A confused uraemic woman.
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Brain Diseases↗
Biomedical subjects
A Y Wang
Publications and source records attributed to A Y Wang.
Immunohistochemical and ultrastructural evidence that dendritic cells infiltrate stenotic aortocoronary saphenous vein bypass grafts.
We earlier speculated that antigen-presenting dendritic cells may be involved in the immune reactions leading to saphenous vein bypass graft failure. The purpose of this study was to confirm whether dendritic cells are present in stenotic human saphenous vein bypass grafts. Segments of stenotic saphenous vein grafts were explanted from 14 patients at re-do bypass operation and ten normal saphenous veins were harvested during femoro-popliteal grafting. Sections of specimens were analysed using cell type specific antibodies to identify dendritic cells (CD1a, S-100), T-lymphocytes (CD3), macrophages (CD68), smooth muscle cells (alpha-SMA) and endothelial cells (FVIII). Dual immunostaining, confocal immunofluorescent laser scanning microscopy and electron microscopy were used. Stenotic grafts showed structural alterations of intimal hyperplasia and varying degrees of atherosclerotic degeneration. No cells expressing CD1a and S-100 were observed in the intima and media of normal saphenous veins. Cells expressing these antigens were present around areas of medial neovascularization and within intimal atherosclerotic lesions in saphenous vein bypass grafts. Electron microscopy demonstrated the presence of cells containing a well-developed tubulovesicular system which is unique to cells from the dendritic cell family. Double immunohistochemistry and confocal immunofluorescent microscopy revealed the co-localization of T-lymphocytes with dendritic cells. Dendritic cells are present in stenotic saphenous vein bypass grafts. Dendritic cells may be responsible for antigen presentation and modulation of immune reactions in accelerated graft atherosclerosis through their interaction with T-lymphocytes.
Adult↗
Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts.
This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.
Aged↗
Selective internal radiation therapy by yttrium-90 microspheres for hepatocellular carcinoma after renal transplantation.
We report a HBsAg-positive patient who developed hepatocellular carcinoma (HCC) 7 years after cadaveric kidney transplantation. The tumor was unresectable because of coexisting cirrhosis. Selective internal radiation (SIR) therapy, a novel therapy with the technique recently perfected, was used. Yttrium-90 microspheres were given via an angiographic catheter under fluoroscopy guidance. Serum alpha-fetal protein (AFP) was normalized within 2 wk. A follow-up abdominal CT scan revealed significant necrosis of the tumor and compensatory hypertrophy of non-diseased liver. The treatment was well tolerated except for transient liver function deterioration. The patient enjoyed 15 months of symptom-free survival before she died of liver failure. Practical aspects and potential applications of SIR therapy in this group of patients are discussed.
Adult↗
Clinical course of peritonitis due to Pseudomonas species complicating peritoneal dialysis: a review of 104 cases.
BACKGROUND: Peritonitis due to Pseudomonas species is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) patients. The clinical course of peritonitis due to Pseudomonas complicating CAPD remains unclear. METHODS: All of the Pseudomonas species episodes of peritonitis in our dialysis unit were studied from 1995 to 1999. During this period, there were 859 episodes of peritonitis recorded, 113 of which were caused by the Pseudomonas species. Nine episodes were excluded because they were mixed growth. The remaining 104 episodes in 68 patients were reviewed. RESULTS: The underlying renal diagnosis and prevalence of comorbid conditions of the 68 patients were similar to those found in our entire dialysis population. There was a history of antibiotic therapy within 30 days of the onset of peritonitis due to the Pseudomonas species in 69 episodes (66.3%). In 47 episodes (45.2%) there was a concomitant exit site infection. The overall primary response rate was 60.6% and the complete cure rate was 22.1%. The presence of exit site infection was associated with a lower primary response rate (22 in 47 vs. 41 in 57 episodes, P < 0.01) and a lower complete cure rate (5 in 47 vs. 18 in 57 episodes, P < 0.02). The episodes that had received recent antibiotic therapy had a significantly lower complete cure rate than the de novo cases (8 in 69 vs. 15 in 35 episodes, P < 0.001). Episodes receiving third-generation cephalosporin as part of the initial antibiotic regimen had a significantly higher primary response rate than the ones that initially received aminoglycoside (54 in 81 episodes vs. 8 in 22 episodes, P < 0.05), but their complete cure rates were similar. Twenty-four cases failed to respond to antibiotics and the Tenckhoff catheter was removed. The chance of returning to CAPD was higher when the Tenckhoff catheter was removed on day 10 than on day 15 (9 in 14 cases vs. 5 in 10 cases), although the result was not statistically significant. The Tenckhoff catheter was removed and replaced at another site simultaneously in another 14 cases after the effluent cleared up. None of these patients had a relapse of peritonitis within three months. CONCLUSIONS: Recent antibiotic therapy is the major risk factor for peritonitis due to the Pseudomonas species. Exit site infection and recent antibiotic therapy are associated with poor therapeutic response to antibiotics. When the therapeutic response is suboptimal, early Tenckhoff catheter removal may help preserve the peritoneum for further peritoneal dialysis. Elective Tenckhoff catheter exchange after clearing up the peritoneal dialysis effluent may also reduce the likelihood of relapse. It is desirable to use third-generation cephalosporin in the initial antibiotic regimen for peritonitis treatment in localities with a high incidence of peritonitis due to the Pseudomonas species.
