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ABSORPTION OF CAFFEINE FROM BEVERAGES
1313 Incubation of this large-molecular fraction with a soluble IgG fraction of goat anti-albumin antiserum resulted in loss of 80% of the factor-vm activity, although none was lost when the fraction was incubated for 60 minutes with an IgG fraction from the serum of a non-immunised goat (see columns 1 and 2 in accompanying table). Absorption of the anti-albumin IgG with albumin prepared from normal, hxmophilic, or vWd plasmas showed that the factor-vm-neutralising ability of the anti-albumin could be blocked by prior absorption with normal and haemophilic but not vWd albumin (see columns 3, 4, 5 in table). Essentially similar results were obtained with the even larger molecular factor VIII active fraction of normal plasma obtained by filtering the plasma through an agarose gel column (M.w.> 2,000,000). In 1968, we suggested that plasma factor VIII consists of a predominantly negatively charged moiety of small molecular weight (ca. 25,000) bound to a carrier of large molecular size.s Our data concerning the small moiety obtained from kidney, plasma, or albumin showed it to be essentially similar in normals, hxmophiliacs, and persons having vWd.3,6,7 On the basis of the new data, we now wish to extend our hypothesis as follows. We now believe factor VIII to be more complex than we had originally suggested. There may well be three separate components of the complex-i.e., the small molecular moiety which we described earlier,5 an albumin carrier which is defective in vWd but not in haemophilia A, and a third moiety (a peptide ?) which is under the genetic control of the hxmophilia-A locus on the X-chromosome. We suggest that the bleeder phenotypes, haemophilia A and vWd, arising from mutations on different chromosomes, are expressed through different conformational abnormalities of the complete factor-vm complex, deformations which prevent the binding (or improperly bind) the coagulant peptide of small molecular size. This is an attractive hypothesis because albumin is known to polymerise and form aggregates of large molecular size especially during plasma fractionation procedures,8 and haemophilia A in dogs and vWd in pigs can be overcome by transplantation of normal livers but not normal kidneys.9,lo Finally, our data almost certainly mean that the " factor-vmrelated antigen " described by other workers consists of highly aggregated albumin.
200,000 daltons.
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, N.C. 27514, U.S.A.
EMILY M. S. BARROW
JOHN B. GRAHAM.
RUBELLA REINFECTION AND THE FETUS SIR,-We have read with great interest your editorial (May 5, p. 978) on reported cases of rubella reinfection with possible virxmia. Concerning our case-report, we have already answered the question on the fate of the fetus. Our conclusion was that there were no indications of in-utero infection."i We had stressed 12 the possibility of hitherto unknown inhibitors which might have produced false-positive reactions. We have now been able to show that what we 5. Barrow, E. M., Graham, J. B. Biochemistry, 1968, 7, 3917. 6. Barrow, E. M., Graham, J. B. Am. J. Physiol. 1971, 220, 1020. 7. Barrow, E. M., Graham, J. B. ibid. 1972, 222, 134. 8. Schultze, H. E., Heremans, J. F. in Molecular Biology of Human Proteins; vol. I, p. 407. Amsterdam, 1966. 9. Webster, W. P., Zukoski, C. F., Hutchin, P., Reddick, R. L., Mandel, S. R., Penick, G. D. Am. J. Physiol. 1971, 220, 1147. 10. Webster, W. P., Mandel, S. R., Muhrer, M., Cornell, C. N., Wagner, J. L., Brinkhous, K. M. III Congress of International Society on Thrombosis and Hæmostasis; p. 156. Washington, 1972. 11. New Engl. J. Med. 1973, 288, 525. 12. ibid. 1972, 287, 1204.
as low-level immunity was based false-positive rubella H.i. reaction. The inhibitor was separated from IgG by flotation centrifugation. We wonder how often such false-positive reactions occur and what role they have in reinfection " by rubella.
had on
diagnosed originally
a
"
G. HAUKENES K. HARAM C. O. SOLBERG.
University Hospital, Bergen, Norway.
ABSORPTION OF CAFFEINE FROM BEVERAGES
SIR,-My interest was Professor Marks and Mr
aroused by the letter from Kelly (April 14, p. 827) concerning the absorption of caffeine from various beverages. The plasma levels of caffeine are considerably higher than those reported by Routh et al.,who described serumcaffeine concentrations of around 3 I-Lg. per ml. thirty minutes after ingestion of 120 mg. caffeine. From the data given by Professor Marks and Mr Kelly, it seems that the total body burden of caffeine, thirty minutes after ingestion of 150 mg. of the drug, is at least 300 mg. Boundary Hall, Tadley, Hampshire.
z* We showed this letter reply follows.-ED. L.
L. A. KING. to
Professor
Marks, whose
SIR,-We are very grateful to Dr King for drawing attention to the tenfold error in our results. The axis should have read " plasma-caffeine (mg. per litre) " or " " plasma-caffeine (g. per ml.) and not mg. per 100 ml." 11
Department of Biochemistry, University of Surrey, Guildford, Surrey GU2 5XH.
VINCENT MARKS.
SOCIAL WORK AND PRIMARY MEDICAL CARE
SIR,-I read with great interest the valuable paper by Elizabeth Daly and Hugh Faulkner (May 26, p. 1171), which I endorse. Two other papers appeared last month emphasising the need for close collaboration between social workers and doctors. These papers 2,3 stressed the unity of the patient/client and demonstrated the need for interdisciplinary teaching at all levels. Knowledge of one training course for social-work students strongly suggests that negative attitudes towards doctors are still nurtured unconsciously by the teaching staff, and this is certainly true when we examine the attitudes of medical students to social workers. Studies of unselected general practitioners show that the majority are indifferent to social work and have little idea of the professional ability and areas of competence of trained social workers.4.5 In a forthcoming paper6have said: " Professional attitudes are implanted early in one’s training and if a long term view is to be taken of this problem then serious consideration will have to be given to finding methods whereby medical students and students of social work, nursing and other related disciplines can meet together at an undergraduate level so that they may learn something 2. 3. 4. 5.
