279 SERUM-AMINOACIDS AND BRAIN TRYPTOPHAN UPTAKE
An important advantage of this said to be the lack of evidence of disseminated intravascular coagulation, compared with other
Haemophilia Centre. concentrate was concentrates.
To
assess
the advantage of this
concentrate
it would be
important to know the quantities of administered concenFurthertrate expressed as units of coagulation activity. believe that the simultaneous administration of heparin very important factor in the good compatibility. In our own investigation, using commercially available factor-vil-rich concentrates, disseminated intravascular coagulation could be controlled in every case by heparin.99 Therefore we believe that a clear advantage of the concentrate has not been proved, but the combined use of heparin should be emphasised.
more,
we
is
of a tracer amount of 3H-tryptophan 6 minutes before death (see accompanying table). The methods used have been described elsewhere.5,r, These observations provide support for the view of Curzon et al. that it is the concentration of freely diffusible tryptophan rather than the total-serum-tryptophan concentration that is important in controlling tryptophan uptake into the brain. Following a single dose of chlorpromazine, the rate of tryptophan uptake increased, despite a fall in the serum-total-tryptophan concentration; this was presumably due to the increase in the proportion of tryptophan that was freely diffusible rather than bound to albumin. However, the results shown here also support the view of Munro et awl. that the concentrations of competing aminoacids are also important. This is especially clear after 11 days repeated administration of the drug; serum-tryptophan (both total and diffusible) was normal, while the concentration of serum-total-aminoacids was depressed, and brain tryptophan uptake (and also serotonin synthesis) increased, compared with control animals. It therefore appears that both diffusible tryptophan concentration and the concentrations of competing aminoacids are important as determinants of the rate of tryptophan uptake into the brain, and hence of serotonin synthesis. These observations of serum parameters which can be correlated with brain-serotonin turnover in laboratory animals may be important not only in furthering our understanding of the processes involved in acute liver failure, 3,4 but also in understanding the underlying neurochemistry of some chronic psychiatric disorders. We have shown that in chlorpromazine-treated patients with chronic schizophrenia, serum tryptophan was lower than normal, while total aminoacids were normal. On withdrawal of the drug for 4 weeks, serum diffusible tryptophan rose considerably, and remained raised, while serum-total-aminoacids rose transiently, and soon returned to the initial level. It is tempting to speculate that these changes, which appeared to coincide with changes in behaviour, may also be related to changes in serotonin turnover in the brain, as the animal model would predict. Courtauld Institute of Biochemistry, Middlesex Hospital Medical School, London W1P 5PR.
Universitäts-Kinderklinik
U. GÖBEL H. v. Voss C. PETRICH.
4 Düsseldorf, Moorenstrasse 5, West Germany.
ABNORMAL HÆMOGLOBINS IN SOUTH-EAST STAFFORDSHIRE
SIR,-The letter by Dr Buckley and his colleagues (July 12, p. 82) raises several interesting points: in particular the extraordinarily high incidence of j3-thalassa:mia in their 142 patients of British origin (18%); and their views on genetic counselling. One would like to know the diagnostic criteria involved, and the relationships of those patients resident in Abbots Bromley. It would appear likely that this incidence of p-thalassaemia is due to gene drift ". As to the suggestion that the gene arrived during the Roman invasion, this is an old chestnut which, although appealing, is by no means certain. Admittedly, the occupying Roman forces-who often stayed on as veteran colonists -were drawn from the entire Mediterranean littoral; but the presence of P-thalassaemia in Norway,10 and in Ireland, 11 areas not occupied by the Romans, indicates that some P-thalassaemic mutations may well have arisen de novo in North European populations. After all, marshes in England "
and the low countries were malarious in medixval times. The question of genetic counselling is more vexed; in this hospital we advise that anyone carrying thalassaemia or an abnormal hxmoglobin should get their fiancés or spouses checked regardless of their race of origin. I have yet to experience requests for testing from otherwise healthy couples before their marriage, but should such persons ever request advice I would have thought that a check for hasmoglobinopathies should be included in all screens for all persons. Department of Hæmatology, The London Hospital Medical
College, London E1 2AD.
F. E. BOULTON.
D. A. BENDER.
USE OF HEPARIN IN COMBINATION WITH FACTOR-VII-RICH PROTHROMBIN COMPLEX CONCENTRATE
SIR,-Green et al. reported the management of clotting defects caused by liver disease with a factor-vn-rich prothrombin concentrate manufactured by the Oxford 5. 6.
a
Bender, D. A. Biochem. Soc. Trans. 1975, 3, 115. Bender, D. A. ibid. (in the press). 7. Bender, D. A., Pigache, R. M., Gruzelier, J., Hammond, N. Psychol. Med. (in the press). 8. Green, G., Poller, L., Dymock, I. W., Thomson, J. M. Lancet 1975, i, 1311.
NEEDLE BIOPSY AND " BLIND " SUBCUTANEOUS MASTECTOMY FOR BREAST DISEASE
SIR,-Mr Watts (July 19, p. 130) commented on the usefulness of a punch needle biopsy providing histological material for the diagnosis of breast cancer, and added that negative histological results may be obtained in small tumours. For nearly three years in Cardiff the’Tru-cut’ needle has been used routinely as a method of obtaining a 9. 10.
Göbel, U., Petrich, C. Mschr. Kinderheilk. 1974, 122, 60. Jakobsen, E., Godal, H. C., Kierulf, P. Acta med. scand. 1975, 197,
11.
