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Interleukin (IL)-23, which is released by activated monocytes and neutrophils, promotes production of high levels of IL-17 by T-helper 17 cells. Cellulose acetate (CA) beads are used as carriers for granulocyte and monocyte (GM) adsorptive apheresis using Adacolumn. Contact between blood and CA beads induces cytokine release; however, their inflammatory effects on IL-23 release are unclear. We aimed to clarify the effect of CA beads on IL-23 release in vitro. We incubated peripheral blood with and without CA beads and measured IL-23. Compared to blood samples incubated without CA beads, blood samples incubated with CA beads had significantly decreased amounts of IL-23. In conclusion, CA beads inhibited IL-23 release from adsorbed GMs. The biological effects of this decrease in IL-23 release during GM adsorption to CA beads need further clarification.

Transforming growth factor-β (TGF-β) is released by activated platelets and induces the differentiation of T-helper 17 from naive T cells. Contact between blood and cellulose acetate (CA) beads induces cytokine release, although their inflammatory effects on TGF-β release are unclear. We aimed to clarify the effect of CA beads on the release of TGF-β in vitro. We incubated peripheral blood with and without CA beads and measured platelets and TGF-β. Compared with blood samples incubated without beads, the platelet count and amount of TGF-β significantly decreased in blood samples incubated with CA beads. In conclusion, CA beads inhibited the release of TGF-β from adsorbed platelets. The biological effects of this reduction of TGF-β release during platelet adsorption to CA beads need further clarification.

Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2–5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.

The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.

The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43-year-old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow-band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low-echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.

Tumor necrosis factor-α, (TNF)-α, a proinflammatory cytokine, is produced by activated granulocytes and monocytes (GMs) and implicated as a major factor in inflammatory bowel disease (IBD) pathogenesis. Reduction of TNF-α should improve IBD pathology. GM adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including IBD. GM adsorption to cellulose acetate (CA) beads induces anti-inflammatory cytokine release, although these effects on TNF-α release are not clarified. We hypothesized that GMA may inhibit TNF-α release. The aim of the present study was to clarify the effects of GM adsorption to CA beads on TNF-α release in vitro. Peripheral blood was incubated with and without CA beads and TNF-α was measured. For comparison, TNF-α was measured in another lipopolysaccharide (LPS)-containing peripheral blood sample incubated similarly. The amount of TNF-α in blood samples incubated with CA beads was significantly higher than in those incubated without beads, although it was significantly lower than TNF-α incubated with LPS-containing sample without beads. The amount of TNF-α after incubation with CA beads positively correlated with GM adsorption ratio. GM adsorption to CA beads induced a small amount of TNF-α release. This is the first report on TNF-α release induced via GM adsorption stimuli. The biological effects of TNF-α release during GM adsorption need to be clarified.

Background and study aims: Intramucosal vascular density differs between differentiated and undifferentiated type gastric carcinomas. This study aimed to evaluate the microvascular density characteristics of these two types of carcinoma using magnifying endoscopy with narrow-band imaging (ME-NBI). Patients and methods: In total, 42 differentiated and 10 undifferentiated types were evaluated. The microvessels observed using ME-NBI were extracted from stored still images and the microvascular density in the two carcinoma types was analyzed. Histological vascular density in resected specimens was also evaluated using CD34 immunostaining. Results: There were significant differences between the microvascular density in the differentiated and undifferentiated types of carcinoma (10.02 ± 4.72 % vs 4.02 ± 0.40 %; P

The human leukocyte antigen (HLA) region has been implicated in the disease susceptibility of inflammatory bowel disease by several linkage and association studies. In Caucasians, HLA-DRB1 has been reported to determine the clinical phenotypes of ulcerative colitis (UC). Others and we previously reported that HLA-DRB1*1502 was strongly associated with UC in the Japanese population. However, the contribution of HLA-DRB1 to the clinical phenotypes in Japanese UC has not been elucidated yet. The aim of this study was to determine whether HLA-DRB1 alleles were associated with the clinical phenotypes in Japanese patients with UC. A total of 353 patients with UC were recruited. Patients were classified into subgroups by sex, age at diagnosis, disease extent, need for steroid therapy or need for surgical treatment. The allele frequency of HLA-DRB1*08 was significantly higher in patients whose disease extended beyond the rectum (left-sided and extensive UC) than in those with proctitis [odds ratio (OR) = 2.20, Pc = 0.043). The allele frequency of HLA-DRB1*09 was significantly higher in patients with UC diagnosed at the age of 40 years or older than in those with UC diagnosed before the age of 40 years (OR = 2.31, Pc = 0.022). Besides these positive associations, no significant differences were found in the allele frequencies between the other subgroups. We conclude that HLA-DRB1*09 is associated with the age at diagnosis and HLA-DRB1*08 is associated with the disease extent of UC in Japanese. These results indicate that HLA-DRB1 is not only associated with the overall UC susceptibility but also associated with the clinical phenotypes in Japanese.

