854 PHENYLALANINE HYDROXYLASE ACTIVITY IN HUMAN TERM

PLACENTA*

Average of five separate experiments. f % of tyrosine is based on the counts recovered by the total radioactivity recovered.

as

tyrosine

divided

Technicon aminoacid analyser. Phenylalanine and tyrosine were separated, and the radioactivity in each fraction was measured (see table). Over 60% of the total radioactivity recovered was in the tyrosine fraction. In control experiments boiled slices of placenta were incubated with L-14C-phenylalanine ; no conversion to tyrosine was detected. These findings indicate that the placenta may be a useful tool for the study of phenylalanine hydroxylase in the various forms of phenylketonuria. Determination of phenylalaninehydroxylase activity at birth may also be used for early diagnosis of phenylketonuria. We are now studying placentas from early pregnancies to see if activity of phenylalanine hydroxylase can be demonstrated and thus used, by placental biopsy, for antenatal detection of phenylketonuria. on a

This work was 2-44-39-66-317.

supported by the

Section of Genetics,

Department of Pediatrics, University of Illinois Medical Center, Chicago, Illinois 60612, U.S.A.

National Foundation grant

REUBEN MATALON PARVIN JUSTICE MINERVA NORELLA DEANCHING

EPIPHYSEAL CARTILAGE CHEMISTRY IN THANATOPHORIC DWARFISM

SiR,—Thanatophohc dwarfism is a congenital chondrodystrophy characterised by short extremities, narrow thorax, a trunk of normal length, and a relatively large head.’ This condition was first described by Maroteaux et al. who coined the term "thanatophoric" from the Greek for "death carrying". Respiratory distress is common, and affected infants usually die soon after birth. Chondro-osseous histopathology in thanatophoric dwarfism is characterised by normal-appearing resting cartilage with a generalised disruption of endochondral ossification.-’ The growth plate shows no sign of cellular column formation, chondrocyte evolution is disoriented, and cartilage may be calcified. Rimoin4 concluded that the hallmark of thanatophoric dwarfism is a general breakdown of endochondral ossification quite distinct from that seen in other forms of chondrodysplasia. Sewell and Pennock’ have reported on the chemical constitution of lower-femoral epiphyseal cartilage from infants who died in the first 4 weeks of life and in whom a skeletal abnormality did not contribute to death. We record here our findings on cartilage from a patient with thanatophoric dwarfism. ’I’he patient was classified as a thanatophoric dwarf by J. W. S. at the Mainz Bone Dysplasia Registry. Cartilage from the left lower-femoral epiphysis was stored at -20°C until analysed.3 1.

Fruchter,

CARTILAGE ANALYSIS IN A CASE OF THANATOPHORIC DWARFISM

j

Z.

Progr. pœdiat. Radiol. 1973, 4, 125. Lamy, M., Robert, J.-M. Press méd, 1967, 75, 2519. L., McAlister, W. H., Saldino, R. M., Hall, J. G. Progr. pœdiat.

2. Maroteaux, R.,

3. Rimoin, D. Radiol. 1973, 4, 68. 4. Rimoin, D. L. Adv. hum. Genet. 1975, 5, 1. 5. Sewell, A. C., Pennock, C. A. Clin. chim. Acta, 1976, 68, 123.

*Abnormal result.

Duplicate portions of cartilage powdered costal cartilage was

analysed and a sample of included as a quality control. The table shows that the abnormal cartilage was chemically normal for hydroxyproline, calcium, magnesium, and the galactosamine/glucosamine ratio. However, the total hexosamine and galactosamine results were below and the glucosamine and sialic-acid contents were at the lower limit of the normal range. These results indicate a decrease in the hexosamine content of the epiphyseal cartilage which is largely due to a decrease in galactosamine. This hexosamine is normally present in chondroitin sulphate and glycoproteins, and the reduction observed may reflect abnormal metabolism of these substances in the cartilage matrix; however, we did not have enough material to investigate further. The normal total calcium content implies that there is no quantitative abnormality of calcification, but it does not exclude an abnormality of calcium distribution. Our data suggest that the primary disturbance is one of glycosaminoglycan or glycoprotein metabolism which might affect calcification secondarily. These preliminary observations justify a more detailed biochemical study of cartilage in patients with thanatophoric dwarfism. were

Department of Child Health, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW; and University Kinderklinik, Mainz, West Germany

A. C. SEWELL J. W. SPRANGER C. A. PENNOCK

PARATHYROID ADENOMAS INDUCED BY

RADIATION

SiR,-Dr Triggs and Professor Williams (March 12, p. 593) suggest that some parathyroid adenomas in man may be induced by radiation. To support this interesting hypothesis we present a case of parathyroid adenoma after external irradiation which had histological features strikingly different from all other adenomas in the 500 hyperparathyroids examined in the period 1942-77 at this hospital. A 66-year-old euthyroid woman had symptoms of hypercalcsemia a few months before admission in 1974. She had had external radiation therapy for a diffuse toxic goitre in 1934. At neck surgery two adenomas were removed-in the upper-right position a 9 g, 8 x 4 x3 cm "clear cell adenoma" located in fibrous tissue, and in the upper-left position a 0.3gchief-cell adenoma. Parathyroidectomy lowered the serum-calcium from 3-63—4-15mmol/1 before surgery to 2 71-2. S2 mmo]/t within 24 h. Histopathological features of the large adenoma differed from other adenomas in our material; dilated and tortuous tubules lined with irregular epithelium consisting of clear cells were found (see figure). This fuzzy cell arrangement was accentuated by irregular positions of the nuclei in the cytoplasm. Some nuclear polymorphism and several giant nuclei

855 ’

of

implants after 23-93 days showed atrophy of exocrine tisIn restituted mice islets, almost always of normal appear-

sue.

ance, were seen in

varying numbers.

