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CHROMOSOMES IN DYSTROPHIA MYOTONICA
1225
METHOD OF COLLECTING SPECIMENS OF URINE SIR,-We were interested to read the article, under New Inventions, on collecting specimens of urine from women/ as it corresponds with a method we have used successfully for the past 18 months. We feel that
our
receptacle
advantage of being conportable, since we use a
has the
siderably cheaper and much more pressed aluminium foil container, similar in size to a strawberry box " but without holes, and retailing at about E9 (New Zealand or sterling) per thousand, which can be sterilised by dry heat at 160°C for 1 hour. This fits into a holder shaped to fit over the front edge of any standard lavatory pan, and is destroyed after use. The holder, made from either stainless-steel wire or plasticcovered galvanised-steel rod, together with packs of sterilised containers, can be obtained from Ethicals Ltd., of Auckland, "
New Zealand.2
(2) Smoking a cigarette has no effect. (3) The blood estimations of both the controls and the patients with Buerger’s disease fall on the textbook " line 4 rather than either of Astrup’s lines. "
Cardio-thoracic Department, Christian Medical College and Hospital, Vellore, South India.
CHROMOSOMES IN DYSTROPHIA MYOTONICA SIR,-Dystrophia myotonica is a disease of muscle manifested by delayed muscular relaxation which is aggravated by cold and after rest. It is associated with atrophy of muscles, cataracts, frontal baldness, and
various endocrinopathies, especially gonadal insufficiency. The disease is inherited, and is generally attributed to an autosomal dominant gene. An additional small acrocentric chromosome was found in cells from five of seven individuals with dystrophia myotonica,5 6 but a study of ten patients did not substantiate the finding of one particular supernumery chromosome and disclosed that additional chromosomes were distributed more or less at random.7 Chromosome analysis of peripheral blood leucocytes was performed in our laboratory on 8 adults (twin females and 6 males), each of whom had the typical clinical picture of some
Medical Laboratory, 127, Grafton Road, Auckland, C.3,
P. H. CURTIS.
New Zealand.
HÆMOGLOBIN IN BUERGER’S DISEASE
SIR,-Following Professor Astrup’s preliminary communication3 we tried to repeat his work on the oxygendissociation curve in patients with Buerger’s disease in South India.
dystrophia myotonica (see accompanying table).
heparinised blood was equilibrated at 38°C in an atmosphere of 5% carbon dioxide and 1-2% oxygen in nitrogen. The oxygen content and capacity In
a
70 ml.
glass
JAMES S. MILLEDGE.
tonometer,
CHROMOSOME COUNTS IN DYSTROPHIA MYOTONICA
Of the 393 cells examined, the distribution in each individual such that the degree of aneuploidy could have been expected by chance alone, as indicated by the respective probabilities. The p values were based on a comparison with 3088 cells examined in 69 chromosome analyses of peripheral blood from normal individuals with no known disease, and individuals with disease states in which no chromosomal abnormality was found. P values were calculated by the n1 Aa Bb Cc=probability of specific sample (a, formula case was
i
-
&0.
,;;)
.
oxygen-dissociation curve for patients with Buerger’s disease (triangles, -S after smoking), and controls (circles).
Lower end of
Also shown (from left to right) are the dissociation curves of " " (1) Astrup’s line for Buerger’s patients, (2) a textbook line, and (3) Astrup’s line for normal haemoglobin.
measured by Van Slyke’s manometric apparatus, and the analysed for carbon dioxide and oxygen in a Lloyd-Haldane
were
gas
apparatus. We made single-point estimations on the blood of 8 patients with Buerger’s disease, and in 2 repeated the estimation after they had smoked a cigarette, since Professor Astrup’s addendum suggested that smoking might affect the position of the curve. Blood estimations were made from 9 controls; these were hospital personnel-6 Indians and 3 Europeans. The results
(see accompanying figure) show that: (1) There is no obvious difference between the estimations on the blood of patients with Buerger’s disease and controls. 1. Fitzgerald, T. B. Lancet, 1964, ii, 1158. 2. Curtis, P. H. N.Z. Jl. med. Lab. Technol. 1964, 18, 69. 3. Astrup, P. Lancet, 1964, ii, 1152.
b, c) occurring by chance alone, when A, B, C, are the respective probabilities of modal, hypomodal, and hypermodal counts derived from the compiled cell count data above, the respective frequencies being a, b, c, from a sample of size n, with a+b+c=n and A+B+C=1. Computer methods as an aid in detecting chromosomal mosaicism were used in these calculations.8 28 cells containing 46 chromosomes were karyotyped. Autosomes and sex chromosomes corresponding to the correct phenotypic sex were normal in every cell. The single cell containing 92 chromosomes had a normal tetraploid karyotype. 2 cells containing 47 chromosomes were karyotyped: the extra chromosomes were of the F (19-20) and D (13-15) groups.
