Risk of complications of ultrasound-guided renal biopsy for adult and pediatric patients with systemic lupus erythematosus.

Objective The objective of this paper is to identify the risk of complications of real-time ultrasound-guided renal biopsy in adult and pediatric patients with systemic lupus erythematosus (SLE). Materials and methods This retrospective study examined outcomes of 296 renal biopsy procedures in 275 SLE patients. Imaging-confirmed symptomatic hematoma was regarded as a major complication when intervention (blood transfusion, angiographic embolization, or surgery) was required or as a minor complication otherwise. Clinical and laboratory data were compared between groups with or without complications after initial or subsequent renal biopsy. Binary logistic regressions were used to evaluate complication risk of initial renal biopsy. Results Overall complication rate of initial renal biopsy was 8.7% (major: 2.9%, minor: 5.8%). Three patients expired from pulmonary hemorrhage, thrombotic microangiopathy, and pneumonia. Pediatric SLE patients tended to have a higher rate of major complications (12.5%) than adult patients (2.3%). According to multivariable analysis results, elevated serum creatinine (SCr) level (OR 1.45; 95% CI 1.17-1.81 per mg/dl), prolonged prothrombin time (PT) (OR 2.2; 95% CI 1.05-4.62 per second), and thrombocytopenia (OR 4.3; 95% CI 1.56-11.9) increased overall complication risk of initial renal biopsy. Age < 18 years (OR 8.43; 95% CI 1.21-58.8), thrombocytopenia (OR 16.4; 95% CI 2.44-110.5), and elevated SCr level (OR 1.97; 95% CI 1.36-2.86 per md/dl) increased risk of major complications. Thrombocytopenia, prolonged PT, and elevated SCr level were associated with complications after subsequent renal biopsy (all p = 0.01). Conclusions SLE patients, particularly patients under 18 years old or with elevated SCr level, prolonged PT, or thrombocytopenia, have an increased risk of complications after initial or subsequent renal biopsy.

Isolated Crystalloid Podocytopathy With Focal Segmental Glomerulosclerosis in Renal Allograft: An Unusual Presentation of Post-Transplant Monoclonal Gammopathy of Renal Significance-A Case Report.

BACKGROUND: Monoclonal gammopathy of renal significance denotes a spectrum of hematologic disorders that cause direct or indirect renal damage. CASE PRESENTATION: A 51-year-old man had received a living-donor kidney transplant from his wife in 2008. He had gradual increased proteinuria 4 years later. His renal biopsy results revealed cytoplasmic crystalloid inclusions in the podocytes. No crystalloid inclusion was found in other renal cells. Despite that immunofluorescent examination failed to show light-chain deposition, the serum immuno-electrophoresis revealed monoclonal immunoglobulin-Gκ. Bone marrow biopsy showed interstitial infiltration of plasma cells of approximately 10%. A follow-up renal biopsy was performed in 2016. Light microscopy showed focal segmental glomerulosclerosis. The immunofluorescent examination remained negative for light chain, but κ-light chain could be demonstrated after antigen retrieval. Similar to previous biopsy results, cytoplasmic inclusions were found only in podocytes without involving other renal cells. CONCLUSIONS: To the best of our knowledge, this is the first report of monoclonal gammopathy of renal significance presenting as isolated crystalloid podocytopathy in the allograft kidney. The mechanism of preferential podocyte deposition of crystalloid immunoglobulin remains unclear. The inherent features of crystalloid podocytopathy may mislead the pathologic diagnosis.

Tubulointerstitial nephritis and uveitis syndrome (TINU) with Fanconi's syndrome.

We report a 57-year-old woman with concurrent tubulointerstitial nephritis and uveitis syndrome (TINU) and Fanconi's syndrome. She presented with sudden onset of bilateral ocular pain, blurred vision, acute renal failure, glucosuria and proteinuria. Slit lamp examination revealed acute bilateral anterior uveitis. Tubulointerstitial nephritis was confirmed by kidney biopsy. Laboratory examination revealed normoglycemic glucosuria, proteinuria, normal anion-gap metabolic acidosis, phosphaturia, urinary uric acid wasting and kaliuresis leading to hypokalemia. Her vision and renal function improved gradually after systemic steroid therapy. There have been rare reports of TINU syndrome which had features of Fanconi's syndrome. The prevalence of TINU syndrome may be underestimated, and its association with Fanconi's syndrome requires further investigation.

Results of kidney transplantation from high-terminal creatinine donors and the role of time-zero biopsy.

