880 the neurologist’s most important function. Little training is neededto reach the decision that, for example, progressive paraparesis is an indication for investigation in hospital. It is the correct assessment of symptoms, often transient but recurring, without recourse to unnecessary investigations, that requires the expert. Department of Clinical Neurology, University of Oxford, Churchill Hospital, Oxford OX3 7LJ
W. B. MATTHEWS
and transverse colon with a diameter of 13 At laparotomy the caecum and ascending and transverse colons were dilated up to the splenic flexure, and there were multiple large serosal tears and small scattered black patches indicative of impending gangrene. Decompression of the bowel was established via a tube caecostomy after which the patient made a rapid recovery, complicated only by a respiratory infection. When seen 6 months later as an outpatient she was very well, and a barium enema revealed no ab-
tended cm
ascending
(see figure).
normality. WAFIK A. DIMYAN JAMES E. ROBB STUART MACPHERSON
Department of Surgery, Western Infirmary, Glasgow G11 6NT INTESTINAL PSEUDO-OBSTRUCTION
SIR,-BX’e enjoyed your editorial of March 10 on intestinal pseudo-obstruction, but would like to draw attention to the importance of early recognition and treatment of acute colonic pseudo-obstruction. This can be a life-threatening condition because of the danger of perforation which has a reported mortality-rate of 43%.1 Serial straight abdominal X-rays are useful in management because a cascum distended to more than 9-10 cm in diameter is in danger of perforation.2 In these cases treatment by surgical decompression via a tube caecostomy (which could be done under local anaesthesia) is often successful.3 Recently, two cases were successfully managed by colonoscopic decompression, but the potential hazard of air insufflation must be recognised.4 We describe below a case treated by csecal decompression. A 29-year-old obese patient (para 1+2) underwent a lower-segment cæsarean section on Aug. 24, 1978, at 37 weeks for fetal distress. 3 days postoperatively she complained of abdominal pain accompanied by distension. She was passing flatus and had audible bowel sounds. At 6 days postoperatively she had a very distended abdomen which was very tender on palpation, and straight abdominal X-ray films showed an enormously dis-
1.
Gierson, E. D., Storm, F. K., Shaw, W., Coyne, S. K. Br. J. Surg. 1975,
2 3 4.
Lowman, R M, Davis, L. Surg. Gynec. Obstet. 1956, 103, 711. Wanebo, H., Mathewson, C., Conolloy, B. ibid. 1971, 133, 44. Bachulis, B. L, Smith, P. E. Am. J. Surg. 1978, 136, 66.
AMNIOTIC-FLUID ACETYLCHOLINESTERASE AND NEURAL-TUBE DEFECTS
SIR The two papers by Dr Smith, Dr Chubb, and their colleagues in your issue of March 31 prompt us to report our experience of measurement of cholinesterases in amniotic fluid. Without foreknowledge of alpha-fetoprotein levels or clinical outcome, we examined 157 samples from pregnancies of 12-25 weeks duration; the samples had been stored at -20°C. Total cholinesterase activity was determined by a reaction-rate method! and acetylcholinesterase (AChE) activity measured by inhibiting the non-specific cholinesterase with ’Lysivane’ (ethopropazine).2,3 Measurements were made at 30°C.
62, 383.
Cholinesterase
Acetylchotinesterase
Amniotic-fluid cholinesterases. N.T.D. pregnancies are indicated by open circles. The 3 blood-stained samples are arrowed.
The 150 samples not associated with neural-tube defects (N.T.D.) had a mean AChE of 3.7 units/I (s.D. 1.3) with a range of 1 - 4-7-8. The 7 samples from pregnancies affected by open N.T.D. had AChE activities ranging from 8.9 to 15.2 (see
figure). Three bloodstained
specimens
were
excluded from the
com-
putation of total cholinesterase data, and the mean value for the remaining 147 samples was 7.8 u/1 (S.D. 2-6) with a range of 2-4—13-6. Non-specific cholinesterase, calculated by differ1. Ellman, G. L., Courtney, K. D., Andres, V., Featherstone, R. M. Biochem. Pharmac. 1961, 7, 88. 2. Dale, G., Bonham, J. R., Riley, K. W. A., Wagget, J. Clin. chim. Acta, 1977,
77, 407. Abdominal
X-rays showing
colonic distension.
