- Email: [email protected]
ACETYLCHOLINE POISONING AND SYMPATHETIC OVERACTIVITY IN TETANUS
1014 We feel it important, in these cases, to make attempt at positive identification by S.E.M., ideally by the method proposed by Wetzel et al.,12 or at least by correlation between light microscopy and S.E.M. differential
separately. some
counts.
Our S.E.M. data on 9 cases of hairy-cell leuksemia do not establish that hairy cells are derived from monocytes, but they indicate that the cells are more likely to be related to cells of the monocyte/histiocyte series. Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel.
AARON POLLIACK.
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland 20014, U.S.A.
patient said that she had noted similar pain and swelling after the two previous courses of methylprednisolone. The symptoms settled promptly and the swelling more slowly, only to recur on day 105. After 48 hours the pain again settled completely, but the swelling resolved more slowly. At the time of these episodes she was taking oral prednisone (15 mg. daily) and azathioprine (150 mg. daily). X-rays of both knees were normal. Thrice weekly estimations of serum-calcium since transplantation had shown mild hypercalca:mia (10-2-12.2 mg. per 100 ml.). Serum-phosphorus levels were correspondingly low (19-34 mg. per 100 ml.). Serum-alkaline-phosphatase was 33-44 I.U. (normal 30-92 i.u.). Serum-uric-acid during the symptoms ranged from 36 to 54 mg. per 100 ml. Department of Renal Medicine, Christchurch Hospital, Christchurch,
RAUL BRAYLAN.
New Zealand.
Ross R. BAILEY PAUL ARMOUR.
University of Chicago Hospitals and Clinics and Franklin McLean Memorial Research Institute, Chicago, Illinois, U.S.A.
HARVEY GOLOMB.
MINOCYCLINE: POSSIBLE VESTIBULAR SIDE-EFFECTS
SIR,—Iam surprised at the high incidence of these side-effects reported by Dr Williams and others (Sept. 28, p. 744). My colleagues and I have treated 30 hospital inpatients with minocycline in a dose of 400 mg. daily for 10 days.13 We kept careful watch for untoward effects on the central nervous system, warned by the previous literature, but found
none.
In our " blind " comparison with tetracycline hydrochloride (2 g. daily), minocycline was significantly better tolerated (at the 5% level). Many of our patients spent long periods in bed, so that postural dizziness might not have been noticed. Nevertheless, the high incidence reported by your contributors is puzzling.
A. PINES.
Herts. SG13 7HU.
ACUTE ARTHRALGIA AFTER HIGH-DOSE INTRAVENOUS METHYLPREDNISOLONE
SIR,—We were very interested in the report by Dr Newmark and others (July 27, p. 229) of severe bilateral knee-joint pain and tenderness in four young renaltransplant recipients 16-168 hours after high-dose intravenous methylprednisolone. We now report a similar
experience. A 30-year-old White woman with chronic renal failure due to reflux nephropathy received a cadaveric renal transplant after home hzemodialysis. She required two dialyses for post-transplant acute renal failure. The early postoperative course was complicated by a pelvic hasmatoma and later by difficulties with the ureteric anastomosis. On the 8th day, when the serum-creatinine had fallen to 21 mg. per 100 ml., acute rejection developed and was treated by three daily 1 g. intravenous " pulses " of methylprednisolone. A further episode of acute rejection followed on day 59 and she was given two 1 g. injections on consecutive days. For a third episode of acute rejection on day 97 she received 1 g. intravenous doses of methylprednisolone on days 97, 98, 103, and 104. On day 100 she complained of very severe pain in both knees, and there was considerable suprapatellar swelling. The joints were not red or hot, but movement was painful and limited. The patella tap was absent on both sides, and aspiration of the joints and suprapatellar burss drew no fluid. The 12.
B. W., Levis, W. R. in Proceedings of 6th Symposium, I.I.T.R.I., Chicago, Illinois, 1973;
Wetzel, B., Erickson, Jr., Annual S.E.M.
p. 535. 13. Practitioner
(in the press).
SIR,—Kerr et, al. 1-3 pointed out the incidence of sympathetic overactivity in patients with severe tetanus treated by curarisation. As confirmed by others,’ this syndrome is characterised by cardiovascular disturbances, hyperthermia, and hyperhydrosis, with an increase in catecholamine, mineralocorticoid, and glucocorticoid metabolism. Therapeutic effects may be obtained only by general anaathesia with nitrous oxide and halothane, or with blockade of alpha and beta adrenergic effectors,2 or with epidural procaine anmsthesia. 5,6 No clear explanation at present exists for this syndrome. Some authors attribute it either to the endotoxins of overinfecting gram-negative flora7 or to the cardiotoxic activity of the tetanolysin.8 Many features of this picture of severe tetanus are related to a "
brainstem intoxication ": in contrast to this view Kerr al.l point to the relatively good prognosis associated with cephalic tetanus, with absence of any sympathetic involveet
ment.
