478 COLD AND WARM B-CELL ANTIBODIES IN RENAL TRANSPLANTATION
SiR,—Iwaki
et
antibodies which
al.demonstrated that
patients with B-cell
reactedonly at 5C (B-cold) in a lymphocytosignificantly better kidney-graft survival-rate
toxic test had a than either patients with B-cell antibodies which reacted at both 5°C and 37°C (B-warm) or patients with no antibodies. They suggested that B-cold antibodies may be enhancing antibodies. However, our results disagree with these observations. We have examined the sera of 23 recipients of a B-cell-positive-crossmatch transplant for cold and warm antibodies against a panel of T and B lymphocytes. In addition the sera of 7 patients were tested under the same conditions against their donor’s B lymphocytes. The cytotoxicity method and the criteria used for the definition of B-cold, B-warm, and T-warm antibodies were those described by Iwaki et al.1Failure of a graft was defined as nephrectomy or return to chronic haemo-
dialysis.
3-MONTH
Department of Surgery, University of Oxford, Radcliffe Infirmary, Nuffield
Oxford OX2 6HE
*Type of antibody assigned according t Includes one technical failure.
Although
the number of
to
patients
the method of Iwaki
et
al.’
in each group is small
those with B-warm and T-warm antibodies certainly do
not
have success-rate at 3 months inferior to that in the groups with either B-cold antibodies or no antibodies (see table). Although we have classified the sera as having only B-cold, B-warm, or T-warm antibodies using Iwaki’s criteria, we feel that this classification is incomplete. We found, as Iwaki noted, that a serum which reacts at 37°C with some panel B cells will in most instances react with the same cells at 5C but that the reverse is not necessarily true-i.e., sera which react with B cells at 5C will not always react with the same cells at 37°C. In addition some sera react with certain B cells at both 5C and 37°C and other B cells at 5C only. These antibodies have been called B-warm by Iwaki, but we feel that they should be defined as B-cold+B-warm. "B-warm" should be reserved only for sera which react with the same cells at both 50C and 37°C. We found, in our 23 patients, 14 (61%) with B-cold+B-warm antibodies (3 had a failed transplant), 8 (35%) with B-cold antibodies (2 had a failed transplant), and 1 with only B-warm antibodies who had a successful transplant. The division of Iwaki’s B-warm antibodies into either B-cold+B-warm or B-warm is particularly relevant in the interpretation of B cell crossmatch results. The crossmatch sera of 7 of the 23 recipients were reacted against their respective donors’ B cells at both 3°C and 37°C. 6 patients had B-cold+B-warm antibodies against panel B cells and 1 had only B-cold antibodies. The 5 successfully transplanted patients with B-cold+B-warm antibodies reacted with their donors’ B cells at both 5C and 37°C. The patient with the failed graft and B-cold+B-warm antibodies also reacted with the donor at 5C and 37°C. As expected the patient with B-cold antibodies reacted only at 5C with the donor’s B cells. Y., Terasaki, P. I., Park, M. S., Billing, R.Lancet, 1977, i, 1228.
ALAN TING PETER J. MORRIS
ENDOSCOPIC DILATATION OF PYLORIC SPHINCTER
GRAFT OUTCOME IN PATIENTS WITH DIFFERENT TYPES
OF ANTIBODIES
1. Iwaki,
Iwaki tested only 1 serum from each recipient, but we have found that the type of antibody can change over time. For example, 1 patient who rejected her first transplant developed B-cold+B-warm antibodies immediately after removal of the graft. 3 months later her serum also reacted with T cells at both 5C and 37°C, but 15 months later had only B-cold antibodies. Therefore for a full picture of the antibodies serial serum-samples from each patients should be tested. When sera from potential transplant recipients are tested for lymphocyte cytotoxic antibodies at both 5C and 37°C there is no doubt that some antibodies react at both temperatures while others react only at 5°C. However, in contrast to Iwaki et al. we feel that transplantation can be carried out with the same degree of success whether a B-cell crossmatch is positive at 50C and 370C or just at 5°C.
SIR,-Instrumental dilatation of stricturing oesophageal lesions is standard practice. There is no reason why it should not be applied to comparable lesions of the pyloric sphincter. Pyloric stenosis is a well-known complication of chronic or recurrent duodenal-ulcer disease, and sometimes it becomes the main indication for surgery. During endoscopic examination of these patients, the passage of the instrument through the pyloric sphincter stretches it. After two patients reported relief of their vomiting following endoscopy, we realised that dilatation of the sphincter could be a deliberate therapeutic objective. We now have a further three patients in whom this has been carried out with success. If this is a major goal of the endoscopic procedure, the instrument should be passed in and out of the sphincter zone several times. Endoscopic dilatation of the pyloric sphincter is feasible in some patients and it works. It may have to be repeated, but this is no different from the management of many oesophageal lesions. In certain patients it can stave off surgery. The endoscope would seem to be the best instrument for the technique, though there will be degrees of stenosis it cannot deal with. Department of Medicine and Gastrointestinal Unit, Victoria Hospital, London, Ontario N6A 4G5, Canada
W. C. WATSON
SUCCESS OR FAILURE OF DIPYRIDAMOLE IN MIGRAINE
SIR,-Dr Hawkes (July 15, p. 153) described a trial of dipyridamole in migraine which had to be stopped because of increased migraine attacks in all patients. Dipyridamole was given because platelet aggregation in migraine patients has been reported to be abnormal.1However, the author did not indicate in how many of his patients platelet aggregation was abnormal. In my experience only a subgroup of migraine patients have abnormal platelet aggregation. Masel et al.noted that only patients with abnormal aggregation improved on dipyridamole (indeed, two of their non-responders had normal platelet aggregation). It thus seems possible that Hawkes’ patients had normal platelet aggregation, which may explain their lack of response.
Migraine may have worsened, on the other hand, because of dosage used by Hawkes (400 mg/day). I have used dipyri-
the
1. Deshmukh, S. V., Meyer, J. S. Neurology, 1976, 26, 347. 2. Couch, J. R., Hassanein, R. S. ibid. p. 348. 3. Masel, B. E., Chesson, A. L., Alpenin, J. B., Levin, H. S., Peters, B. H. ibid.
1978, 28, 371.
479 damole
as a
case, at 200
preventive treatment at 150 mg/day and, in one mg/day. None of the patients reported an increase
in frequency and severity of migraine attacks and in two cases, followed now for 2 Zmonths and 3 months, there was a remarkable lessening in the frequency and severity of attacks. This result is similar to that of Masel et al.,3 who also gave 150 mg/day (although their patients were also taking 600 mg/day
aspirin). Hawkes explains the negative results on the basis of dipyridamole’s action as a vasodilator4 and states that headaches have been mentioned as a side-effect of dipyridamole in the treatment of transient ischsemic attacks.5 However it seems possible that both the vasodilator action and its presumed sideeffect are dose-related. This would explain the absence of headaches in my patients as well as in Masel’s.3 Hawkes’ conclusion that dipyridamole aggravates migraine may be premature.
from vasectomised donors can stimulate allogeneic in culture, and that a small number of cells can be a potent stimulus. The significance of non-spermatozoal seminal cells in infertility and fertility is not yet fully appreciated. Could the local immune response in the female genital tract, upon repeated exposure to seminal cells in the absence of spermatozoa, be diverted towards sensitisation to the alloantigens expressed on the seminal cells? Sensitisation may be of particular relevance if vasovasotomy is contemplated by men with non-spermatozoal cells in their semen, especially if spermatozoa and the seminal cells share antigens. in
semen
leucocytes
Department of Biological Sciences, University of Newcastle, N.S.W. 2308, Australia Newcastle Infertility Centre
I. S. MISKO B. BOETTCHER RHELMA GRUSZYNSKI
Migraine Clinic, University Hospitals and Clinics, Iowa
HANNA DAMASIO
City, IA 52242, U.S.A.
