Evaluation of genetic factors involved in nocturnal electromyographic activity of masticatory muscles in twins.

OBJECTIVES: The objectives of this study were to assess sleep bruxism events by directly recording electromyographic activity during sleep and to reveal the relative importance of genetic and environmental factors involved in sleep bruxism in twins. MATERIAL AND METHODS: The subjects consisted of 108 twins (mean age 22.2 ± 6.4 years). Electromyographic activity of temporalis muscles during sleep was evaluated using a portable automatic sleep bruxism analyzer (Grindcare 3.0, Medotech A/S), and recordings were carried out for at least three consecutive nights. Quantitative genetic statistics based on structural equation modeling was utilized to estimate variance components. RESULTS: Monozygotic twin-pair correlation for the number of nocturnal electromyographic activities recorded in this study (r = 0.463, P = 0.009) was higher than dizygotic twin-pair correlation (r = 0.103, P = 0.725). The proportion of total phenotypic variance in the liability of sleep bruxism to attribute to genetic influences, related to the electromyographic activities, was 48 % (95 % CI 17-95 %) and to unique environmental influences was 52 % (95 % CI 28-82 %). CONCLUSIONS: Additive genetic effects may be a contributing factor to the occurrence of nocturnal EMG activity associated with sleep bruxism. CLINICAL RELEVANCE: A greater understanding of the contribution of genetic factors could have beneficial uses, including enhanced accuracy of sleep bruxism diagnosis, management of sleep bruxism, and enhanced estimation of the prognosis for patients suffering from sleep bruxism. In addition, it could be also important to adequately evaluate the environmental factors in patients with sleep bruxism.

Risk of perforation during dilation for esophageal strictures after endoscopic resection in patients with early squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Growing evidence suggests that esophageal stricture frequently develops after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in early esophageal cancer patients, with an incidence proportional to the greater extent of mucosal defects resulting from improved EMR/ESD techniques. There seems to be a potential risk of perforation during bougienage in such patients. PATIENTS AND METHODS: 648 stricture dilations for 78 lesions in 76 patients were consecutively included. The outcomes after combined use of Maloney and Savary wire-guided bougienage for esophageal strictures after EMR/ESD were analyzed in a single-institute retrospective case series study. The perforation rate was determined and risk factors for perforation were identified. RESULTS: Patients underwent a median of 5.0 dilation procedures performed over a median 3.0 months for post-EMR/ESD strictures. Initial dilation was done a median 14 days following endoscopic resection. Perforations developed in seven patients (7/648 dilation procedures, 1.1%), all in the lower esophagus, and bleeding occurred in one patient (0.1% dilations). Two independent risk factors for development of perforation during dilation therapy for post-EMR/ESD stricture were identified: multiple dilations (odds ratio [OR] 1.2; P=0.012), and lower site of stricture (OR 12.8; P=0.043). Dysphagia was ameliorated by the dilations, and no patient required surgery. CONCLUSIONS: A specific emerging risk of perforation in dilation therapy for post-EMR/ESD strictures was identified. Carefully planned treatment is necessary in patients with severe post-EMR/ESD strictures especially strictures requiring multiple dilations or located in the lower esophagus.

Mean power frequency during speech in myalgia patients.

The purpose of this study was to clarify a difference of mean power frequency (MPF) during speech between control and myalgia patients groups. The control group consisted of 20 asymptomatic volunteers and the myalgia patients group consisted of 19 patients. A bilateral electromyogram (EMG) of masseter muscles during speech movement was recorded using surface electrodes, and the EMG data were stored and analysed with a computer-based EMG analyzer. The MPF during the entire duration of EMG burst during speech was compared between the control and myalgia group. The average (SD) MPFs during speech in the myalgia and control groups were 214.06 (17.23) and 183.39 (22.35) Hz, respectively, significantly higher in the former (P < 0.001). In myalgia patients, firing rates or recruitment of motor units innervated by high threshold motoneurons might decrease and lead to a higher MPF. The result suggests the possibility that muscle pain, that is a subjective experience, could be evaluated by objective data that is calculated from electromyographic activities which is recorded during speech.

