Chronic Hyperglycemia before Spinal Cord Injury Increases Inflammatory Reaction and Astrogliosis after Injury: Human and Rat Studies.

Traumatic spinal cord injury (SCI) can cause permanent disabilities that seriously reduce quality of life. We evaluated the effects of chronic hyperglycemia before SCI on inflammatory markers and functional recovery after SCI in human patients and a rat model. In the human study, multivariate logistical regression analysis revealed that hemoglobin A1c (HbA1c) values, reflecting average plasma glucose concentration over a 3 month period, at admission were a significant risk factor for poor functional recovery. Moreover, patients with chronic hyperglycemia (HbA1c ≥ 6.5%) had high concentrations of inflammatory biomarkers (interleukin [IL]-6 and IL-8) of cerebrospinal fluid after SCI. Consistent with patient findings, chronic hyperglycemia before SCI in rats was associated with increased inflammatory responses and oxygen-free radicals in the spinal cord and blood, thus resulting in poor functional recovery and histological outcomes. Tight glucose control before SCI decreased the harmful effects of hyperglycemia after SCI in both human and rat studies. Our findings suggest that chronic hyperglycemia before SCI may be a significant prognostic factor with a negative impact on functional and histological outcomes, highlighting the importance of tight glucose control before SCI.

Cervical Myelopathy Caused by Intracranial Dural Arteriovenous Fistula.

Intracranial dural arteriovenous fistula (dAVF) usually results in various problems in the brain. But it can be presented as a myelopathy, which may make early diagnosis and management to be difficult. We recently experienced a case of cervical myelopathy caused by intracranial dAVF. A 60-year-old man presented with a 3-year history of gait disturbance due to a progressive weakness of both legs. Neurological examination revealed spastic paraparesis (grade IV) and Babinski sign on both sides. Magnetic resonance imaging showed serpentine vascular signal voids at C2-T1 on T2-weighted image with increased signal intensity and swelling of spinal cord at C1-C4. We performed a brain computed tomography angiography and found intracranial dAVF with multiple arteriovenous shunts. Venous drainages were noted at tentorial veins and cervical perimedullary veins. After Onyx embolization, the patient showed gradual improvement in motor power and gait disturbance. The venous drainage pattern is a well-known prognostic factor of dAVF. In our case, the intracranial dAVF drained to spinal perimedullary vein, which seemed to result in the ischemic myelopathy. Although it is rare condition, it sometimes can cause serious complications. Therefore, we should keep in mind the possibility of intracranial dAVF when a patient presents myelopathy.

Coordinative Amphiphiles as Tunable siRNA Transporters.

In this study, we developed coordinative amphiphiles for use as novel siRNA transporters. As a modification of a conventional cationic lipid structure, we replaced the cationic head with zinc(II)-dipicolylamine complex (Zn/DPA) as a phosphate-directing group, and used various membrane-directing groups in the place of the hydrophobic tails. These simple amphiphiles are readily synthesized and easy to modify. The Zn/DPA head groups bind to the phosphate backbones of siRNAs, and to our surprise, they prevented the enzymatic degradation of siRNAs by RNase A. Interestingly, the Zn/DPA head itself exhibited moderate transfection efficiency, and its combination with a membrane-directing group-oleoyl (CA1), pyrenebutyryl (CA2), or biotin (CA3)-enhanced the delivery efficiency without imparting significant cytotoxicity. Notably, the uptake pathway was tunable depending on the nature of the membrane-directing group. CA1 delivered siRNAs mainly through caveolae-mediated endocytosis, and CA2 through clathrin- and caveolin-independent endocytosis; CA3 recruited siRNAs specifically into biotin receptor-positive HepG2 cells through receptor-mediated endocytosis. Thus, it appears possible to develop tunable siRNA transporters simply by changing the membrane-directing parts. These are the first examples of amphiphilic siRNA transporters accompanying coordinative interactions between the amphiphiles and siRNAs.

The Effects of Spinopelvic Parameters and Paraspinal Muscle Degeneration on S1 Screw Loosening.

