Enhancement of peripheral nerve regeneration using bioabsorbable polymer tubes packed with fibrin gel

Nerve conduit tubes were developed using bioabsorbable polymer membranes, and the effects of tube shape--straight or bellows-shaped tubes--and the fibrin gel filling were investigated. The mechanical properties of the tubes were examined by in vitro tests, and their effectiveness for peripheral nerve regeneration was determined by grafting into experimentally transected sciatic nerves of rats. The bellows tube showed mechanically superior properties, and when used with the fibrin gel, it induced superior tissue formation of myelinated nerve fibers as compared to other tube types. The total area of myelinated axons regenerated in the fibrin-filled bellows tube was comparable to that of an isograft control, whereas those of the other tubes demonstrated inferior regeneration. This result suggests that the mechanically superior bellows tube filled with fibrin gel is an effective graft alternative for peripheral nerve regeneration.     

Two cases of bilateral renal cell carcinoma in patients with Von Hipple-Lindau disease

Von Hipple-Lindau (VHL) disease is a rare familial cancer syndrome that is dominantly inherited and pre-disposes affected individuals to developing various tumors, including hemangioblastoma of the retina and central nervous system, and multicentric renal cell carcinoma. We report two cases of VHL disease with bilateral renal cell carcinoma. Case 1: A 53-year-old woman was referred to our hospital because of bilateral kidney tumor incidentally found. We performed left laparoscopic radical nephrectomy and laparoscopic nephrectomy, ex vivo excision and reconstruction, and autotransplantation for the right kidney. Case 2: A 43-year-old woman was referred to our hospital because of left kidney tumor incidentally found. Because the suspectious lesion in the right kidney was very small, we decided to follow it up with no treatment. We performed laparoscopic nephrectomy, ex vivo excision and reconstruction, and autotransplantation for left kidney.     

Medium- and Long-Term Results of Jejunal Pouch Reconstruction After a Total and Proximal Gastrectomy

Purpose We developed several kinds of jejunal (J)-pouch reconstruction after a gastrectomy for gastric cancer. The aim of this study was to investigate the advantages of these methods. Methods As for the treatment of malignant gastric diseases at stage II or earlier, we employed the J-pouch reconstruction (Roux-en-Y method: JPRY, or J-pouch interposing: JPI) following a total gastrectomy. We also used JPI after a proximal gastrectomy for early gastric cancer located in the upper third of the stomach. Results Out of a total of 80 patients, JPRY was performed in 40 patients and JPI in 40. No anastomotic leaks were associated with the use of an automatic stapler. The stapler (Endo GIA; U.S. Surgical, Norwalk, CT, USA) with a 60-mm-long white cartridge minimized bleeding from the anastomotic site and reduced the operative time. While two patients died of recurrence, all other patients are alive and well for a maximum of 15 years after surgery. The motility of the J pouch was satisfactory after both surgical procedures, as measured by the bile regurgitation test or the transit test employing radiopaque markers. The mean percentage of the radiopaque markers eliminated from the J pouch 1 h after breakfast was 7.5% in the JPRY group and 0%–33% in the JPI group. After another hour, the corresponding percentage was 19.5% in the JPRY group and 14%–60% in the JPI group. Conclusion Our procedures for J-pouch reconstruction are considered to result in a favorable postoperative quality of life and prognosis. J-pouch reconstruction is therefore advantageous in terms of operative morbidity, postoperative clinical signs, symptoms, and dietary status.     

Triterpenoids from the floral spikes of Betula platyphylla var. japonica and their reversing activity against multidrug-resistant cancer cells

Four new triterpenes, together with 16 known triterpenes, were isolated from the floral spikes of Betula platyphylla var. japonica in a search for compounds capable of reversing multidrug resistance in cancer cells. The structures of the new triterpenes were elucidated as 3,4-seco-olean-4(23),13(18)-dien-3-oic acid (1), 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (2), 3-O-methylmalonylepiocotillol II (6), and 3-O-methylmalonylcabraleahydroxylactone (16) by spectroscopic examination. The cytotoxicity of the isolated triterpenes against human cancer cell lines as well as multidrug-resistant cancer cell lines was evaluated. Most of the isolated triterpenes showed very weak cellular toxicities. Although no discernible differences were found in the cytotoxicities for the tested compounds against sensitive and resistant cell lines, the cytotoxicities for several triterpenes against multidrug-resistant cancer cell lines (KB-C2 or K562/Adr) were enhanced in the presence of nontoxic concentrations of colchicine or doxorubicin. Compound 10 reversed the cytotoxicity of colchicine against KB-C2 cells at 8.1 microM and showed comparable potency to 5 microM verapamil.     