Adult↗
Plasminogen activator inhibitor-1 gene polymorphism 4G/4G genotype and lupus nephritis in Chinese patients.
BACKGROUND: Abnormal regulation in the coagulation and fibrinolytic system may play an important role in mediating glomerular damage in lupus nephritis. Indeed, glomerular thrombosis occurs frequently in lupus nephritis and predicts the future development of glomerular sclerosis. In the murine model of active lupus nephritis, plasminogen activator inhibitor-1 (PAI-1) gene was overexpressed throughout the kidney, both within the glomeruli and also in tubules and vessels. The level of PAI-1 expression in the tissues appeared to correlate with the progression of lupus nephritis. Recently, a single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene has been identified and shown to alter plasma PAI-1 activity. This study was therefore conducted to determine the association of the 4G/5G polymorphism of the PAI-1 gene with the development and severity of lupus nephritis. METHODS: The PAI-1 gene polymorphism of 118 systemic lupus erythematosus (SLE) patients and 103 healthy controls who were gender and age matched was determined using standard polymerase chain reaction. PAI-1 genotype results were studied in relationship to the development and severity of lupus nephritis. RESULTS: Allele frequencies of 4G/5G allele were 0.59/0.41 in lupus patients and 0.59/0.41 in controls (P = 1.000). No significant difference was noted in the genotype distribution between SLE patients with and without nephritis. However, lupus nephritis patients with the 4G4G genotype showed significantly heavier proteinuria (5.0 vs. 3.7 g/day; P = 0.023) when compared with patients with 4G5G and 5G5G genotypes. Also, 73.3% patients with 4G4G had an activity index > or =8 versus 37.3% patients with 4G5G and 5G5G (P = 0.003). Extensive necrotizing lesions were seen in 51.7% patients with 4G4G as compared with 23.5% patients with 4G5G and 5G5G (P = 0.014). The association of the 4G4G gene polymorphism with a higher nephritis activity and more severe necrotizing lesions persisted when only class III and class IV nephritis patients were studied. On the other hand, no significant association was noted between the PAI-1 gene polymorphism and the chronicity of the nephritis. CONCLUSION: These findings suggest that the 4G/5G polymorphism of the PAI-1 gene is associated with the activity but not the chronicity of lupus nephritis. The presence of the 4G4G genotype does not increase the risk of developing SLE or lupus nephritis, but predicts the development of higher nephritis activity and more extensive necrotizing lesions.
Adult↗
Reversible renal failure in paroxysmal nocturnal hemoglobinuria.
A Chinese patient with paroxysmal nocturnal hemoglobinuria (PNH) developed acute nonoliguric renal failure with intercurrent urinary tract infection and hemolysis. There was no evidence of renal vein thrombosis. Renal biopsy showed features of acute tubular necrosis (ATN) and hemosiderosis. Magnetic resonance imaging (MRI) showed characteristic features of renal hemosiderosis. The patient was stabilized with temporary hemodialysis and intravenous fluid. The renal function fully recovered 3 weeks later. We review the literature and summarize the clinical features of this disease entity. To our knowledge, this case is the first to report such disorder with thorough investigation including concomitant diagnostic MRI imaging and renal biopsy.
