Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus

BACKGROUND/AIMS: We developed an idiopathic normal-pressure hydrocephalus grading scale (iNPHGS) to classify a triad of disorders (cognitive impairment, gait disturbance and urinary disturbance) of iNPH with a wide range of severity. The purpose of this study was to assess the reliability and validity of this scale in 38 patients with iNPH. RESULTS: The interrater reliability of this scale was high. The iNPHGS cognitive domain score significantly correlated with the cognitive test scores, including the Mini-Mental State Examination (MMSE), the gait domain score with the Up and Go Test and Gait Status Scale scores, and the urinary domain score with the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. The MMSE, Gait Status Scale and ICIQ-SF scores significantly improved in patients whose iNPHGS scores improved after CSF tapping but not in those whose iNPHGS scores did not improve after CSF tapping. Fourteen of the 38 patients received shunt operations. In these 14 patients, changes in the iNPHGS cognitive and urinary domains after CSF tapping were significantly associated with the changes after the shunt operation.     

Long-term outcome after laparoscopic wedge resection for early gastric cancer

Background  Laparoscopic wedge resection (LWR) can be applied for the management of early gastric cancer without the risk of lymph node metastasis. Although LWR for early gastric cancer is one of the minimally invasive procedures, its radicality in cancer therapy is controversial. This study aimed to evaluate the long-term outcomes after LWR. Methods  Data on 43 consecutive cases of LWR performed for preoperatively diagnosed mucosal gastric cancer were analyzed retrospectively in terms of long-term outcomes. Results  No postoperative deaths occurred after LWR. Histologically, resected specimens showed submucosal invasion in 11 cases (26%) and positive surgical margins for cancer in 4 cases (9%). Three patients (7%) showed local recurrence near the staple line, and one patient (2%) died due to the local recurrence, but no lesional lymph node or distant recurrence occurred. The overall 5-year survival rate was 88%. The gastric remnant after LWR developed metachronous multiple gastric cancer in five cases (12%). Conclusions  The findings show a relatively high incidence of positive surgical margin, local recurrence, and gastric remnant cancer after LWR. Although LWR can be performed for properly selected patients, periodic postoperative endoscopic examination is necessary to detect metachronous multiple gastric cancer and local recurrences.     

Immunological status in three patients, thirty years after living related renal transplantation: antibody production in long-term survivors

There have been few studies of the immune status of long-term follow-up patients after living-donor kidney transplantation. We investigated the immune status from the immunologic and pathologic standpoint of three long surviving recipients who had received renal grafts more than 30 years earlier. Anti-HLA antibodies that had not been present before transplantation were detected in one recipient with three HLA mismatches. One recipient with identical HLA showed positive for the crossmatch test, but not for the panel reactive antibody test (PRA), thus showing that this patient had HLA antibodies against HLA minor histocompatibility antigens, etc. Only one patient with established microchimerism was stable without any antibody production. Pathologically, chronic allograft nephropathy with C4d staining suggestive of antibody-mediated rejection was observed in both patients with HLA antibodies. Physicians should clinically manage patients by always bearing in mind the presence of anti-donor antibodies during long-term regular follow-up of transplanted kidneys.     

Correlation of compensatory alignment of the subtalar joint to the progression of primary osteoarthritis of the ankle

BACKGROUND: The etiology of primary osteoarthritis of the ankle is not well understood. The varus deformity of the ankle and the compensatory function of the subtalar joint are expected to be important factors in the progression of osteoarthritis. The purpose of this study was to document joint inclination at the various stages and to try to deduce the mechanism of primary, varus osteoarthritis of the ankle. MATERIALS AND METHODS: Weightbearing ankle anteroposterior (AP) views, lateral views and subtalar views were taken for 133 ankles in 80 patients (OA group) and 62 ankles in 50 subjects (control group). The OA group was divided into 5 radiographic stages. The inclination of the articular surface of the tibial plafond, the talar dome and the posterior facet of the calcaneus were measured from the radiographs. The inclination of the subtalar joint against the ankle was also calculated. At each stage, each value of the OA group was compared with the control group. RESULTS: The varus inclination of the articular surface of the tibial plafond progressed by stages; however, anterior opening was not significant at all stages. The valgus inclination of the subtalar joint progressed until the intermediate stage and converted to varus position at the later stage. CONCLUSION The compensatory function of the subtalar joint was most pronounced at the intermediate ankle arthritis stage.     

Electromagnetic Fields

Establishing a means to prevent osteonecrosis after corticosteroid administration is an important theme. We asked whether pulsed electromagnetic field stimulation, a noninvasive treatment, could prevent osteonecrosis. Ninety rabbits were divided into four treatment groups: (1) exposure of 10 hours per day to electromagnetic stimulation for 1 week, followed by injection of methylprednisolone (20 mg/kg), and exposure of 10 hours per day to electromagnetism for a further 4 weeks (n = 40); (2) methylprednisolone injection only (n = 40); (3) no treatment (n = 5); and (4) exposure of 10 hours per day to electromagnetism for 5 weeks (n = 5). After 5 weeks, we harvested and histologically examined femurs bilaterally. The frequency of osteonecrosis was lower in the steroid-electromagnetism group (15/40) than in the steroid-only group (26/40). No necrotic lesions were found in the two control groups. We observed no clear effects of electromagnetism on the number, location, extent, and repair of necrotic lesions and intramedullary fat cell size in affected rabbits. Pulsed electromagnetic field stimulation reportedly augments angiogenesis factors and dilates blood vessels; these effects may lower the frequency of osteonecrosis. Exposure to pulsed electromagnetic field stimulation before corticosteroid administration could be an effective means to reduce the risk of osteonecrosis. Each author certifies that he has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. One or more of the authors (MF, TK) received funding from the Japanese Investigation Committee for Osteonecrosis of the Femoral Head, under the auspices of the Ministry of Health, Labor and Welfare of Japan; and one of the authors (MF) from the Hip Joint Foundation of Japan, Inc. Each author certifies that his institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.     

Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells

The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell-receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.     

Monitoring neutrophil engraftment in allogeneic stem cell transplantation by flow cytometric analysis of neutrophil-specific antigens NA1 and NA2

Neutrophil-specific antigen (NA) expression on neutrophils was analysed in 18 Japanese children before and after allogeneic stem cell transplantation (allo-SCT) with myeloablative regimen. Donor-recipient NA-incompatibility was present in one of eight NA1/NA2 heterozygous patients and eight of 10 NA1/NA1 or NA2/NA2 homozygous patients. After allo-SCTs from NA-incompatible donors, a neutrophil recipient-to-donor conversion was confirmed in all cases. Conversion to donor NA type was complete before the absolute neutrophil count reached 0.1 x 10(9)/l. These observations indicate that flow cytometric analysis of NA antigens is a simple and useful method for monitoring neutrophil engraftment in NA-incompatible allo-SCT.