Study design This study was aimed at investigating changes in the dorsal horn of the lumbar cord induced by mechanical compression using an in vivo model. Objective To determine the effect of axonal flow disturbance in the dorsal horns induced by nerve root compression. Summary of background data Few studies have looked at changes of synapses within the dorsal horn caused by disturbance of axonal flow and the axon reaction as a result of mechanical compression of the dorsal root. Methods In mongrel dogs, the 7th lumbar nerve root was compressed for 1 week, or 3 weeks using a clip. After intravenous injection of Evans blue albumin, they were observed under a fluorescence microscope for the purpose of clarifying the function of the blood-spinal cord barrier. Morphologic changes of the synapses in the dorsal horns secondary to the nerve fiber degeneration were examined by light and electron microscope. Changes on immuno-staining for substance P, calcitonin gene-related peptide, and somatostatin in the dorsal horn were also examined. Results Light microscope observation conducted 1 week after compression of the nerve roots revealed Wallerian degeneration of the myelinated nerve in the dorsal horn, and fluorescence microscope observation of these areas demonstrated edema formation resulting from damage of the blood-spinal cord barrier. Three weeks after the compression, electron microscope observation revealed shrinkage of the axon terminals, ubiquitous presence of high electron density degeneration and presence of synapses whose contact with synapses was disrupted. Immuno-histochemical studies showed a marked decrease of substance P, calcitonin gene-related peptide, and somatostatin staining in substance gelatinosa with Wallerian degeneration after compression of nerve root. Conclusion It is important to recognize that compressive disturbance of the nerve roots caused Wallerian degeneration not only at the site of compression of nerve roots but also at the synapses of spinal cord dorsal horns.

BackgroundProximal or distal realignment procedures have long been selected as treatment for recurrent patellar dislocation, but associated knee osteoarthritis has been a substantial problem that leads to poor results. A new approach, medial patellofemoral ligament reconstruction, has recently started, but there have been no reports on the long-term follow-up.HypothesisAnatomical medial patellofemoral ligament reconstruction can lead to satisfactory long-term outcome and a low association rate of knee osteoarthritis.Study DesignCase series; Level of evidence, 4.MethodsTwenty-four knees from 22 patients who underwent medial patellofemoral ligament reconstruction for recurrent patellar dislocation were reviewed at a mean follow-up of 11.9 years (range, 8.5-17.2 years). A lateral release was done on 14 of 24 knees. The clinical/physical outcome and the association of knee osteoarthritis were investigated. Patellofemoral and femorotibial osteoarthritis on the radiographs was evaluated using the Crosby/Insall and the Kellgren/Lawrence grading systems.ResultsAccording to the Crosby/Insall criteria, 11 knees (46%) were classified as excellent, 10 (42%) as good, 3 (12%) as fair/poor, and none as worse at follow-up. Further lateral subluxation or dislocation occurred in only 2 knees. The mean Kujala score improved significantly from 63.2 points preoperatively to 94.2 points at follow-up (P < .0001). According to the Crosby/Insall grading system, patellofemoral osteoarthritis was none to mild in 23 of the 24 knees and moderate in 1 knee, preoperatively. At the final follow-up, 21 knees were none to mild, and 3 knees were moderate. There were only 2 knees that had definite progression from none to mild to a moderate grade.ConclusionThe association of definite knee osteoarthritis in medial patellofemoral ligament reconstruction with or without lateral release was small in the long-term follow-up. The conclusion is that medial patellofemoral ligament reconstruction not only prevents further patellar dislocation but also shows no or only slight progression of knee osteoarthritis.

Aims: Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic disease of unknown pathogenesis. However, several reports have demonstrated the involvement of genetic backgrounds in this syndrome. The aim of this study is to examine the genetic disequilibrium in the HLA region in Japanese patients using six microsatellite markers. Methods: Genomic DNAs were obtained from 73 patients with PBC (patient cohort) and 186 healthy volunteers (control cohort). Genetic polymorphisms at six microsatellite markers (D6S1568, DQ.CAR, D6S273, TNF-d, C1-2-A, C3-2-11) were determined using fluorescence-labeled polymerase chain reaction (PCR) genetic analyzer. Allele frequencies were estimated by direct counting and the genotypic differentiation test was performed by the Markov chain method using Genepop software. Results: Among these six microsatellite markers, four markers in the patients significantly (P

This study was designed to investigate retrospectively the efficacy and safety of endoscopic balloon dilation for intestinal strictures in Crohn’s disease. Sixteen patients with 20 strictures were treated. The stricture sites were as follows: at the ileocolonic (n = 6) or ileoileal (n = 1) anastomosis, in the colon (n = 10), ileum (n = 2), and at the ileocecal valve (n = 1). The dilations were performed with through-the-scope balloons, with diameters of 15 to 20 mm on inflation and lengths of 30 to 80 mm. In 15 of 16 patients, the strictures were successfully dilated and the symptoms caused by the strictures disappeared after the first session. The patients were followed for a median of 38.5 months. Repeat symptomatic stricture formation occurred after a mean of 19.7 months in seven patients. Four patients needed second-round dilation and three patients were treated surgically. Complications occurred in four patients who had primary strictures: bleeding in one, high fever in one, and colorectal perforation in two. One of the patients complicated with colorectal perforation was treated surgically, and the other was treated conservatively. The cumulative nonsurgical rates for the dilation strictures were 93 percent at 12 months and 65 percent at 36 months, respectively. Three patients were treated surgically because of strictures or fistulas that were not related to the procedure of dilation. As a whole, the cumulative nonsurgical rates were 81 percent at 12 months and 46 percent at 36 months. Nine patients (56.3 percent) were able to avoid surgery. Using endoscopic balloon dilation, it may be possible to avoid or postpone surgery. Primary strictures seem to have increased risk of perforation.