BACKGROUND: Deceased-donor kidney transplantation (DDKT) from high-terminal creatinine donors is associated with lower graft survival. These kidneys may be considered for discarding, worsening the organ shortage crisis. Using time-zero biopsy for histologic evaluation of these kidneys, we identified those organs eligible for transplantation, seeking to achieve better graft utility with comparable outcomes. METHODS: From April 2004 to April 2008, 55 patients underwent DDKT. A time-zero biopsy was used to examine glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriolar narrowing. A scoring system was used to determine a discard. RESULTS: Twenty-five patients received DDKT from donors whose terminal creatinine levels were >2.0 mg/dL (high terminal creatinine, HTC group) and 30 from donors whose terminal creatinine levels were <2.0 mg/dL (low terminal creatinine, LTC group). Patients who accepted kidneys from HTC donors had shorter waiting times (P = .011) but a higher incidence of delayed graft function after transplantation (P < .001). Nonetheless, 5-year graft survival rates were similar between the two groups. CONCLUSIONS: With a time-zero biopsy for histologic evaluation, kidneys recovered from high-terminal creatinine donors can be transplanted to overcome the organ shortage while achieving reasonable graft survival.

Evaluation of cortical perfusion in renal transplants: application of quantified power Doppler ultrasonography.

Perfusion of renal transplants may be altered by various pathological conditions. This study assessed cortical perfusion of renal transplants during acute rejection episodes using power Doppler quantification. Forty-eight renal transplant patients with clinical indications for biopsy were included in this study. Power Doppler ultrasonography (US) of these renal transplants was performed prior to biopsy. Power Doppler image intensity in the proximal outer cortex of renal transplants was quantified by image analysis software. The results of power Doppler quantification were compared with the clinical data and histological findings. Biopsies were classified into three groups based on Banff diagnostic categories: group 1 (no acute rejection; 26 patients), group 2 (acute cell-mediated rejection alone; 12 patients), and group 3 (acute antibody-mediated rejection with/or without acute cell-mediated rejection; 10 patients). The power Doppler intensity of the outer renal cortex was 1.98 +/- 1.50 dB for group 1, 1.38 +/- 0.86 dB for group 2, and 0.81 +/- 0.66 dB for group 3. Statistically, there was a significant difference between group 1 and group 3 (1.98 vs 0.81 dB, P = .01) but not between group 1 and group 2 (1.98 vs 1.38 dB, P = .34). In conclusion, the status of cortical perfusion of renal transplants can be determined noninvasively by quantified power Doppler US. Accordingly, acute antibody-mediated rejection is associated with significantly decreased cortical perfusion, which, we propose, is due to this distinct pathological process.

Involvement of tumor suppressor in lung cancer 1 gene expression in cervical carcinogenesis.

Tumor suppressor in lung cancer 1 (TSLC1) is a tumor suppressor gene in non-small cell lung cancer, and loss of TSLC1 gene expression has been observed in a number of epithelial carcinomas and cancer-derived cell lines. We analyzed TSLC1 gene expression by real-time reverse transcription-polymerase chain reaction in 39 invasive cervical carcinomas, 34 cervical intraepithelial neoplasia (CIN) IIIs, 35 CIN IIs, 32 CIN I, 36 inflammation cervical tissues, and 30 normal cervix samples. Loss of TSLC1 gene expression was observed in 30 of 39 (77%) cervical carcinomas, 25 of 34 (73%) CIN IIIs, 9 of 35 (26%) CIN IIs, and 7 of 32 (22%) CIN Is but was not found in inflammation and normal cervix samples. Compared to normal cervical tissue, loss of TSLC1 gene was significantly high in CIN IIIs and cervical cancer (P = 0.00). Moreover, loss of TSLC1 gene expression is observed at a significantly higher frequency in CIN IIIs and cervical cancers than in CIN IIs (P < 0.05). The results show that loss of TSLC1 gene expression is an early event in cervical carcinogenesis and often accompanies invasive cervical cancers.

Nodular glomerulosclerosis mimicking diabetic nephropathy without overt diabetes mellitus.

The duration of diabetes mellitus and presence of hyperglycemia appear to be important in the development of diabetic nephropathy. Here, we present three patients with edema, heavy proteinuria, chronic renal failure, in whom no past or present symptomatic glucose intolerance or diabetic retinopathy were found. The kidney biopsy of these patients showed diffuse glomerular basement membrane thickening and nodular glomerulosclerosis, which resembled diabetic nephropathy. The renal function of these patients deteriorated rapidly and renal replacement therapy started later in the average of 11 months since the first visiting. These cases were diagnosed as diabetic nodular glomerulosclerosis, although there was no obvious evidence for diabetes. The absence of overt diabetes and diabetic retinopathy at presentation of nodular glomerulosclerosis in these cases does not refute the hypothesis that metabolic consequence of hyperglycemia is a prerequisite for the pathogenesis of diabetic microangiopathy, but some factors other than hyperglycemia may be responsible for renal damage in our patients. The modifiable risk factors in such a condition are postulated and discussed.

