Magnesium exposure increases hip fracture risks in patients with chronic kidney disease: a population-based nested case-control study.

This population-based study demonstrates a strong link between Mg-containing antacid exposure and hip fracture risk in nondialysis CKD and dialysis patients. As an Mg-containing antacid, MgO is also commonly used as a stool softener, which can be effortlessly replaced by other laxatives in CKD patients to maintain bone health. PURPOSE: Bone fracture is a severe complication in chronic kidney disease (CKD) patients, leading to disability and reduced survival. In CKD patients, blood magnesium (Mg) concentrations are usually above the normal range due to reduced kidney excretion of Mg. The present study examines the association between Mg-containing antacid exposure and the risk of hip fracture of CKD patients. METHODS: In this nationwide nested case-control study, we enrolled 44,062 CKD patients with hip fracture and 44,062 CKD matched controls, among which the mean age was 77.1 years old, and 87.9% was nondialysis CKD. RESULTS: As compared to non-users, Mg-containing antacid users were significantly more likely to experience hip fracture (adjusted odds ratio (OR) 1.36, 95% CI, 1.32 to 1.41; p < 0.001). Subgroup analysis showed that such risk exists in both nondialysis CKD patients and long-term dialysis patients. In contrast, aluminum or calcium-containing-antacid use did not reveal such association. Next, we examined the influence of Mg-containing antacid dosage on hip fracture risk, the adjusted ORs in the first quartile (Q1), Q2, Q3, and Q4 were 1.20 (95% CI, 1.15 to 1.25; p < 0.001), 1.35 (95% CI, 1.30 to 1.41; p < 0.001), 1.49 (95% CI, 1.43 to 1.56; p < 0.001), and 1.54 (95% CI, 1.47 to 1.61; p < 0.001), respectively, showing that such risk exists regardless of the antacid dosage. A receiver operating characteristic curve analysis demonstrated that the best cutoff value of the exposed Mg dose to discriminate the hip fracture is 532 mEq during the follow-up period. CONCLUSION: This population-based study demonstrates a strong link between Mg-containing antacid exposure and the hip fracture risk in both nondialysis CKD and dialysis patients.

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.

Geographical variations of risk factors associated with HCV infection in drug users in southwestern China.

Hepatitis C virus (HCV) has become a global public health problem. Many studies have been conducted to identify risk factors for HCV infection. However, some of these studies reported inconsistent results. Using data collected from 11 methadone clinics, we fit both a non-spatial logistical regression and a geographically weighted logistic regression to analyse the association between HCV infection and some factors at the individual level. This study enrolled 5401 patients with 30·0% HCV infection prevalence. The non-spatial logistical regression found that injection history, drug rehabilitation history and senior high-school education or above were related to HCV infection; and being married was negatively associated with HCV infection. Using the spatial model, we found that Yi ethnicity was negatively related to HCV infection in 62·0% of townships, and being married was negatively associated with HCV infection in 81·0% of townships. Senior high-school education or above was positively associated with HCV infection in 55·2% of townships of the Yi Autonomous Prefecture. The spatial model offers better understanding of the geographical variations of the risk factors associated with HCV infection. The geographical variations may be useful for customizing intervention strategies for local regions for more efficient allocation of limited resources to control transmission of HCV.

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.

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.

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.

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.

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.

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.

High frequency of rearrangement of the RET protooncogene (RET/PTC) in Chinese papillary thyroid carcinomas.

The activation of RET protooncogene, through chromosomal translocation, is unique to papillary thyroid carcinomas. Rearrangement of the RET kinase domain to 3 partner genes has been described, of which the RET/PTC1 is the most common. To investigate the frequency of RET rearrangement in Chinese papillary thyroid carcinomas, we have performed RT-PCR to amplify specific RET/PTC transcripts. Among the papillary thyroid carcinomas of 11 patients examined, we have identified 2 containing RET/PTC1, 3 containing RET/PTC2, and 1 containing RET/PTC3 oncogenes. Although the cause of the high frequency of RET/PTC oncogenes in Chinese papillary thyroid carcinomas is unknown, our study suggests that RET rearrangement is an important genetic lesion underlying the development of thyroid papillary carcinoma in Taiwan.

Comparative radionuclide imaging of metastatic insular carcinoma of the thyroid: value of technetium-99m-(V)DMSA.

We report a case of metastatic insular carcinoma of the thyroid evaluated with 201TI, 99mTc-MIBI, 99mTc-(V)DMSA, 99mTc-MDP and 131I whole-body scans, which were obtained after total thyroidectomy. For the majority of lesions detected in the skeleton and soft tissue, 131I images were generally available, although most were visualized easier with 99mTc-(V)DMSA. Technetium-99m-MDP images were considered better than 99mTc-(V)DMSA images in showing bone lesions but not soft-tissue lesions. Both 201TI and 99mTc-MIBI scans provided sufficient advantage to exhibit neck and mediastinal metastases, but they did not surpass 99mTc-(V)DMSA in detecting abdominal or bony lesions. In this patient with various metastases from insular carcinoma of the thyroid, 99mTc-(V)DMSA seemed to be the tracer of choice for whole-body imaging.

Abnormal transcripts of FHIT gene in thyroid cancer.

