- Email: [email protected]
THEOPHYLLINE PHARMACOKINETICS IN RESPIRATORY VIRAL ILLNESS
160 total of thirteen cycles while only 1 of 8 placebo-treated patients reported this degree of relief during one single menstruation (p=0.02). The patients had the option of taking a supplemental analgesic but only 3 patients treated with naproxen had to resort to further analgesia in a total of five menstrual cycles while all patients treated with placebo had to supplement their treatment with other analgesics in a total of 16 of 24 treatment courses (P=0.01). In our series, no side-effects were observed. a
Manitoba
are at risk of anxmias should significant encourage regular blood-counts with determination of red-cell indices and consideration of how to improve the patient’s diet.
However, the probability that these patients
Department of Hæmatology, General Infirmary at Leeds,
THEOPHYLLINE PHARMACOKINETICS IN RESPIRATORY VIRAL ILLNESS
Clinic,
Winnipeg, Manitoba, Canada R3A 1M3
J. A. CHILD
Leeds LS1 3EX
FERDINAND PAULS
SIR,-As Dr Kelly and Dr O’Malley (July 8,
p. 98) point chromatographic procedures are now available for the measurement of theophylline. However, the Schack and Waxler assay has been widely used in research and it is sufficiently accurate when xanthine-free diets are imposed. The short half-lives of 2.09 and 1.37 h in our patients were not, as Kelly and O’Malley suggest, due to the short sampling period. Theophylline half-lives as short as 1.17,1 1.82,2 and 1.42 hhave been found repeatedly in asthmatic children. We calculated half-lives from six data points (1, 12, 2, 3, 4, and 5 h after intravenous infusion) which represented the terminal exponential (p) phase of a two-compartment kinetics. Since theophylline distribution half-life ((Xtl/2) is about 0-18 h,4the distribution phase will be nearly complete in an hour. We did not include the data in the first hour of sampling in the halflife calculation. In this way the underestimation of half-life, by erroneously treating a two-compartment kinetic model as a single-compartment as suggested in the article Kelly and O’Malley cite,5 is avoided. More data points would allow more accurate calculation of elimination half-life but many of our patients with respiratory viral infection were having asthma attacks and a longer sampling period was not possible because aminophylline was usually required every 6 h. An alternative, however, is the study of steady-state clearance rather than elimination half-
out,
GUT-HORMONE PROFILES
SIR The negative attitude of Dr Low-Beer and coltowards gut-hormone profiles in gastrointestinal diseases is not reasonable. The careful study by Dr Besterman and co-workers,2which Low-Beer et al. criticise, provides a useful background to the much wider application of gut-hormone assays in clinical medicine. The negative attitude of Low-Beer et al. reflects a real problem in gut endocrinology: some gut-hormone assays are technically still so difficult3 that the time definitely is not yet ripe for their application in hospital routine. The cholecystokinin-assay exemplifies the difficult assay;3 and this, apparently, is the assay from which all the grief of Low-Beer et al. originates.56 Consequently, if gut-hormone profiles are to have a future outside the Hammersmith Hospital, it will be necessary to study a few, simple assays, representative of the different regions in the gut. Besterman et
leagues’
al. used
seven
different assays
including the cumbersome secre-
tin-assay, which moreover, besides the convenient meal test, requires an extra test, duodenal acid infusion. For most gastrointestinal diseases useful gut-hormone profiles can probably be established with three simple assays and a single meal test. The hormones to be assayed could well be Gastrin, representing the stomach; GIP (gastric inhibitory polypeptide), representing the upper small intestine; and Gut-GLI (glucagon-like-immunoreactivity) representing the lower small intestine ("the triple G-hormone profile").
Kaiser Foundation
Institute of Medical
Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark
life. The one-tailed t test was used because we were testing the hypothesis that undirectional change occurred (P<0.025). If a two-tailed test is used our results are still significant (P<0.05). Portland, Oregan,
JENS F. REHFELD
Hospitals, K. C. CHANG
U.S.A.
