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Biomedical subjects

T M Chan

Publications and source records attributed to T M Chan.

At least 109 records · Page 6Linked to original sources

Percutaneous transluminal angioplasty for stenosis of arteriovenous fistulae: a review of local experience.

The stenosis and subsequent thrombosis of the arteriovenous fistulae may lead to a loss of vascular access sites; this a major problem in chronic haemodialysis patients. Percutaneous transluminal angioplasty has been a popular way of correcting such lesions in recent years. We have reviewed patients who underwent this operation from 1993 to 1996 at the Queen Mary Hospital. Among 11 patients who were documented as having arteriovenous fistula stenosis, 60% of lesions were in the anastomotic area while 40% were in the venous limb. All patients had abnormal dialysis blood line pressures corresponding to the actual site of stenosis. The initial success rate of percutaneous transluminal angioplasty in treating the stenotic lesions was 73%. This method is thus a promising form of semi-invasive treatment for symptomatic arteriovenous fistula stenosis.

Journal Article↗

Post-transplantation lymphoproliferative disorder of donor origin in a sex-mismatched renal allograft as proven by chromosome in situ hybridization.

We report a case of post-transplantation B-cell lymphoproliferative disorder (PTLPD) associated with Epstein-Barr virus (EBV) that developed in a renal allograft 5 months after transplantation. The lesion had a histologic appearance of diffuse large B-cell lymphoma with monoclonality demonstrated by in situ hybridization (ISH) for kappa and lambda mRNA. Both the male donor and the female recipient were EBV seropositive. The lymphoid cells in this lesion was proven to be of donor origin by ISH for the human Y chromosome on the paraffin-embedded sections of the allograft. The recipient of the other kidney from the same donor did not have evidence of lymphoma, and the patient was also free from disease 2 years after surgical removal of the lymphoma This case is an unusual PTLPD of donor origin; the majority of such lesions in solid organ transplantations are of recipient origin. Our findings demonstrate that the origin of PTLPD can be documented in selected cases using ISH with probes to the Y chromosome.

Adult↗

Identification of endothelial cell membrane proteins that bind anti-DNA antibodies from patients with systemic lupus erythematosus by direct or indirect mechanisms.

A subgroup of murine monoclonal anti-DNA antibodies bind to vascular endothelial cells either directly as a result of cross-reactivity, or indirectly through immunoglobulin-bound DNA and DNA-binding proteins on the endothelial cell membrane. To determine whether these mechanisms apply in human systemic lupus erythematosus (SLE), and to identify endothelial cell membrane protein(s) that bind human anti-DNA antibodies, we examined, by Western blotting, the binding of human polyclonal anti-DNA antibodies (PoAb) isolated from eight patients with SLE to human umbilical vein endothelial cell membrane proteins. PoAbs bind to endothelial membrane proteins with Mr 84,000 and 46,000, which correspond to the DNA-binding proteins previously reported. Such binding is diminished after removal of DNA by DNase treatment. In addition, PoAbs bind to membrane proteins with Mr 180, 000, 110,000, 68,000, 44,000, and 35,000-30,000. Such binding is unaffected by alterations in DNA concentration. Anti-dsDNA and anti-ssDNA PoAbs from individual patients exhibit identical binding patterns, as are PoAbs isolated during active disease or remission. The results show that human anti-DNA antibodies can bind to endothelial cells both indirectly via immunoglobulin-bound DNA, and directly due to cross-reactivity. These mechanisms of cellular binding by anti-DNA antibodies may depict patho-genetic steps in human SLE.

Animals↗

Resolution of eosinophilic peritonitis with ketotifen.

Eosinophilic peritonitis is frequently observed in patients of all ages started on peritoneal dialysis. Peritoneal effluent may or may not become noticeably turbid, and if an aliquot for white cell count is sampled at all, eosinophils will be seen to predominate. It does not usually cause concern and settles spontaneously, many times even without the clinician noticing. Occasionally, this condition lingers on for months, and a short course of intraperitoneal hydrocortisone has been shown to be effective in clearing up the eosinophilia. We report a patient with steroid-resistant eosinophilic peritonitis and its successful resolution with ketotifen.

