CALCITONIN AND OSTEOGENIC SARCOMA

887 and

Illustration

Service, Addenbrooke’s Hospital, for the

photograph. Radiotherapeutic Centre, Addenbrooke’s Hospital,

Cambridge.

J. S. MITCHELL.

ZINC DEFICIENCY IN MAN

SIR,-Your editorial of Feb. 10 (p. 299) called attention to the increase in evidence of zinc deficiency in man. I should like to point out a possible additional aspect of this deficiency. We have suggestedthat there may be a relationship between maternal zinc deficiency and congenital malformations of the central nervous system (c.N.s.) in man. Warkany and Petering2 found high rates of C.N.S. malformations in the fetuses of rats fed zinc-deficient diets during pregnancy. The areas of the world where zinc deficiency has been found to be a significant problem, Egypt 3,4 and Iran 5,6 are also areas of high C.N.S.-malformation rates. Alexandria, Egypt, had a rate of 7-88 per 1000 births in the W.H.O. study of Stevenson et al.,’ which placed it second only to Belfast. To our knowledge the only incidence-rates for C.N.S. malformations in Iran are those from Shiraz for anencephalus of 1-6 per 1000 births.8 This rate is exceeded only by 3 of 16 centres in the W.H.O. study 7-Belfast, Alexandria, and Bombay. It is of interest to note that Shiraz is the centre for the Iranian studies of zinc deficiency discussed in your editorial. The evidence9 that zinc deficiency is more widely spread than was previously thought points to the .need for population studies of the possible relationship between zinc deficiency and C.N.S. malformations. The epidemiological data cited above and elsewherepoint in this direction. School of Public Health and

Community Medicine, University of Washington, Seattle, Washington 98105, U.S.A.

LOWELL E. SEVER.

GLOVES, STARCH, AND POVIDONE IODINE SIR,-Your editorial 10 reiterated the hazard of starch granuloma arising from surgical-glove powder, and the excellent dissertation by Prof. Harold Ellis 11 at the 1972 meeting of the Association of Surgeons brought us up to date and showed how starch granules and a peritoneal defect combine to cause postoperative adhesions. My plea 12 for a more satisfactory lubricant has not brought any response from the pharmaceutical industry, but we now have a simple method of demonstrating powder on the outside of a glove. Surgeons who use an alcoholic solution of povidone iodine for skin preparation 13 may test their gloves and the gloves of their assistants by swabbing them with this skin paint. While this test takes no heed of later glove punctures and tears, the absence of the starch-iodine colour reaction does show that the gloves have been properly washed before the Sever, L. E., Emanuel, I. Teratology, 1973, 7, 117. Warkany, J., Petering, H. J. ibid. 1972, 5, 319. Prasad, A. S., Miale, A., Jr., Farid, Z., Sandstead, H. H., Schulert, A. R. J. Lab. clin. Med. 1963, 61, 537. 4. Sandstead, H. H., Prasad, A. S., Schulert, A. R., Farid, Z., Miale, A., Jr., Bassilly, S., Darby, W. J. Am. J. clin. Nutr. 1967, 20, 422. 5. Ronaghy, H. A., Caughey, J. E., Halsted, J. A. ibid. 1968, 21, 488. 6. Halsted, J. A. Trans. Am. clin. Climat. Ass. 1970, 82, 170. 7. Stevenson, A. C., Johnston, H. A., Stewart, M. I. P., Golding, D. R. Bull. Wld Hlth Org. 1966, 34, suppl. 1. 8. Damyanov, I., Dutz, W. Lancet, 1971, i, 82. 9. Hambridge, K. M., Hambridge, C., Jacobs, M., Baum, J. D. Pediat. Res. 1972, 6, 868. 10. Lancet, 1972, ii, 74. 11. Jagelman, D. G., Ellis, H. Br. J. Surg. 1973, 60, 111. 12. McNaught, G. H. D. ibid. 1964, 51, 845. 13. Lilly, H. A., Lowbury, E. J. L. Br. med. J. 1971, iii, 673. 1. 2. 3.

start of the operation. A separate basin should be used for this wash and the water in it may often be seen to be opaline with powder. This suggestion does not solve the long-term problem, but it may have a place as an interim safety measure. The alcoholic solution of povidone iodine is available under various proprietary names.

Department of Surgery, General Hospital, Hartlepool,

G. H. D. MCNAUGHT.

Co. Durham TS24 9AH.

