Pre- and post-accident (129)I and (137)Cs levels, and (129)I/(137)Cs ratios in soil near the Fukushima Dai-ichi Nuclear Power Plant, Japan.

To evaluate the deposition density and extent of subsurface infiltration of (129)I and (137)Cs in the restricted area that was highly contaminated by the accident of Fukushima Dai-ichi Nuclear Power Plant, cumulative inventories of (129)I and (137)Cs, concentrations of (129)I and (137)Cs, and (129)I/(137)Cs ratio in 30-cm-long soil columns were compared with pre-accident levels from the same area. The cores were collected before and after the accident from locations of S-1 (4 km west of FDNPP) and S-2 (8 km west of FDNPP). Deposition densities of (129)I and (137)Cs in the soil following the accident were 0.90-2.33 Bq m(-2) and 0.80-4.04 MBq m(-2), respectively, which were 14-39 and 320-510 times larger than the pre-accident levels of (129)I (59.3-63.3 mBq m(-2)) and (137)Cs (2.51-7.88 kBq m(-2)), respectively. Approximately 90% of accident-derived (129)I and (137)Cs deposited in the 30-cm soil cores was concentrated in the surface layer from 0 to 44-95 kg m(-2) of mass depth (0-4.3-6.2 cm depth) and from 0 to 16-25 kg m(-2) of mass depth (0-1.0-3.1 cm depth), respectively. The relaxation mass depths (h0) of 10.8-11.2 kg m(-2) for (129)I estimated in the previous study were larger than those of 8.1-10.6 kg m(-2) for (137)Cs at both sites, owing to the larger infiltration depth of radioiodine mainly by the gravitational water penetration in the surface soil in our study sites. Approximately 7-9% of the accident-derived (129)I was present in the lower layer from 44 to 100 kg m(-2) (4.3-8.6 cm depth) at S-1, and from 95 to 160 kg m(-2) (6.2-10.2 cm depth) at S-2. Approximately 1% of (137)Cs seems to infiltrate deeper than (129)I in the lower layer at each site in contrast to the surface layer.

A phase II study of rituximab combined with pirarubicin-cyclophosphamide, vincristine and prednisolone regimen as first-line therapy for patients with indolent B-cell lymphoma.

The anthracycline drug pirarubicin (tetrahydropyranyl-adriamycin [THP]) apparently has been reported to show fewer cardiotoxic effects than doxorubicin. We have previously described the effectiveness of the R-THP-COP regimen comprising rituximab, cyclophosphamide, pirarubicin, vincristine and prednisolone in patients with diffuse large B-cell lymphoma. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) for patients with previously untreated advanced-stage indolent CD20-positive B-cell lymphoma according to the Working Formulation and World Health Organization classification. Four to six courses of the regimen were administered every 3 weeks in 50 patients. The complete remission rate was 57%, while the 3-year overall survival rate was 92%. Regimen-related death was not observed. The R-THP-COP regimen appears very effective for patients with previously untreated advanced-stage indolent CD20-positive B-cell lymphoma. The present results indicate the need for randomized trials of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) and R-THP-COP among patients with CD20-positive indolent lymphoma.

Assessment of individual radionuclide distributions from the Fukushima nuclear accident covering central-east Japan.

A tremendous amount of radioactivity was discharged because of the damage to cooling systems of nuclear reactors in the Fukushima No. 1 nuclear power plant in March 2011. Fukushima and its adjacent prefectures were contaminated with fission products from the accident. Here, we show a geographical distribution of radioactive iodine, tellurium, and cesium in the surface soils of central-east Japan as determined by gamma-ray spectrometry. Especially in Fukushima prefecture, contaminated area spreads around Iitate and Naka-Dori for all the radionuclides we measured. Distributions of the radionuclides were affected by the physical state of each nuclide as well as geographical features. Considering meteorological conditions, it is concluded that the radioactive material transported on March 15 was the major contributor to contamination in Fukushima prefecture, whereas the radioactive material transported on March 21 was the major source in Ibaraki, Tochigi, Saitama, and Chiba prefectures and in Tokyo.

Phase II study of the tetrahydropyranyl adriamycin-cyclophosphamide, vincristine, and prednisolone regimen combined with rituximab as first-line treatment for elderly patients with diffuse large B-cell lymphoma.

