Assessment of maxillary sinus fluid volume for postmortem diagnosis of drowning.

INTRODUCTION: Drowning is a comprehensive and exclusive diagnosis at autopsy. Autopsy findings such as pleural effusion and waterlogged lungs contribute to the diagnosis. Herein, we aim to reveal the practical usefulness and postmortem changes of the maxillary sinus fluid volume to diagnose drowning. METHODS: We evaluated 52 drowning and 59 nondrowning cases. The maxillary sinus fluid volume was measured using a computed tomography (CT) scan, and pleural effusion volume and lung weight were manually measured at autopsy. The utility of these three indices for diagnosing drowning and its postmortem changes was evaluated. RESULTS: The maxillary sinus fluid volume was significantly higher in drowning cases than in other external causes and cardiovascular death cases. Receiver operating characteristic curve analysis revealed that a total maxillary sinus fluid volume >1.04 mL more usefully indicated drowning (odds ratio, 8.19) than a total pleural effusion volume >175 mL (odds ratio, 7.23) and a total lung weight >829 g (odds ratio, 2.29). The combination of maxillary sinus fluid volume and pleural effusion volume more effectively predicted drowning than one index alone. Moreover, the maxillary sinus fluid volume was less influenced by the postmortem interval than the other two indices up to a week after death. CONCLUSION: Maxillary sinus fluid volume can be more useful than pleural effusion volume and lung weight with higher sensitivity and odds ratio for diagnosing drowning. IMPLICATIONS FOR PRACTICE: Fluid accumulation in both the maxillary sinuses strongly predicts drowning in the postmortem imaging.

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.

BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

Exposure-Response Analysis for Efficacy of Daclatasvir, Asunaprevir, and Beclabuvir Combinations in HCV-Infected Patients.

The combination regimen of daclatasvir, asunaprevir, and beclabuvir (3DAA regimen) was developed as a fixed-dose combination for the treatment of hepatitis C virus (HCV) infection in Japan. The objectives of this analysis were to characterize the relationship between drug exposure and sustained virologic response at posttreatment week 12 (SVR12) in HCV-infected subjects and to evaluate the impact of demographic covariates and clinical factors on the exposure-response (E-R) relationship. The E-R efficacy analysis was performed with data from phase 2 and phase 3 studies in HCV-infected subjects treated with the 3DAA regimen. The relationship between the probability of achieving SVR12 and exposure to daclatasvir, asunaprevir, and beclabuvir was described using a logistic regression model and included assessments of the potential covariate effects. The impacts of the covariates on the rate of SVR12 and interactions of covariates with the individual drug effects were tested. The final model for SVR12 included effects of non-genotype-1a status, resistance-associated NS5A-Q30 substitution in genotype-1a subjects, and baseline RNA level on the intercept, and effect of prior peg-interferon failure on the beclabuvir slope. Sex, race, age, weight, fibrosis score, alanine transaminase, and cirrhosis status had no statistically significant impact on the rate of SVR12. The individual E-R relationships with each drug, were relatively flat, and the effects of exposure were not significant. With the exception of the NS5A-Q30 substitution in genotype-1a subjects, statistically significant covariate effects had little impact on SVR12 rates. Overall, the E-R model was developed that captured the high SVR12 rates and the effect of covariates for the 3DAA regimen in HCV-infected patients.

Psychological stress during in vitro fertilization and embryo transfer is influenced by the patients' background and gender.

Purpose: This study evaluated the changes in psychological stress during in vitro fertilization and embryo transfer (IVF-ET) and the relationship of such stress to the patients' background and gender. Methods: Sixty couples undergoing IVF-ET were administered the State-Trait Anxiety Inventory-JYZ (STAI) test at six different points during IVF-ET procedures. Anxiety scores at each time point were recorded and analyzed according to gender, fertility status, and duration of treatment. Results: The median state anxiety score for women increased following induction until oocyte collection, after which it temporarily declined and then increased again until the pregnancy test. No such changes were noted in men. Scores for women who had undergone a shorter period of IVF treatments were higher while state and trait anxiety in men increased with a prolonged treatment period. Unsuccessful treatment increased the state and trait anxiety of women. Conclusions: Psychological stress changed periodically depending on the duration of the patients' treatment and fertility status also influenced anxiety levels. These findings will prove helpful in guiding psychological therapy and counseling for couples attempting to conceive by in vitro fertilization.

Differences in odor identification among clinical subtypes of Parkinson's disease.

