Pregnancy after treatment with paternal lymphocytes.
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Biomedical subjects
Publications and source records attributed to A M MacLeod.
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The influence of allogeneic pregnancies on the survival of subsequent rat renal allografts was investigated in three rat strain combinations. Multiple but not single pregnancies produced significantly more long-term surviving kidney grafts than were found in virgin animals; the effect was specific for paternal antigens, as multiple pregnancies by an unrelated strain did not prolong kidney graft survival. In the multiparous groups, those animals with long-surviving grafts had significantly higher levels of non-cytotoxic antibodies against paternal strain B-lymphocytes (detected by the erythrocyte antibody rosette inhibition assay) than did animals which rejected their grafts. The results show that multiple pregnancies may produce a state of specific unresponsiveness to paternal antigens, similar to enhancement, which is marked by the presence of non-cytotoxic antibodies against paternal B-lymphocytes. It is suggested, therefore, that enhancement may be one of the protective mechanisms which prevent rejection of the fetus during pregnancy.
We have previously shown that the presence in pretransplant recipient sera of Fc receptor blocking antibodies detected by the EA inhibition assay is correlated with improved allograft survival. Twenty-four such sera were assessed for the presence of autoantibodies by the EA inhibition and lymphocytotoxicity assays. No autolymphocytotoxic antibodies were found, and autologous EA inhibition was noted in only one case. EA-inhibiting alloantibodies did occur, and their presence was correlated with improved allograft survival. Sera from 37 dialysis patients were also studied, and neither autologous EA inhibiting nor autologous lymphocytotoxic antibodies were present. Thus Fc receptor blocking alloantibodies that were correlated with improved renal transplant survival were not autoantibodies.
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Free vascularized digital joint transfers should provide joint stability, painless functional range of motion (ROM), tolerance of normal stresses without degeneration, and growth potential in children. In our department since 1977, seven transfers have been carried out in seven patients, including four children aged 4 to 11 years and three adults aged 19 to 46 years. Donor sites were the metatarsophalangeal joint of the second toe (four cases), the proximal interphalangeal (PIP) joint of the second toe (two cases), and the PIP joint of a useless amputated small finger (one case). Recipient sites were digital PIP and metacarpophalangeal (MP) joints (three cases each) and the MP joint of a thumb (one case). Six of the seven procedures were successful. There was retention of normal joint space and stable, painless functional ROM, while epiphyseal centers in the children remained open and showed normal growth. Follow-up ranged from 2 to 4.7 years, averaging 3.5 years. Some adherence of an associated extensor tendon has been observed. The feet have been asymptomatic. When digital joint replacement is required because of local causes of destruction, free toe joint transfer should certainly be considered in children and in young adults.
Four cases are described in which the opposite ring finger was used for finger reconstruction in transmetacarpal hand amputations. Thumb reconstruction was required in three of these four cases. This was achieved by hallux transfer, tube pedicle combined with an innervated first foot web neurovascular free flap, and second toe transfer respectively. In the fourth case, where a thumb was not required, double finger reconstruction was performed by the use of a second toe combined with a ring finger. This case highlights the limitations of the second toe for finger reconstruction, particularly in achieving palmar-digital grip. The advantages of the ring finger are length and mobility, especially sophisticated intrinsic muscle movement, sensory capacity, strength, wider span, and esthetic excellence.
Noncytotoxic antibodies were detected in sera from 6 of 7 primigravid women during the first trimester of pregnancy. Such antibodies directed to antigens expressed on paternal B lymphocytes were detectable within the first 4-5 weeks of gestation. Antibody activity toward paternal B lymphocytes was also detected in 6 of 10 placental eluates, and in 3 of 10 predelivery and 2 of 10 postdelivery maternal serum samples. When B lymphocytes from umbilical cord blood were used as target cells, antibodies were detected in 5 of 7 placental eluates, and in 3 of 7 predelivery and 2 of 7 postdelivery serum samples. These antibodies also reacted with selected members of a normal B lymphocyte panel. The concept of an immunological enhancing mechanism in normal pregnancy is supported by these data.
An unabridged series of 73 thumb amputations subjected to replantation or revascularization surgery in the years 1971 to 1980 has been examined in detail as a combined prospective and retrospective study to determine the factors playing a role in survival and failure. The causes of failure and complications are demonstrated. The overall failure rate was 27%. The factors influencing the outcome were: the injury--mechanical type and degree of amputation; the patient--age and amputation level; and the surgeon--frequency of utilization of vein grafts. The highest failure was seen in the complete amputation with avulsion/diffuse crush injury group (63%). Incomplete amputations had the lowest failure rate, particularly if the injury type was guillotine/local crush and at a level proximal to the metacarpophalangeal joint. Patients aged 11 to 20 years had a low failure rate (18%) whereas children under 5 years had a high failure rate (40%). Arterial thrombosis was the most frequent complication and cause of failure. The surgeon could modify the result by frequent use of vein grafts for arterial reconstruction and by reoperation for thrombotic complication. Five thumbs failed to revascularize at the primary operation and were removed at this primary operation.