The anthracycline drug pirarubicin (tetrahydropyranyl adriamycin; THP) apparently has fewer cardiotoxic effects than doxorubicin. We previously described the benefit of the THP-COP regimen comprising cyclophosphamide, THP, vincristine, and prednisolone for elderly patients with diffuse large B-cell lymphoma (DLBCL). However, that study was completed before rituximab (R) was introduced into clinical practice. Here we report a phase II study of the THP-COP regimen combined with R (R-THP-COP) every 3 weeks. The complete response and 3-year overall survival rates was 63% and 53%, respectively, and no deaths were related to the regimen. We conclude that the R-THP-COP regimen is safe and effective for patients with DLBCL. Based on these results, a randomized controlled trial of rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and R-THP-COP as a phase III study is ongoing.

Long-term survival of a patient with splenic angiosarcoma after resection, high-dose chemotherapy, and autologous peripheral blood stem cell transplantation.

A 48-year-old woman was admitted to our hospital in 2003, complaining of weight loss. Complete blood cell count revealed thrombocytopenia. Abdominal CT demonstrated marked splenomegaly. FDG-PET revealed a hot spot in the whole spleen. A splenectomy was performed. Histological examination was typical for angiosarcoma. Adjuvant chemotherapy was given, and high-dose chemotherapy with autologous peripheral blood stem cell transplantation was performed. Thrombocytopenia developed again in 2008. CT scan showed a hepatic tumor. A fine-needle biopsy of the liver revealed the first relapse. Despite hepatic lobectomy, radiofrequency ablations and administration of recombinant interleukin-2, she died from respiratory failure in 2009.

Phase II study of Rituximab combined with THP-COP as first-line therapy for patients younger than 70 years with diffuse large B cell lymphoma.

INTRODUCTION: We previously described the effectiveness of the THP-COP regimen comprising cyclophosphamide, pirarubicin (tetrahydropyranyl adriamycin; THP), vincristine and prednisolone in patients with diffuse large B-cell lymphoma (DLBCL). The anthracycline drug THP was apparently less cardiotoxic than doxorubicin. However, that study was completed before rituximab was introduced into clinical practice. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) against DLBCL. PATIENTS: Six to 8 courses of the regimen were administered every 2 weeks in 48 patients who were younger than 70 years. RESULTS: The complete remission rate was 92%, the 3-year overall survival rate was 83% and 3-year progression free survival rate was 74%. No deaths were associated with the treatment regimen. CONCLUSION: We conclude that R-THP-COP regimen is very effective against DLBCL. The results of our study urge randomized trials of R-CHOP and R-THP-COP among patients with CD20+ DLBCL.

Serum soluble Fas level determines clinical outcome of patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP.

INTRODUCTION: We previously reported that serum concentrations of soluble Fas (sFas) predict the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) after treatment with CHOP but without rituximab (R). Here, we investigated whether the role of sFas as a prognostic factor remains valid in the R-CHOP era. PATIENTS: We treated 132 patients with DLBCL between October 1995 and September 2002 (group A: without rituximab), and 75 between December 2002 and March 2007 (group B: with rituximab). The patients received eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin)-COP before September 2002, and R-CHOP or R-THP-COP after October 2002. The distribution of patients according to the International Prognostic Index did not significantly differ between the groups. RESULTS: The 5-year overall survival (OS) rates for patients with sFas levels of > or = 3.0 and <3.0 ng/ml in group A were 19.8 and 61.9% (P < 0.0001), whereas the 3-year OS rates in group B were 54.7 and 92.2% (P < 0.01), respectively. Multivariate analysis using the proportional hazards model revealed that sFas most significantly correlated with overall survival (P < 0.05). CONCLUSION: Serum sFas is thus a useful tool for selecting the appropriate therapeutic strategy for DLBCL.

Serum-soluble interleukin-2 receptor (sIL-2R) is an extremely strong prognostic factor for patients with peripheral T-cell lymphoma, unspecified (PTCL-U).

