1198 authonomic nervous system alone,s-7 (indeed an enkephalinergic link-up between the gut and the CNS has been suggested as regulator of hunger drive8). Perhaps in designing physiological studies we should respect local custom (e.g., cooking traditions and eating habits) in order to produce more comparable data.
GIANFRANCO DELLE FAVE LAURA DE MAGISTRIS ANNA KOHN
Medical Clinic II, Policlinico Umberto I, 00100 Rome, Italy
ORIGIN OF MATERNAL SERUM AFP
SIR,—The U.K. Collaborative Study (Sept. 29, p. 651) found correlation between maternal serum alpha-fetoprotein and amniotic fluid AFP in normal pregnancies, and at best a weak correlation in pregnancies with open neural tube defects (NTDs). Your editorial of Nov. 10 commented that the result in NTDs was surprising since the increased serum-AFP among open NTD pregnancies is presumed to be caused by the high levels in the amniotic fluid. There is a plausible explanation for the weakness of these correlations which is an artefact of the way such data are collected. Maternal serum-AFP increases by approximately 10% for every week of gestational age from 10 to 24 weeks of pregnancy,’ whereas amniotic fluid AFP decreases by approximately the same percentage per week at this stage in pregnancy.2 Even the best clinical estimates of gestational age are imprecise when compared with postnatal assessment. In one study3 more than 20% of their best estimates were in error by two weeks or more. In the collaborative study each centre standardised their results by expressing them in terms of their local median for each week of gestation. This corrects for a constant bias in the estimation of gestational age at each centre, but we should still expect that the gestational age assigned to many pregnancies will either overestimate or underestimate the maturity of the fetus compared with the other pregnancies at that centre. Where gestation is underestimated the maternal serum AFP (in multiples of the median) will be falsely high, whereas the amniotic fluid AFP will appear low. The opposite will be true when gestation is overestimated. Thus errors of estimation of gestational age would produce a negative correlation between maternal serum AFP and amniotic fluid AFP even if there were no biological connection between the two measures. Similarly, the underlying correlations between AFP in serum and amniotic fluid may be considerably higher than those estimated in the collaborative study. If an amniotic fluid result is borderline, a very high serumAFP will indeed give extra evidence of the presence of an open NTD. However, we may be confirming our estimate of gestational age, rather than measuring an independent risk factor. no
(AFP)
GILLIAN M. RAAB
5. Pearse AGE, Polak JM. The diffuse neuroendocrine system and the APUD concept. In: Bloom SR, ed. Gut hormones. Edinburgh: Churchill Livingstone, 1978: 33-39. 6. Dockray GJ. Cholecystochinin-like peptides in brain. In: Bloom SR, ed. Gut hormones. Edinburgh. Churchill Livingstone, 1978: 530-33. 7. Rehfeld JF. Localization of gastrins to neuro- and adenohypophysis. Nature
1978; 271: 771-73. RF.
Enkephalins, hunger,
inoculation of blood elements in laboratory animals’ suggests that pin re-use is unwise. However, many examiners use pins which are not disposable. Reflex hammers with built-in pins are still being distributed by drug companies, and Wartenberg wheels (with multiple pinpoints) are still being used on demented patients. This risk was highlighted many years ago with the discovery of the infectious nature of hepatitis. Although the practice of pin re-use has been criticised2 the message has not yet been generally heeded. Department of Neurology, University of California, V. A. Medical Center, Martinez, California 94553, U.S.A.
MIGRAINE,
ROBERT P. FRIEDLAND
A PLATELET DISORDER
SIR,-Hanington3 has proposed that migraine is caused by abnormality of platelet function, and we have reported a reduced accumulation of S-HT in platelets from patients with migraine.4 Dr Coppen and his colleagues (Oct. 27, p. 114) demonstrated that patients who had had a migraine headache within the previous five days had a significantly lower maximum rate of uptake (Vmax) of 5-HT than did healthy controls. These observations accord with our findings of a defect in 5-HT accumulation in platelets from migraine patients. We have also found that the active S-HT uptake mechanism in the migraine platelet is severely disturbed and these changes are accompanied by altered change density of the platelet membrane (unpublished). The low accumulation in the platelets from migraine paan
tients could be associated with the fact that the monoamine oxidase concentration of these platelets is lower than normal.5 The reduced accumulation may be due to a high intracellular concentration of 5-HT, which could further restrict accumulation : if so, release function may also be disturbed. R. MALMGREN
P. OLSSON G. TORNLING G. UNGE
Karolinska Institute, S-104 01 Stockholm, Sweden
AS MOTHER MADE IT? How can The Lancet print news of an important recent advance in the therapy of asthma without any indication of the composition of the medication, the pharmacokinetics of the active ingredient, the legal status of the medicine, and its progress through the Committee on Safety of Medicines (if it has not yet been passed is the delay of 800 years a record?). And why were there no randomised controlled trials of chicken soup versus beef broth, which I use in my personal practice? me.
