1300
Although segments b, c, and e are present only two-fold, of them, especially segment e, would also be inactivated in female somatic cells. This was proved as follows: some
i. Barr bodies of cells with a long-arm isochromosome (46,XXqi) larger than those of normal cells,6 though the double d segments in the long-arm isochromosome should be identical with the a and d segments together in normal X chromosomes. The extra e segment in the long-arm isochromosome has presumably caused this enlargement of the Barr bodies. ii. Barr bodies of cells with a long-arm deletion (46,XXq-) or with the so-called short-arm isochromosome (46,XXpi) are smaller than normal. are
This inactivation of one segment e in female somatic cells is fit for the fact that both female and male somatic cells have only one active segment e. Segments b and c may be the parts of the X chromosome which would not be inactivated at ’alI,1 It is at least certain that not the whole of segments b and c is genetically active, for the centromeric constitutive heterochromatin of the X chromosome is located in this region. Institut für Humangenetik der Universitat Hamburg, 2 Hamburg 54, Butenfeld 32,
Germany.
JOE-JIE HOO.
ANOTHER TRANSLOCATION RELATED TO THE Ph1 CHROMOSOME
SIR,—The Phi chromosome in chronic myelocytic leukxmia (C.M.L.) has been shown to be due to deletion of a no. 22 chromosome, associated with translocation of the deleted part to the long arm of chromosome 9.14 Exceptions to this translocation, however, have been described. Thus, we reported a Phi-positive case of c.M.L., in which 100% of the bone-marrow cells had a translocation onto
cells were shown on three separate examinations have 46 chromosomes, and they invariably contained a Ph chromosome, resulting from deletion of part of the long arm of chromosome 22 and a translocation of the deleted part to the distal end of the satellites of chromosome 13 at band 13pl3 (see figure). No other chromosomal changes were seen, and the no. 9 chromosomes remained intact. Blood-cells were cultured with phytohsmagglutinin (P.H.A.), and examination revealed a normal 46, XY chromosome constitution, whereas cells cultured without P.H.A. showed the abnormal chromosome 13 and PhI chromosome. In addition to this and the previously reported case," we have also observed complicated translocations in three other patients with PhI-positive C.M.L. in whom deletions of chromosome 22 leading to the formation of PhI chromosomes were associated with complex translocations involving chromosomes 9, 10, and 13. A report on these studies will be published in more detail elsewhere. To date, we have studied 42 cases of Phl-positive c.M.L. with banding techniques and have found 5 cases with translocations which were either different from or more complex than the usual no. 9 translocation seen in C.M.L. The cytological findings, clinical picture, and course in the patients with the unusual PhI translocations seemed not to differ from those of patients with the standard type of 22/9 translocation. These observations suggest that, in C.M.L., deletion of a no. 22 chromosome, resulting in the formation of the PhI chromosome, is more essential than the type of translocation associated with the Ph.
marrow
to
Roswell Park Memorial Institute, Buffalo, New York 14203, U.S.A.
ISAMU HAYATA SURABHI KAKATI AVERY A. SANDBERG.
46,XX/47,XYY MOSAICISM
IN A TRUE
HERMAPHRODITE
SIR,-We wish to true hermaphrodite.
G-banding pattern of chromosomes 9, 13, and 22 in
a marrow-
cell of the
patient described. Deletion of a chromosome 22 results in the PhI, and the
deleted material is translocated onto the short arm of a chromoThe no. 9 chromosomes appear normal. some 13.
