1063 pressure about 15 mm Hg. At first, the fetuses reacted by bradycardia and moderate hypertension (mean arterial bloodpressure 80-100 mm Hg) maintained during !--11 h, followed by hypotension. The central venous pressure hardly changed during the procedure. We suggest that the breakdown of the fetal blood/brain barrier to albumin is due to a combination of the initial moderate hypertension and severe vasodilation during asphyxia.7 The permeability of the blood/brain barrier to albumin in asphyxiated babies would facilitate the transport of bilirubin from plasma to neurones and thus explain the increased susceptibility to kernicterus. Department of Neonatology, Rigshospitalet,
Copenhagen, Denmark
Department of Anaesthesia, Winnipeg, Canada
Health Sciences Centre,
Department of Clinical Physiology, Bispebjerg Hospital, Copenhagen
H. C. LOU
oids
can
Division of Nephrology Ospedale Policlinico, 20122 Milan, Italy
and
Dialysis,
C. PONTICELLI A. TARANTINO P. PIOLTELLI F. INVERNIZZI
Medical Clinic IV, University of Milan
W. A. TWEED G. JOHNSON
AUTOLYMPHOCYTOTOXIC ANTIBODIES AND KIDNEY TRANSPLANTATION
M. JONES
on chronic hxmodialysis may have in their lymphocytotoxic antibodies which react with their own lymphocytes. Kidneys have been transplanted successfully in patients with autolymphocytotoxins despite a positive crossmatch with the lymphocytes of the kidney donor.’Among 132 patients we found autolymphocytotoxic antibodies in 9.
SIR,-Patients
N. A. LASSEN
HIGH-DOSE METHYLPREDNISOLONE PULSES IN ACTIVE LUPUS NEPHRITIS
SIR,-Dr Levinsky and his colleagues (March 12, p. 564) reported a rapid reduction of immune-complex levels and clinical improvement in two patients with active lupus nephritis after administration of high-dose methylprednisolone. We can confirm the efficacy of intravenous steroid pulses in exacerbations of this disease. Six women with diffuse proliferative lupus nephritis and severe clinical symptoms and immunological signs of activity were
and his colleagues that intravenous high-dose sterhave an immunosuppressive action as well as an antiinflammatory effect seems confirmed. Active lupus nephritis is a serious disease which often requires a dangerous protracted course of large doses of oral steroids. A very short course of high-dose intravenous methylprednisolone could be a promising alternative, both improving the results and reducing the side-effects.
Levinsky
given methylprednisolone pulse therapy (1000 mg/day
for 3 days) followed by oral prednisone (0-5-1 mg/kg/day). Double-stranded D.N.A. binding and serum C3, C4, and Clq levels were assessed before treatment and serially for 4-8 weeks. In all the patients clinical symptoms (fever, joint pains, malaise, and rash) soon improved. Serum-creatinine levels returned to normal in patient A and fell in another patient (E) who had chronic renal failure. In two patients with stable renal failure before the treatment (C and F) and in the two with normal renal function the serum-creatinine did not alter. Moreover, the percentage of d.S.-D.N.A. binding fell, and serum levels of C3, C4, and Clq rose. In some cases this effect was rapid, in others it was less dramatic, and, particularly for the complement components, normal values were reached slowly. These results show that methylprednisolone pulse therapy can have a useful role in reversing clinical signs of activity in lupus nephritis. Since this improvement is accompanied by an important lowering of d.S.-D.N.A. binding and by a later increase of serum complement components, the suggestion by Dr 7. Häggendal, E., Johansson, B. Acta neurol scand. 1972, 48, 265.
