Successful transplantation of motoneurons into the peripheral nerve depends on the number of transplanted cells.

Transplantation of motoneurons (MN) into the peripheral nerve to provide a source of neurons for muscle reinnervation, termed motoneuron integrated striated muscle (MISM), may provide the potential to restore functional muscle activity, when combined with computer-programmed functional electrical stimulation (FES). The number of MNs required to restore innervation to denervated muscles in adult Fischer 344 rats was investigated by comparing two groups, one transplanted with 2 × 10(5) cells (group A) and the other with 1 × 10(6) cells (group B). Twelve weeks after transplantation, electrophysiological analysis, muscle function analysis, and tissue analysis were performed. The mean motor nerve conduction velocity was faster (12.4 ± 1.0 m/s vs. 8.5 ± 0.7 m/s, P = 0.011) and the mean amplitude of compound muscle action potential was larger (1.6 ± 0.4 mV vs. 0.7 ± 0.2 mV, P = 0.034) in group B. The dorsiflexed ankle angle was larger in group B (27 ± 5° vs. 75 ± 8°, P = 0.02). The mean myelinated axon number in the peroneal nerve and the proportion of reinnervated motor end plates were also greater in group B (317 ± 33 vs. 104 ± 17, 87.5 ± 3.4% vs. 40.6 ± 7.7%; P < 0.01, respectively). When sufficient MNs are transplanted into the peripheral nerve, MISM forms functional motor units. MISM, in conjunction with FES, provides a new treatment strategy for paralyzed muscles.

The results of volar locking plate fixation for the fragility fracture population with distal radius fracture in Japanese women.

The purpose of this study was to determine whether volar locking plate fixation for distal radius fracture benefits the fragility fracture population as much as it benefits the non-fragility fracture population. This matched case-control study was conducted based on a multi-center clinical prospective cohort. A comparison of treatment outcomes after volar locking plate fixation was made between females 55 years of age and older (fragility fracture population) and males less than 75 years of age (non-fragility fracture population) by evaluating clinical, radiological, and subjective outcomes using Hand20, a validated patient-rated disability instrument. A total of 170 patients were enrolled in this study. The two cohorts were matched in terms of AO fracture type. The fragility fracture population group and the non-fragility fracture population group each consisted of 50 patients. All objective measurements including wrist range of motion and radiological evaluations, but excluding grip strength, were not significantly different between the two groups. However, the Hand20 at 18 months after surgery was worse in the fragility fracture population group than in the non-fragility fracture population group. Carpal tunnel syndrome was the most frequently encountered complication in the fragility fracture population group, with one case (2%) in the non-fragility fracture population group and six cases (12%) in the fragility fracture population group, but the difference was not significant. In conclusion, there was a significant deficit in the improvement in disability despite favorable radiological and functional outcomes in fragility fracture population patients. Therefore, the fragility fracture population, especially middle-aged or older women, needs to be informed about prolonged disability and the higher risk of upper extremity disorders prior to surgery.

[Rhabdomyolysis after radical nephrectomy in the lateral decubitus position: report of 2 cases].

Rhabdomyolysis is a rare perioperative complication, however, potentially lead to fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old man was seen in our hospital because of asymptomatic grosshematuria. Computed tomography revealed right renal pelvic cancer, cT3N0M0. Right radical nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and the operation was finished without any trouble. At the post-operative day 1, serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive-care unit (ICU), and serum creatinine and creatine kinase level were decreased. At the post-operative day 1, urine myoglobin level was prominently elevated (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case 2) A 40-years old man was incidentally pointed out of right renal tumor that was seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent, and there was no trouble during the operation. After recovering from anesthesia, the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L after the operation. At the postoperative day 1, serum creatine kinase level was markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml, respectively). We diagnosed it rhabdomyolysis, and he received large amount of fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed.

Resection of the inferior vena cava for urological malignancies: single-center experience.

BACKGROUND: Resection of the inferior vena cava (IVC) is occasionally performed for patients with advanced malignancy in the retroperitoneum. In the current study, we assessed the oncological effectiveness of IVC resection combined with tumor resection. We also addressed peri- and postoperative complications associated with resection and reconstruction of the IVC. METHODS: Between 1984 and 2011, a total of 23 patients underwent caval resection concurrently with retroperitoneal tumor excision. Primary tumor histology was renal cell carcinoma in 19 patients, metastatic germ cell tumor in 2, and leiomyosarcoma, and adrenal cancer in 1 patient each. Clinicopathological data from these patients were retrospectively reviewed. RESULTS: IVC reconstruction was performed by direct suture in 11 patients, patch repair in 8 and graft replacement in 3 patients. Interruption of the IVC was performed in one patient. There was no lethal complication or pulmonary embolism. Intracaval thrombosis, although patent, was observed in four patients after surgery. All patients underwent infrarenal IVC reconstruction. The median follow-up was 12 months (range 1-121 months). Of the 20 patients without distant metastasis at the time of surgery, complete resection was achieved in 14, whereas 6 patients had positive margins. Although nine patients developed distant metastases postoperatively, there was no local recurrence. The overall survival, progression-free survival and cause-specific survival in those RCC patients without distant metastasis at the time of surgery were 56.1, 47.0 and 60.4%, respectively, at 5 years. CONCLUSIONS: For advanced malignancies involving the IVC, resection is a safe and feasible procedure for selected patients.

