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RENAL ALLOTRANSPLANTATION IN PRESENCE OF LYMPHOCYTOTOXIC ANTIBODIES
256 undulant fever (table fll). Active infection was suspected only when the serum, treated with mercaptoethanol, agglutinated to In a titre 1/40 or over or fixed complement at 1/10 or more. the acute cases the titres were usually several times higher. Agreement between the two tests was close but not absolute. Judged by these criteria the diagnosis was confirmed in only 21 cases. The occupations of the victims agreed with previous experience here: 10 were farmers, 5 veterinary surgeons, 1 worked in a slaughter house, and the trades of the rest were either irrelevant or unknown. Because of the frequency of false or doubtful positives I am inclined to doubt whether the standard agglutination test is worth doing, and unless the benefits are plain there are good reasons for not duplicating the other two tests. The choice between agglutination after treatment with mercaptoethanol and the C.F.T. is difficult. I suspect that the latter is, by a small margin, the more reliable, and it is more economical of reagents. A single C.F.T. is, however, a great nuisance, and in laboratories which do not put up these tests several times each week the mercaptoethanol-agglutination test will be less trouble. Public Health Laboratory. Taunton.
J. A. BOYCOTT.
RENAL ALLOTRANSPLANTATION IN PRESENCE OF LYMPHOCYTOTOXIC ANTIBODIES SIR,-" Hyperacute " rejection of allotransplanted kidneys, which is referred to by Dr. Stewart and his colleagues last week (p. 176), is a loose clinical term which i’s meaningless from a pathophysiological basis. What is meant is that acute anuria follows the establishment of the new circulation. By using the term, " hyperacute " rejection, one is committed to an immunological interpretation of the anuria, and the evidence for such an interpretation is rather tenuous. If acute rejection implies the classical cellular infiltration, then " hyperacute " should, logically, imply an accelerated version of this; I have referred to it as an accelerated rejection which, in the dog, occurs on the third day, and this is rare in my experience. But " hyperacute " rejection, as defined by Kissmeyer-Nielsen et a1.2 and Williams et al.,3 does not mean this at all. What they refer to is a lesion very similar if not identical to the second-set reaction,4 but this lesion requires careful differentiation from a technical haEmo-
dynamic upset. The evidence for an immunological reaction in the allotransplanted kidneys described by Kissmeyer-Nielsen et al.2 was glomerular thrombosis, but Duguid et awl. and others have demonstrated that this is a technical artefact of preservation even in autotransplants. Williams et awl. were impressed by red-cell clumping and polymorph margination in the glomeruli but this can occur in autotransplant anurias.6g The conditions under which " hyperacute " rejection has been described are quite different. Hamburger et al.’ reported 3/6 early anurias in first-set kidneys from live donors; in 3 nonparous females and 3 males the presumptive diagnoses were (1) technical failure, and (2) pre-existing cytotoxins-there were no serological studies. Kissmeyer-Nielsen et al.2 reported 2/21 early anurias in first-set kidneys from cadaver donors; in 2 parous females the presumptive diagnosis was pregnancy cytotoxins. Williams et awl. reported 1/111 first-set kidneys from live and cadaver donors, and 5/20 immediate anurias in second-set kidneys from mainly cadaver donors along with 1 case of mismatched ABO group (B O) which showed the same lack of function and microscopic appearances; in 2 males and 3 females (1 parous) the presumptive diagnosis was pre1. 2.
3. 4. 5. 6. 7.
Dempster, W. J. Br. med. J. 1963, i, 1697. Kissmeyer-Nielsen, F., Olsen, S., Petersen, V. P., Fjeldborg, O. Lancet, 1966, ii, 662. Williams, G. M., Hume, D. M., Hudson, R. P., Morris, P. J., Kano, K., Milgrom, F. New Engl. J. Med. 1968, 279, 611. Dempster, W. J. Br. J. Surg. 1953, 40, 447. Duguid, W. P., Hendry, W. F., Struthers, N. W. Lancet, 1967, ii, 990. Dempster, W. J. Acta med. scand. 1954, 148, 91. Hamburger, J., Vaysse, J., Crosnier, J., Auvert, J., Lalanne, C. M., Dormont, J. Revue fr. Étud. clin. biol. 1962, 7, 20.
