407
approaches to the evaluation of myocardial contractility. However, the technique has been in use for some
CHROMOSOME DAMAGE AFTER
tant
time. City of Hope Medical Center, Department of Cardiology, 1500 E. Duarte Road, Duarte, California 91010, U.S.A.
SIMON RODBARD.
LIMULUS TEST IN ESCHERICHIA COLI ENTERITIS SIR,—We have applied the Limulus test to the diagnosis of endotoxsemia in infantile Escherichia coli enteritis. The test was performed by the method of Reinhold and Fine1 in 20 children (4 prematures and the others 1-6 months of age) with enteritis caused by E. coli 0 126: 0 16 in 5 cases, E. coli 0 128: B 12 (5 cases), E. coli 0 111 (2), and by strains of E. coli non-agglutinable by anti-sera directed against the so-called " enteritogens " in the remaining 7. The Limulus test was positive in 10 of 13 patients with enteritis caused by known enteritogens, but in only 2 of 7 with enteritis caused by non-typable E. coli. In the 13 infections caused by known enteritogens there were 3 deaths, all of them among the 4 prematures in this group, whereas in the non-typable group there was 1 death in 7 patients. Thus, the higher positivity of the Limulus test in the infections caused by known-enteritogen E. coli strains cannot be considered an absolute element in poor prognosis, contrary to observations in gram-negative infections other than E. coli enteritis.2-3 Prognostic factors other than the mere presence of endotoxaemia might operate, possibly by modifying the host reactivity to endotoxin itself.4 The test was negative in 20 control plasmas from healthy subjects and in 8 out of 9 plasmas from patients with staphylococcal enteritis in If the reliability of the Limulus a community outbreak. test could be definitely proven, our results demonstrate for the first time the presence of circulating endotoxin-like material in the course of enteritis caused by some strains of E. coli-namely, the so-called " enteropathogenetic " strains. This could be the result of invasion by the organisms of upper intestinal tracts which are normally in a condition near sterility and which are provided with a more intense absorption activity, a situation in many respects similar to a form of diarrhoeal disease which affects calves.5 Probably the passage of endotoxin from intestine to blood is greater in infections caused by those strains inducing more severe functional or anatomical changes in the intestinal tract. However, the specific role of causal pathogens of peculiar E. coli strains may be less important than other factors at higher levels of endotoxaemia. We have seen that one factor is immaturity, with its deficient detoxification of absorbed endotoxin by the reticuloendothelial system, the lack of antiendotoxic immunological factors, and modifications of the intestinal flora in the sense of favouring colonisation by E. coli. 6-7 Institute of Infectious Diseases E. MAGLIULO Università of Pavia, D. SCEVOLA. .
Pavia, Italy.
Institute of Microbiology, Università of Bari,
Bari, Italy.
D. FUMAROLA.
Reinhold, R. B., Fine, J. Proc. Soc. exp. Biol. Med. 1971, 137, 334. Levin, J., Poore, T. E., Young, N. S., Margolis, S., Zauber, N. P., Townes, A. S., Bell, W. R. Ann. intern. Med. 1972, 76, 1. 3. Jorgensen, J. H., Carvajal, H. F., Chipps, B. E. Appl. Microbiol. 1973, 26, 38. 4. Endotoxin Conference. J. infect. Dis. July, 1973, 128 (suppl.). 5. Fey, H. Colibacillosis in Calves. Wien, 1972. 6. Magliulo, E., Fumarola, D., Carosi, G. P., Concia, E., Scevola, D., Cattaneo, E., Bonizzoni, D. Giorn. Mal. inf. Parass. 1973, 25, 513. 7. Magliulo, E., Fumarola, D., Scevola, D., Concia, E., Azzini, M.
1. 2.
Boll. Osp. Mag. Novara, 1974, 3, 253.
