Efficacy of oral myofunctional therapy in middle-aged to elderly patients with obstructive sleep apnoea treated with continuous positive airway pressure.

BACKGROUND: Oral myofunctional therapy (MFT) is an effective treatment for mild-to-moderate obstructive sleep apnoea (OSA) in middle-aged patients. However, few reports have described its use in elderly patients with moderate and severe OSA. Moreover, no studies have examined the relationship between changes in tongue pressure with MFT and the severity of OSA. OBJECTIVE: We conducted an interventional study using MFT to evaluate the effect of MFT on middle-to-senior-aged patients with moderate or severe OSA and compared changes in apnoea-hypopnea index (AHI) and tongue pressure. METHODS: Thirty-two OSA patients (≥45 years) treated with continuous positive airway pressure (CPAP) were included. MFT was performed in parallel with CPAP. Three days after CPAP discontinuation, polysomnographies were performed and tongue pressures were measured before and after MFT. RESULTS: Patients were 69.3 ± 1.5 years old. After 6 months of MFT, AHI decreased significantly from 34.7 to 29.0/h (P = .03), while tongue pressure significantly increased from 35.9 to 45.6 kPa (P < .01). Seven patients (22%), including 6 of the 12 patients with moderate OSA (50%), experienced successful CPAP discontinuation. CONCLUSIONS: MFT can be a useful intervention even among middle-aged to elderly patients with OSA. Increased tongue pressure may have contributed to the AHI improvement. Clinical trials: Trial registration at www.umin.ac.jp UMIN000027547.

The wound/burn guidelines - 3: Guidelines for the diagnosis and treatment for diabetic ulcer/gangrene.

We aimed to prepare guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. They serve as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of the care for diabetic ulcer in Japan by systematically presenting evidence-based recommendations for clinical judgments by incorporating various viewpoints.

The wound/burn guidelines - 6: Guidelines for the management of burns.

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.

Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer.

Recently, analysis of tumor antigens using micro-arrays has revealed upregulation of cancer-testis antigens RNF43 and TOMM34 and vascular endothelial growth factor receptors VEGFR1 and VEGFR2 in colorectal cancer. A phase I clinical trial of peptide vaccine therapy together with oral anticancer drugs was conducted to treat advanced colorectal cancer using synthesized peptides of these tumor antigens in order to confirm the safety, immunogenicity and activity of this treatment. The subjects were patients with a human leukocyte antigen (HLA) type of A2402 who had inoperable colorectal cancer but had failed to respond to or were unable to undergo standard chemotherapy. Four peptides (RNF43, TOMM34, VEGFR1 and VEGFR2) were emulsified with incomplete Freund's adjuvant (Montanide), and the resulting solution was administered subcutaneously once a week. Patients received the oral anticancer drug tegafur-uracil plus leucovorin for four weeks continuously as part of one course followed by one week of rest. The primary endpoint of the trial was observation of adverse events as determined by the NCI-CTCAE criteria, and the secondary endpoints were the size of the tumor and the number of cytotoxic T lymphocytes (CTLs) in the peripheral blood after treatment. Vaccine therapy was administered 148 times to 10 patients from July 2008 to December 2009. The adverse events were grade 1 redness and induration, a grade 2 skin ulcer at the vaccination site and grade 1 pyrexia. All patients tolerated treatment. Tumor imaging revealed that after 1 course of treatment 1 patient had partial response (PR), 7 had stable disease (SD) and 2 had progressive disease. A CTL assay of 10 patients revealed an increase in peptide-specific CTLs in patients with PR and SD, and the clinical responses of those patients were observed. Kaplan­Meier analysis indicated that patients who had a strong CTL reaction had a tendency to have longer progression­free survival and overall survival.

Cortical intrinsic circuits can support activity propagation through an isofrequency strip of the guinea pig primary auditory cortex.

A pure tone evokes propagating activities in a strip of the primary auditory cortex (AI), an isofrequency strip (IS). A fundamental issue concerns the roles that thalamocortical input and intracortical connectivity play in generating the activities. Here we addressed this issue in guinea pigs using in vivo and in vitro real-time optical imaging techniques. As reported previously, tone-evoked activity propagated dorsoventrally along a strip (an IS) in AI. We found that an electrical pulse applied focally within the strip, triggered activity propagation with a spatiotemporal pattern highly similar to tone-evoked activation. The propagation velocity of electrically evoked activity was significantly slower than that of tone-evoked activity, but was comparable to the velocity of lateral activity propagation in cortical slices, suggesting that the electrically evoked activity propagation in vivo is mediated by intracortical circuits. To test this notion, we lesioned the auditory thalamus chemically; in such animals, electrically evoked activity in AI was not affected, although tone-evoked activity was abolished. Further, in slices of the AI, the extent of electrically evoked activity propagation in layer II/III was significantly larger in coronal slices than in horizontal slices. Together, our results suggest that intracortical connectivity in AI enables a focally evoked activity to propagate throughout an IS.