serum
Because these antibodies interfere with the selection of cadaver
kidneys, giving a positive cross-match with all donors, we tried to remove the autolymphocytotoxins without eliminating the antibodies reactive with lymphocytes of unrelated individuals. We found that, at 4°C, autolymphocytotoxic antibodies could be adsorbed onto autologous erythrocytes. Eluates from these erythrocytes were then prepared at 37°C in saline, and the autolymphocytotoxic activity was recovered in the eluate. In 7 of the 9 patients, the autolymphocytotoxins reacted only with the patient’s B lymphocytes at 22°, 30°, and 37°C. In 2 patients, autolymphocytotoxins were additionally reactive with an enriched T-lymphocyte population at 15° and 22°C. We do not know why adsorption onto autologous erythrocytes removed the autoantibodies and we are now investigating this problem. In one patient ’Sephadex G-100’ chromatography of the serum demonstrated that the autoantibody was of the IgG class. In most of the patients the titre of the lymphocytotoxic antibodies was stable for more than a year. No correlation has been found between presence of the autolymphocytotoxins and the cause of renal failure, neither were there signs of autoimmune disease in the patients. Kourilsky et aJ.3 have reported that patients with glomerular diseases may have a positive direct antiglobulin test with anti-complement serum. All our patients had positive direct 1. 2.
Cross, D. E., Greiner, R. R., Whittier, F. C. Transplantation, 1976, 21, 307. Stastny, P., Austin, C. L. ibid. p. 399. 3. Kourilsky, O., Poyau-Lemaux, C., Lucas, J. P., Neuilly, G., Richet, G. Lancet, 1974, ii, 683.
EFFECT OF METHYLPREDNISOLONE PULSE THERAPY ON D.N.A. BINDING, SERUM COMPH.M) NJ SERUM-CREATININE IN SIX PATIENTS WITH ACTIVE LUPUS NEPHRITIC
COMPONENTS,
AND
1064
antiglobulin tests, predominantly with anti-total-humanimmunoglobulin serum, the reaction persisting for more than
ABO BLOOD-GROUP DISTRIBUTION IN PATIENTS WITH CEREBRAL INFARCTION
(WITH AND WITHOUT CAROTID OCCLUSION),
’
a year. For
PATIENTS WITH CEREBRAL HAEMORRHAGE, AND IN CONTROLS
months the Nijmegen regional tissue-typing been has laboratory distributing over the Eurotransplant area sera deprived of autolymphocytotoxins by adsorption onto
eighteen
autologous erythrocytes. Before distribution, removal of auto-
lymphocytotoxic antibodies is checked by cross-matches with autologous lymphocytes. All the adsorbed sera still contained polyvalent lymphocytotoxic antibodies against unrelated individuals. Negative cross-matches were obtained between the adsorbed serum of two patients and the lymphocytes of prospective kidney donors. The cross-match between nonadsorbed serum of the patient and donor lymphocytes was positive in both cases. Despite this finding, kidney transplantation has been performed. In the first operation the recipient All,-/BW22, BW37 and the donor was Al, A3/B7, BW37; in the second the recipient was A3, All/BW35,-and the donor was A3, A29/BW35,-.To prevent possible damage by cold-agglutinins, the kidneys were flushed immediately was
transplantation with warmed Collins perfusion medium until a temperature of 23 °C was reached inside the kidney. These two patients have excellent renal function nineteen and five months after grafting. ’We suggest that in organ-exchange programmes the sera of
before
haemodialysis
patients
containing
autolymphocytotoxins
should be adsorbed with autologous erythrocytes. In this way kidney donors can be selected that have a negative cross-match despite the presence of a positive cross-match with unadsorbed serum.
Tissue Typing Laboratory, Blood Transfusion Service, and Division of Nephrology, Department of Internal Medicin, Radboud University Hospital, Nijmegen, Netherlands
P. REEKERS R. LUCASSEN-HERMANS R. A. P. KOENE
V. A. J. M. KUNST
MYOSPHERULOSIS IN KENYA
SIR,-We read with interest your editorial on myospherulosis p. 842). Sporadic cases have presented in Kenya since the original description by McClatchie et al.’ Two cases within a period of three months have prompted us to re-examine this condition. The histological features seem to be the same as in the American cases discussed by Kyriakos.2 However, East African patients continue to present with the disease as a primary medical complaint, and there is no obvious iatrogenic cause. Presenting signs and symptoms (i.e., painful multinodular cystic lumps affecting the skin and subcutaneous tissues) represent tissue reaction to a foreign substance. We are puzzled by the biological nature of myospherulosis: alterations in the anatomical structure from an early budding form to a mature, fluid-filled cyst containing typical spherules ("bag of marbles") suggest that this condition develops for a period of time while in the tissue.