University of Edinburgh, Edinburgh EH8 9AG
McCloy J, McCloy
SIR,-Your Aug. 18 editorial failed to emphasise an impormechanism by which transmission of Creutzfeldt-Jakob disease could occur. Pins are widely used by neurologists and others doing sensory examinations, and the same pin is often used on more than one patient. The passage of the disease via tant
SiR,-The letter on chicken soup (Nov. 17, p. 1079) surprises
Medical Computing and Statistics Unit, Medical School,
8.
TRANSMISSION OF CREUTZFELDT-JAKOB DISEASE
and
obesity.
Lancet
1979; ii:
University College Hospital London WC1E 6JJ
Medical School,
A. E. M. MCLEAN
156.
1. Kleijer WJ, DeBruijn HWA, Leschot NJ. Amniotic fluid alpha-fetoprotein levels and the prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands. Br J Obstet Gynæcol 1978; 85: 512-17. of the U.K. Collaborative Study on Alpha-fetoprotein in Relation to Neural-Tube Defects. Maternal serum alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet 1977; i: 1323-32. 3. Roberts CJ, Hibbard BM, Evans DR, Evans KT, Laurence KM, Hoole M, Roberts E, Ennis WP. Precision in estimating gestational age and its influence on sensitivity of alphafetoprotein screening. Br Med J 1979; i:
2.
Report
981-03.
1. Manuelidis E, Gorgacz E, Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science 1978; 200: 1069-71. 2. Gajdusek DC, Gibbs CJ, Asher DM, et al. Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease). N Engl J Med 1977; 297: 1253-58. 3. Hanington E. Migraine: a blood disorder? Lancet 1978, ii: 501-02. 4. Malmgren R, Olsson P, Tornling G, Unge G. Acetylsalicylic asthma and migraine: A defect in serotonin (5-HT) uptake in platelets. Thromb Res
1978; 13: 1137-39. 5. Sandler M. Transitory platelet mono-amine oxidase deficit Some reflections. Headache 1977; 17: 153-58.
in
migraine:
GIANFRANCO DELLE FAVE LAURA DE MAGISTRIS ANNA KOHN
Medical Clinic II, Policlinico Umberto I, 00100 Rome, Italy
ORIGIN OF MATERNAL SERUM AFP
SIR,—The U.K. Collaborative Study (Sept. 29, p. 651) found correlation between maternal serum alpha-fetoprotein and amniotic fluid AFP in normal pregnancies, and at best a weak correlation in pregnancies with open neural tube defects (NTDs). Your editorial of Nov. 10 commented that the result in NTDs was surprising since the increased serum-AFP among open NTD pregnancies is presumed to be caused by the high levels in the amniotic fluid. There is a plausible explanation for the weakness of these correlations which is an artefact of the way such data are collected. Maternal serum-AFP increases by approximately 10% for every week of gestational age from 10 to 24 weeks of pregnancy,’ whereas amniotic fluid AFP decreases by approximately the same percentage per week at this stage in pregnancy.2 Even the best clinical estimates of gestational age are imprecise when compared with postnatal assessment. In one study3 more than 20% of their best estimates were in error by two weeks or more. In the collaborative study each centre standardised their results by expressing them in terms of their local median for each week of gestation. This corrects for a constant bias in the estimation of gestational age at each centre, but we should still expect that the gestational age assigned to many pregnancies will either overestimate or underestimate the maturity of the fetus compared with the other pregnancies at that centre. Where gestation is underestimated the maternal serum AFP (in multiples of the median) will be falsely high, whereas the amniotic fluid AFP will appear low. The opposite will be true when gestation is overestimated. Thus errors of estimation of gestational age would produce a negative correlation between maternal serum AFP and amniotic fluid AFP even if there were no biological connection between the two measures. Similarly, the underlying correlations between AFP in serum and amniotic fluid may be considerably higher than those estimated in the collaborative study. If an amniotic fluid result is borderline, a very high serumAFP will indeed give extra evidence of the presence of an open NTD. However, we may be confirming our estimate of gestational age, rather than measuring an independent risk factor. no
(AFP)
GILLIAN M. RAAB
5. Pearse AGE, Polak JM. The diffuse neuroendocrine system and the APUD concept. In: Bloom SR, ed. Gut hormones. Edinburgh: Churchill Livingstone, 1978: 33-39. 6. Dockray GJ. Cholecystochinin-like peptides in brain. In: Bloom SR, ed. Gut hormones. Edinburgh. Churchill Livingstone, 1978: 530-33. 7. Rehfeld JF. Localization of gastrins to neuro- and adenohypophysis. Nature
1978; 271: 771-73. RF.