OBJECTIVE: To investigate risk factors for S1 screw loosening after lumbosacral fusion, including spinopelvic parameters and paraspinal muscles. METHODS: We studied with 156 patients with degenerative lumbar disease who underwent lumbosacral interbody fusion and pedicle screw fixation including the level of L5-S1 between 2005 and 2012. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a halo sign larger than 1 mm around a screw. We checked cross sectional area of paraspinal muscles, mean signal intensity of the muscles on T2 weight MRI as a degree of fatty degeneration, spinopelvic parameters, bone mineral density, number of fusion level, and the characteristic of S1 screw. RESULTS: Twenty seven patients showed S1 screw loosening, which is 24.4% of total. The mean duration for S1 screw loosening was 7.3±4.1 months after surgery. Statistically significant risk factors were increased age, poor BMD, 3 or more fusion levels (p<0.05). Among spinopelvic parameters, a high pelvic incidence (p<0.01), a greater difference between pelvic incidence and lumbar lordotic angle preoperatively (p<0.01) and postoperatively (p<0.05). Smaller cross-sectional area and high T2 signal intensity in both multifidus and erector spinae muscles were also significant muscular risk factors (p<0.05). Small converging angle (p<0.001) and short intraosseous length (p<0.05) of S1 screw were significant screw related risk factors (p<0.05). CONCLUSION: In addition to well known risk factors, spinopelvic parameters and the degeneration of paraspinal muscles also showed significant effects on the S1 screw loosening.

Two Cases of Klippel-Feil Syndrome with Cervical Myelopathy Successfully Treated by Simple Decompression without Fixation.

Klippel-Feil syndrome (KFS) is a congenital developmental disorder of cervical spine, showing short neck with restricted neck motion, low hairline, and high thoracic cage due to multilevel cervical fusion. Radiculopathy or myelopathy can be accompanied. There were 2 patients who were diagnosed as KFS with exhibited radiological and physical characteristics. Both patients had stenosis and cord compression at C1 level due to anterior displacement of C1 posterior arch secondary to kyphotic deformity of upper cervical spine, which has been usually indicative to craniocervical fixation. One patient was referred due to quadriparesis detected after surgery for aortic arch aneurysmal dilatation. The other patient was referred to us due to paraparesis and radiating pain in all extremities developed during gynecological examinations. Decompressive C1 laminectomy was done for one patient and additional suboccipital craniectomy for the other. No craniocervical fixation was done because there was no spinal instability. Motor power improved immediately after the operation in both patients. Motor functions and spinal stability were well preserved in both patients for 2 years. In KFS patients with myelopathy at the C1 level without C1-2 instability, a favorable outcome could be achieved by a simple decompression without spinal fixation.

Distribution of ureteral stones and factors affecting their location and expulsion in patients with renal colic.

PURPOSE: To evaluate the distribution of ureteral stones and to determine their characteristics and expulsion rate based on their location. MATERIALS AND METHODS: We retrospectively reviewed computed tomography (CT) findings of 246 patients who visited our Emergency Department (ED) for renal colic caused by unilateral ureteral stones between January 2013 and April 2014. Histograms were constructed to plot the distribution of stones based on initial CT findings. Data from 144 of the 246 patients who underwent medical expulsive therapy (MET) for 2 weeks were analyzed to evaluate the factors responsible for the stone distribution and expulsion. RESULTS: The upper ureter and ureterovesical junction (UVJ) were 2 peak locations at which stones initially lodged. Stones lodged at the upper ureter and ureteropelvic junction (group A) had a larger longitudinal diameter (4.21 mm vs. 3.56 mm, p=0.004) compared to those lodged at the lower ureter and UVJ (group B). The expulsion rate was 75.6% and 94.9% in groups A and B, respectively. There was no significant difference in the time interval from initiation of renal colic to arrival at the ED between groups A and B (p=0.422). Stone diameter was a significant predictor of MET failure (odds ratio [OR], 1.795; p=0.005) but the initial stone location was not (OR, 0.299; p=0.082). CONCLUSIONS: The upper ureter and UVJ are 2 peak sites at which stones lodge. For stone size 10 mm or less, initial stone lodge site is not a significant predictor of MET failure in patients who have no previous history of active stone treatment in the ureter.

