Multiple coronary artery-left ventricular microfistulae in a patient with apical hypertrophic cardiomyopathy: a demonstration by transthoracic color Doppler echocardiography

Among the congenital coronary artery fistulae, multiple coronary artery microfistulae arising from the left and right coronary artery and emptying into the left ventricle are very rare and little is known of their anatomic and clinical features, especially in apical hypertrophic cardiomyopathy. A 67-year- old woman was referred for the evaluation of chest pain at exertion, and shortness of breath. Electrocardiographic and echocardiographic findings were typical of apical hypertrophic cardiomyopathy. Coronary arteriography showed normal epicardial coronary arteries, but multiple coronary artery-left ventricular microfistulae arising from the left and right coronary arteries. Transthoracic color Doppler echocardiography, using a high frequency transducer with a low Nyquist limit, demonstrated multiple coronary artery-left ventricular microfistulae just beneath the apical impulse window.     

Evaluation of Femoral Tunnel Positioning Using 3-Dimensional Computed Tomography and Radiographs after Single Bundle Anterior Cruciate Ligament Reconstruction with Modified Transtibial Technique

Background

The purpose of this study is to report a modified transtibial technique to approach the center of anatomical femoral footprint in anterior cruciate ligament (ACL) reconstruction and to investigate the accurate femoral tunnel position with 3-dimensional computed tomography (3D-CT) and radiography after reconstruction.

Methods

From December 2010 to October 2011, we evaluated 98 patients who underwent primary ACL reconstruction using a modified transtibial technique to approach the center of anatomical femoral footprint in single bundle ACL reconstruction with hamstring autograft. Their femoral tunnel positions were investigated with 3D-CT and radiography postoperatively. Femoral tunnel angle was measured on the postoperative anteroposterior (AP) radiograph and the center of the femoral tunnel aperture on the lateral femoral condyle was assessed with 3D-CT according to the quadrant method by two orthopedic surgeons.

Results

According to the quadrant method with 3D-CT, the femoral tunnel was measured at a mean of 32.94% ± 5.16% from the proximal condylar surface (parallel to the Blumensaat line) and 41.89% ± 5.58% from the notch roof (perpendicular to the Blumensaat line) with good interobserver (intraclass correlation coefficients [ICC], 0.766 and 0.793, respectively) and intraobserver reliability (ICC, 0.875 and 0.893, respectively). According to the radiographic measurement on the AP view, the femoral tunnel angles averaged 50.43° ± 7.04° (ICC, 0.783 and 0.911, respectively).

Conclusions

Our modified transtibial technique is anticipated to provide more anatomical placement of the femoral tunnel during ACL reconstruction than the former traditional transtibial techniques.     

Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel

BACKGROUND: Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. METHODS: Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. RESULTS: 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. CONCLUSIONS: We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy.     

TGF-β1 induction of p21<Superscript>WAF1/cip1</Superscript> requires smad-independent protein kinase C signaling pathway

Although it has been demonstrated that p21WAF1/Cip1 could be induced by transforming growth factor-beta1 (TGF-beta1) in a Smad-dependent manner, the cross-talk of Smad signaling pathway with other signaling pathways still remains poorly understood. In this study, we investigated a possible role of protein kinase C (PKC) signaling pathway in TGF-beta1 induction of p21WAF1/Cip1 in human keratinocytes HaCaT cells. Our data show that PKC is required for TGF-beta1 induction of p21WAF1/Cip1, as evidenced by the fact that specific inhibition of PKC leads to a decrease in p21WAF1/Cip1 protein and mRNA expression induced by TGF-beta1. And this notion is further supported by the observation that activation of p21WAF1/Cip1 promoter activity is dramatically attenu ated by treatment with PKC inhibitor. However, PKC signaling pathway is not associated with TGF-beta1 activation of Smad signaling pathway, because inhibition of PKC signaling pathway does not affect nuclear translocation of Smads induced by TGF-beta1. Taken together, our data suggest that PKC signaling pathway is required for p21WAF1/Cip1 expression by TGF-beta1, which is independent of Smad signaling pathway.     

功能磁共振和弥散张量纤维束成像中的人脑皮质桥小脑束

The anatomical organization of the corticopontocerebellar tract(CPCT) in the human brain remains poorly understood.The present study investigated probabilistic tractography of the CPCT in the human brain using diffusion tensor tractography with functional magnetic resonance imaging.CPCT data was obtained from 14 healthy subjects.CPCT images were obtained from functional magnetic resonance imaging and diffusion tensor tractography,revealing that the CPCT originated from the primary sensorimotor cortex and descended to the pontine nucleus through the corona radiata,the posterior limb of the internal capsule,and the cerebral peduncle.After crossing the pons through the transverse pontine fibers,the CPCT entered the cerebellum via the middle cerebral peduncle.However,some variation was detected in the midbrain(middle cerebral peduncle and/or medial lemniscus) and pons(ventral and/or dorsal transverse pontine fibers).The CPCT was analyzed in 3 dimensions from the cerebral cortex to the cerebellum.These results could be informative for future studies of motor control in the human brain.     