Routh, J. I., Shane, N. A., Arredondo, E. G., Paul, W. D. Clin. Chem. 1969, 15, 661. Prins, H. A. Social Work Today, 1973, 4, 119. Ratoff, L., Cooper, B., Rockett, D. Br. med. J. 1973, ii, suppl. p. 51. McCulloch, J. W., Brown, M. J. Med. soc. Work, 1970, 22, 300. Harwin, B. G., Cooper, B., Eastwood, M. R., Goldberg, D. P.
6.
Lancet, 1970, ii, 559. Ratoff, L. J. R. Coll. gen. Practnrs (in the press).
1.
200,000 daltons.
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, N.C. 27514, U.S.A.
EMILY M. S. BARROW
JOHN B. GRAHAM.
RUBELLA REINFECTION AND THE FETUS SIR,-We have read with great interest your editorial (May 5, p. 978) on reported cases of rubella reinfection with possible virxmia. Concerning our case-report, we have already answered the question on the fate of the fetus. Our conclusion was that there were no indications of in-utero infection."i We had stressed 12 the possibility of hitherto unknown inhibitors which might have produced false-positive reactions. We have now been able to show that what we 5. Barrow, E. M., Graham, J. B. Biochemistry, 1968, 7, 3917. 6. Barrow, E. M., Graham, J. B. Am. J. Physiol. 1971, 220, 1020. 7. Barrow, E. M., Graham, J. B. ibid. 1972, 222, 134. 8. Schultze, H. E., Heremans, J. F. in Molecular Biology of Human Proteins; vol. I, p. 407. Amsterdam, 1966. 9. Webster, W. P., Zukoski, C. F., Hutchin, P., Reddick, R. L., Mandel, S. R., Penick, G. D. Am. J. Physiol. 1971, 220, 1147. 10. Webster, W. P., Mandel, S. R., Muhrer, M., Cornell, C. N., Wagner, J. L., Brinkhous, K. M. III Congress of International Society on Thrombosis and Hæmostasis; p. 156. Washington, 1972. 11. New Engl. J. Med. 1973, 288, 525. 12. ibid. 1972, 287, 1204.
as low-level immunity was based false-positive rubella H.i. reaction. The inhibitor was separated from IgG by flotation centrifugation. We wonder how often such false-positive reactions occur and what role they have in reinfection " by rubella.
had on
diagnosed originally
a
"
G. HAUKENES K. HARAM C. O. SOLBERG.
University Hospital, Bergen, Norway.
ABSORPTION OF CAFFEINE FROM BEVERAGES
SIR,-My interest was Professor Marks and Mr
aroused by the letter from Kelly (April 14, p. 827) concerning the absorption of caffeine from various beverages. The plasma levels of caffeine are considerably higher than those reported by Routh et al.,who described serumcaffeine concentrations of around 3 I-Lg. per ml. thirty minutes after ingestion of 120 mg. caffeine. From the data given by Professor Marks and Mr Kelly, it seems that the total body burden of caffeine, thirty minutes after ingestion of 150 mg. of the drug, is at least 300 mg. Boundary Hall, Tadley, Hampshire.
z* We showed this letter reply follows.-ED. L.
L. A. KING. to
Professor
Marks, whose
SIR,-We are very grateful to Dr King for drawing attention to the tenfold error in our results. The axis should have read " plasma-caffeine (mg. per litre) " or " " plasma-caffeine (g. per ml.) and not mg. per 100 ml." 11
Department of Biochemistry, University of Surrey, Guildford, Surrey GU2 5XH.
VINCENT MARKS.
SOCIAL WORK AND PRIMARY MEDICAL CARE
SIR,-I read with great interest the valuable paper by Elizabeth Daly and Hugh Faulkner (May 26, p. 1171), which I endorse. Two other papers appeared last month emphasising the need for close collaboration between social workers and doctors. These papers 2,3 stressed the unity of the patient/client and demonstrated the need for interdisciplinary teaching at all levels. Knowledge of one training course for social-work students strongly suggests that negative attitudes towards doctors are still nurtured unconsciously by the teaching staff, and this is certainly true when we examine the attitudes of medical students to social workers. Studies of unselected general practitioners show that the majority are indifferent to social work and have little idea of the professional ability and areas of competence of trained social workers.4.5 In a forthcoming paper6have said: " Professional attitudes are implanted early in one’s training and if a long term view is to be taken of this problem then serious consideration will have to be given to finding methods whereby medical students and students of social work, nursing and other related disciplines can meet together at an undergraduate level so that they may learn something 2. 3. 4. 5.
Routh, J. I., Shane, N. A., Arredondo, E. G., Paul, W. D. Clin. Chem. 1969, 15, 661. Prins, H. A. Social Work Today, 1973, 4, 119. Ratoff, L., Cooper, B., Rockett, D. Br. med. J. 1973, ii, suppl. p. 51. McCulloch, J. W., Brown, M. J. Med. soc. Work, 1970, 22, 300. Harwin, B. G., Cooper, B., Eastwood, M. R., Goldberg, D. P.
6.
Lancet, 1970, ii, 559. Ratoff, L. J. R. Coll. gen. Practnrs (in the press).
1.