Purpose: The purpose of this study was to assess the relation between generalized joint laxity and patellar hypermobility in unilateral recurrent patellar dislocators. Type of Study: Case series. Methods: A total of 82 patients (23 male and 59 female patients) with unilateral recurrent patellar dislocation were studied compared with an age- and sex-matched control group. The modified Carter and Wilkinson criteria for generalized joint laxity and lateral patellar hypermobility test were examined. Results: Generalized joint laxity (score of 4 or 5) was present in 20 patients (24%) with recurrent patellar dislocation in 8 subjects (10%) of the control group. The mean total score was 2.5 (SD, 1.4) in the recurrent patellar dislocators and 1.7 (SD, 1.3) in the control group. The incidence of generalized joint laxity ( P = .013) and the mean total score ( P = .00004) were statistically significant between the two groups. A hypermobile patella was present in 42 patients (51%) and in 5 subjects (6%) of the control group. There was a large statistically significant difference between the two groups ( P Conclusions: Although a hypermobile patella and generalized joint laxity were significant between the recurrent patellar dislocators and the control group, a hypermobile patella was more significant than generalized joint laxity as the predisposing factors of patellar dislocation. Level of Evidence: Level IV, prognostic case series.

Purpose: The purpose of this study was to evaluate the results of a new hybrid medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation. Methods: Hybrid MPFL reconstruction by use of the semitendinous tendon was performed in 12 knees with recurrent patellar dislocation. The results were evaluated at a minimum follow-up of 3 years (mean, 4.2 years). Results: According to the grading system of Insall et al., the results were classified as excellent in 8 knees (66%), good in 2 (17%), and fair in 2 (17%), with none being classified as poor. The mean Kujala score was 56.3 points (range, 29 to 82) preoperatively and 96.0 points (range, 84 to 100) at follow-up. There were no patients with recurrent dislocation and subluxation. No knees had a positive apprehension sign, and there were no postoperative complications. Conclusions: At a midterm follow-up, hybrid MPFL reconstruction by use of the semitendinous tendon for recurrent patellar dislocation should be considered as an effective operation for cases without severe predisposing factors. Level of Evidence: Level IV, therapeutic case series, no or historical control group.

This study was done to investigate the microvascular system of anterior cruciate ligament (ACL) using dogs. The objective was to study the microvascular architecture and the status of the barrier function of the capillary wall in the ACL by using microangiogram, scanning (SEM), and transmission electron microscopy (TEM). The vascular system in the ACL has been intensively studied by a number of researchers, using several microangiographic techniques in dogs, rabbits, and humans. However, most of these microangiographic studies had significant shortcomings, including the lack of three-dimensional observations and function of the blood-joint barrier in the ACL. In this study, the microstructure of the ACL was examined using microangiogram, SEM, and TEM. We investigated the vasculature of the ACL with SEM of vascular corrosion casts. In addition, we examined the status of the barrier function of the capillary wall in the ACL using the protein tracer horseradish peroxidase (HRP). Feeding vessels of the ligament were predominantly coming from the synovial-derived vessels originating from the synovium attached to the ligament near the tibial and femoral bone insertions of the ACL. The anterior cruciate ligament was surrounded by synovium, which had abundant vessels. The branches of these synovial vessels were penetrating into the ligament and making the intrinsic vascular network. It was also ascertained under SEM that the perivascular space around the intrinsic vessels were communicating through the intrinsic ligament fiber bundles and the mesh-like synovial membrane. The capillaries in the ACL were all of the continuous type under TEM. The protein tracer that was injected into the joint space passed through the synovial membrane and entered into the capillary lumen in the ACL, but the tracer that was injected intravenously did not appear in the perivascular space. The existence of a blood-ACL barrier does not necessarily imply the existence of an ACL-blood barrier. We think that the blood flow in the ACL is definitely affected by the status of joint fluid and these barriers of endothelium. The clinical relevance of the fine vascular anatomy of the ACL in trauma surgery is considered. This deserves further consideration.

The purpose of this study was to investigate the anatomical morphology and measurement of the medial patellofemoral ligament (MPFL), especially the femoral attachment. A total of 20 knee specimens were dissected and the total length, width, thickness, inclination, as well as the attachment points of the MPFL were measured. The MPFL was well-developed in seven knees, moderate in ten knees and wispy in three knees. Total length of the MPFL was 58.8 +/- 4.7 mm. The width and thickness was 12.0 +/- 3.1 mm and 0.44 +/- 0.19 mm at the middle point. The long axis of the MPFL inclined at 15.9 +/- 5.6 degrees proximally. The center of the patellar attachment was located at 27 +/- 10% from the upper end of the patella in the longitudinal patellar height. The femoral attachment was superoposterior to the medial femoral epicondyle and just distal to the adductor tubercle. The center of the anterior edge of the femoral attachment was 9.5 +/- 1.8 mm proximally and 5.0 +/- 1.7 mm posteriorly from the center of the medial femoral epicondyle. The femoral attachment was located at 61 +/- 4% of anteroposterior length of the medial femoral condyle from the anterior edge.

This study investigated the results of augmented repair for avulsion-tear type medial patellofemoral ligament (MPFL) injury performed on a total of five knees with initial acute lateral patellar dislocation. Augmented repair was performed using a medial retinaculum slip on all five knees. The average follow-up was 5.9 years. The results were evaluated with the Insall, Aglietti, and Tria grading system. Three knees were classified as excellent, one knee as good, and one knee as fair. The mean Kujala score at follow-up was 97.6 points. Augmented repair of the injured MPFL for avulsion-type MPFL injury may be considered as one good option to prevent subsequent dislocation and subluxation.

