Lower muscle co-contraction in flutter kicking for competitive swimmers.

The purpose of this study was to examine the difference in muscle activation pattern and co-contraction of the rectus and biceps femoris in flutter-kick swimming between competitive and recreational swimmers, to better understand the mechanism of repetitive kicking movements during swimming. Ten competitive and 10 recreational swimmers swam using flutter kicks at three different velocities (100%, 90%, and 80% of their maximal velocity) in a swimming flume. Surface electromyographic signals (EMG) were obtained from the rectus (RF) and biceps femoris (BF), and lower limb kinematic data were obtained at the same time. The beginning and ending of one kick cycle was defined as when the right lateral malleolus reached its highest position in the vertical axis. The offset timing of muscle activation of RF in the recreational swimmers was significantly later at all velocities than in the competitive swimmers (47-48% and 26-33% of kick time of one cycle for recreational and competitive swimmers, respectively), although the kinematic data and other activation timing of RF and BF did not differ between groups. A higher integrated EMG of RF during hip extension and knee extension induced a higher level of muscle co-contraction between RF and BF in the recreational swimmers. These results suggest that long-term competitive swimming training can induce an effective muscle activation pattern in the upper legs.

Effects of 2 weeks of low-intensity cycle training with different pedaling rates on the work rate at lactate threshold.

PURPOSE: This study examined (1) the effects of a single bout of exercise at different pedaling rates on physiological responses, pedal force, and muscle oxygenation, and (2) the effects of 2 weeks of training with different pedaling rates on work rate at lactate threshold (WorkLT). METHODS: Sixteen healthy men participated in the study. An incremental exercise test involving pedaling a cycling ergometer at 50 rpm was conducted to assess maximal oxygen consumption and WorkLT. The participants performed constant workload, submaximal exercise tests at WorkLT intensity with three different pedaling rates (35, 50, and 75 rpm). Oxygen consumption ([Formula: see text]O2), blood pressure, heart rate (HR), blood lactate, and pedal force were measured and oxy-hemoglobin/myoglobin concentration (OxyHb/Mb) at vastus lateralis was monitored by near-infrared spectroscopy during exercise. The participants were then randomly assigned to cycling exercise training at WorkLT in either the low or high frequency pedaling rate (LFTr, 35 rpm or HFTr, 75 rpm) group. Each 60-min training session was performed five times/week. RESULTS: Despite maintaining the same work rate, [Formula: see text]O2 and HR were significantly lower at 35 than 75 rpm. Conversely, integrated pedal force was significantly higher at 35 than 75 rpm. Peripheral OxyHb/Mb was significantly lower at 35 than 75 rpm. After 2 weeks of training, WorkLT normalized to body mass significantly increased in the LFTr, but not the HFTr group. CONCLUSIONS: Pedaling rate and the corresponding pedal force and peripheral oxygenation during cycling exercise influence the effect of training at LT on WorkLT.

Phase II study of ABV (doxorubicin with increased dose, bleomycin and vinblastine) therapy in newly diagnosed advanced-stage Hodgkin lymphoma: Japan Clinical Oncology Group study (JCOG9705).

The role of dacarbazine in ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) therapy in Hodgkin lymphoma (HL) remains unclear. This phase II study assessed the efficacy and safety of ABV therapy with an increased doxorubicin dose (30 mg/m(2)) in advanced-stage HL. The primary endpoint was complete response rate (%CR). Patients received six or eight cycles of ABV every 4 weeks followed by involved-field radiation therapy (IFRT) in residual disease and initial bulky mass. Seventy-two patients were enrolled. An interim analysis in 46 assessable patients showed that %CR had exceeded the stopping criteria.However, the 2-year progression-free survival (%PFS) rate of 49.4% (95% confidence interval [CI] 32.2-66.6) was markedly lower than the 79.2% PFS (95% CI 70.6-87.7) seen in our previously reported study (JCOG9305) of ABVd with two-thirds the dose of dacarbazine of the original ABVD. Therefore, the study was closed early. The %CR in the 70 eligible patients after ABV was 31.4% (95% CI 20.9-43.6) and was increased to 70.0% (95% CI 57.9-80.4) after the addition of IFRT. ABV was inferior to ABVd for PFS in patients with advanced HL, suggesting that dacarbazine is indispensable in ABVD/ABVd.

