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K C Tan

Publications and source records attributed to K C Tan.

At least 145 records · Page 8Linked to original sources
PubMed1993

Influence of human leukocyte antigen matching on liver allograft survival and rejection: "the dualistic effect".

To date only one published large series of human leukocyte antigen matching and liver allograft survival exists, and considerable confusion has arisen about the advantage or disadvantage of human leukocyte antigen matching. In the present study we have reinvestigated the relationship between human leukocyte antigen mismatch and graft survival in 466 first liver allografts, seeking to clarify the relationship between human leukocyte antigen and both acute rejection and the vanishing bile duct syndrome. In view of current criticism regarding the accuracy of serological tissue typing for human leukocyte antigen-DR, we have used both classic serology and restriction fragment length polymorphism analysis to ensure the accurate assignment of recipient DR types. In addition, we have used polymerase chain reaction amplification and allele-specific and sequence-specific oligonucleotide probes to retest the hypothesis that human leukocyte antigen class II matching may increase susceptibility to the vanishing bile duct syndrome. One-year graft survival was significantly lower in patients with zero or two human leukocyte antigen-A mismatches (52% and 63%, respectively) than in those with one human leukocyte antigen--A mismatch (69%) (p = 0.016 and p = 0.018). A similar effect of B mismatching was observed, with a 1-yr graft survival of 73% for those with one compared with 60% for those with two human leukocyte antigen-B mismatches. In contrast no correlation was found between DR mismatch and graft survival. Human leukocyte antigen class I matching appears to influence graft survival largely through the occurrence of acute rejection and the development of the vanishing bile duct syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Rejection↗
PubMed1992

Liver transplantation for fulminant hepatic failure and late-onset hepatic failure in children.

The mortality rate of fulminant hepatic failure (FHF) and late-onset hepatic failure (LOHF) in childhood has remained between 70 and 95 per cent despite recent improvements in medical therapy. Liver transplantation has become an important therapeutic option in adults with this condition but has been performed infrequently in children. Between March 1988 and August 1991, 12 children aged between 1 month and 14 years with FHF or LOHF received 13 liver transplants. The aetiology was viral hepatitis in eight children (non-A non-B in six, A in two), drug hepatotoxicity (carbamazepine) in two, autoimmune hepatitis in one and congenital haemochromatosis in one. Reduced-size livers were used for ten of the 13 transplants. Morbidity after operation included infective complications and abdominal bleeding. Two patients died from graft versus host disease, one from brain aspergillosis and another from graft infarction after portal vein thrombosis. Eight patients survive after a median follow-up of 18 months. Liver transplantation should be the therapeutic choice for children with FHF and LOHF for whom the chances of recovery are poor.

Adolescent↗
PubMed1992

Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and ultraviolet radiation.

I-A+ epidermal antigen-presenting cells (APCs, Langerhans cells) have been shown to present tumor-associated antigens (TAAs) and to induce tumor immunity in vivo. This study examined the effects of ultraviolet radiation (UVR) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha) on the ability of epidermal cells (ECs) to induce or to elicit immunity against the murine spindle cell tumor S1509a. Naive syngeneic mice were immunized three times at weekly intervals with ECs that had been cultured in GM-CSF for 18 h and then pulsed with TAA derived from S1509a. This resulted in protective immunity against subsequent tumor challenge, providing a model to study the conditions required for sensitization against TAAs by epidermal APCs. Culture of ECs in GM-CSF was required for induction of significant protective tumor immunity, and UV irradiation or incubation in TNF-alpha for 2 h after GM-CSF incubation abrogated the immunostimulatory effect of GM-CSF. However, unlike UVR, TNF-alpha did not significantly inhibit the induction of immunity when ECs were exposed to TNF-alpha before overnight incubation in GM-CSF, together with GM-CSF, or after pulsing with TAA, and anti-TNF-alpha antibody treatment did not abrogate the effects of UVR on this system. Furthermore, TNF-alpha incubation of ECs augmented their ability to elicit delayed-type hypersensitivity (DTH) and also enhanced elicitation of DTH by GM-CSF-cultured ECs, whereas UV-irradiation reduced it in a dose-dependent fashion. Taken together, these results demonstrate that GM-CSF, TNF-alpha, and UVR are significant regulators of tumor antigen presentation by epidermal APCs and that the effects of the cytokines examined differ with regard to induction or elicitation of immunity.