Background The etiology of patellar cartilage lesions in recurrent patellar dislocation has been poorly understood. Hypothesis The pathology of cartilage lesions of the patella accompanied by recurrent patellar dislocation can be analyzed. Study Design Series of case reports. Methods In 70 knees from 57 patients with recurrent patellar dislocation, the cartilage lesions of the patella were examined using arthroscopy and/or macroscopic observation. The average age of the patients was 22 years (range, 13 to 40 years). Lesions that involved only softening were not included. Results Sixty-seven knees (96%) had articular cartilage lesions of the patella, and only 3 knees had no change. Fissuring was observed in 53 knees (76%). The most common site of fissuring was on the central dome. There were basically two types of fissuring: multiple longitudinal fissuring and marginal/radial fissuring. Fibrillation and/or erosion were observed in 54 knees (77%). Of these, 40 knees had fissuring and 14 did not have fissuring. The main site of fibrillation and/or erosion was the medial facet. Conclusions Cartilage lesions of the patella in recurrent patellar dislocation cases were very common. Fissuring was observed mainly on the central dome, and fibrillation and/or erosion were observed mainly on the medial facet.

Purpose: The purpose of this study was to evaluate the frequency and precise pathology of articular cartilage injuries after acute patellar dislocation. Type of Study: Case series. Methods: In 39 consecutive knees with initial lateral patellar dislocation, the articular cartilage injuries were examined using arthroscopy or macroscopic observation. Results: Thirty-seven knees (95%) had articular cartilage injuries of the patellofemoral joint and 2 knees (5%) had no cartilage injury. In all 37 knees (95%), articular cartilage injuries were observed in the patella. The appearances were categorized into 3 groups: cracks alone (9 knees), cartilage defect caused by osteochondral or chondral fracture (7 knees), and cartilage defects caused by osteochondral or chondral fracture associated with cracks (21 knees). The main site of osteochondral fracture was the medial facet, and the main site of cracks was the central dome. Twelve knees (31%) had cartilage injury of the lateral femoral condyle. Conclusions: From this study, articular cartilage injuries, especially of the patella, seem to be common occurrences after acute patellar dislocation. Chondral and osteochondral injuries of the patella were classified into 3 groups.

This article describes a medial patellofemoral ligament (MPFL) reconstruction procedure using an artificial ligament for recurrent patellar dislocation. The MPFL has been shown biomechanically to be the primary restraint among the medial patellar stabilizers. Although various predisposing factors are involved in lateral patellar dislocation, we believe that the MPFL, as a primary restraint, should undergo primary reconstruction for patellar dislocation. The results of MPFL reconstruction using a mesh-type artificial ligament and medial retinaculum slip coverage for recurrent patellar dislocation were as good as we had expected. In this article, we describe the detailed surgical technique and its rationale. We believe technique has also wide applications in MPFL reconstruction using autogenous tendons.

Acute patellar dislocation is a common injury that can lead to disabling knee pain and/or recurrent instability. Recent research focuses on patellofemoral anatomy, on the injuries associated with acute patellar dislocation, and the specific contributions the injured structures make to patellar stability in intact knees. The implication is that injury to specific structures may have important consequences in converting a previously asymptomatic, though perhaps abnormal, patellofemoral joint into one that is painful and/or unstable. These studies have been intended to improve the precision of surgical treatment for patellar instability, and their results are driving refinements in our surgical indications as well as technique.

We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.

Recently, a genome-wide association study for ulcerative colitis (UC) in the UK population was reported, and several susceptibility loci including the human leukocyte antigen (HLA) region were identified. The strongest association in the HLA region was found at a 400 kb haplotype block containing HLA-DRB1. In Japanese population, previous study suggested the association between UC and HLA-B*52; however, HLA typing was determined using serotyping with the small sample size. The purpose of this study was to perform an association study in HLA-B by genotyping. A total of 320 patients with UC and 322 healthy controls were recruited in this case-control study. All subjects were Japanese. Genotyping of HLA-B was performed by polymerase chain reaction using a sequence-specific primer. When the allele frequencies were compared, significant associations were found with B*52 [odds ratio (OR) = 3.65, P = 1.6 x 10(-17), P(c) = 3.7 x 10(-16)] and B*4002 (OR = 0.52, P = 0.00030, P(c) = 0.0068). The allele frequency of B*52 was significantly higher in patients diagnosed before 40 years of age than in those diagnosed after 40 years (OR = 1.79, P = 0.010, P(c) = 0.020). A combination association map of Japanese UC using our current and previous studies showed two equal peaks of association on HLA-DRB1 and HLA-B, indicating the possible existence of two casual variants in the HLA region inside and outside the 400 kb block found in UK. We conclude that HLA-B contributes to the susceptibility to Japanese UC, especially cases with younger age of onset. The strength of association for HLA-B was equal to that for HLA-DRB1 in Japanese UC, in contrast to the UK population.

Study Design. This study is to investigate the changes of vasomotion of intraradicular microvessels in vivo. Objective. We have observed microvascular corrosion casts of the lumbar nerve root by scanning electron microscopy and used an immunohistochemical technique to investigate the presence and distribution of autonomic and sensory nerve in blood vessels of the nerve root. Summary of Background Data. It is generally considered that the genesis of radiculopathy associated with the degenerative conditions of the spine may result from both mechanical compression and circulatory disturbance. However, the neurogenic control of intraradicular blood flow has received little attention in the past. Methods. For three-dimensional observation of intraradicular vessels, we used scanning electron microscopic examination of microvascular corrosion casts in ten Wister rats. To investigate the mechanism of vasomotion of the nerve root, we used immunohistochemical methods. The sections were incubated overnight with antisera to tyrosine hydroxylase, choline acetyl transferase, substance P, calcitonin-gene-related peptide, vasoactive intestinal peptide, somatostatin, neuropeptide Y, leucine-enkephalin, cholecystokinin octapeptide, brain-nitric oxide synthase, and endothelium-nitric oxide synthase. Abidin-biotin complex method was used as the immunohistochemical procedure and the sections were observed under the light microscope. Results. The general view of whole vascular casts of the lumbar spinal cord and nerve roots showed a high density of vessels. Bifurcation or anastomoses of capillaries approximately took place at right angles in a T-shaped pattern and capillaries showed a lot of ring-like compressions. This ring-like compression on the cast may represent a vascular sphincter in the microvessels. This study also reveals the existence of perivascular adrenergic, cholinergic, peptidergic, and nitroxydergic innervation with a possible role in neurogenic regulation of nerve root circulation. Conclusion. Perivascular nerve plexuses around intraradicular microvessels suggest that the autonomic nerves play an important role in intraradicular circulation.