East Herts Hospital, Stanstead Road,
Hertford,
ACETYLCHOLINE POISONING AND SYMPATHETIC OVERACTIVITY IN TETANUS
According to the hypothesis of anticholinesterase activity of the tetanus toxin, I and my co-workersobtained significant results in human tetanus by cholinesteraserestoring therapy, which seems to confirm that tetanus is indeed an acetylcholine poisoning. 10 Consequently I suggest that (1) the typical appearance of Kerr’s syndrome in curarised tetanus patients might be a consequence of an interaction between the acetylcholine poisoning induced by tetanus toxin and the curare competitive activity against the acetylcholine at neuromuscular junctions; (2) the sympathetic stimulation might depend on acetylcholine-like effects as observed under other anti-cholinesterase agents,ll,12 for a pregangliar cholinergic hyperactivity; and (3) the opportunity exists to leave the curarisation in Kerr, J. H., Corbett, J. L., Prys-Roberts, C., Crampton Smith, A., Spalding, J. M. K. Lancet, 1968, ii, 236. 2. Prys-Roberts, C., Corbett, J. L., Kerr, J. H., Crampton Smith, A., Spalding, J. M. K. ibid. 1969, i, 542. 3. Kerr, J. H. in Proceedings of 3rd International Conference on Tetanus (edited by G. Edsall); p. 128. Pan American Health Organisation, Washington, 1972. 4. Kryzhanovsky, G. N. ibid. p. 72. 5. Rapin, M., Goulon, M., Chassigneux, J. in Maladies Infectieuses (edited by A. Laffont); vol. 2. Paris, 1965. 6. Rossano, C. Atti III Congresso Nazionale Medici Pronto Soccorso. Castrocaro Terme, Maggio 18-19, 1974. 7. Thambiran, A. K., Holloway, R., Wesley, A., Adams, E. B. in Proceedings of 3rd International Conference on Tetanus (edited by G. Edsall); p. 83. Pan American Health Organisation, Washing1.
ton, 1972.
Colonnello, F., Sueri, L., Jelasi, G., Calonghi, G. F., Fassio, P. G.. Dotti, A. G. Mal. infett. parassit. 1973, 25, 77. 9. Leonardi, G., Nair, K. G., Dastur, F. D., Kamat, J. S., Desai, B. T. J. infect. Dis. 1973, 128, 652. 10. Fal, W., Czerchawski, L. Archs Immunol. Ther. Exp. 1963, 11, 423. 11. Burn, J. H., Rand, M. J. A. Rev. Pharmac. 1965, 5, 163. 12. Koelle, G. B. in The Pharmacological Basis of Therapeutics (edited by L. S. Goodman and A. Gilman); p. 421. London, 1970. 8.
1015 the treatment of tetanus for the above reasons, Kerr’s syndrome with methyldopa. Department of Medicine, St. Thomas Hospital, Portogruaro, Venice,
or
recurrences, 3 have had three recurrences, and 2 have had
to treat
G. LEONARDI.
Italy.
UNEXPLAINED TETANIC SPASMS
SiR,-Dr Morley’s patient (Oct. 12, p. 909) seems to be another example of an acute dystonic reaction misdiagnosed as tetanus. 1-5 This frightening reaction, for some reasons more common in young males,6 occurs within 48 hours of ingestion of a small dose of a phenothiazine derivative (often phentazine), metoclopramide, &c., easily escaping detection in a forensic laboratory. The condition responds dramatically to a wide variety of agents6 (e.g., benztropine 1,3) and also to curarisation and artificial ventilation employed by Dr Morley. Department of Neurology, St. Laurence’s Hospital,
PETR SKRABANEK.
Dublin.
