Ryosuke Kakinoki

Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine

The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status.

Biomechanics of the hand.

By understanding the biomechanical motions that allow the hand to function effectively and how patients used the hand before their injury, the surgeon can best determine which surgical method is most suited to prevent permanent loss of function and significant impairment. The objective of this article is to discuss the biomechanics of the hand and, particularly, to assess the range of biomechanical motions that account for most of the hand functions and to determine the value of each function and which specific surgical procedures best restore the optimum function of the hand.

Preoperative Prediction of Ambulatory Status at 6 Months After Total Hip Arthroplasty

Background Total hip arthroplasty (THA) is an effective procedure that provides patients with long-term relief from pain and enables them to resume their normal daily activities. Preoperative instruction about the functional outcomes and optimum goal of rehabilitation is helpful for patients undergoing THA. Objective The purposes of this study were: (1) to examine the relationships between preoperative physical functions and ambulation following THA and (2) to identify optimal cutoff values for estimating ambulatory status at 6 months after THA. Design This was a retrospective study. Methods The study participants were 204 patients who underwent a unilateral THA. Hip abductor and knee extensor strength were measured and the Timed “Up & Go” Test (TUG) was conducted preoperatively. The patients were divided into 2 groups according to self-reported walking ability at 6 months postoperatively: an independent ambulation group (n=118) and a cane-assisted ambulation group (n=86). Differences between the 2 groups were examined using an unpaired t test or the chi-square test. A stepwise multiple logistic regression analysis was performed with walking ability at 6 months postoperatively as a dependent variable and age, sex, contralateral hip osteoarthritis (ie, whether a participant had contralateral hip osteoarthritis or not), body mass index, hip abductor strength, knee extensor strength, and TUG score as independent variables. Receiver operating characteristic curve analysis was used to identify a cutoff point for classifying the participants into the 2 groups. Results A stepwise multiple logistic regression analysis selected 3 factors (age, knee extensor strength, and TUG score) as significant variables affecting the midterm ambulatory ability after THA. Moreover, receiver operating characteristic curve analyses revealed that the midterm (ie, 6-month) ambulatory status after THA was more accurately predicted by the patients TUG score (cutoff point=10 seconds, sensitivity=76.7%, specificity=93.2%, area under the curve=0.93) than by age and knee extensor strength. Limitations The categorization of ambulatory status in this study was based solely on self-reported walking ability. Conclusion The findings indicate that patients with a preoperative TUG score of less than 10 seconds are likely to walk without an assistive device at 6 months after THA.

LUNATE PLASTY FOR KIENBÖ4'S DISEASE: USE OF A PEDICLED VASCULARISED RADIAL BONE GRAFT COMBINED WITH SHORTENING OF THE CAPITATE AND RADIUS

We treated eight patients with Kienböcks disease (two patients each with stage 1, 2, 3a and 3b disease by Lichtmans classification) by removing a pedicled, vascularised bone segment from the dorsal aspect of the distal radius and engrafting it into the lunate. Additional shortening of the radius was performed in patients with the ulna-minus or null variant. Shortening of the capitate and capito-hamate fusion were also performed in patients with stage 3 disease. All patients were relieved of their wrist pain at rest and during movement, and the mean grip strength increased from 37% of that in the contralateral hand before surgery to 80% after surgery. The mean post-operative range of motion in the affected wrist was 92% of that in the opposite wrist in patients with stage 1 and 2 disease, and 53% in patients with stage 3 disease. Post-operative assessment revealed that four patients had excellent results, three had good results, and one had a fair result.

Relationship between axonal regeneration and vascularity in tubulation — an experimental study in rats

This study investigated the effect of vascularity in a nerve conduit on peripheral nerve regeneration. The effect of three different types of tube (empty, blood vessel-containing and ligated vessel-containing) was compared using a rat sciatic nerve preparation with a 10-mm gap. Nerve regeneration through the vessel-containing tube was more efficient than in the other tubes 6 and 12 weeks after tubulation surgery, but there were no statistically significant differences among the three types of tube after 24 weeks. Electrophysiological, histological and microangiographic studies showed that vessels which were preinserted in the nerve conduit accelerated axonal regeneration through rapid capillary formation in the tube.

The volar approach to proximal interphalangeal joint arthroplasty.

Proximal interphalangeal joint arthroplasty has resulted in good outcomes in patients treated for osteoarthritis, posttraumatic arthritis, and rheumatoid arthritis. Most hand surgeons complete arthroplasties of the proximal interphalangeal joint through a dorsal approach. However, for the past 7 years, we have had positive results with a volar approach. We describe this technique, which avoids injury to the extensor tendon and allows for a more simplified approach to postoperative therapy compared with the therapy regimen required after the dorsal approach.

Treatment of posttraumatic painful neuromas at the digit tip using neurovascular island flaps.

