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R Y Calne

Publications and source records attributed to R Y Calne.

At least 73 records · Page 4Linked to original sources
PubMed1994

Chronic rejection of liver transplants revisited.

We examined 27 hepatectomy specimens to assess the frequency of foam cell endovasculitis and bile duct loss in chronic rejection. Arterial lesions, defined as total occlusion by subintimal foam cells and/or fibromuscular proliferation, were found mainly in hilar and septal arteries, whereas bile duct loss, defined as the absence of bile ducts in more than 50% of portal tracts, affected mainly small tracts. Both were found in 20 livers (74%). In two livers (7%) there was significant bile duct loss but no arterial lesions, whilst in five cases (19%) there were occlusive arterial lesions but no bile duct loss. Small arteries were involved in only 10% of the cases. These results indicate that in one-third of the cases arterial and bile duct lesions develop independently of each other, suggesting different pathogenetic pathways. In addition, liver biopsy may not be pathognomonic since small arteries are involved in only 10% of cases and bile duct loss may not be extensive. In such cases the diagnosis of chronic rejection should only be made in the presence of progressive clinical deterioration.

Adolescent↗
PubMed1994

A comparison of MR and duplex Doppler ultrasound for vascular assessment prior to orthotopic liver transplantation.

A prospective blinded comparison of duplex Doppler ultrasound (DDU) and a magnetic resonance angiography (MRA) 2-D time-of-flight technique was performed to assess the hepatic vasculature in 23 adult patients referred for orthotopic liver transplantation. Both techniques confirmed patency of the inferior vena cava in all patients, demonstrated a complete portal vein occlusion in one patient, and accurately defined the vascular and organ anatomy in a patient with situs inversus. The results were confirmed at surgery in 18 of the patients who have subsequently undergone liver transplantation. In one patient a partial portal vein thrombosis was found at surgery which was not detected by either imaging technique. MRA was more sensitive overall in detecting porto-systemic collaterals (31 locations in 17 patients) compared with ultrasound (24 locations in 17 patients), although ultrasound detected more patients with recanalized para-umbilical veins (DDU: 10 patients; MRA: 8 patients). These results indicate that a simple MRA technique can equal duplex Doppler ultrasound for the non-invasive assessment of patency of the hepatic vasculature and should be considered when DDU examination is equivocal or technically inadequate. MRA may provide additional information on the presence and size of porto-systemic collaterals which may be of value in monitoring portal hypertension.

Adult↗
PubMed1994

Transmission of hepatitis C virus by organ transplantation in the United Kingdom.

This study employed a second-generation anti-HCV ELISA, and a second-generation recombinant immunoblot assay and hepatitis C virus RNA detection by polymerase chain reaction to investigate the anti-HCV prevalence in 554 British organ donors and the transmission of hepatitis C virus to heart, liver and kidney recipients between 1984 and 1991. Serum samples from six (1.08%) donors were reactive in the second-generation anti-HCV ELISA and four (67%) of these gave positive or indeterminate results in the recombinant immunoblot assay-2. Of the 15 recipients of these organs from hepatitis C virus-confirmed positive/indeterminate donors, 14 (93%) acquired hepatitis C virus infection and seven (47%) had evidence of hepatitis C virus-related liver disease after transplantation and no evidence of blood transfusion-related transmission. Only six of the 15 (40%) recipients had detectable anti-HCV after transplantation, while 12 of 14 (86%) patients tested had hepatitis C virus RNA in their serum detectable by "nested" polymerase chain reaction. These data indicate a very high rate of transmission with a major risk of the development of liver disease. We believe our study supports the testing of all British organ donors for anti-HCV and that organs from anti-HCV-positive patients should not be transplanted unless the recipient has life-threatening disease and there is a donor shortage, when their use may be justified. Since there are time constraints on organ donor testing, which may frequently be done on call during unsocial hours, we would recommend second-generation ELISA as the current screening test of choice.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Immunosuppression of canine renal allograft recipients by CD4 and CD8 monoclonal antibodies.

