1278
patients dying within a few hours of admishospital, others recovering rapidly. Certain are of prognostic value-in pneumococcal signs meningitis, for example, coma on presentation and a low c.s.F. white-cell count indicates a gloomy prognosis-but on clinical grounds alone the outcome often cannot be foretold. Bacterial antigen some
sion
to
and endotoxin levels in c.s.F. have therefore been quantitated to see if they could be of help in prognosis. Antigen concentration in c.s.F. is closely related to the c.s.F. bacterial count2 and a relationship between antigen titre and prognosis might therefore be expected. This has proved to be the case, for in meningococcal, 22 21 pneumococcal,2a haemophilus,l 12 16 and E. coli17 meningitis those patients with severe brain damage and late sequelae had a higher concentration of antigen in c.s.F. than patients who recovered uneventfully. However, in most investigations there was considerable overlap between the two groups. Antigen usually disappears from the c.s.F. 24-48 hours from the start of treatment. Longer persistence of antigen is ominous. Persistence of antigen for more than 48 hours after the start of treatment, especially if accompanied by a poor clinical response, may be an indication for a change of therapy. Antigen in the serum, particularly if present in high titre or if present for more than 2 or 3 days, is another bad sign in haemophilus,t6 E. coli,t7 and meningococcal
meningitis.22 Detection of bacterial products in c.s.F. and serum is proving a useful adjunct to the management of patients with pyogenic meningitis. It allows rapid bacteriological diagnosis and, early in the course of their illness, it singles out the patients with a poor prognosis. It should not be regarded as a replacement for routine bacteriological investigations but as a supplement, for the diagnostic success-rate of antigen detection and culture combined is greater than that of either technique alone. In addition, culture may identify one of the more un-usual causes of bacterial meningitis and can provide valuable information on antibiotic sensitivities.
Irradiation of the Thyroid Gland THE people of Hiroshima and Nagasaki were exposed to external gamma and neutron radiation from the nuclear bombs "Fat Man" and "Little Boy", but not to any significant fallout. An accident during a thermonuclear explosion at Bikini in 1954 unfortunately subjected a group of Marshall 22.
Whittle, H. C., Greenwood, B. M., Davidson, N. McD., Tomkins, A., Tugwell, P., Warrell, D. A., Zalin, A., Bryceson, A. D. M., Parry, E. H. O., Brueton, M., Duggan, M., Oomen, J. M. V., Rajkovic, A. D. Am. J. Med. 1975, 58, 823. 23. Hoffman, T. A., Edwards, E. A. J. infect. Dis. 1972, 126, 636. 24. Tugwell, P., Greenwood, B. M., Warrell, D. A. Q. Jl Med. (in the press).
Islanders and Japanese fishermen to acute radiation from fallout-the only population so affected. They have been under surveillance ever since; weI have commented on some of the earlier reports,’ and a twenty-year review has now appeared.2 The fallout was deposited on people’s skin and surroundings and on food and water supplies. This resulted in very high epidermal doses, mostly from nonpenetrating beta rays, and whole-body gamma doses estimated at 175 rads on Rongelap and 14-69 rads in neighbouring islands. Because many radioisotopes of iodine were produced and ingested, thyroid doses were higher, calculated at a total amount of about 220-450 rads to adults and 700-1400 rads to children on Rongelap (because of many uncertainties these are rough estimates). Initially, transient nausea and depression of leucocyte-counts were common, and there were severe skin burns, all of which healed. In the succeeding years a few ill-effects were manifest, such as an increase in miscarriages and stillbirths, and chromosome abnormalities in blood-cells. (There has also been an increase in the incidence of non-thyroid cancer in the heavily exposed group, including a case of acute myeloid leukaemia, but the numbers are small; so far no skin cancers have appeared.) Then growth retardation was noted in 5 of the 19 children exposed before ten years of age. Soon evidence ofmyxoedema became apparent in 2 of them, and when satisfactory methods of measuring thyroxine were devised, low levels were found (the protein-bound iodine levels had, confusingly, been normal, apparently because of an iodoprotein in Marshallese unrelated to thyroid hormone). Thyrotrophin levels were normal. Nine years after exposure, thyroid nodules began to appear (but not in the 2 myxoedematous boys). By 1974, 27 of the 86 exposed people on Rongelap had nodules, with smaller numbers in the less heavily exposed people of the other islands. These nodules were all found clinically; scanning might have revealed larger numbers.3 The highest incidence of nodules has been in the heavily exposed group who were less than ten years old at the time of the accident. 1 of the 4 children exposed in utero developed a thyroid adenoma. 24 of these patients have had thyroid operations, revealing benign lesions in 21 and carcinoma in 3. Many glands had hairlike vessels on the surface, reminiscent of thyroids treated with radioiodine. Many of the adenomas were papillary; some patients were given tracer doses of 1311 before operation, and autoradiography showed diminished or absent function in the nodules. Most of the thyroids contained many minute encapsulated lesions 1. Lancet, 1966, ii, 580; ibid. 1968, i, 625. 2. A Twenty-Year Review of Medical Findings in a Marshallese Population Accidentally Exposed to Radioactive Fallout. By R. A. CONARD and others. Brookhaven National Laboratory, Upton, New York, 1975. 3. Favus, M. J., Schneider, A. B., Stachura, M. E., Arnold, J. E., Yun Ryo, U., Pinsky, S. M., Colman, M., Arnold, M. J., Frohman, L. A. New Engl. J. Med. 1976, 1294, 1019.