Catheter-related bloodstream infection due to Rhodotorula mucilaginosa with normal serum (1→3)-ß-D-glucan level.

Rhodotorula species are environmental basidiomycete yeasts that have emerged as a cause of fungemia in immunocompromised hosts. The insertion of a central venous catheter was identified as a major risk factor for Rhodotorula fungemia. Few cases reports have reported (1→3)-ß-D-glucan testing at the onset of Rhodotorula mucilaginosa fungemia. We report a case of catheter-related bloodstream infection due to R. mucilaginosa. Serum ß-D-glucan level was normal at the onset of the bloodstream infection. It took 5 days to culture the isolate. The patient's fever persisted after empiric treatment with micafungin, and a switch to oral voriconazole immediately resolved the fungemia.

The mouse L-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region.

To investigate the regulation of mouse L-histidine decarboxylase (HDC) gene expression, we isolated genomic DNA clones encoding HDC. Structural analysis revealed that the mouse HDC gene was composed of 12 exons, spanning approximately 24 kb. Northern blotting analysis indicated that, among the cell lines examined, a high level of HDC gene expression was restricted to mature mast cell lines and an erythroblastic cell line. The gene was induced strongly in the mouse immature mast cell line P815 after incubation in the peritoneal cavity of BDF1 mice. We observed that the promoter region was demethylated in the HDC-expressing cell lines and in induced P815 cells. Interestingly, forced demethylation by 5-azacytidine (5-azaC) treatment induced high expression of HDC mRNA in P815 cells. The activity of a mouse HDC promoter-reporter construct stably transfected in P815 cells was repressed by in vitro patch-methylation. This low promoter activity of the patch-methylated reporter construct was restored after 5-azaC treatment, which demethylated the patch-methylated promoter. These results indicate that DNA methylation state of the promoter region controls HDC gene expression.

Clinical significance of dual-energy CT-derived iodine quantification in the diagnosis of metastatic LN in colorectal cancer.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of dual-energy computed tomography (DECT) in detecting lymph node (LN) metastasis in patients with colorectal cancer. METHODS: Data from 81 LNs from 28 patients with colorectal adenocarcinoma were retrospectively analyzed. All patients received DECT before surgery without any neoadjuvant therapy. The diagnostic value was assessed using the iodine concentration (IC). RESULTS: In the pathological findings, 35 (43.2%) LNs from 13 patients were metastatic and 46 (56.8%) LNs from 17 patients were non-metastatic. The mean IC of metastatic LNs in the portal venous phase (PP) was 1.60 mg/ml, which was significantly lower compared with non-metastatic LNs (3.25 mg/ml, p < 0.001). Receiver operating characteristic (ROC) analysis revealed that the IC in PP had the highest ability to discriminate LN metastasis (area under the ROC curve [AUC] 0.932). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IC in PP (cutoff 2.1 mg/ml) were 87.0%, 88.6%, 85.3%, 90.0%, and 87.9%, respectively. When clinically obvious metastatic LNs in conventional CT findings were excluded, 50 LNs remained (5 metastatic and 45 non-metastatic LNs). In this subgroup analysis, the IC in PP remained the most powerful predictor of metastatic LNs (cutoff: 2.1 mg/ml, AUC 0.933). CONCLUSIONS: The evaluation of IC in DECT may improve the diagnostic capabilities of discriminating metastatic LNs. This method may be particularly useful when conventional CT findings lead to equivocal results.

Use of PCR serum in diagnosing and monitoring cytomegalovirus reactivation in bone marrow transplant recipients.

