Measurement of effective renal plasma flow using model analysis of dynamic CT in the preoperative evaluation of the renal transplant donors.

OBJECTIVES: Renal scintigraphy is widely used to evaluate residual function of a transplanted kidney from the donor. Dynamic computed tomography (CT) imaging can evaluate both kidney morphology and regional renal function. The aim of this study was to develop an imaging protocol and a calculation method using dynamic CT for assessing the effective renal plasma flow (ERPF) by model analysis, and to evaluate the validity of the obtained ERPF values. METHODS: Preoperative dynamic CT examination with a low radiation dose exposure system was performed for 25 renal transplant donors, and ERPF was calculated from the obtained images (CT-ERPF). To calculate CT-ERPF, we set the region of interest (ROI) in the renal cortex using automatic ROI-setting software developed in our laboratory. We compared the processing time with automatic and manual ROI settings. To evaluate the validity of CT-ERPF, we examined the correlation of age with CT-ERPF and compared with reported ERPF values. We also compared the uptake rates of technetium-99m-dimercaptosuccinic acid and CT-ERPF in terms of the right-to-left ratio. RESULTS: There was good agreement of CT-ERPF assessed using automatic and manual ROIs. CT-ERPF was negatively correlated with age and showed values below the reference ERPF range in 21 cases. The right-to-left ratio of CT-ERPF showed a significant correlation with that of technetium-99m-dimercaptosuccinic acid. CONCLUSIONS: Using our method, CT-ERPF was a useful indicator for preoperative evaluation of donor's renal function.

[Portal hepatic lymphadenopathy involved by Rosai-Dorfman disease-like changes in a patient with hepatocellular carcinoma].

We report a case of a 68-year-old woman with chronic hepatitis C who presented with a small hepatocellular carcinoma in segment 8 (S8) of liver and a portal hepatic tumor. Transhepatic arterial infusion therapy was performed, followed by partial hepatic resection of S8 and excision of the portal hepatic tumor with lymph node metastasis. Histologically, the lymph nodes showed marked infiltration of large histiocytes with clear cytoplasm and emperipolesis in the specimen stained with hematoxylin-eosin. These findings were generally compatible with the histological features of Rosai-Dorfman disease (RDD). However, immunohistochemical analysis revealed the proliferating histiocytes were negative for CD1a, CD68 and S-100 protein, but positive for only lysozyme. Therefore, we finally diagnosed it as a disease similar to RDD. This was a difficult case diagnostically distinguish between metastasis and benign disease.

Distinct macrophage phenotypes contribute to kidney injury and repair.

The ischemically injured kidney undergoes tubular cell necrosis and apoptosis, accompanied by an interstitial inflammatory cell infiltrate. In this study, we show that iNos-positive proinflammatory (M1) macrophages are recruited into the kidney in the first 48 hours after ischemia/reperfusion injury, whereas arginase 1- and mannose receptor-positive, noninflammatory (M2) macrophages predominate at later time points. Furthermore, depletion of macrophages before ischemia/reperfusion diminishes kidney injury, whereas depletion at 3 to 5 days after injury slows tubular cell proliferation and repair. Infusion of Ifnγ-stimulated, bone marrow-derived macrophages into macrophage-depleted mice at the time of kidney reperfusion restored injury to the level seen without macrophage depletion, suggesting that proinflammatory macrophages worsen kidney damage. In contrast, the appearance of macrophages with the M2 phenotype correlated with the proliferative phase of kidney repair. In vitro studies showed that IFNγ-stimulated, proinflammatory macrophages begin to express markers of M2 macrophages when cocultured with renal tubular cells. Moreover, IL-4-stimulated macrophages with an M2 phenotype, but not IFNγ-stimulated proinflammatory macrophages, promoted renal tubular cell proliferation. Finally, tracking fluorescently labeled, IFNγ-stimulated macrophages that were injected after injury showed that inflammatory macrophages can switch to an M2 phenotype in the kidney at the onset of kidney repair. Taken together, these studies show that macrophages undergo a switch from a proinflammatory to a trophic phenotype that supports the transition from tubule injury to tubule repair.

New therapeutic option for thromboembolism--dabigatran etexilate.