PURPOSE: The aim of this study was to assess the prognostic factors of peripheral T-cell lymphoma, unspecified (PTCL-U). PATIENTS AND METHODS: We retrospectively analyzed 30 cases fulfilling the criteria of PTCL-U defined by the World Health Organization classification. The patients were treated with 6-8 cycles of a CHOP or THP (pirarubicin)-COP regimen. RESULTS: A high serum sIL-2R level (> or =2,000 U/ml) at onset was associated with a low complete remission rate. Patients with high sIL-2R had significantly lower survival rates (5 year, 15.1%) than those with low sIL-2R (<2,000 U/ml) (100%) (P < 0.005). Factors associated with worse overall survival in a univariate analysis were high sIL-2R (P < 0.005), high age (>60 years) (P < 0.05), poor performance status (P < 0.01) and poor international prognostic index (P < 0.05). No correlation was observed between sIL-2R and other markers. Multivariate analysis showed that only sIL-2R was a prognostic factor for overall survival (P < 0.01). CONCLUSION: The results suggest that a high serum sIL-2R level predicts a poor prognosis in PTCL-U.

Immunoproliferative small intestinal disease with protein loss complicated with duodenal T cell lymphoma during progression.

A 52-year-old man was admitted to our hospital in October 2001 with abdominal pain. Abdominal X-ray indicated a diagnosis of ileus. Histopathological and immunological examination resulted in a diagnosis of immunoproliferative small intestinal disease (IPSID). He was treated with THP-COP therapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone), which resulted in complete remission. Outpatient follow-up revealed hypoalbuminemia in May 2003 and upper gastrointestinal endoscopy showed duodenal mucosal nodularity. He was diagnosed with relapsed IPSID and salvage chemotherapy was started. Follow-up endoscopy confirmed that the therapy was effective, but uncovered another duodenal mucosal nodularity. Immunohistochemical staining revealed T-cell lymphoma. Chemotherapy was discontinued and the patient died in December 2004.

Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony-stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy.

BACKGROUNDS AND OBJECTIVES: The optimal strategy for the management of elderly patients with acute myeloid leukaemia (AML) is still controversial. We previously reported the effectiveness of low dose cytarabine (Ara-C) and etoposide (VP-16) (AV therapy) for those elderly AML patients ineligible for intensive chemotherapy. We initiated the present feasibility study to improve the efficacy by using glanulocyte-colony stimulating factor (G-CSF) with AV therapy (AVG therapy). PATIENTS AND METHODS: The eligibility for enrolment was AML patients according to the World Health Organization (WHO) criteria who were over 60 years of age and who had difficulty in tolerating intensive chemotherapy due to their poor performance status (PS) or some comorbidities. They were given continuous drip infusion of Ara-C (20 mg/body) and VP-16 (50 mg/body) for 7-14 days, and were also simultaneously administered G-CSF (150 microg/m2) once daily. RESULTS: The median age of consecutively enrolled 25 patients was 73 years. Eighteen (72%) patients achieved complete remission (CR). The 1-year overall survival (OS) and the 3-year OS rates were 69% and 22%, respectively. The 1-year disease free survival (DFS) rate in CR patients was 44%. The major regimen related toxicities of grade 3 or 4 were only febrile neutropenia in 15 patients (60%). No regimen-related mortality was observed. CONCLUSION: AVG therapy was therefore found to be an effective and well-tolerated regimen for remission induction in elderly AML patients with poor PS or comorbidity.

A comparison of voluntary salt-intake behavior in Nax-gene deficient and wild-type mice with reference to peripheral taste inputs.

The Na(x) channel, a subfamily of voltage-gated sodium channels, is thought to be a specific sodium receptor in the central nervous system. Our previous study revealed that Na(x)-gene-deficient mice consumed excessive amounts of NaCl even under water-deprived conditions. In the present study, to investigate whether the peripheral taste inputs are involved in the abnormal intake of salt in Na(x)-deficient mice (homo), voluntary intake of various taste solutions in homo and wild-type mice (wild) was examined under non-deprived conditions. Homo showed a higher preference for 0.15 M NaCl solution than wild. Preference ratios for other basic tastants were identical between groups. Transection of the chorda tympani (CT) or the glossopharyngeal (GP) nerve had little effect on salt-intake behavior in homo and wild. Although combined transection of the superior laryngeal (SL) and GP nerves decreased NaCl intake in homo but not in wild, there were no differences in preference ratios for NaCl in homo before and after SL+GP transection. On the other hand, preference ratios for NaCl in wild tended to increase after combined SL and GP transection. Consequently, preference ratios for NaCl after SL+GP transection were no different between homo and wild. While electrophysiological responses of the CT and the GP to various taste solutions were indistinguishable between homo and wild, those of the SL to NaCl in homo were smaller than those in wild only at lower concentrations (0.01 and 0.03 M). Thus, chemosensory inputs from the oro-pharyngeal regions had little effect on abnormal salt intake in homo, if any. From these results, it is suggested that the higher preference for NaCl in homo is mainly due to the lack of Na(x) channels in the central nervous system.