1279 ’
of solid masses of cells with no follicles, atypia and mitoses suggesting malignant potential. Of the 4 malignant lesions, 2 were papillary adenocarcinomas with cervical metastases; the 3rd was a follicular adenocarcinoma and the 4th an undifferentiated adenocarcinoma, both without metastases. The last case was in a patient from a neighbouring island who had’ received little exposure (calculated at 31 rads), and may be a chance
composed but with
occurrence.
people in the heavily exposed group were treated with thyroxine in the hope of inhibiting development of tumours, but some new nodules have appeared. There have been no deaths or acute disorders attributable to thyroid disease, but thyroid function is reduced in a few people. The incidence of benign and malignant thyroid nodules is much higher than in other Marshallese and is higher in the residents of Rongelap than in those on the less heavily exposed islands. Most of it is undoubtedly related to radiation, largely to radioiodine in fallout. (The Japanese fishermen who were near Rongelap at the time of the explosion were subjected to similar external radiation from fallout but probably had less internal absorpAll
tion of radionuclides since their food and water covered: they have had no thyroid effects.) External radiation is known to predispose to thyroid tumours. SAMPSON and his colleagues4 found a higher incidence of thyroid carcinoma (mostly occult papillary) in Japanese survivors of atomic bombs than in other Japanese. Many workers have found a high incidence of thyroid (and other local) tumours after therapeutic irradiation of the head and neck. 1 16 After radioiodine treatment for were
hyperthyroidism, thyroid tumours are rare, probably because the high dose of radiation causes so much cell destruction: but MAcDOUGALL has been able to review 15 cases of thyroid cancer after 1311 therapy, in several of which low doses were used, and SHELINE et al.found 8 thyroid nodules in 256 patients who had received radioiodine. The incidence of thyroid tumours per rad is higher in children, perhaps because the gland is smaller and the radiation dose per gramme is greater.2The incidence per rad in the Marshallese is similar to that in people receiving external radiation, though 1311 has been shown in animal experiments to produce fewer tumours, dose for dose, than X rays.9 10 This finding, however, does not apply to the shorter-lived isotopes of iodine, which 4. Sampson, R. J.,
Key, C. R., Buncher, C. R., Iijima, S. J. Am. med. Ass. 1969, 209, 65. 5. Modan, B., Baidatz, D., Mart, H., Steinitz, R., Levin, S. G. Lancet, 1974, i, 277. 6. Hempelmann, L. H., Hall, W. J., Phillips, M., Cooper, R. A., Ames, W. R. J. natn. Cancer Inst. 1975, 55, 519. 7 MacDougall, I. R. J. Am. med. Ass. 1974, 227, 438. 8. Sheline, G. E., Lindsay, S., McCormack, K. R., Galante, M. J. clin. Endocr. Metab. 1962, 22, 8. 9. Doniach, I. Hlth Phys. 1963, 9, 1357. 10 Saenger, E. L., Saltzer, R. A., Sterling, T. D., Kereiakes, J. G. ibid. p. 1371.
