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Biomedical subjects

T M Chan

Publications and source records attributed to T M Chan.

At least 127 records · Page 7Linked to original sources
PubMed1995

Sequential therapy for diffuse proliferative and membranous lupus nephritis: cyclophosphamide and prednisolone followed by azathioprine and prednisolone.

A retrospective single-center cohort study was conducted on 35 patients with diffuse proliferative (WHO type IV) and/or membranous (type V) lupus nephritis (22 with type IV, 6 with type V, and 7 with type IV plus V) who had been treated with a sequential regimen comprising prednisolone and cyclophosphamide during active disease, followed by low-dose prednisolone and azathioprine maintenance. The follow-up period was 33.2 +/- 4.5 months. At presentation, 32 (91.4%) patients were nephrotic, and an abnormal serum creatinine level was noted in 14 (48.3%) patients with type IV changes. Cyclophosphamide was given for 26.8 +/- 2.8 weeks. 33 (94.3%) patients achieved complete or partial renal remissions: 77.3 and 22.7% of the type IV patients, 16.7 and 66.6% of the type V patients, and 14.3 and 71.4% of the type IV plus V patients, respectively (p < 0.0001 for type IV versus type V and for type IV versus type IV plus V). The duration of therapy before renal remissions and normalization of C3 were attained was similar among the three groups of patients. Disease relapse occurred in 4 (18.2%) of 22 IV patients and in 1 of the 5 type V patients in remission. Mortality was not observed, and none of the patients had an increase in serum creatinine level to double the baseline value. Adverse effects related to therapy included: hair loss (42.9%), transient amenorrhea (53.6%), leukopenia (11.4%), febrile episodes (14.3%), and herpes zoster(28.6%). We conclude that sequential use of prednisolone and cyclophosphamide followed by low-dose prednisolone and azathioprine can achieve favorable therapeutic results in the majority of patients with diffuse proliferative and/or membranous lupus nephritis, without excessive toxicities.

Adult↗
PubMed1995

Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect.

To examine potential mechanisms for the blood pressure-lowering action of the thiazolidinedione compound, pioglitazone (PIO), we studied the effects of the drug on blood pressure and insulin action in vivo and on vascular tissue in vitro. In vivo, PIO lowered blood pressure in fructose-fed and chow-fed rats to an extent that could not be explained by alterations in fasting plasma insulin or free magnesium concentrations or by alterations in whole-body insulin sensitivity. In vitro, PIO caused significant blunting of the contractile responses of aortic rings to NE, arginine vasopressin (AVP), and potassium chloride; the blunting of responses to NE was maintained after removal of the endothelium. To assess the potential importance of extracellular calcium to the vasodepressor effect of PIO, we measured contractile responses to NE in the absence of calcium, and then after acute restoration of calcium in the presence of NE. PIO had no effect on the contractile response in the absence of calcium. By contrast, PIO blunted by 42% the contractile response that occurred when the extracellular calcium supply was acutely restored in the presence of NE, suggesting that the blunting was mediated by blockade of calcium uptake by vascular smooth muscle. Such an effect was confirmed in cultured a7r5 vascular smooth muscle cells, which exhibited a brisk increase in intracellular calcium in response to AVP that was blocked by PIO in a dose-dependent fashion. Our data indicate that PIO has a direct vascular effect that appears to be mediated at least in part by inhibition of agonist-mediated calcium uptake by vascular smooth muscle. The direct vascular effect may contribute to the blood pressure-lowering actions of PIO in vivo, because that effect could not be explained by alterations in whole-body insulin sensitivity.

Animals↗
PubMed1995

Spontaneous improvement of renal function following renal allograft rupture associated with acute rejection.

A renal allograft recipient developed acute cellular rejection 7 days after her second cadaveric renal transplantation. Her renal function failed to improve after three 0.5 g pulses of intravenous Methylprednisolone therapy. Spontaneous renal allograft rupture occurred 4 days later, which was successfully salvaged surgically. There was spontaneous rapid improvement of renal function with marked diuresis immediately following the allograft rupture, without additional immunosuppressive therapy. Her clinical course illustrates that delayed improvement of renal allograft function can be a consequence of raised intra-renal pressure during acute rejection. In addition, intensification of anti-rejection therapy is not an absolute requirement in all cases of rejection-associated renal allograft rupture.

Acute Disease↗
PubMed1994

Clinicopathologic features of hepatitis C virus infection in renal allograft recipients.

