Churg-Strauss syndrome in a child with IgA nephropathy.

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with asthma and eosinophilia. Withdrawal of corticosteroids in asthmatic patients is known to be a powerful trigger for the development of CSS. Renal involvement in patients with CSS is commonly manifested as antineutrophil cytoplasm antibody-associated necrotizing crescentic glomerulonephritis, however, concomitant CSS and the nephrotic syndrome or IgA nephropathy are rare. We report a 12-year-old boy with CSS associated with IgA nephropathy that developed while tapering oral steroids. The patient had a history of the nephrotic syndrome and asthma.

alpha-Melanocyte stimulating hormone (MSH) decreases cyclosporine a induced apoptosis in cultured human proximal tubular cells.

The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes. We investigated the ability of CsA to induce apoptosis in cultured human proximal tubular epithelial cells and also the effect of alpha-MSH on them. Fas, Fas ligand, and an intracellular adaptor protein, Fas-associating protein with death domain (FADD) expression, and poly-ADP ribose polymerase (PARP) cleavage were also studied. CsA induced apoptosis in cultured tubular epithelial cells demonstrated by increased number of TUNEL positive cells and it was accompanied by a significant increase in Fas mRNA and Fas ligand protein expressions. FADD and the cleavage product of PARP also increased, indicating the activation of caspase. In alpha-MSH co-treated cells, apoptosis markedly decreased with downregulation of Fas, Fas ligand and FADD expressions and also the cleavage product of PARP. In conclusion, these data suggest that tubular cell apoptosis mediated by Fas system may play a role in tubular atrophy in chronic CsA nephrotoxicity and pretreatment of alpha-MSH may have a some inhibitory effect on CsA induced tubular cell apoptosis.

Renal biopsy in elderly patients: clinicopathological correlation in 117 Korean patients.

AIM: In the elderly with renal disease, the clinical presentations are frequently inconsistent with the pathologic findings. We tried to clarify the differences in pathological findings between the young and the elderly, in Korea and in Western countries, and the usefulness of a percutaneous renal biopsy in the elderly with renal disease. PATIENTS AND METHODS: We analyzed the clinical presentations and spectrums of renal histopathology by reviewing medical records and renal biopsy reports retrospectively in 117 Korean patients aged 60 years or more with renal disease. RESULTS: 85 patients had primary renal disease. The remaining 32 patients had renal diseases associated with systemic conditions. Out of the 85 patients with primary renal disease, 61 cases presented as idiopathic nephrotic syndrome. Compared with renal biopsy results of younger adult patients (age 15-59, n = 1,908), membranous nephropathy, crescentic glomerulonephritis, membranoproliferative glomerulonephritis, amyloidosis, light chain disease, and thrombotic thrombocytopenic purpura were more prevalent, but IgA nephropathy and lupus nephritis were less common in the elderly patients. In clinical presentation, nephrotic syndrome and rapidly progressive renal failure were more prevalent, but asymptomatic urinary abnormality was less common in elderly patients. The responsiveness to treatment was good in elderly patients with minimal-change lesion (complete remission in all patients) but poor in crescentic glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis. From the above findings, the clinical presentation, patterns of histopathology and responsiveness to treatment of elderly Korean patients were similar to those of the younger Korean control group and the Western elderly group. CONCLUSION: Percutaneous renal biopsy is a useful diagnostic aid and can be used as a therapeutic guideline even in elderly patients with renal disease.

alpha-MSH decreases apoptosis in ischaemic acute renal failure in rats: possible mechanism of this beneficial effect.