also present in fallout. WALINDER and his colleagues"suggest that this is because the dose-rate is higher; they found that the higher-energy beta rays of these isotopes caused a highly uniform radiation dose. Turning to civil-defence planning, CONARD and his colleagues2 lay stress on early protective measures-shelter protection to avoid inhalation of radioactive material, consumption of food and water only from closed containers, feeding of protective fodder to cows, and diversion of contaminated milk supplies to processed products so that short-lived nuclides decay before consumption. Addition of stable iodine to food or water in the first week would reduce thyroid uptake of radioiodine. Later, thyroxine treatment of those exposed and surgical treatment of those with nodules would be indicated. Another lesson of their findings and those of MAcDouGALLis not to use low doses of radioiodine when hyperthyroidism is treated, and to use other forms of treatment in children and young adults. are
,
Flushers and Pumpers FOR preserving a kidney between the time it is taken from a donor and the time it is transplanted into a recipient, two techniques are in common use. In the first, the kidney is flushed with an electrolyte solution and then stored in ice; in the second, the kidney is put on a preservation machine and perfused continuously with an oxygenated solution of cold plasma or albumin. Both techniques can give good preservation for up to twenty-four hours but beyond this only perfusion can be relied upon to keep the kidney well-preserved. By giving the transplant team more time, preservation machines have brought order to the work of many units, which can now do transplant operations on ordinary operation lists. In addition, perfusion can provide information on the state of health of the transplant : thus, kidneys that have been severely damaged by ischaemia can be identified and discarded. Nonetheless, perfusion machines are expensive and have to be worked by trained personnel; many transplant teams elect to do without, accepting that transplant operations will be unscheduled and will often have to be carried out at night. Preservation techniques that avoid continuous perfusion have changed in the past few years. Although reasonable preservation may be obtained by merely cooling the kidney, better results can be had when the blood is flushed out of the renal vasculature. A solution of ’Rheomacrodex’ (low-mole11. Walinder, G.,
11, 24.
Jonsson, C. -J., Sjöden, A. Acta radiol.
Ther.
Phys. Biol. 1972,
patients dying within a few hours of admishospital, others recovering rapidly. Certain are of prognostic value-in pneumococcal signs meningitis, for example, coma on presentation and a low c.s.F. white-cell count indicates a gloomy prognosis-but on clinical grounds alone the outcome often cannot be foretold. Bacterial antigen some
sion
to
and endotoxin levels in c.s.F. have therefore been quantitated to see if they could be of help in prognosis. Antigen concentration in c.s.F. is closely related to the c.s.F. bacterial count2 and a relationship between antigen titre and prognosis might therefore be expected. This has proved to be the case, for in meningococcal, 22 21 pneumococcal,2a haemophilus,l 12 16 and E. coli17 meningitis those patients with severe brain damage and late sequelae had a higher concentration of antigen in c.s.F. than patients who recovered uneventfully. However, in most investigations there was considerable overlap between the two groups. Antigen usually disappears from the c.s.F. 24-48 hours from the start of treatment. Longer persistence of antigen is ominous. Persistence of antigen for more than 48 hours after the start of treatment, especially if accompanied by a poor clinical response, may be an indication for a change of therapy. Antigen in the serum, particularly if present in high titre or if present for more than 2 or 3 days, is another bad sign in haemophilus,t6 E. coli,t7 and meningococcal
meningitis.22 Detection of bacterial products in c.s.F. and serum is proving a useful adjunct to the management of patients with pyogenic meningitis. It allows rapid bacteriological diagnosis and, early in the course of their illness, it singles out the patients with a poor prognosis. It should not be regarded as a replacement for routine bacteriological investigations but as a supplement, for the diagnostic success-rate of antigen detection and culture combined is greater than that of either technique alone. In addition, culture may identify one of the more un-usual causes of bacterial meningitis and can provide valuable information on antibiotic sensitivities.
Irradiation of the Thyroid Gland THE people of Hiroshima and Nagasaki were exposed to external gamma and neutron radiation from the nuclear bombs "Fat Man" and "Little Boy", but not to any significant fallout. An accident during a thermonuclear explosion at Bikini in 1954 unfortunately subjected a group of Marshall 22.