Study design The mechanisms responsible for the spontaneous regression of lumbar disc herniation (LDH) were studied by examining herniated tissue collected at operation from patients with LDH. Objective The aim of the present study was to investigate the role of neovascularization and macrophages in hernias when spontaneous regression of LDH occurred. Summary of background data Spontaneous regression of LDHs has already been demonstrated by diagnostic imaging with tools such as magnetic resonance imaging. However, there have been few studies on the mechanisms of spontaneous regression based on pathologic examination of herniated tissue. In particular, there has been no detailed work on the role of macrophages, which are thought to be closely associated with spontaneous regression. Methods The magnetic resonance imaging and operative findings of 73 patients who underwent surgery were investigated, and specimens collected during surgery were examined by light and transmission electron microscopy. Results Capillaries that invade the hernia and macrophages derived from monocytes migrating out of these capillaries are considered to be important factors in the regression of the herniated disc. Macrophages contain lysosomes filled with collagen-degrading enzymes that break down substances after phagocytosis, whereas primary lysosomes are secreted by these cells and break down intercellular substances such as collagen. Both of these mechanisms are closely involved in the regression of herniation. Conclusion The inflammatory response that occurs around hernia tissue in the epidural space is believed to play an important role in herniated disc resorption, although it may also have a harmful effect on the adjacent nerve root. Therefore, control of the inflammatory reaction is an important challenge when treating patients with disc herniation.

Object The vascular terminations (vascular buds) in the bone–disc junction area are structurally very similar to cartilage. In all previous studies to date, however, the roles of cartilage canals and vascular buds were mainly discussed using histological and transparent sections but not electron microscopic sections. The purpose of this study was to clarify the ultrastructure of the vascular bud seen in the bone–disc junction in comparison to the cartilage canal. Methods Japanese white rabbits from 2 days to 6 months of age were used in this study. The bone–disc junctions were examined by microangiogram and light and electron microscopy, and morphological changes and their association with the age of the animals were noted. Results The fine structure of the vascular bud was similar to that of the cartilage canal that nourished the growing cartilage. They were composed of arteries, veins, capillaries, cells resembling fibroblasts, and macrophages. The capillaries in the cartilage canal were all the fenestrated type. Vascular buds were seen over the entire bone–cartilage interface, with maximum density in the area related to the nucleus pulposus. They projected into the bone–disc junction area from the vertebral body contacting the cartilaginous endplate directly. Conclusions The results of this study clarify the formation process and ultrastructure of the vascular bud seen in the bone–disc junction. The authors found a strong structural resemblance between the vascular bud and the cartilage canal and hypothesize that the immature cells seen surrounding the cartilage canal and vascular bud represent a common precursor for the 3 main types of connective tissue cells seen during early vertebral development.

Acute patellar dislocation is a common injury that occurs during a variety of activities and accounts for 2–3% of knee injuries.1 Since 1990, especially over the past 5 years, more attention has focused on the medial patellofemoral ligament (MPFL) of the medial retinacular components. In several biomechanical studies, the MPFL has proved to be the primary restraint to lateral translation of the patella among the medial patellar stabilisers, and many clinical findings have shown that acute patellar dislocation is associated with MPFL injuries at a high rate.2–9 In 1999, Nomura6 classified MPFL injury in acute patellar dislocation into two types, avulsion tear and substantial tear. An avulsion tear is a detachment-type injury limited to the undersurface of the MPFL at the femoral attachment. It was suspected that this injury may result from a specific structure of the MPFL at the femoral attachment. This study was to evaluate the histological findings of the avulsion tear-type injury of the MPFL in acute patellar dislocation. A 23-year-old woman sustained initial dislocation of the left knee while climbing a step (case 1). Five days after the injury, we …

✓The authors describe the clinical course and treatment of a patient with cleidocranial dysplasia in whom spastic myelopathy developed due to atlantoaxial subluxation. This 27-year-old woman with cleidocranial dysplasia and a history of atlantoaxial subluxation presented with spastic myelopathy. Surgery was performed twice for cervical myelopathy and atlantoaxial subluxation, including laminectomy at the atlas and cervicooccipital fusion in which the Luque rod system was used, as well as C1–2 fusion via the transpharyngeal route. Solid bone fusion was achieved by 7 months postsurgery. Postoperative magnetic resonance imaging studies demonstrated that spinal cord compression was relieved, but atrophy persisted. At 2 years postsurgery there was no neurological disease progression, but spasticity persisted. The patient could walk with a cane. Cleidocranial dysplasia is an extremely rare cause of myelopathy in patients with atlantoaxial subluxation; the authors know of only two reports of this condition. When managing cleidocranial dysplasia, the practitioner should always be aware that atlantoaxial subluxation may be the cause of cervical myelopathy.

