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GONADAL DYSGENESIS (TURNER'S SYNDROME) WITH MALE PHENOTYPE AND XO CHROMOSOMAL CONSTITUTION
1059
GONADAL DYSGENESIS (TURNER’S SYNDROME) WITH MALE PHENOTYPE AND XO CHROMOSOMAL CONSTITUTION WALTER BLOISE M.D. São Paulo
L. M.
DE
ASSIS
M.D. São Paulo
CASSIO BOTTURA
IRIS FERRARI
M.D. Ribeirão Preto
M.D. Ribeirao Preto
bladder through a short urethra, and the other led to a closed cavity (fig. 2). When the patient underwent plastic surgery, it was verified this cavity communicated with the uterus. No testes could be felt in the labioscrotal folds or in the inguinal regions. A rudimentary uterus was seen on peritoneoscopy and a laparotomy was done for further investigation of the internal genitalia. Near the small left tube was an elongated, almond-
shaped mass 3/8 in. (1 cm.) long, rudimentary testis (figs. 3 and 4).
From the Department of Endocrinology and Metabolic Disorders, Faculty of Medicine, São Paulo, and the Department of Clinical Medicine, Faculty of Medicine, Ribeirão Preto, Brazil
aged 8, the eldest son of young parents, was admitted to the metabolic department on April 5, 1957, because of poor somatic development. A BOY,
Maternal pregnancy and labour had been normal. General condition was fair. Height 3 ft. 9 in. (113 cm.); weight 45-4 lb.
(20-6 kg.); span 3 ft. 7 in. (110 cm.) (fig. 1). Clinical examination revealed malformed external genitalia and some lesser congenital defects-low hair-line and ears, high-arched palate, and a number of neevi. The penis 1-2 in. (3-1 cm.) long, without urethral meatus, was bent ventrally by a web connect" ing the ventral surface to the perineum. Thus the " scrotum appeared to be bifid, a depression with two small meatuses being visible in the midline; one communicated with the
which was histologically a On the right, instead of an ovary, there was connective tissue, as seen in other cases of gonadal dysgenesis with negative chromatin pattern (Epps et al. 1958). 17-ketosteroids (Drekter) 0-8 mg. per 24 hours. Bone age of 7 years; X-ray examination of the skull, no abnormality. Colour-vision normal (Ishihara tests). The nuclear sex in material obtained from the blood, oral smears, and from the skin biopsy was male. In the blood" drumsticks " were found in 500 leucocytes smears, no counted. Chromosomal counts (Bottura and Ferrari 1960) in the 20 bone-marrow specimens examined gave a constant number of 45 chromosomes. In the 13 cells in optimal condition, 4 small acrocentric chromosomes could be positively identified. After pairing (fig. 5), the absence of a second medium-sized chromosome with subcentral centromere (probably an X chromosome) was noted. In view of these facts, the chromosomal constitution of the patient must be XO. The constancy of the number 45 in the chromosomal counts argues against
Fig. 1-Gonadal dysgenesis (Turner’s drome) in a boy aged 8. Fig. 2-The external genitalia. Fig. 3-Embryonic testis.
sYn...
Fig.
4-Testicular tissue showing niertoli cells, some undifferentiated germ cells, and spermatogonia. No later phases can be identified. Scanty and isolated interstitial cells are present. (Haematoxylin and eosin. x 220.)
Fig. 5-Paired chromosomes from bone-marrow specimen, showing of
one
X chromosome.
absence
1060 the possibility of mosaicism concerned.
as
far
as
bone-marrow cells
are
Discussion
XO chromosomal constitution in gonadal dysgenesis with female phenotype was described by Ford et al. (1959). A reasonable assumption from the study of our case is that XO chromosomal constitution is not incompatible with a male phenotype and with the presence of embryonic testis. Further instances of testicular development with a male phenotype without Y chromosome are represented by the XX true hermaphrodites recently
reported (Harnden and Armstrong 1959, Hungerford et al. 1959, de Assis et al. 1960, Ferguson-Smith et al. 1960). Summary We describe a case of gonadal dysgenesis (Turner’s syndrome) in a boy of 8. He had a rudimentary uterus, and an embryonic testis. No ovaries were found. The nuclear sex was male. " Drumsticks " were absent from the leucocytes. Only 45 chromosomes were present in the cells of all (20) bone-marrow specimens examined, and chromosome analysis pointed to the absence of one X chromosome. His phenotype is, therefore, male with an XO chromosomal constitution. REFERENCES
Bottura, C., Ferrari, I. (1960) Nature, Lond. 186, 904. de Assis, L. M., Epps, D. R., Bottura, C., Ferrari, I. (1960) Lancet, ii, 129. Epps, D. R., Guérios, M. F. M., Coelho Neto, A. S., Leon, N., de Assis, L. M., Ulhoa Cintra, A. B. (1958) J. clin. Endocrin. 18, 892. Ferguson-Smith, M. A., Johnston, A. W., Weinberg, A. N. (1960) Lancet, ii, 126. Ford, C. E., Jones, K. W., Polani, P. E., de Almeida, J. C., Briggs, J. H. (1959) ibid. i, 711. Harnden, D. G., Armstrong, C. N. (1959) Brit. med. J. ii, 1287. Hungerford, D. A., Donnelly, A. J., Nowell, P. C., Beck, S. (1959) Amer. J. hum. Genet. 11, 215.
