1047 bodies. Serum iron, vitamin B12, folate, carotene, and calcium were normal, as was a D-xylose-absorption test. A99 run Tc-sulphur-colloid scan showed no significant isotope uptake in the region of the spleen. After initial carbimazole treatment the patient received 5mCi of iodine-131 in July, 1975. Case 3.-A 65-year-old woman with a history of subtotal thyroidectomy for goitre at the age of 17, was referred in December, 1972, for investigation of ansemia and definitive treatment of thyrotoxicosis. A trial fibrillation and thyrotoxicosis first developed in 1968 and was initially controlled with carbimazole. The thyroid remnant was asymmetrical, with enlargement of the thyroid isthmus. A minor degree of lid retraction and exophthalmos was present. There were extensive areas of vitiligo over the trunk and limbs. She was grossly thyrotoxic
(total serum-thyroxine 20. 6p.g/ dl [normal 5. 5-11.5µg/dl]) free-thyroxine index greater than 40, antithyroglobulin-haemagglutination test positive, thyroid-antimicrosomal-antibody test negative, L.A.T.S. negative. The haemaglobin was 7.7g/dl, and a blood-film showed normochromic cells with macrocytosis, poikilocytosis, target cells, numerous Howell-Jolly bodies, and hypersegmented neutrophils. The bone-marrow was megaloblastic, the red-cell folate level was subnormal at 35ng/ml (normal 160-640ng/ml), serum-iron, serum-vitamin B12, and Schilling test were normal. A99’Tc-sulphur-colloid scan showed a normal-sized liver but no significant isotope uptake in the region of the spleen. The hyperthyroidism was treated with iodine-131 (5mCi December, 1972, and 15mCi August, 1974). She had diarrhoea, which persisted after adequate control of the hyperthyroidism. When she was euthyroid investigations confirmed the clinical diagnosis of malabsorption syndrome (faecal fat 33g/day, 2-hour D-xylose plasma 19m9/dl, serum-carotene unrecordably low, small-bowel biopsy showed subtotal villous atrophy. She has presumed coeliac disease but has not adhered consistently to a gluten-free diet. Graves’ disease is believed to be an autoimmune disorder in which hyperthyroidism results from the stimulatory effect of thyroid-stimulating immunoglobulins.3 Abnormalities of cellmediated immunity may also be involved.4 The discovery of splenic atrophy in 3 patients with thyrotoxicosis in a 7-year period from one centre suggests that this association is not rare. The linking of Graves’ disease with splenic atrophy can be taken as further evidence to implicate a failure of immunological surveillance in thyrotoxicosis. This is further supported by the suggestion that the appearance of thyrotoxicosis many years after ’Thorotrast’ administration may be due to the irradiation of the lymphoreticular system and resulting splenic atrophy.5 This proposal and the association of spontaneous splenic atrophy with thyrotoxicosis raises the possibility that splenectomised patients may have an increased risk of later developing thyrotoxicosis. Although we cannot be certain that the splenic atrophy in our 3 patients antedated the development of thyrotoxicosis, studies of thyroid and immunological function in splenectomised patients probably warrant further
investigation. Department of Nuclear Medicine, Christchurch Hospital. Haematology Department,
BEVAN E. W. BROWNLIE
J. W. HAMER
Christchurch Clinical School.
Gastroenterology Department, Christchurch Hospital.
H. B. COOK
Princess Margaret Hospital, Christchurch, New Zealand.
S. M. HAMWOOD
SAFEGUARDS FOR HEALTHY VOLUNTEERS IN DRUG STUDIES
by Dr Smith (Sept. 6, p. Ramsey (Nov. 1, p. 875), while I agree that a volunteer contract is to be regarded as ideal, the use of the present one, suggested by the Stuart Harris committee, has raised problems. It is admirable to think that this contract should be good enough for all volunteers, but I now have three legal opinions SIR,-Following the 449) and Dr Tidd and
comments
Dr
3. Adams, D. D., Fastier, J. B., Howie, J. B., Kennedy, T. H., Kilpatrick, J. A., Stewart, R. D. H. J. clin. Endocr. Metab. 1974, 39, 826. 4. Volpé, R., Fand, N. R., Von Westarp, C., Row, V. V. Clin Endocr. 1974, 5
3, 239. Langlands, A. O., Herman, K. J.
clin. Path.
1967, 20,
892.
which doubt its legal validity. Furthermore, attempts to use it and obtain insurance cover more than doubles proposed costs. I am also concerned about the lack of cover for the investigators, who, if negligent, can call on their membership of the Medical Protection Society or the Medical Defence Union, but, if no negligence exists, could possibly be subject to separate claims without such protection. I should like to see a new volunteer contract drawn up, which may well have to take into account legal liability, but should preferably retain similar provisions for compensation without litigation. It should also, as at present, make provision for legal proceedings in the event of disagreement by the volunteer at this stage, but it would also place any costs incurred on the company concerned. Separate guidelines should also be given providing written indemnification for the investigator against any separate claims. Organon Laboratories Limited, Crown House, London Road, Morden, Surrey SM4 5DZ.
