It was previously reported the safety and efficacy of oral tapentadol ER switched from other opioids for 8 weeks in subjects with moderate to severe cancer pain, who received opioid analgesics prior to study participation. All treatment emergent adverse events were evaluated in previous safety analysis. In this report, the incidence and timing of opioid specific adverse events related to tapentadol administration were analyzed and compared with those of morphine SR as a reference. Fifty subjects each was randomized to the tapentadol ER group and the morphine SR group. The incidences of major adverse events that are considered related to treatment in the tapentadol ER group and the morphine SR group were nausea (8.0%, 14.0%), vomiting (2.0%, 24.0%), constipation (8.0%, 20.0%), and somnolence (8.0%, 18.0%), the incidences of these events were lower in the tapentadol ER group. These results suggest that tapentadol ER is a orally opioid which has well safety profiles, and is a new option of cancer pain therapy.

In the previous papers, we reported the effects of electronic moxibustion on immune response of experimental rats to the exogeneous antigens, human γ-globulin.
The results supported the theory, “non-specific heat aggregeted autologous tissue protein stimulation therapy” presented by Dr. Shimetaro Hara in 1933.
Therefore, in this paper we chose two kinds of antigens, one is the T-cell dependent antigen, dinitrophenylated keyhole limpet hemocyanin (DNP-KLH), the other is the T-cell independent antigen dinitrophenylated Ficoll (DNP-Ficoll) to analyse the mechanism of electronic moxibustion whether it enhances the immune response or not.
Using 9 weeks old femal SLC-Wistar rats, we administered the electronic moxibustion according to the method reported in the previous papers. Following daily moxibustion for 8 weeks, antigens were giver twice at intervals of one week together with Freund's complete adjuvant. And 4 days later from the last antigen stimulation direct, DNP plaque forming cells in the spleen were counted.
The results obviously showed daily electronic moxibustion for 8 weeks enhanced immune response against the T-cell dependent antigen (DNP-KLH) stimulated rats but no effect on the immune response to the T-cell independent antigen (DNP-Ficoll) stimulated rats.
The daily electronic moxibustion for 4 weeks to rats failed to show any effective results against both antigens stimulation.
The responses of spleen cells against mitogenic lectins, PHA, Con A and PWM were analysed 3 days after the incubation with lectins by tritiated thymidine up takes into cells. The results also showed the animal group received the electronic moxibustion for 8 weeks manifested higher response against the one of T-cell mitogens, Con A compared with either the group received the electronic moxibustion for 4 weeks or the control group, not received any treatment.
These results suggested that the immune activation mechanism exhibited by the electronic moxibustion is via the activation of T-cell function and the electronic moxibustion does not act on B cell nor antibody forming cells.
The direct effects on the animal skin by the electronic moxibustion were shown exactly the same physical characteristics as the conventional moxibustion method as reported in the previous papers. Therefore, we could expect the similar T-cell activation effect on the immune response by the conventional moxibustion.
But from our results to get such a T-cell activation by the electronic moxibustion, it has been necessary to administrate the electronic moxibustion daily at least for more than 4 weeks.
Next we would like to make clear what kinds of subpopulation in the T-cell populations are activated by the electronic moxibustion.
Before the clinical administration of the electronic moxibustion as one of immune activators, it is necessary to investigate further about the optimal amounts of the moxibustion, effects of the moxibustion on the cellular immunity or tumor immunity.

The present multicenter, open-label study evaluated the efficacy and safety of tapentadol ER administered at 50 mg/day to 500 mg/day in opioid-naive and opioid-switching subjects with moderate to severe cancer pain. For opioid-naive subjects, the initial dose was tapentadol ER 50 mg/day. For opioid-switching subjects, the initial dose was determined depending on previously used opioid and was dose-adjusted for each subject. The study design consists of two parts of titration period and maintenance period to which a patient who achieves dose adjustment can proceed. The percentage of subjects achieving dose adjustment in the titration period was 93.3% for opioid-naive subjects and 80.6% for opioid-switching subjects. The percentage of subjects who maintained adequate analgesia throughout the maintenance period (primary endpoint) was 89.7% for opioid-naive subjects and 92.9% for opioid-switching subjects. The most frequent adverse events were were nausea, vomiting, somnolence, and constipation, all of which were commonly reported with the use of opioids. These findings showed that tapentadol ER was well tolerated in the dose range of 50 mg/day to 500 mg/day.