CALCITONIN AND OSTEOGENIC SARCOMA

SIR,-Calcitonin has been used in the management of Paget’s disease of bone for several years, and it is generally agreed that it relieves pain when this is prominent, and z may lead to remodelling of bone to a normal pattern.1,2 sarcoma is not a rare of Osteogenic complication Paget’s disease, and the question arises whether the response to calcitonin in Paget’s disease is matched by any evidence of response in this major complication. Opportunities to treat osteogenic sarcoma with calcitonin in conditions where a firm conclusion can be drawn are likely to be few. We wish, therefore, to report a case of osteogenic sarcoma arising in Paget’s disease of bone, in which treatment with salmon calcitonin had the disease.

no

apparent effect

on

the

course

of

A man aged 72 first presented as an outpatient with a history of constant aching pain in the region of the left hip, of steadily increasing severity, for 6 months. Movement of the joint was restricted by severe pain. Radiography showed extensive Paget’s disease of the left side of the pelvis, the left femur, the lumbar spine, and sacrum. Chest X-ray was negative. The serumalkaline-phosphatase level was as high as 1045 i.u. per 1. On admission 6 weeks later, radiography showed an area of excessive lysis in the neck of the affected femur, and lateral radiographs demonstrated a sponge-like outgrowth of new bone from the posterior aspect of the neck cf the femur, compatible in appearance with an osteogenic sarcoma. Chest X-ray now showed several small metastases, the largest about 15 mm. diameter. Treatment with synthetic salmon calcitonin was begun and the dose was increased gradually to a maximum, after 21 days, of 45 !1-g. twice daily intramuscularly, this dose continuing until shortly before his death, after treatment for a total period of 55 days. A course of deep X-ray therapy was combined with this and given over 15 days to the lesion in the neck of the left femur to assist in pain relief. Cytotoxic drugs were not used at the express wish of the patient. Serum-alkaline-phosphatase levels fell to a minimum of 338 i.u. per 1. 29 days after starting calcitonin therapy, and 21 days after starting deep X-ray therapy. The patient went home 4 weeks after admission almost free of pain, but with radiological evidence of progression of the disease. 6 weeks after admission, and while treatment with calcitonin continued, the largest chest metastasis had grown to 45 mm. diameter. 8 weeks after initial admission he deteriorated rapidly and died of bronchopneumonia. Necropsy confirmed widespread metastatic disease, and the histological diagnosis of

osteogenic

sarcoma.

There is substantial evidence that calcitonin

can

favour-

ably influence Paget’s disease of bone by suppression of pain, when present, by reduction of the serum-alkalinephosphatase concentration, and by modification of radiological and histological appearances towards normal. 1,2 The evidence in this single case, complicated as it is by the use of radiotherapy, would indicate clearly that, under the conditions in which it was used, synthetic salmon calcitonin failed to modify the progress of a rapidly growing osteogenic sarcoma complicating Paget’s disease. It 1. 2.

cannot

be concluded,

however, that this hormone

Woodhouse, N. J. Y., Joplin, G. F., MacIntyre, I., Doyle, F. H. Lancet, 1972, ii, 992. Woodhouse, N. J. Y., Reiner, M., Bordier, P., Kalu, D. N., Fisher, M., Foster, G. V., Joplin, G. F., MacIntyre, I. ibid. 1971, i, 1139.

888 will invariably fail in similar circumstances. When conditions permit, further attempts should be made to assess the value of calcitonin of different types in this lethal

complication. We wish to thank Dr E. R. Evans, medical director of Sandoz for generous supplies of calcitonin.

Products,

Metabolic Unit and University of Edinburgh Department of Medicine, Western General Hospital, Edinburgh EH4 2XU.

I. G. WALTON

J. A. STRONG.

useful information about normal and abnormal functions of the endometrium. We thank Dr H. Henriksson, Department of Pathology, University of Lund, for his valuable help with the histological

BILATERAL LOIN PAIN AFTER ORAL FRUSEMIDE

SiR,—Bilateral loin pain after oral frusemide has, as

I

am

aware,

never

been

as

far

reported before.

A man aged 49 developed heart-failure with atrial fibrillation in 1970. He was treated with digoxin, oral frusemide (40 mg. daily), and potassium supplements, with considerable benefit. However, oedema recurred and the dose of frusemide was doubled and later doubled again, so that he was taking two doses of 80 mg. daily. Shortly after starting this he began to have bilateral loin pain 20 to 30 minutes after taking the frusemide tablets. This pain lasted about three minutes, and ten minutes later he would pass urine at 20-minute intervals for about one hour and then less frequently. He considered the individual volumes of urine passed were not large. He found that with this dose of frusemide he felt much better and was prepared to tolerate the pain and did not want the treatment changed. The loin pain gradually became less frequent as his peripheral oedema increased. After a few months the dose was increased to 120 mg. twice daily, but the loin pain this caused was severe, and the dose was changed to 80 mg. four times a day. On this he had no pain and lost his oedema. The intravenous pyelogram was normal, the urine was free from protein, sugar, casts, and cells, and was sterile on culture. Blood urea and electrolytes were normal. It seems likely that the pain was produced by calyceal dilatation, and it is perhaps surprising that potent diuretics like frusemide do not produce this symptom more often. Luton and Dunstable

Hospital, Luton, Bedfordshire.