Thus, the observed aneuploidy in this series could have been expected by chance alone, and our observations do not support the suggestion that dystrophia myotonica may be associated with a specific additional chromosome. This study was supported in part by United States Public Health Service research grant
no.
CA-07900-02 from the National Cancer
et al. (1904) cited in Handbook of Phys iology; sect. 3, vol. I, Washington, 1964. 5. Fitzgerald, P. H. Lancet, 1962, ii, 456. 6. Fitzgerald, P. H., Caughey, J. E. N.Z. med. J. 1962, 61, 410. 7. Eberle, P., Becker, P. E. Humangenetik, 1964, 1, 92. 8. Jackson, J. F., Pulley, P. E. Unpublished.
4. Bohr
p. 783.
1226 Institute, and Department of Health, Education and Welfare grant 401 from the children’s bureau, Welfare Administration. My thanks are due to Dr. C. L. Brown, Jr., and Dr. R. D. Currier for the no.
opportunity of studying their patients. Department of Preventive Medicine (Medical Genetics), University of Mississippi Medical Center, Jackson, 6, Mississippi, U.S.A.
JOHN F. JACKSON.
XX/XY
MOSAICISM IN MAN SIR,- We wish to suggest another possible mechanism which ought to be contemplated, especially in spon-
taneously
aborted foetuses with chromosome make-up.
an
apparent XX/XY
We recently found such a case in an embryo spontaneously aborted at 12 weeks of age from a woman who had previously had 7 out of 11pregnancies ending in spontaneous abortion. The proportion of XX cells in this conceptus, which was of normal male appearance, was 10% in the blood, 10% in the thymus, and possibly nil in the skin. There was no evidence of a co-twin, and it appeared possible that this situation might have arisen by a breakdown of the placental barrier which allowed colonisation of the embryo by maternal cells leading to XX/XY chimxrism (probably restricted to the hasmopoietic tissue and thymus) and which caused the death of the embryo. Pædiatric Research Unit, Guy’s Hospital Medical School, London, S.E.1.
ANGELA I. TAYLOR PAUL E. POLANI.
CALCIUM AND GLYCINURIA IN OSTEOMALACIA
2. We have investigated twelve children with ordinary rickets: (a) The dose of calcium required to significantly increase the blood-calcium level, and to decrease the phosphaturia, is much higher in the rickets group (8-17 mg. per kg. per hour) than in controls (3-4 mg. per kg. per hour). (b) The curves of oc-aminoacid-nitrogen and phosphorus excretion in the urines are strikingly parallel (see accompanying figure), thus showing a strong positive correlation. (c) The decrease of the aminoaciduria is generalised and not restricted to any particular aminoacid. This effect is more DAY-MEANS DETERMINATIONS IN TWELVE PATIENTS OF K-AMINOACIDNITROGEN/CREATININE AND PHOSPHORUS/CREATININE RATIOS
striking when the calcium is infused with glucose than when it is with sodium chloride (see accompanying table). 3. The alleged relationship between the variations of phosphaturia and aminoaciduria on the one hand, and of secondary hyperparathyroidism on the otherseems very questionable, and will be further discussed in a forthcoming paper.
SIR,-We should like to make a few comments Dr. Dubovsky’s interesting letter (March 13).
on
1. Variations of aminoaciduria with calcium infusion have been found in resistant rickets,! the Toni-Debre-Fanconi syndrome,2 and deficiency rickets.3 8th International Congress of Pædiatrics, Copenhagen, 1956, p. 268. 2. Frézal, J., Lestradet, H., Jacob, P., Lortholary, P. Revue fr. Étud. clin. biol. 1958, 3, 626. 3. De Pra, M., Gandulla, E., Trovini, G. C. Minerva pœdiat. 1962, 14, 164. 1. Royer, P., Lestradet, H., Gilly, R.
