1090 does not suggest any particular occupational liability of the nose and accessory sinuses in Canada.
to cancer
I wish to thank the Dominion Bureau of Statistics, whose collaboration made this study possible.
Department of Epidemiology and Health, McGill University, Montreal 2.
MICHAEL J. BALL.
IMMUNISATION AGAINST HUMAN TUMOURS SIR,—The article by Professor Wolf and colleagues (Oct. 28, p. 905) prompts us to refer to our studies on the influence of cell-surface modification, by coupling either with bovine plasma albumin (B.S.A.) through bisdiazobenzidine1 or with 4-acetamido4’-isothiocyanatostilbene-2,2’-disulphonic acid (s.1. T .S.), on the immunogenicity of a series of transplanted rat tumours
passaged in syngeneic hosts. Using transplanted rat hepatomas, already shown to possess tumour-specific antigens,3 we found that conjugation with either of these reagents did not abolish the viability of the treated cells, which grew progressively on implantation into normal rats. Conjugated hepatoma cells prevented from growth by y-irradiation (15,000r) induced resistance in normal rats to a subsequent challenge with the same tumour, but the degree of resistance evoked was not much greater than that produced by irradiated unmodified cells. We are now assessing the immunogenicity of modified hepatoma cells more quantitatively by a recently developed immunofluorescent-antibody technique for detecting tumourspecific antibody.44 In tests with carcinogen-induced and spontaneously developing mammary carcinomas deficient in tumour-specific antigens, implantation of irradiated cells modified by coupling with B.S.A. or s.I.T.s. has been ineffective in inducing resistance in treated rats, even though low challenge doses of the order of 103 viable tumour cells were given. Within the limits of these studies it thus seems that cell-surface modification by conjugation with heterologous protein does not enhance the antigenicity of the tumour cells. British Empire Cancer Campaign Research Laboratories, University of Nottingham.
R. W. BALDWIN C. R. BARKER.
PRESYMPTOMATIC WILSON’S DISEASE SIR,-It is good news to hear that Dr. Warnock’s patient, who was diagnosed as a case of Wilson’s disease when he went into hepatic failure at the age of 10 years, is still well after many years of treatment with chelating
agents.Iam, however, little concerned at the statement that he has " two normal children ". It would have been more accurate if Dr. Warnock had said, " He has two children, clinically at present normal, who must be heterozygous for the gene of Wilson’s disease ". But the situation may not be as straightforward as this, for Dr. Warnock says of Newtownards in an earlier publication,’7 " In this small area, with a population of 30,000, everybody is related to everybody else, and the gene-carrier incidence for Wilson’s disease is approximately one in forty". If this is indeed correct then there is a significant chance that this patient has married a carrier for the Wilson’s disease gene and that his children may themselves be homozygous abnormal and will eventually develop Wilson’s disease. It would seem that a detailed study of these children should be carried out by either chemical or, preferably, radiochemical techniques without undue delay. University Department of Investigative J. M. WALSHE. Medicine, Cambridge. a
Czajkowski, N. P., Rosenblatt, M., Cushing, F. R., Vasquez, J., Wolf, P. L. Cancer, N.Y. 1966, 19, 739. 2. Maddy, A. H. Biochim. biophys. Acta, 1964, 88, 390. 3. Baldwin, R. W., Barker, C. R. Int. J. Cancer, 1967, 2, 355. 4. Baldwin, R. W., Barker, C. R. Br. J. Cancer (in the press). 5. Baldwin, R. W., Barker, C. R., Embleton, M. J. Progress in Transplantation. Copenhagen (in the press). 6. Warnock, C. G. Lancet, Nov. 4, 1967, p. 990. 7. Warnock, C. G. in Wilson’s Disease: Some Current Concepts (edited by J. M. Walshe and J. N. Cumings); p. 205. Oxford, 1961. 1.