the long arm of chromosome 2 (2q+).15 Subsequently, PhI translocations involving chromosomes 17, 19, and 22 have been reported. 16-18 We now wish to report another new translocation, involving chromosome 13. The patient is a 27-year-old White male with C.M.L., whose clinical picture appears not to differ from that of other patients with this disease. All cells were examined after staining with the usual methods and with Q and G banding techniques. Bone14. Rowley, J. Nature, 1973, 243, 290. 15. Hayata, I., Kakati, S., Sandberg, A. A. Lancet, 1973, ii, 1385. 16. Engel, E., McGee, B. J., Flexner, J. M., Russell, M. T., Myers, B. J., New Engl. J. Med. 1974, 291, 154. 17. Gahrton, G., Zech, L., Lindsten, J. Expl Cell Res. 1974, 86, 214. 18. Foerster, W., Medau, H. J., Löffler, H. Klin. Wschr. 1974, 52, 123
report 46,XX/47,XYY mosaicism in a The clinical features of this patient are: eularged phallus, right ovary, and left ovotestis. The predominant cell line in all tissues examined was 46,XX. Mosaicism was most pronounced in the blood, with 36% of the cultured lymphocytes confirmed by quinacrine fluorescence to be 47,XYY. Fibroblasts cultured from tissues obtained from the ovotestis, fallopian tube, and clitoris contained small proportions of the 47,XYY cell line (6-8%). Only the 46,XX cell line was detected in skin fibroblasts. Tissue from the histologically normal ovary was not available for karyotyping. A buccal smear was for Barr bodies. Studies of the red-cell 49% positive of this individual and enzymes, antigens, serum-proteins provide no evidence for chimaerism. This is, to our knowledge, the first individual known to have this unusual sex-chromosome mosaicism. Departments of Pediatrics (Genetics Division) and Obstetrics and Gynecology,MARYLOU BUYSE Los Angeles County-UniversityDIANE FORDNEY-SETTLAGE of Southern California Medical Center, Los Angeles, California 90033, U.S.A.
JOSEPH W. TOWNER MIRIAM G. WILSON.
BOWIE-DICK TEST FOR AUTOCLAVES
SIR,-We agree with Dr Morris and Mr Everall (April 19, p. 923) and others who say that Diack and Vac tubes should be used in addition to (not as a replacement for) the BowieDick test. We also compliment the authors on their ingenious demonstration in which they seal autoclave indicating tape
1301 in ampoules both with and without water. However, it should be pointed out that when the small amount of water (0.5 ml.) is converted to steam and mixed with the air which is also sealed in the tube, a very poor sterilising mixture occurs. While this mixture quickly’changes the markings on the tape, it does not approach the saturated (almost wet) steam required for efficient sterilisation. We submit that while both the glass-tube-type controls and the Bowie-Dick test are useful for pointing out certain types of mechanical malfunction and human error, even the combination of tests does not prove " sterilisation ". There seems to be a tendency in some hospitals to place too much reliance on various devices and too little reliance on adequate training of steriliser operators and thorough maintenance of equipment. An extrapolation of Morris and Everall’s experiment can be used as an excellent training device for autoclave operators. A Diack tube is wrapped in a few layers of cloth, then placed in an ordinary drinking tumbler which is, in turn, placed upright in an ordinary downward displacement steriliser. After processing through a normal cycle, the tube is examined and the pellet found to be unaffected. This illustrates air entrapment even though the top of the tumbler is unsealed. If a small amount of water is added, or if the tumbler is turned on its side before autoclaving, the pellet will melt as it should. This dramatically illustrates the danger of the common error of attempting to sterilise closed containers in an upright position, a frequent mistake. Smith and Underwood Laboratories,
for the local hospitals (8 deaths and 1 other relapse among 14) indicates that although the two groups had similar overall relapse-rates, the death-rate for the special centres was significantly lower than for the others. Given the small numbers, the limited extent of the analysis by outcome, and the discrepancy between the death and other relapse rates, the data as they stand can hardly be said either to strengthen or to weaken the case for centralising the treatment of childhood leukaemia. Regional Cancer Epidemiology Unit, Christie Hospital and Holt Radium Institute,
IAN LECK.
Manchester M20 9BX.
