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Biomedical subjects

A Ting

Publications and source records attributed to A Ting.

At least 55 records · Page 3Linked to original sources

Spontaneous rupture of renal allografts: the importance of renal vein thrombosis in the cyclosporin era.

Spontaneous renal allograft rupture occurring within 14 days of transplantation occurred in 15 patients from 791 consecutive transplants. In each of eight patients treated with azathioprine and prednisolone there was pathological evidence of rejection and only two patients had thrombosis of the renal vein. Of the seven cases occurring in patients treated with triple therapy regimen (low dose cyclosporin, prednisolone and azathioprine), histological evidence of rejection was present in only three cases, but renal vein thrombosis was found in all seven. Spontaneous rupture of a transplanted kidney, a relatively uncommon complication, is more likely to be due to renal vein thrombosis than to rejection in the cyclosporin era.

Adult↗

Triple therapy immunosuppression in cadaveric renal transplantation.

One hundred and ninety-two patients received 200 consecutive cadaver renal transplants (158 first and 42 regrafts) and were treated with triple therapy immunosuppression consisting of low-dose cyclosporin, azathioprine and prednisolone. One-year patient and graft survival rates were 95% and 82%, respectively. Against this low rate of graft loss, the proportion of rejection-free patients in the first 3 months was strongly related to matching for HLA-DR (P less than 0.01), although HLA-DR matching was not associated with improved graft survival. More grafts were lost to nonimmunological causes than to rejection, and these losses fell into three main categories, namely, losses in elderly and diabetic patients and losses due to renal vascular thrombosis. Thus, triple therapy immunosuppression appears to offer effective immunosuppression, resulting in good graft and patient survival, especially in highly sensitised patients or patients receiving regrafts. There are relatively few serious adverse effects, although elderly and diabetic patients experienced significant morbidity and mortality after transplantation.

Adult↗

The production of a human monoclonal antibody defining a split of HLA-DRw13 (DRw13b).

By use of the heterohybridoma technique we have produced a human monoclonal antibody (NDS40) which detects a split of HLA-DRw13 (DRw13b) which is in linkage with HLA-DQw1. In addition, the antibody reacts with cells positive for HLA-DRw8 and DRw11, but does not react with the commonly found split of DRw13 (DRw13a) which is associated with DQw1. NDS40 is cytotoxic and is of the lambda IgM class.

Antibodies, Monoclonal↗

Capsulorrhaphy with a staple for recurrent posterior subluxation of the shoulder.

Twenty athletes who had recurrent posterior subluxation of the shoulder, eight of whom also had associated anterior instability, were treated with capsulorraphy with a posterior staple. Nine patients had an unsatisfactory result: six had recurrence of the posterior instability and three still had moderate or severe pain. Five of six patients who had lax ligaments had a recurrence. Complications developed in five patients: pain from a staple in one, postoperative adhesions in two, and ectopic bone in two. Only one patient was able to throw as well as he had before the injury. Staple capsulorrhaphy is not acceptable treatment for posterior subluxation of the shoulder because it is associated with a high rate of failure and complications.

Adolescent↗

Positive crossmatches--when is it safe to transplant?

There is no doubt that the interpretation of a positive lymphocytotoxic crossmatch test has changed over the past 10-15 years. It is now generally accepted that the original dogma put forward in the mid-1960s "that a renal transplant must not be performed in the presence of a positive lymphocytotoxic crossmatch" is no longer tenable, and many positive crossmatch transplants have already been successfully carried out. However, the precise conditions under which such a transplant can be performed are still not fully understood. Some factors which should be considered when deciding whether or not to transplant in the presence of a positive crossmatch are: (1) the specificity of the antibody, and this can be HLA class I, class II or non-HLA; (2) the time interval between the last positive crossmatch serum and transplantation; and (3) the immunoglobulin class of the antibody, either IgG or IgM.

Autoantibodies↗

Antithymocyte globulin for steroid resistant rejection in renal transplant recipients immunosuppressed with triple therapy.

Steroid resistant rejection, confirmed histologically, occurred in 35 of 187 consecutive cadaveric renal transplants treated with triple therapy (cyclosporin, azathioprine and prednisolone) in the Oxford Transplant Unit. Twenty-seven of these were treated with a rabbit antithymocyte globulin (ATG) and 19 showed recovery of function. The level of serum creatinine, the renal biopsy appearance and the requirement for dialysis at the start of ATG treatment did not predict which patients would respond to the therapy. One year after transplantation there was no significant difference between the mean plasma creatinine levels of those patients with steroid resistant rejection who had been given ATG and responded (151.6 mumol/l) and those who had responded to steroids alone (165.0 mumol/l). Adverse effects of ATG treatment included a mean fall in white cell count of 62.2% and a mean fall in platelet count of 45.1%. Two of the 27 patients who received ATG died (7.4% mortality). ATG would appear to be an effective treatment of steroid resistant rejection in patients receiving triple therapy immunosuppression, and graft function may subsequently be excellent in those patients who respond to treatment.

Adult↗

Characterization of lymphocytotoxic antibodies causing a positive crossmatch in renal transplantation. Relationship to primary and regraft outcome.

In a series of 123 renal transplants performed in the presence of a positive crossmatch (either peak positive-current positive or peak positive-current negative), we have analyzed the immunoglobulin class and specificity of the donor-reactive antibodies. The immunoglobulin class was determined by dithiothreitol reduction and the specificity by cytotoxicity inhibition using monomorphic antibodies specific for HLA class I, DR, and DQ antigens. There was good primary graft and regraft survival in the presence of peak positive and current positive crossmatches due to IgM non-HLA antibodies. There was also acceptable primary graft and regraft survival with peak positive-current negative crossmatches due to T and B cell IgM HLA class I antibodies, but not with IgG HLA class I antibodies. Positive B cell crossmatches due to IgM or IgG HLA antibodies were associated with good primary graft survival but poor regraft survival.