(April 16,
Department of Human Pathology and Microbiology, Faculty of Medicine, University of Nairobi, Nairobi, Kenya
R. R. ZIMMERMAN R. C. B. SLACK
CEREBRAL INFARCTION, CEREBRAL HÆMORRHAGE, AND ABO BLOOD-GROUPS
SiR,-Myocardial infarction seems to be associated with an of blood-group A. 34 In view of the pathological and epi-
excess
1.
on
the difference between the four groups: 8.35; 9 D.r.;
d-50;>[’>0-40. demiological similarities between coronary and carotid artery disease, such a blood-group pattern might exist also for cerebral infarction, particularly in those caused by carotid-artery occlusion. lonescu et al.,5 reporting on fatal cases of stroke, found an excess of A+AB in cerebral thrombosis and of 0+B in cerebral haemorrhage; cases of carotid occlusion could not be considered separately because the diagnoses were estalr lished on clinical grounds. We have analysed a series of 602 patients admitted to this hospital in the acute phase of stroke; carotid angiography was done in all cases diagnosed as cerebral infarction, and spinal-fluid examination or necropsy was done in all cases of cerebral haemorrhage. The blood-group distribution in cases of cerebral infarction with or without carotid occlusion did not differ significantly from that found in cases of cerebral haemorrhage or in a control series of Danish blood-donors6 (see table). Further, the "relative incidences"’of blood-groups A+AB-i.e., the product of (A+AB)/(O+B) in the patients and (0+B)/(A+AB) in the control group-were, for cerebral infarction with carotid occlusion 1.20, for cerebral infarction without carotid occlusion 1.18, and for cerebral haemorrhage 1.04. The figures were thus higher for cerebral infarction than for cerebral htmorrhage, but none of them differed significantly from unity. It is possible, as pointed out by lonescu et al., that the A+AB excess found in their series of fatal cerebral infarcts is characteristic of very severe thrombotic cases; this might explain the absence of a similar pattern in our series ofischsmic strokes, most of which were not fatal. Department of Neurology, Frederiksberg Hospital, DK-2000 Copenhagen F, Denmark
STEEN LARSEN BENT ANTHONISEN
J. MARQUARDSEN
ULTRASONOGRAPHY IN HÆMOPHILIA
SIR,-Ultrasonography is of proven value in a variety of clinical situations, and in haemophilia it has attractions in the diagnosis of haematomas because it is not invasive and is readily repeatable. We have used this technique routinely since 1971 in this haemophilia centre and have experience of it in the investigation of haematomas in all anatomical sites in over forty haemophilic patients. It is perhaps of greatest value in intra-abdominal lesions, and we have compared this technique with radionuclide visualisation in retroperitoneal hmmatomas.’ Perhaps the real value is the ability to display the anatomical distribution of the lesion and also measure the response to replacement therapy over several months. It is surprising how much more extensive a muscle haematoma appears on ultrasonography than one would judge clinically and how slowly it
McClatchie, S., Warambo, M. W., Bremner, A. D. Am. J. clin. Path. 1969,
51, 699. Kyriakos, M. ibid. 1977, 67, 118. 3. Bronte-Stewart, B., Botha, M. C., Krut, L. H. Br. med. J. 1962, i, 1646. 4. Viskum, K., Astvad, K., Fabricius-Bjerre, N., Kjærulff, J. Dan. med. Bull. 1975, 22, 126. 2.
test
5. lonescu, D. A., Marcu, I., Bicescu, E. Lancet, 1976, i, 278. 6. Bryde Andersen, S. Ugeskr. Lœg. 1955, 117, 932. 7. Wolf, B. Am. J hum. Genet. 1955, 19, 251. 1. Forbes, C. D., Grant, M., Moule, B., Greig, W. R., Prentice, C. R. M. Am. J. Roent. Rad. Ther. nucl. Med. 1974, 121, 173.
