A 70-year-old man had annular erythema on the area extending from the right scapular region to the right axillary region, where he got tick bites on June 20, 1991. The erythema occurred soon after the bites and spread gradually to become as large as 20 square cm within 25 days. He also felt fatigue. An electrocardiogram revealed an atrioventiricular nodal block. We treated the patient with amoxycillin (750 mg daily) for 35 days. He has been now free from any symptoms over one year. Although repeated serological tests could not detect an antibody to Borrelia burgdorferi, typical erythema chronicum migrans and cardiac manifestation strongly suggested that the case could be diagnosed as Lyme disease.

We report a case of Nothnagel syndrome with inattention. A 69-year-old laborer was admitted to our hospital for rehabilitation therapy complaining of gait disturbance a month after the onset of brainstem infarction. He had right oculomotor palsy, ataxia on the left side and upward movement limitation of the left eye. Magnetic resonance imaging demonstrated high signal intensity in the right tegmentum of the midbrain and the medial aspect of the right thalamus on T2-weighted and diffusion weighted images. This lesion involving nuclei in the medial aspect of the right thalamus, which is considered to be closely related with the reticular activating system, might explain his inattention. And it is suggested that the low blood flow in the right basal ganglia and parietal lobe revealed by his SPECT scan, could be related with that as well. We administered rehabilitation programs for his ataxia and inattention. Because diplopia is thought to be difficult to improve, we did not attempt to treat the patient's eye movement limitation. Three months after our intervention, he was able to walk without support. However, his inattention remained. Patients with brainstem infarction are apt to have plural impairments concurrently. In such cases, it is necessary to assess the treatment priority for each impairment adequately. Evidence based guidelines for the assessment of treatment priority would aid in this endeavor and the development of such guidelines is therefore expected.

Purpose：To explore a methodology for evaluating end-of-life （EOL） cancer care using diagnosis procedure combination （DPC） administrative data. Methods： We investigated care provided to inpatients whose deaths were attributed to cancer and occurred between August 2010 and December 2012. We measured the quality of palliative care by dividing the decedents into two groups： those who died in the palliative care unit （PCU） and those who died in the general wards（GW）. Results： A total of 311 inpatient deaths were identified as cancer deaths. Of these, 147 patients were included in the PCU group and 164 in the GW group. We calculated the DPC data as follows： the rates of chemotherapy administered within 30 days before death （PCU 0％, GW 27％） and within 14 days before death （PCU 0％, GW 10％）, admission to the intensive care unit （PCU 0％, GW 2％）, life-sustaining interventions （PCU 0％, GW 3％）, rehabilitation sessions （PCU 10％, GW 26％）, emergency admission （PCU 2％, GW 27％）, and antibiotics （PCU 32％, GW 28％）. In the PCU group, rates of chemotherapy and emergency admission were significantly lower（＜0.0001；＜0.0001, respectively）, and rehabilitation sessions were significantly higher （p＝0.0002） than in the GW group. Conclusion： EOL care in a university hospital can be easily investigated using DPC data. Some limitations are the single-site study design, the health insurance system, and secondary use of administrative data. However, this methodology may be adapted to investigate the entire Japanese claim database and to evaluate EOL cancer care.

Objective: To clarify how and when Japanese family physicians assess families in their daily practice.Methods: Participants were Japanese family physicians with over one year of experience of full-time work in their clinics, and who were able to join the focus group discussions (FGD) and member checking. The study employed a qualitative research design with semi-structured FGD. Two analysts examined video recordings of the FGD, and the results were verified through member checking and the checking by external members.Results: Physicians assessed families naturally while examining patients for common cold, during vaccination, and during registration in the Japanese care insurance system.Additionally, the physicians assessed the families when they observed or suspected something strange regarding the patient and/or the family.Families were assessed based on how they spent their time during special Japanese events that the family members attended together (e.g., Bon festival or Japanese style New Year holidays), the patient's illness behavior in non-reserved outpatient clinics, and their communication patterns. Furthermore, the family photograph technique for family therapy was also used for assessment.Conclusion: Participants utilized skills of family therapy such as communication patterns and family photographs. They also employed unique skills such as assessment of the families' sharing time during traditional events, assessment of the patient's illness behavior, and general assessments regarding the Japanese care insurance system.