3. Dale, G., Bonham, J. R., Lowdon, P.,
D. J. Lancet, 1979, i, 347.
Wagget, J., Rangecroft, L., Scott,
881 was found to have a mean of 42 (s.D. 17) with a range of 0.7-9.0 u/1. Amniotic fluid from the N.T.D. pregnancies had non-specific cholinesterase activities ranging from 10.6to 35-9. The 3 blood-stained samples were found to have high cholinesterase levels (24.9, 21.1, and 20-2) but AChE within the reference range (7.8, 5.5, and 2 7; see figure). The values for AChE in non-N.T.D. pregnancies by our direct, and quicker, method are almost 50% higher than those of Smith et al. (but fall within the range reported by Chubb et al.). Although we would apply a different cut-off point-9 u/1 rather than the 4.5u/I suggested by Smith et al.-we agree that the assay appears to distinguish between pregnancies complicated by N.T.D. and those not so affected. If blood-stained samples are excluded, the non-specific cholinesterase also seems to distinguish between the two groups. The normal AChE levels in bloodstained samples is no doubt due to the removal by centrifugation of the membrane-bound erythrocyte AChE. Measurement of amniotic-fluid AChE may prove to be very useful in the diagnosis of N.T.D.S. Our enzyme measurement is simple, cheap, and rapid and is readily adaptable to automated analysis. In addition, the enzyme activity does not change x between 12 and 25 weeks gestation (AChE=-0.18x weeks+3.94), and the result may not be greatly affected by contamination with maternal blood. However, until the mechanism of the increase in N.T.D. and the specificity of this finding are established, it would be prudent to use amniotic-fluid AChE to supplement alpha-fetoprotein data rather than to replace them. GORDON DALE Department of Clinical Biochemistry,
ence,
J. R. BONHAM
University of Newcastle upon Tyne, Newcastle upon Tyne
P. LOWDON
Department of Human Genetics, University of Newcastle upon Tyne
D. F. ROBERTS
X-LINKED IMMUNOCOMPETENCE AND EPSTEIN-BARR VIRUS ONCOGENESIS
SIR,-Dr Purtilo and colleagues (Feb. 10, p. 327) suggest that the predominance of males with hepatitis B virus and
hepatocarcinoma
may be due to
"immunoincompetence
in immunocompetence. The conclusion that E.B.v. is an oncogen in Purtilo’s syndrome or in Burkitt lymphoma, however, seems premature. Southwest Biomedical Research Institute and Genetics Center, Tempe, Arizona 85281, U.S.A.
FREDERICK HECHT
CARRIER DETECTION IN DUCHENNE MUSCULAR DYSTROPHY
SIR,-Several workers have suggested’-3 that testing for the carrier
of Duchenne muscular dystrophy is best done on since some carriers have been shown to have creyoung girls, atine kinase (c.K.) levels that are higher at young ages, and therefore discrimination between non-carriers and carriers might be better then. Dr Nicholson and his colleagues (March 31, p. 692) rightly emphasise the importance of control c.K. levels, and we agree with them that c.K.s of young girls are higher than those of adult women; in our study they were considerably higher.3 (This contradicts the results of Satapathy and Skinner2but they used hospital patients as controls who, perhaps, were leading unusually quiet lives.) However, the crucial evidence on "detection" is lacking. Are the young girls at risk who had high c.K. levels really heterozygotes? A "detection-rate" that is equal to the expected proportion of carriers merely means that the false negatives and false positives cancel out. Nicholson et al. assume that there may be none of each among young girls, but it is also possible on present evidence that there are more false positives among them than among older women. In the meantime, in order to give reasonably accurate advice to young girls at risk, we need to know not only the distribution of c.K. levels in appropriately aged controls, but also the distribution in similarly aged heterozygotes. Since the distribution in heterozygotes of similar age is not known, we in Birmingham recommend not giving genetic advice to girls at risk for Duchenne muscular dystrophy until they are aged 18. state
Department of Clinical Genetics, Infant Development Unit, Queen Elizabeth Medical Centre, Birmingham B15 2TG
SARAH BUNDEY J. H. EDWARDS
J. INSLEY
based
X-linked recessive immunoregulatory genes". V. A. McKusick’s catalogue2lists 103 X-linked traits with an asterisk, indicating that their pattern of inheritance is now quite certain. 13 (12.6%) of these 103 X-linked traits are immunological, and these include the following immunodeficiency disorders: agammaglobulinsemia of the Bruton type, severe combined immunodeficiency of the Swiss type, WiskottAldrich syndrome, chronic granulomatous disease due to deficiency of N.A.D.P.H.-oxidase, immunodeficiency with increased IgM, and Purtilo’s X-linked lymphoproliferative immunodeficiency disease. There are, incidentally, no map data indicating the location of any immunocompetency gene on the X chromo-
on mutant
some.