Phase II study of ABVd therapy for newly diagnosed clinical stage II-IV Hodgkin lymphoma: Japan Clinical Oncology Group study (JCOG 9305).

Although ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) therapy has been regarded as a standard of care for advanced-stage Hodgkin lymphoma (HL) since 1992, there has been no prospective data of ABVD therapy in Japan. To investigate the efficacy and safety of ABVd therapy with the lower dose of dacarbazine (250 mg/m(2)) in patients with newly diagnosed stage II-IV HL, Lymphoma Study Group of Japan Clinical Oncology Group conducted a phase II study. The primary endpoints were complete response rate (%CR) and progression-free survival (PFS). A total of 128 patients with age less than 70 years were enrolled and received 6-8 cycles of ABVd followed by radiation to initial bulky mass. The %CR in 118 eligible patients was 81.4% [95% confidence interval (CI) 73.1-87.9%]. Major toxicity was grade 4 neutropenia (45.3%). Grade 3 nausea/vomiting was the most frequent non-hematological toxicity (10.9%). Transient grade 4 constipation, infection (abscess), hypoxemia and hyperbilirubinemia were observed in 4 patients. No treatment-related death was observed. PFS and overall survival at 5 years were 78.4% (95% CI 70.9-85.9%) and 91.3% (95% CI 86.1-96.5%), respectively. In conclusion, ABVd is effective in Japanese patients with stage II-IV HL with acceptable toxicities (UMIN-CTR Number: C000000092).

Prognostic analysis and a new risk model for Hodgkin lymphoma in Japan.

The Japan Clinical Oncology Group conducted two multicenter phase II trials in 200 patients with advanced Hodgkin lymphoma (HL) in the 1990s. Among 181 patients whose histopathological specimens were available and reviewed by 6 hematopathologists, 167 (92.3%) were diagnosed with HL. Five-year overall survival (OS) among these 167 patients was 88.3%, including 89.2% among nodular sclerosis and 82.2% among mixed cellularity cases. International prognostic score was not closely associated with OS. Seven unfavorable prognostic factors for OS on univariate analysis were male, B symptoms, clinical stage of III or IV, elevated serum LDH, elevated alkaline phosphatase, elevated beta2-microglobulin, and pathological subtype (mixed cellularity and lymphocyte depletion). On multivariate analysis, male [HR 3.30 (95% CI 1.15-9.52, p = 0.027)] and elevated serum LDH [HR 2.41 (95% CI 1.07-5.43, p = 0.034)] were independent factors for OS. Based on these prognostic factors, the 5-year OS was 95.7% in the low-risk group (no adverse factor), 87.9% in the intermediate-risk group (1 adverse factor) and 73.3% in the high-risk group (2 adverse factors). This simple prognostic model for HL warrants further validation studies.

Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate.

Among methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPD), diffuse large B-cell lymphoma (DLBCL) accounts for about half. We studied the clinicopathological characteristics and prognosis of patients with DLBCL in MTX-LPD. This study included 29 patients who developed DLBCL after receiving MTX for rheumatoid arthritis. MTX was discontinued in all patients. Their median age was 62 years. Elevated lactate dehydrogenase (LDH) level was observed in 97% of the patients, bone marrow involvement in 17%, and involvement of extranodal sites in 41%. As for the cellular immunophenotype, CD20 was positive in 93%, CD5 in 3%, CD10 in 31%, BCL2 in 21%, BCL6 in 69%, and Epstein-Barr virus (EBV)-encoded small non-polyadenylated RNA (EBER) in 24%. Chemotherapy was started within 2 months after MTX withdrawal in 23 patients, of whom 12 patients received combination with rituximab. Spontaneous remission occurred in the remaining six patients. The EEBV-positive rate was 67% (4/6), and the four EBV-positive patients achieved complete response. Among the 23 DLBCL patients treated with chemotherapy, 20 patients achieved complete response. The 5-year overall survival was 74% and the 5-year progression-free survival was 65%. After the development of DLBCL, withdrawal of MTX was the first choice of treatment. Germinal center B-cell type and EBER-positive patients tended to show spontaneous remission. The utility of rituximab should be examined in future studies.