The clinicopathologic features, the natural history, and the prognostic indicators of hepatitis C virus (HCV)-related liver disease in renal allograft recipients have not been well defined. Among 220 renal allograft recipients, 21 were seropositive for HCV RNA, which persisted on prospective follow-up for 40 months. Elevations in alanine aminotransferase and alkaline phosphatase were noted after renal transplantation in 15 (71.4%) and 9 (42.9%) patients, respectively, with 11 (52.4%) showing recurrent or persistent abnormalities. Mortality from liver failure was noted in 1 patient. Persistence of abnormal liver biochemistry was associated with an early onset of biochemical derangement after transplantation, and a longer dialysis duration (P < 0.05). HCV-related liver pathology was assessed in 13 patients by histologic scoring with respect to "hepatitic activity," "bile duct damage," and "architectural abnormality," adding up to a "total" score. Six (46.2%) of 13 initial liver biopsies showed significant chronic liver disease. Liver histology correlated with mean alanine aminotransferase and alkaline phosphatase levels after renal transplantation, and was more severe in patients with persistent biochemical abnormalities. Early onset of abnormal liver biochemistry after transplantation and persistently abnormal biochemistry were independent predictors of worse total and activity scores (P < 0.05). Renal transplant recipients demonstrated lower activity scores when compared with nonimmunosuppressed subjects with chronic hepatitis C (P = 0.03). HCV RNA was detectable in all 23 liver specimens tested. We conclude that significant, potentially life-threatening liver pathology manifests in about half of renal transplant recipients with chronic HCV infection. Liver histology correlates with the longitudinal biochemical profile. Patients with early onset of biochemical abnormalities and persistently deranged liver biochemistry are at risk of developing severe liver disease.

Adult↗
PubMed1994

Treatment of fungal peritonitis complicating continuous ambulatory peritoneal dialysis with oral fluconazole: a series of 21 patients.

Twenty-one episodes of fungal peritonitis occurred over 35 months among 290 patients on CAPD, accounting for 6.3% of all peritonitis episodes. Patients with more frequent bacterial peritonitis were at higher risk of developing fungal peritonitis, and 28.6% of cases followed antimicrobial therapy. Candida species accounted for 85.7% of cases. Oral fluconazole was used as initial therapy in all patients, which was followed by catheter removal if peritonitis failed to improve. The cure rate with fluconazole therapy alone without catheter removal was 9.5%. Fluconazole plus catheter removal, the latter necessitated in 85.7% of cases, resulted in a cure rate of 66.7%. The remaining 3 (14.3%) patients responded to intravenous amphotericin given as salvage therapy. Disease-related mortality was 14.3%. Reinsertion of dialysis catheter was attempted in 15 patients and CAPD was successfully resumed in 13 (86.7%). We conclude that oral fluconazole can be safely used as initial therapy in patients with fungal peritonitis complicating CAPD. Although catheter removal was necessary in the majority of patients, this sequential approach resulted in a relatively low prevalence of peritoneal adhesions and subsequent CAPD failure.

Administration, Oral↗
PubMed1994

Hyperlipidemia after renal transplantation: treatment with gemfibrozil.

Thirty-eight renal allograft recipients who had persistent hyperlipidemia and stable renal function 27.8 +/- 18.2 months after renal transplantation were treated with gemfibrozil. Gemfibrozil therapy resulted in a decrease in the levels of total cholesterol (TC; 297.6 +/- 41.0 mg/dl to 249.2 +/- 43.7 mg/dl, -16.3%; p < 0.0001), triglyceride (TG; 231.9 +/- 116.8 to 125.7 +/- 58.4 mg/dl, -45.8%, p < 0.0005), and LDL-cholesterol (LDL-C; 203.8 +/- 37.4 to 174.5 +/- 42.5 mg/dl, -14.4%; p = 0.001), which were sustained for 29.1 +/- 16.0 months. Comparison of sequential lipid profiles between gemfibrozil-treated individuals and untreated hyperlipidemic controls matched for age, sex, time after transplantation, and the degree of hyperlipidemia, showed that gemfibrozil-treated patients had lower levels of TC (239.9 +/- 39.5 vs. 272.8 +/- 34.1 mg/dl; p < 0.005), TG (125.7 +/- 26.6 vs. 167.3 +/- 69.0 mg/dl; p < 0.05), and LDL-C (160.2 +/- 41.3 vs. 185.3 +/- 26.6 mg/dl; p < 0.05) on serial follow-up. No significant side-effect was observed with gemfibrozil therapy. Our data showed that gemfibrozil was a safe and effective drug for the treatment of hyperlipidemia in renal allograft recipients, which could reduce these patients's long-term cardiovascular risks.

Adult↗
PubMed1994

Delayed recurrent thromboembolism of the allograft kidney.