Animals↗
PubMed1992

Toga virus-like particles in acute liver failure attributed to sporadic non-A, non-B hepatitis and recurrence after liver transplantation.

Toga virus-like particles (typically 60-70 nm: enveloped with small surface spikes) were detected in the native hepatectomy specimens in 7 of 18 patients grafted for acute liver failure attributed to sporadic non-A, non-B hepatitis and in 2 patients grafted for fulminant hepatitis attributed to anti-epileptic drug hepatotoxicity. These particles were not detected in the hepatectomies from 12 other patients grafted for other causes of acute liver failure, 12 for various chronic liver diseases, and 2 histologically normal livers. Acute hepatic failure, characterized histologically by severe haemorrhagic necrosis, developed 7 days after grafting in 5 patients, all in the non-A, non-B group with toga virus-like particles in native liver. Similar virus-like particles were detected in all grafts and were in greater abundance than in the native livers. The agent may be novel because pre- and post-grafting sera were negative for antibodies against representative panels of arboviruses and in first and second generation antibody tests for hepatitis C virus.

Adolescent↗
PubMed1992

Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining.

Little data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL-PCNA (clone PC-10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post-mortem needle-specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid-lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immunoreactivity was higher in samples taken within 5-6 days than in those obtained at 9-11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar 'nodules' in cases with a map-like distribution of collapsed and non-collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA-positive ovoid nuclei, forming periportal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled 'oval cells' described in animal studies.

Acetaminophen↗
PubMed1992

Liver transplantation for fulminant liver failure in children.

The mortality rate of fulminant hepatic failure (FHF) in childhood has remained between 70% and 95% despite recent improvements in medical therapy. Liver transplantation has become an important therapeutic option in adults with this entity, but has been infrequently performed in children. Many children do not receive transplants because of the rapid progression of the illness and the lack of suitable donor livers. We present our experience in liver transplantation in children with FHF. Between March 1988 and December 1989, seven children aged between 15 months and 12 years received eight liver transplants. The aetiology of FHF was viral hepatitis in five and drug hepatotoxicity (carbamazepine) in two. Five of our patients were in grade III-IV coma. Reduced-sized livers were used in six of the eight transplants. The post-operative morbidity included viral and fungal infections, and abdominal bleeding. Two patients died from graft-versus-host disease and one from brain aspergillosis. Four patients (57%) survived a median follow-up of 15 months. Liver transplantation should be the therapeutic option in children with FHF where the chances of medical recovery are poor.

Child↗
PubMed1992

Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications.

The implications of hepatitis B virus (HBV) reinfection after liver transplantation were studied in 29 patients followed for 1.7-15 years. Of 20 patients with HBV infection alone, nine were HBeAg and HBV DNA seronegative and 11 had evidence of HBV replication as measured by HBeAg or HBV DNA seropositivity. Nine patients had co-existing HBV and delta virus (HDV) infection. Five patients became HBsAg seronegative after transplantation (four immediately and one after an hepatitic episode). Of the 20 patients with HBV infection alone, 17 had evidence of viral replication after transplantation with markedly increased HBV DNA levels. Five patients with HDV infection had HBV DNA in serum, but in significantly lower amounts than in those with HBV infection alone. Twenty-five episodes of graft dysfunction attributed to recurrent HBV infection occurred in 19 patients (65.5%). Thirteen episodes (in 12 patients) were self-resolving acute hepatitic illnesses. Six patients had a rapidly progressive illness leading to graft loss within 6 weeks, with the distinctive histological features termed fibrosing cholestatic hepatitis (FCH). Liver function tests in these patients showed markedly abnormal serum bilirubin and prothrombin times, but only modest increases in serum transaminase levels. An additional six patients lost their graft as a consequence of HBV recurrence through various pathogenetic mechanisms including possible (but unproven) FCH, chronic active hepatitis or late-onset hepatic failure. Co-existing HDV infection appeared to confer some medium-term protection from graft loss.