Analyses of early events during chondrogenic repair in rat full-thickness articular cartilage defects

In this study we investigated the cellular events that occur during the onset of chondrogenic differentiation during the repair of full-thickness defects of articular cartilage. The V-shaped full-thickness cartilage defects (width 0.7 or 1.5 mm; depth 0.8 mm; length 4 mm) were created in the femoral patellar groove of rats using a custom-built twin-blade device. The time course of the repair response in these cartilage defects was examined using a semi-quantitative histological grading scale. Cartilaginous repair responses failed to occur in the larger 1.5 mm defects, which was covered only by fibrous scar tissue. In contrast, hyaline-like articular cartilage was regenerated concomitantly with the repair of the subchondral bone by 4 weeks in smaller 0.7 mm width defects. Cells in the reparative regions were then characterized by immunohistochemistry and in situ hybridization. Undifferentiated mesenchymal cells migrate into the defects and fill the cavities within 4 days of their creation. The expression of PCNA, N-cadherin, and PTH/PTHrP receptors was induced in cells at the center of the defects, where type II collagen-positive polygonal-shaped cells also begin to appear at day 7. Marrow-derived mesenchymal cells acquire higher levels of proliferative activity in induced cartilage cavities after their initial migration and filling of the smaller 0.7 mm defects. During the regenerative repair of articular cartilage in the rat, there is a distinctive step that appears to be analogous to the precartilaginous condensation that is pivotal during chondrogenesis in development.     

Usefulness of a navigation system in surgery for scoliosis: segmental pedicle screw fixation in the treatment

Study design  Postoperative outcomes of segmental pedicle screw fixation were evaluated in posterior scoliosis surgery with the use of navigation system. Objectives  We report the usefulness of a navigation system and a segmental pedicle screw fixation in surgery for scoliosis. Summary of background data  Few reports on a segmental pedicle screw fixation method for scoliosis surgery using a navigation system have been published. This is the report on the usefulness of a navigation system in segmental pedicle screw fixation. Methods  We targeted 16 cases in which segmental pedicle screw fixation had been performed using a navigation system at our hospital. We inserted 264 pedicle screws in total, and we did not perform registration for each corpus vertebrate in order to shorten the duration of the surgery. We reviewed screw deviation among the items for review using Neo classification with postoperative CT images (1.25 mm). For screw deviation in this case, grade 2 or higher in the Neo classification system was designated as total deviation. Furthermore, we evaluated the registration period per corpus vertebrae, the complications, duration of surgery, blood loss, Cobb angle, and the correction rate. Results  In terms of screw deviation, 11 (4.2%) of the 264 inserted screws were classified as total deviation. However, there were no neurovascular complications during or after surgery in any cases, and all cases maintained strong internal fixation. In the relationship between the use or nonuse of registration and the deviation, four screws (3.2%) in the corpus vertebrae for which registration was performed and seven screws (5.0%) in the adjacent corpus vertebrae for which registration was not performed had deviated. The duration of registration per corpus vertebrate averaged 4 min and 24 s (58–791 s), but registration also requires a learning curve, so the duration of registration per corpus vertebrae averaged 1 min and 14 s in more recent cases, thus marking a significant shortening. Conclusion  Segmental pedicle screw fixation are excellent in regard to their fixing and correction force and have been clinically applied even in surgery for scoliosis, but the potential risk of neurovascular complications is unavoidable. The adoption of a navigation system in surgery for scoliosis is useful to increase the safety and certainty of the insertion of pedicle screws.     