National Asthma Center, Denver, Colorado
T. D. BELL
University of Colorado Medical Center, B. A. LAUER
Denver, Colorado
ANÆMIA, ANTICONVULSANTS, AND DIET SIR,-The concept that frank megaloblastic ansemia in patients on long-term anticonvulsant therapy is likely to reflect dietary inadequacy, presented by Dr Rose and Mr Johnson,’ is not new. In a study of a probably comparable group of 100 patients, only 8 had a raised mean cell volume, and of these, 2 had slight anaemia: 27 had low serum-folates.8 On the basis of this and other experience in the investigation of such patients, it was suggested that additional factors (e.g., dietary deficiency) should be considered when a major dyscrasia presented. We also pointed out that bone-marrow examination and folate estimations were unlikely to be of practical value in the management of this patient group, a view with which Rose and Johnson would presumably agree. 1.
Low-Beer, T. S., Harvey, R. F., Heaton, K. W., Read, A. Lancet, 1978, i,
2. 3.
Besterman, H. S., and others ibid. p. 785. Rehfeld, J. F. in Gut Hormones (edited by S. R. Bloom); p. 118, Edinburgh,
4. 5. 6.
Rehfeld, J. F. J. biol. Chem. 1978, 253, 4016. Harvey, R. F., Dowsett, L., Hartog, M., Read, A. E. Lancet, 1973, ii, 826. Low-Beer, T. S., Harvey, R. F., Davies, E. R., Read, A. E. New Engl. J. Med. 1975, 292, 961. Rose, M., Johnson, I. Lancet, 1978, i, 1349. Child, J. A., Khattack, B. Z., Knowles, J. P. Br. J. Hæmat. 1969, 16, 451
1100.
SIR,—The increased plasma half-life of theophylline during viral illness described by Dr Chang and colleagues is
acute
probably due to a decrease in hepatic theophylline biotransformation by cytochrome P-450 dependent mixed-function oxidase.. In our laboratory lower steady-state levels of cytochrome P-450 and a decreased capacity for drug biotransformation have been demonstrated in animals treated with agents which can induce the production of interferon.6-8 Included in this study was an acute viral infection with Mengo virus which lowered cytochrome P-450 levels and ethylmorphine N-demethylation by 20% and 42%, respectively. Recent most
1. 2.
Ellis, E. F., Yaffe, S. J., Levy, G. J. Allergy clin. Immun. 1974, 53, 79. Loughman, P. M., Sitar, D. S., Ogilivie, R. I., Eisen, A., Fox, Z., Neims, A. H. J. Pediat. 1976, 88, 874. 3. Ellis, E. F., Koysooko, R., Levy, G. Pediatrics, 1976, 58, 542. 4. Piafsky, K. M., Sitar, D. S., Ogilvie, R. I. Clin. Pharmac. Ther. 1977, 22,
1978.
7. 8.
336. 5.
Gibaldi, M., Weintraub, H. J. pharm. Sci. 1971, 60, 624. 6. Renton, K. W., Mannering, G. J. Drug Metab. Disposition, 1976, 4, 223. 7. Renton, K W., Mannering, G. J. Biochem. Biophys. Res. Comm. 1976, 73, 343. 8. Renton, K. W., V. Ullrich); p.
Mannering, G. J. in 483. Oxford, 1977.
Microsomes and
Drug
Oxidation
(ed.
161
experiments in rats have demonstrated that the interferoninducing agents Bordetella pertussis vaccine and the synthetic polynucleotide poly-rI.rC cause a fourfold increase in phenytoin half-life and a decrease in phenytoin hydroxylation by cytochrome P-450 dependent mixed-function oxidase in the liver.4 Since the half-life of theophylline is at least partially dependent on oxidation by cytochrome P-4505 the observations of Chang et al. are consistent with what we have observed in animals. Therefore our hypothesis that agents (infectious or otherwise) which can induce the formation of interferon also decrease the oxidation of drugs in the liver appears to hold good for man. This raises the interesting possibility that in man
many other agents which induce the formation of inter-
feron, including certain viruses, bacteria, and vaccines, will alter drug biotransformation and elimination. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H
4H7.
