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D Talbot

Publications and source records attributed to D Talbot.

At least 73 records · Page 4Linked to original sources
PubMed1995

The clinical significance of post-transplantation non-HLA antibodies in renal transplantation.

This study was undertaken to examine the clinical relevance of antibodies detected in the sera of patients following renal transplantation. The sera from 23 transplant recipients with acute rejection and 10 transplant recipients with diagnosed chronic rejection were tested against various epithelial, monocyte and endothelial cell lines (A549, HTB44, primary renal epithelial, U937 and Ea-hy 926). The test used for detecting binding antibodies was a simple, indirect immunofluorescence flow cytometric technique. The level of IgG antibodies directed against the test cell lines was examined in the sera of patients with mild or severe rejection and compared to those of patients showing no signs of rejection. Patients with chronic rejection were found to have increased levels of antibodies (IgG and IgM) when compared to patients with either end-stage renal failure or patients with stable post-transplant renal function. Antibodies detected by the present technique were directed against antigens found on all cell lines tested, and immunoblotting indicated that they were directed against non-HLA antigens. In conclusion, monitoring for the presence of such antibodies may provide a valuable prognostic indicator of graft rejection in renal transplant patients.

Antibodies↗
PubMed1995

Developing the ideal immunosuppressive protocol by internal audit.

To identify the best immunosuppressive protocol in a centre where five different regimens are employed, 227 consecutive renal recipients who were transplanted over a 2.5-year period were studied. The five different regimens employed were cyclosporin monotherapy, dual therapy (cyclosporin and prednisolone), triple therapy (cyclosporin, azathioprine, prednisolone), antithymocyte globulin (ATG) followed by dual therapy and ATG followed by triple therapy. Recipients were chosen for the different regimens according to HLA mismatch, positive donor crossmatch due to IgM, regraft and delayed graft function. The group with the lowest risk, cyclosporin monotherapy, had the highest acute rejection rate, with only 13% free of acute rejection (in comparison to triple immunosuppression, P = 0.024, chi-square test). The overall infection rate and graft success rate were similar between the different groups.

Adult↗
PubMed1995

Flow cytometric crossmatching in renal transplantation--the long-term outcome.

The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor outcome is well described in renal transplantation. Until now no long-term follow-up on such patients has been available. In this study, 117 renal transplant patients were followed up for a period of 5 years. Of these 21 were known to have donor T cell directed IgG and five had B lymphocyte directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (p < 0.0001, Handel Maenzel test). Patients with antibody detected preoperatively were tested again either at the time of graft failure or at 5 years post-transplantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts the levels increased in 60% of cases, but those who retained their grafts also had an increase in levels of donor directed antibody in 50% of cases. The changing levels of antibody therefore appeared to have little relevance to outcome. However when IgG isotypes were considered, in those who experienced graft failure and also had a gamma 3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with gamma 3 had a decline in levels between preoperative and 5-year samples in three of the four cases (not significant).

Flow Cytometry↗
PubMed1994

The 5' flanking region of the rat LAP (C/EBP beta) gene can direct high-level, position-independent, copy number-dependent expression in multiple tissues in transgenic mice.

The efficiency and tissue-specificity of transgene expression in animals is usually subject to the position of integration into the host chromatin. We have discovered that a 2.8kbp fragment flanking the rat gene encoding the transcription factor LAP (C/EBP beta) directs position-independent, copy number-dependent expression in transgenic-mouse livers. Concomitantly, the DNAse I hypersensitivity pattern normally observed in the liver is established in the integrated transgene construct demonstrating that this region is capable of creating chromatin structures equivalent to the endogenous situation. These observations are reminiscent of the locus control regions (LCR) described for several genes. Additionally, this LAP element functions with both intron-less and intron-containing genes. The tissue specificity of this element, however, is not restricted to liver. The 2.8kbp region is capable of allowing position-independent, copy number-dependent expression in brain, kidney, heart, spleen, and lung, but in a construct-dependent manner. This is, to our knowledge, the first transcription factor gene with which a cis-linked LCR-like element has been associated.

Animals↗
PubMed1994

Characterization of donor-directed antibody class in the post-transplant period using flow cytometry in renal transplantation.

Over the past few years there has been increasing awareness of the importance of humoral mechanisms in the rejection of renal transplants. In this study we have monitored the development of antibodies directed against donor T and B lymphocytes using the sensitive flow cytometric technique. Forty-two cadaveric renal transplants were studied both before and for a maximum of 14 days after transplantation. Donor cells were separated from spleen on the day of transplantation and stored in liquid nitrogen until required. The dual colour flow cytometric assay was used to detect IgG or IgM directed against donor T or B lymphocytes. Using AB sera as controls, results were expressed as relative median fluorescence (RMF) and then correlated with the clinical performance of the grafts. Significant associations were found between the incidence of donor-directed antibodies and the development of clinical rejection. The magnitude of the rise in antibody levels was also related to graft performance. In patients showing severe graft rejection, high levels of antibodies of the IgG class developed before the clinical diagnosis of rejection was made. The routine use of this test allows the prediction of impending severe rejection to be made and may have important implications for immunosuppressive therapy.

B-Lymphocytes↗
PubMed1994

Duodenal leiomyosarcoma presenting with iron deficiency anemia.