EROSION OF TEETH BY GASTRIC CONTENTS LYMPHOCYTE STIMULATION BY ALLOGENEIC CELLS IN SPERM-FREE EJACULATES
.
SIR,-I believe it is
SIR,-In our experience, all normal human semen samples contain non-spermatozoal cells, although the number and types of cells may vary between donors. We suggested’ that the non-spermatozoal cells, particularly macrophages and lymphocytes, contaminating crude preparations of spermatozoa, triggered lymphocyte activation in allogeneic mixed sperm/leucocyte cultures. We have examined microscopically semen samples from six vasectomised donors. All the samples contained large numbers of vesicles and granules, but only three (from donors A, C, and E) contained non-spermatozoal cells (range 1-5 x 105 cells/ml semen). The seminal cells, many of which morphologically resembled active macrophages (histiocytes?), were washed three times by centrifugation and set up as stimulators with responder leucocytes from the semen donor and an unrelated individual. Corresponding mixed leucocyte cultures, using leucocytes from the semen-donor and from the responder, were set up as controls. 3H-THYMIDINE
INCORPORATION ON DAY
6
OF
recognised widely enough that vomiting regurgitation of gastric contents over a sufficiently long period can lead to erosion of the teeth. Anorrecurrent
CULTURE IN
COUNTS/MIN (S.E.M.)
not
or
exia nervosa and hiatus hernia are two conditions which have been implicated but frequently regurgitation may occur alone, sometimes in relation to the intake of certain foods. The acid material dissolves enamel and at a more advanced stage the dentine also is involved. This affects mainly the lingual sur-
faces of the upper teeth. Sensitivity to thermal and sweet stimuli may occur and eventually the teeth become so short as to be unsightly, function is affected, and, rarely, the pulps may be exposed. The effect on the dentition can be devastating, particularly in children and teenagers. The treatment of patients should include early referral to a dentist or dental consultant. Prevention of damage to the teeth is not easy, and its success is difficult to measure, but topical application of fluoride in the form of a mouthwash or gel until the original condition can be resolved, is thought to be of value. Should prevention not be successful, the earlier treatment is begun the more successful the results are likely to be. Treatment consists of crowning some or all of the teeth in one or both arches, and is consequently expensive. It requires a high degree of skill and is more difficult in young people. A similar condition can arise from prolonged high consumption of citrus fruits, fruit juices, or acid beverages. This tends to affect the labial surfaces of the anterior teeth. I have had a special interest in such dentitions for some years and have realised the damage, discomfort, and loss of appearance which can arise, and the cost of treatment. I appeal to your readers to give thought to the dental welfare of these patients. Department of Conservative Dentistry, Welsh National School of Medicine,
J. D. ECCLES
Cardiff CF4 4XY
*2 104 seminal cells cultured with 5 x 104 responder leucocytes.
t 5 x 101 mitomycin-treated leucocytes cultured with 5 x 104 responder
JEJUNAL BIOPSY WITHOUT THE NEED FOR
leucocytes.
SCREENING
Donors A, C, and E mal and unrelated. n.t.=not tested.
were
vasectomised; donors B, D, and F
were nor-
Vigorous stimulation was observed in the allogeneic culture containing seminal cells from donor A (see table) and the seminal cells from donors C and E were weakly stimulatory. Our findings clearly demonstrate that non-spermatozoal cells 4.
Vineberg,
A. M.,
SIR,-I am surprised that Holstock’ in his description of a method for jejunal biopsy without screening made no reference to the article by Prout who described the same technique, investigated a similar number of patients, and came to the same conclusion as Dr Holstock, but four years earlier. St. Bartholomew’s Hospital, London EC1A 7BE
Chari, R. S., Pifarre, R., Mercier, C. Can. med. Ass. J.
1962, 87, 336. 5. Acheson, J., Danta, G., Hutchinson, E. C.Br. med. J. 1969, i, 614. 1. Misko, I. S., Boettcher, B., Roberts, T. K., Kay, D. Lancet, 1978, 1,
560.
1. 2.
Holstock, G. Lancet, 1978, i, 1236. Prout, B. J. Gut, 1974, 15, 571.