Mechanical advantages of a truss-structure-based fracture fixation system--a novel fracture fixation device "PinFix".

A small, light, ball-joint device called PinFix, which can instantly convert a simple percutaneous cross pin fracture fixation system into a rigid external fracture fixation system based on truss structure, was developed. The purpose of this study was to compare the mechanical load and breaking strength of this truss-structure-based fixation system to that of the conventionally used external cantilever structure-based fixation system. Three types of mechanical loading tests, axial, bending, and torsion, were performed on an artificial fractured bone treated with either three-dimensional PinFix fixation, two-dimensional PinFix fixation, or conventional external fixation. The three- and two-dimensional PinFix fixations showed significantly more stiffness than conventional fixation on all three loading tests. Finite element analysis was next performed to calculate the stress distribution of the parts in PinFix and in the conventional fixator. The applied stress to the rod and connectors of PinFix was much less than that of the conventional external fixator. These results reflected the physical characteristic of truss structure in which applied load is converted to pure tension or compression forces along the members of the PinFix. In conclusion, PinFix is a simple fracture fixation system that has a truss-structure with a high rigidity.

[Case of infected renal cyst in polycystic kidney disease].

A 56-year-old woman with polycystic kidney disease (PKD) presented with high fever and left back pain. Abdominal computed tomography (CT) scan showed multiple renal cysts, left hydronephrosis and a left ureteral stone. Her condition could not be managed with antibiotic therapy and indwelling left ureteral stent. Infected of left renal cysts was suspected, we performed diffusion-weighted magnetic resonance imaging (MRI). Diffusion-weighted MRI showed higher signal intensity in one renal cyst than in other renal cysts. CT-guided percutaneous puncture of an infected cyst was performed. Her symptoms and fever resolved following the procedure. Identification of an infected renal cyst in PKD is often difficult on either ultrasonography or CT. Diffusion-weighted MRI allowed exact localization of the infected cyst among many cysts in PKD.

[Treatment of hemodialyzed patient by targeted therapy in metastatic renal cell carcinoma: a case report].

Experience with treatment of hemodialyzed patients by targeted therapy is limited to the few cases reported. Little information has been provided on the safety and toxicity profile of temsirolimus and sorafenib when administered in hemodialyed patients with renal cell carcinoma (RCC). Herein, we report an RCC patient undergoing hemodialysis treated with temsirolimus and sorafenib for 16 months. The patient was a 69-year-old man who was diagnosed with right RCC. He underwent nephrectomy for a pT1b tumor in December 2002. Hemodialysis was introduced in July 2003 (7 months after nephrectomy). Seven years later, CT showed retroperitoneal nodal metastases. He was started on temsirolimus. Although 8 cycles of this therapy were done, we discontinued it because of progressive disease. The CTCAE (Common Terminology Criteria for Adverse Events) grade 3 adverse events were thrombopenia, but no adverse events of grade 4 or greater developed. Secondly, he was started on sorafenib. CT showed a partial response with a 45% decrease in tumor bulk using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. He has partial response for 13 months. He presented high blood pressure requiring pharmacological treatment, but no adverse events of grade 4 or greater developed. Patients with terminal renal failure can be offered temsirolimus and sorafenib treatment with close clinical and laboratory monitoring. Treatment of RCC patient undergoing hemodialysis by targeted therapy appears to be feasible and effective.

Efficacy of cognitive behavioral therapy using self-check sheet for patients with nocturia in real-world clinical practice.

