Transarterial NBCA embolization with transvenous partial outflow obstruction for superior petrosal sinus dural arteriovenous fistula: a case report

We encountered a case of superior petrosal sinus dural arteriovenous fistula (SPS DAVF) which was treated by a combination of a transvenous and a transarterial approach after the failure of the transvenous approach alone. A 69-year-old man presented with a complaint of progressive left bulbar conjunctival conjestion, exophthalmos, and impaired vision. Cerebral angiography revealed a left SPS DAVF fed by the left middle meningeal artery, the meningeal branches of the left internal carotid artery and the left posterior meningeal artery. Venous drainage proceeded through the cavernous sinus (CS) toward the left superior ophthalmic vein (SOV). Transvenous embolization via the SOV was indicated because the left ipsilateral inferior petrosal sinus contributed to the normal venous return. However the microcatheter to the CS couldn't go through the tortuous SOV. Next a transarterial NBCA (n-butyl-cyanoacrylate) embolization of the affected sinuses was performed under arterial flow control with balloons and the partial coil embolization of the origin of the SOV. The coils in the SOV trapped NBCA and the sinuses were filled slowly with NBCA. The postoperative angiogram confirmed complete obliteration of the DAVF and the patient's ocular symptoms disappeared. DAVF is usually difficult to treat by transarterial embolization with NBCA because of its multiple feeders and high flow drainage. We should therefore carefully observe its structure and the blood flow change with 3D-DSA and the selective angiography while embolizing the DAVE.     

The sinusoidal pressure during ischemia-reperfusion injury in perfused mouse liver pretreated with or without L-NAME

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on I/R injury of isolated mouse liver. MATERIALS AND METHODS: Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with L-NAME (100 microm) or D-NAME (100 microm), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT). RESULTS: In the d-NAME group (n=7), immediately after reperfusion, the portal pressure increased by 2.8 +/- 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 +/- 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 +/- 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the D- and L-NAME (n=7) groups. In the time-matched non- I/R control group (n=6), no changes in variables were observed for 2 h. CONCLUSIONS: Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.     

Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

BACKGROUND: DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer. METHODS: Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis. RESULTS: We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma. CONCLUSIONS: Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.     

Riles type 1A common carotid artery occlusion diagnosed by specific external carotid artery Doppler waveform pattern in carotid ultrasonography. Case report

A 67-year-old man was admitted for evaluation of left homonymous hemianopsia. Carotid ultrasonography showed that the right common carotid artery (CCA) was occluded up to just proximal to the carotid bifurcation, and the patent external carotid artery showed retrograde flow to the patent internal carotid artery via the carotid bifurcation. The Doppler waveform pattern of the external carotid artery showed high end-diastolic flow velocity and low pulsatility index. The diagnosis was Riles type 1A CCA occlusion. Digital subtraction angiography and iodine-123 N-isopropyl-p-iodoamphetamine single photon emission computed tomography were performed to confirm the collateral circulation and adequate intracranial hemodynamic sufficiency. Nonsurgical treatment with antiplatelet therapy was performed for the CCA occlusion. No stroke events have occurred within the 2-year follow-up period.     

The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on β-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland–Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 μg/mL, 10.91 μg/mL, and 4.41 μg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130–250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.     

Pharmacokinetics of 4′-cyano-2′-deoxyguanosine,a novel nucleoside analog inhibitor of the resistant hepatitis B virus,in a rat model of chronic kidney disease

IntroductionThe novel nucleoside analog, 4′-cyano-2′-deoxyguanosine (CdG), possesses inhibitory activity against both the wild-type and resistant hepatitis B virus. Since the dosage of the currently available nucleoside analog preparations needs to be adjusted, depending on renal function, we investigated the effect of renal dysfunction on the pharmacokinetics of CdG in a rat model of chronic kidney disease (CKD).MethodsCKD model rats were either intravenously or orally administered CdG at a dose of 1 mg/kg. The concentration of CdG in plasma, organs (liver and kidney) and urine samples were determined by means of a UPLC system interfaced with a TOF-MS system.ResultsFollowing intravenous administration, the plasma retention of CdG was prolonged in CKD model rats compared to healthy rats. In addition, the clearance of CdG was well correlated with plasma creatinine levels in CKD model rats. Similar to the results for intravenous administration, the plasma concentration profiles of CdG after oral administration were also found to be much higher in CKD model rats than in healthy rats. However, the results for the organ distribution and urinary excretion of CdG, the profiles of which were similar to that of healthy rats, indicated that CdG did not accumulate to a significant extent in the body.ConclusionThe extent of renal dysfunction has a direct influence on the pharmacokinetics (plasma retention) of CdG without a significant accumulation, indicating that the dosage of CdG will be dependent on the extent of renal function. .     

Contribution of increased minimal coronary resistance and attenuated vascular adaptive remodeling to myocardial ischemia in patients with systemic hypertension and ventricular hypertrophy

This study assessed the impact of coronary vascular adaptive remodeling and coronary vascular reactivity on myocardial ischemia in patients with hypertension and left ventricular hypertrophy. Myocardial ischemia is associated with impaired endothelium-independent vasodilation of resistance coronary arteries and increased minimal coronary resistance. These changes may occur in association with lumen reduction caused by attenuated adaptive remodeling in response to plaque accumulation.