Purtilo proposes that the X-linked lymphoproliferative syndrome’ is "a model for viral induced oncogenesis", the idea
being that Epstein-Barr virus (E.B.v.) is an oncogen. E.B.v. has been generally thought to be the oncogen in Burkitt lymphoma. Burkitt lymphoma can, however, occur without E.B.V. infection. Irrespective of E.B.V. status, Burkitt’s lymphomas have an 8;14 translocation.2,3 The translocation may be more fundamental
the malignant process in Burkitt lymphoma E.B.v. appears at most to be a co-oncogen in Burto
than E.B.V. kttt lymphoma. In summary, X-linked genes 1
3
clearly play
an
important part
Purtilo, D. T, and others. New Engl. J. Med. 1977, 297, 1077. 2 Kaiser-McCaw, B., Epstein, A. L., Kaplan, H. S., Hecht, F. Int. J. Cancer,
1977, 19, 482. Zech, L., Haglund, U., Milsson, K., Klein, G
ibid
1976, 17, 47.
CYCLICAL COMBINATION CHEMOTHERAPY AND GONADAL FUNCTION
SIR,—In their paper of Feb. 10 Dr Chapman and her colleagues noted increased levels of prolactin in 42% of patients, "of whom about a half had an identifiable cause for hyperprolactinaemia." This is misleading in that 10 of these 31 patients did not, in fact, have increased levels of prolactin upon repeat measurement. 3 patients were suspected of having pituitary microadenomas on X-ray of the sella turcica. Thus, prolactin increases in 18 of 21 patients were unexplained. Chapman et al. do not say if these patients were taking psychotropic drugs which have been associated with increased prolactin levels. Division of Oncology, Stanford University Medical Center, Stanford, California 94305, U.S.A.
*** Dr Horning’s letter has been shown whose reply follows.-ED.L.
SANDRA HORNING
to
the Bart’s
workers,
SIR,-None of the patients were on psychotropic or antiemetic medications that could explain the raised levels of pro1. Moser, H Praxis, 1977, 66, 814. 2. Satapathy, R. K., Skinner, R. J. med. Genet. 1979, 16, 49. 3. Bundey, S., Crawley, J. M , Edwards, J. H., Westhead, R 1979, 16, 117.
A. J.
med. Gener.
W. B. MATTHEWS
and transverse colon with a diameter of 13 At laparotomy the caecum and ascending and transverse colons were dilated up to the splenic flexure, and there were multiple large serosal tears and small scattered black patches indicative of impending gangrene. Decompression of the bowel was established via a tube caecostomy after which the patient made a rapid recovery, complicated only by a respiratory infection. When seen 6 months later as an outpatient she was very well, and a barium enema revealed no ab-
tended cm
ascending
(see figure).
normality. WAFIK A. DIMYAN JAMES E. ROBB STUART MACPHERSON
Department of Surgery, Western Infirmary, Glasgow G11 6NT INTESTINAL PSEUDO-OBSTRUCTION
SIR,-BX’e enjoyed your editorial of March 10 on intestinal pseudo-obstruction, but would like to draw attention to the importance of early recognition and treatment of acute colonic pseudo-obstruction. This can be a life-threatening condition because of the danger of perforation which has a reported mortality-rate of 43%.1 Serial straight abdominal X-rays are useful in management because a cascum distended to more than 9-10 cm in diameter is in danger of perforation.2 In these cases treatment by surgical decompression via a tube caecostomy (which could be done under local anaesthesia) is often successful.3 Recently, two cases were successfully managed by colonoscopic decompression, but the potential hazard of air insufflation must be recognised.4 We describe below a case treated by csecal decompression. A 29-year-old obese patient (para 1+2) underwent a lower-segment cæsarean section on Aug. 24, 1978, at 37 weeks for fetal distress. 3 days postoperatively she complained of abdominal pain accompanied by distension. She was passing flatus and had audible bowel sounds. At 6 days postoperatively she had a very distended abdomen which was very tender on palpation, and straight abdominal X-ray films showed an enormously dis-
1.
Gierson, E. D., Storm, F. K., Shaw, W., Coyne, S. K. Br. J. Surg. 1975,
2 3 4.
Lowman, R M, Davis, L. Surg. Gynec. Obstet. 1956, 103, 711. Wanebo, H., Mathewson, C., Conolloy, B. ibid. 1971, 133, 44. Bachulis, B. L, Smith, P. E. Am. J. Surg. 1978, 136, 66.