DEANOL IN SPONTANEOUS AND INDUCED DYSKINESIAS SIR,-In the hope of controlling abnormal movements in Huntington’s chorea, the levodopa-induced dyskinesias, and the late dyskinesias provoked by phenothiazines, some authors l,2 have used a presumed precursor of acetylcholine, 2-dimethylaminoethanol (deanol), which crosses the blood-brain barrier. Results with 300-900 mg. daily were so interesting that they prompted us to give the drug to 25 patients with dyskinesias of various kinds. Tablets of 75 mg. of dimethylaminoethanol-p-acetylaminobenzoate were used and the number of tablets was gradually increased from 3 to 12, in three equal doses a day. In the senile
1023 Troy
Court, Troy, Michigan 48084, U.S.A.
EFFECT OF DEANOL ON DYSKINESIAS
ROBERT F. SMITH.
MIXED VENOUS AND ARTERIAL
PCO2
of the rebreathing method SIR,-In on 100 consecutive patients the venoarterial CO2 tension difference was measured on paired venous and arterial blood-samples as reported by Lesh et al.l Results were in close accord with a new formula Paco2=0-8 PvC02 given by McEvoy et al.2 I prefer blood-gas analysis to the rebreathing method. One need only use arm venous blood to obtain a fairly accurate arterial PCo2 value. a
recent assessment
+ improvement. 0 no effect.
25 Lon Derw,
Abergele, Clwyd LL22 7EA.
WALTER LESH.
-
aggravation.
and
MEDICAL CARE OF CHILDHOOD LEUKÆMIA
SIR,-Dr McCarthy’s paper (May 17, p. 1128) comparing the results achieved by special centres and district general hospitals in treating childhood leukaemia is to be welcomed as an attempt to provide objective data of the kind on which the regional planning of cancer services should be based; but he goes beyond the evidence of his data on survival when he concludes that the policy in childhood leukaemia should be " to improve treatment regimens at local hospitals rather than attempt to concentrate care at a few centres ". The one objective finding cited in support of this view was that " the survival of children given optimal regimens at local hospitals was equivalent to thatof two of the three special centres ". However, among the children with acute lymphatic leukaemia in this series (who included all the survivors) only 10 were treated at these two centres; the 10 did not differ significantly in terms of survival or relapse from those treated at the third special centre; and a comparison between the figures for all three centres combined (4 deaths and 13 other relapses among 27 cases) and those 1. Lesh, W., Portwood, W. E., Morrison, J. B. Lancet, 1967, ii, 891. 2. McEvoy, J. D. S., Jones, N. L., Campbell, E. J. M. Br. med. J. 1974, iv, 687.
degenerative (Huntington) dyskinesias, the drug was given only after other therapy had been stopped. Treatment was continued for two weeks after the maximum dose was reached. The results are shown in the accompanying table. Evaluation was carried out at a dosage of 225 mg. per day and at 450-900 mg. per day. Transient improvement was observed in 6 patients; it persisted only in 1 patient. 7 patients became worse (6 with Huntington’s chorea and 1 with tardive dyskinesia); these patients had been previously treated successfully with tetrabenazine, and deterioration with deanol must be considered as a return to the pre-tetrabenazine state. In the 12 cases of levodopa-induced dyskinesias, deanol was a complete failure. Besides certain positive effects, such as an increase in alertness - in 8 patients, unpleasant side-effects were noted: gastrointestinal upset in 4 patients, asthma and tachycardia in 1 patient, and hypomania in 3 patients.
We
were
thus unable
to
confirm the benefits
reported
by other workers.3.4 Service de Neurologie-
Neurochirurgie, Université de Louvain,
Louvain, Belgium. 1. 2. 3. 4.
Walker, J. Miller, E. Miller, E. Casey, D.
E. CHRISTIAN LATERRE ERNEST FORTEMPS.
E., Hoehn, M., Sears, E., Lewis, J. Lancet, 1973, i, 1512. M. Neurology, 1974, 24, 116. M. New Engl. J. Med. 1974, 291, 796. E., Denney, D. ibid. p. 797.