Enkephalins, hunger,
inoculation of blood elements in laboratory animals’ suggests that pin re-use is unwise. However, many examiners use pins which are not disposable. Reflex hammers with built-in pins are still being distributed by drug companies, and Wartenberg wheels (with multiple pinpoints) are still being used on demented patients. This risk was highlighted many years ago with the discovery of the infectious nature of hepatitis. Although the practice of pin re-use has been criticised2 the message has not yet been generally heeded. Department of Neurology, University of California, V. A. Medical Center, Martinez, California 94553, U.S.A.
MIGRAINE,
ROBERT P. FRIEDLAND
A PLATELET DISORDER
SIR,-Hanington3 has proposed that migraine is caused by abnormality of platelet function, and we have reported a reduced accumulation of S-HT in platelets from patients with migraine.4 Dr Coppen and his colleagues (Oct. 27, p. 114) demonstrated that patients who had had a migraine headache within the previous five days had a significantly lower maximum rate of uptake (Vmax) of 5-HT than did healthy controls. These observations accord with our findings of a defect in 5-HT accumulation in platelets from migraine patients. We have also found that the active S-HT uptake mechanism in the migraine platelet is severely disturbed and these changes are accompanied by altered change density of the platelet membrane (unpublished). The low accumulation in the platelets from migraine paan
tients could be associated with the fact that the monoamine oxidase concentration of these platelets is lower than normal.5 The reduced accumulation may be due to a high intracellular concentration of 5-HT, which could further restrict accumulation : if so, release function may also be disturbed. R. MALMGREN
P. OLSSON G. TORNLING G. UNGE
Karolinska Institute, S-104 01 Stockholm, Sweden
AS MOTHER MADE IT? How can The Lancet print news of an important recent advance in the therapy of asthma without any indication of the composition of the medication, the pharmacokinetics of the active ingredient, the legal status of the medicine, and its progress through the Committee on Safety of Medicines (if it has not yet been passed is the delay of 800 years a record?). And why were there no randomised controlled trials of chicken soup versus beef broth, which I use in my personal practice? me.
University of Edinburgh, Edinburgh EH8 9AG
McCloy J, McCloy
SIR,-Your Aug. 18 editorial failed to emphasise an impormechanism by which transmission of Creutzfeldt-Jakob disease could occur. Pins are widely used by neurologists and others doing sensory examinations, and the same pin is often used on more than one patient. The passage of the disease via tant
SiR,-The letter on chicken soup (Nov. 17, p. 1079) surprises
Medical Computing and Statistics Unit, Medical School,
8.
TRANSMISSION OF CREUTZFELDT-JAKOB DISEASE
and
obesity.
Lancet
1979; ii:
University College Hospital London WC1E 6JJ
Medical School,
A. E. M. MCLEAN
156.
1. Kleijer WJ, DeBruijn HWA, Leschot NJ. Amniotic fluid alpha-fetoprotein levels and the prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands. Br J Obstet Gynæcol 1978; 85: 512-17. of the U.K. Collaborative Study on Alpha-fetoprotein in Relation to Neural-Tube Defects. Maternal serum alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet 1977; i: 1323-32. 3. Roberts CJ, Hibbard BM, Evans DR, Evans KT, Laurence KM, Hoole M, Roberts E, Ennis WP. Precision in estimating gestational age and its influence on sensitivity of alphafetoprotein screening. Br Med J 1979; i:
2.
Report
981-03.
1. Manuelidis E, Gorgacz E, Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science 1978; 200: 1069-71. 2. Gajdusek DC, Gibbs CJ, Asher DM, et al. Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease). N Engl J Med 1977; 297: 1253-58. 3. Hanington E. Migraine: a blood disorder? Lancet 1978, ii: 501-02. 4. Malmgren R, Olsson P, Tornling G, Unge G. Acetylsalicylic asthma and migraine: A defect in serotonin (5-HT) uptake in platelets. Thromb Res
1978; 13: 1137-39. 5. Sandler M. Transitory platelet mono-amine oxidase deficit Some reflections. Headache 1977; 17: 153-58.
in
migraine:
