The Comparison of Clinical Outcomes in Elderly (≥75 Years) and Non-Elderly (<75 Years) Patients with Acute Cholangitis Due to Choledocholithiasis.

Background and Objectives: Acute cholangitis may be fatal, particularly in elderly patients. According to the Tokyo Guidelines 2018, those aged ≥75 years are classified as moderate (Grade II) severity. However, it has not been established whether age itself is the deciding factor of poor outcomes. We studied the impact of old age (≥75 years) on the mortality and morbidity of acute cholangitis due to choledocholithiasis. Materials and Methods: We retrospectively examined 260 patients with calculous acute cholangitis who had undergone biliary drainage. Patients were divided into two groups: elderly (≥75 years) and non-elderly (<75 years). We aimed to compare organ dysfunction, in-hospital mortality, intensive care unit (ICU) hospitalization, and the severity of acute cholangitis. Results: Of 260 patients, 134 (51.5%) were in the elderly group and 126 (48.5%) were in the non-elderly group. The mean age was 72.3 ± 14.4 years, and 152 (58.5%) were men. The elderly patients showed a higher incidence of shock (12.7% vs. 4.8%, p = 0.029), respiratory dysfunction (7.5% vs. 0%, p = 0.002), and renal dysfunction (8.2% vs. 0.8%, p = 0.006) than the non-elderly patients. The overall in-hospital mortality rate was 2.7%, with no significant differences between the elderly and the non-elderly (4.5% vs. 0.8%, p = 0.121). The incidence of severe acute cholangitis was significantly higher in the elderly group (26.9% vs. 9.5%, p < 0.001). However, there was no significant difference in the rates of ICU hospitalization (9.7% vs. 4%, p = 0.088) and lengths of hospital stay (LOS) (8.3 d vs. 7.1 d, p = 0.086). Conclusions: No difference was observed in the in-hospital mortality, ICU hospitalization, or LOS between the elderly (≥75 years) and the non-elderly (<75 years) with calculous acute cholangitis. However, severe acute cholangitis was significantly more frequent in elderly patients.

Safety and effectiveness of intra-articular injection of a highly cross-linked hyaluronic acid, LBSA0103 (Synovian): Results from a post-marketing surveillance study in South Korea.

This study aimed to assess the safety and effectiveness of the highly cross-linked hyaluronic acid-LBSA0103-in patients with knee osteoarthritis (OA) as per the prescribing information (PI) in South Korea. A total of 3,140 subjects aged ≥19 years were enrolled in this post-marketing surveillance (PMS) study from 2013 to 2019. The subjects received one or two injections of LBSA0103. The median duration of follow-up was 308 days. Adverse events (AEs), adverse drug reactions (ADRs), and serious AEs (SAEs) were monitored. Effectiveness was evaluated based on an index of effectiveness in accordance with the guidelines established by the Ministry of Food and Drug Safety and using a 100-mm visual analog scale (VAS) for weight-bearing pain. Overall, 250 subjects (7.96%) experienced 292 AEs and of these, unexpected AEs occurred in 114 subjects (3.63% [95% CI: 3.00-4.35]). Injection site pain was the most frequent AE reported by 81 subjects (2.58% [95% confidence intervals (CI): 2.05-3.20]). One hundred subjects experienced 108 ADRs (3.18% [95% CI: 2.60, 3.86]) and 15 unexpected ADRs were experienced by 13 subjects (0.41% [95% CI: 0.22-0.71]). Seventeen subjects experienced 22 SAEs (0.54% [95% CI: 0.32-0.87]) during the entire PMS period, and all were considered "unlikely" related to the study drug. Most AEs were mild in terms of severity and resolved during the study period. LBSA0103 was also effective in relieving symptomatic pain in knee OA patients. The condition in more than 80% of the subjects was considered to be improved when assessed by the investigators. LBSA0103 resulted in a significant reduction in the mean VAS score at 12 weeks after the first and second injections (24.79 (± 20.55) mm and 17.63 (±12.31) mm, respectively; p<0.0001). In conclusion, LBSA0103, used for the treatment of knee OA in a real-world setting, was well tolerated, with an acceptable safety profile and consistent therapeutic effect.

PPARδ Agonist Promotes Type II Cartilage Formation in a Rabbit Osteochondral Defect Model.

Osteoarthritis (OA) is a chronic degenerative joint disease accompanied by an inflammatory milieu that results in painful joints. The pathogenesis of OA is multifactorial, with genetic predisposition, environmental factors, and traumatic injury resulting in the direct or indirect loss of cartilage. The articular cartilage can also be damaged by direct focal traumatic injury. Articular cartilage provides a smooth, deformable bearing surface with a low coefficient of friction, increased contact area, and reduced contact stress. Articular type II hyaline cartilage lines the synovial joints and, when injured, has a limited ability for repair, except for the most superficial layers via diffusion from the synovial fluid, secondary to no blood supply, a complex structure, and a low metabolic rate. Restoring the articular surface can relieve pain and restore function. Although many strategies have been developed to regenerate type II collagen based on the extent of the lesion, surgical treatments are still evolving. The peroxisome proliferator-activated receptor delta (PPARδ) agonist and collagen treatment of mesenchymal stem cells (MSCs) enhance the chondrogenic capacity in vitro. We present a novel technique for cartilage restoration in a rabbit cartilage osteochondral defect model using a PPARδ agonist (GW0742)-infused 3D collagen scaffold to induce type II cartilage from MSCs.

Clinical Comparison of Medial Patellofemoral Ligament Reconstruction With or Without Tibial Tuberosity Transfer for Recurrent Patellar Instability.

BACKGROUND: No clear guidelines or widespread consensus has defined a threshold value of tibial tuberosity-trochlear groove (TT-TG) distance for choosing the appropriate surgical procedures when additional tibial tuberosity osteotomy (TTO) should be added to augment medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar instability. PURPOSE: To compare the clinical outcomes between MPFL reconstruction and MPFL reconstruction with TTO for patients who have patellar instability with a TT-TG distance of 15 to 25 mm. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively analyzed 81 patients who underwent surgical treatment using either MPFL reconstruction or MPFL reconstruction with TTO for recurrent patellar instability with a TT-TG distance of 15 to 25 mm; the mean follow-up was 25.2 months (range, 12.0-53.0 months). The patients were divided into 2 groups: isolated MPFL reconstruction (iMPFL group; n = 36) performed by 2 surgeons and MPFL reconstruction with TTO (TTO group; n = 45) performed by another 2 surgeons. Clinical outcomes were assessed using the Kujala score, Knee injury and Osteoarthritis Outcome Score, and Tegner activity score. Radiological parameters, including patellar height, TT-TG distance, patellar tilt, and congruence angle were compared between the 2 groups. Functional failure based on clinical apprehension sign, repeat subluxation or dislocation, and subjective instability and complications was assessed at the final follow-up. We also compared clinical outcomes based on subgroups of preoperative TT-TG distance (15 mm ≤ TT-TG ≤ 20 mm vs 20 mm < TT-TG ≤ 25 mm). RESULTS: All of the clinical outcome parameters significantly improved in both groups at the final follow-up (P < .001), with no significant differences between groups. The radiological parameters also showed no significant differences between the 2 groups. The incidence of functional failure was similar between the 2 groups (3 failures in the TTO group and 2 failures in the iMPFL group; P = .42). In the TTO group, 1 patient experienced a repeat dislocation postoperatively and 2 patients had subjective instability; in the iMPFL group, 2 patients had subjective instability. The prevalence of complications did not differ between the 2 groups (P = .410). In the subgroup analysis based on TT-TG distance, we did not note any differences in clinical outcomes between iMPFL and TTO groups in subgroups of 15 mm ≤ TT-TG ≤ 20 mm and 20 mm < TT-TG ≤ 25 mm. CONCLUSION: MPFL reconstruction with and without TTO provided similar, satisfactory clinical outcomes and low redislocation rates for patients who had patellar instability with a TT-TG distance of 15 to 25 mm, without statistical difference. Thus, our findings suggest that iMPFL reconstruction is a safe and reliable treatment for patients with recurrent patellar dislocation with a TT-TG distance of 15 to 25 mm, without the disadvantages derived from TTO.

Automatic Meniscus Segmentation Using Adversarial Learning-Based Segmentation Network with Object-Aware Map in Knee MR Images.

Meniscus segmentation from knee MR images is an essential step when analyzing the length, width, height, cross-sectional area, surface area for meniscus allograft transplantation using a 3D reconstruction model based on the patient's normal meniscus. In this paper, we propose a two-stage DCNN that combines a 2D U-Net-based meniscus localization network with a conditional generative adversarial network-based segmentation network using an object-aware map. First, the 2D U-Net segments knee MR images into six classes including bone and cartilage with whole MR images at a resolution of 512 × 512 to localize the medial and lateral meniscus. Second, adversarial learning with a generator based on the 2D U-Net and a discriminator based on the 2D DCNN using an object-aware map segments the meniscus into localized regions-of-interest with a resolution of 64 × 64. The average Dice similarity coefficient of the meniscus was 85.18% at the medial meniscus and 84.33% at the lateral meniscus; these values were 10.79%p and 1.14%p, and 7.78%p and 1.12%p higher than the segmentation method without adversarial learning and without the use of an object-aware map with the Dice similarity coefficient at the medial meniscus and lateral meniscus, respectively. The proposed automatic meniscus localization through multi-class can prevent the class imbalance problem by focusing on local regions. The proposed adversarial learning using an object-aware map can prevent under-segmentation by repeatedly judging and improving the segmentation results, and over-segmentation by considering information only from the meniscus regions. Our method can be used to identify and analyze the shape of the meniscus for allograft transplantation using a 3D reconstruction model of the patient's unruptured meniscus.

Magnetic Resonance Imaging Evaluation of Physeal Violation in Adolescents After Transphyseal Anterior Cruciate Ligament Reconstruction.

PURPOSE: To quantify and compare the amount and location of physis violation of the distal femur and proximal tibia after transphyseal anterior cruciate ligament (ACL) reconstruction in skeletally immature patients. METHODS: This study included 19 patients with open physes of the distal femur and proximal tibia who underwent ACL reconstruction with tibialis anterior allografts. Physeal tunnel volume and location on the growth plate, as well as obliquity to the growth plate, were measured by 3-dimensional postoperative magnetic resonance imaging of the distal femur and proximal tibia. RESULTS: The percentage of physeal violation (ratio of the tunnel to the entire growth plate area) was similar for the distal femur and proximal tibia (3.95% vs 3.65%, P = .582). There were no differences in tunnel obliquity to the growth plate in the coronal (56.1° vs 71.6°, P = .061) and sagittal (85.9° vs 74.9°, P = .092) planes. The distal femoral tunnel was located 6.2% (17.2% vs 23.4%, P = .001) more peripherally in the anteroposterior direction and 9.7% (27.1% vs 36.8%, P < .001) more peripherally in the mediolateral direction than was the tibial tunnel. CONCLUSIONS: The mean percentages of physeal violation of tunnel creation during ACL reconstruction in adolescent patients were 3.95% for the distal femur and 3.65% for the proximal tibia. Moreover, femoral tunnels were located more peripherally on the growth plate than were tibial tunnels, in both the anteroposterior and mediolateral directions. LEVEL OF EVIDENCE: Level IV, case series.

Double-bundle anterior cruciate ligament reconstruction with split Achilles allograft and single tibia tunnel for small ACL tibial footprint : technical note with clinical results.

PURPOSE: We describe a surgical technique of double-bundle ACL reconstruction with a single tibia tunnel and report the clinical outcome. METHODS: The Achilles tendon portion was split longitudinally into two separate bundles, namely, an anteromedial (AM) bundle with 7-8 mm diameter and a posterolateral (PL) bundle with 4-6 mm diameter. The central portion of the calcaneal bone plug was prepared with a diameter of 10 mm and a length of 30 mm. For the femoral tunnel preparation, we preferred inside out target through an accessory anteromedial portal for an approach to native ACL footprint and outside in reaming through separate incision on the lateral aspect of distal thigh to prevent cartilage injury of medial femoral condyle. 10 mm diameter of single tibia tunnel was prepared at the central portion of ACL tibial footprint. After graft passage from tibia to femoral side, fixation of calcaneal bone plug within the tibia tunnel was performed using two bioabsorbable cross pins. Then, AM bundle was first fixed at 45° of flexion while the PL bundle was fixed at 10° of flexion using bioabsorbable interference screws and augmented staples. Clinical results of 22 patients (18 males and 4 females, average age 30.7 years) who underwent double-bundle anterior cruciate ligament (ACL) reconstruction with this technique were evaluated. RESULTS: At an average follow-up of 30 months, there was significant improvement of the Lysholm knee score, the 2,000 IKDC subjective knee score, the median Tegner activity score and the side-to-side difference. According to the 2,000 IKDC knee examination form, the grade rated as normal in seven patients, nearly normal in 14 patients and abnormal in one patient at the latest follow-up. There were no postoperative complications and revisional surgeries. CONCLUSIONS: Split Achilles allograft and single tibia tunnel technique for double-bundle ACL reconstruction can be an alternative option for patients with small tibial insertion sites. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Anatomical versus non-anatomical single bundle anterior cruciate ligament reconstruction: a cadaveric study of comparison of knee stability.

BACKGROUND: The purpose of this study was to compare the initial stability of anatomical and non-anatomical single bundle anterior cruciate ligament (ACL) reconstruction and to determine which would better restore intact knee kinematics. Our hypothesis was that the initial stability of anatomical single bundle ACL reconstruction would be superior to that of non-anatomical single bundle ACL reconstruction. METHODS: Anterior tibial translation (ATT) and internal rotation of the tibia were measured with a computer navigation system in seven pairs of fresh-frozen cadaveric knees under two testing conditions (manual maximum anterior force, and a manual maximum anterior force combined with an internal rotational force). Tests were performed at 0, 30, 60, and 90 degrees of flexion with the ACL intact, the ACL transected, and after reconstruction of one side of a pair with either anatomical or non-anatomical single bundle ACL reconstruction. RESULTS: Under manual maximal anterior force, both reconstruction techniques showed no significant difference of ATT when compared to ACL intact knee state at 30° of knee flexion (p > 0.05). Under the combined anterior and internal rotatory force, non-anatomical single-bundle ACL reconstruction showed significant difference of ATT compared to those in ACL intact group (p < 0.05). In contrast, central anatomical single bundle ACL reconstruction showed no significant difference of ATT compared to those in ACL intact group (p > 0.05). Internal rotation of the tibia showed no significant difference in the ACL intact, the ACL transected, non-anatomical reconstructed and anatomical reconstructed knees. CONCLUSIONS: Anatomical single bundle ACL reconstruction restored the initial stability closer to the native ACL under combined anterior and internal rotational forces when compared to non-anatomical ACL single bundle reconstruction.

Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum.

Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal L-glutamate (L-Glu) and 5'-inosine monophosphate (IMP) synergistically increases duodenal HCO3- secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3- secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3- secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. L-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without luminal perfusion (0.1 mM) or intravenous (iv) injection (3 µmol/kg) of the DPPIV inhibitor NVP728. The loop was also perfused with a selective TGR5 agonist betulinic acid (BTA, 10 µM) or the non-bile acid type TGR5 agonist 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide (CCDC; 10 µM). DPPIV activity visualized by use of the fluorogenic substrate was present on the duodenal brush border and submucosal layer, both abolished by the incubation with NVP728 (0.1 mM). An iv injection of NVP728 enhanced L-Glu/IMP-induced HCO3- secretion, whereas luminal perfusion of NVP728 had no effect. BTA or CCDC had little effect on HCO3- secretion, whereas NVP728 iv markedly enhanced BTA- or CCDC-induced HCO3- secretion, the effects inhibited by a GLP-2 receptor antagonist. Coperfusion of the TGR5 agonist enhanced L-Glu/IMP-induced HCO3- secretion with the enhanced GLP-2 release, suggesting that TGR5 activation amplifies nutrient sensing signals. DPPIV inhibition potentiated luminal L-Glu/IMP-induced and TGR5 agonist-induced HCO3- secretion via a GLP-2 pathway, suggesting that the modulation of the local concentration of the endogenous secretagogue GLP-2 by luminal compounds and DPPIV inhibition helps regulate protective duodenal HCO3- secretion.

Umami receptor activation increases duodenal bicarbonate secretion via glucagon-like peptide-2 release in rats.

Luminal nutrient chemosensing during meal ingestion is mediated by intestinal endocrine cells, which regulate secretion and motility via the release of gut hormones. We have reported that luminal coperfusion of L-Glu and IMP, common condiments providing the umami or proteinaceous taste, synergistically increases duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers, taste receptor type 1, member 1 (T1R1)/R3. We hypothesized that glucose-dependent insulinotropic peptide (GIP) or glucagon-like peptide (GLP) is released by duodenal perfusion with L-Glu/IMP. We measured DBS with pH and CO(2) electrodes through a perfused rat duodenal loop in vivo. GIP, exendin (Ex)-4 (GLP-1 receptor agonist), or GLP-2 was intravenously infused (0.01-1 nmol/kg/h). l-Glu (10 mM) and IMP (0.1 mM) were luminally perfused with or without bolus intravenous injection (3 or 30 nmol/kg) of the receptor antagonists Pro(3)GIP, Ex-3(9-39), or GLP-2(3-33). GIP or GLP-2 infusion dose-dependently increased DBS, whereas Ex-4 infusion gradually decreased DBS. Luminal perfusion of l-Glu/IMP increased DBS, with no effect of Pro(3)GIP or Ex-3(9-39), whereas GLP-2(3-33) inhibited L-Glu/IMP-induced DBS. Vasoactive intestinal peptide (VIP)(6-28) intravenously or N(G)-nitro-L-arginine methyl ester coperfusion inhibited the effect of L-Glu/IMP. Perfusion of L-Glu/IMP increased portal venous concentrations of GLP-2, followed by a delayed increase of GLP-1, with no effect on GIP release. GLP-1/2 and T1R1/R3 were expressed in duodenal endocrine-like cells. These results suggest that luminal L-Glu/IMP-induced DBS is mediated via GLP-2 release and receptor activation followed by VIP and nitric oxide release. Because GLP-1 is insulinotropic and GLP-2 is intestinotrophic, umami receptor activation may have additional benefits in glucose metabolism and duodenal mucosal protection and regeneration.

Importance of independent measurement of width and length of lateral meniscus during preoperative sizing for meniscal allograft transplantation.

BACKGROUND: Successful meniscus transplantation depends on an accurate sizing of the meniscal allograft. Although accurate sizing of the meniscal allograft is crucial during meniscus transplantation, the accuracy of meniscal measurement methods is still in debate. PURPOSE: This study was undertaken to evaluate the relationship between the width and length of the lateral meniscus. These anatomic dimensions were also evaluated in the context of the patient's height, weight, gender, and body mass index (BMI). STUDY DESIGN: Descriptive laboratory study. METHODS: Ninety-one samples of fresh lateral meniscus were obtained during total knee arthroplasty. The samples were obtained carefully without injuring the meniscus itself and the bony attachment sites. For each lateral meniscus, the anatomic dimensions (width [LMW] and length [LML]) were recorded. The height, weight, gender, and BMI of the patients were also recorded. The Pearson correlation and multivariate and linear regression analysis were applied for each variable. The accuracy was defined as those measures that fell within 10% of the original size. A P value ≤ .05 was considered significant. RESULTS: The mean LMW was 30.7 mm (standard deviation [SD] = 3.5) and 27.0 mm (SD = 2.6) for men and women, respectively. The mean LML was 33.7 mm (SD = 4.3) and 30.8 mm (SD = 2.6) for men and women, respectively. Thirty-nine samples (42.5%) showed LMW measurements within a 10% difference of LML, whereas 50 samples (55%) showed an LMW greater than a 10% difference of LML. Although there were correlations between LML with LMW in men and correlations between weight and LMW with LML in women, the accuracy for the derived linear regression formulas was 3%, 9%, and 12%, respectively. CONCLUSION: The length cannot be predicted accurately from the width of the lateral meniscus. The height, weight, gender, and BMI failed to estimate the dimensions of the lateral meniscus. Therefore, it is essential to measure the width and length separately and match it with the allograft with other size measuring methods. CLINICAL RELEVANCE: This study emphasizes the importance of measuring the width and length of the lateral meniscus independently during preoperative sizing for a meniscal allograft transplantation procedure. The height, weight, gender, and body mass index may not be reliable parameters for estimating the size of the meniscus.

Anterior and posterior knee laxity in a young adult Korean population.

PURPOSE: The purposes of this study were (1) to determine normal anterior and posterior knee laxity in a healthy young adult (20-30 years old) Korean population, (2) to compare knee laxity between the male and female populations, (3) to investigate whether generalized joint laxity affects anterior and posterior knee laxity, (4) to determine side-side differences between right and left knees, and thus, to determine normal values of side-side differences. METHODS: Normal values of anterior and posterior knee laxity were measured in 100 healthy volunteers (50 men and 50 women) aged between 20 and 30 years. Stress radiography using a Telos device was performed in 20 and 70° of knee flexion for 134N anterior and posterior loads. Anterior and posterior tibial displacements relative to the femur condyle were measured using a computerized system. RESULTS: In the 100 subjects (200 knees), anterior knee laxity was greater at 20° of flexion with a mean of 4.9 ± 2.3 mm (P < 0.05) and posterior knee laxity was greater at 70° of flexion with a mean of 4.6 ± 2.7 mm (P < 0.05). The mean side-side difference was 1.4 ± 0.9 mm (range, -3 to +3). Women had greater anterior laxity (P < 0.05) than men at both 20 and 70° of flexion, but posterior laxity was not different (ns). Generalized joint laxity was greater in women compared to men (P < 0.05). Subjects with generalized joint laxity had greater laxity than normal populations in both 20 and 70° of flexion (P < 0.05). Side-side differences between right and left knees were not significantly different in women and men or between subjects with normal and generalized joint laxity (ns). CONCLUSIONS: This study suggests that the Korean population exhibits a wide range of normal anterior and posterior knee laxity, but small side-side differences. Subjects with generalized laxity showed greater knee laxity than those without, but side-side differences were less than 3 mm in all subjects. Thus, clinical guideline that a side-side difference more than 3 mm of anterior knee laxity is abnormal can be applicable for the subjects with generalized laxity.

Endogenous luminal surface adenosine signaling regulates duodenal bicarbonate secretion in rats.

Luminal ATP increases duodenal bicarbonate secretion (DBS) via brush border P2Y receptors. Because ATP is sequentially dephosphorylated to adenosine (ADO) and the brush border highly expresses adenosine deaminase (ADA), we hypothesized that luminal [ADO] regulators and sensors, including P1 receptors, ADA, and nucleoside transporters (NTs) regulate DBS. We measured DBS with pH and CO(2) electrodes, perfusing ADO ± adenosine receptor agonists or antagonists or the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR(inh)-172 on DBS. Furthermore, we examined the effect of inhibitors of ADA or NT on DBS. Perfusion of AMP or ADO (0.1 mM) uniformly increased DBS, whereas inosine had no effect. The A(1/2) receptor agonist 5'-(N-ethylcarboxamido)-adenosine (0.1 mM) increased DBS, whereas ADO-augmented DBS was inhibited by the potent A(2B) receptor antagonist N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]-acetamide (MRS1754) (10 µM). Other selective adenosine receptor agonists or antagonists had no effect. The A(2B) receptor was immunolocalized to the brush border membrane of duodenal villi, whereas the A(2A) receptor was immunolocalized primarily to the vascular endothelium. Furthermore, ADO-induced DBS was enhanced by 2'-deoxycoformycin (1 µM) and formycin B (0.1 mM), but not by S-(4-nitrobenzyl)-6-thioinosine (0.1 mM), and it was abolished by CFTR(inh)-172 pretreatment (1 mg/kg i.p). Moreover, ATP (0.1 mM)-induced DBS was partially reduced by (1R,2S,4S,5S)-4-2-iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (MRS2500) or 8-[4-[4-(4-chlorophenzyl)piperazide-1-sulfonyl)phenyl]]-1-propylxanthine (PSB603) and abolished by both, suggesting that ATP is sequentially degraded to ADO. Luminal ADO stimulates DBS via A(2B) receptors and CFTR. ATP release, ecto-phosphohydrolases, ADA, and concentrative NT may coordinately regulate luminal surface ADO concentration to modulate ADO-P1 receptor signaling in rat duodenum.

Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus.

OBJECTIVES: This study was conducted to investigate the expression of cytokines and growth factors in disc specimens obtained from patients with herniated nucleus pulposus (HNP) and degenerated disc disease (DDD). DESIGN AND METHODS: MRI and Western blot analyses were performed to evaluate the levels of disc degeneration and the expression levels of cytokines and growth factors. RESULTS: The levels of TNF-alpha and IL-8 were significantly greater in the DDD group than in the HNP group, but no statistical differences were observed in the expression of IL-1beta, IL-6 and IL-12 between the HNP and DDD groups. In addition, the expression of TGF beta, VEGF and NGF was significantly higher in the DDD group than in the HNP group. CONCLUSION: The greater levels of cytokine and growth factor expression in the DDD group than in the HNP explain why discogenic patients usually have more severe back pain than patients with herniated discs.

Clearing a blind spot in knee arthroscopy: popliteal bursa.

Each arthroscopic portal to the knee has a blind area that cannot be inspected directly. In particular, visualization of the posterior compartment is difficult to access. Although arthroscopic procedures for the posterior compartment of the knee joint have been developed through posteromedial, posterolateral and posterior trans-septal portal, the popliteal bursa remains as an area that is difficult to access and manipulate. We report a surgical procedure that can examine one of the blind spots in knee arthroscopy, popliteal bursa.

Gene profiling of colonic serrated adenomas by using oligonucleotide microarray.

PURPOSE: The serrated pathway has been proposed as an important concept explaining the colorectal carcinogenesis. However, the key molecules of the serrated pathway which contribute to the formation of serrated polyp are still poorly understood. To elucidate the molecular genetic basis of the serrated pathway, we performed an initial oligonucleotide microarray to analyze the gene expression pattern of patients with colonic serrated adenomas. METHODS: Oligonucleotide microarrays containing 3,096 genes were used to compare individual gene profiles of serrated adenoma samples (n = 5) and normal mucosal samples obtained from colon in patients by colonoscopy. Three genes were further investigated by means of quantitative reverse transcription polymerase chain reaction (RT-PCR) for validation. The Significance Analysis of Microarray (SAM) package method was used to identify differentially expressed genes. RESULTS: Compared with normal colonic mucosa tissue, 73 genes were upregulated at least twofold, and 51 genes were downregulated by at least 50% in serrated polyp samples (approximately 3.6% of genes evaluated) with a p-value of less than 0.05. Moreover, some of the gene expression patterns observed were similar to those of previously reported in colorectal cancer, suggesting reinforcement of tendency to malignancy. Three genes (TNFRSF10A, BENE, RARA) with strongly significant expression intensities in the oligonucleotide microarray results were validated by quantitative RT-PCR. TNFRSF10A had upregulated expression patterns while BENE, RARA had downregulated expression pattern. CONCLUSION: Although our report presents only preliminary results, we think they provide important data regarding serrated adenomas not only to better define the precise mechanism of genetic changes involved as the main member in serrated pathway of colorectal carcinogenesis but also to yield practical information for identifying optimized diagnostic modalities.

An anatomical study of Morton's interdigital neuroma: the relationship between the occurring site and the deep transverse metatarsal ligament (DTML).

BACKGROUND: Using clinical and cadaver studies, we examined the relationship between the location of Morton interdigital neuromas and the surrounding structures, including the deep transverse metatarsal ligament (DTML), which has been suspected as a major causative factor in neuroma formation. METHODS: Seventeen fresh-frozen cadavers were evaluated to determine the relationship between the location of Morton interdigital neuromas and the DTML at two phases of the gait cycle with 60 degrees of metatarsophalangeal dorsiflexion and with 15 degrees of ankle dorsiflexion. We measured the distance from the bifurcation of the common digital nerve in the foot to the anterior margin of the DTML and also measured the length of the DTML itself. Clinically, we checked the location of the Morton interdigital neuroma and its length during surgery in 32 feet. RESULTS: In the second and third webspace, the mean distance from the bifurcation of the common digital nerve of the foot to the anterior margin of the DTML was 16.7 mm, 15.1 mm in the mid-stance position, and 15.9 mm and 14.6 mm in the heel-off position. The length of the second and third DTML averaged 12.8 mm and 10.6 mm. Clinically, all of the cases of Morton interdigital neuroma started at the bifurcation area of the common digital nerve, and the mean neuroma length was 7.5 mm (6 to 11). CONCLUSIONS: Morton interdigital neuromas were located more distally than the DTML in both the mid-stance and the heel-off stage during walking. The main lesion was located between the metatarsal head and the metatarsophalangeal joint and more distal than the DTML, questioning previous studies suggesting that the DTML is the major causative factor in development of Morton interdigital neuroma.

Modified inside-out technique for meniscal repair.

A modified technique of the inside-out suture for arthroscopic repair of meniscus is described. Although the conventional inside-out technique is a fine modality of a meniscal repair, it is difficult to perform vertical suture and to attain good coaptation and strong fixation. We introduce a modified inside-out suture, which uses a suture hook, a zone-specific cannula, and a specially designed looped needle for an efficient meniscal repair. The modified inside-out suture technique provides vertically oriented suture, excellent tissue coaptation, and firm fixation. We recommend this technique as an excellent method for repairing a tear in most parts of the meniscus, especially the posteromedial corner.