KENNETH W. RENTON
UPTAKE OF 14C-DOPAMINE IN PLATELETS OF HUNTINGTON’S CHOREA PATIENTS AND SYMPTOM-FREE OFFSPRING
SIR,-Altered metabolism of brain dopamine may be one of the factors explaining the pathophysiology of choreic movements.’,2 A reduced dopamine concentration has been demonstrated in the caudate nucleus of Huntington’s chorea patients.3,4 Taking blood platelets as a readily accessible model of brain synaptosomal function, Aminoff et al. found that platelet-rich plasma from patients with Huntington’s chorea took up significantly more dopamine than did control plasma. Since there is no satisfactory test to determine whether any of the offspring of an affected patient have inherited the disease before it becomes clinically apparent, Aminoff et al. suggested that their observations might be of value as a predictive test in individuals at risk of Huntington’s chorea. We have studied the uptake of dopamine in platelets of patients with Huntington’s chorea and their symptom-free offspring in an attempt to evaluate this problem.
LOW-DOSE RADIATION
SIR,-Dr Mole6 has wisely drawn attention
to the fact that of "bone-marrow" cancers (myeloma and myeloid leukxmia) among Hanford employees in the analysis carried out by Stewart and her coworkers,7 this excess was more than compensated by a large deficit in deaths ascribed to other neoplasms of the reticuloendothelial system. An additional reason for being cautious in interpreting this initial analysis of the Hanford data is that, although Stewart et al. classified "observed" deaths by the 8th revision of the International Classification of Diseases (I.C.D.), they classified "expected" deaths according to the 7th revision. This had the effect of greatly increasing the apparent excess of deaths due to myeloid leukaemia, since under the rules of the 7th revision any form of acute leukxmia (many of which are of the myeloid type) was ascribed to "other" leukaemia (I.C.D. 204.3). On recalculation using ,the 7th revision for observed as well as expected,8 and adjusting for the age distribution of the Hanford deaths (which Mancuso et al. had failed to do) the excess of 3 ’2myeloid leuksemia cited by Mole is reduced to 1.4.9 Doubtless much remains to be learned from the experience of the Hanford employees and of similar groups handling radioactive materials, but in the present highly emotional climate the data will need to be analysed with unusual care and detachment if wise conclusions are to be reached.
although
there
was
an
apparent
excess
of Preventive Medicine and Biostatistics,
Department
Faculty of Medicine, University of Toronto, Toronto, Canada M5S 1A8.
TERENCE W. ANDERSON
MALLORY-WEISS SYNDROME
SIR,-Your editorial’° emphasises the role of fibreoptic in the diagnosis of the Mallory-Weiss syndrome. I think that it should also be mentioned that this condition may in fact be produced by endoscopy. One of the most spectacular tears I have seen I produced myself in a patient who retched violently during the procedure. He made an uneventful recovery on conservative management, and did not require bloodtransfusion.
endoscopy
Derbyshire Royal Infirmary, Derby DE1 2QY
G. K. T. HOLMES
Renton, K. W. Proc. Can. Fed. biol. Soc. 1978, 21, 159. Aranda, J. V., Sitar, D. S., Parsons, W. D., Loughan, P. M., Neims, New Engl. J. Med. 1976, 295, 413. 6. Mole, R H. Lancet, 1978, i, 1155. 7. Mancuso, I F., Stewart, A , Kneale, G. Hlth Phys. 1977, 33, 369.
4. 5.
8. Stewart, A. Personal communication. 9. Anderson, T. W Hlth Phys. in the press) 10. Lancet, 1978, i, 1294.
A. H.
UPTAKE OF
CHOREA
14C-DOPAMINE PATIENTS,
IN PLATELETS OF
THEIR
OFFSPRING,
HUNTINGTON’S
AND CONTROLS
Figures in parentheses represent number of individuals studied.