AMNIOTIC-FLUID ACETYLCHOLINESTERASE AND NEURAL-TUBE DEFECTS
SIR The two papers by Dr Smith, Dr Chubb, and their colleagues in your issue of March 31 prompt us to report our experience of measurement of cholinesterases in amniotic fluid. Without foreknowledge of alpha-fetoprotein levels or clinical outcome, we examined 157 samples from pregnancies of 12-25 weeks duration; the samples had been stored at -20°C. Total cholinesterase activity was determined by a reaction-rate method! and acetylcholinesterase (AChE) activity measured by inhibiting the non-specific cholinesterase with ’Lysivane’ (ethopropazine).2,3 Measurements were made at 30°C.
62, 383.
Cholinesterase
Acetylchotinesterase
Amniotic-fluid cholinesterases. N.T.D. pregnancies are indicated by open circles. The 3 blood-stained samples are arrowed.
The 150 samples not associated with neural-tube defects (N.T.D.) had a mean AChE of 3.7 units/I (s.D. 1.3) with a range of 1 - 4-7-8. The 7 samples from pregnancies affected by open N.T.D. had AChE activities ranging from 8.9 to 15.2 (see
figure). Three bloodstained
specimens
were
excluded from the
com-
putation of total cholinesterase data, and the mean value for the remaining 147 samples was 7.8 u/1 (S.D. 2-6) with a range of 2-4—13-6. Non-specific cholinesterase, calculated by differ1. Ellman, G. L., Courtney, K. D., Andres, V., Featherstone, R. M. Biochem. Pharmac. 1961, 7, 88. 2. Dale, G., Bonham, J. R., Riley, K. W. A., Wagget, J. Clin. chim. Acta, 1977,
77, 407. Abdominal
X-rays showing
colonic distension.
3. Dale, G., Bonham, J. R., Lowdon, P.,
D. J. Lancet, 1979, i, 347.
Wagget, J., Rangecroft, L., Scott,
881 was found to have a mean of 42 (s.D. 17) with a range of 0.7-9.0 u/1. Amniotic fluid from the N.T.D. pregnancies had non-specific cholinesterase activities ranging from 10.6to 35-9. The 3 blood-stained samples were found to have high cholinesterase levels (24.9, 21.1, and 20-2) but AChE within the reference range (7.8, 5.5, and 2 7; see figure). The values for AChE in non-N.T.D. pregnancies by our direct, and quicker, method are almost 50% higher than those of Smith et al. (but fall within the range reported by Chubb et al.). Although we would apply a different cut-off point-9 u/1 rather than the 4.5u/I suggested by Smith et al.-we agree that the assay appears to distinguish between pregnancies complicated by N.T.D. and those not so affected. If blood-stained samples are excluded, the non-specific cholinesterase also seems to distinguish between the two groups. The normal AChE levels in bloodstained samples is no doubt due to the removal by centrifugation of the membrane-bound erythrocyte AChE. Measurement of amniotic-fluid AChE may prove to be very useful in the diagnosis of N.T.D.S. Our enzyme measurement is simple, cheap, and rapid and is readily adaptable to automated analysis. In addition, the enzyme activity does not change x between 12 and 25 weeks gestation (AChE=-0.18x weeks+3.94), and the result may not be greatly affected by contamination with maternal blood. However, until the mechanism of the increase in N.T.D. and the specificity of this finding are established, it would be prudent to use amniotic-fluid AChE to supplement alpha-fetoprotein data rather than to replace them. GORDON DALE Department of Clinical Biochemistry,
ence,
J. R. BONHAM
University of Newcastle upon Tyne, Newcastle upon Tyne
P. LOWDON
Department of Human Genetics, University of Newcastle upon Tyne
D. F. ROBERTS
X-LINKED IMMUNOCOMPETENCE AND EPSTEIN-BARR VIRUS ONCOGENESIS
SIR,-Dr Purtilo and colleagues (Feb. 10, p. 327) suggest that the predominance of males with hepatitis B virus and
hepatocarcinoma
may be due to
"immunoincompetence
in immunocompetence. The conclusion that E.B.v. is an oncogen in Purtilo’s syndrome or in Burkitt lymphoma, however, seems premature. Southwest Biomedical Research Institute and Genetics Center, Tempe, Arizona 85281, U.S.A.