BACKGROUND: Apoptosis frequently occurs in acute renal injury but the molecular mechanisms responsible for this distinct form of cell death are largely unknown. Fas belongs to the tumour necrosis factor (TNF)/nerve growth factor superfamily and engagement by Fas ligand induces apoptosis in various epithelial cells. To investigate the role of apoptosis and associated mechanisms, we examined the occurrence of apoptosis and Fas and Fas ligand expression, and the therapeutic effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory cytokine in an ischaemic acute renal failure (ARF) rat model. We also examined neutrophil infiltration together with intercellular adhesion molecule-1 (ICAM-1) expression because of their possible involvement in apoptosis due to their ability to release various inflammatory cytokines and reactive oxygen species. METHODS: After unilateral nephrectomy in female Sprague-Dawley rats, the renal artery of the contralateral kidney was clamped for 40 min and reperfused. alpha-MSH or vehicle was injected intraperitoneally immediately after reperfusion and at 1, 6, or 24 h after reperfusion. The expression of Fas and Fas ligand was studied by western blot analysis and semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method, and neutrophil infiltration by naphthol AS-D chloracetate staining. The degree of apoptosis, neutrophil infiltration, and Fas and Fas ligand, and ICAM-1 expression, as well as biochemical and histological data were compared between the alpha-MSH and the vehicle-treated groups. RESULTS: Intraperitoneally administered alpha-MSH significantly reduced renal injury, measured by blood urea nitrogen (BUN) and creatinine and by the degree of tubular necrosis (109.6+/-7.1/54.7+/-3.1 mg/dl for BUN, and 1.6+/-0.2/1.03+/-0.06 mg/dl for creatinine 24 h after ischaemia) (5.4+/-0.8/2.6+/-0.3 for injury score 24 h after ischaemia). Ischaemia caused an increase in Fas and Fas ligand expression and was accompanied by morphological evidence of apoptosis. alpha-MSH significantly reduced the degree of apoptosis, as well as Fas and Fas ligand expression (mean apoptotic cell number, 41.7+/-3.5/14.2+/-2.2 per x200 field at 24 h after ischaemia. Fas protein expression: sham, 1409+/-159 DI (densitometric index); vehicle/alpha-MSH, 2818+/-635/1306+/-321 DI at 24 h and 5542+/-799/2867+/-455 DI at 72 h after ischaemia. Fas ligand protein expression: sham, 1221+/-181 DI; vehicle/alpha-MSH, 2590+/-85/1279+/-169 DI at 4 h, 4376+/-268/2432+/-369 DI at 24 h and 5200+/-648/2253.7+/-1104 DI at 72 h after ischaemia). Neutrophil infiltration and ICAM-1 expression were also significantly reduced in alpha-MSH group (neutrophil infiltration: vehicle/ alpha-MSH, 5.05+/-1.8/1.59+/-0.4) (ICAM-1 expression, vehicle/alpha-MSH 0.46+/-0.21/0.29+/-0.19). CONCLUSION: These results suggest that apoptosis clearly contributes to tubular cell loss in ischaemia/reperfusion (I/R) injury possibly by neutrophil-mediated pathways or an increase in Fas-Fas ligand expression. The observed beneficial effect of alpha-MSH could be related to these mechanisms.

Role of vascular endothelial growth factor in diabetic nephropathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent cytokine that is considered to be an important mediator in the pathogenesis of endothelial dysfunction in diabetes. METHODS: This study investigates the effect of high glucose on the signaling and production of VEGF in rat mesangial cells in culture and measures the urinary VEGF level in patients with different stages of diabetic nephropathy. To elucidate the role of VEGF in vivo further, expression of VEGF in control and diabetic kidneys was examined using immunohistochemistry. RESULTS: A high ambient glucose concentration in the culture medium increased VEGF mRNA expression and protein production within 3 h in a concentration-dependent manner. A protein kinase C (PKC) inhibitor and PKC down-regulation inhibited glucose-induced increases in VEGF production. Urinary excretion of VEGF significantly increased according to the degree of proteinuria in patients with diabetes. A weak but significant correlation was found between urinary VEGF excretion and the levels of serum creatinine, creatinine clearance, microalbuminuria, and proteinuria. Immunohistochemistry revealed marked differences in the extent of mesangial VEGF staining between diabetic and control kidneys. Pronounced up-regulation of VEGF was observed in the glomerular epithelial cell in the early phase of diabetic kidney disease, whereas widespread expression of VEGF was found in the tubular segments, especially the proximal segment, in advanced diabetic nephropathy. CONCLUSIONS: These results suggest that VEGF may play a role in the pathogenesis of diabetic nephropathy.