Preliminary genome-wide association study of bipolar disorder in the Japanese population.

Recent progress in genotyping technology and the development of public databases has enabled large-scale genome-wide association tests with diseases. We performed a two-stage genome-wide association study (GWAS) of bipolar disorder (BD) in Japanese cohorts. First we used Affymetrix 100K GeneChip arrays in the analysis of 107 cases with bipolar I disorder and 107 controls, and selected markers that were nominally significant (P < 0.01) in at least one of the three models (1,577 markers in total). In the follow-up stage, we analyzed these markers using an Illumina platform (1,526 markers; 51 markers were not designable for the platform) and an independent sample set, which consisted of 395 cases (bipolar I + II) and 409 controls. We also assessed the population stratification of current samples using principal components analysis. After the two-stage analysis, 89 markers remained nominally significant (allelic P < 0.05) with the same allele being consistently over-represented in both the first and the follow-up stages. However, none of these were significant after correction for multiple-testing by false discovery rates. Sample stratification was virtually negligible. Collectively, this is the first GWAS of BD in the Japanese population. But given the small sample size and the limited genomic coverage, these results should be taken as preliminary.

Clinical significance of 8q24/c-MYC translocation in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) has heterogeneous clinical, histological, and molecular features. We evaluated the clinical characteristics and prognoses of patients with DLBCL carrying 8q24 translocations. A total of 1864 consecutive patients with non-Hodgkin's lymphoma were treated in the Adult Lymphoma Treatment Study Group from 1998 to 2005. Of the 252 patients with DLBCL with abnormal karyotypes, 28 patients with DLBCL with the 8q24 translocation were identified. There were 14 men and 14 women, with a median age of 61 years. The 8q24 translocation was observed significantly more frequently among patients with poor performance status, among patients with high lactate dehydrogenase level, and among patients with bone marrow involvement. The 5-year overall survival was 43.9% among the patients with 8q24 translocation, and 67% among the patients with other chromosomal abnormalities. The 8q24 translocation group showed significantly poorer prognosis than the group with other translocations. In addition, patients with t(14;18) and 8q24 translocation showed significantly poorer prognosis than those with 8q24 translocation alone. It will be necessary to study whether more aggressive chemotherapy or rituximab combination chemotherapy is effective in 8q24 translocation cases.

De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients.

BACKGROUND: De novo CD5-positive diffuse large B-cell lymphoma (CD5(+) DLBCL) is clinicopathologically and genetically distinct from CD5-negative (CD5(-)) DLBCL and mantle cell lymphoma. The aim of this retrospective study was to clarify the histopathological spectrum and obtain new information on the therapeutic implications of CD5(+) DLBCL. DESIGN AND METHOD: From 1984 to 2002, 120 patients with CD5(+) DLBCL were selected from 13 collaborating institutes. We analyzed the relationship between their morphological features and long-term survival. The current series includes 101 patients described in our previous study. RESULTS: Four morphological variants were identified: common (monomorphic) (n=91), giant cell-rich (n=13), polymorphic (n=14), and immunoblastic (n=2). Intravascular or sinusoidal infiltration was seen in 38% of the cases. BCL2 protein expression in CD5(+) DLBCL was more frequent than in CD5(-) DLBCL (p=0.0003). Immunohistochemical analysis in 44 consecutive cases of CD5(+) DLBCL revealed that 82% of these cases (36/44) were non-germinal center B-cell type DLBCL. The 5-year overall survival rate of the patients with CD5(+) DLBCL was 38% after a median observation time of 81 months. Patients with the common variant showed a better prognosis than those with the other three variants (p=0.011), and this was confirmed on multivariate analysis. Overall, 16 patients (13%) developed central nervous system recurrence. CONCLUSIONS: Our study revealed the morphological spectrum of CD5(+) DLBCL, found that the incidence of central nervous system recurrence in this form of lymphoma in high, confirmed that CD5(+) DLBCL frequently expresses BCL2 protein and showed that it is mainly included in the non-germinal center B-cell type of DLBCL.