PREMEDICATION WITH ATROPINE BY MOUTH M. C. JOSEPH M.D. Cantab., M.R.C.P., D.C.H. ASSISTANT TO THE DIRECTOR OF THE DEPARTMENT OF CHILD HEALTH
R. M.B.
J. VALE
Lond., M.R.C.P.E., F.F.A. R.C.S. CONSULTANT ANÆSTHETIST
GUY’S HOSPITAL, LONDON, S.E.I IN 1872 Heidenhain demonstrated that the salivary secretion produced by stimulation of the chorda tympani was prevented by atropine, and, in the next year, Ebstein used it therapeutically in a patient with apoplexy. In 1875 Munro reported its use in cats for preventing early cardiac arrest during chloroform anaesthesia, but it was not until after 1890 that the subcutaneous injection of atropine before induction of anaesthesia came into general use in this country. There seems to be no record of the oral administration of atropine before operation, though it is used therapeutically for various conditions. Even when sedative drugs are given by mouth preoperatively, it has still been common practice to inject atropine, though Dr. W. S. McConnell tells us he has used it by mouth effectively. In children it is especially desirable to avoid injections; hence we conducted this trial of the effect of atropine given by mouth. The Trial
All children admitted to the Evelina Hospital, under the surgeon and anaesthetist for tonsillectomy, were included in the trial. When admitted, the day before the same
the child was placed in an " oral " or " subcutaneous " group by random allocation, the anaesthetist being unaware of the grouping. The trial lasted fifteen months, and ended when the anaesthetist ceased to work at this hospital. 240 children were admitted to the trial, but 93 were excluded because a different anaesthetist was working on that occasion or because the data were incomplete. There remained 147 children for study. Their sex, average weights, and ages were:
operation,
Oral.... Subcutaneous..
No. 74 73
Males
and the age-distribution
Age (yr.)
Females 33 34
41 39
Weight (lb.)
65 6-7
49 51
was:
6-8 yr.
3-5 yr.
No. 73 Oral Subcutaneous ..... ...... 74
2117
9-12 yr.
9
4445
11
The average interval between administration of atropine and induction of anxsthesia was 95 and 87 minutes for the oral and subcutaneous groups respectively. During the night before operation the sleeping pulse was measured twice. Next morning, an hour before the expected time of operation, atropine was given-either 0-85 mg. by mouth or 0-64 mg. subcutaneously-with butobarbitone, in a dose of 75 mg. per stone body-weight. The pulse-rate was recorded again just before the child was taken to the operatingtheatre, and the state of consciousness was noted. In the anaesthetic-room the size of the pupils was measured to the nearest millimetre by comparison with a prepared scale, and the reaction to light was noted. All patients were anxsthetised with ether after induction with either ethyl chloride on a Schimmelbusch mask or nitrous oxide and oxygen through a semiopen circuit. The degree of salivation was assessed during induction by inserting a finger into the buccal sulcus; if it was dry or slightly moist, it was recorded as 0, if wet but not dripping off the finger as +, and if copious and stringy as z- +. Additionally, if salivation interfered with induction, it was recorded as + +.
Results
Salivation
The
degree of salivation was:
Oral Subcutaneous ..... ......
No.
0
+
+ +
7473
6368
94
21
Excessive salivation was uncommon in either group, occurring only twice in the oral group and once in the subcutaneous group. There was a little more mild salivation in the oral group than in the subcutaneous group, but the difference was small and not significant at the 5% level.
Pupils The average size of the pupils was identical in the two groups, and the incidence of negative reaction to light was similar: No.
Size
73 Oral Subcutaneous ........ ...... 74
(mm.)