LATE URINARY-TRACT INFECTION AFTER RENAL TRANSPLANTATION
SiR,—We have compared the results of Mr Hamshere colleagues (Oct. 5, p. 793) with the results of a similarly selected group of patients who had received a
and his
kidney graft.
patients who have been followed up for (mean follow-up 3-2 years, range 1-8 years), all of whom received a cadaver kidney. All but 4 had undergone bilateral nephrectomy before or at transplantation. Fresh mid-stream specimens of urine were examined for pyuria and cultured at each visit. Infection was diagnosed when organisms were found in concentrations exceeding 105 per ml. on one occasion only (as against two occasions in Mr Hamshere’s study) though in all such cases pyuria was also present. None of the patients had urinary symptoms We have 42
longer than
a
Only 1 patient with urinary infection had diabetes and she had three recurrences’. Long-term therapy has not been necessary in any patient. Most of the infections in our patients were caused by coliform organisms, which were responsible for eight of the eleven first infections, while proteus (one) and streptococci (two) accounted for the remainder. The primary diagnosis in relation to the occurrence of urinary infection is shown in the accompanying table. We also found that infection was common in patients with pyelonephritis as the primary disease, but, unlike their experience, half of our females escaped infection and there was no sex difference in the first infection. Infection occurred in 2 of the 4 non-nephrectomised patients, recurred in 1. The remaining 38 patients had undergone bilateral nephrectomy, and those with ureteric reflux demonstrable on a micturating cystogram had undergone complete bilateral ureterectomy at the time of the nephrectomy. Like Hamshere et al. we have not noted a decline in renal function following urinary infection, but in all our patients the infections were quickly eliminated by the appropriate antimicrobiotic treatment. There has been no need for prolonged therapy. Hamshere et al. do not routinely carry out pre-transplant nephrectomy and they suggest that their overall incidence of infection (61 %) might have been lower if they had done so. Our retrospective study, showing an incidence of 26% of urinary infection in an otherwise comparable group, tends to confirm this view. There is as yet no evidence that repeated urinary infection causes damage to the transplanted kidney although it would seem to be undesirable even if the patients are symptom-free as ours were. There are other indications for bilateral nephrectomy in some patients
two recurrences.
year
_
-
recorded. We found infection in only 11 (26%) of the 42 patients compared with 32 (61-5%) out of 52 patients in the Ham‘
awaiting kidney graft. Renal Unit, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland.
FOOD ANTIBODIES AND MYOCARDIAL INFARCTION
PRIMARY DIAGNOSIS IN RELATION TO LATE URINARY-TRACT
INFECTION
mersmith group. We did notobserve the striking sex difference they reported-6 (35%) out of 17 females and 5 (20%) out of 25 males having an infection at least once in our series compared with 20 (83%) out of 24 females and 12 (43%) out of 28 males in theirs. Infections were diagnosed more than once in 6 (54%) of the 11 patients while 3 females and 2 males did not have recurrences. 1 patient has had numerous recurrences, 1 has had five 1. Ramsden, P. D., Froggatt, D. L. Br. med. J. 1972, i, 246. 2. Mandal, B. K., Sengupta, P. ibid. p. 441. 3. Snowdon, J. ibid. p. 572. 4. Venkateswaran, P. S., Otto, A. G. ibid. 1972, iv, 178. 5. Okojie, X. G. ibid. p. 796. 6. American College of Neuropsychopharmacology: Members Drug Administration Task Force. New Engl. J. Med. 1973, 289,
J. F. DOUGLAS S. CLARKE J. KENNEDY J. MCEVOY MARY G. MCGEOWN.
SiR,-Dr Galen (Oct. 5, p. 832), in writing to criticise the paper by Dr Davies and his co-workers,2 claims to show that the results are not useful as a test for predicting death, and he finds difficulty in understanding how a causal hypothesis can be formulated. The causal hypothesis derives from the evidence that immune-complex disease (serum sickness) is a potent agent in accelerating and exacerbating lipid-induced atherogenesis in animals, probably by damaging the arterial intima and increasing the influx of cholesterol. The results of Davies et awl. have to be considered in the light of this evidence and of the fact that dietary antigens constitute a continuing immunological challenge throughout life. Some dietary protein is absorbed unchanged in the majority of the population. The chronic formation of soluble circulating immune complexes between the absorbed protein and its antibody may produce arterial damage, or affect platelets to aid thrombosis. Dr Davies and I have reviewed the subject in a recent publication3 to which reference was made in the Lancet paper. To argue that dissatisfaction with one aspect of one part Hill, C., Douglas, J. F., Kumar, R., McEvoy, J., McGeown, M. G. Lancet, Aug. 31, 1974, p. 490. 2. Davies, D. F., Johnson, A. P., Rees, B. W. G., Elwood, P. C., Abemethy, M. Lancet, 1974, i, 1012. 3. Poston, R. N., Davies, D. F. Atherosclerosis, 1974, 19, 353. 1.
of
20.
separately. some
counts.