Clinical Outcomes of CyberKnife Radiotherapy in Prostate Cancer Patients: Short-term, Single-Center Experience.

PURPOSE: In this retrospective study, we analyzed the outcomes of prostate cancer patients treated with the CyberKnife radiotherapy system (Accuray). MATERIALS AND METHODS: Between 2007 and 2010, 31 patients were treated for prostate cancer by use of the CyberKnife radiotherapy system. After excluding six patients who were lost to follow-up, data for the remaining 25 patients were analyzed. Patients were divided into the CyberKnife monotherapy group and a postexternal beam radiotherapy boost group. Clinicopathologic features and treatment outcomes were compared between the groups. The primary endpoint was biochemical recurrence-free survival period based on the Phoenix definition. Toxicities were evaluated by using the Radiation Therapy Oncology Group scoring criteria. RESULTS: Of 25 patients, 17 (68%) and 8 (32%) were classified in the monotherapy and boost groups, respectively. With a median follow-up of 29.3 months, most of the toxicities were grade 1 or 2 except for one patient in the boost group who experienced late grade 3 gastrointestinal toxicity. The overall biochemical recurrence rate was 20% (5/25) and the median time to biochemical recurrence was 51.9 months. None of the patients with low or intermediate risk had experienced biochemical recurrence during follow-up. Among D'Amico high-risk populations, 16.7% (1/6) in the monotherapy group and 50.0% (4/8) in the boost group experienced biochemical recurrence. CONCLUSIONS: Our data support that prostate cancer treatment by use of the CyberKnife radiotherapy system is feasible. The procedure can be a viable option for managing prostate cancer either in a monotherapy setting or as a boost after conventional radiotherapy regardless of the patient's risk stratification.

TLR7 expression is decreased during tumour progression in transgenic adenocarcinoma of mouse prostate mice and its activation inhibits growth of prostate cancer cells.

PROBLEM: Although various Toll-like receptors (TLRs) have been associated with immune response and tumorigenesis in the prostate cells, little is known about the role of TLR7. Accordingly, we examined the expression of TLR7 during tumour progression of TRMAP (transgenic mouse model for prostate cancer) mice and its role on cell growth. METHOD OF STUDY: Toll-like receptor7 expression was examined by RT-polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Cell growth was examined by MTT assay. Colony formation was investigated by crystal violet staining. RESULTS: Strong expression of TLR7 was detected in the normal prostate epithelia of Wild-type (WT) mice, but not in TLR7-deficient mice. In contrast, TLR7 expression was weak in transgenic adenocarcinoma of mouse prostate (TRAMP)-C2 cells, as compared with murine bone marrow-derived macrophages (BMDMs). Moreover, TLR7 mRNA was markedly expressed in RWPE-1 cells (non-cancerous prostate epithelial cells), but not in PC3 and DU145 (prostate cancer cells). Immunohistochemically, TLR7 expression gradually decreased in TRAMP mice depending on the pathologic grade of the prostate cells. TLR7 agonists increased both the gene and protein expression of TLR7 and promoted production of proinflammatory cytokines/chemokines and IFN-ß gene expression in prostate cancer cell lines. Moreover, loxoribine inhibited the growth and colony formation of TRAMP-C2 cells dependent of TLR7. CONCLUSION: These findings suggest that TLR7 may participate in tumour suppression in the prostate cells.

Curved biodegradable microneedles for vascular drug delivery.

Curved biodegradable microneedles for application to the outer surface of blood vessels are produced to enhance drug delivery to vascular tissues suffering from hyperplasia or atherosclerosis. Spatially discrete thermal drawing and post-annealing processes are employed to fabricate microneedles on a curved surface. Insertion of microneedles into arteries in vivo and ex vivo is demonstrated, and their mechanical properties and drug-delivery function are studied.