We present a case of sigmoid colon to skin fistula following surgery for abdominal aortic aneurysm that was believed to have resulted from nonocclusive mesenteric ischemia involved in low cardiac output syndrome. A 65-year-old man underwent surgical treatment for an abdominal aortic aneurysm. Although the patient had operative risks of renal dysfunction and left ventricular dysfunction due to an old myocardial infarction, the abdominal aortic aneurysm was 6cm in diameter and threatened to rupture, thus prompting surgical removal. For the operation, the abdominal aorta was clamped above the renal arteries and the aneurysm was replaced with a Y-shaped prosthetic graft following the aneurysmectomy. Among the vessels supplying the sigmoid colon, both the inferior mesenteric artery and the left internal iliac artery had become obstructed and thus only the right internal iliac artery could be successfully reconstructed. The patient suffered from low cardiac output syndrome after surgery and subsequently experienced renal dysfunction, liver dysfunction and a disturbance of the peripheral circulation. On postoperative day number 7, the patient complained of watery diarrhea occurring several times a day and abdominal distension as a result of the ischemic colitis. On day number 16, the sigmoid colon to skin fistula developed. Oral intake was discontinued and nutritional support thereafter consisted of intravenous hyperalimentation. In addition, enteral nutrition using an elemental diet was begun. The fistula was successfully closed two weeks later and the patient recovered with no further complications.

A 78-year-old man with obstruction of the right common femoral artery due to arteriosclerosis obliterans underwent successful amputation of his leg. On the first postoperative day he received transfusion of three units of preserved blood. He continued to recover until postoperative day 7, when he developed a high fever, erythroderma and diarrhea. His condition gradually deteriorated and on postoperative day 15 he demonstrated severe and progressive leukopenia and thrombocytopenia. Although he underwent intensive treatment he died on postoperative day 20. A skin biopsy specimen revealed evidence of post-transfusion graft-versus-host disease.

Introduction: We aimed to evaluate the impact of lifestyle modifications on the risk of eradication failure in patients undergoing first-line therapy for Helicobacter pylori infection.Methods: A survey was conducted in a community pharmacy to assess changes in alcohol consumption, smoking, and high-fat diet intake before, during, and after first-line therapy for H. pylori infection in enrolled patients.Results: A total of 100 patients (response rate: 3.4%) were included in the analysis. Before therapy, 20 patients (20%) smoked, 35 patients (35%) consumed alcohol, and 91 patients (91%) had a high-fat diet. During therapy, the proportion of patients who changed their habits was 15.0% (3/20) for smoking, 71.4% (25/35) for alcohol consumption, and 28.6% (26/91) for high-fat diet. However, the continuation of these changes post-therapy was minimal.Conclusion: Among patients undergoing first-line therapy for H. pylori infection, lifestyle habits that increase the risk of eradication failure were prevalent, with many patients maintaining their habits during therapy except for alcohol consumption. These findings provide fundamental data for lifestyle counselling during eradication therapy.

No study has described Streptococcus dysgalactiae subsp. equisimilis (SDSE) isolates that cause repetitive infections (recurrence and reinfection). We compared the microbiological characteristics of SDSE causing repetitive infections with those causing single infections. Three patients with invasive infections were identified based on their medical records, and multiple SDSE isolates were collected at intervals over three weeks, using a laboratory repository. Isolates from 12 patients with single-episode infections served as controls. Six isolates were collected from three patients with first and second episodes of infection. All isolates causing either repetitive or single-episode infection were subjected to emm typing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and random amplified polymorphic DNA (RAPD) analyses. Amplification of five virulence genes (sicG, prtF1, prtF2, lmb, and cbp), biofilm formation (BF), and cell invasion abilities (CIAs) were measured as virulent phenotypes. We observed close genetic similarities in the data obtained by emm typing, MLST, PFGE, and RAPD in four isolates from two patients, suggesting recurrence, whereas two isolates from one patient indicated genetic differences in these data, suggesting re-infection. The presence of the five virulence genes and the BF and CIA measurements appeared not to contribute to repetitive infections, compared with isolates causing single-episode infection. In conclusion, clinicians encountering patients with repetitive infections should be aware of both possibilities: recurrence with closely related strains and reinfection with different strains.
Biofilms ; DNA ; Electrophoresis, Gel, Pulsed-Field ; Humans ; Medical Records ; Multilocus Sequence Typing ; Phenotype ; Recurrence ; Streptococcus ; Virulence

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.