Whittle, H. C., Greenwood, B. M., Davidson, N. McD., Tomkins, A., Tugwell, P., Warrell, D. A., Zalin, A., Bryceson, A. D. M., Parry, E. H. O., Brueton, M., Duggan, M., Oomen, J. M. V., Rajkovic, A. D. Am. J. Med. 1975, 58, 823. 23. Hoffman, T. A., Edwards, E. A. J. infect. Dis. 1972, 126, 636. 24. Tugwell, P., Greenwood, B. M., Warrell, D. A. Q. Jl Med. (in the press).
Islanders and Japanese fishermen to acute radiation from fallout-the only population so affected. They have been under surveillance ever since; weI have commented on some of the earlier reports,’ and a twenty-year review has now appeared.2 The fallout was deposited on people’s skin and surroundings and on food and water supplies. This resulted in very high epidermal doses, mostly from nonpenetrating beta rays, and whole-body gamma doses estimated at 175 rads on Rongelap and 14-69 rads in neighbouring islands. Because many radioisotopes of iodine were produced and ingested, thyroid doses were higher, calculated at a total amount of about 220-450 rads to adults and 700-1400 rads to children on Rongelap (because of many uncertainties these are rough estimates). Initially, transient nausea and depression of leucocyte-counts were common, and there were severe skin burns, all of which healed. In the succeeding years a few ill-effects were manifest, such as an increase in miscarriages and stillbirths, and chromosome abnormalities in blood-cells. (There has also been an increase in the incidence of non-thyroid cancer in the heavily exposed group, including a case of acute myeloid leukaemia, but the numbers are small; so far no skin cancers have appeared.) Then growth retardation was noted in 5 of the 19 children exposed before ten years of age. Soon evidence ofmyxoedema became apparent in 2 of them, and when satisfactory methods of measuring thyroxine were devised, low levels were found (the protein-bound iodine levels had, confusingly, been normal, apparently because of an iodoprotein in Marshallese unrelated to thyroid hormone). Thyrotrophin levels were normal. Nine years after exposure, thyroid nodules began to appear (but not in the 2 myxoedematous boys). By 1974, 27 of the 86 exposed people on Rongelap had nodules, with smaller numbers in the less heavily exposed people of the other islands. These nodules were all found clinically; scanning might have revealed larger numbers.3 The highest incidence of nodules has been in the heavily exposed group who were less than ten years old at the time of the accident. 1 of the 4 children exposed in utero developed a thyroid adenoma. 24 of these patients have had thyroid operations, revealing benign lesions in 21 and carcinoma in 3. Many glands had hairlike vessels on the surface, reminiscent of thyroids treated with radioiodine. Many of the adenomas were papillary; some patients were given tracer doses of 1311 before operation, and autoradiography showed diminished or absent function in the nodules. Most of the thyroids contained many minute encapsulated lesions 1. Lancet, 1966, ii, 580; ibid. 1968, i, 625. 2. A Twenty-Year Review of Medical Findings in a Marshallese Population Accidentally Exposed to Radioactive Fallout. By R. A. CONARD and others. Brookhaven National Laboratory, Upton, New York, 1975. 3. Favus, M. J., Schneider, A. B., Stachura, M. E., Arnold, J. E., Yun Ryo, U., Pinsky, S. M., Colman, M., Arnold, M. J., Frohman, L. A. New Engl. J. Med. 1976, 1294, 1019.
1279 ’
of solid masses of cells with no follicles, atypia and mitoses suggesting malignant potential. Of the 4 malignant lesions, 2 were papillary adenocarcinomas with cervical metastases; the 3rd was a follicular adenocarcinoma and the 4th an undifferentiated adenocarcinoma, both without metastases. The last case was in a patient from a neighbouring island who had’ received little exposure (calculated at 31 rads), and may be a chance
composed but with
occurrence.