Fine needle aspiration cytology of the breast. Experience at an outpatient breast clinic.

OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) of the breast at our institution and to perform quality assurance. STUDY DESIGN: Two hundred forty-six cases with pathologic confirmation were selected and reviewed. A pathologist performed most of the aspirations at an outpatient breast clinic. We correlated cytologic and histologic findings and evaluated the influence of the size, location, grade, and pathologic subtypes and fibrosis in breast lesions on diagnostic results. RESULTS: The likelihood ratios for malignant, suspicious, atypical, benign and unsatisfactory cytologic diagnoses were 98.71, 5.48, 1.09, 0.07 and 0.55, respectively. The absolute and complete sensitivities for malignant lesions were 64.5% and 90.3%, respectively. The specificity was 71.9%. False negative and positive rates were 4.3% and 0.7%, respectively. The predictive value for a malignant cytologic diagnosis was 98.4%. The rate of unsatisfactory samples was 9.3%. The rate of concordance between cytologic and histologic diagnosis was lower for large and diffusely growing lesions (benign and malignant), for malignancies with abundant fibrosis and of unusual types and for carcinomas of low grade. All axillary and recurrent chest wall lesions were diagnosed cytologically. Cell block sections were useful in a small number of cases. CONCLUSION: Understanding the performance and limitations of FNAC can enhance its value as a diagnostic technique in the management of breast disease.

Fas (APO-1/CD95) ligand and Fas expression in renal cell carcinomas: correlation with the prognostic factors.

BACKGROUND AND OBJECTIVE: Fas ligand (FasL, CD95L) is a type II transmembrane protein of the tumor necrosis factor family that induces cells to send an apoptotic signal to cells expressing Fas (CD95, APO-1). It has been shown that cancers have a dysregulated expression of Fas and FasL system, conferring a survival advantage. It is important to understand FasL and Fas expression in tumors, because the growth of cancer might be controlled by Fas-mediated apoptosis. METHODS: The expressions of FasL and Fas were studied by immunohistochemical analyses in 51 cases of renal cell carcinomas and the adjacent normal renal tissues, respectively. In addition, their expressions were compared with prognostic factors, such as tumor size, nuclear grade, TNM stage, and histologic types. RESULTS: In nonneoplastic renal tissues, FasL was expressed in all nephron segments, whereas Fas also expressed in all tubules, except for glomeruli. In renal cell carcinomas, FasL protein was detected in 50 (98.0%) of 51 cases, whereas Fas expressed in 38 (74.5%) of 51 cases. In fact, the immunostaining of Fas was less intense than that in the adjacent normal segments of all cases. The staining pattern showing both high expression of FasL and low expression of Fas was found in 36 (70.6%) (P = .04) of 51 cases, most of which were Fuhrman grade 2 or 3 tumors. However, the expression pattern did not correlate statistically with the tumor size, histologic type, or clinical stage. On the other hand, most grade 4 tumors displayed high expression of both FasL and Fas (P<.001). CONCLUSION: These data indicate that high expression of FasL and low expression of Fas protein in renal cell carcinomas may play a role in evading surveillance of the immune system. In addition, the FasL and Fas expressions appear to have a therapeutic implication for high-grade tumors rather than a prognostic one.

Protein-losing enteropathy with an endoscopic feature of 'the watermelon colon'.

A watermelon lesion involving the gastrointestinal tract other than the stomach has not been reported previously except for two cases with rectal involvement and another case with caecal involvement. This report describes a case of protein-losing enteropathy with endoscopic features of 'the watermelon lesion' involving nearly the entire colon. A 57-year-old man presented with a six-month history of generalized oedema and diarrhoea. Laboratory findings included elevated erythrocyte sedimentation rate and decreased serum total protein and albumin. Serum fluorescent anti-nuclear antibody, anti-dsDNA antibody and anti-La antibody were positive. Upper gastrointestinal endoscopy was unremarkable. Colonoscopy showed seven or eight longitudinal reddish stripes along the entire length of the colon and rectum sparing the caecum. Biopsies from the duodenum and colon revealed mildly ectatic lymphatics in the submucosa. Colonic biopsy also exhibited some haemosiderin-laden macrophages in the muscularis mucosae and submucosa. 99mTc-human serum albumin scintigraphy demonstrated a leak into the intestinal lumen. Oral prednisolone therapy was started and his symptoms and signs gradually improved over months. Steroid could be withdrawn after 7 months of therapy, and the patient has remained free of symptoms for 1 year of follow-up after withdrawal of the steroid.