OBJECTIVES: We previously demonstrated the efficacy of cognitive behavioral therapy (CBT) using a self-check sheet for patients with nocturia in a randomized controlled study. Additionally, we investigated the efficacy of the intervention in real-world clinical practice. METHODS: Two hundred forty-three outpatients with complaint of nocturia who practiced CBT for 4 weeks using a self-check sheet were included in this trial, which took place from April 2021 to March 2022 in 20 institutions. RESULTS: Of the 243 patients, 215 who achieved 50% or more of the behavioral therapy tasks were included in the analysis. Their mean age ± SD was 77.1 ± 7.7. A significant decrease was observed in nighttime frequency at 4 weeks after CBT using self-check sheets (pre 3.3 and post 2.8, p < .001). Nighttime frequency was decreased one or more times and was defined as treatment success in 102 patients (47.4%). Pretreatment nighttime frequency in the treatment-success group was significantly higher than that of the failure group (3.5 ± 1.0 vs. 3.2 ± 1.0, p = .013). In multivariate logistic regression analysis, predictive factors of treatment success were pretreatment nocturnal frequency of four or more (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.01-3.30; p = .046) and the absence of diabetes mellitus (OR 3.08, 95% CI 1.34-7.06; p = .008). CONCLUSIONS: CBT using a self-check sheet requiring less time, less labor, less cost, and less medication is very beneficial for both patients and medical staff in real-world clinical practice.

Analysis of outer membrane vesicle protein involved in biofilm formation of Helicobacter pylori.

Helicobacter pylori is one of the most common causes of bacterial infection in humans. Infection with H. pylori is closely associated with gastritis and peptic ulcers and is a risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma. H. pylori forms biofilms on glass surfaces at the air-liquid interface in in-vitro batch cultures. We previously reported that strain TK1402 showed a strong biofilm-forming ability in vitro. We also suggested the outer membrane vesicles (OMV) produced by strain TK1402 might be related to its biofilm forming ability. In the present study, we analyzed the protein profile of the OMV produced by strain TK1402 and found a unique 22-kDa protein in TK1402 OMV cultured for 2-3 days. In addition, this protein could not be detected in the OMVs produced by other H. pylori strains. These results suggest that the 22-kDa protein is involved in effective biofilm formation by strain TK1402.

[VESICOVAGINAL FISTULA CAUSED BY CYSTOCELE: A CASE REPORT].

Typical etiologies of vesicovaginal fistula (VVF) include obstructed labor, iatrogenic surgical injury, pelvic irradiation and cancer invasion. VVF caused by cystocele are very rare. To date, there are no documented cases in Japanese literature.A 74-year-old woman presented with near total incontinence. On physical examination, she was found to have severe cystocele and pressure necrosis of anterior vaginal wall, which caused partial breakdown of vaginal mucosa and VVF. She underwent vesicovaginal fistula repair using transvaginal and transabdominal approaches. Catheter drainage was performed for 10 days and postoperative cystogram showed no sign of leakage. She is currently symptom-free at 55 months.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071 ± 0.011% vs. 0.051 ± 0.007%, p = .006; area 355.6 ± 345.2 vs. 114.0 ± 132.0 µm2 , p < .001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle.

Transplantation of embryonic motor neurons into peripheral nerve combined with functional electrical stimulation restores functional muscle activity in the rat sciatic nerve transection model.

Reinnervation of denervated muscle by motor neurons transplanted into the peripheral nerve may provide the potential to excite muscles artificially with functional electrical stimulation (FES). Here we investigated whether transplantation of embryonic motor neurons into peripheral nerve combined with FES restored functional muscle activity in adult Fischer 344 rats after transection of the sciatic nerve. One week after sciatic nerve transection, cell culture medium containing (cell transplantation group, n = 6) or lacking (surgical control group, n = 6) dissociated embryonic spinal neurons was injected into the distal stump of the tibial and peroneal nerves. Electrophysiological and tissue analyses were performed in the cell transplantation and surgical control groups 12 weeks after transplantation, as well as a in naïve control group (n = 6) that received no surgery. In the cell transplantation group, ankle angle was measured during gait, with and without FES of the peroneal nerve. Ankle angle at mid-swing was more flexed during gait with FES (26.6 ± 8.7°) than gait without FES (51.4 ± 12.8°, p = 0.011), indicating that transplantated motor neurons in conjunction with FES restored ankle flexion in gait, even though no neural connection between central nervous system and muscle was present. These results indicate that transplantation of embryonic motor neurons into peripheral nerve combined with FES can provide a novel treatment strategy for paralysed muscles. Copyright © 2013 John Wiley & Sons, Ltd.

Who needs further evaluations to diagnose upper urinary tract urothelial cancers among patients with abnormal findings by enhanced CT?