Renal artery thromboembolism is a rare event in native kidneys and has never been reported to occur in allograft kidney. We report a case of allograft kidney infarction secondary to embolisation from thrombus in the hypogastric artery supplying the allograft on two separate occasions 1 and 2 years after transplant. Anticoagulation therapy alone was given and the patient responded well with partial recovery of renal function.

Adult↗
PubMed1994

Endothelial-dependent vascular effects of insulin and insulin-like growth factor I in the perfused rat mesenteric artery and aortic ring.

Insulin and insulin-like growth factor I (IGF-I) exhibit vasoactivity. To examine the role of the endothelium in mediating the vascular responses to insulin and IGF-I, we exposed both isolated intact rat mesenteric arteries and rat aortic rings to these growth factors in the presence and absence of endothelium. Perfusion of rat mesenteric arteries with insulin, IGF-I, or IGF-II resulted in the potentiation of arginine vasopressin (AVP)-induced vasoconstriction. Of these growth factors, IGF-I was the most potent, with a significant effect at 0.6 nM and maximal effects at 6.0 nM, followed by IGF-II and insulin. Endothelial denudation or addition of cycloheximide prevented the growth-factor effects. Tissue cGMP levels in the mesenteric artery were minimally affected by growth factors. Insulin and IGF-I vascular effects were not inhibited by BQ123, an endothelin (ET) antagonist that blocked ET-1 enhancement of AVP response. Perfusion of mesenteric arteries with IGF-I for 1 h did not alter vessel ET-1 or ET-1 mRNA contents. Addition of indomethacin markedly inhibited the IGF-I effect on AVP contraction. Thus, the mesenteric vascular effect of insulin and IGF-I is not associated with ET-1 release but appears to link to an increased release of an endothelial-derived contracting factor or the decreased production of an endothelial-derived relaxing factor from the cyclooxygenase pathway. In contrast to their action in the mesenteric artery, insulin (exceeding 100 nM) and IGF-I (1-30 nM) attenuated AVP- and norepinephrine-induced contraction in rat aortic rings. Endothelial-denudation abolished this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Serological, histological and polymerase chain reaction studies of Helicobacter pylori infection in patients with gastric adenocarcinoma.

The association between Helicobacter pylori (H. pylori) and gastric adenocarcinoma remains controversial. However, the prevalence of H. pylori infection in gastric adenocarcinoma varies with the method of detection used, eg, serology, histology, culture, and polymerase chain reaction. However, studies on gastric adenocarcinoma by these methods remain inconclusive. We compared the results of serology, histology, and polymerase chain reaction for detection of H. pylori infection in 12 patients with gastric adenocarcinoma to investigate the actual status of H. pylori infection in gastric adenocarcinoma. IgG antibodies to H. pylori were examined in the sera, and histology and polymerase chain reaction were used for identification of H. pylori on the resected gastric tissues of 12 patients with gastric adenocarcinoma. Among them. H. pylori infection was verified by serology in eight, polymerase chain reaction in seven, and histology in five. In all positive cases, H. pylori was identified only in the non-tumorous part of the gastric tissue. In all four seronegative patients, H. pylori was not present in any of the tissues examined by histology and polymerase chain reaction. We conclude that: 1) polymerase chain reaction is more sensitive than histology; 2) a good correlation between serology and polymerase chain reaction is found; and 3) H. pylori infection is absent in a proportion of patients with gastric adenocarcinoma identified by these methods.

Adenocarcinoma↗
PubMed1993

Orthovanadate and 2,3-dimethoxy-1,4-naphthoquinone augment growth factor-induced cell proliferation and c-fos gene expression in 3T3-L1 cells.

Our previous study demonstrated an increase in tyrosine protein phosphorylation and phosphatidylinositol phosphorylation induced by oxidants, suggesting a proliferative potential for these reactive substances. In the present study, we focus our investigation on the similarity between a redox cycling naphthoquinone and orthovanadate (VO), an oxidant generator as well as a potent phosphotyrosyl phosphatase inhibitor, in growth of 3T3-L1 cells cultured in serum-free media. Vanadate increased [3H]thymidine incorporation in a concentration-dependent manner. However, in the presence of insulin, epidermal growth factor, or platelet-derived growth factor, VO synergistically augmented, by as much as fivefold, DNA synthesis stimulated by these growth factors. An increase in the association of PI 3-kinase with the insulin receptor was also observed in cells treated with insulin + VO. Expression of the c-fos gene, a marker of early nuclear event in mitogenesis induced by insulin, EGF, and PDGF, but not vasopressin, a non-tyrosine kinase-linked mitogen, was also enhanced by VO. Flow cytometric analysis indicated an acceleration of cell cycle progression when VO and insulin were present simultaneously. Striking similarity was observed between VO and 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in PI 3-kinase activation, c-fos proto-oncogene expression, and DNA synthesis, key events associated with cell growth. Additionally, both VO and DMNQ gave rise to DMPO-.OH adduct EPR signal measured with cell suspensions. These data support an oxidant-mediated increase in tyrosine protein phosphorylation early in the signal transduction cascade of growth factor receptors, leading to augmentation of cell proliferation.

