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Biomedical subjects

A D Hibberd

Publications and source records attributed to A D Hibberd.

At least 19 recordsLinked to original sources
PubMed2001

Successful ex vivo renal artery reconstruction and renal autotransplantation.

BACKGROUND: The increasing experience with renal allotransplantation has led to continuing development in vascular surgical techniques. These improvements have enabled complex ex vivo renal artery surgery and renal autotransplantation to be performed. The aims of the present study were to describe the results achieved with renal autotransplantation and ex vivo renal artery reconstruction (RAR) at the Newcastle Transplant Unit, John Hunter Hospital, and to review the current indications for such surgery. METHODS: A retrospective review was performed of patients who required renal autotransplantation with or without RAR at John Hunter Hospital, between 1991 and 1999. Data were obtained from the Newcastle Transplant Unit and the Medical Record Department of John Hunter Hospital. RESULTS: Two patients required ex vivo RAR and renal autotransplantation for severe fibromuscular dysplasia (FMD) complicated by stenoses and renal artery branch aneurysms. The third patient required autotransplantation for bilateral retroperitoneal fibrosis. There was one postoperative complication of pelviureteric junction obstruction that was treated successfully with a temporary ureteric stent. All patients demonstrated normal graft function and were normotensive on follow up, which ranged from 2.5 to 5 years. CONCLUSION: The present review confirms the long-term benefits of ex vivo RAR and renal autotransplantation that have been demonstrated by previous studies. In transplant units experienced with this surgery it has been shown to be a successful and durable technique for the treatment of a variety of vascular, urologic and other diseases.

Female↗
PubMed1996

Castanospermine, an oligosaccharide processing inhibitor, reduces membrane expression of adhesion molecules and prolongs heart allograft survival in rats.

The inhibition of intracellular oligosaccharide processing is a new approach to immunosuppression in allotransplantation. The net effect of such inhibition is reduction in the membrane expression of certain glycoproteins. Hence cell-cell interaction in allorejection may be impaired in the presence of glycoprotein processing inhibitors because the expression of key ligand-receptor pairs of N-linked glycoproteins including adhesion molecules is inhibited. The aims of this study were to measure the immunosuppressive ability of castanospermine (CAST) in a rat heart allograft model, to measure its effect on membrane expression of adhesion molecules (LFA-1 alpha, LFA-1 beta, ICAM-1), class I and class II MHC antigens and on other T cell associated molecules (CD4, CD8, CD39, CD45, W3/13), to test its tolerogenic potential and its toxicity. Membrane expression of these molecules was measured by flow cytometry for single cells and by immunoperoxidase staining for the allograft. In grafted rats CAST significantly reduced the expression of LFA-1 alpha on lymphoid cells in the thymus, lymph node, spleen and heart allografts. ICAM-1 expression on endothelial cells of the allograft vasculature, class I and class II MHC expression on lymphoid cells in the thymus, class II MHC expression on lymphoid cells in the allograft; and CD4, CD8, CD45 and W3/13 expression on lymphoid cells in some organs. By contrast, in non-grafted rats CAST significantly upregulated expression of class I MHC and CD45 in the thymus, lymph node and spleen, ICAM-1 and CD4 on lymphoid cells in the spleen, but reduced expression of LFA-1 alpha on lymphoid cells in the thymus. It also prolonged rat heart allograft survival in a dose-dependent manner and with limited testing was relatively non-toxic. In conclusion, CAST is an immunosuppressive molecule which may work by downregulation of the ligand-receptor adhesion molecule pair, LFA-1 alpha-ICAM-1 although subtle downregulation of class I and II MHC, CD4 and CD8 molecules could also contribute to its immunosuppressive activity. Hence, both lymphocyte-endothelial cell binding and lymphocyte activation may be inhibited by CAST. This work suggests that CAST may hold significant potential as a transplant immunosuppressant probably as an adjuvant agent to inhibitors of interleukin 2 secretion.

Animals↗
PubMed1995

The identification of potential cadaveric organ donors.

Most Australian transplantation programs are severely restricted in their activities by a limited availability of cadaveric donor organs. To investigate possible reasons for this problem, an audit was undertaken over three 12-month periods of all deaths in 13 hospitals in New South Wales and the Australian Capital Territory. From 7406 deaths, 271 patients were classified as having been realistic, medically suitable potential donors. Of these, only 60 (22%) became actual donors. In the other 211 patients, donation did not occur because of unsuccessful resuscitation (30%), permission refusal by relatives (34%), and failure to identify or support the potential donors (36%). If the impediments to organ donation which were identified in this study could be overcome, allowing a greater number of potential donors to become actual donors, the chronic shortage of cadaveric donor organs for transplantation could be at least partly relieved.