Antibodies↗

HLA type in bullous pemphigoid, cicatricial pemphigoid and linear IgA disease.

In a study of 32 patients with bullous pemphigoid (BP), 16 patients with cicatricial pemphigoid (CP) and 10 patients with linear IgA disease (LAD) no significant association was found between these diseases and HLA type of the A, B, C and DR loci. In order to determine whether HLA type modified the clinical expression of these subepidermal diseases, the results were analysed for any association with mucosal involvement, the presence of scarring or the occurrence of a circulating anti-basement membrane zone antibody. No significant associations were found.

Adolescent↗

HLA class I antigens in severe RSV bronchiolitis.

Cytotoxic T-lymphocytes (CTL) recognize virus-infected cells in association with HLA class I antigens. There is strong evidence of the importance of CTL in respiratory syncytial virus (RSV) infections. We looked for but were unable to demonstrate an association between particular HLA class I antigens and severe RSV bronchiolitis in infants.

Bronchiolitis, Viral↗

Biochemically detected HLA-DQ polymorphism in DR-matched donors and recipients of renal allografts.

We performed a retrospective biochemical analysis of HLA-D-region antigens of serologically DR-compatible donors and recipients of renal allografts. No incompatible D-region antigens were detected in grafts with a stable clinical course--i.e., there were no rejection episodes--whereas incompatibility for one or more D-region antigens was found in all 13 grafts with rejection. Thus, mismatched D-region antigens may provide a stimulus for early rejection in these grafts.

Cell Line↗

Triple therapy in cadaver renal transplantation.

One hundred consecutive first (n = 72) and regrafted (n = 28) cadaver renal allograft recipients were immunosuppressed with cyclosporin, azathioprine and prednisolone (triple therapy) and followed for a median of 17.3 months (range, 7-26 months). Actuarial patient survival at 12 and 24 months was 97.7 per cent. Actuarial graft survival at 12 and 24 months was 79.5 per cent (first graft recipients 81.3 per cent and regrafted recipients 75 per cent). HLA-DR matching significantly improved graft survival which was 93 per cent at 1 year in patients given HLA-DR compatible kidneys, compared with 83 and 54 per cent, respectively, in patients who received kidneys mismatched for one or two HLA-DR antigens. There were 0.8 (s.d. = 0.7) episodes of acute rejection per patient during the first 3 months after transplantation. Triple therapy provides effective immunosuppression without evidence of over immunosuppression and reduces the incidence of cyclosporin side-effects. Although acute nephrotoxicity was uncommon, serum creatinine remained elevated 6 and 12 months after transplantation.

Adolescent↗

Renal transplantation in patients over 55 years old.

From 1975 to 1987, 507 patients, of whom 63 (12.4 per cent) were over 55 years old at the time of operation, received first cadaver renal transplants. The annual percentage of recipients given transplants after the age of 55 has risen from 0 per cent in 1975 to 44 per cent in 1987. Of the 63 older patients, 41 had at least one serious non-renal disease at the time of transplantation. Perioperative mortality rate was 3 per cent. After successful transplantation these patients remained subject to a significant number of serious complications, even in the cyclosporin era. Despite these adverse factors, actuarial graft survival for the population over 55 years of age was no worse than for those patients receiving first cadaver grafts who were under 55 years old, although patient survival was poorer in the former group (P = 0.027). Analysis of the subgroup of 56 patients treated with an immunosuppression protocol containing cyclosporin failed to show any adverse effect of age on either graft or patient survival. It is concluded that renal transplantation can be as successful in patients over 55 years of age as it is in younger patients and, given an adequate supply of kidneys, should be considered the treatment of choice for the elderly patient with end-stage renal failure.

Age Factors↗

Immunoglobulin class and specificity of lymphocytotoxic antibodies after kidney transplantation.

The immunoglobulin class and specificity of the cytotoxic antibodies were investigated in sera collected during the first weeks following transplantation from 35 patients with functioning and 20 patients with failed grafts. No patient had had cytotoxic antibodies before the transplant, but 71.5% (25 of 35) of patients with functioning and 75% (15 of 20) of patients with failed graft subsequently developed them. The addition of dithiothreitol, which digests IgM antibodies, resulted in the disappearance of cytotoxicity in all positive sera from patients with a functioning graft. However, in the patients with failed grafts, the immunoglobulin class of the antibody varied; seven patients had only IgM antibodies, and seven had both IgM and IgG. After graft nephrectomy, IgG antibodies appeared in another six patients. In five of six patients with functioning grafts, mouse monoclonal antibodies blocked the cytotoxic activity; four with HLA-DQ monoclonal antibodies (Leu 10), one with HLA Class I (GD5). In the patients with failed grafts, blocking was seen in all nine patients studied; eight by GD5, six by Leu 10, and two by a monoclonal antibody to a monomorphic determinant of HLA-DR (100/77). Although the frequency of antibody-positive patients was similar in the successful and failed groups, the immunoglobulin class of the antibodies developed was IgM in the former group, whereas in the latter group some were IgM and others were IgG. Characterisation of the antibodies could be useful in the interpretation of a positive cross-match, since IgG antibodies are damaging to the graft whereas IgM antibodies are not.

Adult↗