Preoperative evaluation of pleural adhesions with dynamic chest radiography: a retrospective study of 146 patients with lung cancer.

AIM: To assess the utility of dynamic chest radiography (DCR) during the preoperative evaluation of pleural adhesions. MATERIALS AND METHODS: Sequential chest radiographs of 146 patients with lung cancer were acquired during forced respiration using a DCR system. The presence of pleural adhesions and their grades were determined by retrospective surgery video assessment (absent: 121, present: 25). The maximum inspiration to expiration lung area ratio was used as an index for air intake volume. A ratio of ≥0.65 was regarded as insufficient respiration. Two radiologists assessed the images for pleural adhesions based on motion findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared for each adhesion grade and patient group (patients with sufficient/insufficient respiration). Pearson's chi-squared test compared the group. Statistical significance was set at p<0.05. RESULTS: DCR correctly identified 22/25 patients with pleural adhesions, with 20 false-positive results (sensitivity, 88%; specificity, 83.5%; PPV, 52.4%; NPV, 97.12%). Although the diagnostic performances for the various adhesion grades were similar, specificity in patients with sufficient respiration increased to 93.9% (31/33), identifying all cases except for those with loose adhesions. CONCLUSIONS: DCR images revealed restricted and/or distorted motions in lung structures and structural tension in patients with pleural adhesions. DCR could be a useful technique for routine preoperative evaluation of pleural adhesions. Further development of computerised methods can assist in the quantitative assessment of abnormal motion findings.

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

Relationships among maxillofacial morphologies, bone properties, and bone metabolic markers in patients with jaw deformities.

The aim of this study was to determine the relationships among bone properties, bone metabolic markers, and types of jaw deformity. The subjects were 55 female patients with jaw deformities. Skeletal morphology was examined using lateral cephalograms, and the patients were divided into three groups according to the type of anteroposterior skeletal pattern. Serum osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase isoform 5b, as well as deoxypyridinoline in urine, were measured as bone metabolic markers. Quantitative ultrasound (QUS) measurements were used to assess bone properties at the calcaneal bone. The bone volume and bone density of the condylar process were measured in 43 patients by computed tomography. There were no significant differences in bone metabolic markers and QUS parameters between the groups, although bone formation and resorption markers tended to be higher in patients with a protrusive mandible. On the other hand, patients with mandibular retrusion had a higher tendency to have small and dense condylar processes. In conclusion, the results suggest that growth depression or a degenerative change in the mandibular condyle is involved in the pathogenesis of mandibular retrusion, although risk factors for progressive condylar resorption were not determined.

A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: synthesis and structure-activity relationships.

A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior.

The frequency of Fabry disease with the E66Q variant in the α-galactosidase A gene in Japanese dialysis patients: a case report and a literature review.

Fabry disease (FD) is an Xlinked disorder resulting in a deficiency in α-galactosidase A (α-Gal) activity. FD is one of the causes of progressive renal dysfunction, but its diagnosis is often delayed or missed completely. We herein report the case of a 70-year-old male who had been receiving hemodialysis (HD) for 23 y who was diagnosed with FD after his participation in a screening program for plasma α-Gal activity for 892 HD patients. He had a low plasma α-Gal activity level and was demonstrated to have an E66Q mutation in exon 2 of the α-Gal gene. One of his daughters had the same mutation. The proband died due to aspiration pneumonia before receiving enzyme replacement therapy. We reviewed previous studies and found E66Q mutation in 36% of Japanese FD patients on HD including the present case. The clinical characteristics of E66Q variant are also discussed.

[One-stage coronary artery bypass grafting and revascularization in a patient with ischemic heart disease and arteriosclerosis obliterans].

With the overall increase in ischemic heart disease (IHD), cases combining arteriosclerosis obliterans (ASO) of the lower extremities and IHD are on the rise. Therefore, it is necessary to consider methods and timing of operation. These cases have occasionally large collateral pathways from the internal thoracic artery (ITA) to the femoral artery via the epigastric artery. To prevent irreversible ischemia of the lower limbs after harvesting of ITA, we planned to perform a one-stage operation for ASO-combined IHD. Revascularization of the lower extremities was performed 1st. Subsequently coronary artery bypass grafting with ITA was completed. The operative courses were uneventful.

Intermittent administration of a sustained-release prostacyclin analog ONO-1301 ameliorates renal alterations in a rat type 1 diabetes model.