The data indicate that there is a middle secretory peak, corresponding with the plasma progesterone peak. No individual correlation between plasma and tissue could be found. Close inspection of the data suggests a peak on day 18, but the number of observations is too small to allow definite conclusions. Change in the normal tissue concentration of progesterone is a composite of several factors, such as corpus luteum function, availability of binding proteins, and rate of metabolism, and might give

B. P. HARROLD.

PROGESTERONE CONCENTRATION IN HUMAN ENDOMETRIUM

SiR,—The progesterone concentration of normal secretory endometrium has not previously been reported. Using a method developed in our laboratory,! we have studied the progesterone concentration in endometrium from 29 women, aged 18-40, who had regular menstrual intervals. Indications for curettage were cervical dysplasia or carcinoma in situ. Part of the endometrium obtained was immediately fixed in formalin, stained with hasmatoxylin and eosin, and classified according to Noyes et al.2 as either belonging to early (days 14-17, E.s.), middle (days 18-23, M.S.), or late (days 24-28, L.s.) secretory phase. The remaining tissue, usually 0-1-0-5 g. was analysed for progesterone. 1/20th of the homogenate was taken for D.N.A. determination as described by Bonting and Jones.3 Progesterone concentration was expressed as ng. per mg. D.N.A. Peripheral blood was drawn for progesterone determination using the method of Johansson.44

classification and Mrs Astrid Persson and Mrs Bodil Nilsson for their skilled technical assistance. The

study

was

supported by the Ford Foundation.

Department of Obstetrics and Gynæcology, University Hospital, Lund, Sweden.

TREATMENT OF VITREOUS HÆMORRHAGE WITH UROKINASE

SIR,-We have reported1 the effect of an intravitreal injection of urokinase in a diabetic patient who had had a vitreous haemorrhage of over 4 years’ duration. The patient’s vision improved from perception of light to 6/36 within a week of the treatment. Dugmore and Raichand2 later described 3 patients treated successfully with 25,000 Ploug units of urokinase in 0-5 ml. of sterile water. We have now treated 4 patients. The first patient, described in our letter, has achieved a further improvement in vision to 6/18 and has maintained this level of visual acuity for 5 months. A diabetic aphakic patient, aged 72, has shown complete resolution of her intravitreal haemorrhage after an injection of 15,000 Ploug units of urokinase in 0-5 ml. of sterile water. Although her present visual acuity is only 6/60, further improvement is expected to follow a needling operation for removal of capsular Our third patient was a woman of 56 with remnants. labile hypertension, who had had recurrent intravitreal hxmorrhages in her right eye for 6 years. These had usually resolved spontaneously, but the most recent episode had occurred 18 months previously and had not cleared. Visual acuity was recorded as perception of light only. 4-6 weeks after an injection of 25,000 Ploug units of urokinase in 0-5 ml. of sterile water her visual acuity had improved to 6/36. 5 months later, her vision was 6/12. Our most recent case was a 38-year-old welder with a post-traumatic intravitreal clot. 6 months after the injury we were still unable to record a red reflex in his left eye, and his visual acuity was perception of light. The patient’s confidence for work and social activities had been undermined mainly because of his monocular state. We decided

to treat

Nilsson, I. Acta obstet. gynec. scand. 1972, 51, 117. Noyes, R. W., Hertig, A. T., Rock, J. Fertil. Steril. 1950, 1, 3. Bonting, S. L., Jones, M. Archs Biochem. Biophys. 1957, 66, 340. Johansson, E. D. B. Acta endocr., Copenh. 1969, 61, 592.

him with

an

intravitreal injection of

15,000 Ploug units of urokinase in 0-5 ml. of sterile

water.

A month later his vision had improved to 6/18, and his peripheral field had returned to such an extent that he was able to resume work. Our initial impression of this form of treatment of vitreous haemorrhage seems to be substantiated by these results. The exact mode of action of urokinase in altered blood clot and its effect (if any) on normal vitreous remain to be determined. Eye Department,

1. 2. 3. 4.

HANS GRUNDSELL INGRID NILSSON STAFFAN NORDQVIST.

Victoria Infirmary, Glasgow S2. 1. 2.

JOHN WILLIAMSON JOHN V. FORRESTER.

Williamson, J., Forrester, J. V. Lancet, 1972, ii, Dugmore, W. N., Raichand, M. ibid. p. 660.

488.