BACKGROUND: Thrombin plays a key role in blood coagulation and haemostasis; thus its inhibition has been identified as a reasonable target to block the coagulation cascade. Direct thrombin inhibitors are potential prophylactic agents for venous thromboembolism and arterial thrombosis, which often accompany operative procedures and cardiac disease, especially orthopedic surgery and atrial fibrillation, respectively. New orally available anticoagulant agents with a wide therapeutic window are keenly anticipated because warfarin and heparins have some disadvantages, and recent progress in pharmaceutical techniques has led to the development of orally administered direct thrombin inhibitors. OBJECTIVES: In this review, we discuss the usefulness of dabigatran etexilate as a new therapeutic option for preventing thromboembolism, including chemistry, pharmacokinetics, and pharmacodynamics, from the results of recent clinical studies. METHODS: We systematically focused on relevant published studies, as data from recent clinical studies were difficult to obtain owing to their ongoing status. CONCLUSIONS: Dabigatran etexilate is a promising new oral anticoagulant that offers greatly expanded therapeutic options for both patients and physicians.

[Study on usefulness of different APTT test kit in variable coagulopathy].

A number of test kits are available for measuring activated partial thromboplastin time (APTT) and are used to screen for intrinsic coagulation reactions. However, results obtained with the same sample by different test kits often vary, causing confusion regarding potential hemostatic activity in the specimen. We investigated the usefulness of 6 different APPT kits, which utilize various phospholipids and activators, to detect prolonged clotting time in plasma from subjects with abnormal coagulopathy, including lupus anticoagulant(LA). In samples from subjects with intrinsic coagulation factor deficiencies and subjects taken heparin, the abnormal APTT detection ratio was high regardless of the kit used, thus any would be acceptable for measuring APTT in such patients. In contrast, that ratio in patients with von Willebrand disease was relatively low regardless of the kit, probably because factor VIII activities in those patients were slightly decreased. The ratio of detected subjects with LA and subjects taking warfarin varied among the APTT kits, however, those that utilized synthetic phospholipids were useful for the detection of LA. Our results suggest that an APTT kit should be selected according to the kind of disorder in the patient. Further, kits that employ synthetic phospholipids are useful for detecting abnormal coagulopathy in patients with intrinsic coagulation factor deficiencies and patients taken heparin, as well as for detection of LA.

VEGF attenuates hyperoxic injury through decreased apoptosis in explanted rat embryonic lung.

Ambient oxygen concentration and vascular endothelial growth factor (VEGF)-A are vital in lung development. Since hypoxia stimulates VEGF-A production and hyperoxia reduces it, we hypothesized that VEGF-A down-regulation by exposure of airways to hyperoxia may result in abnormal lung development. An established model of in vitro rat lung development was used to examine the effects of hyperoxia on embryonic lung morphogenesis and VEGF-A expression. Under physiologic conditions, lung explant growth and branching is similar to that seen in vivo. However, in hyperoxia (50% O2) the number of terminal buds and branch length was significantly reduced after 4 d of culture. This effect correlated with a significant increase in cellular apoptosis and decrease in proliferation compared with culture under physiologic conditions. mRNA for Vegf164 and Vegf188 was reduced during hyperoxia and addition of VEGF165, but not VEGF121, to explants grown in 50% O2 resulted in partial reversal of the decrease in lung branching, correlating with a decrease in cell apoptosis. Thus, hyperoxia suppresses VEGF-A expression and inhibits airway growth and branching. The ability of exogenous VEGF165 to partially reverse apoptotic effects suggests this may be a potential approach for the prevention of hyperoxic injury.

Stromal cells protect against acute tubular injury via an endocrine effect.

Emerging evidence suggests that the intravenous injection of bone marrow-derived stromal cells (BMSC) improves renal function after acute tubular injury, but the mechanism of this effect is controversial. In this article, we confirm that intravenous infusion of male BMSC reduced the severity of cisplatin-induced acute renal failure in adult female mice. This effect was also seen when BMSC (or adipocyte-derived stromal cells (AdSC)), were given by intraperitoneal injection. Infusion of BMSC enhanced tubular cell proliferation after injury and decreased tubular cell apoptosis. Using the Y chromosome as a marker of donor stromal cells, examination of multiple kidney sections at one or four days after cell infusion failed to reveal any examples of stromal cells within the tubules, and only rare examples of stromal cells within the renal interstitium. Furthermore, conditioned media from cultured stromal cells induced migration and proliferation of kidney-derived epithelial cells and significantly diminished cisplatin-induced proximal tubule cell death in vitro. Intraperitoneal administration of this conditioned medium to mice injected with cisplatin diminished tubular cell apoptosis, increased survival, and limited renal injury. Thus, marrow stromal cells protect the kidney from toxic injury by secreting factors that limit apoptosis and enhance proliferation of the endogenous tubular cells, suggesting that transplantation of the cells themselves is not necessary. Identification of the stromal cell-derived protective factors may provide new therapeutic options to explore in humans with acute kidney injury.