RADIOTHERAPY SIR,-Chromosome preparations from over 200 patients with lung cancer have been studied before and after treatment by radiotherapy. Peripheral blood-cultures were set up
using phytohaemagglutinin (P.H.A.)
to
study changes
in the immunological status of the patient brought about by treatment.1,2 Chromosome preparations were also made from these cultures to investigate possible cytogenetic damage caused by irradiation. 6 patients (3%) were found to have chromosome damage, consisting of dicentrics, acentrics, and fragments at the end of treatment and/or at follow-up. Polyploid cells were not considered significant unless they contained an aberration. The small number of patients with demonstrable chromosome damage in this study may be attributed to the poor response of the lymphocytes to P.H.A. after treatment by radiotherapy.2 It is also likely that grossly abnormal cells were lost during division in culture and therefore not noted in the final preparation. However, abnormalities were noted three and five months after the completion of treatment. Since no abnormalities were found before treatment, it may be assumed that the chromosome damage was caused by the irradiation. The presence of abnormal cells months after treatment adds to the existing evidence of the presence of a long-lived population in the peripheral blood. Chromosome damage has been reported in survivors of atomic bombing,s and in patients with ankylosing spondylitis after treatment by radiation.4 However, our report is one of the few findings of cytogenetic damage following small-field therapeutic irradiation. Velindre Hospital, Whitchurch, Cardiff CF4 7XL. JUDITH BRAEMAN.
DOES T4 TOXICOSIS EXIST ?
SIR,—In 1957 Maclagen
et a1.5 reported thyrotoxicosis increased accompanying plasma-triiodothyronine (T3) concentration and normal thyroxine concentration. This was the first identifiable instance of what is now called " T3 toxicosis ".* Our experience over the past 18 months with a radioimmunoassay for total serum-T3 indicates that this condition is rare iri New Zealand. Despite this, estimation of total serum-T3 has proved to be a very useful additional test of thyroid function, especially in patients with marginal clinical evidence of thyrotoxicosis or with minimally increased total serum-thyroxine (T4) level or free thyroxine index (F.T.I.) in whom it has often allowed a definitive diagnosis. However, lately we have observed very low total serumT3 levels in a group of euthyroid patients with severe Total serum-T4 debilitating non-thyroidal illness. (competitive-protein binding assay), F.T.I., and thyroidstimulating hormone (T.S.H.) values were within normal limits in these patients. Our findings agree with those of Carter et al.7 Subnormal total serum-T3 levels in severely ill patients may not therefore necessarily indicate reduced thyroid function. Results in this group prompted us to ask whether a similar reduction in total serum-T3 levels 1. Braeman, J., Deeley, T. 2. Braeman, J., Deeley, T. 3. Bloom, A. D., Neriishi,
J. Ann. clin. Res. 1972, 4, 355. J. Br. J. Radiol. 1973 46, 446. S., Kamada, N., Iseki, T., Keehn, R. J.
Lancet, 1966, ii, 672. Buckton, K. E., Langlands, A. D., Smith, P. G., McLelland, J. in Human Radiation Cytogenetics (edited by H. J. Evans, W. M. Court Brown, and A. S. McLean). Amsterdam, 1967. 5. Maclagen, N. F., Bowden, C. H., Wilkinson, J. H. Biochem. J. 1957, 67, 5. 6. Stirling, K., Refetoff, S., Sclenkow, H. J. Am. med. Ass. 1970, 213,
4.
571.
7.
Carter, J. N., Eastman, C. J., Corcoran, J. M., Lazarus, L. Lancet, 1974, ii, 971.
408 would be found in thyrotoxic patients with severe nonthyroidal illness. We believe we have found such a case. In November, 1973, a 63-year-old woman presented with carcinoma of the colon and pelvic metastases. She gave a history of a unilateral thyroid swelling since childhood and she had had an intravenous pyelogram in May, 1973. Clinically she was thyrotoxic. She complained of heat intolerance and excessive She seemed hyperkinetic and the reflexes were nervousness. brisk. Pulse-rate was 96 per minute. There was no significant tremor. Since surgery was regarded as urgent, she was referred to our unit for further evaluation. The thyroid scan appearances were consistent with a " hot " nodule replacing the right lobe with resultant suppression of the left lobe. 10-minute 99MTc Total serum-T4 was uptake was 2-5% (normal
approaches to the evaluation of myocardial contractility. However, the technique has been in use for some
CHROMOSOME DAMAGE AFTER
tant
time. City of Hope Medical Center, Department of Cardiology, 1500 E. Duarte Road, Duarte, California 91010, U.S.A.