Our S.E.M. data on 9 cases of hairy-cell leuksemia do not establish that hairy cells are derived from monocytes, but they indicate that the cells are more likely to be related to cells of the monocyte/histiocyte series. Hadassah University Hospital and Hebrew University Medical School, Jerusalem, Israel.
AARON POLLIACK.
National Cancer Institute, National Institutes of Health,
Bethesda, Maryland 20014, U.S.A.
patient said that she had noted similar pain and swelling after the two previous courses of methylprednisolone. The symptoms settled promptly and the swelling more slowly, only to recur on day 105. After 48 hours the pain again settled completely, but the swelling resolved more slowly. At the time of these episodes she was taking oral prednisone (15 mg. daily) and azathioprine (150 mg. daily). X-rays of both knees were normal. Thrice weekly estimations of serum-calcium since transplantation had shown mild hypercalca:mia (10-2-12.2 mg. per 100 ml.). Serum-phosphorus levels were correspondingly low (19-34 mg. per 100 ml.). Serum-alkaline-phosphatase was 33-44 I.U. (normal 30-92 i.u.). Serum-uric-acid during the symptoms ranged from 36 to 54 mg. per 100 ml. Department of Renal Medicine, Christchurch Hospital, Christchurch,
RAUL BRAYLAN.
New Zealand.
Ross R. BAILEY PAUL ARMOUR.
University of Chicago Hospitals and Clinics and Franklin McLean Memorial Research Institute, Chicago, Illinois, U.S.A.
HARVEY GOLOMB.
MINOCYCLINE: POSSIBLE VESTIBULAR SIDE-EFFECTS
SIR,—Iam surprised at the high incidence of these side-effects reported by Dr Williams and others (Sept. 28, p. 744). My colleagues and I have treated 30 hospital inpatients with minocycline in a dose of 400 mg. daily for 10 days.13 We kept careful watch for untoward effects on the central nervous system, warned by the previous literature, but found
none.
In our " blind " comparison with tetracycline hydrochloride (2 g. daily), minocycline was significantly better tolerated (at the 5% level). Many of our patients spent long periods in bed, so that postural dizziness might not have been noticed. Nevertheless, the high incidence reported by your contributors is puzzling.
A. PINES.
Herts. SG13 7HU.
ACUTE ARTHRALGIA AFTER HIGH-DOSE INTRAVENOUS METHYLPREDNISOLONE
SIR,—We were very interested in the report by Dr Newmark and others (July 27, p. 229) of severe bilateral knee-joint pain and tenderness in four young renaltransplant recipients 16-168 hours after high-dose intravenous methylprednisolone. We now report a similar
experience. A 30-year-old White woman with chronic renal failure due to reflux nephropathy received a cadaveric renal transplant after home hzemodialysis. She required two dialyses for post-transplant acute renal failure. The early postoperative course was complicated by a pelvic hasmatoma and later by difficulties with the ureteric anastomosis. On the 8th day, when the serum-creatinine had fallen to 21 mg. per 100 ml., acute rejection developed and was treated by three daily 1 g. intravenous " pulses " of methylprednisolone. A further episode of acute rejection followed on day 59 and she was given two 1 g. injections on consecutive days. For a third episode of acute rejection on day 97 she received 1 g. intravenous doses of methylprednisolone on days 97, 98, 103, and 104. On day 100 she complained of very severe pain in both knees, and there was considerable suprapatellar swelling. The joints were not red or hot, but movement was painful and limited. The patella tap was absent on both sides, and aspiration of the joints and suprapatellar burss drew no fluid. The 12.
B. W., Levis, W. R. in Proceedings of 6th Symposium, I.I.T.R.I., Chicago, Illinois, 1973;
Wetzel, B., Erickson, Jr., Annual S.E.M.
p. 535. 13. Practitioner
(in the press).
SIR,—Kerr et, al. 1-3 pointed out the incidence of sympathetic overactivity in patients with severe tetanus treated by curarisation. As confirmed by others,’ this syndrome is characterised by cardiovascular disturbances, hyperthermia, and hyperhydrosis, with an increase in catecholamine, mineralocorticoid, and glucocorticoid metabolism. Therapeutic effects may be obtained only by general anaathesia with nitrous oxide and halothane, or with blockade of alpha and beta adrenergic effectors,2 or with epidural procaine anmsthesia. 5,6 No clear explanation at present exists for this syndrome. Some authors attribute it either to the endotoxins of overinfecting gram-negative flora7 or to the cardiotoxic activity of the tetanolysin.8 Many features of this picture of severe tetanus are related to a "
brainstem intoxication ": in contrast to this view Kerr al.l point to the relatively good prognosis associated with cephalic tetanus, with absence of any sympathetic involveet
ment.