Aged↗

Interferon treatment for hepatitis C virus infection in patients on haemodialysis.

BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24-month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.

Adult↗

Distinct genotypic distributions of cytomegalovirus (CMV) envelope glycoprotein in bone marrow and renal transplant recipients with CMV disease.

A prospective study of the spectrum of glycoprotein B (gB) and glycoprotein H (gH) genotypes of cytomegalovirus (CMV) was conducted with five categories of patients: viremic bone marrow-transplant (BMT) recipients who developed CMV disease after BMT (n = 22), viremic BMT recipients without CMV disease (n = 11), viremic renal-transplant recipients who developed CMV disease after transplantation (n = 14), viremic renal-transplant recipients without CMV disease (n = 13), and premature babies with asymptomatic congenital CMV infections (n = 13). Genotypic stability was observed because the gB and gH genotypes of multiple isolates obtained from a single patient were identical. The distribution of gH genotypes in patients of all groups studied were similar. However, there was a unique distribution of the gB genotype in the first category of patients, i.e., BMT recipients with CMV disease, which was distinct from those of all other categories (P < 0.05). CMV isolates from 54% of BMT recipients with CMV disease exhibited gB type 2, while isolates from 46, 50, 69, and 77% of the BMT recipients without CMV disease, renal-transplant recipients with and those without CMV disease, and premature babies with congenital CMV infection, respectively, were of gB type 1. An analysis of the clinical characteristics of BMT recipients with CMV disease indicated that all underwent either an allogeneic or matched, unrelated donor transplant, and half had severe acute graft-versus-host disease (grades 2 to 4). The statistically significant genotypic difference between CMV isolates from BMT recipients with and without CMV disease was not observed between isolates from renal-transplant recipients with and without CMV disease. We speculate that differences in pathogenesis in different patient groups might account for these observations. These findings would also facilitate decision making about the choice of recombinant CMV glycoprotein vaccine required to immunize transplant donors and the subsequent adoptive transfer of immunity to BMT recipients. When the source of CMV DNA required for genotyping was investigated among renal-transplant recipients, direct use of peripheral blood leukocytes was 95% effective compared to the effectiveness of cells obtained from conventional culture of peripheral blood specimens.

Adult↗

Diagnosing cytomegalovirus disease in CMV seropositive renal allograft recipients: a comparison between the detection of CMV DNAemia by polymerase chain reaction and antigenemia by CMV pp65 assay.

The optimal diagnostic test for CMV disease in renal allograft recipients in a locality with a high CMV seropositive rate has not been fully determined. We compared the usefulness of the CMV pp65 antigenemia (CMV-Ag) assay with the detection of DNAemia by a nested polymerase chain reaction (PCR) method in diagnosing CMV disease in 56 renal allograft recipients, of whom 50 (89.2%) were CMV seropositive prior to transplant (tx). Positive CMV-Ag assays were found in 126/281 samples (44.8%) of 27 patients (48.2%) of whom five had seven episodes of CMV disease. The remaining 22 patients were asymptomatic. The symptomatic patients had significantly higher median peak CMV-Ag levels than the asymptomatic patients [800 (160-1380) vs. 5 (1-604) per 2 x 10(5) peripheral blood leukocyte (PBL), p < 0.0001]. One hundred and eight samples were tested by both CMV-Ag and PCR methods. Out of the 108 samples, 89 showed concordant results (37 positive and 52 negative for both tests). Seventeen samples of 11 patients were CMV-Ag negative/PCR positive. Out of these 11 patients, two had CMV disease and the discrepancy in the results was due to blood samples taken after the start of ganciclovir therapy. Falsely negative PCR tests were found in two samples of two patients with positive CMV-Ag assays. With a outoff antigenemia level of 100 per 2 x 10(5) PBL, the sensitivity, specificity, positive and negative predictive values for diagnosing CMV disease were 100, 96, 71.4 and 100%, respectively. On the other hand, CMV DNAemia was detected in many asymptomatic patients, and the PCR test results correlated poorly with the clinical manifestations of the disease. In symptomatic patients undergoing ganciclovir therapy, the quantification of antigenemia level allowed the assessment of treatment efficacy. In addition, positive CMV-Ag assays at the end of therapy were associated with the subsequent relapse of CMV disease in two patients. The high specificity, together with the short processing time of 4 h, make the CMV-Ag assay the test-of-choice for diagnosing CMV disease in a renal transplant population with a predominance of CMV seropositive patients.