Negative reaction
15 (15’o) (19%)
6-1 6-1
11
Pulse-rate
The response of the No. Oral...... 74 Subcutaneous .... 73
pulse-rate
was:
Before atropine
After atropine
Rise
85 86
107 111
22 25
The mean rate before atropine was similar in both groups, there being a rise of 22 and 25 beats per minute in the oral and subcutaneous groups respectively. Discussion Dose
Unna et al. (1950) have shown that the smallest effective dose of atropine for suppression of salivation in children aged 3-12 years is about 0-007 mg. per kg. body-weight subcutaneously, or three times this dose by mouth. The dose for a 20 kg. child is about a quarter the dose of
GONADAL DYSGENESIS (TURNER’S SYNDROME) WITH MALE PHENOTYPE AND XO CHROMOSOMAL CONSTITUTION WALTER BLOISE M.D. São Paulo
L. M.
DE
ASSIS
M.D. São Paulo
CASSIO BOTTURA
IRIS FERRARI
M.D. Ribeirão Preto
M.D. Ribeirao Preto
bladder through a short urethra, and the other led to a closed cavity (fig. 2). When the patient underwent plastic surgery, it was verified this cavity communicated with the uterus. No testes could be felt in the labioscrotal folds or in the inguinal regions. A rudimentary uterus was seen on peritoneoscopy and a laparotomy was done for further investigation of the internal genitalia. Near the small left tube was an elongated, almond-
shaped mass 3/8 in. (1 cm.) long, rudimentary testis (figs. 3 and 4).
From the Department of Endocrinology and Metabolic Disorders, Faculty of Medicine, São Paulo, and the Department of Clinical Medicine, Faculty of Medicine, Ribeirão Preto, Brazil
aged 8, the eldest son of young parents, was admitted to the metabolic department on April 5, 1957, because of poor somatic development. A BOY,
Maternal pregnancy and labour had been normal. General condition was fair. Height 3 ft. 9 in. (113 cm.); weight 45-4 lb.
(20-6 kg.); span 3 ft. 7 in. (110 cm.) (fig. 1). Clinical examination revealed malformed external genitalia and some lesser congenital defects-low hair-line and ears, high-arched palate, and a number of neevi. The penis 1-2 in. (3-1 cm.) long, without urethral meatus, was bent ventrally by a web connect" ing the ventral surface to the perineum. Thus the " scrotum appeared to be bifid, a depression with two small meatuses being visible in the midline; one communicated with the
which was histologically a On the right, instead of an ovary, there was connective tissue, as seen in other cases of gonadal dysgenesis with negative chromatin pattern (Epps et al. 1958). 17-ketosteroids (Drekter) 0-8 mg. per 24 hours. Bone age of 7 years; X-ray examination of the skull, no abnormality. Colour-vision normal (Ishihara tests). The nuclear sex in material obtained from the blood, oral smears, and from the skin biopsy was male. In the blood" drumsticks " were found in 500 leucocytes smears, no counted. Chromosomal counts (Bottura and Ferrari 1960) in the 20 bone-marrow specimens examined gave a constant number of 45 chromosomes. In the 13 cells in optimal condition, 4 small acrocentric chromosomes could be positively identified. After pairing (fig. 5), the absence of a second medium-sized chromosome with subcentral centromere (probably an X chromosome) was noted. In view of these facts, the chromosomal constitution of the patient must be XO. The constancy of the number 45 in the chromosomal counts argues against
Fig. 1-Gonadal dysgenesis (Turner’s drome) in a boy aged 8. Fig. 2-The external genitalia. Fig. 3-Embryonic testis.
sYn...
Fig.
4-Testicular tissue showing niertoli cells, some undifferentiated germ cells, and spermatogonia. No later phases can be identified. Scanty and isolated interstitial cells are present. (Haematoxylin and eosin. x 220.)
Fig. 5-Paired chromosomes from bone-marrow specimen, showing of
one
X chromosome.
absence
1060 the possibility of mosaicism concerned.
as
far
as
bone-marrow cells
are
Discussion
XO chromosomal constitution in gonadal dysgenesis with female phenotype was described by Ford et al. (1959). A reasonable assumption from the study of our case is that XO chromosomal constitution is not incompatible with a male phenotype and with the presence of embryonic testis. Further instances of testicular development with a male phenotype without Y chromosome are represented by the XX true hermaphrodites recently
reported (Harnden and Armstrong 1959, Hungerford et al. 1959, de Assis et al. 1960, Ferguson-Smith et al. 1960). Summary We describe a case of gonadal dysgenesis (Turner’s syndrome) in a boy of 8. He had a rudimentary uterus, and an embryonic testis. No ovaries were found. The nuclear sex was male. " Drumsticks " were absent from the leucocytes. Only 45 chromosomes were present in the cells of all (20) bone-marrow specimens examined, and chromosome analysis pointed to the absence of one X chromosome. His phenotype is, therefore, male with an XO chromosomal constitution. REFERENCES
Bottura, C., Ferrari, I. (1960) Nature, Lond. 186, 904. de Assis, L. M., Epps, D. R., Bottura, C., Ferrari, I. (1960) Lancet, ii, 129. Epps, D. R., Guérios, M. F. M., Coelho Neto, A. S., Leon, N., de Assis, L. M., Ulhoa Cintra, A. B. (1958) J. clin. Endocrin. 18, 892. Ferguson-Smith, M. A., Johnston, A. W., Weinberg, A. N. (1960) Lancet, ii, 126. Ford, C. E., Jones, K. W., Polani, P. E., de Almeida, J. C., Briggs, J. H. (1959) ibid. i, 711. Harnden, D. G., Armstrong, C. N. (1959) Brit. med. J. ii, 1287. Hungerford, D. A., Donnelly, A. J., Nowell, P. C., Beck, S. (1959) Amer. J. hum. Genet. 11, 215.