3T3 Cells↗
PubMed1993

A prospective study of hepatitis C virus infection among renal transplant recipients.

BACKGROUND: Chronic non-A, non-B hepatitis is a major cause of liver disease in renal transplant recipients. METHODS: One hundred eight-five renal allograft recipients, including 151 who had been prospectively followed up for 24 months, were studied to determine the prevalence and course of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was measured by enzyme immunoassay, and HCV RNA was measured by nested polymerase chain reaction assay. RESULTS: Twenty-three (12.4%) patients were positive for anti-HCV and/or HCV RNA: 19 (10.3%) were anti-HCV positive; and HCV RNA was detected in 18 (94.7%) anti-HCV-positive and 4 (2.4%) anti-HCV-negative patients. Markers of HCV infection persisted in all HCV-positive patients over the 2-year period. Most HCV-positive patients acquired HCV infection before or at the time of transplantation. The incidence of new infection after transplantation was 0.45% per patient-year. Anti-HCV and/or HCV RNA was detected in 75% of patients with biochemical chronic non-A, non-B hepatitis, but transaminase levels were persistently normal in 30.4% of HCV-positive individuals. CONCLUSIONS: HCV infection is common among renal transplant recipients. Testing for HCV RNA is important because some patients might not produce anti-HCV. Transaminase levels cannot be used as a surrogate marker of HCV infection in these patients.

Adult↗
PubMed1993

Clinical significance of anti-endothelial cell antibodies in systemic vasculitis: a longitudinal study comparing anti-endothelial cell antibodies and anti-neutrophil cytoplasm antibodies.

Ten patients with systemic vasculitis, all positive for anti-neutrophil cytoplasm antibody (ANCA), were followed for a mean of 36 weeks to determine the prevalence of anti-endothelial cell antibodies (AECAs) and the relationship between AECAs, ANCAs, and disease activity. Anti-endothelial cell antibodies were detected in eight (80%) patients at some time during the study. The levels of both AECAs and ANCAs changed with time, and these autoantibodies were present in 48% and 63% of the total 100 serum samples, respectively. Eighteen clinical remissions were observed; in 16 (88.9%) cases the level of ANCAs dropped. Fifteen (83.3%) of the 18 remissions were among the AECA-positive patients and the level of AECAs decreased in 13 (86.7%) instances (P = not significant). There were 11 episodes of disease relapse; all were associated with an increase in the level of ANCAs. Nine (81.8%) of the 11 relapses were among AECA-positive patients, and the level of AECAs increased in eight (88.9%) cases (P = not significant). Serum levels of AECAs appeared less suppressible by cyclophosphamide therapy compared with ANCAs, and patients who were persistently positive for AECAs despite being ANCA-negative during remissions were at risk of subsequent relapse. Disease recrudescense was not observed in patients persistently tested negative for both AECAs and ANCAs. Intravenous immunoglobulin therapy was used in four patients and resulted in clinical improvement in all cases, but with variable changes in the levels of AECAs and ANCAs. We conclude that AECAs are commonly detected in patients with systemic vasculitis and their levels show a relationship to disease activity similar to that for ANCAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Identification of DNA-binding proteins on human umbilical vein endothelial cell plasma membrane.

The binding of anti-DNA antibodies to the endothelial cell is mediated through DNA, which forms a bridge between the immunoglobulin and the plasma membrane. We have shown that 32P-labelled DNA bound to the plasma membrane of human umbilical vein endothelial cells (HUVEC) by a saturable process, which could be competitively inhibited by non-radiolabelled DNA. In addition, DNA-binding was enhanced in HUVEC that had been treated with IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha). DNA-binding proteins of mol. wt 46,000, 92,000, and 84,000 were identified by the binding of 32P-labelled DNA to plasma membrane proteins separated on SDS-PAGE. DNA-binding proteins of mol. wt 46,000 and 84,000 were also present in the cytosol and nucleus. Murine anti-DNA MoAb410 bound to a single band, at mol. wt 46,000, of plasma membrane protein, in the presence of DNA. Our results showed that DNA-binding proteins are present in different cellular fractions of endothelial cells. DNA-binding proteins on the cell membrane could participate in the in situ formation of immune deposits; and their presence in the cell nucleus suggests a potential role in the modulation of cell function.