Adolescent↗

A prospective study on anti-endothelial cell antibodies in patients with systemic lupus erythematosus.

IgG anti-endothelial cell antibodies (AECA) were detected in 48.5% of patients with active systemic lupus erythematosus (SLE) and in 7% of patients during remission and were associated with the development of diffuse proliferative lupus nephritis. Sixteen AECA-positive patients were prospectively studied for 25.2 +/- 2.9 months. Serial AECA levels correlated with disease activity in 10 (62.5%) patients. Seven (43.8%) of 16 patients remained AECA positive during clinical remission. Among four episodes of disease exacerbation and 16 instances of clinical improvement, 85% (17 episodes) were accompanied by corresponding changes in the level of AECA, while corresponding changes in C3, anti-nuclear antibodies, and anti-double-stranded DNA antibodies were noted in 60, 60, and 80% of cases, respectively (p = not significant). AECA served as the only serologic marker of altered disease activity in five episodes, when C3, ANA, and anti-double-stranded DNA levels remained unaltered. We conclude that the level of AECA can serve as a marker of disease activity in SLE and that serial monitoring of AECA can complement other serologic parameters in the management of patients.

Adult↗

Correlation between serum HCV RNA and aminotransferase levels in patients with chronic HCV infection.

Cross-sectional studies on the correlation between serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C have yielded conflicting results. We conducted a longitudinal study to examine the correlation between HCV viremia and serum ALT levels in individual patients over time. Serial samples (mean 9) from 25 patients with chronic HCV infection, including interferon-treated and untreated immunocompetent and immunosuppressed patients, collected over a period of 1-4.8 years (mean 2.6 years) were tested for HCV RNA and ALT levels using a highly reproducible quantitative (bDNA) assay. A significant correlation was found between serum HCV RNA and ALT levels in the patients who received IFN therapy, but no correlation was observed in the untreated patients. Among the untreated patients, the immunosuppressed patients had significantly higher HCV RNA levels (39 +/- 4 vs 3.6 +/- 8 Meq/ml, P < 0.0001) but significantly lower ALT (56 +/- 11 vs 97 +/- 12 units/liter, P = 0.03) levels when compared to the immunocompetent ones. In summary, we found no correlation between serum HCV RNA and ALT levels in chronic hepatitis C patients who are not receiving interferon therapy. Immunosuppression results in higher HCV RNA but lower ALT levels.

Adult↗

Optimal treatment and long-term outcome of tuberculous peritonitis complicating continuous ambulatory peritoneal dialysis.

A retrospective study of the treatment and short- and long-term outcomes of tuberculous peritonitis (TBP) complicating continuous ambulatory peritoneal dialysis (CAPD) among our dialysis patients over a 6-year period was performed. Ten cases of TBP complicating CAPD were identified among 601 dialysis patients between January 1988 and December 1994. There were four male and six female patients. The most common clinical features were abdominal pain, fever, and cloudy peritoneal fluid (PDF). Two patients had concurrent bacterial peritonitis. Extraperitoneal tuberculosis was not observed. The majority of the patients showed neutrophil predominance in the PDF. Only one patient had a positive acid-fast bacilli smear of the PDF. The acid-fast bacilli culture of the PDF was positive in all patients. The patients were treated with isoniazid, rifampicin, and pyrazinamide for 9 to 12 months (mean, 11 months). Continuous ambulatory peritoneal dialysis was continued in all patients. Two patients died, one from multiorgan failure at 2 months and the other from sudden cardiac death at 9 months. Two patients were converted to hemodialysis at 3 months. Six patients continued to receive CAPD after completion of the antituberculous treatment. Four of these six patients were still alive 5 years after the TBP. Three patients were still undergoing CAPD with satisfactory ultrafiltration and solute clearance. None of the patients developed relapse of TBP. We concluded that (1) TBP is a rare but important complication of CAPD, (2) removal of the Tenckhoff catheter is not mandatory in the management of TBP complicating CAPD, and (3) long-term continuation of CAPD is possible after TBP.

