant difference between the Yf/Yi1 vaiues for criminals and controls (see accompanying table), but there was a remarkable difference in the number of cases with one and three segments between the two groups. So far no differences in psychiatric background, violence, and brutality have been found between those men with short Y (one segment) chromosomes and those with large Y (three segments) chromo-
Furthermore,
does not suggest that long Y chromosomes in criminals. So far it seems that the genetic material in Yf is inert, and that the YY condition may be due to the genetic material in the short arm of the Y, which determines male sex.7
study
are more common
Norsk Hydro’s Institute for Cancer Research,
Montebello, Oslo 3, Norway.
increase of 3000 pg. of calcitonin was a patient with hyper-
phosphate infusion in
University of Liège, Radioimmunoassay Laboratory, Boulevard Piercot 23, B-4000 Liège, Belgium.
TRYGVE URDAL ANTON BRØGGER. 1.
Deftos,
L.
G. HEYNEN P. FRANCHIMONT.
J., Powell, D., Parthemore, J. G., Potts, J. T., Jr.,
J. clin. Invest. 1973, 52, 3109.
1. Nordland, E. Nord. Tidskr. kriminalvidenskab, 1969, 57, 74. 2. Harvey, P. W., Muldal, S., Wauchob, D. Lancet, 1970, i, 887. 3. Nielsen, J., Friedrich, U. Clin. Genet. 1972, 3, 281. 4 Bobrow, M., Pearson, P. L., Pike, M. C., El-Alfi, O. S. Cytology, 1971, 10, 190. 5. Schnedl, W. Humangenetik, 1972, 12, 188. 6 Wahlström, J. Hereditas, 1971, 69, 125. 7. Krmpotic, E., Szego, K., Modestas, R., Molabola, G. B. Clin. Genet. 1972, 3, 381.
2.
Heymen, C., Franchimont, P. in Rapports et communications du XVe Colloque Médecine Nucléaire (Louvain, June 1-2, 1973).
3.
Swaminathan, R., Bates, R. F. L., Bloom, S. R., Ganguli, P. C., Care, A D. J. Endocr. 1973, 59, 217. Kessler, G., Wolfman, M. Clin. Chem. 1964, 10, 686. Kennedy, J. W , III, Talmage, R. V. in Calcium, Parathyroid Hormone and the Calcitonins (edited by R. Y. Talmage and
(in the press.) 4. 5.
P. L.
Munson);
p. 407.
Amsterdam, 1972.
TRANSFER FACTOR IN JUVENILE RHEUMATOID ARTHRITIS
HUMAN CALCITONIN AND SERUM-PHOSPHATE
SIR,-Following the paper by Deftos et al.’ about secretion of calcitonin in hypocalcaemic states in man, we should like to draw attention to a point which has probably been overlooked by most investigators. We have developed a very sensitive radioimmunoassay of human "dkitonin which can detect as little as 10 pg. per ml. of Serum.2 In chronic renal failure we found raised serumr;,1citonin levels, but could not conclusively demonstrate Lypersecretion or reduced metabolism or excretion of ,;:1citonin. In patients with hyperparathyroidism, however, , were surprised to find a significant rise (P < 0.01) :erum-calcitonin levels during the 24-42 hours after removal of the hyperfunctioning gland(s). Moreover, ":.1citonin was raised in two patients who had hypocal’,(-rJ1ia and hyperphosphataemia without impaired renal :’:).ct)on (500-1000 pg. per ml. in a case of idiopathic : :. [1(Jparathyroidism and 600-800 pg. per ml. in a case of : ,r:urlohypoparathyroidism). In these two cases, a calcium;rrru’ion test produced a large rise (500-1000 pg.) in levels, as Deftos found.’ The rise in serumlevels in association with both lowered and =F-i calcium levels suggests that some factor other than ";’:m-c?dcium controls calcitonin levels, and for this
a
Kennedy and Talmagé have postulated that the influence of calcitonin on phosphate transport could be a primary effect, preceding the well-known modification of calcium transport. Our results show both that phosphate and calcitonin levels are closely related in the basal state in normal man and that high calcitonin levels may be found in states where there is a tendency to hyperphosphataemia. It is suggested that a new concept of the physiopathological role of calcitonin secretion is required.
somes.
Our
an
observed after calcaemia.
,
SIR,-In both juvenile and adult rheumatoid arthritis deposition of immune complexes probably contributes to the inflammatory tissue reactions.°2 These patients, however, also have deficient cell-mediated immune responses.3,4 Immunopotentiation therefore-for example, with dialysable transfer factor5-could be a therapeutic alternative to immunosuppression. We have attempted treatment with transfer factor of patients having juvenile rheumatoid arthritis. The three patients (aged 3-7 years) selected for this study all had very active juvenile rheumatoid arthritis, with pronounced general illness in addition to synovitis in multiple joints. Two of the patients had typical fluctuating high fever. All had received conventional therapy, including corticosteroids, and two of them had also received azathioprine without improvement. After withdrawal of azathioprine, administration of transfer factor was started, accompanied by corticosteroids in unchanged doses. During a treatment period varying from three to five months the three patients received from five to ten injections of transfer factor, each dose corresponding to the biological material prepared from 400-450 ml. of normal blood.6