PREMEDICATION WITH ATROPINE BY MOUTH M. C. JOSEPH M.D. Cantab., M.R.C.P., D.C.H. ASSISTANT TO THE DIRECTOR OF THE DEPARTMENT OF CHILD HEALTH
R. M.B.
J. VALE
Lond., M.R.C.P.E., F.F.A. R.C.S. CONSULTANT ANÆSTHETIST
GUY’S HOSPITAL, LONDON, S.E.I IN 1872 Heidenhain demonstrated that the salivary secretion produced by stimulation of the chorda tympani was prevented by atropine, and, in the next year, Ebstein used it therapeutically in a patient with apoplexy. In 1875 Munro reported its use in cats for preventing early cardiac arrest during chloroform anaesthesia, but it was not until after 1890 that the subcutaneous injection of atropine before induction of anaesthesia came into general use in this country. There seems to be no record of the oral administration of atropine before operation, though it is used therapeutically for various conditions. Even when sedative drugs are given by mouth preoperatively, it has still been common practice to inject atropine, though Dr. W. S. McConnell tells us he has used it by mouth effectively. In children it is especially desirable to avoid injections; hence we conducted this trial of the effect of atropine given by mouth. The Trial
All children admitted to the Evelina Hospital, under the surgeon and anaesthetist for tonsillectomy, were included in the trial. When admitted, the day before the same
the child was placed in an " oral " or " subcutaneous " group by random allocation, the anaesthetist being unaware of the grouping. The trial lasted fifteen months, and ended when the anaesthetist ceased to work at this hospital. 240 children were admitted to the trial, but 93 were excluded because a different anaesthetist was working on that occasion or because the data were incomplete. There remained 147 children for study. Their sex, average weights, and ages were:
operation,
Oral.... Subcutaneous..
No. 74 73
Males
and the age-distribution
Age (yr.)
Females 33 34
41 39
Weight (lb.)
65 6-7
49 51
was:
6-8 yr.
3-5 yr.
No. 73 Oral Subcutaneous ..... ...... 74
2117
9-12 yr.
9
4445
11
The average interval between administration of atropine and induction of anxsthesia was 95 and 87 minutes for the oral and subcutaneous groups respectively. During the night before operation the sleeping pulse was measured twice. Next morning, an hour before the expected time of operation, atropine was given-either 0-85 mg. by mouth or 0-64 mg. subcutaneously-with butobarbitone, in a dose of 75 mg. per stone body-weight. The pulse-rate was recorded again just before the child was taken to the operatingtheatre, and the state of consciousness was noted. In the anaesthetic-room the size of the pupils was measured to the nearest millimetre by comparison with a prepared scale, and the reaction to light was noted. All patients were anxsthetised with ether after induction with either ethyl chloride on a Schimmelbusch mask or nitrous oxide and oxygen through a semiopen circuit. The degree of salivation was assessed during induction by inserting a finger into the buccal sulcus; if it was dry or slightly moist, it was recorded as 0, if wet but not dripping off the finger as +, and if copious and stringy as z- +. Additionally, if salivation interfered with induction, it was recorded as + +.
Results
Salivation
The
degree of salivation was:
Oral Subcutaneous ..... ......
No.
0
+
+ +
7473
6368
94
21
Excessive salivation was uncommon in either group, occurring only twice in the oral group and once in the subcutaneous group. There was a little more mild salivation in the oral group than in the subcutaneous group, but the difference was small and not significant at the 5% level.
Pupils The average size of the pupils was identical in the two groups, and the incidence of negative reaction to light was similar: No.
Size
73 Oral Subcutaneous ........ ...... 74
(mm.)
Negative reaction
15 (15’o) (19%)
6-1 6-1
11
Pulse-rate
The response of the No. Oral...... 74 Subcutaneous .... 73
pulse-rate
was:
Before atropine
After atropine
Rise
85 86
107 111
22 25
The mean rate before atropine was similar in both groups, there being a rise of 22 and 25 beats per minute in the oral and subcutaneous groups respectively. Discussion Dose
Unna et al. (1950) have shown that the smallest effective dose of atropine for suppression of salivation in children aged 3-12 years is about 0-007 mg. per kg. body-weight subcutaneously, or three times this dose by mouth. The dose for a 20 kg. child is about a quarter the dose of