Adult↗
PubMed1992

Synthesis and metabolism of cysteinyl leukotrienes by the isolated pig kidney.

The metabolism and synthesis of cysteinyl leukotrienes by the isolated perfused pig kidney has been investigated. Kidneys were maintained for up to six hours in a recirculating perfusion system by using an oxygenated Krebs-Henseleit buffer containing albumin and the perfluorinated oxygen carrier, FC-43. Perfusion pressure was maintained at 12-13.5 kPa, with perfusion flow rates of 150-250 ml/min resulting in a urine output of between 20-180 ml/hr. Infusion of 3H-LTC4 into the renal artery resulted in rapid and complete metabolism, with the major urinary metabolites comprising LTE4, omega-hydroxy-LTE4, omega-carboxy-LTE4 and N-acetyl-omega-hydroxy-LTE4. The capacity of the isolated kidney to synthesize cysteinyl leukotrienes was monitored by measuring urinary LTE4 excretion; there was a basal urinary excretion of LTE4 (median 43 pg/min, range 8-470 pg/min). Neither lipopolysaccharide or human recombinant tumor necrosis factor alpha had any effect on basal excretion. Treatment with the calcium ionophore A23187, however, resulted in a 38.1 +/- 9.6-fold increase in urinary LTE4 excretion. We conclude that the isolated pig kidney, in the absence of circulating cells, can synthesize cysteinyl leukotrienes in the absence of circulating cells, which can then undergo extensive oxidative metabolism.

Animals↗
PubMed1992

A new portal venous shunt for bypass in orthotopic hepatic grafting.

A new heparin bonded portal venous cannula is described for use during orthotopic hepatic transplantation. This new shunt has a "shoulder" 4 centimeters from the caged tip, allowing it to be securely maintained within the portal vein. With a 60 degree curvature 7 centimeters from the tip, the shunt can conveniently be positioned away from the operative field.

Catheterization↗
PubMed1991

Liver transplantation after paracetamol overdose.

OBJECTIVE: To evaluate the role of liver transplantation after paracetamol overdose. DESIGN: Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING: Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES: Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS: 30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION: Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol.

Acetaminophen↗
PubMed1991

Surgical anatomy of donor extended right trisegmentectomy before orthotopic liver transplantation in children.

Liver transplantation is now accepted as the treatment of choice for children with end stage liver disease. A major constraint has been the shortage of donor organs of appropriate size. The use of reduced size adult organs has partially alleviated this problem but the previous technique employed was limited to a donor:recipient body-weight disparity of not greater than 3:1. Recently a new technique has been described that allows safe transplantation with a donor:recipient weight ratio of greater than 10:1. This should greatly increase the paediatric donor pool. Anatomical landmarks and techniques necessary for donor reduction hepatectomy are described from the dissection of 50 adult cadaveric livers. Variations in all important biliary and vascular structures necessitated adjustments in operative technique.

Bile Ducts↗
PubMed1991

Increased platelet aggregate formation in patients with chronic airflow obstruction and hypoxaemia.

Platelet aggregate formation in vivo was assessed by means of the platelet aggregate ratio and from platelet release products (beta thromboglobulin, platelet factor 4, thromboxane B2) in 23 patients with chronic airflow obstruction with and without hypoxaemia and in 10 control subjects without respiratory disease. Eight of the 11 hypoxaemic patients were having long term oxygen therapy. The platelet aggregate ratio was lower in the hypoxaemic patients (0.88 (SE 0.03] than in the non-hypoxaemic (0.97 (0.01] and control groups (1.00 (0.02], and there was a trend to lower aggregate ratios in the more hypoxaemic patients. Platelet release products in the peripheral venous blood were not increased in the patients or control subjects. Platelet behaviour is altered in chronic hypoxaemia and this enhanced platelet activity could contribute to the pulmonary vascular damage found in these patients through direct effects or mediator release.

Aged↗