Clinicopathologic features and treatment outcome of primary breast diffuse large B-cell lymphoma.

We studied the clinicopathologic features and treatment outcome of patients with breast diffuse large B-cell lymphoma. As to the cellular immunophenotype, CD5 was detected in two patients, CD10 in 4, BCL2 in 20, BCL6 in 11, and MUM-1 in 17. The 5-year progression-free survival was 77% and the 5-year overall survival was 87%. Patients with the germinal center B-cell (GCB) type had a significantly better prognosis than those with the non-GCB type. The combination of anthracycline-containing chemotherapy and/or involved-field radiotherapy produced a relatively good prognosis. However, it is a heterogeneous disease with regard to histological type and pathological state.

Clinico-pathologic features and outcome of Japanese patients with peripheral T-cell lymphomas.

We studied the clinico-pathologic features and treatment outcome of patients with peripheral T-cell lymphoma (PTCL). This study included 215 patients with T/natural killer (NK)-cell lymphoma, including 59 with PTCL-unspecified (PTCL-U), 42 with angioimmunoblastic T-cell lymphoma (AILT) and 20 with anaplastic large-cell lymphoma (ALCL). Most of the analyses were performed on patients with AILD, ALCL and PTCL-U. The patients with AILT and PTCL-U tended to be older than those with ALCL. Stage III/IV disease was seen in 90.5% of the AILT cases, 55% of the ALCL cases and 67.8% of the PTCL-U cases. In addition, 61.9% of the AILT cases had an international prognostic index (IPI) of H-I or H risk. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 72.2 and 76.1% among the ALCL cases, 40.7 and 42.2% among the PTCL-U cases and 31.2 and 49.3% among the AILT cases, respectively. Among the patients with PTCL-U, the 5-year PFS and OS rates in group low (L), low-intermediate (L-I), high-intermediate (H-I) or high (H) risk group of IPI were: 47.6 and 56.1%, 55.6 and 53.8%, 42.4 and 40.1% and 9.1 and 9.1%, respectively. The 5-year PFS and OS rates in group 1, 2, 3 or 4 by prognostic index of PTCL-U (PIT) were: 88.9 and 85.7%, 57.1 and 54.9%, 33.5 and 28.8% or 13.3 and 13.3%, respectively. The 5-year PFS and OS rates among patients who received CHOP therapy, CyclOBEAP [cyclophosphamide (CPA), vincristine (VCR), bleomycine, etoposide, doxorubicin (DXR), prednisone (PDN)] therapy or autologous stem cell transplantation were: 22 and 25.7%, 59 and 61.7% or 33.3 and 60%, respectively. Multivariate analysis revealed that the PIT score was associated with OS and PFS. These results indicate that the presence of bone marrow (BM) involvement is an independent prognostic factor which may predict both OS and PFS. PTCL-U is a heterogeneous disease with regard to histological type and pathological state. Because PTCL-U is generally not responsive to CHOP therapy, new treatment strategies need to be developed.

[Multi-center trial on the early effects of silodosin on lower urinary tract symptoms associated with benign prostatic hyperplasia].

Silodosin (URIEF), a new so-called 3rd generation alpha-1 blocker, is widely expected to be effective and useful for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), due to its high specificity to alpha-1A receptor. We evaluated the efficacy of Silodosin, on 187 males 50 years old or over with the diagnosis of BPH. Silodosin significantly improved the International Prostate Symptom Score (IPSS) and quality of life (QOL) score from the day after administration was started. Among 166 patients whose data were available for the analysis of efficacy of Silodosin, 77.5% showed apparent subjective improvement. Eighty three patients, who had been taking another alpha-1 blocker but without satisfactory effects, showed almost the same improvements in IPSS and QOL score after switching to Silodosin as the remaining 83 patients who had no preceding treatment with an alpha-1 blocker. The improvements were not only in voiding symptoms but also in storage symptoms. The patients, who had serious storage symptoms, responded rather well to Silodosin and showed significant improvement. Taken together, Silodosin showed a quick effect for improving subjective symptoms and QOL, and was found to be useful for the management of LUTS with BPH.