Surgical treatment for local control of extremity and trunk desmoid tumors

Introduction  Surgical treatment has been the mainstay for extremity and trunk desmoid tumors with a negative surgical margin. However, even when resection with a wide surgical margin is achieved, the local recurrence rate remains high. The purpose of this study was to analyze the clinical outcome of patients with extremity and trunk desmoid tumors after surgical treatment and to determine the factors influencing local recurrence. Materials and methods  Between January 1991 and December 2003, 30 of 58 patients with desmoid tumors referred to our institutions and surgically treated and followed up for more than 2 years were selected for this study. Patient age, gender, tumor size, location, status of disease (primary or recurrent), and surgical margins were analyzed as possible risk factors for recurrence. Results  Sixteen (53%) of the 30 patients had a local recurrence. Eight of the 19 patients (42.1%) with a negative surgical margin experienced a recurrence. Younger age (<30 years) was a significant risk factor for local recurrence (P < 0.05). Tumor size, surgical margin and previous surgical history were not associated with local recurrence. Younger age and female gender had a propensity for local recurrence, suggesting that the biological behavior of desmoid tumor may depend on the status of the disease at presentation. Conclusions  These results suggest that radical surgical treatment causing severe functional impairment should be avoided in selected cases on the basis of patient characteristics, and that other novel therapeutic tools may be necessary for patients in whom a higher risk of local recurrence is assumed or severe complications after surgical treatment are predicted.     

Deep venous thrombosis in patients with acute cervical spinal cord injury in a Japanese population: assessment with Doppler ultrasonography

Background  Deep venous thrombosis (DVT) and pulmonary thromboembolism are major complications in patients with acute spinal cord injury. The incidence of DVT in patients with a spinal cord injury has ranged from 5% to 26% in several countries; however, the incidence in Japan is unknown. Methods  We retrospectively assessed 52 patients with acute cervical spinal cord injury. According to the American Spinal Injury Association Impairment Scale (AIS) at admission, 17 patients were grade A, 15 grade B, 17 grade C, and 3 grade D. These patients were assessed for a DVT using color Doppler ultrasonography (US) regardless of whether they were symptomatic. As standard protocol, we perform Doppler US 5 days after injury; however, this retrospective research included patients who were assessed 2–13 days after injury. Results  In this study, 11 of 52 (21%) patients had DVT. Three patients had DVT of the right leg, six of the left leg, and two of bilateral legs. There were two proximal-type DVTs and nine distal-type DVTs. No patients had a symptomatic thrombopulmonary embolism. In all, 10 of 41 (24%) men had DVT and 1 of 11 (9%) women had DVT (P = 0.26). A total of 7 of 32 (22%) patients who had complete motor palsy (AIS A or B) had DVT, and 4 of 20 (20%) with incomplete motor palsy (AIS C or D) had DVT (P = 0.58). DVT was found 2–13 days after injury. Conclusions  In this study of the Japanese population, 11 of 52 (21%) patients with acute cervical spinal cord injury had DVT. Several studies showed there were no differences in the incidence of DVT between patients with complete or incomplete palsy, and our study showed the same results. Many asymptomatic patients had DVT, so asymptomatic patients should not be neglected.     

A comparison of uptake of metformin and phenformin mediated by hOCT1 in human hepatocytes

Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1). The objective of this study was to investigate differences in the hepatic uptake of metformin and phenformin, a biguanide derivative similar to metformin. Special focus was on the role of active transport into cells. Experiments were therefore performed using human cryopreserved hepatocytes and hOCT1 expressing oocytes. Both biguanides proved to be good substrates for hOCT1. However, phenformin exhibited a much higher affinity and transport activity, with a marked difference in uptake kinetics compared with metformin. Both biguanides were transported actively by hOCT1, with the active transport components much greater than passive transport components in both cases, suggesting that functional changes in hOCT1 might affect the transport of both compounds to the same degree. This study for the first time produced detailed comparative findings for uptake profiles of metformin and phenformin in human hepatocytes and hOCT1 expressing oocytes. It is considered that hOCT1 may not be the only key factor that determines the frequency of metformin and phenformin toxicity, considering the major contribution of this transporter to the total hepatic uptake and comparable width of their therapeutic concentrations. Copyright © 2009 John Wiley & Sons, Ltd.