[Usefulness of Palliative Gastrojejunal Bypass Surgery].

OBJECTIVES: The aim of this study was to evaluate the usefulness of gastrojejunal bypass surgery performed in patients presenting with upper gastrointestinal tract obstruction due to unresectable advanced cancer. SUBJECTS AND METHODS: The subjects were 21 patients who underwent gastrojejunal bypass surgery at our division between 2010 and 2014 for symptom palliation. We retrospectively evaluated the operative outcomes, whether chemotherapy was administered, the oral ingestion period, and survival time. RESULTS: The median postoperative day of starting oral ingestion was 6 (range: 2-42), and the median period from decreased oral ingestion to death was 4 (range: 0-26) days. Twelve patients (57%) were discharged. Postoperative chemotherapy was prescribed to all the 9 patients who desired treatment. The median duration of oral digestion time was 61 days, and the median overall survival time was 92 days. CONCLUSION: Gastrojejunal bypass surgery is found to have the potential to not only make relatively long-term oral ingestion possible, but also broaden available treatment options, such as home care or chemotherapy, thereby contributing to improved quality of life.

The area and attachment abnormalities of the gubernaculum in patients with undescended testes in comparison with those with retractile testes.

PURPOSE: In order to evaluate the gubernaculum (GN) abnormalities quantitatively in patients with undescended testes (UDT), the area and attachment site of the gubernaculum were evaluated. PATIENTS AND METHODS: Sixty-seven testes from 61 patients with an undescended testis treated in the past 11 years at our institution were examined. Using intraoperative photographs or DVDs, the area of the GN inside the processus vaginalis was measured, and the ratio to that of the testis was determined. When the GN was attached to the vas deferens, the GN distance from the testis was also measured, and the ratio to that of the transverse length of the testis (deviation index) was calculated. Reference values were obtained from 23 testes from 15 patients with mobile testes. RESULTS: In cases with mobile testes, the GN attached to the bottom of the testis, and involved the lower pole of the epididymis. Even though the GN was attached to the bottom of the testis in 43 testes in the UDT patients (64 %), the GN was found to be elongated. The mean GN area ratio was 1.58 (1SD, 0.6) in the UDT cases, in comparison to 0.47 (0.2) in the cases with mobile testes. The GN was attached to the vas deferens in 24 testes (36 %). The deviation index was 1.34 (1.0), but the GN area ratio of these cases was 1.56 (0.7), which was similar to that of the GN attached to the bottom of the testis. CONCLUSION: The present study revealed that an increase in the GN area ratio was the most common imaging abnormality in cases with UDT.

[Invasive pneumococcal disease of serotype 6C with skin and soft tissue infections in an immunocompetent adult].

We report herein on a rare case of deep-soft tissue infection due to invasive pneumococcal disease (IPD). A 77-year-old woman was admitted to our hospital with progressive pain in the right upper arm and the distal leg associated with swelling. We diagnosed the condition as multiple instances of cellulitis that were initially treated with ceftriaxone and clindamycin. Penicillin-susceptible Streptococcus pneumoniae (PSSP) was isolated from blood cultures on admission. Although inflammatory marker levels improved following susceptive antibiotic therapy (ampicillin), multiple abscesses, septic arthritis and osteomyelitis were detected with image testing. The antibiotic was then changed to meropenem and arthroscopic surgery was performed for the right shoulder; the patient's clinical symptoms improved. Since pneumococcal infection including skin and soft tissue infection (SSTI) often causes blood stream invasion or metastatic suppurative complications, metastatic lesions or multiple abscesses should be taken care of.

Effect of information provision by familial nudging on attitudes toward offshore wind power.

Offshore wind power (OWP) is a promising way to achieve decarbonization and tackle global climate change, but acceptance by residents is an important issue for site location. Information provision could be a more cost-effective intervention than debates or subsidies, assuming that scientifically correct information alone is insufficient and information design to boost the message effects considering realistic human responses is necessary. Thus, we designed nudging messages to increase acceptance of OWP, using a message framework to moderate risk-averse attitudes by reminding readers of familial support based on insights from kin selection theory from evolutionary psychology. A randomized controlled trial based on an internet survey of more than 4000 responses from the general public was performed to investigate the message effects. The messages significantly moderated the risk-averse attitudes toward OWP by 0.228 on average on a five-point Likert scale, which meant that about 5 people out of 100 changed their attitudes to be safer by 1 point. This suggests that disseminating flyers using nudging messages might be an effective way to increase acceptance. We also extracted responses from those who mentioned fisheries in an open-ended question as an alternative to actual fishers. Responses from this segment were more complex and the message effects were limited compared with those who did not mention fisheries; although the attitudes toward OWP before receiving the messages were safer, reading descriptions for potential risks on fisheries may have unexpectedly led them to focus on the risks of which they were unaware at first. Because information provision based on nudging is effective but just one of a wide variety of political interventions available, practitioners should consider a combination of multiple options instead of using only nudging messages.