Diabetic nephropathy is the most common pathological disorder predisposing end-stage renal disease. ONO-1301 is a novel sustained-release prostacyclin analog possessing thromboxane (TX) synthase inhibitory activity. Here, we aimed to investigate the therapeutic efficacies of ONO-1301 in a rat type 1 diabetic nephropathy model. Streptozotocin (STZ)-induced diabetic rats received injections of slow-release form of ONO-1301 (SR-ONO) every 3 weeks. Animals were sacrificed at Week 14. SR-ONO significantly suppressed albuminuria, glomerular hypertrophy, mesangial matrix accumulation, glomerular accumulation of monocyte/macrophage, increase in glomerular levels of pro-fibrotic factor transforming growth factor (TGF)-beta1 and the number of glomerular alpha-smooth muscle actin (SMA)(+) cells in diabetic animals. The glomerular levels of hepatocyte growth factor (HGF) were significantly increased in SR-ONO-treated diabetic animals. Taken together, these results suggest the potential therapeutic efficacy of intermittent administration of SR-ONO in treating diabetic nephropathy potentially via inducing HGF, thus counteracting the pro-fibrotic effects of TGF-beta1.

Comparative aspects of gonadal sex differentiation in medaka: a conserved role of developing oocytes in sexual canalization.

Medaka is a differentiated gonochoristic species with a male heterogametic sex determination. Here, we review recent studies on gonadal sex differentiation in medaka, as well as the experimental sex-reversal models available for this organism. The accumulated literature on teleost gonadal development facilitates comparative interspecies studies. Among these, comparison between medaka and zebrafish is of special interest, because zebrafish is an undifferentiated gonochorist that, nevertheless, shares many similarities with medaka and is also used as a small fish model for developmental biology. Accordingly, here we focus on the comparative aspects of gonadal development in medaka and zebrafish. In medaka, oogenesis begins in female gonads, whereas oogenesis is suppressed and germ cells remain in an undifferentiated state in male gonads. In zebrafish, oogenesis begins in all individuals, regardless of their future sex, while actual sex differentiation begins later in gonadal development, which means that degeneration of immature oocytes occurs in presumptive males, while oogenesis proceeds to completion in presumptive females. Despite these apparent differences between medaka and zebrafish, the process of gonadal development comprises similar stages: early oogenesis, early aromatase expression, later oocyte development or loss, sexually dimorphic expression of somatic genes, and spermatogenesis. We propose the concept of canalization as a key to gaining a comprehensive understanding of gonadal sex differentiation. In this respect, the possible role of the male-determining gene DMY/dmrt1bY is also discussed.

Assessment of intraradicular bacterial composition by terminal restriction fragment length polymorphism analysis.

BACKGROUND: The aim of the study was to assess the bacterial community structures associated with endodontic infections using terminal restriction fragment length polymorphism (T-RFLP), and to investigate the correlation of whole community profiles with the manifestation of particular clinical features. METHODS: Intraradicular samples were collected from 34 subjects and classified into three study groups based on the observed clinical symptoms: acute (n = 16), sub-acute (n = 8), and asymptomatic (n = 10). Genomic DNA was extracted from each sample, submitted to polymerase chain reaction using a fluorescently labeled 16S ribosomal DNA forward primer, and digested with two tetrameric endonucleases (HhaI and MspI). The terminal restriction fragments (T-RFs) were subsequently discriminated in an automated DNA sequencer, and the results were filtered using a statistics-based criterion. RESULTS: Totals of 138 (HhaI) and 145 (MspI) unique T-RFs were detected (means 13.1 and 11.9) and there was high inter-subject variability in the bacterial assemblages. Odds-ratio analysis unveiled the existence of higher order groups of positively associated T-RFs, restating the concept that intricate ecological relationships may take place in the root canal space. A significantly greater T-RF prevalence was detected in acute cases, suggesting a straight correlation between species richness and spontaneous pain. CONCLUSION: Overall, no T-RFLP profile representing a specific bacterial consortium could be associated with the manifestation of symptoms of endodontic origin.

The oro-ileal transit of cellulose.