Molecular cloning, recombinant gene expression, and antifungal activity of cystatin from taro (Colocasia esculenta cv. Kaosiung no. 1).

A cDNA clone, designated CeCPI, encoding a novel phytocystatin was isolated from taro corms (Colocasia esculenta) using both degenerated primers/RT-PCR amplification and 5'-/3'-RACE extension. The full-length cDNA gene is 1,008 bp in size, encodes 206 amino acid residues, with a deduced molecular weight of 29 kDa. It contains a conserved reactive site motif Gln-Val-Val-Ser-Gly of cysteine protease inhibitors, and another consensus ARFAV sequence for phytocystatin. Sequence analysis revealed that CeCPI is phylogenetically closely related to Eudicots rather than to Monocots, despite taro belonging to Monocot. Recombinant GST-CeCPI fusion protein was overexpressed in Escherichia coli and its inhibitory activity against papain was identified on gelatin/SDS-PAGE. These results confirmed that recombinant CeCPI protein exhibited strong cysteine protease inhibitory activity. Investigation of its antifungal activity clearly revealed a toxic effect on the mycelium growth of phytopathogenic fungi, such as Sclerotium rolfsii Sacc. etc., at a concentration of 80 microg recombinant CeCPI/ ml. Moreover, mycelium growth was completely inhibited and the sclerotia lysed at a concentration of 150-200 microg/ml. Further studies have demonstrated that recombinant CeCPI is capable of acting against the endogenous cysteine proteinase in the fungal mycelium.

Epithelioid sarcoma metastasis to the gingivae: a case report.

We present a rare case of oral metastatic epithelioid sarcoma rapidly growing over the mandibular gingivae; the primary lesion occurred on the wrist and was treated 18 months earlier by surgery and radiotherapy. The oral metastatic lesion was resected and controlled by chemotherapy. This case has been followed for 2 years with good control of the resected oral metastatic lesion. Histologically, round to oval-shaped tumour cells with abundant eosinophylic globular cytoplasm and eccentrically localized nuclei, lack of epithelial features by electron microscopic study, and the immunohistochemical and cytologic features of tumour cells led into the diagnosis of epithelioid sarcoma. To our knowledge, no reports have been published of its occurrence in the oral cavity

Aspergillosis of the temporomandibular joint following irradiation of the parotid region: a case report.

We report a case of aspergillosis in the right temporomandibular joint (TMJ) with a history of parotid carcinoma and post-irradiation otitis. Previous treatment attempts with surgery and antibiotics were unsuccessful. Radical debridement of the glenoid fossae, supplemented with amphotericin B and adjunct hyperbaric oxygen (HBO) therapy, was provided to resolve the symptoms. This case report highlights the need to be aware of the possibility of invasive mycosis in immunocompromised patients.

Primary ectopic thyroid papillary carcinoma in the floor of the mouth and tongue: a case report.

We report a rare case of papillary carcinoma in the tongue and floor of the mouth with metastasis in cervical lymph nodes. Treatment was by total thyroidectomy with right radical lymph node dissection of the neck, followed by 60 Gy of radiotherapy and 100 mCi (131)I. Pathological examination of the thyroid gland showed no primary cancer. We review publications about ectopic thyroid and the value of antithyroglobulin immunostaining for diagnosis and treatment of the tumour.

Fibrillary glomerulonephritis.

The occurrence of fibrillary glomerulonephritis is unusual in Taiwan, whereas it occurs in approximately 1% of renal biopsy specimens taken in the United States of American. This disease is characterized by extracellular randomly arranged non-branching Congo red-negative microfibrils within glomeruli. The microfibrils are less than 30 nm in diameter, and electron microscopy is essential for diagnosis. Differential diagnosis of the deposition of extracellular non-branching microfibrils within glomeruli is important because discrete diseases have different therapeutic and prognostic implications. The report will discuss two cases of biopsy-proved fibrillary glomerulonephritis who presented with proteinuria, hematuria, renal insufficiency, and hypertension. It is noteworthy that the renal function persistently went downhill, even though the physician treated the patients with corticosteroids, pulse treatment and immunosuppressive agents.