SEX-RATIO IN KLINEFELTER SIBSHIPS
SIR,-A study by Akesson and Hambertshowed a statistically significant higher frequency of males in the sibships of 73 patients with Klinefelter’s syndrome. The pooled studies by Court Brown et al .2 and Fr0land 3 showed, however, no statistically significant sex difference in Klinefelter sibships (187 brothers and 176 sisters of 107 patients with Klinefelter’s syndrome). Their findings correlate well with our finding of 61 brothers and 57 sisters of 20 patients with Klinefelter’s syndrome and sex chromosomes XXY, the mothers of whom were all over 45 years old. Pooling the Scottish and the two Danish studies, 127 patients with Klinefelter’s syndrome thus had 248 brothers and 233 sisters. This finding does not correlate with the findings of Akesson and Hambert1 or support their hypothesis of repeated non-disjunction. Further studies of the sex-distribution in Klinefelter sibships would, however, be of interest. The Cytogenetic Laboratory, Århus State Hospital, Risskov, Denmark.
JOHANNES NIELSEN.
EMERGENCY TREATMENT OF HYPERCALCÆMIA SIR,-In a review on dialysis treatment of intoxications Maher and Schreiner notedthat hypercalcaemia was best treated by dialysis if conservative treatment had failed to control the state. Successful dialysis treatment has repeatedly been reported.5 Despite the self-evident facts that this treatment causes a loss of calcium from the body and that the decrease of blood-calcium level obtained is of a temporary character only, it is nevertheless surprising that your excellent leading article (Sept. 2, p. 501) does not mention dialysis as an easily accessible measure against a life-threatening condition. The transient effect of dialysis is of special value if the underlying disease state can be immediately corrected after the decrease of the serum-calcium concentration. Surgically correctable hyperparathyroidism is an example of this situation. The following short case-report illustrates the value of dialysis in this category of patients. A housewife of 54 had two parathyroid adenomas, located at the lower thyroid poles, removed in 1953. A preoperative serum-calcium concentration of 15-5 mg. per 100 ml. was decreased to a postoperative value of 10-4 mg. per 100 ml. In the next years the blood-calcium level was fairly stable in the range of 12-13 mg. per 100 ml.; she developed nephrocalcinosis and became hypertensive. A surgical exploration in 1956 failed to demonstrate parathyroid tissue in the neck or in the superior mediastinum. The patient was not seen in the outpatient clinic until May, 1967, when she attended with hypertension, malaise, nausea, and signs of acute pancreatitis. The serum-calcium concentration was 19-6 mg. per 100 ml. Surgical exploration of the neck and the mediastinum was planned; but preoperative reduction of the high serum calcium level was desirable, and the patient was therefore tranferred to this unit from the department of thoracic surgery, Bispebjerg Hospital. Immediately after admission peritoneal dialysis was started, and in the next 63 hours a total of 144 litres of dialysate was used. Initially 92 litres of dialysate with a mean calcium concentration of 6-1 mg. per 100 ml. was used for the dialysis. The patient’s serum-calcium concentration rose from 21-2 to 24-5 mg. per 100 ml. in this period. The dialysis was therefore continued for the next 25 hours with 52 litres of fluid with an average concentration of calcium of 4-1mg. per 100 ml. This caused a removal of 2600 mg. of calcium from the patient, and
1. Åkesson,
H. O., Hambert, G. Lancet, 1966, ii, 106. Brown, W. M., Harnden, D. G., Jacobs, P. A., Maclean, N., Mantle, D. J. Spec. Rep. Ser. med. Res. Coun. 1964, no. 305. 3. Frøland, A. Lancet, 1966, ii, 1365. 4. Maher, J. F., Schreiner, G. E. Trans. Am. Soc. artif. intern. Organs, 1965, 11, 349. 5. Maxwell, M. H., Rockney, R. F., Kleeman, C. R., Twiss, M. R. J. Am. med. Ass., 1959, 170, 917. Boen, S. T. Thesis, University of Amsterdam, 1959, p. 118.
2. Court
1091 the serum-calcium level decreased to 20-5 mg. per 100 ml. Because of the relative ineffectiveness of the treatment, haonodialysis was thereafter performed with a Scribner-Kiil artificial kidney. In a dialysis of 10 hours the serum-level was decreased to 14-0 mg. per 100 ml. immediately, and after the dialysis she was operated upon with the removal of an adenoma from the upper left thyroid pole. The patient tolerated the operation well, and the postoperative serum-calcium concentration was in the range of 11-7-12-6 mg. per 100 ml. A month later the clinical state had again deteriorated, and pronounced hypercalcoemia was again found (16-6-20-7 mg. per 100 ml.). On reoperation a fourth adenoma was removed from the upper right thyroid pole, and the histological diagnosis was, as expected, water-clear hyperplasia. Postoperatively the with developed hypoparathyroidism hypocalca:mia and patient tetany. At present the calcium level is kept normal with calciferol and she receives oral magnesium chloride because of persistent hypomagneswmia. She has been followed as an outpatient for the past 2 months, and the serum-calcium concentration has been kept within the normal range (8-8-10-4 mg. per 100 ml.). I think that this case illustrates the usefulness of dialysis as an emergency procedure for the control of severe hypercalcxmia. I have found hsmodialysis to be the most effective treatment, but peritoneal dialysis may be as effective provided calciumfree dialvsate fluid is used. Nephrological Unit, 3rd Medical Department, Kommunehospitalet,
Copenhagen K.