The effects of cellulose and the interindividual variations on the transit time in the small intestine remain unclear, but no previous study has to date taken these factors into sufficient consideration. We assessed the oro-ileal transit time and the recovery percentage of cellulose in the terminal ileum looking at interindividual variations. Seven healthy males received 100 mL of a dietary fiber-free basal diet with 5 g cellulose and 5 g of polyethylene glycol 4000. The ileal contents were aspirated every 30 min via an experimental tube placed in the terminal ileum to assess the oro-ileal transit time and the recovery percentage of cellulose. The mean percentage (with standard deviation) of the amounts of cellulose collected in the terminal ileum was 98.4%+/- 16.5% (ranging from 67.4% to 114.5%) with a coefficient variation of 16.8%. The average times (in hours) taken for 20%, 40%, 60%, and 80% of cellulose to reach the terminal ileum were 5.5 +/- 1.1, 6.7 +/- 0.7, 8.5 +/- 1.3, and 8.8 +/- 1.2, respectively, with large interindividual variations. In conclusion, the averaged recovery percentage of cellulose in the terminal ileum was approximately 100%, in accordance with the present generally accepted definition of dietary fiber. However, there were large interindividual variations in the oro-ileal transit time and the percentage of cellulose recovered.

Treatment strategy after non-curative endoscopic resection of early gastric cancer.

BACKGROUND: Endoscopic resection (ER) is indicated for patients with early gastric cancer who have a negligible risk of lymph node metastasis (LNM). Histological examination of the resected specimen may indicate a possible risk of LNM or a positive resection margin. These patients are considered to have undergone non-curative ER. The aim of this study was to determine the appropriate treatment strategy for such patients. METHODS: A total of 298 patients who had non-curative ER were classified into those with a positive lateral margin only (group 1; 72 patients) and those with a possible risk of LNM (group 2; 226 patients). RESULTS: Surgery was performed within 6 months of non-curative ER in 19 patients in group 1 and 144 in group 2. In group 1, nine patients were found to have local residual tumours, all limited to the mucosal layer without LNM. In Group 2, 13 patients had residual disease, including four local tumours without LNM, two local tumours with LNM and seven cases of LNM alone. The rate of LNM after surgery was 6.3 per cent in group 2. CONCLUSION: Surgery remains the standard treatment after non-curative ER in patients with a possible risk of LNM.

Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection--an analysis of risk factors.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) has been reported to be associated with a higher complication rate than standard endoscopic mucosal resection. We aimed to clarify the risk factors for delayed bleeding after ESD for early gastric cancer (EGC). METHODS: 1083 EGCs in 968 consecutive patients undergoing ESD during a 4-year period were reviewed. Post-ESD coagulation (PEC) preventive therapy of visible vessels in the resection area, using a coagulation forceps, was introduced and mostly performed during the later 2 years. Various factors related to patients, tumors, and treatment including PEC were investigated using univariate and multivariate analysis with regard to delayed post-ESD bleeding, evidenced by hematemesis or melena, that required endoscopic treatment. RESULTS: Delayed bleeding occurred after ESD of 63 lesions (5.8 % of all lesions and 6.5 % of patients), controlled in all cases by endoscopic hemostasis; blood transfusion was required in only one case. Tumor location in the upper third of the stomach and PEC were independent factors indicating a lower rate of delayed bleeding according to both univariate and multivariate analysis. CONCLUSIONS: This retrospective study suggested that preventive coagulation of visible vessels in the resection area after ESD may lead to a lower bleeding rate.

Evaluation of 18F-2-deoxy-2-fluoro-glucose positron emission tomography for gastric cancer screening in asymptomatic individuals undergoing endoscopy.

(18)F-2-deoxy-2-fluoro-glucose Positron Emission Tomography (FDG-PET) has been recently proposed as a promising cancer-screening test. However, the validity of FDG-PET in cancer screening has not been evaluated. We investigated the sensitivity of FDG-PET compared with upper gastric endoscopy in gastric cancer screening for asymptomatic individuals. A total of 2861 consecutive subjects (1600 men and 1261 women) who were asymptomatic and who underwent both FDG-PET and upper gastrointestinal endoscopy between 1 February 2004 and 31 January 2005 were included in this study. Both endoscopists and a radiologist were unaware of the results of the other diagnostic tests. The FDG-PET images were examined using criteria determined by the pattern of FDG accumulation. Sensitivity and specificity of FDG-PET were calculated compared with endoscopic diagnosis as the gold standard. Among 2861 subjects enrolled in the study, there were 20 subjects with gastric cancer, of whom 18 were T1 in depth of cancer invasion. Positive FDG-PET results were obtained only in 2 of the 20 cancer subjects. The calculated sensitivity and specificity for overall gastric cancers were 10.0% (95% confidence interval (CI): 1.2-31.7%) and 99.2% (95% CI: 98.8-99.5%), respectively. (18)F-2-deoxy-2-fluoro-glucose Positron Emission Tomography was poorly sensitive for detection of gastric cancer in the early stages.