Copenhagen, Denmark
Department of Anaesthesia, Winnipeg, Canada
Health Sciences Centre,
Department of Clinical Physiology, Bispebjerg Hospital, Copenhagen
H. C. LOU
oids
can
Division of Nephrology Ospedale Policlinico, 20122 Milan, Italy
and
Dialysis,
C. PONTICELLI A. TARANTINO P. PIOLTELLI F. INVERNIZZI
Medical Clinic IV, University of Milan
W. A. TWEED G. JOHNSON
AUTOLYMPHOCYTOTOXIC ANTIBODIES AND KIDNEY TRANSPLANTATION
M. JONES
on chronic hxmodialysis may have in their lymphocytotoxic antibodies which react with their own lymphocytes. Kidneys have been transplanted successfully in patients with autolymphocytotoxins despite a positive crossmatch with the lymphocytes of the kidney donor.’Among 132 patients we found autolymphocytotoxic antibodies in 9.
SIR,-Patients
N. A. LASSEN
HIGH-DOSE METHYLPREDNISOLONE PULSES IN ACTIVE LUPUS NEPHRITIS
SIR,-Dr Levinsky and his colleagues (March 12, p. 564) reported a rapid reduction of immune-complex levels and clinical improvement in two patients with active lupus nephritis after administration of high-dose methylprednisolone. We can confirm the efficacy of intravenous steroid pulses in exacerbations of this disease. Six women with diffuse proliferative lupus nephritis and severe clinical symptoms and immunological signs of activity were
and his colleagues that intravenous high-dose sterhave an immunosuppressive action as well as an antiinflammatory effect seems confirmed. Active lupus nephritis is a serious disease which often requires a dangerous protracted course of large doses of oral steroids. A very short course of high-dose intravenous methylprednisolone could be a promising alternative, both improving the results and reducing the side-effects.
Levinsky
given methylprednisolone pulse therapy (1000 mg/day
for 3 days) followed by oral prednisone (0-5-1 mg/kg/day). Double-stranded D.N.A. binding and serum C3, C4, and Clq levels were assessed before treatment and serially for 4-8 weeks. In all the patients clinical symptoms (fever, joint pains, malaise, and rash) soon improved. Serum-creatinine levels returned to normal in patient A and fell in another patient (E) who had chronic renal failure. In two patients with stable renal failure before the treatment (C and F) and in the two with normal renal function the serum-creatinine did not alter. Moreover, the percentage of d.S.-D.N.A. binding fell, and serum levels of C3, C4, and Clq rose. In some cases this effect was rapid, in others it was less dramatic, and, particularly for the complement components, normal values were reached slowly. These results show that methylprednisolone pulse therapy can have a useful role in reversing clinical signs of activity in lupus nephritis. Since this improvement is accompanied by an important lowering of d.S.-D.N.A. binding and by a later increase of serum complement components, the suggestion by Dr 7. Häggendal, E., Johansson, B. Acta neurol scand. 1972, 48, 265.
serum
Because these antibodies interfere with the selection of cadaver
kidneys, giving a positive cross-match with all donors, we tried to remove the autolymphocytotoxins without eliminating the antibodies reactive with lymphocytes of unrelated individuals. We found that, at 4°C, autolymphocytotoxic antibodies could be adsorbed onto autologous erythrocytes. Eluates from these erythrocytes were then prepared at 37°C in saline, and the autolymphocytotoxic activity was recovered in the eluate. In 7 of the 9 patients, the autolymphocytotoxins reacted only with the patient’s B lymphocytes at 22°, 30°, and 37°C. In 2 patients, autolymphocytotoxins were additionally reactive with an enriched T-lymphocyte population at 15° and 22°C. We do not know why adsorption onto autologous erythrocytes removed the autoantibodies and we are now investigating this problem. In one patient ’Sephadex G-100’ chromatography of the serum demonstrated that the autoantibody was of the IgG class. In most of the patients the titre of the lymphocytotoxic antibodies was stable for more than a year. No correlation has been found between presence of the autolymphocytotoxins and the cause of renal failure, neither were there signs of autoimmune disease in the patients. Kourilsky et aJ.3 have reported that patients with glomerular diseases may have a positive direct antiglobulin test with anti-complement serum. All our patients had positive direct 1. 2.