Prognostic impact of chromosomal alteration of 3q27 on nodal B-cell lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 329 consecutive patients.

Rearrangements involving the BCL6 gene are found in 30% of diffuse large B-cell lymphomas (DLBCLs). We evaluated the clinical characteristics and prognoses of patients with B-cell lymphoma carrying 3q27 translocations. Among the 59 patients having 3q27 translocation, 10.9% had follicular lymphoma (FL) and 23.1% had DLBCL. It is of interest that the prognostic significance was not found between FL and DLBCL with 3q27 translocations. Progression-free survival (PFS) rate was significantly higher in the FL patients with 3q27 translocation than in those with 18q21 translocation. PFS rate was significantly higher in the DLBCL patients with 3q27 translocation than in those with 18q21 translocation. These findings suggest that the presence of 3q27 translocation is a significant prognostic factor in DLBCL.

t(8;14)(q24;q32) in two patients with CD10-negative primary thyroid diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) with the 8q24 translocation is occasionally seen in the gastrointestinal tract, but has rarely been reported in the thyroid gland. We experienced two cases of primary thyroid DLBCL having t(8;14)(q24;q32). The immunophenotype and karyotype of Case 1 (66-year-old female) and Case 2 (70-year-old female) were: CD10-, CD20+, BCL-2+/add(13)(q34), t(8;14)(q24;q32) and CD10-, CD20-, CD79a+, BCL-2-/t(8;14)(q24;q32), respectively. Although long-term complete remission could be achieved in both of our patients by conventional chemotherapy with/without radiation therapy, accumulation of further such cases is necessary to develop a standard treatment protocol and also to elucidate the pathogenesis of t(8;14)(q24;q32)-positive primary thyroid DLBCL.

Multicentre phase II study of the baseline BEACOPP regimen for patients with advanced-stage Hodgkin's lymphoma.

A German Hodgkin's lymphoma (HL) study group designed the BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) regimen. In the BEACOPP regimen, treatment intervals were shortened and the dose-intensity was increased compared with those in the ABVD regimen (doxorubicin, bleomycin, vinblastine and darcarbacine), resulting in a long-term disease-free survival rate of approximately 75-80%. In the present study, we evaluated the safety and efficacy of the BEACOPP regimen. Between April 2001 and February 2004, 20 patients with HL of stage IIB or higher who had received no previous treatment were enrolled. The patients were aged 17-69 years (median 22 years). The histologic types were mixed cellularity in four cases and nodular sclerosis in 16 cases. The stages were stage IIB in four cases, stage III in 12 cases, and stage IV in four cases. Nineteen (95%) of the 20 patients achieved complete remission. The 3-year survival rate was 100% and the 3-year progression-free survival rate was 89.7%. Adverse drug reactions were grade 4 neutropenia in 12 patients, grade 3-4 thrombocytopenia in seven patients, and grade 3 or higher non-hematologic toxicities in two patients (stomatitis in one patient and ALT/AST elevation in one patient). The BEACOPP regimen for advanced-stage HL showed an excellent complete remission rate and high efficacy even in stage III/IV patients. However, a long-term risk of the BEACOPP regimen is the development of secondary leukemia or myelodysplastic syndrome. Therefore, long-term follow-up of these patients, including monitoring for toxicities, is necessary.

Multicenter Phase II study of CyclOBEAP regimen for elderly patients with poor-prognosis aggressive lymphoma.