Venous blood was collected in the fasting state between 8 and 9 A.M. in plastic syringes, and platelet-rich plasma was prepared.b Within 2 h of blood-sampling platelet uptake of l4C-dopamine (Amersham-Searle) was determined.7 After 10 min of preincubation, 14C-dopamine was added to platelet-rich plasma and incubated for 30 min at 37°C. Platelets were isolated by centrifugation and the radioactivity determined by liquid scintillation spectrometry. Platelets were counted in platelet-rich plasma microscopically (Neubauer Hemocytometers). Dopamine uptake was expressed in nmol 14C-dopamine per 10" platelets. The final concentrations of 14C-dopamine used were 1, 10, and 100 mol/1. The control group matched the patients as well as the symptom-free offspring for age within a decade. We included in our results individuals of either sex because no sex difference in platelet dopamine uptake had been found in a large number of normal subjects studied previously. None of the patients had received drugs known to influence dopamine metabolism. Informed consent was obtained in all cases. Statistical analysis was by Student’s t test. The results are given in the table. No difference in dopamine uptake was seen between the Huntington’s chorea patients and controls. Nor did the values of the offspring differ from those of normal or choreic patients. Thus we could not confirm the findings of Aminoff et al. The normal dopamine uptake found in the offspring makes it unKlawans, H. L. Eur. Neurol. 1970, 4, 148. Bonilla, E. Psych. Forum, 1976, 6, 45. Barbeau, A. ibid. 1973, 4, 8. Bernheimer, H., Birkmayer, W., Hornykiewicz, O, Jellinger, K., Seitelberger, F. J. neurol. Sci. 1973, 20, 415. 5. Aminoff, M. J., Trenchard, A., Turner, P., Wood, W. G., Hills, M. Lancet, 1974, ii, 1115. 6. Boullin, D. J., O’Brien, R. A. Br. J. Pharmac. 1971, 42, 114. 7. Barbeau, A., Campanella, G., Butterworth, R. F., Yamada, K. Neurology, 1975, 25, 1.
1. 2. 3. 4.
Manitoba
are at risk of anxmias should significant encourage regular blood-counts with determination of red-cell indices and consideration of how to improve the patient’s diet.
However, the probability that these patients
Department of Hæmatology, General Infirmary at Leeds,
THEOPHYLLINE PHARMACOKINETICS IN RESPIRATORY VIRAL ILLNESS
Clinic,
Winnipeg, Manitoba, Canada R3A 1M3
J. A. CHILD
Leeds LS1 3EX
FERDINAND PAULS
SIR,-As Dr Kelly and Dr O’Malley (July 8,
p. 98) point chromatographic procedures are now available for the measurement of theophylline. However, the Schack and Waxler assay has been widely used in research and it is sufficiently accurate when xanthine-free diets are imposed. The short half-lives of 2.09 and 1.37 h in our patients were not, as Kelly and O’Malley suggest, due to the short sampling period. Theophylline half-lives as short as 1.17,1 1.82,2 and 1.42 hhave been found repeatedly in asthmatic children. We calculated half-lives from six data points (1, 12, 2, 3, 4, and 5 h after intravenous infusion) which represented the terminal exponential (p) phase of a two-compartment kinetics. Since theophylline distribution half-life ((Xtl/2) is about 0-18 h,4the distribution phase will be nearly complete in an hour. We did not include the data in the first hour of sampling in the halflife calculation. In this way the underestimation of half-life, by erroneously treating a two-compartment kinetic model as a single-compartment as suggested in the article Kelly and O’Malley cite,5 is avoided. More data points would allow more accurate calculation of elimination half-life but many of our patients with respiratory viral infection were having asthma attacks and a longer sampling period was not possible because aminophylline was usually required every 6 h. An alternative, however, is the study of steady-state clearance rather than elimination half-
out,
GUT-HORMONE PROFILES