Cross, D. E., Greiner, R. R., Whittier, F. C. Transplantation, 1976, 21, 307. Stastny, P., Austin, C. L. ibid. p. 399. 3. Kourilsky, O., Poyau-Lemaux, C., Lucas, J. P., Neuilly, G., Richet, G. Lancet, 1974, ii, 683.
EFFECT OF METHYLPREDNISOLONE PULSE THERAPY ON D.N.A. BINDING, SERUM COMPH.M) NJ SERUM-CREATININE IN SIX PATIENTS WITH ACTIVE LUPUS NEPHRITIC
COMPONENTS,
AND
1064
antiglobulin tests, predominantly with anti-total-humanimmunoglobulin serum, the reaction persisting for more than
ABO BLOOD-GROUP DISTRIBUTION IN PATIENTS WITH CEREBRAL INFARCTION
(WITH AND WITHOUT CAROTID OCCLUSION),
’
a year. For
PATIENTS WITH CEREBRAL HAEMORRHAGE, AND IN CONTROLS
months the Nijmegen regional tissue-typing been has laboratory distributing over the Eurotransplant area sera deprived of autolymphocytotoxins by adsorption onto
eighteen
autologous erythrocytes. Before distribution, removal of auto-
lymphocytotoxic antibodies is checked by cross-matches with autologous lymphocytes. All the adsorbed sera still contained polyvalent lymphocytotoxic antibodies against unrelated individuals. Negative cross-matches were obtained between the adsorbed serum of two patients and the lymphocytes of prospective kidney donors. The cross-match between nonadsorbed serum of the patient and donor lymphocytes was positive in both cases. Despite this finding, kidney transplantation has been performed. In the first operation the recipient All,-/BW22, BW37 and the donor was Al, A3/B7, BW37; in the second the recipient was A3, All/BW35,-and the donor was A3, A29/BW35,-.To prevent possible damage by cold-agglutinins, the kidneys were flushed immediately was
transplantation with warmed Collins perfusion medium until a temperature of 23 °C was reached inside the kidney. These two patients have excellent renal function nineteen and five months after grafting. ’We suggest that in organ-exchange programmes the sera of
before
haemodialysis
patients
containing
autolymphocytotoxins
should be adsorbed with autologous erythrocytes. In this way kidney donors can be selected that have a negative cross-match despite the presence of a positive cross-match with unadsorbed serum.
Tissue Typing Laboratory, Blood Transfusion Service, and Division of Nephrology, Department of Internal Medicin, Radboud University Hospital, Nijmegen, Netherlands
P. REEKERS R. LUCASSEN-HERMANS R. A. P. KOENE
V. A. J. M. KUNST
MYOSPHERULOSIS IN KENYA
SIR,-We read with interest your editorial on myospherulosis p. 842). Sporadic cases have presented in Kenya since the original description by McClatchie et al.’ Two cases within a period of three months have prompted us to re-examine this condition. The histological features seem to be the same as in the American cases discussed by Kyriakos.2 However, East African patients continue to present with the disease as a primary medical complaint, and there is no obvious iatrogenic cause. Presenting signs and symptoms (i.e., painful multinodular cystic lumps affecting the skin and subcutaneous tissues) represent tissue reaction to a foreign substance. We are puzzled by the biological nature of myospherulosis: alterations in the anatomical structure from an early budding form to a mature, fluid-filled cyst containing typical spherules ("bag of marbles") suggest that this condition develops for a period of time while in the tissue.