Abnormalities of the FHIT gene were found in many carcinoma cell lines and human tumors as reported which suggest an etiological function in tumorigenesis. To investigate whether the FHIT gene is a target of thyroid tumor specific 3p alterations, we screened the FHIT gene for alteration in thyroid tumors and found that the tumors exhibited aberrant FHIT gene expression. The complete sequence of the FHIT gene in seven cases was determined and deletions between exon 2-9 in different regions were found. Goiter samples as control had normal FHIT transcripts while both normal and aberrant transcripts of FHIT were found not only in the tumor samples but also in the adjacent non-tumorous portion of the thyroid tumor. Our results support the hypothesis that FHIT gene alteration is involved in tumorigenetic development of human neoplasms in thyroid glands.

Reiter's syndrome caused by Streptococcus viridans in a patient with HLA-B27 antigen.

A 26-year-old male patient with mitral valve prolapse and HLA-B27 antigen received endodontic treatment for dental caries. Two weeks later fever, dysuria, diarrhea, sterile inflammatory arthritis of lower limbs, enthesitis, dactylitis, conjunctivitis, and uveitis consecutively developed. Blood culture performed at the time of active arthritis yielded Streptococcus viridans. He did not have any history of psoriasis, acute infectious diarrhea, chronic inflammatory bowel diseases, or sexually transmitted diseases. Laboratory studies also excluded the possibility of infections by human immunodeficiency virus, hepatitis B or C virus, chlamydia, and streptococci from the upper airway. This report indicates that Streptococcus viridans can be the triggering microorganisms of Reiter's syndrome in some circumstances.

Establishment and characterization of a strial marginal cell line maintaining vectorial electrolyte transport.

E6/E7 genes of human papilloma virus type 16 were used to immortalize a primary culture of marginal cells (MC) from gerbils. One of the cloned lines was selected which demonstrated preservation of the main characteristics of the MC, both morphologically and physiologically. Electron microscopic examination showed well-developed junctional complexes and apical microvilli which suggested its epithelial origin. Polymerase chain reaction (PCR) demonstrated the incorporation of E6/E7 genes with the genome. Reverse transcription PCR revealed the existence of mRNA of the IsK channel, a unique marker of MC among the inner ear cells, in this clone. Flow cytometric analysis of this cell line's DNA content was diploid. Numerous large domes formed after confluence of the cell monolayer. Electrophysiologic studies displayed evidence of apical K+ and Na+ channels which were blocked by Ba2+ (2 mM) and amiloride (10(-5) M), respectively. Existence of basolateral Na,K-ATPase and Na+/Cl-/K+ cotransporter was shown by blockage by ouabain (10(-3) M) and bumetanide (50 microM), individually. Injection of the cell line to nude mice failed to induce growth of tumors. This cell line was serum-, density- and anchorage-dependent when cultured in plastic dishes. In conclusion, this cell line shows characteristics of well-differentiated MC maintaining the major ionic transport processes, and provides us a good model to study the possible mechanisms and regulating factors of endolymph production.

Human peritoneal mesothelial cells produce nitric oxide: induction by cytokines.

OBJECTIVE: To investigate the induction of nitric oxide synthase type II (iNOS) in human peritoneal mesothelial cells (HPMC) using cytokines and bacterial lipopolysaccharide (LPS). DESIGN: Confluent monolayers of HPMC were exposed to cytokines [tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interferon gamma (IFNgamma)] or LPS, individually or in various double and triple combinations, for 24-72 hours. Concentrations of nitrate and nitrite in the media were quantified using the Griess reaction and used as indirect indices of nitric oxide (NO) production. The expression of iNOS was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Neither single cytokines nor LPS was able to induce iNOS mRNA or NO production. Both double combinations of TNFalpha + IFNgamma and IL-1beta + IFNgamma were able to induce iNOS mRNA expression, but only TNFalpha + IFNgamma induced significant NO production. The triple combination of TNFalpha + IFNgamma + IL-1beta induced even more NO production than TNFalpha + IFNgamma. There was no constitutive NO synthase type III (eNOS) expression in HPMC. CONCLUSIONS: Certain combinations of cytokines could stimulate cultured HPMC to produce NO, and HPMC might be a source of intraperitoneal NO production during peritonitis.

Absence of modulating effects of cytokines on antioxidant enzymes in peritoneal mesothelial cells.

OBJECTIVE: To investigate the modulation of superoxide dismutase, glutathione peroxidase, and catalase by cytokines and endotoxin in human peritoneal mesothelial cells. DESIGN: Cultured human peritoneal mesothelial cells were treated with various concentrations of interleukin-1 alpha, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, interleukin-8, transforming growth factor-beta (TGF beta), and lipopolysaccharide. Cell morphology was observed and the activities of superoxide dismutase, catalase, and glutathione peroxidase were assayed. The antioxidant enzyme activities of human peritoneal mesothelial cells were also compared with those of human liver and kidney tissues. RESULTS: Interleukin-1 alpha, TNF alpha, TGF beta, and lipopolysacharide caused dose-dependent cytotoxicities in mesothelial cells. The activities of these three antioxidant enzymes did not change after treatment with cytokines and endotoxin. The total superoxide dismutase activity of confluent human peritoneal mesothelial cells was found to be greater than that of human liver and kidney tissues and was composed mostly of manganese superoxide dismutase activity. Furthermore, glutathione peroxidase and catalase activities of human peritoneal mesothelial cells were lower than those of human liver and kidney tissues. CONCLUSION: In human peritoneal mesothelial cells, lack of induction of antioxidant enzymes by inflammatory cytokines, as well as high superoxide dismutase activity accompanied by insufficient glutathione peroxidase and catalase activities may both contribute to the susceptibility of these cells to oxidative damage. Therefore, appropriate management to decrease oxidative injury to the peritoneum should be taken into consideration when treating long-term continuous ambulatory peritoneal dialysis patients.

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.

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