We treated elderly patients (65-69 years) who had aggressive lymphoma with the CyclOBEAP regimen, and we studied the safety and efficacy of this treatment. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin 40 mg/m(2) was given every 2 weeks in combination with either cyclophosphamide 800 mg/m(2) or etoposide 70 mg/m(2) qd x 3. During the alternate weeks, non-myelosuppressive vincristine 1.0 mg/m(2) was given either with bleomycin 10 mg/m(2) or alone. Prednisolone 40 mg/m(2) was administered daily for three 14-day periods during weeks 1-2, 5-6 and 9-10. There were 51 eligible patients. A complete response was achieved in 42 patients (82%). The 5-year overall survival (OS) rate was 60.6% and progression-free survival (PFS) rate was 51.8%. WHO grade 4 neutropenia was observed in 32 patients and thrombocytopenia in 8 patients. We showed that the CyclOBEAP regimen can be safely used in the treatment of aggressive lymphoma in elderly patients and it achieved a high rate of remission.

Impairment of theory of mind in patients in remission following first episode of schizophrenia.

The aim of this study was to investigate theory of mind (ToM) ability in patients in remission after the first episode of schizophrenia. A ToM task which contained four pictures was given to 30 patients with schizophrenia in remission and 30 matched healthy controls. Patients with schizophrenia in remission showed statistically significant impairment in the ToM tasks. ToM impairment was not correlated with psychiatric symptoms. Thus, ToM deficit in schizophrenia may be a trait marker.

Multicenter phase II study of the CyclOBEAP (CHOP-like + etoposide and bleomycin) regimen for patients with poor-prognosis aggressive lymphoma.

Our aim was to study the efficacy of the addition of etoposide and bleomycin to a [cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PDN)] CHOP-like regimen for the treatment of aggressive lymphoma. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin, 50 mg/m(2), was given every 2 weeks in combination with either cyclophosphamide, 1,000 mg/m(2), (weeks 1, 5, 9) or etoposide, 70 mg/m(2) qd x4 (weeks 3, 7, 11). During the alternate weeks, non-myelosuppressive vincristine, 1.4 mg/m(2) (maximum, 2.0 mg/body), was given either with bleomycin, 10 mg/m(2) (weeks 2, 6, 10), or alone (weeks 4,8,12). Prednisolone, 40 mg/m(2), was administered daily for 14 days during weeks 1-2, 5-6, and 9-10. There were 121 eligible patients and median age of 51 years. A complete response was achieved in 106 patients (88%) and a partial response in 11 patients. The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 62%. When the patients were divided according to the International Prognostic Index (IPI), the 5-year OS and PFS rates did not significantly differ among risk groups. When the patients with DLBCL were divided according to the IPI, the 5-year OS and PFS rates also did not significantly differ. World Health Organization (WHO) grade 4 neutropenia was observed in 91 patients and thrombocytopenia in 13 patients. No treatment-related deaths were observed. The addition of etoposide and bleomycin to CHOP therapy may enhance the effect of CHOP therapy for aggressive lymphoma. We will perform a prospective study of CyclOBEAP regimen combined with rituximab and test its safety and efficacy.

Efficacy and safety of imatinib mesylate for patients in the first chronic phase of chronic myeloid leukemia: results of a Japanese phase II clinical study.

Imatinib mesylate is a relatively new drug that targets the BCR-ABL chimeric protein, the molecular basis of chronic myeloid leukemia (CML). A phase II clinical trial in 39 Japanese patients in the first chronic phase of CML was conducted with imatinib mesylate at a dose of 400 mg/day. Hematologic complete response was obtained in 92.3% of the patients, complete cytogenetic response (CR) was obtained in 43.6%, and major partial CR was obtained in 20.5% of the patients. Although 29 of 39 patients required an adjustment of dosing because of grade 3 or 4 adverse events, most of the events were reversible, and 25 of the 29 patients were able to resume therapy. Between day 15 and day 35, grade 3 or 4 neutropenia and/or leukocytopenia occurred in 13 patients, and grade 3 thrombocytopenia occurred in 5 patients. Overall, nonhematologic grade 3 adverse events occurred in 28.2% of the patients. These data support the use of imatinib mesylate as the treatment of choice for chronic-phase CML patients.