East Herts Hospital, Stanstead Road,
Hertford,
ACETYLCHOLINE POISONING AND SYMPATHETIC OVERACTIVITY IN TETANUS
According to the hypothesis of anticholinesterase activity of the tetanus toxin, I and my co-workersobtained significant results in human tetanus by cholinesteraserestoring therapy, which seems to confirm that tetanus is indeed an acetylcholine poisoning. 10 Consequently I suggest that (1) the typical appearance of Kerr’s syndrome in curarised tetanus patients might be a consequence of an interaction between the acetylcholine poisoning induced by tetanus toxin and the curare competitive activity against the acetylcholine at neuromuscular junctions; (2) the sympathetic stimulation might depend on acetylcholine-like effects as observed under other anti-cholinesterase agents,ll,12 for a pregangliar cholinergic hyperactivity; and (3) the opportunity exists to leave the curarisation in Kerr, J. H., Corbett, J. L., Prys-Roberts, C., Crampton Smith, A., Spalding, J. M. K. Lancet, 1968, ii, 236. 2. Prys-Roberts, C., Corbett, J. L., Kerr, J. H., Crampton Smith, A., Spalding, J. M. K. ibid. 1969, i, 542. 3. Kerr, J. H. in Proceedings of 3rd International Conference on Tetanus (edited by G. Edsall); p. 128. Pan American Health Organisation, Washington, 1972. 4. Kryzhanovsky, G. N. ibid. p. 72. 5. Rapin, M., Goulon, M., Chassigneux, J. in Maladies Infectieuses (edited by A. Laffont); vol. 2. Paris, 1965. 6. Rossano, C. Atti III Congresso Nazionale Medici Pronto Soccorso. Castrocaro Terme, Maggio 18-19, 1974. 7. Thambiran, A. K., Holloway, R., Wesley, A., Adams, E. B. in Proceedings of 3rd International Conference on Tetanus (edited by G. Edsall); p. 83. Pan American Health Organisation, Washing1.
ton, 1972.
Colonnello, F., Sueri, L., Jelasi, G., Calonghi, G. F., Fassio, P. G.. Dotti, A. G. Mal. infett. parassit. 1973, 25, 77. 9. Leonardi, G., Nair, K. G., Dastur, F. D., Kamat, J. S., Desai, B. T. J. infect. Dis. 1973, 128, 652. 10. Fal, W., Czerchawski, L. Archs Immunol. Ther. Exp. 1963, 11, 423. 11. Burn, J. H., Rand, M. J. A. Rev. Pharmac. 1965, 5, 163. 12. Koelle, G. B. in The Pharmacological Basis of Therapeutics (edited by L. S. Goodman and A. Gilman); p. 421. London, 1970. 8.
1015 the treatment of tetanus for the above reasons, Kerr’s syndrome with methyldopa. Department of Medicine, St. Thomas Hospital, Portogruaro, Venice,
or
recurrences, 3 have had three recurrences, and 2 have had
to treat
G. LEONARDI.
Italy.
UNEXPLAINED TETANIC SPASMS
SiR,-Dr Morley’s patient (Oct. 12, p. 909) seems to be another example of an acute dystonic reaction misdiagnosed as tetanus. 1-5 This frightening reaction, for some reasons more common in young males,6 occurs within 48 hours of ingestion of a small dose of a phenothiazine derivative (often phentazine), metoclopramide, &c., easily escaping detection in a forensic laboratory. The condition responds dramatically to a wide variety of agents6 (e.g., benztropine 1,3) and also to curarisation and artificial ventilation employed by Dr Morley. Department of Neurology, St. Laurence’s Hospital,
PETR SKRABANEK.
Dublin.