Acute Kidney Injury↗
Rapid recurrence of ANCA-negative pauci-immune vasculitis after cadaveric renal transplantation.
We report a patient with renal failure secondary to antineutrophil cytoplasmic autoantibody (ANCA)-negative pauci-immune systemic vasculitis who developed rapid recurrence of vasculitis involving skin, eye, and kidney allograft 1 month after cadaveric renal transplant while being maintained on cyclosporine, mycophenolate mofetil, and prednisolone. Despite early institution of aggressive treatment with plasma exchange, the disease remained uncontrolled and resulted in substantial morbidity and subsequent graft failure within 1 year post-transplantation. This case confirms that ANCA-negative vasculitides may recur in transplanted patients taking mycophenolate mofetil. Transplantation is contraindicated when active disease is evident.
Adult↗
Nonconvulsive status epilepticus in peritoneal dialysis patients.
This report describes nonconvulsive status epilepticus (NCSE) in four patients with end-stage renal disease (ESRD) on peritoneal dialysis therapy. All patients presented with acute confusion or stuporous state without clinical motor seizures. Three patients had active systemic infections and were being administered antibiotics. Diagnoses were confirmed in all cases by electroencephalogram (EEG), which showed characteristic diffuse sharp waves and spikes. The EEG appearance improved after anticonvulsant therapy. All patients had satisfactory control of their electrical seizure activity and made varying degrees of mental recovery. To our knowledge, this is the first reported series of NCSE in patients with ESRD on peritoneal dialysis therapy. It shows NCSE as a differential diagnosis for acute confusion. We emphasize the need for nephrologists to consider NCSE as a differential diagnosis for uremic encephalopathy.
Aged↗
Recurrent IgA nephropathy in renal transplant allografts.
Previous reports of renal transplantation for patients with underlying immunoglobulin A (IgA) nephropathy suggested a recurrence rate greater than 50% for transplant IgA nephropathy. Initially regarded as a benign condition, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We performed a retrospective analysis in a single center of 48 kidney transplant recipients, all of Chinese origin, with biopsy-proven IgA nephropathy as the cause of end-stage renal failure to determine the recurrence rate of IgA nephropathy in the transplant allograft and subsequent clinical course in Chinese patients. Median duration of follow-up was 52 months (range, 18 to 155 months). Fourteen patients (29%) had biopsy-confirmed recurrent transplant IgA nephropathy after a median of 52 months (interquartile range, 23 to 82 months) posttransplantation. Recurrent transplant IgA nephropathy was associated with greater serum IgA levels (P = 0.01). The presence of HLA-A2 in transplant recipients (P = 0.002) appeared to protect them from developing recurrent IgA nephropathy in the transplant allograft. Twenty-nine percent of patients with recurrent transplant IgA nephropathy had progressive deterioration of graft function. The progressive graft dysfunction (GD) rate was greater in patients with a transplant from a living related donor (LRD; 21%) compared with those with a transplant from a cadaveric or living unrelated donor (URD; 3%; P = 0.062). Although the cumulative graft survival rate was 100% at 5 years for transplants from both LRDs and URDs, the 10-year graft survival rate was only 63% for a graft from an LRD versus 93% for a URD (log-rank test, P = 0.19). A review of other reported series of recurrent transplant IgA nephropathy also showed an apparently greater incidence of GD for a graft from an LRD (28%) compared with a URD (15%). Our data suggest that although recurrent transplant IgA nephropathy is highly prevalent among the Chinese population, the risk for disease recurrence is not particularly increased compared with other ethnic groups. The trend toward a greater risk for GD for living related compared with unrelated allografts in patients with IgA nephropathy needs to be confirmed with further prospective study.
Adult↗
Severe bone marrow failure associated with the use of alternating steroid with chlorambucil in lupus membranous nephropathy in Chinese.
Severe pancytopenia associated with the use of alternating steroid with chlorambucil regimen was described in six patients with nephrotic syndrome secondary to lupus membranous nephropathy (WHO class V). We believe this is the first report describing the life-threatening degree of marrow toxicity associated with this regimen of alternating steroid with chlorambucil in a Chinese population. Our data suggests that the susceptibility to marrow toxicity with the use of chlorambucil may only be applicable to Chinese patients with underlying systemic lupus erythematosus as a similar degree of toxicity has neither been reported in lupus patients of other ethnic groups nor in non-lupus patients of Chinese origin.
