The case is a 6-year-0-month-old girl. She was referred to our department at the age of 5 years and 10 months due to persistent fever over 38.0 ℃. Since blood tests and contrast-enhanced computed tomography showed no abnormalities and there was no response to antipyretics, psychogenic fever was suspected, but psychological factors were unclear. She had lived in father’s home country until the age of 4 years and 11 months (father is foreign national/mother is Japanese), had plans to return to father’s home country. Her height was 117.5 cm, weight 18.7 kg, body temperature 37.4 ℃, and her cardiopulmonary findings were normal. She tried five types of Kampo preparations sequentially. Her body temperature less frequently exceeded 38.0 ℃ with kamishoyosan and yokukansan, and never exceeded 38.0 ℃ with kamikihito. Suspecting that family relationships and vague insecurities were behind her symptoms, it was found that she was stressed about plans to return to father’s home country, leading to the diagnosis of psychogenic fever. When investigating the etiology behind the symptoms, it is useful to refer to the responsiveness to Kampo medicines.

Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking. Methods: This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines.Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. Conclusion Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.

Introduction：Respiratory failures are categorized into types I and II. To our knowledge, we report the first case of pulmonary rehabilitation in a patient with systemic sclerosis/polymyositis overlap syndrome who developed type II respiratory failure.Methods：The patient was a 77-year-old woman who had received treatment for systemic sclerosis and polymyositis at another hospital. When she visited our hospital to obtain a second opinion, she suddenly lost consciousness and underwent trachea intubation because of typeⅡrespiratory failure. She received physical therapy on the third day of hospitalization and underwent a tracheotomy on the 16th day. As her thoracic movement was markedly restricted, we started physical training. After she was weaned off from the ventilator on the 43rd day, we performed muscular strength training and aerobic exercise. No exacerbation of CO2 storage was observed even if chest motion training was performed. She was discharged on the 72nd day and advised to wear retina®．Administration of therapeutic drugs such as steroids was maintained at the same dose.Conclusion：Physical therapy, such as chest mobilization, was effective for marked restriction of chest movement in a patient who had both polymyositis and systemic sclerosis.

Introduction：Respiratory failures are categorized into types I and II. To our knowledge, we report the first case of pulmonary rehabilitation in a patient with systemic sclerosis/polymyositis overlap syndrome who developed type II respiratory failure.Methods：The patient was a 77-year-old woman who had received treatment for systemic sclerosis and polymyositis at another hospital. When she visited our hospital to obtain a second opinion, she suddenly lost consciousness and underwent trachea intubation because of typeⅡrespiratory failure. She received physical therapy on the third day of hospitalization and underwent a tracheotomy on the 16th day. As her thoracic movement was markedly restricted, we started physical training. After she was weaned off from the ventilator on the 43rd day, we performed muscular strength training and aerobic exercise. No exacerbation of CO2 storage was observed even if chest motion training was performed. She was discharged on the 72nd day and advised to wear retina®．Administration of therapeutic drugs such as steroids was maintained at the same dose.Conclusion：Physical therapy, such as chest mobilization, was effective for marked restriction of chest movement in a patient who had both polymyositis and systemic sclerosis.

Background: We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful.

Methods: A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m²) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m²) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient’s quality of life.

Results: Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2–9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly.

Conclusions: Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.

The temporal expression of estrogen receptor (ER)-alpha and ER-beta mRNA was examined in male Japanese quails. Femurs of quails receiving 17beta-estradiol underwent RTPCR and histochemical analysis 1 to 15 days after treatment. Untreated quails were used as controls (day 0). Between days 0 and 5, cells lining the bone endosteal surface differentiated into osteoblasts, which in turn formed medullary bone. Expression of ER-alpha was already observed on day 0 and increased slightly during bone formation whereas ER-beta was hardly detected throughout this process. After osteoclasts appeared on the medullary bone surface, this type of bone disappeared from the bone marrow cavity (days 7~15). ER-alpha expression simultaneously decreased slightly and ER-beta levels remained very low. These results suggest that estrogen activity mediated by ER-alpha not only affects medullary bone formation but also bone resorption.
Animals ; Bone Resorption/genetics ; Bone and Bones/chemistry/cytology/*metabolism ; Cells, Cultured ; Coturnix/*metabolism ; Estradiol/*pharmacology ; Estrogen Receptor alpha/genetics/*metabolism ; Estrogen Receptor beta/genetics/*metabolism ; Gene Expression Regulation ; Male ; Osteoblasts/chemistry/cytology/*metabolism ; Osteogenesis/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction

We tested the hypothesis that a force reduction in soleus muscles from hyperthyroid rats would be associated with oxidative modification of myofibrillar proteins. Daily injection of thyroid hormone [3, 5, 3’-triiodo-_L-thyronine (T₃)] for 21 days depressed isometric forces in whole soleus muscle across a range of stimulus frequencies (1, 10, 20, 40, 75 and 100 Hz) (P<0.05). In fiber bundles, hyperthyroidism also led to pronounced reductions (P<0.05) in both K⁺- and 4-chloro-m-cresol-induced contracture forces. The degrees of the reductions were similar between these two contractures. These reductions in force production were accompanied by a remarkable increment (103% ; P<0.05) in carbonyl groups comprised in myofibrillar proteins. In additional experiments, we have also tested the efficacy of carvedilol, a non-selective β₁-β₂-blocker that possesses anti-oxidative properties. Treatment with carvedilol prevented T₃-induced oxidation of myofibrillar proteins. However, carvedilol did not improve the hyperthyroid-induced reductions in force production. These data suggest that oxidative modification of myofibrillar proteins may not account for the reductions in force production of hyperthyroid rat soleus muscle.

Between 1968 and 1992, a total of 174, 632 people were discharged from our hospital, of which 6, 265, or 3.6%, were dead. During the 25-year period, the number of discharges increased by 1.5 times, while the number of deaths by 2.6 times. We looked into, physicians' reports to find out the age, sex and the cause of death of the patients. Age-wise death rates have been on the decline among the younger patients and on the increase among the eledery patients of 60 years and above, during the period under review. Malignant neoplasms accounted for 62.2% of the causes of death. Especially worthy of note was the fact that deaths from lung cancer have increased at an alarmingly fast rate.

In this symposium, author's opinion about the balneotherapeutic practice of the digestive disorders was expressed.
1) At the beginning of this speech, author's fundermental studies on this theme hitherto were shortly summerized as premise.
2) According to these conclusions, it is very neccesary for the indication of the balneotherapy of digestive disorders to classify thermal springs (not only thermal water, but also hot spring place included) into two groups: one is so-called medicinal or therapeutic spring (“Heilquelle”) and the other is “recreation hot spring” (“Erhohmgsquelle”) (that is hot spring for maintenance and improvement of health).
3) The former is the hot spring intend to medical treatment of digestive diseases and the latter is that intend to health preservation, health promotion, normalising or adjusting the digestive dysfunction.
4) From this point of view, the author mentioned my own opinion concretely and practically about the indication of both “Heilquelle” and “Evholungsquelle” for the digestive diseases and disorders.