people in the heavily exposed group were treated with thyroxine in the hope of inhibiting development of tumours, but some new nodules have appeared. There have been no deaths or acute disorders attributable to thyroid disease, but thyroid function is reduced in a few people. The incidence of benign and malignant thyroid nodules is much higher than in other Marshallese and is higher in the residents of Rongelap than in those on the less heavily exposed islands. Most of it is undoubtedly related to radiation, largely to radioiodine in fallout. (The Japanese fishermen who were near Rongelap at the time of the explosion were subjected to similar external radiation from fallout but probably had less internal absorpAll
tion of radionuclides since their food and water covered: they have had no thyroid effects.) External radiation is known to predispose to thyroid tumours. SAMPSON and his colleagues4 found a higher incidence of thyroid carcinoma (mostly occult papillary) in Japanese survivors of atomic bombs than in other Japanese. Many workers have found a high incidence of thyroid (and other local) tumours after therapeutic irradiation of the head and neck. 1 16 After radioiodine treatment for were
hyperthyroidism, thyroid tumours are rare, probably because the high dose of radiation causes so much cell destruction: but MAcDOUGALL has been able to review 15 cases of thyroid cancer after 1311 therapy, in several of which low doses were used, and SHELINE et al.found 8 thyroid nodules in 256 patients who had received radioiodine. The incidence of thyroid tumours per rad is higher in children, perhaps because the gland is smaller and the radiation dose per gramme is greater.2The incidence per rad in the Marshallese is similar to that in people receiving external radiation, though 1311 has been shown in animal experiments to produce fewer tumours, dose for dose, than X rays.9 10 This finding, however, does not apply to the shorter-lived isotopes of iodine, which 4. Sampson, R. J.,
Key, C. R., Buncher, C. R., Iijima, S. J. Am. med. Ass. 1969, 209, 65. 5. Modan, B., Baidatz, D., Mart, H., Steinitz, R., Levin, S. G. Lancet, 1974, i, 277. 6. Hempelmann, L. H., Hall, W. J., Phillips, M., Cooper, R. A., Ames, W. R. J. natn. Cancer Inst. 1975, 55, 519. 7 MacDougall, I. R. J. Am. med. Ass. 1974, 227, 438. 8. Sheline, G. E., Lindsay, S., McCormack, K. R., Galante, M. J. clin. Endocr. Metab. 1962, 22, 8. 9. Doniach, I. Hlth Phys. 1963, 9, 1357. 10 Saenger, E. L., Saltzer, R. A., Sterling, T. D., Kereiakes, J. G. ibid. p. 1371.
also present in fallout. WALINDER and his colleagues"suggest that this is because the dose-rate is higher; they found that the higher-energy beta rays of these isotopes caused a highly uniform radiation dose. Turning to civil-defence planning, CONARD and his colleagues2 lay stress on early protective measures-shelter protection to avoid inhalation of radioactive material, consumption of food and water only from closed containers, feeding of protective fodder to cows, and diversion of contaminated milk supplies to processed products so that short-lived nuclides decay before consumption. Addition of stable iodine to food or water in the first week would reduce thyroid uptake of radioiodine. Later, thyroxine treatment of those exposed and surgical treatment of those with nodules would be indicated. Another lesson of their findings and those of MAcDouGALLis not to use low doses of radioiodine when hyperthyroidism is treated, and to use other forms of treatment in children and young adults. are
,
Flushers and Pumpers FOR preserving a kidney between the time it is taken from a donor and the time it is transplanted into a recipient, two techniques are in common use. In the first, the kidney is flushed with an electrolyte solution and then stored in ice; in the second, the kidney is put on a preservation machine and perfused continuously with an oxygenated solution of cold plasma or albumin. Both techniques can give good preservation for up to twenty-four hours but beyond this only perfusion can be relied upon to keep the kidney well-preserved. By giving the transplant team more time, preservation machines have brought order to the work of many units, which can now do transplant operations on ordinary operation lists. In addition, perfusion can provide information on the state of health of the transplant : thus, kidneys that have been severely damaged by ischaemia can be identified and discarded. Nonetheless, perfusion machines are expensive and have to be worked by trained personnel; many transplant teams elect to do without, accepting that transplant operations will be unscheduled and will often have to be carried out at night. Preservation techniques that avoid continuous perfusion have changed in the past few years. Although reasonable preservation may be obtained by merely cooling the kidney, better results can be had when the blood is flushed out of the renal vasculature. A solution of ’Rheomacrodex’ (low-mole11. Walinder, G.,
11, 24.
Jonsson, C. -J., Sjöden, A. Acta radiol.
Ther.
Phys. Biol. 1972,