J.
KINGHAM
SiR,—Iwaki
et
antibodies which
al.demonstrated that
patients with B-cell
reactedonly at 5C (B-cold) in a lymphocytosignificantly better kidney-graft survival-rate
toxic test had a than either patients with B-cell antibodies which reacted at both 5°C and 37°C (B-warm) or patients with no antibodies. They suggested that B-cold antibodies may be enhancing antibodies. However, our results disagree with these observations. We have examined the sera of 23 recipients of a B-cell-positive-crossmatch transplant for cold and warm antibodies against a panel of T and B lymphocytes. In addition the sera of 7 patients were tested under the same conditions against their donor’s B lymphocytes. The cytotoxicity method and the criteria used for the definition of B-cold, B-warm, and T-warm antibodies were those described by Iwaki et al.1Failure of a graft was defined as nephrectomy or return to chronic haemo-
dialysis.
3-MONTH
Department of Surgery, University of Oxford, Radcliffe Infirmary, Nuffield
Oxford OX2 6HE
*Type of antibody assigned according t Includes one technical failure.
Although
the number of
to
patients
the method of Iwaki
et
al.’
in each group is small
those with B-warm and T-warm antibodies certainly do
not
have success-rate at 3 months inferior to that in the groups with either B-cold antibodies or no antibodies (see table). Although we have classified the sera as having only B-cold, B-warm, or T-warm antibodies using Iwaki’s criteria, we feel that this classification is incomplete. We found, as Iwaki noted, that a serum which reacts at 37°C with some panel B cells will in most instances react with the same cells at 5C but that the reverse is not necessarily true-i.e., sera which react with B cells at 5C will not always react with the same cells at 37°C. In addition some sera react with certain B cells at both 5C and 37°C and other B cells at 5C only. These antibodies have been called B-warm by Iwaki, but we feel that they should be defined as B-cold+B-warm. "B-warm" should be reserved only for sera which react with the same cells at both 50C and 37°C. We found, in our 23 patients, 14 (61%) with B-cold+B-warm antibodies (3 had a failed transplant), 8 (35%) with B-cold antibodies (2 had a failed transplant), and 1 with only B-warm antibodies who had a successful transplant. The division of Iwaki’s B-warm antibodies into either B-cold+B-warm or B-warm is particularly relevant in the interpretation of B cell crossmatch results. The crossmatch sera of 7 of the 23 recipients were reacted against their respective donors’ B cells at both 3°C and 37°C. 6 patients had B-cold+B-warm antibodies against panel B cells and 1 had only B-cold antibodies. The 5 successfully transplanted patients with B-cold+B-warm antibodies reacted with their donors’ B cells at both 5C and 37°C. The patient with the failed graft and B-cold+B-warm antibodies also reacted with the donor at 5C and 37°C. As expected the patient with B-cold antibodies reacted only at 5C with the donor’s B cells. Y., Terasaki, P. I., Park, M. S., Billing, R.Lancet, 1977, i, 1228.
ALAN TING PETER J. MORRIS
ENDOSCOPIC DILATATION OF PYLORIC SPHINCTER
GRAFT OUTCOME IN PATIENTS WITH DIFFERENT TYPES
OF ANTIBODIES
1. Iwaki,
Iwaki tested only 1 serum from each recipient, but we have found that the type of antibody can change over time. For example, 1 patient who rejected her first transplant developed B-cold+B-warm antibodies immediately after removal of the graft. 3 months later her serum also reacted with T cells at both 5C and 37°C, but 15 months later had only B-cold antibodies. Therefore for a full picture of the antibodies serial serum-samples from each patients should be tested. When sera from potential transplant recipients are tested for lymphocyte cytotoxic antibodies at both 5C and 37°C there is no doubt that some antibodies react at both temperatures while others react only at 5°C. However, in contrast to Iwaki et al. we feel that transplantation can be carried out with the same degree of success whether a B-cell crossmatch is positive at 50C and 370C or just at 5°C.