Synthesis of vitamin D3 derivatives with nitrogen-linked substituents at A-ring C-2 and evaluation of their vitamin D receptor-mediated transcriptional activity.

Binding of a series of novel 1α,25-dihydroxyvitamin D(3) (1,25-VD(3)) derivatives, having a nitrogen-linked substituent at the 2α- or 2ß-position of the A-ring (2-N-substituted compounds), with the vitamin D receptor (VDR) was investigated by means of computational docking studies. Selected compounds were synthesized by coupling A-ring synthons and/or with CD-ring-bearing bromomethylene under Trost's conditions. The 2α- and 2ß-stereoisomers of the A-ring synthons were synthesized from l-serine () as a single chiral source by installing vinyl and propargyl groups at opposite ends of the molecule. The activity of the obtained compounds was evaluated by means of a luciferase-based VDR transcriptional activity assay in NIH3T3 cells. Relatively small substituents incorporating a hydrogen-bonding donor, i.e., NHAc and NHMs, were effective for eliciting VDR transcriptional activity, and 2ß-NHMs-1,25-VD(3) () showed the highest activity, being more potent than 1,25-VD(3). Derivatives with bulky substituents were inactive. These new insights into the structure-activity relationships of 1,25-VD(3) derivatives may be helpful in separating the various biological activities of 1,25-VD(3) and in generating novel therapeutic drug candidates.

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor: a case of a rare malignancy.

BACKGROUND: A gastric adenosquamous carcinoma (ASC) that produces granulocyte-colony stimulating factor (G-CSF) is an uncommon malignancy with a poor prognosis. Due to the rarity of this lesion, a standard treatment for the disease has not been established. CASE PRESENTATION: We describe a case of a 66-year-old male with a G-CSF-producing gastric ASC who presented with severe anemia and leukocytosis. A radical resection was performed, followed by a course of adjuvant chemotherapy. Histopathologic examination revealed that the tumor consisted of areas of both squamous cell carcinoma and adenocarcinoma. Immunohistochemical staining with an anti-G-CSF antibody was also positive. He was started on adjuvant capecitabine and oxaliplatin (CapeOX) 6 weeks after surgery. The patient stopped treatment after 3 months due to his own preference. Eight months following surgery, the patient was found to have diffuse lymph node, liver, and peritoneal metastases. CONCLUSIONS: G-CSF-producing gastric ASC is a rare and aggressive tumor. Because patients are usually diagnosed at an advanced stage, multidisciplinary evaluation and innovative treatments are needed. The rarity of this disease, with its aggressive features, poses a significant challenge in its treatment. In this brief case report, we summarize the management and outcomes of G-CSF-producing gastric ASC.

Phototoxic effect of na-pheophorbide a toward osteosarcoma cells in vitro using a laser diode.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of photodynamic therapy (PDT) with Na-pheophorbide A in anticancer treatment, using osteosarcoma cells in vitro. BACKGROUND DATA: It has been reported that PDT with chlorophyll derivatives inhibits the proliferation of various cancer cells. However, there have been no reports that have evaluated the effectiveness of PDT in suppressing osteosarcoma cells. MATERIALS AND METHODS: Uptake of Na-pheophorbide A into Hu09 cells (osteosarcoma cells) was assayed using fluorescence microscopy following incubation of the cells with 28 µmol/L of Na-pheophorbide A. The viability of Hu09 cells after PDT treatment was assessed using trypan blue dye staining and MTS assays. PDT-induced apoptosis was determined by evaluation of the activity of selected members of the caspase family and by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of cells. RESULTS: Na-pheophorbide A uptake by cells was rapid, being observed after 60 min of treatment, and Na-pheophorbide A persisted in cells for >24 h. PDT treatment decreased cell viability compared with the control group, indicating high cytocidal activity of PDT. This cytocidal effect was dependent upon drug concentration, light dose, and the number of irradiation times. An increase in the number of cells positive for TUNEL staining and increases in the activity of caspases-3, -8 and -9 were observed in the first 2 h after PDT treatment. CONCLUSIONS: A cytotoxic effect of PDT with Na-pheophorbide A on an osteosarcoma cell line in vitro was shown. Caspase activity assays suggested that PDT with Na-pheophorbide A induced an apoptotic change in HuO9 cells, mainly via activation of mitochondrial caspase -9 and -3 pathways.