OBJECTIVE: Olfactory dysfunction is a non-motor symptom in idiopathic Parkinson's disease (PD). We investigated whether this dysfunction differs among clinical subtypes of PD. METHODS: Participants comprised of 90 patients with idiopathic PD and without dementia. Olfactory function was evaluated using the odor stick identification test for Japanese, which evaluated the detection of 12 odorants familiar to Japanese participants. Patients were divided into tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT) PD subgroups using part III of the Unified Parkinson's Disease Rating Scale. RESULTS: Fifty-five patients were classified as ART, 21 as MXT, and 14 as TDT. There were no differences in age, sex, or duration of illness among the subtypes. Subjective symptoms of impaired sense of smell were significantly higher (P<0.05) in the ART than in the TDT. Mean odor identification score was 4.3 in the ART, 5.2 in MXT, and 6.6 in TDT. It was significantly lower in the ART than in the TDT (P<0.01). CONCLUSION: Olfactory dysfunction differed among the clinical subtypes of PD. This suggests that olfactory function might relate to prognosis of patients with PD.

Disruption of endothelial tight junctions in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS).

An electron microscopic study revealed disruption of capillary endothelial tight junctions (TJs) in both biopsied muscle, taken at 5 years and 1 month of age, and the autopsied brain, taken at 13 years and 6 months of age, in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and mitochondrial DNA (mtDNA) point mutation A3243G. This endothelial barrier disruption might result in vasogenic edema and systemic lactic acidosis, possibly the critical pathology of MELAS.

Inorganic polyphosphate induces osteoblastic differentiation.

Inorganic polyphosphate [Poly(P)] is especially prevalent in osteoblasts. We tested the hypothesis that Poly(P) stimulates osteoblastic differentiation and polyphosphate metabolism for bone formation. The osteoblast-like cell line, MC 3T3-E1, was cultured with Poly(P), and gene expression was evaluated by real-time reverse-transcription polymerase chain-reaction. Phosphatase activity and extracellular matrix mineralization were also determined. The role of Poly(P) was assessed in a beagle dog alveolar bone regeneration model. Poly(P) increased osteocalcin, osterix, bone sialoprotein, and tissue non-specific alkaline phosphatase gene expression, with a high level of end-polyphosphatase activity, resulting in low-chain-length Poly(P), inorganic pyrophosphate, and inorganic phosphate production. MC3T3-E1 cells differentiated into mature osteoblasts and showed expression of ectonucleotide pyrophosphatase phosphodiesterase 1, while mouse progressive ankylosis gene expression remained unchanged. Promotion of alveolar bone regeneration was observed in Poly(P)-treated beagle dogs. These findings suggest that Poly(P) induces osteoblastic differentiation and bone mineralization, and acts as a resource for mineralization.

Molecular characterization of quinolone resistance-determining regions and their correlation with serotypes and genotypes among Streptococcus pneumoniae isolates in Japan.

We established the distribution of amino acid alterations in quinolone resistance-determining regions (QRDRs) of Streptococcus pneumoniae isolates in Japan and described the correlation of these alterations with serotypes determined by multilocus sequencing typing. Among 141 S. pneumoniae isolates, five levofloxacin-resistant isolates harbored mutations in both gyrA and parC and/or parE and were clonally unrelated. Among 136 levofloxacin-susceptible isolates, one isolate (MIC = 2 mg/l) had a first-step parC mutation at Asp78. Twenty isolates had Lys137Asp in parC and Ile460Val in parE and contained nine serotypes and eight clonal complexes (CCs), including all eight Colombia(23F)-26 (CC138) isolates. Eighty-one isolates had Ile460Val in parE alone and contained 14 serotypes and 16 CCs, including 36 of 37 Netherlands(3)-31 (CC180) isolates and all 22 Taiwan(19F)-14 (CC271) isolates. In contrast, seven of ten Taiwan(23F)-15 (CC242) isolates were wild-type. Although each QRDR genotype contained various serotypes and CCs, prevalent clones were mostly associated with a single QRDR genotype.

Characteristics of neurons and glia in the brain of Fukuyama type congenital muscular dystrophy.

Fukuyama type congenital muscular dystrophy accompanies central nervous system and ocular lesions. Morphological findings suggest that major central nervous system lesions, such as cortical dysplasia, are caused by the abnormal glia limitans due to an impairment of astrocytes. Increase of corpora amylacea and neurofibrillary tangles suggests acceleration of the aging process in the Fukuyama type congenital muscular dystrophy brain. Glycosylation of alpha-dystroglycan is decreased in the central nervous system of Fukuyama type congenital muscular dystrophy in a similar manner to the skeletal muscle, but dystroglycan mRNA levels appear to be increased. Glycosylated alpha-dystroglycan is reduced in the glia limitans formed by astrocytic endfeet. Slight accumulation of N(epsilon)-(carboxymethyl)lysine, an oxidative modification product, is observed in astrocytes of Fukuyama type congenital muscular dystrophy and in an astrocytoma cell line with suppressed fukutin expression. Cerebral cortical neurons of Fukuyama type congenital muscular dystrophy and controls react with an antibody for core alpha-dystroglycan but not with an antibody for glycosylated alpha-dystroglycan. Carboxymethyl lysine is accumulated in cortical neurons of a severe case of Fukuyama type congenital muscular dystrophy. Both astrocytes and neurons appear to be sensitive to oxidative stress when fukutin is suppressed. However, it is still unclear how the loss of fukutin causes astrocytic and neuronal dysfunction. Since the central nervous system is composed of several components that are closely related to each other, more investigations are needed for thorough understanding of the Fukuyama type congenital muscular dystrophy brain. Moreover, since astrocytes and epithelial cells may show different cellular responses to fukutin suppression, it seems important to evaluate the functions of fukutin in each type of cell or tissue, not only to prove the pathogenesis of Fukuyama type congenital muscular dystrophy, but also for applying appropriate therapies, especially those at molecular level.