Difficulties in obtaining human fetal tissues for transplantation in nude mice-because of a new abortion law and altered technique in induction of abortion-prevented us from doing functional studies in the man/nude-mouse system. We hope our results with rat pancreas in the nude mouse will encourage Dr Usadel’s group and others to report on the functional outcome of man/mouse combination. Pathological-antomical Institute, Kommunehospitalet, DK-1399 Copenhagen K, Denmark

K. BUSCHARD

J. RYGAARD

INTERNATIONAL VARIATIONS IN BREAST-CANCER INCIDENCE

Clear-ceff parathyroid

adenoma

with

dilated and tortuous

tubules.

fuzzy cell arrangement (Hxmatoxylin and eosin; x 120.) Note the

and the nuclei

polymorphism.

Department of Pathology, University College Hospital,

JONATHAN

London WC1E 6AU

with large nucleoli were seen in the tumour cells. Mitosis and invasive growth were not observed. The adenoma could have been present at the time of irradiation, and its development might have been independent of the radiotherapy. However, the presence of periadenomatous fibrous tissue and the unique morphological appearance of the adenoma support the assumption that the tumour was induced by radiation. A radiation-induced tumour should be considered when a parathyroid adenoma with this unusual histopathological pattern is found. Departments of Endocrine Surgery and Pathology, University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark

SIR,-Your editorial (March 26, p. 685) on the prevention of cancer states that common cancers in women, such as breast cancer, vary less in incidence than do carcinomas in males. This you ascribe to a lesser exposure of females to chemical carcinogens. The frequency of carcinoma of the breast varies tenfold, and is unrelated to the state of "civilisation" of the population studied. The epidemiology of breast cancer has been well reviewed by Wynder.I

R. ALBRECHTSEN E. BRUUN E. HASNER J. VISFELDT

FUNCTIONAL STUDIES OF PANCREAS HETEROGRAFTS IN NUDE MICE

SIR,-Dr Usadel and his colleagues (Feb. 12, p. 365) describe the heterotransplantation of human fetal pancreas in nude mice. Immunohistological examination revealed numerous cells containing insulin and glucagon in the epithelium of the ductulus and the islets, but no functional tests were reported. In a continuation of our work’ on the transplantation of human fetal organs, including pancreas, in nude mice we did functional studies of pancreatic heterografts in nude mice with streptozotocin-induced diabetes mellitus.23 We used pancreatic grafts from newborn rats. Subcutaneous transplantation of one whole pancreas led to restoration of function in 1 out of 9 diabetic nude mice. 3 out of 6 nude mice were restituted by two or three grafts. The criterion for return of function was a normal blood-sugar. Histological examination

SPIRONOLACTONE IN ACUTE MOUNTAIN SICKNESS

SIR,-In view of the paper

on acute

mountain sickness

(A.M.S.) by Hackett et al.2 we thought it useful to record our experience with spironolactone as prophylaxis against this condition. Our attention was drawn to the use of this drug by an uncontrolled trial in the Himalayas.3 15 people, aged 12 to 35 years, climbing Kilimanjaro in Tanzania, took part in a double-blind trial of spironolactone for prophylaxis against A.M.s. The climbers were non-acclimatised Europeans living at sea level, apart from one member normally residing at an altitude of 2000 m. The ascent was done in stages with nights spent at 2750, 3720, and 4703 m. The summit (5895 m) was reached on the morning of the fourth day. All members started taking spironolactone 25 mg or placebo tablets three times daily from 48 h before reaching 3000 m. 3 climbers dropped out before 3700 m without evidence of A.M.S. and are not included in the results given below. Of the remaining 12, 7 had A.M.S. and 5 did not, according to the criteria of Hackett et al. Of the 6 on spironolactone 2 got A.M. S. compared with 5 of the 6 on placebo. All retinas were examined daily, and the only abnormal finding was retinal venous congestion in one subject, who was on placebo and had A.M.S. with severe headache and vomiting. No member of the party spent more than 20 h above 4500m. The numbers in this study are small, but our results suggest that spironolactone is of benefit in the prevention of A.M.S. A larger study is necessary to confirm this finding and to compare this drug with acetazolamide. G. V. BROWN Faculty of Medicine, W. A. LISTON University of Tanzania, D. S. K. BROOKFIELD Dar Es Salaam, Tanzania

1.

1. Povlsen, C. O., Skakkebæk, N. E., Rygaard, J., Jensen, G. Nature, 1974, 248, 247. 2. Buschard, K., Rygaard, J. Acta endocr. 1976, suppl. 203, p. 13. 3 Buschard, K., Rygaard, J. Acta path. microbiol. scand. C, 1976, 84, 221.

WAXMAN

Wynder,

E. L. in

posium

Prognostic

Factors in Breast Cancer: First Tenovus

Sym-

(edited by A. P. M. Forrest and P. B. Kunkler); p. 32. Edinburgh,

1968. 2. Hackett, P. H., Rennie, D., Levine, H. D. Lancet, 1976, 3. Currie, T. T., and others, Med. J. Aust. 1976, ii, 168.

ii, 1149.

Parathyroid adenomas induced by radiation.

854 PHENYLALANINE HYDROXYLASE ACTIVITY IN HUMAN TERM PLACENTA* Average of five separate experiments. f % of tyrosine is based on the counts recovere...
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