INTERSTITIAL TESTICULAR OESTROGEN-SECRETING TUMOURS AND CHLOROQUINE

817 used available hospital and physician records. Presumably, NTD cases are much more likely to be noted on such records than are normal sibs so the denominator may be under-reported. Our study does not include sibs who were born before 1967, but this does not represent biased selection. Some of the differences between studies may be due to the fact that the rate of NTDs in Norway is about one-fourth of that in England and Montreal. Fraser proposes that there may be a factor that increases the probability of various fusion defects, which is most often manifested as an association with NTDs because they are the most common and the most environmentally influenced of these defects. If areas with low prevalence ofNTDs represent areas with a lower environmental component in the aetiology,4we would not expect concurrence of these fusion defects to be as readily detectable in Norway as in areas with higher prevalence. Further studies in areas with differing prevalences are warranted before we embark on prenatal diagnosis ofNTDs in pregnancies subsequent to an atresia, as suggested by Fraser. Institute of Preventive Medicine, University of Oslo,

Oslo-4, Norway

GAYLE C. WINDHAM TOR BJERKEDAL

INTERSTITIAL TESTICULAR OESTROGENSECRETING TUMOURS AND CHLOROQUINE

SIR,-Only about 20% of interstitial testicular tumours are oestrogen secreting. During the past year we have studied four patients with such tumours (see table).’ Three of these four patients had been taking chloroquine regularly (100 mg per day). SUMMARY OF FINDINGS IN FOUR CASES OF OESTRADIOL SECRETING TESTICULAR TUMOUR — i —

DEGLYCYRRHIZINATED LIQUORICE FOR PEPTIC ULCER

SIR,-Your Aug. 28 editorial (p. 473) does not mention deglycyrrhizinated liquorice (DGL). As the U.K. suppliers of ’Caved-S’ (containing DGL) we have noted over recent years in journal articles the gradual dismissal of the drug as a treatment of value in peptic ulcer. This has probably been largely due to the advent of histamine H2 receptor antagonists. Even so the downgrading of caved-S in review articles on ulcer therapy seems unwarranted, on scientific and clinical grounds. Several pharmacological studies have demonstrated the significant cytoprotective effect of DGL 1-4 and the reduction of gastric mucosal blood flow(thought to play an important protective role against mucosal injury) in both laboratory animals and man. Similar

’

efficacy of DGL in gastric and duodenal ulcer healing, compared with carbenoxolone, cimetidine, and ranitidine has been demonstrated. 6-8 Morgan et al. found no significant difference, in ulcer recurrence after one year maintenance treatment, between caved-S and cimetidine, in 100 gastric ulcer patients. A further study has shown caved-S 8to be as effective as ranitidine in the healing of duodenal ulcers.8 Other studies have shown DGL not to be superior to placebo when administered as capsules (’Ulcedal’).9, 10 However, the bioavailability of DGL from the capsule formulation is poor 7 and ulcedal has been withdrawn from the market pending reformulation. In 1981 the numbers of patients treated with caved-S in the U.K., exceeded the total treated with carbenoxolone or colloidal bismuth. There has been no significant commercial promotion of caved-S in the past three years. LAURENCE

Tillotts Laboratories, Henlow, Bedfordshire SG 16 6DS

GLICK,

Director

MASTODYNIA

SIR,-In your well-documented editorial (Sept. 11,

p. 590) you that the best treatment for mild to moderately severe breast pain is a careful examination and confident reassurance by an experienced doctor. You also quote Preece and his colleagues who found that one-third of patients with subclinical cancer present with pain. There is no way that the most experienced doctor can exclude subclinical malignancy on clinical examination, and I would suggest that mammography is the only technique competent to identify these cases. It would be a great pity if either reassurance or even hormone therapy were given to patients with breast pain before every effort had been made to exclude malignancy. Certainly in women aged 35 and over, this possibility must be considered; and, even in the younger women, breast cancer is almost as common as invasive cervical cancer.

state

Chloroquine has been and still is widely used in the world and no association with interstitial testicular (or any other) tumour has been reported before. A review of published cases of interstitial testicular oestradiol-secreting tumours might reveal if this type is more frequent in countries where chloroquine use is widespread. Treatment of pituitary and granulosa cells with chloroquine increases the accumulation of cell-associated epidermal growth factor (EGF), and chloroquine also inhibits the mitogenic activity of EGF.2 EGF may inhibit steroidogenesis in testicular cells in primary culture.3If a link between testicular interstitial tumours and chloroquine were to be confirmed it might be worth looking at the interrelations between chloroquine, growth factors, and the steroid microenvironment.

Centre Hospitalier Universitaire, 29200 Brest, France

BERCOVICI SL. KHOURY TH. MAUDELONDE D. TATER

Blood Transfusion Centre, Brest

J-P. SALEUN

Medical Clinic B, Tours

P. GROUSSIN

J.-P. Endocrinology Service,

4. Windham

GC, Sever LE. Neural tube defects among twin births Am JHum Genet (in

press) 1 Bercovici

J-P, Tater D, Khoury SI, et al. Leydig cell tumour with gnecomastia hormonal effects of an estrogen producing tumor J Clin Endocrinol Metab 1981; 53: 1291-96. 2. King AC, Cuatrecasas P. Peptide hormone induced receptor mobility, aggregation and internalization. N Engl J Med 1981; 305: 77-88 3. Hsueh JW, Welish TH, Jones PBC. Inhibition of ovarian testicular steroidogenesis by epidermal growth factor. Endocrinology 1981; 108: 2002-04.

BUPA Medical Centre, Battle Bridge House, 300 Gray’s Inn Road, London WC 1X 8DU

PATRICIA A. LAST

1. Rees

WDW, Rhodes J, Wright JE, Stamford IF, Bennett A. Effect ofdeglycrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol 1979; 14: 605-07. 2. Morris TJ, Calcraft BJ, Rhodes J, Hole D, Morton MS Effect ofa deglycyrrhizinated liquorice compound on the gastric mucosal barrier of the dog Digestion 1974; 11: 355-63 3. Morgan RJ, Nelson LM, Russell RI, Docherty C. The effect of deglycyrrhizinised liquorice on the occurrence of aspirin and aspirin plus bile acid-induced gastric lesions, and aspirin absorption in rats. Gastroenterology 1982; 82: 1134. 4. van Marle J, Aarsen PN, Lind A, van Weeren-Kramer J. Deglycyrrhizinised liquorice and the renewal of rat stomach epithelium. Eur J Pharmacol 1981, 72: 219-25. 5 Johnston BJ, McIsaac RL. The effects of deglycyrrhizinised liquorice and cimetidine on resting gastric mucosal blood flow in man. Br J Pharmacol 1981; 74: 971-72. 6. Morgan AG, et al. Cimetidine: an advantage in gastric ulcer treatment? Br Med J 1978; ii: 1323-26. 7. Morgan AG, et al. Comparison between cimetidine and caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy Gut 1982, 23: 545-51. 8 McAdam WAF, et al. A comparison between ranitidine and caved-S in duodenal ulcer treatment World Congress of Gastroenterology (Stockholm, June, 1982): abstr 9. Feldman H, Gilat T. A trial of deglycyrrhizinated liquorice in the treatment of duodenal ulcer. Gut 1971; 12: 449. 10. Multicentre Trial Treatment of duodenal ulcers with glycyrrhizinic acid-reduced

liquorice. Br Med J 1973, iii:

501.