Adult↗
Culling a clinical terminology: a systematic approach to identifying problematic content.
The College of American Pathologists and the National Health Service (NHS) in the United Kingdom are merging their respective clinical terminologies, SNOMED RT and Clinical Terms Version 3, into a new terminology, SNOMED CT. This requires mapping concept descriptions between the two existing terminologies. During the mapping process, many descriptions were identified as being potentially problematic. They require further review by the SNOMED editorial process before either (1) being incorporated into SNOMED CT, or (2) retired from active use. This article presents data on the concept descriptions that were identified as needing further review during the early phases of SNOMED CT development. Based on this work, we describe fourteen types of problematic terminology content. Identifying problematic terminology content can be approached in a systematic manner.
Clinical Medicine↗
SNOMED clinical terms: overview of the development process and project status.
Two large health care reference terminologies, SNOMED RT and Clinical Terms Version 3 , are in the process of being merged to form a comprehensive new work referred to as SNOMED Clinical Terms. The College of American Pathologists and the United Kingdom s National Health Service have entered into a collaborative agreement to develop this new work. Both organizations have extensive terminology development and maintenance experience. This paper discusses the process and status of SNOMED CT development and how the resources and expertise of both organizations are being used to develop this new terminological resource. The preliminary results of the merger process, including mapping, the merger of upper levels of each hierarchy, and attribute harmonization are also discussed.
Clinical Medicine↗
Mapping between SNOMED RT and Clinical terms version 3: a key component of the SNOMED CT development process.
SNOMED RT and Clinical Terms Version 3 are two large, controlled medical terminologies that are being merged to form a new work titled SNOMED Clinical Terms (SNOMED CT). One of the first steps in this process was to create maps between semantically equivalent and proximate concepts in the two terminologies. Same-as and is-a relationships were used to map the descriptions from one terminology to concepts in the other terminology. The objectives were to identify semantically equivalent concepts in the two terminologies, to find the most semantically proximate is-a relationships for non-equivalent concepts, and to evaluate the synonymy in the source terminologies. The results suggest that the rate of semantic overlap between descriptions in SNOMED RT and CTV3 is approximately 28%. This article discusses the methodology, issues, and findings of the description mapping process.
Clinical Medicine↗
Posttransplant Epstein-Barr virus-associated myogenic tumors involving bone.
BACKGROUND: Epstein-Barr virus (EBV)-associated myogenic tumors in immunocompromised patients were recently recognized, but their biologic behavior remains only partially understood. Although observations so far have permitted the recognition of similarities between posttransplant myogenic tumors and posttransplant lymphoproliferative disorders (PTLD), the number of reports are still few, and new experiences continue to be informative. METHODS: The authors describe what they believe is the first example of posttransplant EBV-associated myogenic tumor involving bone, which is also remarkable for its multicentric symmetric limb distribution. Immunohistochemistry of tumor cells for myogenic antigens (desmin and smooth muscle actin), EBV antigens (latency proteins latent membrane protein-1 [LMP-1], Epstein-Barr nuclear antigen-2 [EBNA-2], and ZEBRA), p53, and bcl-2 was examined by standard avidin-biotin-peroxidase complex methods. Molecular techniques investigated in situ hybridization for Epstein-Barr virus-encoded messenger RNAs (EBERs) and single-strand conformation polymorphism analysis for p53 mutation. RESULTS: Although the biologic behavior of this tumor was uncertain, the reduction of immunosuppression arrested tumor growth for 5 years, at the expense of some loss in renal function. The occurrence of episodes of acute cellular rejection required pulse therapy, resulting in the appearance of new lesions in both liver and lungs. Despite these complications, a balance between control of this multicentric tumor growth and allograft survival has been maintained for 8 years. CONCLUSIONS: To the authors' knowledge, this example of posttransplant myogenic tumor is the first described in the bone. It shows partial response to immunomodulation with persistent tumor, with prolonged survival of the renal allograft.
Adult↗
Outcome of IgA nephropathy in adults graded by chronic histological lesions.