Clinical outcome after endoscopic mucosal resection for esophageal squamous cell carcinoma invading the muscularis mucosae--a multicenter retrospective cohort study.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) is now commonly indicated for esophageal squamous cell carcinoma (ESCC) within the lamina propria mucosa. However, EMR for ESCC that has invaded the muscularis mucosa is controversial because the risk of lymph node metastasis is not negligible. We conducted a multicenter retrospective cohort study to investigate the incidence of lymph node metastasis and survival after EMR for ESCC invading the muscularis mucosa. PATIENTS AND METHODS: A total of 104 patients with 111 lesions invading the muscularis mucosa, were retrospectively studied at eight institutes. No patients exhibited evidence of metastasis of lymph nodes or distant organs prior to EMR. Overall and cause-specific survival rates were calculated from the date of EMR to the date of death or the most recent follow-up visit. Survival curves were plotted according to the Kaplan-Meier method. RESULTS: In total, 86 patients (82.7%) who did not receive further treatment such as chemotherapy, irradiation therapy, chemoradiotherapy, or esophagectomy after EMR were followed up. Only two patients (1.9%) developed lymph node metastasis after EMR. With a median follow-up period of 43 months (range, 8-134 months), overall and cause-specific survival rates at 5 years after EMR were 79.5% and 95.0%, respectively. CONCLUSIONS: EMR for ESCC that invades the muscularis mucosa has curative potential as a minimally invasive treatment option.

Determining the treatment strategy for colorectal neoplastic lesions: endoscopic assessment or the non-lifting sign for diagnosing invasion depth?

BACKGROUND AND STUDY AIMS: Assessment of the invasion depth of colorectal neoplasia is important in deciding between endoscopic and surgical resection treatment methods. Prior to attempting endoscopic resection, the lesion is lifted by submucosal injection, and a positive "non-lifting sign" is usually considered to indicate deeper submucosal infiltration. The purpose of this prospective multicenter study was to assess the predictive value of the non-lifting sign for differentiating between adenoma and early cancer (up to discrete submucosal infiltration [sm1]) and cancer with deeper infiltration (sm2). PATIENTS AND METHODS: During an 11-month period, a total of 271 colorectal neoplastic lesions in 239 patients were included in the study. Apart from the location, size, and macroscopic type of the lesion, the presence or absence of the non-lifting sign was recorded and compared with the endoscopic assessment of invasion depth. RESULTS: The non-lifting sign had a sensitivity of 61.5 %, a specificity of 98.4 %, a positive predictive value of 80.0 %, a negative predictive value of 96.0 %, and an accuracy of 94.8 %. Endoscopic diagnosis of deeper infiltration had a sensitivity of 84.6 %, a specificity of 98.8 %, a positive predictive value of 88.0 %, a negative predictive value of 98.4 %, and an accuracy of 97.4 %. Statistically significant differences were found in terms of sensitivity and accuracy. CONCLUSION: Because of its lower sensitivity and accuracy, the non-lifting sign will not replace endoscopic assessment. If a lesion does not lift, this can make resection technically difficult, but does not reliably predict deeper cancerous invasion.

Gastric perforation during endoscopic resection for gastric carcinoma and the risk of peritoneal dissemination.

BACKGROUND: The potential risk of peritoneal seeding following perforation caused by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is unknown. METHODS: Between January 1991 and December 2003, 90 patients suffered gastric perforation during EMR or ESD at the National Cancer Centre Hospital, Tokyo. The clinical and pathological evidence for peritoneal dissemination in these patients was assessed retrospectively. RESULTS: Eighty-four patients were followed up at this hospital for a median of 53.6 (range 7.0-136.6) months; the remaining six patients were followed up at other institutions. In 83 patients the perforation was repaired by endoscopic clip application and seven patients underwent emergency surgery. Gastrectomy was carried out in 33 patients who had non-curative endoscopic surgery. Among these, peritoneal fluid was sampled during operation in nine patients and was cytologically negative for malignancy. The other 24 patients who had a gastrectomy did not have ascites so cytology was not performed. No peritoneal dissemination was noted during follow-up. CONCLUSION: This study suggests that perforation associated with EMR and ESD does not lead to peritoneal dissemination even in the long term.