The effect of oral appliances that advanced the mandible forward and limited mouth opening in patients with obstructive sleep apnea: a systematic review and meta-analysis of randomised controlled trials.

Oral appliances (OAs) have demonstrated efficacy in treating obstructive sleep apnea (OSA), but many different OA devices are available. The Japanese Academy of Dental Sleep Medicine supported the use of OAs that advanced the mandible forward and limited mouth opening and suggested an evaluation of their effects in comparison with untreated or CPAP. A systematic search was undertaken in 16 April 2012. The outcome measures of interest were as follows: Apnea Hypopnea Index (AHI), lowest SpO2 , arousal index, Epworth Sleepiness Scale (ESS), the SF-36 Health Survey. We performed this meta-analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Five studies remained eligible after applying the exclusion criteria. Comparing OA and control appliance, OA significantly reduced the weighted mean difference (WMD) in both AHI and the arousal index (favouring OA, AHI: -7.05 events h(-1) ; 95% CI, -12.07 to -2.03; P = 0.006, arousal index: -6.95 events h(-1) ; 95% CI, -11.75 to -2.15; P = 0.005). OAs were significantly less effective at reducing the WMD in AHI and improving lowest SpO2 and SF-36 than CPAP, (favouring OA, AHI: 6.11 events h(-1) ; 95% CI, 3.24 to 8.98; P = 0.0001, lowest SpO2 : -2.52%; 95% CI, -4.81 to -0.23; P = 0.03, SF-36: -1.80; 95% CI, -3.17 to -042; P = 0.01). Apnea Hypopnea Index and arousal index were significantly improved by OA relative to the untreated disease. Apnea Hypopnea Index, lowest SpO2 and SF-36 were significantly better with CPAP than with OA. The results of this study suggested that OAs improve OSA compared with untreated. CPAP appears to be more effective in improving OSA than OAs.

Effect of a speech aid prosthesis on reducing muscle fatigue.

It has been reported that the levator veli palatini muscles of speakers with velopharyngeal incompetence tend to demonstrate muscle fatigue during speech. This study examined whether a speech aid prosthesis might reduce levator muscle fatigue in such speakers. Eight individuals with post-surgical cleft palates, and who wore a speech aid prosthesis, were studied. Each person was asked to pronounce the syllable [pu] more than 50 times. Mean power frequency (MPF) of one syllable was obtained from electromyographic data from the levator muscle. The MPF regression line was calculated during the course of syllable repetition. The absolute values of the slopes of the regression lines with the prosthesis were significantly smaller than those without the prosthesis. It was shown that the prosthesis reduced the decrease in MPF during speech. These results suggested that speech aid prostheses reduce levator muscle fatigue during speech in persons with velopharyngeal incompetence.

Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene.

The HLA-Cw6 antigen has been associated with psoriasis vulgaris despite racial and ethnic differences. However, it remains unclear whether it is the HLA-Cw6 antigen itself or a closely linked, hitherto unidentified, locus that predisposes to the disease. Here, in order to map the susceptibility locus for psoriasis vulgaris precisely within the HLA class I region, 11 polymorphic microsatellite markers distributed throughout a 1060 kb segment surrounding the HLA-C locus were subjected to association analysis in Japanese psoriasis vulgaris patients. Statistical analyses of the distribution and deviation from Hardy-Weinberg equilibrium of the allelic frequency at each micro-satellite locus revealed that the pathogenic gene for psoriasis vulgaris is located within a reduced interval of 111 kb spanning 89-200 kb telomeric of the HLA-C gene. In addition to three known genes, POU5F1, TCF19 and S, this 111 kb fragment contains four new, expressed genes identified in the course of our genomic sequencing of the entire HLA class I region. Therefore, these seven genes are the potential candidates for susceptibility to psoriasis vulgaris.

HLA-A33 and -B44 and susceptibility to postherpetic neuralgia (PHN).

HLA class I and class II alleles of 32 Japanese patients with postherpetic neuralgia (PHN) and 136 healthy controls were analyzed by serological (class I) and DNA (class II) typing for any significance in the susceptibility to varicella-zoster virus (VZV). We recognized positive associations of the development of PHN with the HLA class I antigens HLA-A33 and -B44, and the HLA-A33-B44 haplotype. This haplotype is tightly linked to DRB1*1302 in a Japanese healthy population. However, no significant association between PHN and HLA class II alleles was observed with no linkage of the HLA haplotype HLA-A33-B44 to HLA-DRB1*1302 in the patients with PHN. These findings suggest that HLA class I gene may genetically control the immune response against VZV in the pathogenesis of PHN.

Follow-up of clinical efficacy of iontophoresis therapy for postherpetic neuralgia (PHN).

