The serum vaspin levels are reduced in Japanese chronic hemodialysis patients

Background

Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified in genetically obese rats that correlates with insulin resistance and obesity in humans. Recently, we found that 7% of the Japanese population with the minor allele sequence (A) of rs77060950 exhibit higher levels of serum vaspin. We therefore evaluated the serum vaspin levels in Japanese chronic hemodialysis patients.

Methods

Healthy Japanese control volunteers (control; n?=?95, 49.9±6.91?years) and Japanese patients undergoing hemodialysis therapy (HD; n?=?138, 51.4±10.5?years) were enrolled in this study, and serum samples were subjected to the human vaspin RIA system.

Results

The measurement of the serum vaspin levels demonstrated that a fraction of control subjects (n?=?5) and HD patients (n?=?11) exhibited much higher levels (> 10?ng/ml; Vaspin_High group), while the rest of the population exhibited lower levels (< 3?ng/ml; Vaspin_Low group). By comparing the patients in the Vaspin_Low group, the serum vaspin levels were found to be significantly higher in the control subjects (0.87±0.24?ng/ml) than in the HD patients (0.32±0.15?ng/ml) (p?<?0.0001). In the stepwise regression analyses, the serum creatinine and triglyceride levels were found to be independently and significantly associated with the vaspin concentrations in all subjects.

Conclusions

The creatinine levels are negatively correlated with the serum vaspin levels and were significantly reduced in the Japanese HD patients in the Vaspin_Low group.

     

Effects of aliskiren-based therapy on ambulatory blood pressure profile, central hemodynamics, and arterial stiffness in nondiabetic mild to moderate hypertensive patients

J Clin Hypertens (Greenwich). 2012;00:000–000. ©2012 Wiley Periodicals, Inc. Aliskiren is a direct renin inhibitor that exerts its effect at the rate‐limiting step of the renin‐angiotensin system. This study was performed to examine the beneficial effects of aliskiren‐based antihypertensive therapy on the ambulatory blood pressure (BP) profile, central hemodybamics, and arterial stiffness in untreated Japanese patients with mild to moderate hypertension. Twenty‐one Japanese nondiabetic patients with untreated mild to moderate essential hypertension were initially given aliskiren once daily at 150 mg, and the dose was titrated up to 300 mg as needed. After 12 weeks of aliskiren‐based therapy, the clinic, ambulatory, and central BP values as well as brachial‐ankle pulse wave velocity (baPWV) were all significantly decreased compared with baseline (clinic systolic BP, 151±11 mm Hg vs 132±11 mm Hg; clinic diastolic BP, 91±13 mm Hg vs 82±9 mm Hg; 24‐hour systolic BP, 144±12 mm Hg vs 133±11 mm Hg; 24‐hour diastolic BP, 88±8 mm Hg vs 81±9 mm Hg; central BP, 162±16 mm Hg vs 148±14 mm Hg; baPWV, 1625±245 cm/s vs 1495±199 cm/s; P<.05). These results show that aliskiren, as a first‐line regimen, improves the ambulatory BP profile and may have protective vascular effects in Japanese nondiabetic patients with untreated mild to moderate essential hypertension.     

Lung metastasis from an ovarian granulosa cell tumor 36 years after the initial diagnosis: report of a case

This report presents the case of a late relapse of an ovarian granulosa cell tumor (GCT) that metastasized to the lung 36 years after the initial diagnosis. A 72-year-old female demonstrated multiple nodules with extrapleural signs on chest computed tomography. Positron emission tomography with ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG-PET) showed that the nodules had no FDG avidity. The nodules, which appeared as polypoid lesions of the visceral pleura on thoracoscopy, were resected and diagnosed as pulmonary metastases from the GCT. This case report indicates that thorough thoracoscopic exploration of the pleural cavity is essential when intrathoracic nodules are seen on postoperative imaging examinations in GCT patients, even when the [¹⁸F]FDG-PET results are negative.     

Developing a novel custom cutting guide for curved peri-acetabular osteotomy

Purpose

Curved peri-acetabular osteotomy (CPO) produces excellent clinical results, but the surgical procedure is technically demanding, and severe complications related to the osteotomy have been reported. To provide a safe, accurate surgical procedure, we have developed a novel method for setting the cutting line and direction. We have designed and made a custom cutting guide for individual patients. The purpose of the study was to evaluate the efficacy of this new method and cutting guide.