Although segments b, c, and e are present only two-fold, of them, especially segment e, would also be inactivated in female somatic cells. This was proved as follows: some
i. Barr bodies of cells with a long-arm isochromosome (46,XXqi) larger than those of normal cells,6 though the double d segments in the long-arm isochromosome should be identical with the a and d segments together in normal X chromosomes. The extra e segment in the long-arm isochromosome has presumably caused this enlargement of the Barr bodies. ii. Barr bodies of cells with a long-arm deletion (46,XXq-) or with the so-called short-arm isochromosome (46,XXpi) are smaller than normal. are
This inactivation of one segment e in female somatic cells is fit for the fact that both female and male somatic cells have only one active segment e. Segments b and c may be the parts of the X chromosome which would not be inactivated at ’alI,1 It is at least certain that not the whole of segments b and c is genetically active, for the centromeric constitutive heterochromatin of the X chromosome is located in this region. Institut für Humangenetik der Universitat Hamburg, 2 Hamburg 54, Butenfeld 32,
Germany.
JOE-JIE HOO.
ANOTHER TRANSLOCATION RELATED TO THE Ph1 CHROMOSOME
SIR,—The Phi chromosome in chronic myelocytic leukxmia (C.M.L.) has been shown to be due to deletion of a no. 22 chromosome, associated with translocation of the deleted part to the long arm of chromosome 9.14 Exceptions to this translocation, however, have been described. Thus, we reported a Phi-positive case of c.M.L., in which 100% of the bone-marrow cells had a translocation onto
cells were shown on three separate examinations have 46 chromosomes, and they invariably contained a Ph chromosome, resulting from deletion of part of the long arm of chromosome 22 and a translocation of the deleted part to the distal end of the satellites of chromosome 13 at band 13pl3 (see figure). No other chromosomal changes were seen, and the no. 9 chromosomes remained intact. Blood-cells were cultured with phytohsmagglutinin (P.H.A.), and examination revealed a normal 46, XY chromosome constitution, whereas cells cultured without P.H.A. showed the abnormal chromosome 13 and PhI chromosome. In addition to this and the previously reported case," we have also observed complicated translocations in three other patients with PhI-positive C.M.L. in whom deletions of chromosome 22 leading to the formation of PhI chromosomes were associated with complex translocations involving chromosomes 9, 10, and 13. A report on these studies will be published in more detail elsewhere. To date, we have studied 42 cases of Phl-positive c.M.L. with banding techniques and have found 5 cases with translocations which were either different from or more complex than the usual no. 9 translocation seen in C.M.L. The cytological findings, clinical picture, and course in the patients with the unusual PhI translocations seemed not to differ from those of patients with the standard type of 22/9 translocation. These observations suggest that, in C.M.L., deletion of a no. 22 chromosome, resulting in the formation of the PhI chromosome, is more essential than the type of translocation associated with the Ph.
marrow
to
Roswell Park Memorial Institute, Buffalo, New York 14203, U.S.A.
ISAMU HAYATA SURABHI KAKATI AVERY A. SANDBERG.
46,XX/47,XYY MOSAICISM
IN A TRUE
HERMAPHRODITE
SIR,-We wish to true hermaphrodite.
G-banding pattern of chromosomes 9, 13, and 22 in
a marrow-
cell of the
patient described. Deletion of a chromosome 22 results in the PhI, and the
deleted material is translocated onto the short arm of a chromoThe no. 9 chromosomes appear normal. some 13.