Validity of the specialized columnar epithelium as a diagnostic criterion of the short segment Barrett's esophagus.

OBJECTIVE: In the areas where intestinal metaplasia of the stomach is highly prevalent, diagnosing Barrett's esophagus solely by the presence of specialized columnar epithelium in the distal esophagus may lead to many false positive diagnoses. The aim of this study was to test validity of the specialized columnar epithelium as a diagnostic criterion of the short segment Barrett's esophagus in Korea. METHODS: During routine gastroscopy, the length of columnar-lined esophagus was measured and biopsy samples were taken from the mucosa immediately distal to the squamocolumnar junction. Under light microscopy, alcian blue-positive cells were identified. RESULTS: Prevalence of the specialized columnar epithelium in cases without the columnar-lined esophagus and with the short segment columnar-lined esophagus were 57.1% and 31.2%, respectively (P = 0.0281). The specialized columnar epithelium is frequently seen around the cardia in Koreans with or without the columnar-lined esophagus. CONCLUSION: Simple presence of the specialized columnar epithelium is not a valid criterion for a diagnosis of Barrett's esophagus. We propose that both the short segment Barrett's esophagus and the goblet cell metaplasia of the cardia might be grouped together under a title of "the specialized columnar epithelium around the gastroesophageal junction" as a potential preceding condition of adenocarcinoma around the cardia.

A case of Wegener's granulomatosis complicated by diffuse pulmonary hemorrhage and thrombotic thrombocytopenic purpura.

Wegener's granulomatosis is a distinct form of necrotizing granulomatous vasculitis which usually affects the kidneys and the upper and lower respiratory tracts. Unusual manifestations have also been reported, and these include colitis, urethritis and diabetes insipidus. We describe a case of Wegener's granulomatosis which presented with rapidly progressive renal insufficiency, sudden deafness, red eye, facial palsy, and complicated by uncommon manifestations that were diffuse pulmonary hemorrhage and thrombotic thrombocytopenic purpura.

Fibrous histiocytoma of the lacrimal sac.

BACKGROUND: Fibrous histiocytoma is a slow-growing tumor that most commonly occurs in the superficial and deep soft tissue, with an occasional occurrence in the orbit. However, fibrous histiocytoma of the lacrimal sac is very rare. METHODS: A case report of a 33-year-old man with a palpable mass in the right lacrimal sac and epiphora is presented, with a review of the literature pertaining to this unusual case. RESULTS: The patient was found to have a 3 x 2-cm-sized mass in the right lacrimal sac. Under the impression of benign tumor, the tumor was excised. Histopathological diagnosis of fibrous histiocytoma was made on the surgical specimen. Following surgical treatment, the patient has remained free of symptoms. CONCLUSIONS: Fibrous histiocytoma of the lacrimal sac is a rare disease. This case report and a review of the literature demonstrated that surgical excision appears to control the tumor.

Jejunal inflammatory fibroid polyp presenting as intussusception--a case report with review of the literature.

A 52-year-old woman was presented with intermittent abdominal pain and vomiting for 10 days. Abdominal CT scan disclosed a dilated small bowel loop with a round solid mass in the right anterior supravesical space. The clinical impression was intussusception caused by small bowel tumor. She underwent an exploratory laparotomy. The macroscopic and microscopic findings confirmed an inflammatory fibroid polyp of jejunum causing intussusception. To the best of our knowledge, this was the 5th reported case of such a presentation in English medical literature.