BENT NIELSEN.
CALCIUM METABOLISM AFTER CASTRATION
SIR,-The excellent paper by Dr. Young and Dr. Nordin (July 15, p. 118) prompts us to report here our own work on the effects of artificial menopause on plasma and urinary calcium and phosphorus. Six women, aged 20-56, before and within 2-10 weeks after castration for breast or uterine cancer were studied while on a constant and controlled diet containing an average of 600 mg. calcium and 900 mg. phosphorus per day. Urine samples were collected over a 24-hour period after a preceding 2-day equilibration to the diet, and blood-samples were taken under anaerobic conditions at the end of the urine collection.
Anaerobic ultrafiltration was performed on fresh plasma by the method of Lavietes1 as modified by Smarsz.2 Calcium in plasma, plasma ultrafiltrate, and nitric-acid and perchloric-acid digest of urine was determined by the method of Bett and Fraser 3; phosphorus in plasma, plasma ultrafiltrate, and urine by the method of Gomori 4 ; and creatinine in plasma and urine by the method of Bonsnes and Taussky.5 The percentage of ultrafiltrable calcium and phosphorus was calculated according to Walser."Tables i and n summarise the results. The mean plasma levels of total calcium (CaT) and ultrafiltrable calcium (CaUF) were 8-78 and 4-94 mg. per 100 ml., respectively, before castration, and rose to 9-73 and 5-62 mg. per 100 ml., respectively, after castration. The differences between the levels in the pre-castration and post-castration for CaT; t=2-24, periods are significant (t=3-57, P<0-01 P < 0-05 for CaUF)’ However, the percentage of ultrafiltrable calcium in both periods agreed closely (the means were 55-6% and 58-5% respectively). The filtered load of calcium (FLca) averaged 4-07 mg. per minute before, and rose to 5-12 mg. per minute after, castration. The difference is significant (t=2-17, P < 0.05). The urinary calcium (UCa) averaged 150 mg. per day before, and rose to 203 mg. per day after, castration. The The tubular difference is significant (r=2-49, P<0-05). reabsorption of calcium (Tca) per 100 ml. glomerular filtrate (G.F.), represented by y, correlated with the level of CaUF, represented by x, according to the regression y=0-95 x +0-11 (r=0=998, p< 0-001). The phosphorus data did not show significant differences between the pre-castration and postcastration periods. Here again, the tubular reabsorption of phosphorus per 100 ml. glomerular filtrate, y, correlated with the level of plasma ultrafiltrable phosphorus, x, according to the regression y=0-89 x -0-10 (r=0-955, p<0-01). These results indicate that: (a) artificial menopause raises both total and ultrafiltrable plasma-calcium levels without change in protein binding, thus supporting the presumption of Dr. Young and Dr. Nordin that increased protein binding of calcium after castration is improbable; (b) hypercalciuria results from the increased filtered load of calcium because of 1. Lavietes, P. H. J. Biol. Chem. 1937, 120, 267. 2. Smarsz, C. Polskie Archwm Med. wewn. 1967, 38, 767. 3. Bett, I. M., Fraser, G. P. Clin. chim. Acta, 1959, 4, 346. 4. Gomori, G. J. Lab. clin. Med. 1942, 27, 955. 5. Bonsnes, R. W., Taussky, H. H. J. biol. Chem. 1945, 158, 581. 6. Walser, M. J. clin. Invest. 1961, 40, 723.
TABLE I-EFFECT OF CASTRATION ON CALCIUM METABOLISM
TABLE II-EFFECT OF CASTRATION ON PHOSPHORUS METABOLISM
Abbreviations
are as
for calcium in table
i.