Revisiting the Concept of Lymph Node Metastases of Pancreatic Head Cancer: Number of Metastatic Lymph Nodes and Lymph Node Ratio According to N Stage

Background

Some suggest that metastatic lymph node ratio (LNR) may be prognostic of survival in patients with pancreatic cancer. However, this phenomenon was confused by inclusion of node-negative patients in the analysis. The present study was designed to evaluate the prognostic impact of metastatic LNR and the absolute number of metastatic LNs in patients resected for pancreatic cancer.

Methods

Data were collected from 398 patients who underwent curative surgery for pancreatic head cancer at Seoul National University Hospital. Long-term survival was analyzed according to LNR and absolute number of metastatic LNs.

Results

Of the patients, 227 (57.0 %) had LN metastasis. The mean numbers of total retrieved and metastatic LNs were 19.5 and 1.9, respectively, and the mean LNR was 0.11. Median overall survival (OS) of patients was significantly higher in N0 than in N1 patients after curative resection (25.4 vs. 14.8 months, p < 0.001). Median OS was significantly lower in patients with 1 than in those with 0 positive LNs (17.3 vs. 25.4 months, p = 0.001). Among N1 patients, those with 0 < LNR ≤ 0.2 had comparable prognosis than those with >0.2 LNR (median OS 17.2 vs. 12.8 months, p = 0.096), and the number of metastatic LNs did not correlate with median OS (p = 0.365).

Conclusions

The presence of a single positive metastatic LN was associated with significantly poorer OS in patients with pancreatic cancer. When LN metastasis was present, the number of metastatic LNs and LNR had limited prognostic relevance.     

Diffusion‐weighted imaging of human carotid artery using 2D single‐shot interleaved multislice inner volume diffusion‐weighted echo planar imaging (2D ss‐IMIV‐DWEPI) at 3T: Diffusion measurement in atherosclerotic plaque

Purpose:

To determine if 2D single‐shot interleaved multislice inner volume diffusion‐weighted echo planar imaging (ss‐IMIV‐DWEPI) can be used to obtain quantitative diffusion measurements that can assist in the identification of plaque components in the cervical carotid artery.

Materials and Methods:

The 2D ss‐DWEPI sequence was combined with interleaved multislice inner volume region localization to obtain diffusion weighted images with 1 mm in‐plane resolution and 2 mm slice thickness. Eleven subjects, six of whom have carotid plaque, were studied with this technique. The apparent diffusion coefficient (ADC) images were calculated using DW images with b = 10 s/mm² and b = 300 s/mm².

Results:

The mean ADC measurement in normal vessel wall of the 11 subjects was 1.28 ± 0.09 × 10^?3 mm²/s. Six of the 11 subjects had carotid plaque and ADC measurements in plaque ranged from 0.29 to 0.87 × 10^?3 mm²/s. Of the 11 common carotid artery walls studied (33 images), at least partial visualization of the wall was obtained in all ADC images, more than 50% visualization in 82% (27/33 images), and full visualization in 18% (6/33 images).

Conclusion:

2D ss‐IMIV‐DWEPI can perform diffusion‐weighted carotid magnetic resonance imaging (MRI) in vivo with reasonably high spatial resolution (1 × 1 × 2 mm³). ADC values of the carotid wall and plaque are consistent with similar values obtained from ex vivo endarterectomy specimens. The spread in ADC values obtained from plaque indicate that this technique could form a basis for plaque component identification in conjunction with other MRI/MRA techniques. J. Magn. Reson. Imaging 2009;30:1068–1077. © 2009 Wiley‐Liss, Inc.

     

Potent inhibition of lipopolysaccharide-inducible nitric oxide synthase expression by dibenzylbutyrolactone lignans through inhibition of I-kappaBalpha phosphorylation and of p65 nuclear translocation in macrophages.