We previously reported that the use of polymerase chain reaction (PCR) in detecting cytomegalovirus (CMV) DNA in serum (sPCR) enables the detection of CMV viremia, which has not been possible with other methods. In this study, the clinical usefulness of sPCR was investigated by comparison with the results of three other diagnostic methods, i.e., antigenemia assay (AG), shell vial culture test (shell vial), and complement-fixing (CF) antibody titer. The present study included 26 patients with hematological diseases who had undergone allogeneic bone marrow transplantation (BMT). A total of 347 samples were collected, and the results of the sPCR and AG methods were in agreement in 91.1% of the samples. When a subject was positive in both the sPCR and AG tests, and the other two tests (shell vial and CF) were also positive, CMV reactivation was surmised as definite. When only the result of the shell vial test or the CF test was positive, these results were taken as false-positives. The time at which the samples became positive in each of these four tests was 7.5 weeks post-BMT for sPCR, 7.0 weeks post-BMT for the AG test, 7.4 weeks post-BMT for the shell vial test, and 9.7 weeks post-BMT for the CF test. Thus, it was found that samples became positive at almost the same time for the sPCR, AG, and shell vial tests. Interstitial pneumonitis (IP) due to CMV developed in 3 subjects. These cases were positive in the sPCR, AG, and shell vial tests prior to the manifestation of symptoms of IP. The CF test did not become positive until after the onset of the disease. As the IP due to CMV was controlled with treatment, the sPCR and AG tests became negative. With the shell vial and CF tests, on the other hand, the test results continued to be positive even after the IP was cured. These findings demonstrate that the sPCR test method--like the AG test--yields few false-positive results. Therefore, the sPCR method is useful in early diagnosis of reactivation of CMV and for evaluation of the efficacy of therapy administered for IP. In addition, sPCR can be performed simultaneously on a large number of samples, and the evaluation of the test results is simple. We conclude that the sPCR test may be superior to the three other diagnostic methods for evaluation of serum samples from multiple institutions.

Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia.

An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats.

Determination of antigenic epitopes recognized by four monoclonal antibodies to glutathione S-transferase pi (GST-pi).

Four independent antibodies (6A, 5F, 2H and 2F) to Glutathione S-transferase pi (GST-pi) were selected to characterize their epitopes. Amino acid analysis of 5.6 K and 7.4 K tryptic peptides appeared to suggest that the epitope recognized by antibodies 2H and 2F is located in the N-terminal 44 peptides of GST-pi, and that of 6A and 5F is located in the C-terminal 69 peptides. Reactivities of antibodies 6A and 5F with two synthetic peptides indicated that 6A recognized an epitope in the C-terminal hydrophilic fragment 176Leu-209Gln, and could be distinguished from 5F which recognized an epitope in the 141Thr-176Leu hydrophobic fragment. The differential immuno-reactivity of antibodies 6A and 5F with GST-pi itself, was characterized by the particularly high reactivity of 6A and almost no reactivity of 5F with the natural conformation of GST-pi in solution. This may be explained by differences in the hydropathic natures of their epitopes. The 6A antibody was useful for immunodetection of GST-pi in circulation, while 5F was found to be most suitable for histochemical staining of tumor tissue.

[Evaluation of a new method for antifungal drugs susceptibility testing to yeasts].