Antibodies, Monoclonal↗
PubMed1993

Resolution of membranoproliferative glomerulonephritis complicating angiofollicular lymph node hyperplasia (Castleman's disease).

A novel renal complication was reported in a patient with angiofollicular lymph node hyperplasia (Castleman's Disease), who developed acute renal failure due to membranoproliferative glomerulonephritis. Renal biopsy showed marked mesangial hyperplasia, basement membrane thickening with subendothelial electron-dense deposits, interstitial plasma cell infiltration, and glomerular deposition of IgM and complement components. A resolution of systemic manifestations and an improvement in renal function followed prednisolone and azathioprine therapy. Disease relapse, with increasing proteinuria and the development of factor 8 inhibitor, occurred 3 months later. Sustained remission was achieved with prednisolone and cyclophosphamide therapy, which were given for 42 and 12 months, respectively. Renal biopsy during remission showed significant resolution of the mesangial hyperplasia and disappearance of interstitial plasmacytic infiltration as well as subendothelial electron-dense deposits.

Adult↗
PubMed1993

Prevalence of hepatitis C virus infection in hemodialysis patients: a longitudinal study comparing the results of RNA and antibody assays.

We longitudinally studied 51 patients from two hemodialysis centers to determine the prevalence of hepatitis C virus infection in hemodialysis patients. Serum samples were tested for antibody to HCV by first- and second-generation enzyme immunoassays and for hepatitis C virus RNA by nested polymerase chain reaction assay. Antibody to hepatitis C virus was detected in the initial serum samples by first-generation enzyme immunoassay and second-generation enzyme immunoassay in 6 (11.8%) and 11 (21.6%) patients, respectively. First-generation enzyme immunoassay had a false-positive rate of 33.3% and a false-negative rate of 63.6%. Hepatitis C virus RNA was found in eight second-generation enzyme immunoassay-positive patients (72.7%) and in one patient negative for antibody to hepatitis C virus (2.5%) giving an overall positivity rate of 17.6%. After 19 mo, antibody to hepatitis C virus was detected in 15 patients (29.4%) on second-generation enzyme immunoassay; hepatitis C virus RNA was found in 13 patients (25.5%). Hepatitis C virus markers persisted in all 12 patients with initial evidence of hepatitis C virus infection. Three patients acquired hepatitis C virus infection during the interim, giving a new infection rate of 4.9% per patient-year. Antibody to hepatitis C virus, hepatitis C virus RNA or both was detected in 55.6% of patients with biochemical changes suggestive of non-A, non-B hepatitis. Of the 15 antibody to hepatitis C virus, second-generation enzyme immunoassay-positive patients, 66.7% had persistently normal serum transaminase levels. In summary, hepatitis C virus infection is common among hemodialysis patients. First-generation enzyme immunoassay is an unreliable assay for antibody to hepatitis C virus in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Antibody response to core, envelope and nonstructural hepatitis C virus antigens: comparison of immunocompetent and immunosuppressed patients.

Some immunosuppressed patients with hepatitis C virus infection do not have detectable levels of antibody to hepatitis C virus on second-generation enzyme immunoassay. Antibodies to the envelope and nonstructural region 5 proteins have not been examined. Four groups of patients with hepatitis C virus infection were studied: (a) 20 immunocompetent patients, (b) 15 hemodialysis patients, (c) 17 kidney transplant recipients and (d) 3 acute leukemia patients who underwent bone marrow transplantation. Serum samples were tested for antibody to hepatitis C virus with a second-generation enzyme immunoassay and multi-antigen enzyme immunoassays and for hepatitis C virus RNA with a nested polymerase chain reaction assay. All the immunocompetent patients reacted to C25, C22 and C33C; 90% reacted to nonstructural region 5 antigen and 80% reacted to C100-3. Only 55% reacted against yeast-derived e1 and e2 antigens, but all reacted against vaccinia virus--expressed N e1 and e2 antigens, indicating that the envelope epitopes are conformational and glycosylated. Sixty-five percent to 90% of dialysis and kidney transplant patients reacted to C25, C22 and N e1 and e2, but only 12% to 60% reacted to C100-3, C33C and nonstructural region 5 antigen. Diminution or loss of reactivity to hepatitis C virus antigens was observed after kidney and bone marrow transplantation, with C25 and N e1 and e2 less affected. Our data suggest that incorporation of C25 and N e1 and e2 antigens in the assay for antibody to hepatitis C virus would improve the detection of hepatitis C virus infection in immunosuppressed patients.

Antibody Formation↗