The human leukocyte antigen (HLA) region has been implicated in the pathogenesis of inflammatory bowel disease (IBD), which is classified into Crohn’s disease (CD) and ulcerative colitis (UC). Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene was reported. BTNL2 is located in the HLA region and its messenger RNA is expressed most abundantly in the intestine. In this study, we performed a case–control association study of BTNL2 in the Japanese patients with IBD and performed linkage disequilibrium (LD) analysis between BTNL2 and HLA-DRB1. We analyzed eight polymorphisms selected after direct sequencing and found that none of the polymorphisms were associated with the Japanese CD cohort. In contrast, five polymorphisms were significantly associated with UC, especially three single nucleotide polymorphisms (BTNL2_19, BTNL2_22 and BTNL2_23) were associated as a haplotype. The most frequent haplotype (GGC haplotype) was a low-risk haplotype (P= 0.000052), whereas the other TCT haplotype was a high-risk haplotype (P= 0.0000085). Among the eight polymorphisms, the strongest association with UC was found in BTNL2_19 (OR = 1.92, P= 0.0000035). As expected, the BTNL2_19-T allele showed strong LD with DRB1*1502 (D′= 0.92). When BTNL2_19 was tested as conditional on the DRB1*1502 carrier status, the significant association disappeared, suggesting that the association was because of its strong LD with DRB1*1502. We conclude that BTNL2 does not contribute to the susceptibility to Japanese CD but is associated with Japanese UC because of the strong LD with HLA-DRB1*1502. The strong LD between BTNL2 and HLA-DRB1 raises another issue about the potential role of BTNL2 in other diseases associated with HLA-DRB1.

Study design The aim of this study is to investigate changes in lumbar motor neurons induced by mechanical nerve root compression using an in vivo model. This study is to investigate the changes of lumbar motor neuron induced by mechanical nerve root compression using in vivo model. Objectives The effect of axonal flow disturbance induced by nerve root compression was determined in lumbar motor neuron. Summary of background data The lumbar motor neuron should not be overlooked when considering the mechanism of weakness, so it is important to understand the morphologic and functional changes that occur in motor neurons of the spinal cord as a result of nerve root compression. However, few studies have looked at changes of neurons within the caused by disturbance of axonal flow, the axon reaction, chromatolysis, and cell death as a result of mechanical compression of the ventral root. Methods In mongrel dogs, the seventh lumbar nerve root was compressed for 1 week, or 3 weeks using a clip. Morphologic changes of the motor neurons secondary to the axon reaction were examined by light and electron microscopy. Results Light and electron microscopy showed central chromatolysis of motor neurons in the lumbar cord from 1 week after the start of compression. After 3 weeks, some neurons undergoing apoptosis were seen in the ventral horn. Conclusion It is important to be aware that, in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression but also extends to the motor neurons within the lumbar cord as a result of the axon reaction. Patients with weakness of lower leg should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.

Objective In recent years, percutaneous laser disc decompression (PLDD) has become a routine surgical procedure because it can be performed under local anesthesia and is minimally invasive. However, there is a risk of nerve root and endplate injury owing to heat generated by laser irradiation during PLDD. We recently performed salvage surgery on a patient with heat injury to the L5 nerve root that developed after PLDD. Clinical presentation One month before presenting to our hospital, the patient underwent two sessions of PLDD for lumbar vertebral disk herniation at another institution. The patient developed worsening sciatica, as well as bowel and urinary problems after the PLDD. Intervention We performed salvage surgery after PLDD. The intraoperative findings in the present case included carbon spots in the dura mater of the nerve root and a disc herniation strongly adherent to the nerve roots. These findings indicate that the area adjacent to the nerve roots was damaged by excessive heat during laser irradiation. Conclusion When salvage surgery is performed after a PLDD procedure, disc and nerve root injuries owing to laser heat energy must be considered.

Su1487 Impact of Diabetes Mellitus on Postoperative Bleeding After Endoscopic Submucosal Dissection for Esophago-Gastric Tumor Yu Sasaki*, Yasuhiko Abe, Kazuya Yoshizawa, Takeshi Sato, Eiki Nomura, Daisuke Iwano, Makoto Yagi, Kazuhiro Sakuta, Rika Shibuya, Naoko Mizumoto, Nana Kanno, Shoichi Nishise, Yoshiyuki Ueno Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan Metabolic syndrome has been more widespread due to a rise in obesity rates among adults. We have thus increased opportunities to perform endoscopic submucosal dissection (ESD) for patients with esophago-gastric tumors complicated with type 2 diabetes (DM), hypertension (HT) and hyperlipidemia (HL). These patients are at risk for atherosclerosis and often taking antithrombotic agents, which are likely to be risk for bleeding in ESD. However, the potential risk of post-ESD bleeding in these patients was still unclear. Therefore, we investigated whether DM, HT and HL were associated with increased risk of bleeding post-ESD. Methods: 185 consecutive patients, who underwent ESD for 28 esophageal tumors and 159 gastric tumors at Yamagata University Hospital, between January 2009 and December 2011, were enrolled and reviewed retrospectively. ESD was performed by using standard techniques. Antithrombotic agents were interrupted preoperatively with/without using heparin as a bridge therapy, and were restarted when hemostasis was confirmed by second-look endoscopy. All patients were treated with proton pump inhibitors after ESD. Post-ESD bleeding was defined as an episode of any of the following: overt hematemesis/hematochezia; a drop of hemoglobin O2 g/dL; or requirement of endoscopic hemostasis and/or transfusion. The risk of post-ESD bleeding was evaluated by logistic regression analysis. Results: Post-ESD bleeding occurred in 8 patients (4.3%). In comparison with the nonbleeding group, individuals in the postESD bleeding group have had a significantly higher proportion of DM (62.5% vs. 14.8%, p!0.01) and antithrombotic agents usage (50% vs. 15.3%, p Z 0.03). There were no significant differences between the groups in the proportion of male, HT (p Z 0.07) and HL (p Z 0.06). Similarly, no differences were observed in median age, BMI, blood pressure, PT-INR, APTT, counts of platelets and specimen diameter. Univariate analysis indicated that DM (OR, 9.6; 95%CI, 2.16-42.6) had a greater odds ratio (OR) for post-ESD bleeding than antithrombotic agents usage (OR, 5.5; 95%CI, 1.31-23.5). Multivariate-adjusted ORs of post-ESD bleeding for the bleeding group compared with the nonbleeding group were 7.7 (95%CI, 1.68-35.8), 4.1 (95%CI, 0.91-19.2) and 29.5 (95%CI, 5.00-174) for DM, antithrombotic agents usage and DM with antithrombotic agents usage, respectively. Furthermore, none of the patients had thromboembolism. In conclusion, this study suggests that DM is associated with the risk of postoperative bleeding after esophago-gastric ESD. Given that patients with DM carry more comorbidities, ESD should be done more carefully for these patients. To prevent post-ESD bleeding, further studies will be needed to confirm our findings and to elucidate the underlying the mechanisms.