SIR The negative attitude of Dr Low-Beer and coltowards gut-hormone profiles in gastrointestinal diseases is not reasonable. The careful study by Dr Besterman and co-workers,2which Low-Beer et al. criticise, provides a useful background to the much wider application of gut-hormone assays in clinical medicine. The negative attitude of Low-Beer et al. reflects a real problem in gut endocrinology: some gut-hormone assays are technically still so difficult3 that the time definitely is not yet ripe for their application in hospital routine. The cholecystokinin-assay exemplifies the difficult assay;3 and this, apparently, is the assay from which all the grief of Low-Beer et al. originates.56 Consequently, if gut-hormone profiles are to have a future outside the Hammersmith Hospital, it will be necessary to study a few, simple assays, representative of the different regions in the gut. Besterman et
leagues’
al. used
seven
different assays
including the cumbersome secre-
tin-assay, which moreover, besides the convenient meal test, requires an extra test, duodenal acid infusion. For most gastrointestinal diseases useful gut-hormone profiles can probably be established with three simple assays and a single meal test. The hormones to be assayed could well be Gastrin, representing the stomach; GIP (gastric inhibitory polypeptide), representing the upper small intestine; and Gut-GLI (glucagon-like-immunoreactivity) representing the lower small intestine ("the triple G-hormone profile").
Kaiser Foundation
Institute of Medical
Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark
life. The one-tailed t test was used because we were testing the hypothesis that undirectional change occurred (P<0.025). If a two-tailed test is used our results are still significant (P<0.05). Portland, Oregan,
JENS F. REHFELD
Hospitals, K. C. CHANG
U.S.A.
National Asthma Center, Denver, Colorado
T. D. BELL
University of Colorado Medical Center, B. A. LAUER
Denver, Colorado
ANÆMIA, ANTICONVULSANTS, AND DIET SIR,-The concept that frank megaloblastic ansemia in patients on long-term anticonvulsant therapy is likely to reflect dietary inadequacy, presented by Dr Rose and Mr Johnson,’ is not new. In a study of a probably comparable group of 100 patients, only 8 had a raised mean cell volume, and of these, 2 had slight anaemia: 27 had low serum-folates.8 On the basis of this and other experience in the investigation of such patients, it was suggested that additional factors (e.g., dietary deficiency) should be considered when a major dyscrasia presented. We also pointed out that bone-marrow examination and folate estimations were unlikely to be of practical value in the management of this patient group, a view with which Rose and Johnson would presumably agree. 1.
Low-Beer, T. S., Harvey, R. F., Heaton, K. W., Read, A. Lancet, 1978, i,
2. 3.
Besterman, H. S., and others ibid. p. 785. Rehfeld, J. F. in Gut Hormones (edited by S. R. Bloom); p. 118, Edinburgh,
4. 5. 6.
Rehfeld, J. F. J. biol. Chem. 1978, 253, 4016. Harvey, R. F., Dowsett, L., Hartog, M., Read, A. E. Lancet, 1973, ii, 826. Low-Beer, T. S., Harvey, R. F., Davies, E. R., Read, A. E. New Engl. J. Med. 1975, 292, 961. Rose, M., Johnson, I. Lancet, 1978, i, 1349. Child, J. A., Khattack, B. Z., Knowles, J. P. Br. J. Hæmat. 1969, 16, 451
1100.
SIR,—The increased plasma half-life of theophylline during viral illness described by Dr Chang and colleagues is
acute
probably due to a decrease in hepatic theophylline biotransformation by cytochrome P-450 dependent mixed-function oxidase.. In our laboratory lower steady-state levels of cytochrome P-450 and a decreased capacity for drug biotransformation have been demonstrated in animals treated with agents which can induce the production of interferon.6-8 Included in this study was an acute viral infection with Mengo virus which lowered cytochrome P-450 levels and ethylmorphine N-demethylation by 20% and 42%, respectively. Recent most
1. 2.