Role of the pharyngeal branch of the vagus nerve in laryngeal elevation and UES pressure during swallowing in rabbits.

Elevation of the larynx during swallowing plays an important role in protecting the laryngeal inlet and in the opening of the upper esophageal sphincter (UES). The thyrohyoid (TH) muscle is the most important muscle for laryngeal elevation, and it is thought to be innervated by the thyrohyoid branch. However, in preliminary studies we found that laryngeal elevation was severely disturbed after sectioning of the pharyngeal branch of the vagus nerve (X-ph). In the present study, we examined the role of the X-ph in laryngeal elevation and the contribution of this nerve to UES pressure. Ten male rabbits under anesthesia were used. Sectioning of the X-ph not only abolished the electromyographic activities of the TH and cricopharyngeus (CP) muscles, it also greatly reduced the maximal value of laryngeal elevation during swallowing. On the other hand, sectioning of the hypoglossal nerve, which contains the thyrohyoid branch, produced no appreciable change in the electromyographic activity of either muscle and it reduced the maximal value of the elevation only slightly. These results indicate that the X-ph innervates the TH and CP muscles and suggest that the X-ph plays an important role in elevating the larynx and in regulating the UES pressure in rabbits.

Sour taste stimulation facilitates reflex swallowing from the pharynx and larynx in the rat.

Chemical stimulation of the pharynx and larynx is effective in eliciting reflex swallowing. A sour taste bolus facilitates the onset of swallowing in patients with neurogenic dysphagia, but the mechanism of the facilitation has not been clarified. We investigated the effect of sour solutions on the elicitation of reflex swallowing in anesthetized rats. The main ducts of salivary glands were ligated to avoid the effect of saliva. A small amount of water, sour solutions, and other taste solutions were applied to the mucosa of the pharyngolaryngeal region. Acetic acid and citric acid, which provide a sour taste, had a stronger effect on evoking reflex swallowing as compared with other taste solutions. The effectiveness of these acids increased with increasing concentrations. We also examined the contribution of the superior laryngeal nerve (SLN) and the pharyngeal branch of the glossopharyngeal nerve (GPNph) to reflex swallowing. Acetic acid was greatly effective in evoking swallowing in both the region innervated by the SLN and the GPNph. On the other hand, water was effective in the SLN region but only slightly effective in the GPNph region. The results indicate that stimulation of the pharyngolaryngeal region with sour solutions facilitates reflex swallowing, suggesting that the facilitation may be due to increases of sensory inputs via the SLN and GPNph.

Pharyngeal branch of the glossopharyngeal nerve plays a major role in reflex swallowing from the pharynx.

Mechanical stimulation of the pharyngeal areas readily elicits reflex swallowing. However, it is much more difficult for electrical stimulation of the glossopharyngeal nerve (GPN) to evoke reflex swallowing than it is for stimulation of the superior laryngeal nerve (SLN) to do so. These paradoxical findings remain unexplained; hence, the main purpose of this study was to explain this contradiction by using a urethane-anesthetized rat. Mechanical stimulation easily elicited reflex swallowing from the pharynx. The posterior pillars, posterior pharyngeal wall, and the soft palate of the rat were extremely reflexogenic areas for swallowing. Sectioning the pharyngeal branch of the GPN (GPN-ph), however, eliminated the swallowing reflex from these areas. In contrast, sectioning the lingual branch of the GPN had no effect on the elicitation of swallowing. Electrical stimulation of the GPN-ph and SLN elicited sequentially occurring swallows. The relationship between stimulus frequency and the latency of swallowing for the GPN-ph was approximately the same as that for the SLN. These results indicate that the GPN-ph plays a major role in the initiation of reflex swallowing from the pharynx in rats.