Growing evidence suggests that metabolic syndrome is not only a cluster of risk factors for cardiovascular disease and type 2 diabetes, but also for some cancer including a colorectal cancer. We have previously shown that insulin resistance, an increased visceral fat, hypoadiponectinemia and low-grade systemic inflammation assessed by serum IL-6 levels are linked to the risk of colorectal adenoma. Recently, it has been reported that chemerin, as a novel adipokine, can act as a chemoattractant for immune cells. And obesity, insulin resistance and inflammation have shown to have elevated serum levels of chemerin. However, the role of chemerin in human colorectal adenoma is still unknown. Therefore, we investigated the relationship between serum chemerin levels and the incidence of colorectal adenoma. Methods: We conducted a total colonoscopy-based cross-sectional case-control study. 76 male individuals with an endoscopically diagnosed colorectal adenoma were enrolled along with 72 age-matched male for our control group. Both cohort groups underwent health checkups, between 2007 and 2009, at Tohoku Central Hospital. Serum levels of chemerin were measured in samples of venous blood obtained from the participants after an overnight fast. The risk for colorectal adenoma was evaluated by logistic regression analysis. Results: In the colorectal adenoma group, the mean levels of serum insulin, fasting, plasma glucose, value of HOMA-IR and HbA1c were higher than those in the control group. There were no differences between the groups in the proportions of current smokers, alcohol consumers, mean BMI, bold pressure and serum triglyceride. The mean concentration of serum chemerin was significantly higher in the colorectal adenoma group than in the control group (791±354 ng/ml vs. 538±401 ng/ml, p

Patella aplasia-hypoplasia is a rare condition characterized by the congenital absence or marked reduction of the patellar bone. It is well known that patella aplasia-hypoplasia occurs in nail-patella syndrome, small patella syndrome, and several other syndromes. However, isolated patella aplasia-hypoplasia without associated clinical or radiologic anomalies, first described by Kutz in 1949, is an extremely rare condition. This report describes 12 years' follow-up after medial patellofemoral ligament reconstruction surgery performed for bilateral recurrent patellar dislocation in a 29-year-old patient with isolated patella aplasia-hypoplasia. The patient had no radiographic findings of elbow abnormalities, exostoses of the ilia, or abnormal ossification of the ischiopubic junction. The right patella was severely subluxated, and the left patella was mildly subluxated. The preoperative Kujala score was 28 points for the right patella and 23 points for the left. Medial patellofemoral ligament reconstruction, wide lateral release, and patellaplasty with multiple drilling were done in July 1993 for the left knee and in August 1993 for the right. At 12 years' follow-up, the Kujala score was 68 points for the right patella and 73 points for the left, and the patient was satisfied with the result. Magnetic resonance images showed both patellae without subluxation and bulky regenerated ligaments.

Individuals with inflammatory bowel disease (IBD) are at increased risk of developing gastrointestinal cancer. Here, we have tested the possibility that chronic inflammation could trigger mutations. For this, we have used IL-10-deficient (IL-10 -/- ) mice, which spontaneously develop intestinal inflammation, in combination with a transgenic gpt gene and redlgam gene (gpt + IL-10 -/- ), which is a well-characterized mutation reporter locus. The total mutation frequency in the colon of gpt + IL-10 -/- mice was about five times higher than that in normal gpt + IL-10 +/+ mice. In the particular case of G:C to A:T transitions, the frequency of mutations in gpt + IL-10 -/- mice was 4.1 times higher than that in control mice. Interestingly, the frequency of small deletions and insertions was also strikingly increased (∼10 times). The majority of the deletion or insertion mutations were observed in the monotonous base runs or adjacent repeats of short tandem sequences. In contrast, the frequency of large deletions, detected by loss of the Spi marker present in the red/gam transgene, was similar among the mouse strains. Finally, as a control, the mutation frequency in non-inflamed tissues, such as the liver, were similar between gpt + IL-10 -/- mice and gpt + IL-10 +/+ mice. Our data demonstrate that the chronic inflammatory environment in the colon promotes the generation of mutations.