Unité de Recherches de Génétique Médicale, Hôpital des Enfants-Malades, Paris, France.
JEAN FRÉZAL JEAN REY MAURICE LAMY.
POSTOPERATIVE ANTICOAGULANTS SIR,-Ishould like to record our recently compiled statistics of the incidence of " postoperative thromboembolism " after major gynxcological operations-a subject discussed by Professor Tinckler (Jan. 9) and Dr. Sevitt (Jan. 23 and April 17). Our material reveals an extremely low mortality from thromboembolism after gynxcological surgery. In the past 4 years 9 months there were at our hospital 3 postoperative deaths in a total of 852 laparotomies in gynaecological patients, whose average age was 40-5 years-an extremely low primary mortality-rate of 0-34%. The 3 who died were 50, 74, and 75 years old-well above the average. The first and third came to necropsy: the first died of bronchopneumonia; and the second died suddenly of possible pulmonary embolism. The third had a large simple cyst of the left ovary removed and died suddenly nine days later of massive pulmonary embolism. This might’have been anticipated since histological examination after surgery revealed a thrombus already present in the ovarian vein, in my opinion a clear example of how the most critical hypercoagulable period-namely, the para-operative period-causes thrombosis at the time of surgery and leads to pulmonary embolism in the postoperative period. It also may explain the high rate of failure with prophylactic preventive anticoagulation by whatever method when administered for the postoperative period only.
Thus, our figures show a confirmed incidence of fatal thromboembolism in major gynaecological surgery of 0-11%. This is notably low when compared with a 1-7% confirmed mortality in major surgery of all types performed during the same period on 2922 individuals (average age 46-5
years).
Department of Pathology, v
a-aminoacid-nitrogen and phosphorus excretion. Each point is the mean of the determination in twelve patients.
Mount Vernon Hospital, Mount Vernon, New York. 4. Keiser, H. R., Gill, J. R., Jr., Invest. 1964, 43, 1073.
J. G. SHARNOFF. Sjœrdsma, A., Bartter, F. C. J. clin.
METHOD OF COLLECTING SPECIMENS OF URINE SIR,-We were interested to read the article, under New Inventions, on collecting specimens of urine from women/ as it corresponds with a method we have used successfully for the past 18 months. We feel that
our
receptacle
advantage of being conportable, since we use a
has the
siderably cheaper and much more pressed aluminium foil container, similar in size to a strawberry box " but without holes, and retailing at about E9 (New Zealand or sterling) per thousand, which can be sterilised by dry heat at 160°C for 1 hour. This fits into a holder shaped to fit over the front edge of any standard lavatory pan, and is destroyed after use. The holder, made from either stainless-steel wire or plasticcovered galvanised-steel rod, together with packs of sterilised containers, can be obtained from Ethicals Ltd., of Auckland, "
New Zealand.2
(2) Smoking a cigarette has no effect. (3) The blood estimations of both the controls and the patients with Buerger’s disease fall on the textbook " line 4 rather than either of Astrup’s lines. "
Cardio-thoracic Department, Christian Medical College and Hospital, Vellore, South India.
CHROMOSOMES IN DYSTROPHIA MYOTONICA SIR,-Dystrophia myotonica is a disease of muscle manifested by delayed muscular relaxation which is aggravated by cold and after rest. It is associated with atrophy of muscles, cataracts, frontal baldness, and
various endocrinopathies, especially gonadal insufficiency. The disease is inherited, and is generally attributed to an autosomal dominant gene. An additional small acrocentric chromosome was found in cells from five of seven individuals with dystrophia myotonica,5 6 but a study of ten patients did not substantiate the finding of one particular supernumery chromosome and disclosed that additional chromosomes were distributed more or less at random.7 Chromosome analysis of peripheral blood leucocytes was performed in our laboratory on 8 adults (twin females and 6 males), each of whom had the typical clinical picture of some
Medical Laboratory, 127, Grafton Road, Auckland, C.3,
P. H. CURTIS.
New Zealand.