Mayne, E. E. Personal communication.
19.
.
An important advantage of this said to be the lack of evidence of disseminated intravascular coagulation, compared with other
Haemophilia Centre. concentrate was concentrates.
To
assess
the advantage of this
concentrate
it would be
important to know the quantities of administered concenFurthertrate expressed as units of coagulation activity. believe that the simultaneous administration of heparin very important factor in the good compatibility. In our own investigation, using commercially available factor-vil-rich concentrates, disseminated intravascular coagulation could be controlled in every case by heparin.99 Therefore we believe that a clear advantage of the concentrate has not been proved, but the combined use of heparin should be emphasised.
more,
we
is
of a tracer amount of 3H-tryptophan 6 minutes before death (see accompanying table). The methods used have been described elsewhere.5,r, These observations provide support for the view of Curzon et al. that it is the concentration of freely diffusible tryptophan rather than the total-serum-tryptophan concentration that is important in controlling tryptophan uptake into the brain. Following a single dose of chlorpromazine, the rate of tryptophan uptake increased, despite a fall in the serum-total-tryptophan concentration; this was presumably due to the increase in the proportion of tryptophan that was freely diffusible rather than bound to albumin. However, the results shown here also support the view of Munro et awl. that the concentrations of competing aminoacids are also important. This is especially clear after 11 days repeated administration of the drug; serum-tryptophan (both total and diffusible) was normal, while the concentration of serum-total-aminoacids was depressed, and brain tryptophan uptake (and also serotonin synthesis) increased, compared with control animals. It therefore appears that both diffusible tryptophan concentration and the concentrations of competing aminoacids are important as determinants of the rate of tryptophan uptake into the brain, and hence of serotonin synthesis. These observations of serum parameters which can be correlated with brain-serotonin turnover in laboratory animals may be important not only in furthering our understanding of the processes involved in acute liver failure, 3,4 but also in understanding the underlying neurochemistry of some chronic psychiatric disorders. We have shown that in chlorpromazine-treated patients with chronic schizophrenia, serum tryptophan was lower than normal, while total aminoacids were normal. On withdrawal of the drug for 4 weeks, serum diffusible tryptophan rose considerably, and remained raised, while serum-total-aminoacids rose transiently, and soon returned to the initial level. It is tempting to speculate that these changes, which appeared to coincide with changes in behaviour, may also be related to changes in serotonin turnover in the brain, as the animal model would predict. Courtauld Institute of Biochemistry, Middlesex Hospital Medical School, London W1P 5PR.
Universitäts-Kinderklinik
U. GÖBEL H. v. Voss C. PETRICH.
4 Düsseldorf, Moorenstrasse 5, West Germany.
ABNORMAL HÆMOGLOBINS IN SOUTH-EAST STAFFORDSHIRE
SIR,-The letter by Dr Buckley and his colleagues (July 12, p. 82) raises several interesting points: in particular the extraordinarily high incidence of j3-thalassa:mia in their 142 patients of British origin (18%); and their views on genetic counselling. One would like to know the diagnostic criteria involved, and the relationships of those patients resident in Abbots Bromley. It would appear likely that this incidence of p-thalassaemia is due to gene drift ". As to the suggestion that the gene arrived during the Roman invasion, this is an old chestnut which, although appealing, is by no means certain. Admittedly, the occupying Roman forces-who often stayed on as veteran colonists -were drawn from the entire Mediterranean littoral; but the presence of P-thalassaemia in Norway,10 and in Ireland, 11 areas not occupied by the Romans, indicates that some P-thalassaemic mutations may well have arisen de novo in North European populations. After all, marshes in England "
and the low countries were malarious in medixval times. The question of genetic counselling is more vexed; in this hospital we advise that anyone carrying thalassaemia or an abnormal hxmoglobin should get their fiancés or spouses checked regardless of their race of origin. I have yet to experience requests for testing from otherwise healthy couples before their marriage, but should such persons ever request advice I would have thought that a check for hasmoglobinopathies should be included in all screens for all persons. Department of Hæmatology, The London Hospital Medical
College, London E1 2AD.
F. E. BOULTON.
D. A. BENDER.
USE OF HEPARIN IN COMBINATION WITH FACTOR-VII-RICH PROTHROMBIN COMPLEX CONCENTRATE
SIR,-Green et al. reported the management of clotting defects caused by liver disease with a factor-vn-rich prothrombin concentrate manufactured by the Oxford 5. 6.
a
Bender, D. A. Biochem. Soc. Trans. 1975, 3, 115. Bender, D. A. ibid. (in the press). 7. Bender, D. A., Pigache, R. M., Gruzelier, J., Hammond, N. Psychol. Med. (in the press). 8. Green, G., Poller, L., Dymock, I. W., Thomson, J. M. Lancet 1975, i, 1311.
NEEDLE BIOPSY AND " BLIND " SUBCUTANEOUS MASTECTOMY FOR BREAST DISEASE
SIR,-Mr Watts (July 19, p. 130) commented on the usefulness of a punch needle biopsy providing histological material for the diagnosis of breast cancer, and added that negative histological results may be obtained in small tumours. For nearly three years in Cardiff the’Tru-cut’ needle has been used routinely as a method of obtaining a 9. 10.
Göbel, U., Petrich, C. Mschr. Kinderheilk. 1974, 122, 60. Jakobsen, E., Godal, H. C., Kierulf, P. Acta med. scand. 1975, 197,
11.
Mayne, E. E. Personal communication.
19.
.