Antitubercular Agents↗

Endothelial cell binding by human polyclonal anti-DNA antibodies: relationship to disease activity and endothelial functional alterations.

Polyclonal anti-dsDNA and anti-ssDNA antibodies (PoAb) that showed significant binding to human umbilical vein endothelial cells (HUVEC) were isolated from eight patients with systemic lupus erythematosus (SLE). Anti-dsDNA PoAbs from five patients and anti-ssDNA PoAbs from seven patients demonstrated enhanced binding to HUVEC during active disease, compared with PoAbs obtained from corresponding patients during remission. Reduction of the DNA content in the PoAb preparations by DNase treatment was associated with enhanced binding to HUVEC in 20 of 32 PoAbs tested, which included 75% 'active disease' PoAbs, and with reduced binding to HUVEC in three of 32 PoAbs tested, all obtained during remission. Such altered endothelial cell binding was reversed with DNA reconstitution. Binding of the remaining nine PoAbs to HUVEC was not altered by variations in their DNA content. Induced plasma membrane expression of E-selectin, but reduced expression of vascular cell adhesion molecule-1 (VCAM-1) by HUVEC, was observed following incubation of HUVEC with 'active disease' PoAbs from three and two of the eight patients, respectively. PoAbs and serum samples from two of the eight patients during active disease induced von Willebrand factor release from HUVEC, which was not observed during remission. We conclude that anti-DNA antibodies from selected patients with SLE can bind to endothelial cells. Correlation between cellular binding and disease activity suggests that such binding of anti-DNA antibodies to endothelial cells could be of pathogenic significance. Preliminary data also suggest that the expression of adhesion molecules and haemostatic factor(s) by endothelial cells may be modified following their binding by anti-DNA antibodies.

Adolescent↗

Peliosis of the spleen: possible association with chronic renal failure and erythropoietin therapy.

Splenic peliosis was identified at necropsy in a 62-year-old woman receiving continuous ambulatory peritoneal dialysis for end-stage renal failure, and erythropoietin therapy for uraemia and anaemia. The immediate cause of death was arrhythmia related to ischaemic heart disease, following an episode of intramuscular haematoma (secondary to platelet dysfunction). The unusual association between peliosis and renal failure, and possibly erythropoietin therapy, is discussed.

Anemia↗

Clinicopathological features of hepatitis C virus antibody negative fatal chronic hepatitis C after renal transplantation.

Clinical course and serial liver histology of a patient who developed fatal chronic active hepatitis C after renal transplantation are presented. This patient developed persistently deranged liver biochemistry 3 months after transplantation, despite normal liver enzyme values during the preceding 3 years on hemodialysis. In addition to increased parenchymal enzyme concentrations, the levels of ductal enzymes were also markedly elevated, with peak levels of alanine aminotransferase and gamma-glutamyl transpeptidase 7 and 100 times, respectively, the normal upper limit. The patient was persistently seronegative for hepatitis C virus (HCV) antibodies, but positive for HCV RNA. Treatment with alpha-interferon for 6 months, initiated after the development of early cirrhosis, resulted in no improvement, and the patient died from liver failure 36 months after renal transplantation. Serial liver histology, examined four times from 11 months to 36 months after transplantation, showed progressive deterioration from chronic active hepatitis to cirrhosis. This patient illustrates the uncommon complication of rapidly progressive and ultimately fatal liver disease due to HCV infection after renal transplantation. Early recognition with anti-HCV and HCV RNA assays as well as histologic assessment are crucial for the identification of patients with a poor prognosis who might benefit from therapeutic intervention before irreversible liver damage.

Adult↗