We compared the Etest with a broth microdilution method (FP panel), performed according to the National Committee for modified Clinical Laboratory Standards (NCCLS) document M27-P guidelines, for determining the MICs of 81 clinical isolates of yeasts (7 Candida albicans, 8 Candida glabrata, 10 Candida parapsilosis, 6 Pichia anomala, 10 Candida tropicalis, 4 Candida guilliermondii, 4 Candida krusei, 6 Trichosporon cutaneum, 5 Candida ciferrii, 3 Candida famata, 4 Candida norvegensis, 2 Rhodotorula rubra, 3 Candida lusitaniae, 2 Candida curvata, 1 Candida inconspicua, 1 Candida intermedia, 1 Candida colliculosa, 1 Cryptococcus spp, 1 Tricosporon capitatum, 1 Pichia ohmeri, 1 Saccharomyces cerevisiae). The Etest results for 6 ATCC standard strains correlated well with reference MICs except those of flucytosine (5-FC) for C. krusei, which tended to be 1 to 2 log2 dilution higher than the MIC range determined by NCCLS guidelines. However, the best agreement between the results for clinical isolates was seen with 5-FC (100% agreement [Within +/- 2 log2 dilutions] between the results of the two methods). There was a 91.4% agreement between the results of the two methods with amphotericin B (Etest MICs tended to be 1 to 2 log2 dilution lower than those of the FP panel). The Etest results with litraconazole for clinical isolates except C. tropicalis were similar to MICs of the FP panel (Etest for C. tropicalis showed 1 to 2 log2 dilution lower than FP panel). Also, the Etest results with fluconazole for clinical isolates except C. tropicalis were similar of 1 log2 dilution higher than MICs of the FP panel (Etest for C. tropicalis showed more than 2 log2 dilution lower than FP panel). These results showed a good level of overall agreement between the Etest method and the broth microdilution test (FP panel). Since the Etest is a less laborintensive and much simpler method, it appears to be a useful procedure for testing the susceptibility of yeasts to antifungal agents.

Vibration analysis of the temporomandibular joints with meniscal displacement with and without reduction.

The vibrations of 102 joints demonstrating meniscal displacement with either early or late reduction (MDR-early/MDR-late) and 70 joints displaying meniscal displacement without reduction either incomplete or complete (MD-incomplete/MD-complete) were analyzed and compared to 83 arthrographically normal but symptomatic joints (NID) using electrovibratography (EVG). The total power density of the vibration [I(T)], peak power density [I(max)] and power density at each 50Hz range between O to 600 Hz [I(f)] showed the highest in the MDR-late group followed by the MDR-early group, suggesting that the level of vibration is related to the degree of disk displacement and reduction. The wave characteristic parameters such as the correlation coefficients between I(T) and each I(f) showed higher correlation at higher frequency ranges as the degree of disk displacement progressed, from MDR-early to MDR-late to MD-incomplete. The diagnostic sensitivity of EVG when using I(T) as a determining parameter was 96.6% for the MDR-early group, 91.8% for the MDR-late group, 77.8% for the MD-incomplete group and 57.4% for the MD-complete group with the specificity for the NID group at 75%.

A clinical study of temporomandibular joint (TMJ) vibrations in TMJ dysfunction patients.

Using electrovibratography (EVG), the vibrations of 309 temporomandibular joints (TMJs) from 213 patients with clinical symptoms of temporomandibular joint dysfunction (TMD) were compared to TMJ arthrography. Of 309 imaged joints, 221 had an internal derangement (ID) and 88 were arthrographically normal (NID). Among the parameters derived from the power spectrum function of joint vibration, the total power density from 0 to 600 Hz (I(T)), the peak power density I(max)), and the power density at each 50 Hz frequency range (I(f)), each of these was significantly greater in ID than in NID patients. The frequency range that included (I(max) and the frequency range containing 50%, 75%, and 90% of I(T) was significantly lower in ID than in NID patients. The diagnostic sensitivity and specificity of a patient's perception of TMJ sounds were 43% and 80%, respectively, while those for a doctor's perception were 54% and 72%. When using I(T) as a parameter, the sensitivity and specificity of the EVG were 75% and 77%, respectively. By using these parameters of TMJ vibration energy analysis, a separation may be made between patients with normal joint anatomy and internal derangement.

Vibration analysis of the temporomandibular joints with degenerative joint disease.