Serial pelvic imaging after injection of autologous platelets labelled with 111In was used to study 22 consecutive patients following cadaver renal transplantation. Increases in isotope uptake by the allografts were observed during episodes of acute rejection (12/22) but not during acute tubular necrosis (4/22). The technique was not influenced by oliguria or hemodialysis therapy. Extra-renal accumulations of labelled platelets were noted in perinephric hematomata and deep vein thromboses.
Non-cytotoxic antibodies to paternal B lymphocytes were detected in sera from 11 of 11 multiparous women and from 11 of 16 normal primigravidae during the first trimester of pregnancy. These antibodies were not, however, detected in sera from 9 of 10 women of comparable gestation at the time of spontaneous abortion. By means of a rosette inhibition assay, the difference in antibody activity between the primigravidae (mean 37.9 +/- 19%, median 36.5%) and the women subject to spontaneous abortion (mean 7.3 +/- 11.6%, median 0%) was statistically significant. This antibody activity was not directed to the known HLA specificities (HLA--A, B, C, or DR), but linkage to the HLA gene complex was suggested by family studies. These results provide evidence for an HLA-linked antigen system not defined by conventional tissue-typing techniques. Fetomaternal disparity at this antigenic site may be important for successful pregnancy.
Bovine erythrocytes were coated with avidin using a chromic chloride coupling technique and used successfully in an indirect rosette assay to identify and quantitate: (a) T-lymphocyte helper and suppressor subpopulations, and (b) Ia positive B-lymphocyte populations. Using mouse monoclonal antibodies to the T-lymphocyte markers OKT3, OKT4, and OKT8 it was shown that the proportion of OKT4 and OKT8 positive cells were respectively 60.9 and 39.2% of the total OKT-3 positive T lymphocytes. In a similar way, using a monoclonal anti-human Ia antibody, the percentage Ia positive cells in B-lymphocyte enriched preparations was shown to vary between 18 and 55% for normal peripheral blood and 31 and 58% for chronic lymphocytic leukaemia derived peripheral blood.
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Fc receptor blocking antibodies directed against autologous lymphocytes were present in pretransplant sera from only one of a group of 24 cadaver donor renal transplant recipients. Such antibodies were present in recipient sera against B lymphocytes from the donor in 11/24, against normal B lymphocytes in 12/24 and against leukaemic B lymphocytes in 15/24 cases. There was a significant correlation between EA inhibiting antibodies directed against donor (p less than 0.01), normal (p less than 0.05) and leukaemic B lymphocytes (p less than 0.001) and improved one year allograft survival. No autolymphocytotoxic antibodies were detected. Fc receptor blocking antibodies detected by the Erythrocyte Antibody Inhibition assay may thus have a beneficial effect on graft outcome but do not appear to be autoantibodies.
This study shows that non-cytotoxic Fc receptor blocking antibodies occurred more frequently in pre-transplant sera when the recipient had been transfused over five units of blood. Moreover 7/12 previously untransfused patients developed Fc receptor blocking antibodies during an elective blood transfusion regime. Erythrocyte antibody-rosette-inhibiting antibodies were also found at significantly higher values in the sera of women during the first trimester of a normal first pregnancy than in women studied at the time of spontaneous abortion. Family studies showed that this activity was linked to the HLA gene complex. These results indicate that EA inhibiting antibodies directed against MHC linked antigens are associated with specific abrogation of the immune response.
We describe the clinical and pathological features of acute renal failure which occurred in a patient receiving a first course of antituberculous therapy, including daily rifampicin. Renal biopsy specimens demonstrated an interstitial nephritis. The renal lesion resolved three weeks after the cessation of rifampicin, as evidenced by improvement in renal function and the return of nuclear magnetic resonance tomographic studies to normal. This is only the fifth reported instance of renal impairment following continuous rifampicin therapy, despite widespread use of the drug in a daily dose. The possible toxic interaction of rifampicin and antituberculous drugs which are excreted predominantly by the kidneys is also described.
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The mechanism by which blood transfusions given before renal transplantation improves allograft survival was studied in 31 transplant recipients. The presence of non-cytotoxic, Fc receptor blocking antibodies to donor and leukaemic B lymphocytes in pre-transplant sera correlated with both improved graft survival (p less than 0.03 and less than 0.1, respectively) and the number of blood transfusions given (p less than 0.05 and less than 0.03, respectively). Moreover, 6 out of 10 previously untransfused prospective transplant recipients developed these potentially protective antibodies during a course of elective blood transfusions. These results indicate that such non-cytotoxic, Fc receptor blocking antibodies in pretransplant recipient sera (a) are associated with improved allograft survival, (b) correlate with the number of blood transfusions given, and (c) can develop in response to blood transfusion.
Microsurgical transfer of a compound osteo-cutaneous free flap derived from the dorsal foot skin and second ray can provide a satisfactory reconstruction for defects of the mandible and floor of the mouth. The procedure is particularly recommended for anterior segment losses where a thin flap and a curved skeleton is required. The flap can be prepared at the time of tumour resection without inconvenience to either surgical team and the surgery does not significantly affect either the operative or post-operative condition of the patient. No external bony fixation is required and no case of non-union has been encountered.