Brain Death↗
PubMed1995

Obtaining consent for organ donation in nine NSW metropolitan hospitals.

Organ donation rates vary markedly around the world. In an attempt to analyse why some patients' families are not asked about organ donation, the case notes of 6080 patients who died over a twelve-month period from April 1991 to March 1992 in nine hospitals in Sydney, NSW, were studied. Irreversible coma occurred in 515 patients. Of these, 177 were considered to be potentially brain dead donors, 126 of whom had a formal diagnosis of brain death. The clinicians caring for the patients at the time of death were asked at follow-up about the reasons for not considering donation, or the reasons for family refusal. Consent to proceed to organ donation was requested in 112 cases (49 donated and 63 refused) and not requested in 65. Analysis of the proportions asked and consenting in each hospital revealed no correlation. Half of the families refusing gave no reason (24/50) while eleven gave religious or cultural reasons, and six expressed a desire to prevent mutilation of the body as their primary reason for not consenting. There was universal failure to gain consent from families when the patient was not in an Intensive Care Unit. Analysis of those patients of whom consent was not sought showed that they died more quickly after admission, were older and died from causes other than trauma or intracranial haemorrhage. The odds of the family being asked dropped by about half as the age increased from one group to the next.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Can cadaveric organ donation rates be improved?

There are many reasons why potential cadaveric organ donors may fail to become actual donors. These include permission refusal by the next of kin, incorrect assumptions about medical suitability and, occasionally, an excessive workload in the intensive care unit. Some potential donors currently regarded in Australia as "unrealistic" might become actual donors if attitudes were to change towards ventilation of patients with a clearly hopeless prognosis who have expressed a wish to be organ donors. "Required request" legislation ignores the wishes of the potential donor and "presumed consent" laws also present some ethical difficulties, but a suggested "required response" process could ensure that an individual's wishes concerning organ donation would be known and able to be carried out after death. For the present, however, it is clear that operating within existing Australian legislation and abiding by currently accepted codes of practice, we can still find considerable scope for improving cadaveric organ donation rates.

Age Factors↗
PubMed1995

The renal medulla in acute renal allograft rejection: comparison with renal cortex.

A retrospective cohort study was undertaken to evaluate the diagnostic value of the renal medulla in acute renal allograft rejection (ARAR). One hundred and ninety-five biopsies from 98 patients were randomly selected out of 565 transplant biopsies. Biopsies were graded blindly from Grade 0 (no rejection) to Grade 3 (severe rejection) using standard criteria; ARAR was confirmed by a fall in all cases of mean serum creatinine concentration from 0.331 +/- 0.182 to 0.184 +/- 0.079 mmol/l, with anti-rejection therapy. In the 43 biopsies which contained both cortex and medulla, the ARAR grades and the intensities of mononuclear cell, plasma cell, polymorphonuclear cell and eosinophil infiltrates, and of interstitial oedema and haemorrhage, were similar in cortex and medulla (Spearman's Rank Correlation r = 0.55-0.81, P < 0.001). The sensitivity, specificity and overall accuracy of medullary changes in predicting ARAR changes in the cortex were 77%, 100% and 38%, respectively. Acute vascular rejection changes could not be compared between renal cortex and renal medulla because of the anatomical differences between cortex and medulla. Further evaluation of ARAR in the all 195 biopsies, of which 188 had cortical tissue and 50 had medullary tissue, showed no significant differences in histological features (P > 0.05), except for more cortical biopsies with plasma cells (29%) than medullary biopsies with plasma cells (10%; P < 0.02). It is concluded that: (1) ARAR histological changes are similar in cortex and medulla; (2) the predictive value of ARAR medullary changes for cortical rejection changes has low sensitivity (77%) and high specificity (100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Eosinophils in acute renal allograft rejection.