Niche required for inducing quiescent stem cells.

Quiescence is an important feature distinguishing stem cells (SCs) from other compartments for most SC systems. Evidence suggests that the quiescent state is directed by external cues expressed in the presumptive microenvironment, the niche, although the cellular and molecular nature of the niche remains obscure in most SC systems. Our group has been addressing this question using the melanocyte (MC) as a model, because MC SCs (MSCs) and other compartments are distinguished by their location in the hair follicle, the former in the bulge and the other in the hair matrix. On the basis of the gene expression profiles of MSCs, we developed a method to distinguish MSCs from other compartments by using their own characteristics. Using the new criterion for MSCs, we investigated the molecular cues that induce the quiescent MSCs from proliferating melanoblasts. Our study showed that fibroblast growth factor-2 (FGF-2), or an equivalent signal, is essential for inducing a set of MSC signatures, although additional signals required for inducing the ultimate MSCs remain to be identified.

Novel mutations in Myoclonin1/EFHC1 in sporadic and familial juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME. OBJECTIVE: To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1. METHODS: We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing. RESULTS: We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c.755C>A and c.1523C>G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C.789del.AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c.829C>T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c.829C>T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364--362del.GAT) in the promoter region in a family from Japan. CONCLUSION: Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.

Early-onset form of benign childhood epilepsy with centro-temporal EEG foci--a different nosological perspective from Panayiotopoulos syndrome.

PURPOSE: We have studied the clinical differences between early-onset benign epilepsy with centro-temporal spikes (early-onset BECT) and Panayiotopoulos syndrome (PS) to investigate the hypothesis that BECT and PS nosologically constitute age-dependent benign childhood seizure susceptibility syndromes based on a common etiopathogenesis. SUBJECTS AND METHODS: The subjects were 24 patients with BECT and 62 patients with PS, who satisfied the following definitions: 1) onset of epilepsy before 5 years of age; 2) the BECT and PS seizures started mainly with orofacial focal motor attacks and emetic symptoms followed by focal seizures, respectively; 3) follow-up examinations for longer than 2 years. We compared the various clinical features between these two groups. RESULTS: In children with early-onset BECT, the seizures at times manifested with hypersalivation, vomiting, and focal motor seizures, but the vomiting that developed in the middle of seizures was different from the initial vomiting observed in patients with PS. Although the seizures recurred more frequently in patients with early-onset BECT, the incidence of status epilepticus as well as prolonged seizures was higher in those with PS. The patients demonstrating below borderline IQ scores and mild developmental behavioral disorders were more frequently seen in early-onset BECT than PS, accounting for 37.5 and 14.6% (P<0.05), and for 8% and 21%, respectively (P<0.05). DISCUSSION: Early-onset BECT and PS have heterogeneous clinical characteristics, except for the same onset age, and appear to be nosologically different epileptic syndromes. The former seems to develop in combination with other acquired disturbances based on a BECT predisposition, while the latter develops based on a PS predisposition and involves a better prognosis.

Pneumococcal surface protein A family types of Streptococcus pneumoniae from community-acquired pneumonia patients in Japan.

We assessed pneumococcal surface protein A (PspA) family types of 141 isolates of Streptococcus pneumoniae from community-acquired pneumonia patients in Japan. Families 1 and 2 were expressed in 78 (55.3%) and 58 (41.1%) isolates, respectively. Five isolates were not typed either as family 1 or 2. PspA family types were not associated with age, sex, or pneumonia severity. Penicillin-resistant S. pneumoniae was more likely to belong to family 2 whereas organisms highly resistant to erythromycin and positive for ermB were more prevalent in family 1. The association of PspA type with antimicrobial resistance was possibly affected by prevalent serotypes or resistance clones. It would therefore be necessary to include both family 1 and 2 proteins in a PspA-containing vaccine to cover the major PspA families and to reduce antimicrobial resistance.