This prognostic study of primary immunoglobulin A (IgA) nephropathy focused on chronic irreversible glomerular sclerosis and interstitial fibrosis, based on the premise that this disease is characterized by a protracted and, for many, progressive course. We used a chronicity-based histological grading system to assess the biopsy specimens of 126 adults with IgA nephropathy over a median follow-up of 10 years. Our grading system included a glomerular grading (GG) of 1 to 3 based on the extent of glomerular sclerosis, a tubulointerstitial grading (TIG) of 1 to 3 based on the degree of tubular loss or interstitial fibrosis, and the evaluation of hyaline arteriolosclerosis (HA). These three histological parameters were correlated with each other and with serum creatinine level, degree of proteinuria, and blood pressure at the time of renal biopsy. Univariate analysis showed that these three histological and three clinical parameters were significantly correlated with renal survival. By multivariate analysis using the Cox regression model, GG, serum creatinine level, and degree of proteinuria represented independent prognostic factors of renal survival. For a subset of patients at a relatively early stage of disease with a serum creatinine level less than 130 micromol/L at the time of biopsy, all three histological features and degree of proteinuria were significantly correlated with renal survival, and GG was the only independent prognostic factor for renal outcome. This study shows that glomerular sclerosis represents the most important prognostic factor in adult patients with primary IgA nephropathy and has a strong predictive value. Our chronicity-based histological grading system not only correlates well with the natural history of IgA nephropathy but is also reproducible and relatively simple to apply.
Adolescent↗
Identification of dendritic cells in ePTFE grafts explanted from humans.
Following implantation different cell types interact with synthetic vascular prostheses resulting in a complex immuno-inflammatory response. Dendritic cells are responsible for activating the primary T-lymphocyte immune response in various pathological conditions by their role as antigen-presenters. This study aimed at examining whether dendritic cells accumulate within small diameter expanded polytetrafluoroethylene (ePTFE, Goretex(R)) grafts explanted from humans. Segments of expanded polytetrafluoroethylene were explanted from 11 patients (6 male, 5 female), aged between 60 and 83 years (mean 70.7 years) at secondary or revision bypass operation. The graft implant duration varied from 4 months to 12 years (mean 40.5 months). Dendritic cells were identified immunohistochemically using S-100 antibody, as well as by electron microscopy. Immunohistochemical examination showed that all 11 explanted synthetic grafts contained S-100(+) cells colonising both the synthetic matrix itself, and the adjacent perigraft tissue. Electron microscopic analysis confirmed the presence of cells with a characteristic dendritic cell morphology within the grafts. Dendritic cells which accumulated within synthetic grafts were found to co-localise with T-lymphocytes. Based on these observations, we speculate that dendritic cells may be involved in the immuno-inflammatory responses following the implantation of synthetic vascular prostheses through their interaction with T-lymphocytes.
Aged↗
Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions.
The present study was undertaken to examine the cellular composition of the aortic wall in Takayasu's arteritis and to investigate the association of different cell types in the immuno-inflammatory reactions of this disease. Specimens of aortic wall affected by Takayasu's arteritis were obtained from 10 patients (five male, five female), aged 32 to 68 years (mean 49.5 years) at elective operation. The mean duration of disease was 6.5 years (range 2 months to 13 years). Specimens were embedded in paraffin and the sections stained with antibodies to CD3 (to identify T cells), CD20 (B cells), S-100 (dendritic cells), CD15 (granulocytes), CD68 (macrophages), alpha-SMA (smooth muscle cells) and von Willebrand factor (endothelial cells). Immunohistochemical examination demonstrated that all specimens showed histological alteration with the replacement of the muscular and elastic layers of the media and adventitia by dense fibrous tissue, and were characterized by varying degrees of inflammatory cell infiltration. In five cases, inflammatory nodules consisting of numerous T cells and B cells were observed in the adventitia. Within the inflammatory nodules, as well as around areas of neovascularization in the deep portion of the intima, lymphocytes were co-localized with dendritic cells. In addition, in the adventitia, the accumulation of a large number of granulocytes was observed. The present study demonstrates that immune inflammation is a typical feature of Takayasu's disease, and that the interactions between dendritic cells and lymphocytes may be important in the control of the immune reactions in this vascular pathology.
Adult↗