Tissue eosinophils have been previously implicated in allograft rejection and graft loss. The aim of this study was to evaluate the role of eosinophils in acute renal allograft rejection. Data from 71 patients with 114 renal biopsies with acute allograft rejection were compared with those from 26 controls. The median tissue eosinophil density (0.4-1.1 eosinophils per micron2 x 10(6)) and the median peripheral blood eosinophilia (1.5-3.0%) in all grades of acute interstitial rejection and in acute vascular rejection were higher than in controls (0.0 eosinophils per micron2 x 10(6), p < 0.0023, and 0.9%, p < 0.035). In all grades of rejection, 36-54% of biopsies had tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6), and 20-36% of patients had peripheral blood eosinophilia > or = 4%, compared with 0% and 4%, respectively, in controls (p < 0.000 and p = 0.0245). The sensitivity, specificity and overall accuracy of predicting acute rejection with tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6) is 41%, 100% and 52%, and for peripheral blood eosinophila > or = 4% is 23%, 96% and 40%, respectively. The median tissue eosinophil density in acute rejection with graft loss was 1.9 eosinophils per micron2 x 10(6) compared to 0.2 eosinophils per micron2 x 10(6) in acute rejection without graft loss (p = 0.014), and 67% of acute rejection with graft loss had tissue eosinophil density > or = 1 eosinophil per micron2 x 10(6) compared with 28% of acute rejection without graft loss (p = 0.028).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Potential for cadaveric organ retrieval in New South Wales.

OBJECTIVES: To measure the potential for cadaver organ retrieval in New South Wales and to determine the reasons for potential donors failing to become actual donors. DESIGN: Prospective audit of all patients dying in five hospitals in New South Wales between 1 December 1989 and 30 November 1990; quality assurance of the data by independent medical specialist and if disagreement by study committee. PATIENTS: 2879 patients (100% of all deaths) yielding 364 patients with coma and 181 potential donors. OUTCOME MEASURES: Realistic medically suitable potential donor rate, missed potential donor rate, rate of potential donors with permission refused, donor rate, reasons for realistic medically suitable potential donors failing to become actual donors. RESULTS: 2879 deaths yielded 73 medically suitable potential donors, resulting in 19 actual donors, 30 missed potential donors, 19 potential donors with permission refused, and five in whom adequate resuscitation failed. The most common reason for a potential donor failing to become an actual donor was a decision by the senior medical practitioner to withdraw or not to institute ventilatory or haemodynamic support (26/73). The second major obstacle was refusal of permission by the next of kin (17/73). Assuming that the potential donor rate was that implied by the observed donor rate (13/million population/year) the projected missed potential donor rate was 9/million population/year (95% confidence interval 4 to 15) and the projected rate of potential donors with permission refused was 13/million population/year (95% confidence interval 5 to 22). Assuming that the rate of potential donors in the study hospitals was the same as in the other New South Wales hospitals, the projected donor rate for New South Wales was 18/million population/year (10 to 26); the projected missed potential donor rate was 15/million population/year (7 to 23); and the projected rate of potential donors with permission refused was 18/million population/year (10 to 27). CONCLUSIONS: The donor rate could be increased 70%-80% by overcoming the reluctance of medical practitioners to resuscitate missed potential donors and increased further by gaining permission for organ retrieval from the next of kin.

Cadaver↗
PubMed1991

Behavioral conditioning prolongs heart allograft survival in rats.

Conditioned immunosuppression using a taste aversion paradigm has been demonstrated in a number of laboratory models but few reports have demonstrated changes in immunity sufficient to be of clinical relevance. The experiments reported here demonstrate that the survival of heart allografts in rats can be prolonged by behaviorally conditioned immunosuppression using cyclosporin A (CsA) as an unconditioned stimulus in taste aversion conditioning. Conditioned animals received saccharin as the conditioned stimulus paired with an injection of CsA at 10 and 6 days prior to transplantation. They were reexposed to saccharin alone 1 day prior to and 3 days after transplantation. On these occasions the conditioned group displayed taste aversion behavior when offered saccharin and a significant prolongation of heart graft survival was observed compared to the conditioned and nonconditioned control groups. These experiments suggest that behaviorally conditioned immunosuppression may have important clinical implications as an adjunct to drug treatments in transplantation medicine.

Abdomen↗
PubMed1991

Use of the fistula assessment monitor to detect stenoses in access fistulae.

Twenty-three unselected hemodialysis patients with functioning access arteriovenous fistulae were studied prospectively to determine the best technique for detecting stenoses within the fistulae. Combined clinical assessment and fistula assessment monitoring were compared with transbrachial angiography. Fistula assessment monitoring was more accurate (96%) than combined clinical assessment (accuracy, 52%) in stenosis detection. Complications of angiography occurred in 17% of patients; there were no complications of fistula assessment monitoring. Fistula assessment monitoring was better than combined clinical assessment in predicting clinical outcome for arteriovenous fistulae over 6 months and was as good as angiography. Routine fistula assessment monitoring could reduce inappropriate angiography and detect clinically significant silent stenoses. It is an ideal method for monitoring arteriovenous access fistulae.

Angiography↗