SIMON RODBARD.
LIMULUS TEST IN ESCHERICHIA COLI ENTERITIS SIR,—We have applied the Limulus test to the diagnosis of endotoxsemia in infantile Escherichia coli enteritis. The test was performed by the method of Reinhold and Fine1 in 20 children (4 prematures and the others 1-6 months of age) with enteritis caused by E. coli 0 126: 0 16 in 5 cases, E. coli 0 128: B 12 (5 cases), E. coli 0 111 (2), and by strains of E. coli non-agglutinable by anti-sera directed against the so-called " enteritogens " in the remaining 7. The Limulus test was positive in 10 of 13 patients with enteritis caused by known enteritogens, but in only 2 of 7 with enteritis caused by non-typable E. coli. In the 13 infections caused by known enteritogens there were 3 deaths, all of them among the 4 prematures in this group, whereas in the non-typable group there was 1 death in 7 patients. Thus, the higher positivity of the Limulus test in the infections caused by known-enteritogen E. coli strains cannot be considered an absolute element in poor prognosis, contrary to observations in gram-negative infections other than E. coli enteritis.2-3 Prognostic factors other than the mere presence of endotoxaemia might operate, possibly by modifying the host reactivity to endotoxin itself.4 The test was negative in 20 control plasmas from healthy subjects and in 8 out of 9 plasmas from patients with staphylococcal enteritis in If the reliability of the Limulus a community outbreak. test could be definitely proven, our results demonstrate for the first time the presence of circulating endotoxin-like material in the course of enteritis caused by some strains of E. coli-namely, the so-called " enteropathogenetic " strains. This could be the result of invasion by the organisms of upper intestinal tracts which are normally in a condition near sterility and which are provided with a more intense absorption activity, a situation in many respects similar to a form of diarrhoeal disease which affects calves.5 Probably the passage of endotoxin from intestine to blood is greater in infections caused by those strains inducing more severe functional or anatomical changes in the intestinal tract. However, the specific role of causal pathogens of peculiar E. coli strains may be less important than other factors at higher levels of endotoxaemia. We have seen that one factor is immaturity, with its deficient detoxification of absorbed endotoxin by the reticuloendothelial system, the lack of antiendotoxic immunological factors, and modifications of the intestinal flora in the sense of favouring colonisation by E. coli. 6-7 Institute of Infectious Diseases E. MAGLIULO Università of Pavia, D. SCEVOLA. .
Pavia, Italy.
Institute of Microbiology, Università of Bari,
Bari, Italy.
D. FUMAROLA.
Reinhold, R. B., Fine, J. Proc. Soc. exp. Biol. Med. 1971, 137, 334. Levin, J., Poore, T. E., Young, N. S., Margolis, S., Zauber, N. P., Townes, A. S., Bell, W. R. Ann. intern. Med. 1972, 76, 1. 3. Jorgensen, J. H., Carvajal, H. F., Chipps, B. E. Appl. Microbiol. 1973, 26, 38. 4. Endotoxin Conference. J. infect. Dis. July, 1973, 128 (suppl.). 5. Fey, H. Colibacillosis in Calves. Wien, 1972. 6. Magliulo, E., Fumarola, D., Carosi, G. P., Concia, E., Scevola, D., Cattaneo, E., Bonizzoni, D. Giorn. Mal. inf. Parass. 1973, 25, 513. 7. Magliulo, E., Fumarola, D., Scevola, D., Concia, E., Azzini, M.
1. 2.
Boll. Osp. Mag. Novara, 1974, 3, 253.