SIR,-Instrumental dilatation of stricturing oesophageal lesions is standard practice. There is no reason why it should not be applied to comparable lesions of the pyloric sphincter. Pyloric stenosis is a well-known complication of chronic or recurrent duodenal-ulcer disease, and sometimes it becomes the main indication for surgery. During endoscopic examination of these patients, the passage of the instrument through the pyloric sphincter stretches it. After two patients reported relief of their vomiting following endoscopy, we realised that dilatation of the sphincter could be a deliberate therapeutic objective. We now have a further three patients in whom this has been carried out with success. If this is a major goal of the endoscopic procedure, the instrument should be passed in and out of the sphincter zone several times. Endoscopic dilatation of the pyloric sphincter is feasible in some patients and it works. It may have to be repeated, but this is no different from the management of many oesophageal lesions. In certain patients it can stave off surgery. The endoscope would seem to be the best instrument for the technique, though there will be degrees of stenosis it cannot deal with. Department of Medicine and Gastrointestinal Unit, Victoria Hospital, London, Ontario N6A 4G5, Canada
W. C. WATSON
SUCCESS OR FAILURE OF DIPYRIDAMOLE IN MIGRAINE
SIR,-Dr Hawkes (July 15, p. 153) described a trial of dipyridamole in migraine which had to be stopped because of increased migraine attacks in all patients. Dipyridamole was given because platelet aggregation in migraine patients has been reported to be abnormal.1However, the author did not indicate in how many of his patients platelet aggregation was abnormal. In my experience only a subgroup of migraine patients have abnormal platelet aggregation. Masel et al.noted that only patients with abnormal aggregation improved on dipyridamole (indeed, two of their non-responders had normal platelet aggregation). It thus seems possible that Hawkes’ patients had normal platelet aggregation, which may explain their lack of response.
Migraine may have worsened, on the other hand, because of dosage used by Hawkes (400 mg/day). I have used dipyri-
the
1. Deshmukh, S. V., Meyer, J. S. Neurology, 1976, 26, 347. 2. Couch, J. R., Hassanein, R. S. ibid. p. 348. 3. Masel, B. E., Chesson, A. L., Alpenin, J. B., Levin, H. S., Peters, B. H. ibid.
1978, 28, 371.
479 damole
as a
case, at 200
preventive treatment at 150 mg/day and, in one mg/day. None of the patients reported an increase
in frequency and severity of migraine attacks and in two cases, followed now for 2 Zmonths and 3 months, there was a remarkable lessening in the frequency and severity of attacks. This result is similar to that of Masel et al.,3 who also gave 150 mg/day (although their patients were also taking 600 mg/day
aspirin). Hawkes explains the negative results on the basis of dipyridamole’s action as a vasodilator4 and states that headaches have been mentioned as a side-effect of dipyridamole in the treatment of transient ischsemic attacks.5 However it seems possible that both the vasodilator action and its presumed sideeffect are dose-related. This would explain the absence of headaches in my patients as well as in Masel’s.3 Hawkes’ conclusion that dipyridamole aggravates migraine may be premature.
from vasectomised donors can stimulate allogeneic in culture, and that a small number of cells can be a potent stimulus. The significance of non-spermatozoal seminal cells in infertility and fertility is not yet fully appreciated. Could the local immune response in the female genital tract, upon repeated exposure to seminal cells in the absence of spermatozoa, be diverted towards sensitisation to the alloantigens expressed on the seminal cells? Sensitisation may be of particular relevance if vasovasotomy is contemplated by men with non-spermatozoal cells in their semen, especially if spermatozoa and the seminal cells share antigens. in
semen
leucocytes
Department of Biological Sciences, University of Newcastle, N.S.W. 2308, Australia Newcastle Infertility Centre
I. S. MISKO B. BOETTCHER RHELMA GRUSZYNSKI
Migraine Clinic, University Hospitals and Clinics, Iowa
HANNA DAMASIO
City, IA 52242, U.S.A.
EROSION OF TEETH BY GASTRIC CONTENTS LYMPHOCYTE STIMULATION BY ALLOGENEIC CELLS IN SPERM-FREE EJACULATES
.