Failed iron therapy warrants investigation to rule out disorders of iron absorption or intestinal blood loss. The authors report the third case of duodenal leiomyosarcoma in childhood, which presented with iron deficiency anemia. Endoscopy failed to elicit the cause of this problem. Wide surgical resection, sparing the pancreas, was possible.

Anemia, Hypochromic↗
PubMed1994

Flow cytometric crossmatching in human organ transplantation.

When donor class I directed 'warm' antibodies are detected by the conventional cytotoxic crossmatch preoperatively, there is a negative correlation with outcome in renal, liver, cardiac and pancreatic transplantation. When the cytotoxic crossmatch assay is negative and IgG antibodies to T donor lymphocytes are shown to be present in the recipient sera by flow cytometry then there is an increase in postoperative complications in renal transplants. This includes primary nonfunction and treatable rejection which in some cases results in graft failure. Since its introduction into clinical practice for recipient selection in Newcastle, the complication rate of rejection episodes, primary nonfunction and graft failure has been reduced. When applied to other organs there seems to be a definite detrimental association between a positive flow cytometric crossmatch preoperatively and rejection in cardiac transplantation, in some cases leading to death. The role in liver and pancreas transplants to date has not been determined. In the postoperative period there appears to be a limited role for the flow cytometric crossmatch in the detection of antibody prior to the first clinical episode of rejection. This has been applied to renal transplants but to no other organ.

Flow Cytometry↗
PubMed1994

Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.

PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.

Adult↗
PubMed1994

Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: a prospective study.

The Alvarado score was assessed as to its accuracy in the preoperative diagnosis of acute appendicitis. A series of 49 consecutive patients was studied prospectively over a period of 9 months in two hospitals (Gateshead and Sunderland). The presence of a high score was found to be an easy and satisfactory aid to early diagnosis of appendicitis in children and men. However, the false-positive rate for appendicitis in women was unacceptably high.

Acute Disease↗
PubMed1993

Synthetic human beta-globin 5'HS2 constructs function as locus control regions only in multicopy transgene concatamers.

Transgenes linked to the beta-globin locus control region (LCR) are transcribed in a copy-dependent manner that is independent of the integration site. It has previously been shown that the LCR 5'HS2 region does not require its NF-E2 dimer binding site for LCR activity. In this paper we analyse synthetic 5'HS2 core constructs containing point mutations in the other factor binding sites 3' of the NF-E2 dimer site. The results show that 5'HS2 core is a partially active LCR that functions in a concatamer of at least two copies but not when present as a single copy in transgenic mice and that no single binding site within 5'HS2 is required for position-independent expression. In addition, the H-BP factor is identical to upstream stimulatory factor (USF) and full enhancement levels by 5'HS2 core in MEL cells require a combination of all the factor binding sites. We suggest that 5'HS2 cores in a concatamer interact with each other to establish an area of open chromatin and that this process may be the basis of LCR function.

Animals↗
PubMed1993

Induction of a proteoglycan core protein mRNA in mouse T lymphocytes.

The mouse T lymphocyte cell line EL4.E1 synthesizes a proteoglycan core protein (PGCP) mRNA which is identical to serglycin mRNA found in mouse bone marrow-derived mast cells and a mouse mastocytoma cell line. PGCP mRNA was strongly induced in EL4.E1 cells by phorbol myristate acetate, which also induces mRNAs for several cytokines in these cells. In contrast to the induction of cytokine mRNAs, however, the induction of PGCP mRNA was not inhibited by Cyclosporine. PGCP mRNA was also inducible by allogeneic stimulation of normal mouse spleen cells, and by Con A stimulation of an Interleukin 2-producing T hybridoma cell line. A number of other cell lines expressed an identical or similar, mRNA, including two cytotoxic T cell lines, and three tumor cell lines related to bone marrow-derived cells. The levels of several proteoglycans have previously been reported to increase in cells of bone marrow origin under activating conditions, but this appears to be the first report of an induction of the corresponding PGCP mRNA by immune stimulation of T lymphocytes.

Animals↗
PubMed1993

A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia.

Patients with breast cancer treated with MPA often report an improvement in appetite. Similar appetite stimulation is seen in patients treated with some corticosteroids, but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect. MPA (100 mg tds orally) has therefore been compared with placebo in 60 patients with advanced malignant disease. Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy. Patients were treated for 6 weeks and were assessed at weeks 0, 3 and 6 for appetite, energy, mood and pain using visual analogue scales. Nutritional status was assessed by the measurement of serum proteins and anthropometrics. Karnofsky score was recorded as a measure of performance status. There was a significant improvement in appetite in the MPA group between weeks 0 (pre-study) and 3 (P = 0.0002) and 0 and 6 (P = 0.015). There was no significant improvement in appetite in the placebo group. Supporting this finding was the significant increase in serum thyroid binding pre-albumin and retinol binding protein in the MPA group between weeks 0 and 3 and 0 and 6 (P = 0.023 and P = 0.039 respectively). These two parameters showed no significant change in the placebo group. There was no change in anthropometric measurements, weight, performance status, energy, mood or pain in either group. These data indicate that there was a significant increase in appetite in anorexic patients with advanced cancer treated with MPA which was reflected in increases in rapid turnover proteins reported to reflect nutritional status. However, this apparent increase in appetite did not result in improved weight, performance status, energy levels, mood or relief of pain. Further studies to investigate the effect of higher doses of MPA are indicated.

Appetite↗