A nonclassical vitamin D receptor pathway suppresses renal fibrosis.

The TGF-ß superfamily comprises pleiotropic cytokines that regulate SMAD and non-SMAD signaling. TGF-ß-SMAD signal transduction is known to be involved in tissue fibrosis, including renal fibrosis. Here, we found that 1,25-dihydroxyvitamin D3-bound [1,25(OH)2D3-bound] vitamin D receptor (VDR) specifically inhibits TGF-ß-SMAD signal transduction through direct interaction with SMAD3. In mouse models of tissue fibrosis, 1,25(OH)2D3 treatment prevented renal fibrosis through the suppression of TGF-ß-SMAD signal transduction. Based on the structure of the VDR-ligand complex, we generated 2 synthetic ligands. These ligands selectively inhibited TGF-ß-SMAD signal transduction without activating VDR-mediated transcription and significantly attenuated renal fibrosis in mice. These results indicate that 1,25(OH)2D3-dependent suppression of TGF-ß-SMAD signal transduction is independent of VDR-mediated transcriptional activity. In addition, these ligands did not cause hypercalcemia resulting from stimulation of the transcriptional activity of the VDR. Thus, our study provides a new strategy for generating chemical compounds that specifically inhibit TGF-ß-SMAD signal transduction. Since TGF-ß-SMAD signal transduction is reportedly involved in several disorders, our results will aid in the development of new drugs that do not cause detectable adverse effects, such as hypercalcemia.

Therapeutic effect of photodynamic therapy using Na-pheophorbide a on osteomyelitis models in rats.

OBJECTIVE: In this study, we examined the therapeutic effect of photodynamic therapy (PDT) using the photosensitizer Na-Pheophorbide a (Na-Phde a) on osteomyelitis models in rats. BACKGROUND: Osteomyelitis is one of the most serious infectious problems in the orthopedic field. Recently, as a new clinical approach against septic arthritis, an experimental in vivo and in vitro model for the inactivation of methicillin-resistant-Staphylococcus aureus by PDT using Na-Phde a has been developed. METHODS: Methicillin-sensitive Staphylococcus aureus (MSSA) was injected into the tibia of the rats to create osteomyelitis models (n = 10, 10 legs). A total of 560 µmol/l of Na-Phde a solution was injected into five of these tibial osteomyelitis models (five legs) 48 h after the initial MSSA infection. Sixty minutes after the Na-Phde a injection, a semiconductor laser (125 mW, 670 nm) was used to irradiate the models for 10 min with a total energy of 93.8 J/mm(2). As a control group, five rats (five legs) were treated with a phosphate buffered saline injection at 48 h after MSSA infection. Weight and leg perimeter changes were plotted. Bacterial growth, histological examination and radiological examination were evaluated at 14 days after initial treatment. RESULTS: PDT with Na-Phde a significantly prevented leg swelling. In the PDT group, bone destruction owing to osteomyelitis was inhibited not only histologically but also radiographically. CONCLUSIONS: The results in these experiments show that PDT using Na-Phde a improved osteomyelitis in rats. This suggests that PDT using Na- Phde a can be a useful treatment for osteomyelitis.

Bactericidal effect of photodynamic therapy using Na-pheophorbide a: evaluation of adequate light source.

OBJECTIVE: To evaluate the efficacy of photodynamic therapy (PDT) against methicillin resistant-Staphylococcus aureus (MRSA) by selecting different light sources for irradiation and combining them with the photosensitizer Na-Pheophorbide a (Na-Phde a). BACKGROUND: The treatment of drug-resistant bacterial infection is a serious issue. Recently, as a new clinical approach against septic arthritis, an experimental in vivo and in vitro model for the inactivation of MRSA by PDT using the photosensitizer Na-Phde a has been developed. MATERIALS AND METHODS: Na-Phde a solution (280 micromol/L) was mixed with MRSA strain bacterial inoculum. After 60 minutes, light was irradiated for 30 minutes using the following light sources: GaA1p semiconductor laser (300 mW, 670 nm), halogen lamp (75 W), xenon lamp (300 W) and fluorescent lamp (27 W). Bacterial growth was evaluated after 24 hours incubation in a blood agar culture. RESULTS: The semiconductor laser and halogen lamp groups showed perfect bactericidal effects after PDT. The xenon lamp and fluorescent lamp groups showed partial bactericidal effects. CONCLUSIONS: The results of this experiment showed that PDT using the combination of Na-Phde a with a semiconductor laser or halogen lamp showed a better bactericidal performance than with xenon or fluorescent lamps. These findings indicated that PDT using Na-Phde a could be a useful treatment for septic arthritis and soft tissue infection.