SIR,-I believe it is
SIR,-In our experience, all normal human semen samples contain non-spermatozoal cells, although the number and types of cells may vary between donors. We suggested’ that the non-spermatozoal cells, particularly macrophages and lymphocytes, contaminating crude preparations of spermatozoa, triggered lymphocyte activation in allogeneic mixed sperm/leucocyte cultures. We have examined microscopically semen samples from six vasectomised donors. All the samples contained large numbers of vesicles and granules, but only three (from donors A, C, and E) contained non-spermatozoal cells (range 1-5 x 105 cells/ml semen). The seminal cells, many of which morphologically resembled active macrophages (histiocytes?), were washed three times by centrifugation and set up as stimulators with responder leucocytes from the semen donor and an unrelated individual. Corresponding mixed leucocyte cultures, using leucocytes from the semen-donor and from the responder, were set up as controls. 3H-THYMIDINE
INCORPORATION ON DAY
6
OF
recognised widely enough that vomiting regurgitation of gastric contents over a sufficiently long period can lead to erosion of the teeth. Anorrecurrent
CULTURE IN
COUNTS/MIN (S.E.M.)
not
or
exia nervosa and hiatus hernia are two conditions which have been implicated but frequently regurgitation may occur alone, sometimes in relation to the intake of certain foods. The acid material dissolves enamel and at a more advanced stage the dentine also is involved. This affects mainly the lingual sur-
faces of the upper teeth. Sensitivity to thermal and sweet stimuli may occur and eventually the teeth become so short as to be unsightly, function is affected, and, rarely, the pulps may be exposed. The effect on the dentition can be devastating, particularly in children and teenagers. The treatment of patients should include early referral to a dentist or dental consultant. Prevention of damage to the teeth is not easy, and its success is difficult to measure, but topical application of fluoride in the form of a mouthwash or gel until the original condition can be resolved, is thought to be of value. Should prevention not be successful, the earlier treatment is begun the more successful the results are likely to be. Treatment consists of crowning some or all of the teeth in one or both arches, and is consequently expensive. It requires a high degree of skill and is more difficult in young people. A similar condition can arise from prolonged high consumption of citrus fruits, fruit juices, or acid beverages. This tends to affect the labial surfaces of the anterior teeth. I have had a special interest in such dentitions for some years and have realised the damage, discomfort, and loss of appearance which can arise, and the cost of treatment. I appeal to your readers to give thought to the dental welfare of these patients. Department of Conservative Dentistry, Welsh National School of Medicine,
J. D. ECCLES
Cardiff CF4 4XY
*2 104 seminal cells cultured with 5 x 104 responder leucocytes.
t 5 x 101 mitomycin-treated leucocytes cultured with 5 x 104 responder
JEJUNAL BIOPSY WITHOUT THE NEED FOR
leucocytes.
SCREENING
Donors A, C, and E mal and unrelated. n.t.=not tested.
were
vasectomised; donors B, D, and F
were nor-
Vigorous stimulation was observed in the allogeneic culture containing seminal cells from donor A (see table) and the seminal cells from donors C and E were weakly stimulatory. Our findings clearly demonstrate that non-spermatozoal cells 4.
Vineberg,
A. M.,
SIR,-I am surprised that Holstock’ in his description of a method for jejunal biopsy without screening made no reference to the article by Prout who described the same technique, investigated a similar number of patients, and came to the same conclusion as Dr Holstock, but four years earlier. St. Bartholomew’s Hospital, London EC1A 7BE
Chari, R. S., Pifarre, R., Mercier, C. Can. med. Ass. J.
1962, 87, 336. 5. Acheson, J., Danta, G., Hutchinson, E. C.Br. med. J. 1969, i, 614. 1. Misko, I. S., Boettcher, B., Roberts, T. K., Kay, D. Lancet, 1978, 1,
560.
1. 2.
Holstock, G. Lancet, 1978, i, 1236. Prout, B. J. Gut, 1974, 15, 571.
J.
KINGHAM