OBJECTIVE: We evaluated who would need further evaluations such as retrograde pyelography (RP) and/or ureteroscopy to diagnose upper urinary tract urothelial cancers (UUTUCs) when abnormal findings for the upper urinary tract (UUT) were detected by enhanced computed tomography (CT). METHODS: We retrospectively analyzed 125 patients who underwent enhanced CT for various reasons and had abnormal findings for the UUT. Patients whose tumors were suspected to be of extraureteral origin were excluded. All patients received RP and/or ureteroscopy to evaluate the UUTUCs. RESULTS: The median age of the 125 patients was 70 years and gross hematuria (26.4%) was the most frequently observed symptoms. RP, ureteroscopy and both were performed for 121, 59 and 55 patients, respectively. CT revealed tumor-like lesions in 58 patients and the other patients had non-tumor-like lesions. UUTUCs were found in 43 (34.4%) of the 125 patients. All of them had tumor-like lesions on CT. In 58 patients who had tumor-like lesions on CT, univariate and multivariate analyses revealed that tumor diameter and tumor enhancement were significant predictive factors for UUTUCs. ROC curve analysis of enhanced CT to diagnose UUTUCs revealed that a tumor diameter of 18 mm was the best cutoff point. The sensitivity, specificity and accuracy were 90.0%, 98.8% and 92.7% for RP and 95.5%, 100% and 97.1% for ureteroscopy, respectively. Both of them had high sensitivity, specificity and accuracy. CONCLUSION: We should decide to evaluate the UUT according to the tumor diameter on enhanced CT. When we evaluate the UUT in patients with tumor diameters of less than 20 mm, ureteroscopy is recommended.

Pathological mechanism of musculoskeletal manifestations associated with CRPS type II: an animal study.

Patients with complex regional pain syndrome (CRPS) often complain of abnormal sensations beyond the affected body part, but causes of this spread of musculoskeletal manifestations into contiguous areas remain unclear. In addition, immobilization can predispose to the development of CRPS. We examined functional, biochemical, and histological alterations in affected parts, including contiguous zones, using an animal model. Ten-week-old male Wistar rats were assigned to 5 groups: a normal group receiving no treatment, a sham operation group with surgical exploration, an immobilization group with surgical exploration plus internal knee joint immobilization, a surgical neuropathy group prepared by spinal nerve ligation (SNL) of the left L5 nerve root, and a surgical neuropathy+immobilization group with simultaneous SNL and knee joint immobilization. Mechanical allodynia and knee contracture were compared between groups, and tissues were harvested for histological assessments and gene and protein expression analyses. Neither surgical procedures nor immobilization induced detectable mechanical sensitivity. However, the addition of nerve injury resulted in detectable mechanical allodynia, and immobilization not only accelerated hyperalgesia, but also resulted in muscle fibrosis. Nerve growth factor (NGF) and other mediators of neurogenic inflammation were highly expressed not only in denervated muscles, but also in innervated muscles in contiguous areas, suggesting the spread of NGF production beyond the myotome of the injured nerve. Transforming growth factor ß was involved in the development of contracture in CRPS. These findings imply that neuroinflammatory components play major roles in the progression and dispersion of both sensory pathologies and pathologies that are exacerbated by immobilization.

Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain.

Tumor necrosis factor-α plays important roles in immune system development, immune response regulation, and T-cell-mediated tissue injury. The present study assessed the net value of anti-tumor necrosis factor-α treatment in terms of functional recovery and inhibition of hypersensitivity after peripheral nerve crush injury. We created a right sciatic nerve crush injury model using a Sugita aneurysm clip. Animals were separated into 3 groups: the first group received only a skin incision; the second group received nerve crush injury and intraperitoneal vehicle injection; and the third group received nerve crush injury and intraperitoneal etanercept (6 mg/kg). Etanercept treatment improved recovery of motor nerve conduction velocity, muscle weight loss, and sciatic functional index. Plantar thermal and von Frey mechanical withdrawal thresholds recovered faster in the etanercept group than in the control group. On day 7 after crush injury, the numbers of ED-1-positive cells in crushed nerves of the control and etanercept groups were increased compared to that in the sham-treated group. After 21 days, ED-1-positive cells had nearly disappeared from the etanercept group. Etanercept reduced expression of interleukin-6 and monocyte chemotactic and activating factor-1 at the crushed sciatic nerve. These findings demonstrate the utility of etanercept, in terms of both enhancing functional recovery and suppressing hypersensitivity after nerve crush. Etanercept does not impede the onset or progression of Wallerian degeneration, but optimizes the involvement of macrophages and the secretion of inflammatory mediators.

Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin.

We investigated the potential usefulness of vesnarinone, a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Mice were fed a control diet (n=42), or a diet containing low (n=42) or high (n=42) dose of vesnarinone. Dietary intake of vesnarinone minimized the BLM toxicity as reflected by significant decreases in numbers of inflammatory cells, KC, and soluble TNF receptors in the bronchoalveolar lavage fluid. A quantitative evaluation of histology demonstrated significantly mild lung parenchymal lesions in BLM-treated mice fed with diet containing high dose of vesnarinone than in the control diet group. Consistent with the histopathology, hydroxyproline levels in lung tissue from BLM-treated mice fed with diet containing vesnarinone were significantly lower than that from mice fed with control diet. We concluded that vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase.