In vivo three-dimensional evaluation of the functional length of glenohumeral ligaments

Background

Glenohumeral ligaments play an important role in stabilizing the shoulder. However, it is impossible to know how they function in vivo during shoulder motion. To help elucidate this stabilizing role, we studied the in vivo three-dimensional kinematics of the normal shoulder joint using a markerless bone-registration technique.

Methods

Our technique utilized image registration to determine corresponding relations between several image volumes represented at different coordinates. Magnetic resonance images of 14 shoulder joints of seven healthy volunteers were acquired for seven isometric abduction orientations between 0° and 180°. We then calculated three-dimensional shortest path between the origin and insertion of each ligament based on anatomical study in each abduction orientation.

Findings

At 0° of abduction, the posterior band of the coracohumeral ligament displayed the maximum length. At 30° of abduction, the superior glenohumeral ligament displayed the maximum length. At 60° of abduction, the anterior band of the coracohumeral ligament and the middle glenohumeral ligament displayed the maximum length. At 120° of abduction, the anterior band of the inferior glenohumeral ligament displayed the maximum length.

Interpretation

Based on progressive abduction of the arm, each ligament had different pattern in change of length. At different arm orientation of abduction, each ligament displayed the maximum length. We think that each ligament might play an important role in stabilizing the shoulder at different arm orientation.     

Current situation and need for prevention of invasive pneumococcal disease and pneumococcal pneumonia in 6- to 64-year-olds in Japan

We conducted a systematic review of the literature to evaluate the reported epidemiology and burden of invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) among children and adults aged 6–64 years in Japan. Studies published from Japan between September 2009 and September 2019 and indexed in the MEDLINE/PubMed or ICHUSHI databases were evaluated. A majority of the studies reported overlapping age ranges, including children aged <6 years and adults aged >64 years. According to the national surveillance data, 19% of the IPD cases were patients aged 5–59 years, and an increasing trend in IPD cases was reported from 2013 to 2017. Comorbidities were consistent with those reported by the Advisory Committee on Immunization Practices. Deaths from IPD appeared to increase nearly 3-fold between 2013 and 2017. Overall, both 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) coverage was higher for IPD compared with PP. All the serotypes known to be prominent in Japan were also identified as common serotypes (3, 6A, 19A: PCV13 serotypes; 12F: outbreak serotype; 15A, 35B: drug-resistant serotypes). This systematic literature review suggests a substantial burden of IPD and PP in Japanese children and adults aged 6–64 years. The burden of comorbidities, hospitalizations, and mortality was particularly high among adults. Concerted pneumococcal vaccination strategies may help to reduce the incidence and burden of IPD and PP in this large proportion of the Japanese population.     

Psoitis and multiple venous thromboses caused by Panton Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus in a 12-year-old girl: A case report

Panton Valentine Leukocidin (PVL) is one of the many toxins produced by Staphylococcus aureus. In Japan, PVL-positive S. aureus strains are mainly methicillin-resistant S. aureus (MRSA). Data regarding PVL-positive methicillin-sensitive S. aureus (MSSA) are scarce. In this report, we describe a case of severe infection by PVL-positive MSSA. A 12-year-old healthy girl was admitted with high fever and pain in the lower back. Computed tomography revealed a diagnosis of psoitis and multiple venous thromboses. Blood cultures obtained after admission revealed infection with MSSA. Her fever continued despite adequate antibiotic therapy. On the fifth hospitalization day, she developed bladder dysfunction, and an abscess was noted near the third lumbar vertebra. She underwent an emergency operation and recovered. Bacterial analyses revealed that the causative MSSA was a PVL-producing single variant of ST8 (related to USA300clone), of sequence type 2149. PVL is known to cause platelet activation. This case demonstrates the need for detailed analyses of the causative strain of bacteria in cases of S. aureus infection with deep vein thrombosis, even in cases of known MSSA infection.     

Induction of autologous CD4- and CD8-mediated T-cell responses against acute lymphocytic leukemia cell line using apoptotic tumor cell-loaded dendritic cells

OBJECTIVE: Several studies have demonstrated that dendritic cells (DCs) pulsed with tumor lysate or apoptotic tumor cells can elicit effective T-cell responses. This technique does not require the identification of the tumor antigen or HLA haplotype of the patient. We applied this approach to induce HLA class I- and class II-restricted T-cell responses directed against autologous acute lymphocytic leukemia (B-ALL) cell line NH-1. METHODS: Autologous T cells were stimulated by apoptotic tumor cell-loaded DCs generated from a patient with ALL. The stimulated and expanded T cells were isolated into CD8(+) T-cell line and CD4(+) T-cell line, and each of them was examined as to their functions. RESULTS: Both CD8(+) and CD4(+) T-cell lines demonstrated cytotoxicity against NH-1 in an major histocompatibility complex-dependent manner. Finally, we established two independent CD4(+) T-cell clones restricted to HLA-DR. The CD4(+) T-cell line responded strongly to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) but not to autologous normal cells. Furthermore, the T-cell clones also responded to allogeneic EBV-LCLs and B-ALL cell lines in the context of the HLA-DRB1( *)04051 molecule. Interestingly, 293T and COS-7 cells, which had been transfected with the HLA-DRB1( *)04051, were also recognized by T-cell clones. CONCLUSION: These findings indicate that B-ALL has shared and strong immunogenic epitopes expressed on HLA class II molecules, the expression of which is limited to immortalized cells. These data suggest that vaccinations using DCs loaded with apoptotic tumor cells might be a potent strategy in the treatment of B-ALL.     

Studies of treatment for Haemophilus influenzae type b meningitis in children

We summarize 41 cases of bacterial meningitis in the last 11 years caused by Haemophilus influenzae. All isolates were serotype b strain (Hib). Initial chemotherapy was started with ceftriaxone (CTRX) in 22 cases, ampicillin plus cefotaxime (CTX) in 9, CTRX plus panipenem/betamipron in 5, and CTX in 2. Some 31 cases were treated mainly with CTRX. Although therapeutic antibiotics showed good susceptibility for isolates, 8 complicated cases (19.5%) occurred. Sequalae were observed in 7 (17.1%) but none were fatal. Five strains with elevated MIC of CTX (0.12 to 1 microg/mL) recovered after 2001, and 3 of 5 strains also showed elevated MIC of CTRX (0.12 to 0.5 microg/mL), but all were cured completely with CTRX. At present, no treatment failures due to antibiotic resistance have been observed, and CTRX remains suitable as initial therapy for Hib meningitis. A decline in susceptibility for third-generation cephalosporin against beta-lactamase-nonproducing ampicillin-resistant H. influenzae is emerging, however, so it will be necessary to consider combination therapy with CTRX given the foreseeable trend in MICs.     

Etodolac inhibits EBER expression and induces Bcl-2-regulated apoptosis in Burkitt's lymphoma cells

Cyclooxygenase-2 (COX-2) is reported to be an important cellular target for therapy in malignancies. The growth inhibitory effects of COX-2 inhibitors on malignancies have been demonstrated to be through not only COX-2 dependent, but also independent mechanisms. In this study, we showed that etodolac, COX-2 inhibitor, induced apoptosis via COX-2 independent pathway, and investigated the molecular details of etodolac-induced apoptosis in Burkitt's lymphoma cells. In Daudi and Raji Burkitt's lymphoma cell lines, which expressed no COX-2 enzyme, etodolac more strongly induced apoptosis compared to meloxicam. Moreover, etodolac did not induce apoptosis to normal B-lymphocytes. For the pathway of etodolac-induced apoptosis, reduction of anti-apoptotic bcl-2 mRNA and Bcl-2 protein, activation of Caspase-9 and -3, down-regulation of caspase inhibitors, c-IAP-1 and Survivin were involved. Moreover, EBER-1 and -2 expression in Epstein-Barr virus positive Daudi and Raji cells were reduced to result in down-regulation of Bcl-2 by treatment with etodolac. It has been reported that etodolac has stereoisomers, R- and S-etodolac. We found that racemate of etodolac more strongly induced apoptosis in Daudi and Raji cells compared to R- or S-etodolac. In conclusion, our findings indicated etodolac inhibited EBERs expression and induced apoptosis via a Bcl-2-regulated pathway. Moreover, racemate of etodolac more effectively induced apoptosis than R- and/or S-etodolac. Therefore, these activities of etodolac potentially extend to the treatment of patients with Burkitt's lymphoma resistant to chemotherapy.     

Biliary drainage tube evaluation after common bile duct exploration for choledocholithiasis

BACKGROUND/AIMS: We studied the postoperative evaluation of transcystic duct tube drainage (C-tube), T-tube drainage (T-tube), and retrograde transhepatic biliary drainage after common bile duct exploration for patients with choledocholithiasis. METHODOLOGY: We analyzed the preoperative clinical features of patients, intraoperative findings, postoperative status and management, daily output of bile, liver function, postoperative infections, and postoperative complications for patients who underwent common bile duct exploration including 16 C-tube, 17 T-tube, and 8 retrograde transhepatic biliary drainage cases. RESULTS: There were no significant differences in the preoperative clinical features, intraoperative findings, or the daily output of bile from the tube. The removal day of the biliary drainage tube and postoperative hospital stay were shorter in the C-tube group than in the T-tube and retrograde transhepatic biliary drainage groups. Aspartate amino-transferase level and body temperature in the C-tube group on day 7 were lower than those in the T-tube group, and the total bilirubin level in the C-tube group on day 14 was lower than in the T-tube and retrograde transhepatic biliary drainage groups. Moreover, postoperative complications occurred significantly less frequently in the C-tube group (25.0%) than in the T-tube group (76.5%). CONCLUSIONS: C-tube drainage is thought to be most useful after common bile duct exploration for patients with choledocholithiasis.     

Eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, prevents dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C.

Aim: We conducted a trial to evaluate whether eight-week oral administration of meloxicam, a non-steroidal anti-inflammatory drug, would decrease the rate of the patients who required dose reduction of pegylated interferon alpha-2a in the treatment of chronic hepatitis C. Methods: Sixty patients given weekly subcutaneous administration of pegylated interferon alpha-2a at a dose of 180 mug for 48 weeks were allocated into the meloxicam group (n = 22) and the control group (n = 38) before interferon treatment. Meloxicam was given orally at a dose of 10 mg once a day for eight weeks from the start of interferon treatment. Results: The cumulative rate of dose-reduction-free patients was significantly higher in the meloxicam group (P < 0.05). Until week eight, 44.7% of the control group and 9.1% of the meloxicam group required dose reduction. Dose was modified by neutropenia in 31.6% and 18.2% of the control and meloxicam groups, respectively. Meloxicam relieved a declineof neutrophil count within the first eight weeks from 54.2% to 44.2% (P < 0.05). Multivariate analysis revealed that greater pretreatment neutrophil count and the use of meloxicam were independent factors associated with avoiding dose reduction. Sustained virological response was obtained in 52.6% of the patients. The multivariate logistic analysis revealed that viral serotype and viral load were the only independent factors associated with sustained virological response. Conclusion: Eight-week administration of meloxicam prevented dose reduction of pegylated interferon by relieving a decline of neutrophil count in the treatment of chronic hepatitis C.     

Multifocal intraportal invasion of breast carcinoma diagnosed by laparoscopy-assisted liver biopsy

Hepar lobatum carcinomatosum (HLC) is defined as an acquired hepatic deformity consisting of an irregularly lobulated hepatic contour caused by intravascular infiltration of metastatic carcinoma. To date, only nine cases of HLC have been reported in the literature. We report a case of a 68-year-old woman showing hepatic metastasis of breast carcinoma in radiologically unidentified form. Initially, she received left partial mastectomy for breast cancer but solid hepatic metastases were identified in S2 and S6, 9 mo after surgery. Then, they responded to chemotherapy and radiologically disappeared. After radiological disappearance of the liver tumors, the patient's blood chemistry showed abnormal liver function. A CT scan demonstrated heterogeneous enhancement effect in the liver in the late phase, suggesting uneven hepatic blood supply. Hepatic deformity was not obvious. Laparoscopy revealed a slightly deformed liver surface with multiple indentations and shallow linear depressions. Furthermore, a wide scar was observed on the surface of S2 possibly at the site where the metastatic tumor existed before chemotherapy. Liver biopsy from the wide scar lesion showed intraportal tumor thrombi with desmoplastic change. Because of its similarity to the histology of the original breast cancer, we concluded that the hepatic functional abnormalities and slightly deformed liver surface were derived from the circulatory disturbance caused by microscopic tumor thrombi. Besides, since the wide scar was located at the site of the pre-existing tumor, it is probable that chemotherapy was an important cause of fibrous scarring as a result of tumor regression. These morphologic findings are compatible with those of HLC. Laparoscopy-assisted liver biopsy was useful to make definite diagnosis, even though the hepatic deformity was radiologically undetectable.     

Chemotherapy and serum hyaluronic acid levels in malignant peritoneal mesothelioma

We report a case of malignant peritoneal mesothelioma in a 63-year-old man. Right hemicolectomy, partial ileectomy, partial omentectomy, excision of the abdominal wall, and catheterization for intraperitoneal infusion chemotherapy were performed as surgery. Histopathologically, the tumor was composed of papillary and sheet-like proliferation of atypical cells for which an Alcian Blue digestive test with hyaluronidase was positive. By immunohistochemical staining, the tumor cells were stained against HBME-1 and thrombomodulin antibodies. The final diagnosis was a diffuse malignant mesothelioma of the epithelial type. Sequential adjuvant chemotherapies of cisplatin (ip) plus 5-fluorouracil (iv), cisplatin (iv) plus 5-fluorouracil (iv), and mitomycin C (iv) were administered. He is still alive 46 months after surgery. Moreover, the increase in serum hyaluronic acid levels has been related to tumor volume, and has been useful for clinical follow-up. Secondly, we reviewed major chemotherapy previously described for malignant mesothelioma. The total response rate was 469 of 2,493 cases (18.8%). The response rates with single agent chemotherapy, combination chemotherapy, intraperitoneal or intracavitary chemotherapy, continuous hyperthermic peritoneal perfusion chemotherapy, and immunochemotherapy were 150 of 1,146 cases (13.1%), 209 of 1,019 cases (20.5%), 63 of 133 cases (47.4%), 11 of 13 cases (84.6%), and 36 of 182 cases (19.8%), respectively. Direct exposure of antitumor agent to the peritoneal surface is considered to be most effective against malignant peritoneal mesothelioma.