Increased expression and activity of RhoA are associated with increased DNA synthesis and reduced p27(Kip1) expression in the vasculature of hypertensive rats.

We have previously shown that the function of the small G protein Rho is required for vascular smooth muscle cell proliferation and migration. We hypothesized that changes in Rho or Rho signaling might contribute to enhanced vascular proliferative responses associated with hypertension. Western blot analysis revealed that total RhoA expression was approximately 2-fold higher in aortas, tail arteries, and aortic smooth muscle cells (ASMCs) obtained from adult male spontaneously hypertensive rats (SHR) compared with those from Wistar Kyoto rats (WKY). An increase in active GTP-bound RhoA was detected in aortic homogenates by affinity precipitation with the RhoA effector rhotekin and by examining RhoA-[(35)S]GTPgammaS binding. RhoA protein and activity were also increased in vessels from rats treated with N-nitro-L-arginine methyl ester to increase blood pressure. Thrombin-stimulated RhoA activation was also significantly greater in ASMCs from SHR. As a functional correlate of these changes in Rho signaling, thrombin-stimulated DNA synthesis was enhanced in tail arteries and ASMCs from SHR. Expression of the cyclin-dependent kinase inhibitor p27(Kip1) was decreased by two thirds in SHR, and this decrease was mimicked in ASMCs by expression of a constitutively active (GTPase-deficient) mutant of RhoA. Wortmannin (10 nmol/L) fully inhibited the decrease in p27(Kip1) induced by RhoA, and a membrane-targeted catalytic subunit of phosphatidylinositol-3 kinase (PI3K [p110(CAAX)]) decreased p27(Kip1) expression, suggesting that RhoA signals through PI3K. These data provide evidence that RhoA brings about changes in DNA synthesis through reduced expression of p27(Kip1), mediated in part via PI3K, and suggest that increases in RhoA expression and activity contribute to the enhanced vascular responsiveness observed in hypertension.

Immunohistochemical studies of Na+/I- symporter in human thyroid tissues--a correlation with clinical thyroid scintigraphy.

BACKGROUND: Thyroid Na+/I- symporter (NIS) is thought to play an important role in iodide uptake in thyrocytes. We hypothesize that there is correlation between the expression of NIS protein in the normal and diseased thyroid tissues and their clinical thyroid scintigraphy. METHODS: Twenty-seven patients, aged from 21 to 81, were studied from the surgical department of a tertiary referral center. Ten patients were with papillary carcinoma, 5 with follicular carcinoma, 5 with follicular adenoma, 5 with nodular goiter and 2 with Graves' disease. All the carcinoma patients underwent total thyroidectomy while others had lobectomy or subtotal thyroidectomy. The thyroid tissue sections prepared for study were stained with polyclonal hNIS antibody (SS Chiang, Ohio). RESULTS: Most of the nodular goiters were negatively stained except 2 samples that showed weak signal focally. All cases with follicular adenoma or follicular carcinoma were negative for NIS expression, while some with papillary carcinoma were stained positive at sporadic follicles with weak signal. The thyroid tissue of Graves' disease was stained positive for NIS expression. CONCLUSIONS: Thyroid tissues with hypofunctioning nodules displayed significantly reduced or undetectable level of NIS expression. It correlated well with pre-operative thyroid scans.

Rapidly progressive interstitial renal fibrosis associated with Chinese herbal medications.

BACKGROUND/AIM: Nephropathy after ingestion of Chinese herbs is known as a rapidly progressive form of interstitial renal fibrosis after a slimming regimen containing aristolochic acid that was identified first in Belgium. Intake of traditional Chinese herbal medicines is very popular in Taiwan. So we looked for similar cases in our hospital. METHODS: From 1994 to 1998, we observed 20 Taiwanese patients who underwent renal biopsy for rapidly progressive renal failure of unknown origin. The medical history of these patients gave no clue to the origin of renal impairment, except for the administration of Chinese herbs before the development of renal failure in all cases. RESULTS: Although these patients took herbal medications from various sources for different purposes, their renal biopsy specimens showed strikingly similar histological patterns: extensive paucicellular interstitial fibrosis and tubular atrophy, but the glomeruli were apparently intact. They also had similar clinical features, such as a nearly normal blood pressure, obvious anemia, insignificant edema, low-grade proteinuria, and glucosuria. The renal function declined rapidly in most cases; 15 patients underwent dialysis within 3 months of renal biopsy, and 7 patients received emergency dialysis when they first came to our hospital. On clinical and morphological grounds, the nephropathy in our patients appears similar to Chinese herb nephropathy. CONCLUSIONS: Because of the diversity of the herbal regimens used, in addition to aristolochic acid, other unidentified phytotoxins may also play a role in this particular disease entity. There is a strong relation between rapidly progressive interstitial renal fibrosis and the consumption of Chinese herbs.