Objective: To clarify the involvement of Japanese family physicians with patients and their families in their daily practice.Methods: Participants were Japanese family physicians with over one year of experience of full-time work in their clinics, and who were able to join the focus group discussions (FGD) and member checks. The study employed a qualitative research design with semi-structured FGD. Two analysts examined video recordings of the FGD, and the results were verified through member checks and external checks.Results: Eight physicians participated at first, but five of them dropped out because of job commitments or death. The involvement by Japanese family physicians consisted of three stages. The first stage was "the approach of repeated hypothesis testing and normalizing" as safety interventions. The second stage was "reevaluation of the family" utilizing family genograms, family conferences, and others. After exhausting all other efforts, they engaged in "accepting the one who comes to them" in collaboration with the patient and families. The outcomes included awareness of patients, their smiles due to feeling accepted, and their expressed emotions. They did not explicitly boast that they were able to engage with family members. In addition, they also needed case studies of instances of "failure." Conclusion: Japanese family physicians engaged in three-stage involvement with families.

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs. METHODS: Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for 14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44, EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM). RESULTS: The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited. CONCLUSION: EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigeniccapacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.METHODS:Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJgenes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).RESULTS:The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathwayPtch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal markerVimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.CONCLUSION:EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.
Vitamin K 2/chemistry/metabolism/*pharmacology ; Tomography, X-Ray Computed ; Tibia/pathology ; Rats ; Osteoporosis/*drug therapy/*prevention & control ; Male ; Magnesium Deficiency/diagnosis ; Magnesium/metabolism ; Homeostasis ; Female ; *Disease Models, Animal ; Diphosphonates ; Calcium/metabolism ; Bone and Bones/*drug effects/metabolism ; Bone Resorption ; Bone Diseases, Metabolic/*metabolism ; Animals

Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects.
Administration, Oral ; Bone Diseases/*drug therapy ; Etidronic Acid/*administration & dosage ; Humans ; Japan

Osteoporosis is one of the most serious complications of corticosteroid treatment. Loss of bone mineral density (BMD) and fractures occur early in the course of corticosteroid treatment, and thus early recognition of fracture risk and effective intervention based on evidence-based-medicine (EBM) are needed. A study of meta-analysis representing the highest level in a hierarchy of evidence showed that when the outcome measure of interest was limited to changes in lumbar spine BMD, bisphosphonates were the most effective of the agents studied in comparison with no therapy or treatment with calcium, and were also more efficacious than either vitamin D or calcitonin; the efficacy of bisphosphonates was enhanced when used in combination with vitamin D. Randomized controlled trials (RCTs) representing the second level in a hierarchy of evidence showed that bisphosphonates stabilized BMD not only in the lumbar spine, but also in the hip, and that parathyroid hormone (PTH) markedly increased lumbar spine BMD. According to the EBM, bisphosphonates and possibly PTH are suggested to be the most efficacious for preserving BMD. The efficacy of these agents in reducing the incidence of vertebral fractures in patients exposed to corticosteroids remains to be established in meta-analysis studies, although some RCTs have demonstrated the anti-fracture effects of etidronate, alendronate, and risedronate in the spine. Further RCTs of fracture prevention conducted on a large number of patients and their meta-analysis are needed to confirm the efficacy of bisphosphonates, PTH, or other agents in preventing vertebral and nonvertebral fractures.
Adrenal Cortex Hormones/*adverse effects ; Bone Density ; Diphosphonates/therapeutic use ; Estrogens/therapeutic use ; Humans ; Osteoporosis/*chemically induced/*drug therapy/prevention & control ; Parathyroid Hormone/therapeutic use ; Vitamin K 2/therapeutic use