AIMS: Arctigenin and demethyltraxillagenin, dibenzylbutyrolactone lignans, are phenylpropanoid metabolites with antioxidant and anti-inflammatory activities. The effects of arctigenin and demethyltraxillagenin on the nuclear factor-kappaB (NF-kappaB)-mediated inducible nitric oxide synthase (iNOS, EC1.14.13.39) gene expression were studied in Raw264.7 cells. METHODS: Activation of NF-kappaB was determined by gel mobility shift assay, immunocytochemistry and immunoblot analysis of I-kappaBalpha. Expression of the iNOS gene was assessed by Northern and Western blot analyses. NO production was monitored by chemiluminescent detection using a nitric oxide analyzer. RESULTS: Arctigenin (1 microM) inhibited lipopolysaccharide (LPS)-inducible nuclear NF-kappaB activation and nuclear translocation of p65, which was accompanied by inhibition of I-kappaBalpha phosphorylation, whereas demethyltraxillagenin was less active. LPS-inducible increase in the iNOS mRNA was 80-90% inhibited by 0.01-1 microM arctigenin, whereas similar extents of inhibition were noted by 50-100 microM demethyltraxillagenin. Immunoblot analysis revealed that arctigenin potently inhibited the induction of iNOS by LPS (IC50 < 0.01 microM). The IC50 value of demethyltraxillagenin was approximately 50 microM. Production of nitrite and nitrate by LPS in culture medium was also comparably suppressed by the lignans. CONCLUSION: These results demonstrated that arctigenin potently inhibited LPS-inducible iNOS expression in murine macrophages through suppression of I-kappaBalpha phosphorylation and nuclear translocation of p65. Potent inhibition of LPS-inducible NO production in macrophages may constitute anti-inflammatory effects of the dibenzylbutyrolactone lignans.     

Use of long-term cultured embryoid bodies may enhance cardiomyocyte differentiation by BMP2

Purpose

Human embryonic stem cells (hESCs) can proliferate for a prolonged period and differentiate into cardiomyocytes in vitro. Recent studies used bone morphogenetic protein 2 (BMP2) to generate cardiomyocytes from hESCs, however, all those studies used early embryoid bodies (EBs) and did not retrieve cardiomyocytes with a high yield. In this study, we treated long-term cultured EBs with BMP2 in order to promote differentiation into cardiomyocytes from hESCs.

Materials and Methods

hESC lines, including SNUhES3 and SNUhES4, were used in this study. Undifferentiated hESC colonies were detached to form EBs and cultured for up to 30 days. These long-term cultured EBs were differentiated into cardiomyocytes in serum-containing media. In our protocol, BMP2 was applied for 5 days after attachment of EBs. Cardiac specific markers, beating of differentiated cells and electron microscopic (EM) ultrastructures were evaluated and analyzed.

Results

Compared to 10-day or 20-day EBs, 30-day EBs showed a higher expression level of cardiac specific markers, Nkx2.5 and α-myosin heavy chain (αMHC). Treatment of BMP2 increased expression of cardiac troponin (cTn) I and α-actinin when evaluated at 20 days after attachment of 30-day EBs. Beating of differentiated cells was observed from 7 to 20 days after attachment. Moreover, EM findings demonstrated fine structures such as Z bands in these differentiated cardiomyocytes. These long-term cultured EBs yielded cardiomyocytes with an efficiency of as high as 73.6% when assessed by FACS.

Conclusion

We demonstrated that the use of long-term cultured EBs may enhance differentiation into cardiomyocytes from hESCs when treated with BMP2.     

Robot Versus Laparoscopic Gastrectomy for Cancer by an Experienced Surgeon: Comparisons of Surgery, Complications, and Surgical Stress

Background

No previous robotic studies present an equivalent surgical quality comparison in an experienced setting for gastric cancer. In addition, a reliable postoperative complication assessment is needed to accurately evaluate surgical outcomes.

Methods

After 20 cases of robotic-assisted gastrectomy (RAG), a total of 121 consecutive gastric cancer patients underwent gastrectomy (38 RAG vs 83 laparoscopic-assisted gastrectomy [LAG]) from February 2009 to November 2010 at the Department of Surgery, Korea University Anam Hospital, Seoul, Korea. The Clavien-Dindo (C-D) classification was used to classify surgical complications. The granulocyte-to-lymphocyte (G:L) ratio was analyzed to evaluate surgical stress.

Results

The baseline characteristics, with the exception of age, were similar. The mean total operation time for RAG (234.4 ± 48.0 min) was not significantly different than that for LAG (220.0 ± 60.6 min; P = 0.198). However, in obese patients, fewer lymph nodes were harvested by RAG (23.4 ± 7.0) than by LAG (32.2 ± 12.5, P = 0.006). Overall C-D complications were more common for RAG (47.3 vs 38.5 %), but the difference was not significant (P = 0.361). The mean hospital stay was similar for the 2 groups. Surgical stress as estimated by the G:L ratio was comparable between the 2 groups.

Conclusions

RAG performed by an experienced surgeon resulted in similar postoperative outcomes and complications to those of LAG. Assessment of operation time, C-D complication grade, and G:L ratio revealed that RAG is a practical and feasible alternative to LAG, with the possible exception of obese patients.