C.
J. MUGGLESTONE
UPPER-GASTROINTESTINAL ENDOSCOPY
SIR,-Dr Salter (Nov. 1, p. 863) makes
a number of importhat endoscopy is over-employed, since enthusiasts. From his own experience, he notes agreement with a double-contrast barium meal in 85-96% of his patients, but offers no breakdown of his data to enable a more detailed assessment to be made. This is similar to early experience from Glasgow’ where disagreement between endoscopy and a routine barium meal was as high as 49%, but much reduced to 16% with double-contrast radiology. The radiologist at Carlisle is an enthusiastic pioneer of the double-contrast barium meal2 and it is likely that if his technique and enthusiasm were applied to all departments of radiology than the need for endoscopy could well be reduced. The need for emergency endoscopy remains however. Endoscopy can visualise the bleeding source in 92% of cases,3 against 46% by radiology. Since the surgeon benefits by prior knowledge of the site of the bleeding lesion and since more rational decisions regarding management of this dangerous condition can be made, it is disappointing that Dr Salter does not offer this service. In the diagnosis of gastric cancer the correct diagnosis can best be achieved only by additional biopsy and cytology (97% diagnosis rate; compared with 59% by radiology and 88% by visual endoscopic opinion only4). Dr Salter also suggests that the ward is a suitable environment for outpatient endoscopies. Even with a comparably light load of 2-3 cases a week (average), this would not find favour among many endoscopists or ward sisters, because of the simple logistical problem of finding empty beds for a few hours--or 2 patients using the same bed. The aim of Dr Salter’s article was to evaluate the role of endoscopy by examining his patients within one month of a barium meal. The workload of 2-3 patients a week being investigated in this way is much lower than the experience of most endoscopists (e.g., Portsmouth, two endoscopists, averaging 16 cases a week). The British Society for Digestive Endoscopy regards it as vital for the efficient running of a unit and care of equipment that it be located in a designated room and that there be an assistant. Although the experience of Dr Salter does well to stress the value of good radiology and the need for close cooperation between clinician and radiologist, the calls upon his service are so much less than most endoscopists and his data are so inadequate that his conclusions cannot be applied universally. D. G. COLIN-JONES Queen Alexandra Hospital, Hon. Secretary, British Society Cosham, for Digestive Endoscopy Portsmouth PO6 3LY.
points. He argues endoscopists are often tant
1. Moule, B. et al. Gut, 1975, 16, 411. 2. Scott-Horden, W. G. Br. J. Radiol 1973, 46, 153. 3 McGinn, F S., et al. Gut, 1975, 16, 707 4. Smithies, A., et al. Br. med. J. 1975, iv, 326 5. Memorandum on Future National Needs for Fibreoptic Gastrointestinal Tract. 1973.
Endoscopy
of the
(total serum-thyroxine 20. 6p.g/ dl [normal 5. 5-11.5µg/dl]) free-thyroxine index greater than 40, antithyroglobulin-haemagglutination test positive, thyroid-antimicrosomal-antibody test negative, L.A.T.S. negative. The haemaglobin was 7.7g/dl, and a blood-film showed normochromic cells with macrocytosis, poikilocytosis, target cells, numerous Howell-Jolly bodies, and hypersegmented neutrophils. The bone-marrow was megaloblastic, the red-cell folate level was subnormal at 35ng/ml (normal 160-640ng/ml), serum-iron, serum-vitamin B12, and Schilling test were normal. A99’Tc-sulphur-colloid scan showed a normal-sized liver but no significant isotope uptake in the region of the spleen. The hyperthyroidism was treated with iodine-131 (5mCi December, 1972, and 15mCi August, 1974). She had diarrhoea, which persisted after adequate control of the hyperthyroidism. When she was euthyroid investigations confirmed the clinical diagnosis of malabsorption syndrome (faecal fat 33g/day, 2-hour D-xylose plasma 19m9/dl, serum-carotene unrecordably low, small-bowel biopsy showed subtotal villous atrophy. She has presumed coeliac disease but has not adhered consistently to a gluten-free diet. Graves’ disease is believed to be an autoimmune disorder in which hyperthyroidism results from the stimulatory effect of thyroid-stimulating immunoglobulins.3 Abnormalities of cellmediated immunity may also be involved.4 The discovery of splenic atrophy in 3 patients with thyrotoxicosis in a 7-year period from one centre suggests that this association is not rare. The linking of Graves’ disease with splenic atrophy can be taken as further evidence to implicate a failure of immunological surveillance in thyrotoxicosis. This is further supported by the suggestion that the appearance of thyrotoxicosis many years after ’Thorotrast’ administration may be due to the irradiation of the lymphoreticular system and resulting splenic atrophy.5 This proposal and the association of spontaneous splenic atrophy with thyrotoxicosis raises the possibility that splenectomised patients may have an increased risk of later developing thyrotoxicosis. Although we cannot be certain that the splenic atrophy in our 3 patients antedated the development of thyrotoxicosis, studies of thyroid and immunological function in splenectomised patients probably warrant further
investigation. Department of Nuclear Medicine, Christchurch Hospital. Haematology Department,
BEVAN E. W. BROWNLIE
J. W. HAMER
Christchurch Clinical School.