Analyzing the effect of distance from skin to stone by computed tomography scan on the extracorporeal shock wave lithotripsy stone-free rate of renal stones.

PURPOSE: To determine whether the distance from skin to stone, as measured by computed tomography (CT) scans, could affect the stone-free rate achieved via extracorporeal shock wave lithotripsy (ESWL) in renal stone patients. MATERIALS AND METHODS: We retrospectively reviewed the records 573 patients who had undergone ESWL at our institution between January 2006 and January 2010 for urinary stones sized from about 5 mm to 20 mm and who had no evidence of stone movement. We excluded patients with ureteral catheters and percutaneous nephrostomy patients; ultimately, only 43 patients fulfilled our inclusion criteria. We classified the success group as those patients whose stones had disappeared on a CT scan or simple X-ray within 6 weeks after ESWL and the failure group as those patients in whom residual stone fragments remained on a CT scan or simple X-ray after 6 weeks. We analyzed the differences between the two groups in age, sex, size of stone, skin-to-stone distance (SSD), stone location, density (Hounsfield unit: HU), voltage (kV), and the number of shocks delivered. RESULTS: The success group included 33 patients and the failure group included 10. In the univariate and multivariate analysis, age, sex, size of stone, stone location, HU, kV and the number of shocks delivered did not differ significantly between the two groups. Only SSD was a factor influencing success: the success group clearly had a shorter SSD (78.25±12.15 mm) than did the failure group (92.03±14.51 mm). The results of the multivariate logistic regression analysis showed SSD to be the only significant independent predictor of the ESWL stone-free rate. CONCLUSIONS: SSD can be readily measured by CT scan; the ESWL stone-free rate was inversely proportional to SSD in renal stone patients. SSD may therefore be a useful clinical predictive factor of the success of ESWL on renal stones.

Three-dimensional biodegradable microscaffolding: scaffold characterization and cell population at single cell resolution.

Engineering artificial tissue scaffolds with a similar organization to that of the natural tissue is a key element to the successful recapitulation of function. However, three-dimensional (3-D) fabrication of tissue scaffolds containing complex microarchitectures still remains a challenge. In addition, little attention has been paid to the issue of how to incorporate cells within 3-D tissue scaffolds that contain precisely engineered architectures. Here we report a 3-D biodegradable microscaffolding (3D-BMS) technology and its process characterization as well as a microscale cellular loading technology as an efficient way to massively populate biodegradable polymers with cells at single cell resolution. In this study a particular emphasis was given to characterization of the material properties of the biodegradable polymers undergoing the 3D-BMS processes. Optimal process conditions were identified in order to avoid any unwanted change in material properties, such as crystallinity and scaffold strength, that have a direct impact on the degradation speed and physical integrity of the constructed scaffolds. For precise control of the cell distribution within the microstructured scaffolds a high precision microsieve structure was designed to localize rat hepatocytes and human articular chondrocytes in the biodegradable polymers. Cell suspensions were passed at a predetermined flow rate through biodegradable polymer layers that contained tapered microholes in a massively parallel process. This high resolution cell seeding method allows accurate manipulation of cell placement in thin layers of biodegradable polymers.

Prostate-Specific Antigen Density as a Powerful Predictor of Extracapsular Extension and Positive Surgical Margin in Radical Prostatectomy Patients with Prostate-Specific Antigen Levels of Less than 10 ng/ml.