Analysis of a human immunodeficiency virus type 1 gag mutant with an engineered 110-amino-acid insertion in the matrix protein domain.

A human immunodeficiency virus (HIV) matrix (MA) protein mutant was constructed by duplication of 107 codons of the HIV-1 MA domain. This MA protein duplication mutant (MAII) still could assemble and process particles, had a wild-type (wt) HIV particle density, and possessed reverse transcriptase activity of about 80% of the wild type virus level. The incorporation of HIV Env and viral RNA genome was not greatly affected. The MAII was noninfectious or poorly infectious, however, when pseudotyped with an amphotropic murine leukemia virus envelope protein or with the HIV envelope protein. Although the MAII mutant displayed an immunofluorescence staining pattern similar to that of the wild type virus, subcellular fractionation studies indicated that the membrane association of MAII Gag precursors was unstable under high-salt conditions. Electron microscopic studies showed that the mutant had a decreased density of particle cores compared with that of the wild type virus, suggesting an altered arrangement of the packed proteins. As this insertion in the MA gene caused no major effects on virus assembly implies that the HIV-1 gag has the potential to adapt large insertions of extra coding sequences without loss of the ability to direct particle assembly and release.

Crystal structures of two mutants (K206Q, H207E) of the N-lobe of human transferrin with increased affinity for iron.

The X-ray crystallographic structures of two mutants (K206Q and H207E) of the N-lobe of human transferrin (hTF/2N) have been determined to high resolution (1.8 and 2.0 A, respectively). Both mutant proteins bind iron with greater affinity than native hTF/2N. The structures of the K206Q and H207E mutants show interactions (both H-bonding and electrostatic) that stabilize the interaction of Lys296 in the closed conformation, thereby stabilizing the iron bound forms.

Mitochondrial DNA deletion of the human detrusor after partial bladder outlet obstruction-correlation with urodynamic analysis.

OBJECTIVES: To investigate mitochondrial DNA (mtDNA) mutations in human detrusor after partial bladder outlet obstruction (BOO) and correlate the findings with the results of urodynamic studies. METHODS: Sixty-two male patients with and without BOO were recruited and assessed by the International Prostate Symptom Score, a quality-of-life assessment index, and sonography. The severity of partial BOO was determined by pressure-flow study with an International Continence Society (ICS) nomogram. Random detrusor biopsies obtained cystoscopically were analyzed by polymerase chain reaction (PCR) techniques to detect possible mtDNA deletions. Primer-shift PCR and DNA sequencing were then performed to characterize specific mtDNA deletions. A semiquantitative PCR method was used to determine the proportion of the deleted mtDNA in detrusor. Finally, the mtDNA deletion and the urodynamic results were compared statistically. RESULTS: A 4977-bp mtDNA deletion was identified in the human detrusor. Its incidence and proportion were found to increase after partial BOO (P = 0.005 and 0.012, respectively). The incidence of the mtDNA deletion was 4.2% (1 of 24) in the unobstructed group, 27.8% (5 of 18) in the equivocal group, and 40% (8 of 20) in the obstructed group. The mean proportion of the 4977-bp deleted mtDNA was 23.7 and 12.7 times higher in the obstructed and equivocal groups, respectively, compared with that of the unobstructed group. CONCLUSIONS: We found mtDNA with the 4977-bp deletion in human detrusor and an increase of this deletion after partial BOO. This molecular change might account for the previous observations of mitochondrial functional impairment and voiding dysfunction after partial BOO.

Cholesterol crystal embolization causing acute renal failure.

Acute renal failure due to cholesterol embolization is a complication of severe generalized arteriosclerotic disease. It occurs spontaneously, or more often, as a complication of major medical or surgical procedures such as angiography and vascular surgery. The demonstration of characteristic cholesterol crystals in tissue biopsy specimens is a pathognomonic finding. However, renal cholesterol embolism may be clinically diagnosed when renal failure develops after known inciting factors or together with systemic manifestations of atheromatous embolization such as lower extremity livedo reticularis and focal digital ischemia. We report two cases of acute renal failure in which cholesterol embolization was found in skin and renal biopsies. One patient's renal function stabilized, but not to the basal level and the other patient developed end-stage renal disease.