A great variety of therapies have been attempted for PHN, including pharmacotherapy and physical therapy. However, there has been no decisive treatment, and reports of the clinical efficacy of all available therapies have been rather controversial. Almost all studies conducted so far have looked only at short-term therapeutic efficacy, and only a few investigators have conducted long-term observations or studies on long-term outcome. We followed up the clinical efficacy of iontophoresis therapy using lidocaine and methylprednisolone in 197 PHN patients. Monitoring conducted for an average of 4 years after completion of the treatment showed that pain remained unchanged or improved compared to pain observed upon completion of the treatment in 90.4% of patients. Although 42.6% of patients were still continuing some treatment, 90.9% were found to be able to take care of themselves. Findings obtained were reviewed and discussed from various viewpoints. Our findings showed that iontophoresis therapy is not only effective at the end of the treatment, but its efficacy is maintained over a long period of time, indicating that it is clinically very useful for the treatment of PHN.

Role of patellar tendon on the population of muscle fiber types and the contractile properties of single glycerinated muscle fibers in quadriceps muscles of rats.

The role of the patellar tendon (PT) in the contractile properties of quadriceps muscle was investigated. After PT resection (partial or complete), PT reconstruction, or a sham operation, rats were forced to run on a rodent treadmill. The histochemical and mechanical characteristics of the vastus medialis (VM) and vastus lateralis (VL) muscles were examined 2, 4, and 8 weeks after treatment. There were no significant changes in either fiber type population or the contractile properties of glycerinated single muscle fibers from VM and VL 2 and 4 weeks after partial PT resection. Complete PT resection caused a decrease in the population of type I fibers in VM, while the running training after PT reconstruction increased the population of type I fibers in VM. For both the PT resection and PT reconstruction groups, the Hill coefficient, an indicator of the Ca2+ sensitivity of myofilaments, was calculated from the pCa-tension relationship of glycerinated single muscle fibers. In the PT reconstruction group, the Hill values for fibers isolated from VM were significantly decreased by running training, but the Hill values for VL were not. The effect of running training on the Ca2+ sensitivity of myofilaments in muscle fibers with PT reconstruction was different from that in muscle fibers without PT treatment. Both resection and partial resection of the PT in this animal model had heterogeneous effects on the contractile properties of quadriceps muscles; we presume that, clinically, we must give careful consideration to PT treatment.

[Ultrastructural alterations of Golgi tendon organs in disuse atrophy induced by muscle immobilization in rats].

In order to investigate changes in the ultrastructure of Golgi tendon organs (GTOs), the leg muscles of Wistar strain rats were immobilized over various periods. The immobilized triceps surae muscles were divided into three categories: a stretched-position group, a relaxed-position group, and Achilles tendon tenotomy group. After 1, 2, 3, 4, 6 and 8 weeks the muscle preparations dissected from the muscle belly and from the muscle-tendon junction were processed for classification of the fiber type histochemically and to find GTOs in plastic embedded-preparations. In the Achilles tenotomy group, an early fiber transformation from type I to type II fiber was observed, but in the other two groups a low rate of transition of fiber type occurred. At the end of 8 weeks, similar tendencies were observed in all groups. The ultrastructures of GTOs were not significantly different among three groups in basic and general structure when compared with the control group. However, swollen mitochondria in axons and axon terminals and damage in the lamina structure of the myelin sheath were seen in the capsule, axon terminal, and myelinated nerve fiber of GTOs. Although some differences were observed with shorter periods of immobilization, several structural changes were observed over longer periods, indicating the more profound effect of the length of the period rather than the type of immobilization.

Alteration of catalytic properties of chymosin by site-directed mutagenesis.

Artificial mutations of chymosin by recombinant DNA techniques were generated to analyze the structure--function relationship in this characteristic aspartic proteinase. In order to prepare the mutant enzymes in their active form, we established procedures for purification of correctly refolded prochymosin from inclusion bodies produced in Escherichia coli transformants and for its subsequent activation. Mutagenesis by linker insertion into cDNA produced several mutants with an altered ratio of milk clotting activity to proteolytic activity and a different extent of stability. In addition to these mutants, several mutants with a single amino acid exchange were also constructed by site-directed mutagenesis and kinetic parameters of these mutant enzymes were determined by using synthetic hexa- and octa-peptides as substrates. Exchange of Tyr75 on the flap of the enzyme to Phe caused a marked change of substrate specificity due to the change of kcat or Km, depending on the substrate used. Exchange of Val110 and Phe111 also caused a change of kinetic parameters, which indicates functional involvement of these hydrophobic residues in both the catalytic function and substrate binding. The mutant Lys220----Leu showed a marked shift of the optimum pH to the acidic side for hydrolysis of acid-denatured haemoglobin along with a distinct increase in kcat for the octa-peptide in a wide pH range.