HÆMOGLOBIN IN BUERGER’S DISEASE
SIR,-Following Professor Astrup’s preliminary communication3 we tried to repeat his work on the oxygendissociation curve in patients with Buerger’s disease in South India.
dystrophia myotonica (see accompanying table).
heparinised blood was equilibrated at 38°C in an atmosphere of 5% carbon dioxide and 1-2% oxygen in nitrogen. The oxygen content and capacity In
a
70 ml.
glass
JAMES S. MILLEDGE.
tonometer,
CHROMOSOME COUNTS IN DYSTROPHIA MYOTONICA
Of the 393 cells examined, the distribution in each individual such that the degree of aneuploidy could have been expected by chance alone, as indicated by the respective probabilities. The p values were based on a comparison with 3088 cells examined in 69 chromosome analyses of peripheral blood from normal individuals with no known disease, and individuals with disease states in which no chromosomal abnormality was found. P values were calculated by the n1 Aa Bb Cc=probability of specific sample (a, formula case was
i
-
&0.
,;;)
.
oxygen-dissociation curve for patients with Buerger’s disease (triangles, -S after smoking), and controls (circles).
Lower end of
Also shown (from left to right) are the dissociation curves of " " (1) Astrup’s line for Buerger’s patients, (2) a textbook line, and (3) Astrup’s line for normal haemoglobin.
measured by Van Slyke’s manometric apparatus, and the analysed for carbon dioxide and oxygen in a Lloyd-Haldane
were
gas
apparatus. We made single-point estimations on the blood of 8 patients with Buerger’s disease, and in 2 repeated the estimation after they had smoked a cigarette, since Professor Astrup’s addendum suggested that smoking might affect the position of the curve. Blood estimations were made from 9 controls; these were hospital personnel-6 Indians and 3 Europeans. The results
(see accompanying figure) show that: (1) There is no obvious difference between the estimations on the blood of patients with Buerger’s disease and controls. 1. Fitzgerald, T. B. Lancet, 1964, ii, 1158. 2. Curtis, P. H. N.Z. Jl. med. Lab. Technol. 1964, 18, 69. 3. Astrup, P. Lancet, 1964, ii, 1152.
b, c) occurring by chance alone, when A, B, C, are the respective probabilities of modal, hypomodal, and hypermodal counts derived from the compiled cell count data above, the respective frequencies being a, b, c, from a sample of size n, with a+b+c=n and A+B+C=1. Computer methods as an aid in detecting chromosomal mosaicism were used in these calculations.8 28 cells containing 46 chromosomes were karyotyped. Autosomes and sex chromosomes corresponding to the correct phenotypic sex were normal in every cell. The single cell containing 92 chromosomes had a normal tetraploid karyotype. 2 cells containing 47 chromosomes were karyotyped: the extra chromosomes were of the F (19-20) and D (13-15) groups.
Thus, the observed aneuploidy in this series could have been expected by chance alone, and our observations do not support the suggestion that dystrophia myotonica may be associated with a specific additional chromosome. This study was supported in part by United States Public Health Service research grant
no.
CA-07900-02 from the National Cancer
et al. (1904) cited in Handbook of Phys iology; sect. 3, vol. I, Washington, 1964. 5. Fitzgerald, P. H. Lancet, 1962, ii, 456. 6. Fitzgerald, P. H., Caughey, J. E. N.Z. med. J. 1962, 61, 410. 7. Eberle, P., Becker, P. E. Humangenetik, 1964, 1, 92. 8. Jackson, J. F., Pulley, P. E. Unpublished.
4. Bohr
p. 783.
1226 Institute, and Department of Health, Education and Welfare grant 401 from the children’s bureau, Welfare Administration. My thanks are due to Dr. C. L. Brown, Jr., and Dr. R. D. Currier for the no.
opportunity of studying their patients. Department of Preventive Medicine (Medical Genetics), University of Mississippi Medical Center, Jackson, 6, Mississippi, U.S.A.
JOHN F. JACKSON.