A state of tolerance to MHC mismatched allografts can be generated in rodents by treatment with CD4 and CD8 monoclonal antibodies (mAb). In order to transpose this type of therapy to large animals and ultimately to the clinic, a suitable model is required. To this end we have generated a series of mAb to the canine CD4, CD8, and Thy-1 antigens and have tested their ability to prevent rejection of renal allografts. Donor-recipient pairs were selected from a colony of mongrel dogs in which untreated rejection of two haplotype-mismatched kidneys occurred by day 7 (defined as a serum creatinine > 300 mumol/l). Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival. Depletion of T cells by a Thy-1 mAb prior to surgery only extended graft survival to day 9. However, treating with combinations of mAb up to day 10 (CD4 plus Thy-1; CD4 plus CD8; or CD4 plus CD8 plus Thy-1) prolonged renal allograft function up to 25 days. Combination of the triple mAb therapy with a sub-therapeutic immunosuppressive drug regimen (cyclosporin A plus azathioprine that alone gave a median survival of 15 days) favored survival to a median of 38 days. This protocol also inhibited the antiglobulin response that had curtailed the effects of mAb treatment, opening the way to more extended, and potentially tolerizing, mAb plus drug regimens.

Animals↗
PubMed1994

CD4 and CD8 monoclonal antibody therapy in canine renal allografts.

Therapy with CD4 and CD8 monoclonal antibodies was evaluated in dogs which received double-haplotype MHC-mismatched renal allografts. Neither CD4 nor CD8 monoclonal antibodies given alone prolonged allografts survival (creatinine > or = 300 micromol/l) beyond 7 days. However, combined therapy with CD4 and CD8 antibodies given up to day 10 did prolong allograft survival to a median of 14 days. A longer (21 day) course of CD4 and CD8 antibodies did not extend allograft survival further. The effect of prolonged antibody therapy was restricted by the occurrence of both an antiglobulin response and an anaphylactoid reaction to the monoclonal antibody preparation. When the CD4 and CD8 antibodies were combined with a pan-T-cell-depleting Thy-1 antibody, the survival of double-haplotype mismatched allografts was further prolonged (median 16 days). The median survival of single-haplotype mismatched renal allografts on this triple therapy was 21 days, with one surviving to day 36.

Anaphylaxis↗
PubMed1994

Does intrathymic injection of alloantigen-presenting cells before islet allo-transplantation prolong graft survival?

Current immunosuppressive agents have potentially dangerous side-effects, are non-specific and most are also diabetogenic. We investigated tolerance induction with intrathymic injection of purified antigen-presenting cells (APC) plus a single dose of antilymphocyte serum (ALS) intraperitoneally before allogeneic islet transplantation in the rat model WAG to Lewis (RT1u to RT1l). Purified donor APC [non-parenchymal cells (NPC) or dendritic cells (DC)] were prepared from liver and spleen, respectively. Isograft function for more than 120 days proved that islet isolation, purification and transplantation procedures were adequate. A total of WAG DC (4 x 10(5)) or NPC (2 x 10(6)) in 20 microl were injected into both lobes of the thymus of 140-210 g Lewis recipients followed by a single injection of ALS. Three days later, diabetes was induced with streptozotocin (60 mg/kg). Four days later allogeneic islets were grafted into the liver by intraportal injection of 3000 WAG islets. Control animals (n = 8) received 20 microl saline intrathymically instead of APC. Graft function was assessed by blood glucose measurements with glucose levels above 15 mmol/l on 3 consecutive days defined as graft rejection. Animals given DC (n = 9) or NPC (n = 8) intrathymically plus 1 ml of ALS, rejected their grafts in an accelerated fashion with a median survival time (MST) of 3 days. However, control animals rejected their grafts with a MST of 7 days, but with two animals surviving for more than 2 months. In conclusion, intrathymic inoculation with purified APC plus a single dose of ALS did not prolong allogeneic islet graft function but induced accelerated rejection of the islet allografts.

Animals↗
PubMed1994

Distribution and persistence of antigen-presenting cells after intrathymic injection.

Intrathymic injection of donor immune cells has been shown by previous studies to prolong survival of rat allogeneic tissues. The aim of this pilot study was to assess the distribution and the persistence of intrathymically (i.t.) injected purified antigen presenting cells (APC) over a period of time in the rat model DA-to-WAG (RT1av to RT1u) using a specific monoclonal antibody (Mab) with RT1Aa class I polymorphic specificity (R3/13 clone). Purified non-parenchymal cells (NPC) or dendritic cells (DC) were prepared from liver and spleen of DA rats with a purity of greater than 60% and 90%, respectively, shown by selected Mab staining methods. DA NPC (1 x 10(6)) or DC (5 x 10(5)) in 20 microl were injected into both lobes of the thymus of WAG rats with or without 1 ml antilymphocyte serum (ALS) intraperitoneally. Thymus tissue was removed on days 3, 5, 10, 20 and 30, and processed for frozen sections and immunohistochemical staining with R3/13. Numerous DA-positive cells were detected in the first 3-10 days post-i.t. inoculation in both NPC- and DC-treated rats, with or without ALS. After day 10, the proportion of positive cells decreased in all cases except in rats given NPC and ALS, where similar numbers of R3/13-positive cells were seen throughout. These DA-positive cells were mostly found in the medullary portion of the thymus at the corticomedullary junction in close proximity to thymic dendritic interdigitating cells. We concluded from this pilot study that the injected cells remained in the thymus for a limited period. However, the immunosuppressive effect of ALS promoted some degree of persistence of donor APC in the thymus beyond 30 days. Further studies are in progress to reveal the specificity of these cells.