Methods

The cutting line was designed on a full-scale three-dimensional plaster model made from computed tomography (CT) data for each case. The surface of each plaster model was colour-coded according to the distance from the centre of the femoral head. A custom cutting guide was designed based on this cutting line on the workstation. A titanium custom cutting guide was fabricated using rapid prototyping technology. The cutting guide directed the cutting direction of the osteotome. We evaluated the outcomes for seven consecutive hips in seven patients who underwent CPO using the system between April and December 2011. All peri-operative complications were recorded. The accuracy of the cutting line was evaluated using CT data obtained two weeks after the operation.

Results

There were no major complications related to the osteotomy such as posterior column fracture or intra-articular osteotomy. The actual cutting line corresponded almost exactly to the planned cutting line in all cases.

Conclusions

The colour-coded plaster model and the custom cutting guide were effective for avoiding severe complications associated with a CPO.     

Application of 4D-CTA using 320-row area detector computed tomography on spinal arteriovenous fistulae: initial experience

Time-resolved computed tomography angiography (4D-CTA) using a 320-row area detector CT scanner has recently been applied in the evaluation of cranial vascular disorders. However, application of 4D-CTA to spinal vascular disorder evaluation has never before been described. The authors herein report their initial experience of 4D-CTA in the evaluation of spinal arteriovenous fistulas (AVFs) and compare this novel modality with other imaging modalities. Four consecutive patients with spinal AVF underwent time-resolved contrast-enhanced magnetic resonance angiography (trMRA), 4D-CTA, and selective catheter angiography (CA). In 4D-CTA, volume data was transformed into 3D volume-rendered images and maximum intensity projection. These images were also evaluated by time-resolved serial phases. Then, images of each modality were compared, focusing on the detection of perimedullary draining veins and the prediction of AVF location and drainage flow direction. All modalities successfully detected perimedullary draining veins in all cases. Location of the AVF was detected in all cases by CA. trMRA and 4D-CTA detected the AVF in three out of the four cases. With regard to flow direction, while 4D-CTA successfully depicted ascending or descending drainage flow in the spinal canal, CA failed to detect the flow direction in one case while trMRA failed in two cases. In the case with epidural AVF, 4D-CTA was the only technique to detect the flow direction of perimedullary drainage. Although this is only an initial experience of the application of 4D-CTA to spinal vascular diseases, 4D-CTA was capable of detecting the dynamic vascular flow of spinal AVFs. The authors believe that 4D-CTA can be a useful option in the evaluation of spinal AVFs.     

Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone,the murine model of X‐linked hypophosphatemia

X‐linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc‐metallopeptidase PHEX gene (phosphate‐regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization‐inhibiting, acidic serine‐ and aspartate‐rich motif (ASARM)‐containing peptides, which are proteolytically derived from the mineral‐binding matrix proteins of the SIBLING family (small, integrin‐binding ligand N‐linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full‐length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ～35 kDa OPN fragment that was not present in wild‐type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild‐type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full‐length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization‐inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research.     

Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.     

Usefulness of right ventricular tissue Doppler imaging for diagnosis of right ventricular myocardial infarction

Background

Right ventricular myocardial infarction (RVMI) is a complication of acute inferior myocardial infarction and sometimes causes severe hemodynamic disturbance. It is therefore important to promptly detect RVMI and assess the severity of right ventricular (RV) dysfunction. Tissue Doppler imaging (TDI) is a useful method to assess left ventricular function and RV function. In this study, we investigated the possibility of diagnosing RVMI using tricuspid annular velocity determined by TDI.

Methods

Thirty consecutive patients with first acute inferior myocardial infarction were studied. The diagnosis of RVMI was based on an ST-segment elevation of at least 0.1 mV in lead V4R. The patients were classified into 12 patients with RVMI (the RVMI group) and 18 patients without RVMI (non-RVMI group). All patients underwent two-dimensional echocardiography, pulsed Doppler and TDI, and coronary angiography within 48 h after onset of myocardial infarction. Tricuspid inflow velocity was recorded by pulsed Doppler and early diastolic tricuspid inflow velocity (TVE) was measured. Peak early diastolic velocity of the tricuspid annulus (TVe’) at the RV free wall was recorded using TDI. The ratio of TVE to TVe’ (TVE/TVe’) was calculated.

Results

TVe’ was significantly lower in the RVMI group compared to that in the non-RVMI group (5.9 ± 1.3 vs. 9.1 ± 3.1; p = 0.0025). On the basis of a TVe’ cutoff value of less than 8.3 cm/s, RVMI was diagnosed with 100 % sensitivity and 61 % specificity.

Conclusions

The early diastolic tricuspid annular velocity determined by TDI is a noninvasive and sensitive index for diagnosing RVMI.