FREDERICK HECHT
CARRIER DETECTION IN DUCHENNE MUSCULAR DYSTROPHY
SIR,-Several workers have suggested’-3 that testing for the carrier
of Duchenne muscular dystrophy is best done on since some carriers have been shown to have creyoung girls, atine kinase (c.K.) levels that are higher at young ages, and therefore discrimination between non-carriers and carriers might be better then. Dr Nicholson and his colleagues (March 31, p. 692) rightly emphasise the importance of control c.K. levels, and we agree with them that c.K.s of young girls are higher than those of adult women; in our study they were considerably higher.3 (This contradicts the results of Satapathy and Skinner2but they used hospital patients as controls who, perhaps, were leading unusually quiet lives.) However, the crucial evidence on "detection" is lacking. Are the young girls at risk who had high c.K. levels really heterozygotes? A "detection-rate" that is equal to the expected proportion of carriers merely means that the false negatives and false positives cancel out. Nicholson et al. assume that there may be none of each among young girls, but it is also possible on present evidence that there are more false positives among them than among older women. In the meantime, in order to give reasonably accurate advice to young girls at risk, we need to know not only the distribution of c.K. levels in appropriately aged controls, but also the distribution in similarly aged heterozygotes. Since the distribution in heterozygotes of similar age is not known, we in Birmingham recommend not giving genetic advice to girls at risk for Duchenne muscular dystrophy until they are aged 18. state
Department of Clinical Genetics, Infant Development Unit, Queen Elizabeth Medical Centre, Birmingham B15 2TG
SARAH BUNDEY J. H. EDWARDS
J. INSLEY
based
X-linked recessive immunoregulatory genes". V. A. McKusick’s catalogue2lists 103 X-linked traits with an asterisk, indicating that their pattern of inheritance is now quite certain. 13 (12.6%) of these 103 X-linked traits are immunological, and these include the following immunodeficiency disorders: agammaglobulinsemia of the Bruton type, severe combined immunodeficiency of the Swiss type, WiskottAldrich syndrome, chronic granulomatous disease due to deficiency of N.A.D.P.H.-oxidase, immunodeficiency with increased IgM, and Purtilo’s X-linked lymphoproliferative immunodeficiency disease. There are, incidentally, no map data indicating the location of any immunocompetency gene on the X chromo-
on mutant
some.
Purtilo proposes that the X-linked lymphoproliferative syndrome’ is "a model for viral induced oncogenesis", the idea
being that Epstein-Barr virus (E.B.v.) is an oncogen. E.B.v. has been generally thought to be the oncogen in Burkitt lymphoma. Burkitt lymphoma can, however, occur without E.B.V. infection. Irrespective of E.B.V. status, Burkitt’s lymphomas have an 8;14 translocation.2,3 The translocation may be more fundamental
the malignant process in Burkitt lymphoma E.B.v. appears at most to be a co-oncogen in Burto
than E.B.V. kttt lymphoma. In summary, X-linked genes 1
3
clearly play
an
important part
Purtilo, D. T, and others. New Engl. J. Med. 1977, 297, 1077. 2 Kaiser-McCaw, B., Epstein, A. L., Kaplan, H. S., Hecht, F. Int. J. Cancer,
1977, 19, 482. Zech, L., Haglund, U., Milsson, K., Klein, G
ibid
1976, 17, 47.
CYCLICAL COMBINATION CHEMOTHERAPY AND GONADAL FUNCTION
SIR,—In their paper of Feb. 10 Dr Chapman and her colleagues noted increased levels of prolactin in 42% of patients, "of whom about a half had an identifiable cause for hyperprolactinaemia." This is misleading in that 10 of these 31 patients did not, in fact, have increased levels of prolactin upon repeat measurement. 3 patients were suspected of having pituitary microadenomas on X-ray of the sella turcica. Thus, prolactin increases in 18 of 21 patients were unexplained. Chapman et al. do not say if these patients were taking psychotropic drugs which have been associated with increased prolactin levels. Division of Oncology, Stanford University Medical Center, Stanford, California 94305, U.S.A.
*** Dr Horning’s letter has been shown whose reply follows.-ED.L.
SANDRA HORNING
to
the Bart’s
workers,
SIR,-None of the patients were on psychotropic or antiemetic medications that could explain the raised levels of pro1. Moser, H Praxis, 1977, 66, 814. 2. Satapathy, R. K., Skinner, R. J. med. Genet. 1979, 16, 49. 3. Bundey, S., Crawley, J. M , Edwards, J. H., Westhead, R 1979, 16, 117.
A. J.
med. Gener.