Gastroenterology Department, Christchurch Hospital.
H. B. COOK
Princess Margaret Hospital, Christchurch, New Zealand.
S. M. HAMWOOD
SAFEGUARDS FOR HEALTHY VOLUNTEERS IN DRUG STUDIES
by Dr Smith (Sept. 6, p. Ramsey (Nov. 1, p. 875), while I agree that a volunteer contract is to be regarded as ideal, the use of the present one, suggested by the Stuart Harris committee, has raised problems. It is admirable to think that this contract should be good enough for all volunteers, but I now have three legal opinions SIR,-Following the 449) and Dr Tidd and
comments
Dr
3. Adams, D. D., Fastier, J. B., Howie, J. B., Kennedy, T. H., Kilpatrick, J. A., Stewart, R. D. H. J. clin. Endocr. Metab. 1974, 39, 826. 4. Volpé, R., Fand, N. R., Von Westarp, C., Row, V. V. Clin Endocr. 1974, 5
3, 239. Langlands, A. O., Herman, K. J.
clin. Path.
1967, 20,
892.
which doubt its legal validity. Furthermore, attempts to use it and obtain insurance cover more than doubles proposed costs. I am also concerned about the lack of cover for the investigators, who, if negligent, can call on their membership of the Medical Protection Society or the Medical Defence Union, but, if no negligence exists, could possibly be subject to separate claims without such protection. I should like to see a new volunteer contract drawn up, which may well have to take into account legal liability, but should preferably retain similar provisions for compensation without litigation. It should also, as at present, make provision for legal proceedings in the event of disagreement by the volunteer at this stage, but it would also place any costs incurred on the company concerned. Separate guidelines should also be given providing written indemnification for the investigator against any separate claims. Organon Laboratories Limited, Crown House, London Road, Morden, Surrey SM4 5DZ.
C.
J. MUGGLESTONE
UPPER-GASTROINTESTINAL ENDOSCOPY
SIR,-Dr Salter (Nov. 1, p. 863) makes
a number of importhat endoscopy is over-employed, since enthusiasts. From his own experience, he notes agreement with a double-contrast barium meal in 85-96% of his patients, but offers no breakdown of his data to enable a more detailed assessment to be made. This is similar to early experience from Glasgow’ where disagreement between endoscopy and a routine barium meal was as high as 49%, but much reduced to 16% with double-contrast radiology. The radiologist at Carlisle is an enthusiastic pioneer of the double-contrast barium meal2 and it is likely that if his technique and enthusiasm were applied to all departments of radiology than the need for endoscopy could well be reduced. The need for emergency endoscopy remains however. Endoscopy can visualise the bleeding source in 92% of cases,3 against 46% by radiology. Since the surgeon benefits by prior knowledge of the site of the bleeding lesion and since more rational decisions regarding management of this dangerous condition can be made, it is disappointing that Dr Salter does not offer this service. In the diagnosis of gastric cancer the correct diagnosis can best be achieved only by additional biopsy and cytology (97% diagnosis rate; compared with 59% by radiology and 88% by visual endoscopic opinion only4). Dr Salter also suggests that the ward is a suitable environment for outpatient endoscopies. Even with a comparably light load of 2-3 cases a week (average), this would not find favour among many endoscopists or ward sisters, because of the simple logistical problem of finding empty beds for a few hours--or 2 patients using the same bed. The aim of Dr Salter’s article was to evaluate the role of endoscopy by examining his patients within one month of a barium meal. The workload of 2-3 patients a week being investigated in this way is much lower than the experience of most endoscopists (e.g., Portsmouth, two endoscopists, averaging 16 cases a week). The British Society for Digestive Endoscopy regards it as vital for the efficient running of a unit and care of equipment that it be located in a designated room and that there be an assistant. Although the experience of Dr Salter does well to stress the value of good radiology and the need for close cooperation between clinician and radiologist, the calls upon his service are so much less than most endoscopists and his data are so inadequate that his conclusions cannot be applied universally. D. G. COLIN-JONES Queen Alexandra Hospital, Hon. Secretary, British Society Cosham, for Digestive Endoscopy Portsmouth PO6 3LY.
points. He argues endoscopists are often tant
1. Moule, B. et al. Gut, 1975, 16, 411. 2. Scott-Horden, W. G. Br. J. Radiol 1973, 46, 153. 3 McGinn, F S., et al. Gut, 1975, 16, 707 4. Smithies, A., et al. Br. med. J. 1975, iv, 326 5. Memorandum on Future National Needs for Fibreoptic Gastrointestinal Tract. 1973.
Endoscopy
of the