XX/XY
MOSAICISM IN MAN SIR,- We wish to suggest another possible mechanism which ought to be contemplated, especially in spon-
taneously
aborted foetuses with chromosome make-up.
an
apparent XX/XY
We recently found such a case in an embryo spontaneously aborted at 12 weeks of age from a woman who had previously had 7 out of 11pregnancies ending in spontaneous abortion. The proportion of XX cells in this conceptus, which was of normal male appearance, was 10% in the blood, 10% in the thymus, and possibly nil in the skin. There was no evidence of a co-twin, and it appeared possible that this situation might have arisen by a breakdown of the placental barrier which allowed colonisation of the embryo by maternal cells leading to XX/XY chimxrism (probably restricted to the hasmopoietic tissue and thymus) and which caused the death of the embryo. Pædiatric Research Unit, Guy’s Hospital Medical School, London, S.E.1.
ANGELA I. TAYLOR PAUL E. POLANI.
CALCIUM AND GLYCINURIA IN OSTEOMALACIA
2. We have investigated twelve children with ordinary rickets: (a) The dose of calcium required to significantly increase the blood-calcium level, and to decrease the phosphaturia, is much higher in the rickets group (8-17 mg. per kg. per hour) than in controls (3-4 mg. per kg. per hour). (b) The curves of oc-aminoacid-nitrogen and phosphorus excretion in the urines are strikingly parallel (see accompanying figure), thus showing a strong positive correlation. (c) The decrease of the aminoaciduria is generalised and not restricted to any particular aminoacid. This effect is more DAY-MEANS DETERMINATIONS IN TWELVE PATIENTS OF K-AMINOACIDNITROGEN/CREATININE AND PHOSPHORUS/CREATININE RATIOS
striking when the calcium is infused with glucose than when it is with sodium chloride (see accompanying table). 3. The alleged relationship between the variations of phosphaturia and aminoaciduria on the one hand, and of secondary hyperparathyroidism on the otherseems very questionable, and will be further discussed in a forthcoming paper.
SIR,-We should like to make a few comments Dr. Dubovsky’s interesting letter (March 13).
on
1. Variations of aminoaciduria with calcium infusion have been found in resistant rickets,! the Toni-Debre-Fanconi syndrome,2 and deficiency rickets.3 8th International Congress of Pædiatrics, Copenhagen, 1956, p. 268. 2. Frézal, J., Lestradet, H., Jacob, P., Lortholary, P. Revue fr. Étud. clin. biol. 1958, 3, 626. 3. De Pra, M., Gandulla, E., Trovini, G. C. Minerva pœdiat. 1962, 14, 164. 1. Royer, P., Lestradet, H., Gilly, R.
Unité de Recherches de Génétique Médicale, Hôpital des Enfants-Malades, Paris, France.
JEAN FRÉZAL JEAN REY MAURICE LAMY.
POSTOPERATIVE ANTICOAGULANTS SIR,-Ishould like to record our recently compiled statistics of the incidence of " postoperative thromboembolism " after major gynxcological operations-a subject discussed by Professor Tinckler (Jan. 9) and Dr. Sevitt (Jan. 23 and April 17). Our material reveals an extremely low mortality from thromboembolism after gynxcological surgery. In the past 4 years 9 months there were at our hospital 3 postoperative deaths in a total of 852 laparotomies in gynaecological patients, whose average age was 40-5 years-an extremely low primary mortality-rate of 0-34%. The 3 who died were 50, 74, and 75 years old-well above the average. The first and third came to necropsy: the first died of bronchopneumonia; and the second died suddenly of possible pulmonary embolism. The third had a large simple cyst of the left ovary removed and died suddenly nine days later of massive pulmonary embolism. This might’have been anticipated since histological examination after surgery revealed a thrombus already present in the ovarian vein, in my opinion a clear example of how the most critical hypercoagulable period-namely, the para-operative period-causes thrombosis at the time of surgery and leads to pulmonary embolism in the postoperative period. It also may explain the high rate of failure with prophylactic preventive anticoagulation by whatever method when administered for the postoperative period only.
Thus, our figures show a confirmed incidence of fatal thromboembolism in major gynaecological surgery of 0-11%. This is notably low when compared with a 1-7% confirmed mortality in major surgery of all types performed during the same period on 2922 individuals (average age 46-5
years).
Department of Pathology, v
a-aminoacid-nitrogen and phosphorus excretion. Each point is the mean of the determination in twelve patients.
Mount Vernon Hospital, Mount Vernon, New York. 4. Keiser, H. R., Gill, J. R., Jr., Invest. 1964, 43, 1073.
J. G. SHARNOFF. Sjœrdsma, A., Bartter, F. C. J. clin.