RADIOTHERAPY SIR,-Chromosome preparations from over 200 patients with lung cancer have been studied before and after treatment by radiotherapy. Peripheral blood-cultures were set up
using phytohaemagglutinin (P.H.A.)
to
study changes
in the immunological status of the patient brought about by treatment.1,2 Chromosome preparations were also made from these cultures to investigate possible cytogenetic damage caused by irradiation. 6 patients (3%) were found to have chromosome damage, consisting of dicentrics, acentrics, and fragments at the end of treatment and/or at follow-up. Polyploid cells were not considered significant unless they contained an aberration. The small number of patients with demonstrable chromosome damage in this study may be attributed to the poor response of the lymphocytes to P.H.A. after treatment by radiotherapy.2 It is also likely that grossly abnormal cells were lost during division in culture and therefore not noted in the final preparation. However, abnormalities were noted three and five months after the completion of treatment. Since no abnormalities were found before treatment, it may be assumed that the chromosome damage was caused by the irradiation. The presence of abnormal cells months after treatment adds to the existing evidence of the presence of a long-lived population in the peripheral blood. Chromosome damage has been reported in survivors of atomic bombing,s and in patients with ankylosing spondylitis after treatment by radiation.4 However, our report is one of the few findings of cytogenetic damage following small-field therapeutic irradiation. Velindre Hospital, Whitchurch, Cardiff CF4 7XL. JUDITH BRAEMAN.
DOES T4 TOXICOSIS EXIST ?
SIR,—In 1957 Maclagen
et a1.5 reported thyrotoxicosis increased accompanying plasma-triiodothyronine (T3) concentration and normal thyroxine concentration. This was the first identifiable instance of what is now called " T3 toxicosis ".* Our experience over the past 18 months with a radioimmunoassay for total serum-T3 indicates that this condition is rare iri New Zealand. Despite this, estimation of total serum-T3 has proved to be a very useful additional test of thyroid function, especially in patients with marginal clinical evidence of thyrotoxicosis or with minimally increased total serum-thyroxine (T4) level or free thyroxine index (F.T.I.) in whom it has often allowed a definitive diagnosis. However, lately we have observed very low total serumT3 levels in a group of euthyroid patients with severe Total serum-T4 debilitating non-thyroidal illness. (competitive-protein binding assay), F.T.I., and thyroidstimulating hormone (T.S.H.) values were within normal limits in these patients. Our findings agree with those of Carter et al.7 Subnormal total serum-T3 levels in severely ill patients may not therefore necessarily indicate reduced thyroid function. Results in this group prompted us to ask whether a similar reduction in total serum-T3 levels 1. Braeman, J., Deeley, T. 2. Braeman, J., Deeley, T. 3. Bloom, A. D., Neriishi,
J. Ann. clin. Res. 1972, 4, 355. J. Br. J. Radiol. 1973 46, 446. S., Kamada, N., Iseki, T., Keehn, R. J.
Lancet, 1966, ii, 672. Buckton, K. E., Langlands, A. D., Smith, P. G., McLelland, J. in Human Radiation Cytogenetics (edited by H. J. Evans, W. M. Court Brown, and A. S. McLean). Amsterdam, 1967. 5. Maclagen, N. F., Bowden, C. H., Wilkinson, J. H. Biochem. J. 1957, 67, 5. 6. Stirling, K., Refetoff, S., Sclenkow, H. J. Am. med. Ass. 1970, 213,
4.
571.
7.
Carter, J. N., Eastman, C. J., Corcoran, J. M., Lazarus, L. Lancet, 1974, ii, 971.
408 would be found in thyrotoxic patients with severe nonthyroidal illness. We believe we have found such a case. In November, 1973, a 63-year-old woman presented with carcinoma of the colon and pelvic metastases. She gave a history of a unilateral thyroid swelling since childhood and she had had an intravenous pyelogram in May, 1973. Clinically she was thyrotoxic. She complained of heat intolerance and excessive She seemed hyperkinetic and the reflexes were nervousness. brisk. Pulse-rate was 96 per minute. There was no significant tremor. Since surgery was regarded as urgent, she was referred to our unit for further evaluation. The thyroid scan appearances were consistent with a " hot " nodule replacing the right lobe with resultant suppression of the left lobe. 10-minute 99MTc Total serum-T4 was uptake was 2-5% (normal