Animals↗
PubMed1994

Intrapulmonary shunting in the biliary atresia/polysplenia syndrome: reversal after liver transplantation.

UNLABELLED: One hundred and seventy three children, including 93 with biliary atresia, received liver grafts at Addenbrooke's Hospital between 1983 and 1993. Of these, only seven developed cyanosis due to intrapulmonary shunting as a complication of their liver disease, and all seven of these had the biliary atresia/polysplenia syndrome. Intrapulmonary shunting was confirmed by a radioisotope scan in four children. Only one child with the syndrome did not have cyanosis when undergoing transplantation. Seven of the eight children are alive 6-54 months after transplantation, with normal pulmonary and hepatic function. Cyanosis recurred in one child who developed chronic rejection with liver failure. IN CONCLUSION: (a) there is a strong association between the biliary atresia/polysplenia syndrome and cyanosis due to intrapulmonary shunting; (b) intrapulmonary shunting is fully reversible after successful liver transplantation; and (c) cyanosis, once present, is progressive, and these children should be considered for liver transplantation as soon as it occurs.

Arteriovenous Fistula↗
PubMed1994

Liver transplantation for hepatic cirrhosis in cystic fibrosis.

Five children with cystic fibrosis complicated by hepatic cirrhosis received liver grafts. They all had portal hypertension with varices and three had variceal bleeding; respiratory function was only moderately impaired, but four were colonised with pseudomonas and one with aspergillus. Liver transplantation was well tolerated and there was no increase in respiratory or other early postoperative complications. Four of the children were fully well from 14 to 35 months after transplantation; the most recently transplanted had problems from a biliary stricture. In spite of the need for immunosuppression there was no increase in infection and respiratory function improved or remained stable. Once the children were stabilised after transplantation their nutrition and general health were greatly improved.

Adolescent↗
PubMed1993

CD4 and CD8 monoclonal antibody therapy: strategies to prolong renal allograft survival in the dog.

The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy-1 monoclonal antibody. Alone Thy-1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival.

Animals↗
PubMed1993

Liver transplantation for primary hepatocellular carcinoma: tumor size and number determine outcome.

Liver transplantation for primary hepatocellular carcinoma (HCC) has in general been complicated by high recurrence rates. In the present study results from experience of 87 patients were analyzed [56 cirrhotic, 31 non-cirrhotic, 6 with the fibrolamellar (FL) variant] in relation to curative potential. Sixty-two survived > 90 days and form the study cohort. Fifty-six had non-fibrolamellar HCC and, of these, 39 had discrete lesions, measuring 0.8-21 cm (median 5.0 cm) including 4 in whom the diagnosis was made after examination of the explanted liver; 23 had multifocal lesions (> 2 tumor masses). There was no tumor recurrence in the group of 14 cases with single dominant lesions measuring < 4 cm, whereas in the 15 cases with lesions of 4-8 cm the recurrence rate was 40%, and 78% in those > 8 cm and the multifocal lesions (n = 27, P = 0.0001). Five-year actuarial survival figures were 57.1%, 44.4% and 11.1% (P < 0.003) respectively. The mean survival times in patients who died of recurrence were: 4-8 cm, 3.3 years (range 10 months to 6.3 years); > 8 cm or multifocal, 13 months (3-25 months). Reduction of serum alpha-fetoprotein (AFP) to normal levels does not exclude a later recurrence (7 of 17 cases) and this was documented after maintenance of normal AFP levels for up to 29 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗
PubMed1993

A comparative study of cyclosporine and its derivative SDZ IMM-125 in canine renal allografts.

The immunosuppressive efficacy of CsA and its derivative SDZ IMM-125 was compared in highly mismatched mongrel dogs in receipt of renal allografts. At an equal dose of 15 mg/kg/day and in the same drug vehicle, SDZ IMM-125 was not superior to CsA in prolonging allograft survival. Whole blood levels of SDZ IMM-125 were lower than those achieved for CsA. No specific drug-related side effects were noticed in this model.

Animals↗