PURPOSE We report the treatment of 9 patients with 9 painful neuromas at the tips of the digits using reverse pedicled island flaps containing subcutaneous nerves that were connected to the digital nerve stumps after removal of the neuromas. METHODS There were 9 patients (7 men and 2 women) with painful cutaneous neuromas at the tips of the digits. The ages of the patients at time of surgery were 21 to 66 years (mean, 46 y). All neuromas were formed in the palmar digital nerves in the hand. Preoperative and postoperative status of the patients with neuromas were assessed and graded using a system modified from previously described grading systems for patients with neuromas. Recovery of sensation in the transplanted skin islands was assessed using the Semmes-Weinstein monofilament test. RESULTS In the preoperative assessment of patients using the grading system for neuromas, 3 patients were assessed as grade 4 (severe), 5 patients as grade 3 (moderate), and the remaining patient as grade 2 (mild). After surgery, Tinel sign disappeared completely in 6 of 9 patients. According to the grading system for neuromas, 6 patients were assessed as grade 1 (normal), and the other 3 patients were assessed as grade 2 (mild) postoperatively. Using the Semmes-Weinstein monofilament test for assessing recovery of sensation of the skin islands, 3 patients recognized the 2.83 monofilament (normal), 2 patients recognized the 3.22 monofilament (loss of tactile sense), and the remaining 4 patients recognized the 3.66 monofilament applied (loss of tactile sense). CONCLUSIONS This skin island approach provided us with good pain control and recovery of hand function after painful neuromas. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

Nerve regeneration promoted in a tube with vascularity containing bone marrow-derived cells.

Bone marrow-derived cells (BMCs) are multipotent cells that have the potential to differentiate into bone, cartilage, fat, muscle, or neuronal lineages such as neurons and glial cells. A silicone tube model containing reverse-pedicled sural vessels was created in the sciatic nerves of Lewis rats. About 1 × 107 BMCs, removed from the bone marrow of synergetic rat femurs and cultured in vitro, were transplanted into the 15-mm-long chambers of the silicone tubes. Nerve regeneration in vessel-containing tubes that had received BMCs was significantly greater at 12 and 24 weeks after surgery than in tubes that did not receive cells. Transplantation of fibroblasts instead of BMCs into the vessel-containing tube resulted in reduced axonal regeneration, which was inferior to regeneration in the vessel-containing tube that did not receive cells. Polymerase chain reaction (PCR) studies revealed that in vessel-containing tubes containing transplanted BMCs, about 29% of cells in the regenerated nerve originated from BMCs. Cells identified by in situ hybridization and PKH26 prelabeling as being of BMC origin stained positively for S100 and GFAP. Transplanted BMCs differentiated into cells with phenotypes similar to those of Schwann cells under the influence of neurochemical factors and survived by obtaining nutrients from vessels that had been preinserted into the tube. They thus functioned similarly to Schwann cells, promoting nerve regeneration.

Regeneration of osteonecrosis of canine scapho-lunate using bone marrow stromal cells: Possible therapeutic approach for Kienböck disease

We evaluated the ability of canine bone marrow stromal cells (cBMSCs) to regenerate bone in a cavity of the scapholunate created by curretage and freeze–thawing with liquid nitrogen (LN). Autologous BMSCs were harvested from the iliac crest and expanded in vitro. Their potential to differentiate into osteo-, chondro-, and adipogenic lineages was confirmed using a standard differentiation induction assay. LN-treated scapholunates showed no regeneration of bone tissue when the cavity was left alone, demonstrating severe collapse and deformity as observed in human Kienböck disease. A combination of β-tri-calcium phosphate and a vascularized bone graft with autologous fibroblasts failed to regenerate bone in the LN-treated cavity. When the same procedure was performed using BMSCs, however, LN-treated scapholunates showed no collapse and deformity, and the cavity was completely filled with normal cancerous bone within 4 weeks. These results suggested the potential of using BMSCs to treat Kienböck disease.

Nerve regeneration over a 25 mm gap in rat sciatic nerves using tubes containing blood vessels: the possibility of clinical application

Summary. This study was undertaken to investigate the effect of including vessels in a tube used to promote nerve regeneration across a gap. A tube containing sural vessels was designed in a rat model and interposed between the proximal and distal stumps of a divided sciatic nerve, leaving a 25 mm gap. At 12 weeks, a few myelinated axons were seen at the most distal parts of regenerated nerves in 6 out of 10 rats, none of which evoked action potentials in the tibialis anterior muscle, but by 24 weeks all the rats had developed neural tissue in the tubes, which evoked action potentials in the muscle. The vessels within the tube enhanced nerve regeneration and its distance up 25 mm. This type of vessel-containing tube would be useful for the repair of divided human peripheral nerves with long gaps, almost equivalent to or slightly longer than the maximum length over which nerve fibres can regenerate through a unvascularised unmodified tube.Résumé. Plusieurs auteurs ont rapporté que la repousse maximum des axones du nerf sciatique de rat, dans un tube, est d’environ 10 mm. La présente étude a été réalisée pour confirmer que la mise en place d’un tube dans un vaisseau permet aux fibres nerveuses d’atteindre une régénération de plus de 10 mm par cette technique de tubulation. Chez un rat, une veine surale contenant un tube a été utilisée et interposée entre les moignons sectionnés d’un nerf sciatique avec’un espace de 25 mm. A la 12 ème semaine, quelques axones myélinisés ont été observés à la partie la plus distale des nerfs régénérés chez 6 rats sur 10. Aucun de ceux-ci n’a pû donner de potentiels d’action dans les muscles tibiaux antérieurs. Après 24 semaines, tous les rats ont développé une repousse neuronale dans les tubes, qui ont donné des potentiels d’action dans les muscles tibiaux antérieurs. Cette chambre intravasculaire augmente la régénération des nerfs ainsi que la distance de régénération jusqu’à 25 mm pour un nerf sciatique de rat. Un vaisseau contenant un tube est considéré comme étant cliniquement, utile pour la réparation de la section de nerf périphérique avec un espace important, qui sont équivalents ou légèrement supérieurs, au maximum de longueur dont les nerfs peuvent repousser dans des tubes nonvascularisés classiques.