Population-specific differences in the genetic susceptibility to inflammatory bowel disease (IBD) are indicated by the fact that Crohn's disease (CD) in Japanese patients does not have any of the common CARD15 variants that are associated with CD in Caucasians. Recently, the disease-causing mutation in the IBD5 haplotype was identified. The TC haplotype, composed of L503F in SLC22A4 and -207G/C in SLC22A5 promoters, was reported to alter the function of the organic cation transporter and to be associated with CD in Caucasians. To determine whether the TC haplotype is also associated with IBD in a Japanese population, we genotyped L503F and -207G/C variants in Japanese subjects. Furthermore, we also performed a case-control association study with all representative single nucleotide polymorphisms (SNPs) in IBD5 using previous information of linkage disequilibrium extension reported in Japanese patients to determine whether there were variants in IBD5 specifically associated with IBD in Japanese patients.A total of 758 Japanese individuals, 241 patients with CD, 247 patients with ulcerative colitis (UC) and 270 healthy controls, were analyzed in this study. Genotyping for SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis.We found L503F and -207G/C to be very rare (1% frequency) in CD, UC and HC in the Japanese population. Furthermore, we also found that none of the representative SNPs in IBD5 was associated with CD or UC in the Japanese subjects.In contrast to Caucasians, IBD5 is not a major component of the susceptibility to IBD in the Japanese population.

In a total of 15 knees from 15 patients undergoing medial patellofemoral ligament reconstruction using an artificial substitute and a medial retinaculum slip coverage for recurrent patellar dislocation, the reconstructed ligaments were histologically evaluated using hematoxilin-eosin and elastic van Gieson stains. The artificial substitute was a mesh-type Leeds–Keio ligament. The mean age of the patients at the time of surgery was 20 years (range; 13–38 years). The mean interval from initial reconstruction to gathering was 53 months (range; 11–109 months). In the tissue over the artificial ligament, longitudinally aligned collagen fiber bundles with spindle-shaped nuclei were formed in all specimens except one specimen of 11 months postsurgery, but it seemed to be mature ligament only in specimens more than 60 months postsurgery. The tissue inside the artificial ligament was immature as a whole in all specimens, although 13 out of the 15 specimens had regularly aligned collagen fiber bundles slightly or in some portions.

The remnants of the medial patello-femoral ligament (MPFL) of 67 knees, 18 with acute patellar dislocation and 49 with chronic patellar dislocation, were studied. The MPFL injuries of the acute cases were categorised into 2 groups: an avulsion tear type and a substantial tear type. The chronic cases were put into 3 groups: those with loose femoral attachment (9 knees), those with scar tissue formation or abnormal scar branch formation (29 knees), and those with no evidence or continuity of the ligament (absent type) (11 knees). It is concluded that incompetence of the medial patello-femoral ligament is a major factor in the occurrence of recurrent patellar dislocation and/or an unstable patella following an acute patellar dislocation.

9, respectively) were cultured on the rat or human subcutaneous adipose tissue-embedded or -nonembedded gel. Adipose tissue promoted the expression of the growth markers, Ki67 antigen and 24 h-labeling bromodeoxyuridine (BrdU) in the cancer cell types, whereas it inhibited that of the apoptosis marker, cleaved caspase 3. Adipose tissue promoted the basal and superficial expression of the differentiation markers, p63 and involucrin, respectively, within the epithelial layer formed by cancer cell types. Adipose tissue accelerated the invasion of cancer cell types into the gel, together with increased expression of filamin A, laminin-5 and membrane type 1-matrix metalloproteinase (MT1-MMP), and with decreased display of E-cadherin. Adipose tissue promoted the expression of mitogen-activated protein kinase (MAPK: Raf-1, MEK-1 and pERK-1/2) and phosphoinositide 3-kinase-Akt (PI3K-Akt: PTEN, p-4E-BP1 and S6) pathways, and insulin-like growth factor-I receptor (IGF-IR) in the cell types, while it decreased that of the molecularly targeted protein, human epidermal growth factor receptor 2 (HER2). Adipose tissue did not affect the expression of the prostaglandin biosynthetic enzyme cyclooxgenase-2 (COX-2) in the cell types. The COX-2 inhibitor celecoxib did not affect the morphology and invasion of the cell types. Cancer cell types in turn decreased adiponection, leptin and registin production in adipose tissue. The data suggest, first, that adipose tissue may influence the progression of esophageal cancer with the increased growth/invasion and the decreased apoptosis through MAPK, PI3K-Akt and IGF-IR up-regulation in a COX-2-independent way, although adipose tissue seems to induce the differentiation of cancer cells; second, that adipose tissue may adversely affect the HER2targeted therapy; and third, that the cancer cells may affect adipokine production of adipose tissue. Collectively, we conclude that adipose tissue may be involved in the progression of esophageal cancer under adipose tissue-cancer cell interaction.

Objective Stress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake. Design A retrospective cohort study. Settings 13 hospitals in Japan. Participants 546 ulcerative colitis (UC) and 357 Crohn's disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patient's clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records. Primary outcome We evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined ‘active’ as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD). Results Among the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p

We present an instructive case of habitual left patellar dislocation in which the patella had appeared odd due to lateral tilt relative to contralateral side, but had been radiologically confirmed to be on the trochlea at 1 year prior to the referral. An 11-year-old girl presented to our hospital 2 years after the left patella had dislocated with a 'giving way' when cutting to the left. Our physical and radiological examinations confirmed that the left patella was laterally tilted in the patellar groove with the knee in extension but was dislocated in flexion beyond 45°. In spite of these findings, she had been untreated at the previous hospital since all plain X-rays, including a skyline patellar view, had failed to demonstrate the dislocation. Consequently, in addition to reconstruction of medial patellofemoral ligament, she had to undergo a lateral retinacular release, which might have been unnecessary if treated earlier. This case illustrates that first-time patellar dislocation can gradually lead to habitual dislocation subsequently, and that cautious physical examinations in regard to patella tracking are essential since radiological examinations do not always reveal the pathophysiology of patellar instability.