The surface vibrations of 42 temporomandibular joints (TMJ) with degenerative joint disease (DJD) and/or perforation of the disk were evaluated using electrovibratography and compared to the surface vibrations of 83 joints with normal TMJ imagings and 61 joints with meniscal displacement without reduction. Through the frequency spectrum analysis, TMJs with DJD showed higher vibration energy above 350-450 Hz and TMJs with perforation showed higher vibration energy between 100-150 and 300-450 Hz. The presence of perforation did not seem to affect the characteristic of vibrations when TMJs were associated with DJD. A threshold was set for the total vibration energy as described in our previous report and used as a parameter in order to separate patients with internal derangement from a pool of TMJ dysfunction patients (diagnostic specificity = 75%, diagnostic sensitivity = 80.2%). Using this criteria, the following were correctly identified as internal derangement and/or DJD: a) 100% of the TMJs with meniscal displacement without reduction associated with DJD; b) 87.0% of the TMJs with meniscal displacement without reduction associated with perforation; c) 88.9% of the TMJs with meniscal displacement without reduction associated with DJD and perforation; and d) 100% of the TMJs with perforation.

The distribution of internal derangement in patients with temporomandibular joint dysfunction--prevalence, diagnosis, and treatments.

This study consisted of 355 patients referred to a surgical practice complaining of facial pain, temporomandibular joint (TMJ) sounds, and limited jaw opening. In 247 patients, 360 TMJs were evaluated by arthrography. While 72.2% of them had internal derangement, the remaining 27.8% had normal arthrograms (NID). Among the patients with internal derangement, meniscal displacement with reduction (MDR) was the largest group (47.3%), followed by meniscal displacement without reduction (MD) (32.3%), meniscal displacement without reduction associated with perforation (MDP) (15.4%), and perforation with normal disk position (P) (5.0%). The NID, MDR, and MD groups showed similar age distributions. The MDP and P groups showed a significantly older mean age. Gender distribution was biased toward females (82.0%). Of the total number of joints, 183 (50.8%) had a history of trauma, 69.9% of which had an internal derangement. In terms of treatment, 100% of the NID group was treated by splint therapy. The MDR group was mostly treated by partial meniscectomy (49.6%) and splint therapy (41.5%). The MD group was mostly treated by total meniscectomy (53.6%) followed by splint therapy (32.1%). The MDP or P groups mostly underwent total meniscectomy (72.5% and 61.5%, respectively).

Vibration of the temporomandibular joints with normal radiographic imagings: comparison between asymptomatic volunteers and symptomatic patients.

In order to estimate the effect of a background noise during temporomandibular joint (TMJ) vibration analysis, 40 recordings from sensors not attached to subjects and sensors attached to subjects without any jaw movement were evaluated. Both of them showed very small energy density, close to 0, throughout 0 to 600 Hz and flat frequency distributions. To evaluate the vibration energy of asymptomatic TMJs with normal joint anatomy and symptomatic TMJs with normal arthrographic imagings, 20 TMJs from 10 clinically normal and asymptomatic volunteers with bilateral normal TMJ computerized tomography (CT) scanning (N-control) were analyzed at four mandibular positions. Results from intercuspal position and maximal opening were identical to the background noise. Results from closing and opening phase showed higher energy, especially below 150 Hz, than the background noise. Surface vibrations of 83 TMJs from patients with arthrographically normal imagings but having symptoms (NID) showed significantly higher energy than the N-control group above 300 Hz. When the total vibration energy (I(T)) is used to set the threshold for the separation of internal derangement, at I(T) = 2.06, the diagnostic specificity for the NID group is 75%, while the diagnostic sensitivity is 82.4% for internal derangement. At the same time, 98.3% of the N-control group was involved below the threshold.

Diagnostic accuracy of TMJ vibration analysis for internal derangement and/or degenerative joint disease.