LATE URINARY-TRACT INFECTION AFTER RENAL TRANSPLANTATION
SiR,—We have compared the results of Mr Hamshere colleagues (Oct. 5, p. 793) with the results of a similarly selected group of patients who had received a
and his
kidney graft.
patients who have been followed up for (mean follow-up 3-2 years, range 1-8 years), all of whom received a cadaver kidney. All but 4 had undergone bilateral nephrectomy before or at transplantation. Fresh mid-stream specimens of urine were examined for pyuria and cultured at each visit. Infection was diagnosed when organisms were found in concentrations exceeding 105 per ml. on one occasion only (as against two occasions in Mr Hamshere’s study) though in all such cases pyuria was also present. None of the patients had urinary symptoms We have 42
longer than
a
Only 1 patient with urinary infection had diabetes and she had three recurrences’. Long-term therapy has not been necessary in any patient. Most of the infections in our patients were caused by coliform organisms, which were responsible for eight of the eleven first infections, while proteus (one) and streptococci (two) accounted for the remainder. The primary diagnosis in relation to the occurrence of urinary infection is shown in the accompanying table. We also found that infection was common in patients with pyelonephritis as the primary disease, but, unlike their experience, half of our females escaped infection and there was no sex difference in the first infection. Infection occurred in 2 of the 4 non-nephrectomised patients, recurred in 1. The remaining 38 patients had undergone bilateral nephrectomy, and those with ureteric reflux demonstrable on a micturating cystogram had undergone complete bilateral ureterectomy at the time of the nephrectomy. Like Hamshere et al. we have not noted a decline in renal function following urinary infection, but in all our patients the infections were quickly eliminated by the appropriate antimicrobiotic treatment. There has been no need for prolonged therapy. Hamshere et al. do not routinely carry out pre-transplant nephrectomy and they suggest that their overall incidence of infection (61 %) might have been lower if they had done so. Our retrospective study, showing an incidence of 26% of urinary infection in an otherwise comparable group, tends to confirm this view. There is as yet no evidence that repeated urinary infection causes damage to the transplanted kidney although it would seem to be undesirable even if the patients are symptom-free as ours were. There are other indications for bilateral nephrectomy in some patients
two recurrences.
year
_
-
recorded. We found infection in only 11 (26%) of the 42 patients compared with 32 (61-5%) out of 52 patients in the Ham‘
awaiting kidney graft. Renal Unit, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland.
FOOD ANTIBODIES AND MYOCARDIAL INFARCTION
PRIMARY DIAGNOSIS IN RELATION TO LATE URINARY-TRACT
INFECTION
mersmith group. We did notobserve the striking sex difference they reported-6 (35%) out of 17 females and 5 (20%) out of 25 males having an infection at least once in our series compared with 20 (83%) out of 24 females and 12 (43%) out of 28 males in theirs. Infections were diagnosed more than once in 6 (54%) of the 11 patients while 3 females and 2 males did not have recurrences. 1 patient has had numerous recurrences, 1 has had five 1. Ramsden, P. D., Froggatt, D. L. Br. med. J. 1972, i, 246. 2. Mandal, B. K., Sengupta, P. ibid. p. 441. 3. Snowdon, J. ibid. p. 572. 4. Venkateswaran, P. S., Otto, A. G. ibid. 1972, iv, 178. 5. Okojie, X. G. ibid. p. 796. 6. American College of Neuropsychopharmacology: Members Drug Administration Task Force. New Engl. J. Med. 1973, 289,
J. F. DOUGLAS S. CLARKE J. KENNEDY J. MCEVOY MARY G. MCGEOWN.
SiR,-Dr Galen (Oct. 5, p. 832), in writing to criticise the paper by Dr Davies and his co-workers,2 claims to show that the results are not useful as a test for predicting death, and he finds difficulty in understanding how a causal hypothesis can be formulated. The causal hypothesis derives from the evidence that immune-complex disease (serum sickness) is a potent agent in accelerating and exacerbating lipid-induced atherogenesis in animals, probably by damaging the arterial intima and increasing the influx of cholesterol. The results of Davies et awl. have to be considered in the light of this evidence and of the fact that dietary antigens constitute a continuing immunological challenge throughout life. Some dietary protein is absorbed unchanged in the majority of the population. The chronic formation of soluble circulating immune complexes between the absorbed protein and its antibody may produce arterial damage, or affect platelets to aid thrombosis. Dr Davies and I have reviewed the subject in a recent publication3 to which reference was made in the Lancet paper. To argue that dissatisfaction with one aspect of one part Hill, C., Douglas, J. F., Kumar, R., McEvoy, J., McGeown, M. G. Lancet, Aug. 31, 1974, p. 490. 2. Davies, D. F., Johnson, A. P., Rees, B. W. G., Elwood, P. C., Abemethy, M. Lancet, 1974, i, 1012. 3. Poston, R. N., Davies, D. F. Atherosclerosis, 1974, 19, 353. 1.
of
20.