(April 16,
Department of Human Pathology and Microbiology, Faculty of Medicine, University of Nairobi, Nairobi, Kenya
R. R. ZIMMERMAN R. C. B. SLACK
CEREBRAL INFARCTION, CEREBRAL HÆMORRHAGE, AND ABO BLOOD-GROUPS
SiR,-Myocardial infarction seems to be associated with an of blood-group A. 34 In view of the pathological and epi-
excess
1.
on
the difference between the four groups: 8.35; 9 D.r.;
d-50;>[’>0-40. demiological similarities between coronary and carotid artery disease, such a blood-group pattern might exist also for cerebral infarction, particularly in those caused by carotid-artery occlusion. lonescu et al.,5 reporting on fatal cases of stroke, found an excess of A+AB in cerebral thrombosis and of 0+B in cerebral haemorrhage; cases of carotid occlusion could not be considered separately because the diagnoses were estalr lished on clinical grounds. We have analysed a series of 602 patients admitted to this hospital in the acute phase of stroke; carotid angiography was done in all cases diagnosed as cerebral infarction, and spinal-fluid examination or necropsy was done in all cases of cerebral haemorrhage. The blood-group distribution in cases of cerebral infarction with or without carotid occlusion did not differ significantly from that found in cases of cerebral haemorrhage or in a control series of Danish blood-donors6 (see table). Further, the "relative incidences"’of blood-groups A+AB-i.e., the product of (A+AB)/(O+B) in the patients and (0+B)/(A+AB) in the control group-were, for cerebral infarction with carotid occlusion 1.20, for cerebral infarction without carotid occlusion 1.18, and for cerebral haemorrhage 1.04. The figures were thus higher for cerebral infarction than for cerebral htmorrhage, but none of them differed significantly from unity. It is possible, as pointed out by lonescu et al., that the A+AB excess found in their series of fatal cerebral infarcts is characteristic of very severe thrombotic cases; this might explain the absence of a similar pattern in our series ofischsmic strokes, most of which were not fatal. Department of Neurology, Frederiksberg Hospital, DK-2000 Copenhagen F, Denmark
STEEN LARSEN BENT ANTHONISEN
J. MARQUARDSEN
ULTRASONOGRAPHY IN HÆMOPHILIA
SIR,-Ultrasonography is of proven value in a variety of clinical situations, and in haemophilia it has attractions in the diagnosis of haematomas because it is not invasive and is readily repeatable. We have used this technique routinely since 1971 in this haemophilia centre and have experience of it in the investigation of haematomas in all anatomical sites in over forty haemophilic patients. It is perhaps of greatest value in intra-abdominal lesions, and we have compared this technique with radionuclide visualisation in retroperitoneal hmmatomas.’ Perhaps the real value is the ability to display the anatomical distribution of the lesion and also measure the response to replacement therapy over several months. It is surprising how much more extensive a muscle haematoma appears on ultrasonography than one would judge clinically and how slowly it
McClatchie, S., Warambo, M. W., Bremner, A. D. Am. J. clin. Path. 1969,
51, 699. Kyriakos, M. ibid. 1977, 67, 118. 3. Bronte-Stewart, B., Botha, M. C., Krut, L. H. Br. med. J. 1962, i, 1646. 4. Viskum, K., Astvad, K., Fabricius-Bjerre, N., Kjærulff, J. Dan. med. Bull. 1975, 22, 126. 2.
test
5. lonescu, D. A., Marcu, I., Bicescu, E. Lancet, 1976, i, 278. 6. Bryde Andersen, S. Ugeskr. Lœg. 1955, 117, 932. 7. Wolf, B. Am. J hum. Genet. 1955, 19, 251. 1. Forbes, C. D., Grant, M., Moule, B., Greig, W. R., Prentice, C. R. M. Am. J. Roent. Rad. Ther. nucl. Med. 1974, 121, 173.