Lower joint arthrography and videofluoroscopy were used to diagnose 297 joints from temporomandibular disorders (TMD) patients. The surface vibrations of the temporomandibular joints (TMJs) were recorded by electrovibratography and a parameter set was derived through frequency analysis. Total vibration energies were used as the primary separating threshold for abnormal joints. The following conditions were statistically discriminated by multi-variate analyses: I) meniscal displacement with reduction; II) meniscal displacement with a partial disk reduction; III) meniscal displacement without reduction; and IV) degenerative joint disease and/or perforation of the disk. Using the total vibration energy as a threshold, the diagnostic sensitivity for the abnormal joints was 82%, while the diagnostic specificity for the joints with no evidence of internal derangement was 75%. Discriminant analysis for the above-mentioned four conditions revealed a diagnostic sensitivity of 79.0%, 85.7%, 77.1% and 76.3% for conditions I, II, III and IV, respectively. The diagnostic specificity was 76.2%, 79.9%, 59.0% and 77.9% for conditions I, II, III and IV, respectively. It was concluded that vibration analysis of the TMJ could be clinically useful as a screening examination for TMD patients.

[Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE].

A 48-year-old woman, who had been suffering from systemic lupus erythematosus (SLE), developed normochromic normocytic anemia after receiving clomipramine hydrochloride. Her reticulocyte count was low, and a bone marrow aspirate revealed erythroid hypoplasia without involvement of other cell lines. Thus a diagnosis of pure red cell aplasia (PRCA) was made. The anemia gradually resolved following withdrawal of the drug. Although several drugs are known to cause PRCA, this is the first time that clomipramine hydrochloride has been reported to have such an effect. The underlying SLE in this case suggested the possible immunological pathogenesis of drug-induced PRCA.

[A case of advanced mediastinal choriocarcinoma showing complete remission for two years by high-dose chemotherapy with peripheral blood stem cell transplantation].

A twenty-six-year-old male patient with advanced choriocarcinoma originated from mediastinum was treated by high-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation. He had massive tumors in the cervical, mediastinal and bilateral lung fields. After 3 kur of PVeBV therapy (CDDP 60 mg x day 1-3, etoposide 160 mg x day 1-3, BLM 30 mg x day 1, VBL 12 mg x day 1), he obtained complete remission. PBSC was collected at the time of hematopoietic recovery and high-dose chemotherapy with PBSC transplantation was conducted because of the high possibility of recurrence. The hematopoietic recovery was rapid, and the patient remained well with no sign of recurrence for 24 months.

[A remarkable effect of K-18 (IgG-melphalan complex) in a case of RAEB with hypoplastic marrow].

A 63-year-old male with refractory anemia with excess of blasts (RAEB) and hypoplastic marrow was treated with K-18 (240 mg/day P.O.). On admission, peripheral blood revealed pancytopenia. Bone marrow specimen revealed severe hypocellularity with 18.9% of the blast cells. Ten months later, the blast cells in the bone marrow decreased to 3.8%, and complete remission (CR) was obtained. CR was eight weeks. Duration of response (CR + PR) continued for about eight months. K-18 is an antitumor agent with minimal side effects, and seems to be effective for RAEB with hypoplastic marrow.

[Studies on platelet aggregation induced by human cultured carcinoma cell lines].

Attempts were made to clarify the mechanism of platelet aggregation and to characterize the platelet aggregating material employing established human cancer cell lines. Eleven out of the nineteen human cancer cell lines investigated showed platelet aggregating activity. The existence of divalent cation was required for the platelet aggregation induced by HMV-1 tumor cells. The platelet aggregations induced by tumor cells (HMV-1, PC-10, 3LL) were not suppressed by specific thrombin inhibitor (MD-805). The platelet aggregating activities of tumor cells (HMV-1, M 7609) were diminished by treatment with trypsin but not with collagenase or neuraminidase. Aggregating activity was preserved with a preparation of membrane from these tumor cells, although it was abolished by heating(100 degrees C 15 min) or sonication. By SDS PAGE (autoradiography), membrane proteins with MW of 20,000 daltons which specifically bound to platelets were commonly found in cells with platelet aggregating activity (HMV-1, M 7609), but were absent in platelet non-aggregating cells (HGC-25). It is therefore concluded that platelet aggregation induced by human tumor cells does not require the coexistence of thrombin, but is evoked by direct interaction of platelets with aggregating proteins (MW 20,000 daltons) on the cell membrane.