PURPOSE: To assess the ability of preoperative variables to predict extracapsular extension (ECE) and positive surgical margin (PSM) in radical prostatectomy patients with prostate-specific antigen (PSA) levels of less than 10 ng/ml. MATERIALS AND METHODS: From January 2008 to December 2009, 121 patients with prostate cancer with PSA levels lower than 10 ng/ml who underwent radical prostatectomy were enrolled in the study. The differences in clinical factors (age, PSA, PSA density [PSAD], digital rectal examination [DRE] positivity, positive magnetic resonance imaging [MRI], Gleason sum, positive core number, and positive biopsy core percentage) with ECE and the presence of positive margins were determined and their independent predictive significances were analyzed. RESULTS: The ECE-positive patients had higher PSA, PSAD, and MRI-positive percentages, and PSM patients had higher PSA, PSAD, MRI-positive percentages, Gleason sum, and positive biopsy core percentages for prostate cancer. In the multivariate analysis, PSAD and MRI positivity were the best independent predictors for ECE, and PSA and PSAD were the best independent predictors of PSM. By receiver operating characteristic curve analysis, PSAD had better discriminative area under the curve value than did PSA for ECE (0.765 vs 0.661) and PSM (0.780 vs 0.624). The best predictive PSAD value was 0.29 ng/ml/cc for ECE and 0.27 ng/ml/cc for PSM. CONCLUSIONS: PSAD has relevance to ECE (plus MRI findings) and PSM (plus PSA). PSAD might be a powerful predictor of ECE and PSM preoperatively in patients undergoing a radical prostatectomy with PSA levels of less than 10 ng/ml.

Analysis of initial baseline clinical parameters and treatment strategy associated with medication failure in the treatment of benign prostatic hyperplasia in Korea.

PURPOSE: To analyze the baseline clinical factors and medication treatment strategy used in cases with medication treatment failure of benign prostatic hyperplasia (BPH). METHODS: From January 2006 to December 2009, 677 BPH patients with at least 3 months of treatment with medication were enrolled. We analyzed clinical factors by medication failure (n=161) versus maintenance (n=516), by prostate size (less than 30 g, n=231; 30 to 50 g, n=244; greater than 50 g, n=202), and by prostate-specific antigen (PSA) levels (less than 1.4 ng/mL, n=324; more than 1.4 ng/mL, n=353). RESULTS: Age, combination medication rate, PSA, and prostate volume were statistically different between the medication treatment failure and maintenance groups. By prostate size, the PSA and medication failure rates were relatively higher and the medication period was shorter in patients with a prostate size of more than 30 g. The combination medication rate was higher in patients with a prostate size of more than 50 g. The medication failure rate and prostate volume were higher in patients with a PSA level of more than 1.4 ng/mL. However, the combination treatment rate was not significantly different in patients with a PSA level lower than 1.4 ng/mL. Suggestive cutoffs for combination medication are a prostate volume of 34 g and PSA level of 1.9 ng/mL. CONCLUSIONS: The clinical factors associated with medication failure were age, treatment type, and prostate volume. Combination therapy should be considered more in Korea in patients with a PSA level higher than 1.4 ng/mL and a prostate volume of between 30 and 50 g to prevent medication failure.

Organ intact retrieval via umbilical incision after simultaneous bilateral laparoscopic radical nephrectomy for renal masses.

PURPOSE: We report on two cases of laparoscopic bilateral nephrectomy for renal-cell carcinoma (RCC) in patients with end-stage renal disease. PATIENTS AND METHODS: Bilateral renal masses were detected in two patients with acquired renal cystic disease. They underwent bilateral laparoscopic nephrectomy. The specimens were removed intact via an umbilical incision. RESULTS: The operative times were 8 hours and 6 hours and the estimated blood loss was 154 mL and 120 mL. Both patients resumed oral intake on postoperative day 1 and were discharged on postoperative day 6. No intraoperative and postoperative complications occurred. The pathology report revealed bilateral RCC. The original length of the umbilical incision was 4 cm which shrank to 3 cm by 2 months after the operation. CONCLUSIONS: Bilateral laparoscopic radical nephrectomy including intact organ retrieval for bilateral renal masses via a small umbilical incision is feasible.

Conjugate additions of carbon nucleophiles to cyclopentadienones.

[reaction: see text] Reactions of cyclopentadienones 1 with alkylmagnesium bromides were investigated and gave 1,4 adduct and/or 1,2 adduct.

Silicon-tethered cyclocarbonylation of alkynes.

[reaction: see text] Temporary union of alkynes in the Fe(CO)5-promoted cyclocarbonylation provides a method for carbonylative cross-coupling of alkynes to construct unsymmetrically substituted cyclopentadienones.