existing antibodies, although Williams et al. have shown that they are not always associated with rejection. In 1 instance, both kidneys of a cadaver donor failed to function, which could indicate a technical mishap. 5/20 immediate anurias in second kidneys from different donors implies cross-sensitisation. One can distinguish a technical from an immunological anuria, and one can distinguish anuria in a sensitised individual from anuria in a hypersensitised individual.The technical anuria (haemoconcentration, &c.) occurs about 5-10 minutes after the circulation has been opened up. The anuria in the sensitised individual occurs some hours (12 to 24 or 36) after quite a brisk diuresis. The anuria in the hypersensitised individual occurs immediately-as in ABO incompatibility, or after multiple grafts of skin before the kidney transplantation. Since Williams et al. encountered " hyperacute " rejection only once in 111 first allotransplants without all the testing carried out by Dr. Stewart and his colleagues, are there any real grounds for believing that pregnancy antibodies and antibodies due to blood-transfusions play any major role in causing immediate anuria in first-set kidneys ? Najarian et al.9 were courageous in confessing to technical failures due to haemoconcentration. And there are those who believe that the more blood-transfusions before kidney transplantation the better the kidney likes it. The demonstration that serum antibodies cross-react with lymphocytes is presumptive evidence but not unequivocal proof that cytopathological effects will be produced by these antibodies on renal allotransplants. Nakhla and Glynn 10 have reported the surprising fact that they cannot attribute any cytopathological effects to the p-haemolytic streptococcal antigen which cross-reacts with an antigen in human mvocardium. Department of Surgery, Royal Postgraduate Medical School, London W.12. W. J. DEMPSTER.
ORAL CONTRACEPTIVES AND THE URETHRAL SYNDROME women who have frequency and dysuria and a SIR,-Many normal upper urinary tract do not have significant numbers of organisms or pus cells in the urine. Pathogens, including Trichomonas and Monilia, may not be isolated from the urethra, and there may be no history to suggest a chemical cause due to douches, aerosols, or contraceptive methods. Many women with the urethral syndrome relate the symptoms to a few days before the onset of menstruation; this was the case in 1 out of 30 of the women attending my clinic. The urethra and trigone are influenced by the menstrual cycle,ll and oestrogens have been used with good effect in senile urethritis.12 I have found that some premenopausal women improve with an oral oestrogen, quinestradol (’ Pentovis ’), but that most patients with the urethral syndrome respond to urethral dilatation and instillation of chlorhexidine. Of 200 women of childbearing age referred to me with the urethral syndrome, 80 were taking oral contraceptives when first seen. 20 women started taking oral contraceptives before treatment for the urethral condition was begun; I observed that the urinary symptoms disappeared in 15-10 were taking sequential preparations, and 5 preparations containing a combination of progesterone and oestrogen. All the contraceptive preparations were strongly oestrogenic. Among the 5 women taking oral contraceptives without any change in the urinary symptoms, 3 took combinations which were of high progesterone and low oestrogen activity. Regional Urological Centre, Sefton General Hospital, Liverpool 15. Dempster, W. J. Br. J.
R. M.
JAMESON.
plast. Surg. 1953, 5, Najarian, J. S., Gulyassy, P. P., Stoney, R. J., Duffy, G., Braunstein, P. Ann. Surg. 1966, 164, 398. 10. Nakhla, L. S., Glynn, L. E. Immunology, 1967, 13, 209. 11. Br. med. J. 1968, ii, 192. 12. Quinlivan, L. G. Am. J. Obstet. Gynec. 1965, 92, 172. 8. 9.
228.
J. A. BOYCOTT.
RENAL ALLOTRANSPLANTATION IN PRESENCE OF LYMPHOCYTOTOXIC ANTIBODIES SIR,-" Hyperacute " rejection of allotransplanted kidneys, which is referred to by Dr. Stewart and his colleagues last week (p. 176), is a loose clinical term which i’s meaningless from a pathophysiological basis. What is meant is that acute anuria follows the establishment of the new circulation. By using the term, " hyperacute " rejection, one is committed to an immunological interpretation of the anuria, and the evidence for such an interpretation is rather tenuous. If acute rejection implies the classical cellular infiltration, then " hyperacute " should, logically, imply an accelerated version of this; I have referred to it as an accelerated rejection which, in the dog, occurs on the third day, and this is rare in my experience. But " hyperacute " rejection, as defined by Kissmeyer-Nielsen et a1.2 and Williams et al.,3 does not mean this at all. What they refer to is a lesion very similar if not identical to the second-set reaction,4 but this lesion requires careful differentiation from a technical haEmo-
dynamic upset. The evidence for an immunological reaction in the allotransplanted kidneys described by Kissmeyer-Nielsen et al.2 was glomerular thrombosis, but Duguid et awl. and others have demonstrated that this is a technical artefact of preservation even in autotransplants. Williams et awl. were impressed by red-cell clumping and polymorph margination in the glomeruli but this can occur in autotransplant anurias.6g The conditions under which " hyperacute " rejection has been described are quite different. Hamburger et al.’ reported 3/6 early anurias in first-set kidneys from live donors; in 3 nonparous females and 3 males the presumptive diagnoses were (1) technical failure, and (2) pre-existing cytotoxins-there were no serological studies. Kissmeyer-Nielsen et al.2 reported 2/21 early anurias in first-set kidneys from cadaver donors; in 2 parous females the presumptive diagnosis was pregnancy cytotoxins. Williams et awl. reported 1/111 first-set kidneys from live and cadaver donors, and 5/20 immediate anurias in second-set kidneys from mainly cadaver donors along with 1 case of mismatched ABO group (B O) which showed the same lack of function and microscopic appearances; in 2 males and 3 females (1 parous) the presumptive diagnosis was pre1. 2.