the long arm of chromosome 2 (2q+).15 Subsequently, PhI translocations involving chromosomes 17, 19, and 22 have been reported. 16-18 We now wish to report another new translocation, involving chromosome 13. The patient is a 27-year-old White male with C.M.L., whose clinical picture appears not to differ from that of other patients with this disease. All cells were examined after staining with the usual methods and with Q and G banding techniques. Bone14. Rowley, J. Nature, 1973, 243, 290. 15. Hayata, I., Kakati, S., Sandberg, A. A. Lancet, 1973, ii, 1385. 16. Engel, E., McGee, B. J., Flexner, J. M., Russell, M. T., Myers, B. J., New Engl. J. Med. 1974, 291, 154. 17. Gahrton, G., Zech, L., Lindsten, J. Expl Cell Res. 1974, 86, 214. 18. Foerster, W., Medau, H. J., Löffler, H. Klin. Wschr. 1974, 52, 123
report 46,XX/47,XYY mosaicism in a The clinical features of this patient are: eularged phallus, right ovary, and left ovotestis. The predominant cell line in all tissues examined was 46,XX. Mosaicism was most pronounced in the blood, with 36% of the cultured lymphocytes confirmed by quinacrine fluorescence to be 47,XYY. Fibroblasts cultured from tissues obtained from the ovotestis, fallopian tube, and clitoris contained small proportions of the 47,XYY cell line (6-8%). Only the 46,XX cell line was detected in skin fibroblasts. Tissue from the histologically normal ovary was not available for karyotyping. A buccal smear was for Barr bodies. Studies of the red-cell 49% positive of this individual and enzymes, antigens, serum-proteins provide no evidence for chimaerism. This is, to our knowledge, the first individual known to have this unusual sex-chromosome mosaicism. Departments of Pediatrics (Genetics Division) and Obstetrics and Gynecology,MARYLOU BUYSE Los Angeles County-UniversityDIANE FORDNEY-SETTLAGE of Southern California Medical Center, Los Angeles, California 90033, U.S.A.
JOSEPH W. TOWNER MIRIAM G. WILSON.
BOWIE-DICK TEST FOR AUTOCLAVES
SIR,-We agree with Dr Morris and Mr Everall (April 19, p. 923) and others who say that Diack and Vac tubes should be used in addition to (not as a replacement for) the BowieDick test. We also compliment the authors on their ingenious demonstration in which they seal autoclave indicating tape
1301 in ampoules both with and without water. However, it should be pointed out that when the small amount of water (0.5 ml.) is converted to steam and mixed with the air which is also sealed in the tube, a very poor sterilising mixture occurs. While this mixture quickly’changes the markings on the tape, it does not approach the saturated (almost wet) steam required for efficient sterilisation. We submit that while both the glass-tube-type controls and the Bowie-Dick test are useful for pointing out certain types of mechanical malfunction and human error, even the combination of tests does not prove " sterilisation ". There seems to be a tendency in some hospitals to place too much reliance on various devices and too little reliance on adequate training of steriliser operators and thorough maintenance of equipment. An extrapolation of Morris and Everall’s experiment can be used as an excellent training device for autoclave operators. A Diack tube is wrapped in a few layers of cloth, then placed in an ordinary drinking tumbler which is, in turn, placed upright in an ordinary downward displacement steriliser. After processing through a normal cycle, the tube is examined and the pellet found to be unaffected. This illustrates air entrapment even though the top of the tumbler is unsealed. If a small amount of water is added, or if the tumbler is turned on its side before autoclaving, the pellet will melt as it should. This dramatically illustrates the danger of the common error of attempting to sterilise closed containers in an upright position, a frequent mistake. Smith and Underwood Laboratories,
for the local hospitals (8 deaths and 1 other relapse among 14) indicates that although the two groups had similar overall relapse-rates, the death-rate for the special centres was significantly lower than for the others. Given the small numbers, the limited extent of the analysis by outcome, and the discrepancy between the death and other relapse rates, the data as they stand can hardly be said either to strengthen or to weaken the case for centralising the treatment of childhood leukaemia. Regional Cancer Epidemiology Unit, Christie Hospital and Holt Radium Institute,
IAN LECK.
Manchester M20 9BX.