Ellis, E. F., Yaffe, S. J., Levy, G. J. Allergy clin. Immun. 1974, 53, 79. Loughman, P. M., Sitar, D. S., Ogilivie, R. I., Eisen, A., Fox, Z., Neims, A. H. J. Pediat. 1976, 88, 874. 3. Ellis, E. F., Koysooko, R., Levy, G. Pediatrics, 1976, 58, 542. 4. Piafsky, K. M., Sitar, D. S., Ogilvie, R. I. Clin. Pharmac. Ther. 1977, 22,
1978.
7. 8.
336. 5.
Gibaldi, M., Weintraub, H. J. pharm. Sci. 1971, 60, 624. 6. Renton, K. W., Mannering, G. J. Drug Metab. Disposition, 1976, 4, 223. 7. Renton, K W., Mannering, G. J. Biochem. Biophys. Res. Comm. 1976, 73, 343. 8. Renton, K. W., V. Ullrich); p.
Mannering, G. J. in 483. Oxford, 1977.
Microsomes and
Drug
Oxidation
(ed.
161
experiments in rats have demonstrated that the interferoninducing agents Bordetella pertussis vaccine and the synthetic polynucleotide poly-rI.rC cause a fourfold increase in phenytoin half-life and a decrease in phenytoin hydroxylation by cytochrome P-450 dependent mixed-function oxidase in the liver.4 Since the half-life of theophylline is at least partially dependent on oxidation by cytochrome P-4505 the observations of Chang et al. are consistent with what we have observed in animals. Therefore our hypothesis that agents (infectious or otherwise) which can induce the formation of interferon also decrease the oxidation of drugs in the liver appears to hold good for man. This raises the interesting possibility that in man
many other agents which induce the formation of inter-
feron, including certain viruses, bacteria, and vaccines, will alter drug biotransformation and elimination. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H
4H7.
KENNETH W. RENTON
UPTAKE OF 14C-DOPAMINE IN PLATELETS OF HUNTINGTON’S CHOREA PATIENTS AND SYMPTOM-FREE OFFSPRING
SIR,-Altered metabolism of brain dopamine may be one of the factors explaining the pathophysiology of choreic movements.’,2 A reduced dopamine concentration has been demonstrated in the caudate nucleus of Huntington’s chorea patients.3,4 Taking blood platelets as a readily accessible model of brain synaptosomal function, Aminoff et al. found that platelet-rich plasma from patients with Huntington’s chorea took up significantly more dopamine than did control plasma. Since there is no satisfactory test to determine whether any of the offspring of an affected patient have inherited the disease before it becomes clinically apparent, Aminoff et al. suggested that their observations might be of value as a predictive test in individuals at risk of Huntington’s chorea. We have studied the uptake of dopamine in platelets of patients with Huntington’s chorea and their symptom-free offspring in an attempt to evaluate this problem.
LOW-DOSE RADIATION
SIR,-Dr Mole6 has wisely drawn attention
to the fact that of "bone-marrow" cancers (myeloma and myeloid leukxmia) among Hanford employees in the analysis carried out by Stewart and her coworkers,7 this excess was more than compensated by a large deficit in deaths ascribed to other neoplasms of the reticuloendothelial system. An additional reason for being cautious in interpreting this initial analysis of the Hanford data is that, although Stewart et al. classified "observed" deaths by the 8th revision of the International Classification of Diseases (I.C.D.), they classified "expected" deaths according to the 7th revision. This had the effect of greatly increasing the apparent excess of deaths due to myeloid leukaemia, since under the rules of the 7th revision any form of acute leukxmia (many of which are of the myeloid type) was ascribed to "other" leukaemia (I.C.D. 204.3). On recalculation using ,the 7th revision for observed as well as expected,8 and adjusting for the age distribution of the Hanford deaths (which Mancuso et al. had failed to do) the excess of 3 ’2myeloid leuksemia cited by Mole is reduced to 1.4.9 Doubtless much remains to be learned from the experience of the Hanford employees and of similar groups handling radioactive materials, but in the present highly emotional climate the data will need to be analysed with unusual care and detachment if wise conclusions are to be reached.
although
there
was
an
apparent
excess
of Preventive Medicine and Biostatistics,
Department
Faculty of Medicine, University of Toronto, Toronto, Canada M5S 1A8.