3. 4. 5. 6. 7.
Dempster, W. J. Br. med. J. 1963, i, 1697. Kissmeyer-Nielsen, F., Olsen, S., Petersen, V. P., Fjeldborg, O. Lancet, 1966, ii, 662. Williams, G. M., Hume, D. M., Hudson, R. P., Morris, P. J., Kano, K., Milgrom, F. New Engl. J. Med. 1968, 279, 611. Dempster, W. J. Br. J. Surg. 1953, 40, 447. Duguid, W. P., Hendry, W. F., Struthers, N. W. Lancet, 1967, ii, 990. Dempster, W. J. Acta med. scand. 1954, 148, 91. Hamburger, J., Vaysse, J., Crosnier, J., Auvert, J., Lalanne, C. M., Dormont, J. Revue fr. Étud. clin. biol. 1962, 7, 20.
existing antibodies, although Williams et al. have shown that they are not always associated with rejection. In 1 instance, both kidneys of a cadaver donor failed to function, which could indicate a technical mishap. 5/20 immediate anurias in second kidneys from different donors implies cross-sensitisation. One can distinguish a technical from an immunological anuria, and one can distinguish anuria in a sensitised individual from anuria in a hypersensitised individual.The technical anuria (haemoconcentration, &c.) occurs about 5-10 minutes after the circulation has been opened up. The anuria in the sensitised individual occurs some hours (12 to 24 or 36) after quite a brisk diuresis. The anuria in the hypersensitised individual occurs immediately-as in ABO incompatibility, or after multiple grafts of skin before the kidney transplantation. Since Williams et al. encountered " hyperacute " rejection only once in 111 first allotransplants without all the testing carried out by Dr. Stewart and his colleagues, are there any real grounds for believing that pregnancy antibodies and antibodies due to blood-transfusions play any major role in causing immediate anuria in first-set kidneys ? Najarian et al.9 were courageous in confessing to technical failures due to haemoconcentration. And there are those who believe that the more blood-transfusions before kidney transplantation the better the kidney likes it. The demonstration that serum antibodies cross-react with lymphocytes is presumptive evidence but not unequivocal proof that cytopathological effects will be produced by these antibodies on renal allotransplants. Nakhla and Glynn 10 have reported the surprising fact that they cannot attribute any cytopathological effects to the p-haemolytic streptococcal antigen which cross-reacts with an antigen in human mvocardium. Department of Surgery, Royal Postgraduate Medical School, London W.12. W. J. DEMPSTER.
ORAL CONTRACEPTIVES AND THE URETHRAL SYNDROME women who have frequency and dysuria and a SIR,-Many normal upper urinary tract do not have significant numbers of organisms or pus cells in the urine. Pathogens, including Trichomonas and Monilia, may not be isolated from the urethra, and there may be no history to suggest a chemical cause due to douches, aerosols, or contraceptive methods. Many women with the urethral syndrome relate the symptoms to a few days before the onset of menstruation; this was the case in 1 out of 30 of the women attending my clinic. The urethra and trigone are influenced by the menstrual cycle,ll and oestrogens have been used with good effect in senile urethritis.12 I have found that some premenopausal women improve with an oral oestrogen, quinestradol (’ Pentovis ’), but that most patients with the urethral syndrome respond to urethral dilatation and instillation of chlorhexidine. Of 200 women of childbearing age referred to me with the urethral syndrome, 80 were taking oral contraceptives when first seen. 20 women started taking oral contraceptives before treatment for the urethral condition was begun; I observed that the urinary symptoms disappeared in 15-10 were taking sequential preparations, and 5 preparations containing a combination of progesterone and oestrogen. All the contraceptive preparations were strongly oestrogenic. Among the 5 women taking oral contraceptives without any change in the urinary symptoms, 3 took combinations which were of high progesterone and low oestrogen activity. Regional Urological Centre, Sefton General Hospital, Liverpool 15. Dempster, W. J. Br. J.
R. M.
JAMESON.
plast. Surg. 1953, 5, Najarian, J. S., Gulyassy, P. P., Stoney, R. J., Duffy, G., Braunstein, P. Ann. Surg. 1966, 164, 398. 10. Nakhla, L. S., Glynn, L. E. Immunology, 1967, 13, 209. 11. Br. med. J. 1968, ii, 192. 12. Quinlivan, L. G. Am. J. Obstet. Gynec. 1965, 92, 172. 8. 9.
228.