DEANOL IN SPONTANEOUS AND INDUCED DYSKINESIAS SIR,-In the hope of controlling abnormal movements in Huntington’s chorea, the levodopa-induced dyskinesias, and the late dyskinesias provoked by phenothiazines, some authors l,2 have used a presumed precursor of acetylcholine, 2-dimethylaminoethanol (deanol), which crosses the blood-brain barrier. Results with 300-900 mg. daily were so interesting that they prompted us to give the drug to 25 patients with dyskinesias of various kinds. Tablets of 75 mg. of dimethylaminoethanol-p-acetylaminobenzoate were used and the number of tablets was gradually increased from 3 to 12, in three equal doses a day. In the senile
1023 Troy
Court, Troy, Michigan 48084, U.S.A.
EFFECT OF DEANOL ON DYSKINESIAS
ROBERT F. SMITH.
MIXED VENOUS AND ARTERIAL
PCO2
of the rebreathing method SIR,-In on 100 consecutive patients the venoarterial CO2 tension difference was measured on paired venous and arterial blood-samples as reported by Lesh et al.l Results were in close accord with a new formula Paco2=0-8 PvC02 given by McEvoy et al.2 I prefer blood-gas analysis to the rebreathing method. One need only use arm venous blood to obtain a fairly accurate arterial PCo2 value. a
recent assessment
+ improvement. 0 no effect.
25 Lon Derw,
Abergele, Clwyd LL22 7EA.
WALTER LESH.
-
aggravation.
and
MEDICAL CARE OF CHILDHOOD LEUKÆMIA
SIR,-Dr McCarthy’s paper (May 17, p. 1128) comparing the results achieved by special centres and district general hospitals in treating childhood leukaemia is to be welcomed as an attempt to provide objective data of the kind on which the regional planning of cancer services should be based; but he goes beyond the evidence of his data on survival when he concludes that the policy in childhood leukaemia should be " to improve treatment regimens at local hospitals rather than attempt to concentrate care at a few centres ". The one objective finding cited in support of this view was that " the survival of children given optimal regimens at local hospitals was equivalent to thatof two of the three special centres ". However, among the children with acute lymphatic leukaemia in this series (who included all the survivors) only 10 were treated at these two centres; the 10 did not differ significantly in terms of survival or relapse from those treated at the third special centre; and a comparison between the figures for all three centres combined (4 deaths and 13 other relapses among 27 cases) and those 1. Lesh, W., Portwood, W. E., Morrison, J. B. Lancet, 1967, ii, 891. 2. McEvoy, J. D. S., Jones, N. L., Campbell, E. J. M. Br. med. J. 1974, iv, 687.
degenerative (Huntington) dyskinesias, the drug was given only after other therapy had been stopped. Treatment was continued for two weeks after the maximum dose was reached. The results are shown in the accompanying table. Evaluation was carried out at a dosage of 225 mg. per day and at 450-900 mg. per day. Transient improvement was observed in 6 patients; it persisted only in 1 patient. 7 patients became worse (6 with Huntington’s chorea and 1 with tardive dyskinesia); these patients had been previously treated successfully with tetrabenazine, and deterioration with deanol must be considered as a return to the pre-tetrabenazine state. In the 12 cases of levodopa-induced dyskinesias, deanol was a complete failure. Besides certain positive effects, such as an increase in alertness - in 8 patients, unpleasant side-effects were noted: gastrointestinal upset in 4 patients, asthma and tachycardia in 1 patient, and hypomania in 3 patients.
We
were
thus unable
to
confirm the benefits
reported
by other workers.3.4 Service de Neurologie-
Neurochirurgie, Université de Louvain,
Louvain, Belgium. 1. 2. 3. 4.
Walker, J. Miller, E. Miller, E. Casey, D.
E. CHRISTIAN LATERRE ERNEST FORTEMPS.
E., Hoehn, M., Sears, E., Lewis, J. Lancet, 1973, i, 1512. M. Neurology, 1974, 24, 116. M. New Engl. J. Med. 1974, 291, 796. E., Denney, D. ibid. p. 797.