TERENCE W. ANDERSON
MALLORY-WEISS SYNDROME
SIR,-Your editorial’° emphasises the role of fibreoptic in the diagnosis of the Mallory-Weiss syndrome. I think that it should also be mentioned that this condition may in fact be produced by endoscopy. One of the most spectacular tears I have seen I produced myself in a patient who retched violently during the procedure. He made an uneventful recovery on conservative management, and did not require bloodtransfusion.
endoscopy
Derbyshire Royal Infirmary, Derby DE1 2QY
G. K. T. HOLMES
Renton, K. W. Proc. Can. Fed. biol. Soc. 1978, 21, 159. Aranda, J. V., Sitar, D. S., Parsons, W. D., Loughan, P. M., Neims, New Engl. J. Med. 1976, 295, 413. 6. Mole, R H. Lancet, 1978, i, 1155. 7. Mancuso, I F., Stewart, A , Kneale, G. Hlth Phys. 1977, 33, 369.
4. 5.
8. Stewart, A. Personal communication. 9. Anderson, T. W Hlth Phys. in the press) 10. Lancet, 1978, i, 1294.
A. H.
UPTAKE OF
CHOREA
14C-DOPAMINE PATIENTS,
IN PLATELETS OF
THEIR
OFFSPRING,
HUNTINGTON’S
AND CONTROLS
Figures in parentheses represent number of individuals studied.
Venous blood was collected in the fasting state between 8 and 9 A.M. in plastic syringes, and platelet-rich plasma was prepared.b Within 2 h of blood-sampling platelet uptake of l4C-dopamine (Amersham-Searle) was determined.7 After 10 min of preincubation, 14C-dopamine was added to platelet-rich plasma and incubated for 30 min at 37°C. Platelets were isolated by centrifugation and the radioactivity determined by liquid scintillation spectrometry. Platelets were counted in platelet-rich plasma microscopically (Neubauer Hemocytometers). Dopamine uptake was expressed in nmol 14C-dopamine per 10" platelets. The final concentrations of 14C-dopamine used were 1, 10, and 100 mol/1. The control group matched the patients as well as the symptom-free offspring for age within a decade. We included in our results individuals of either sex because no sex difference in platelet dopamine uptake had been found in a large number of normal subjects studied previously. None of the patients had received drugs known to influence dopamine metabolism. Informed consent was obtained in all cases. Statistical analysis was by Student’s t test. The results are given in the table. No difference in dopamine uptake was seen between the Huntington’s chorea patients and controls. Nor did the values of the offspring differ from those of normal or choreic patients. Thus we could not confirm the findings of Aminoff et al. The normal dopamine uptake found in the offspring makes it unKlawans, H. L. Eur. Neurol. 1970, 4, 148. Bonilla, E. Psych. Forum, 1976, 6, 45. Barbeau, A. ibid. 1973, 4, 8. Bernheimer, H., Birkmayer, W., Hornykiewicz, O, Jellinger, K., Seitelberger, F. J. neurol. Sci. 1973, 20, 415. 5. Aminoff, M. J., Trenchard, A., Turner, P., Wood, W. G., Hills, M. Lancet, 1974, ii, 1115. 6. Boullin, D. J., O’Brien, R. A. Br. J. Pharmac. 1971, 42, 114. 7. Barbeau, A., Campanella, G., Butterworth, R. F., Yamada, K. Neurology, 1975, 25, 1.
1. 2. 3. 4.