Homozygous M34T mutation of the GJB2 gene associates with an autosomal recessive nonsyndromic sensorineural hearing impairment in Finnish families

Conclusions. Patients with hereditary hemorrhagic telangiectasia genotype ALK-1 (HHT2-ALK-1) with nonsense mutation demonstrated tendentially higher health-related quality of life (HR-QOL) scores than patients with HHT with genotype ENG (HHT1-ENG) with missense mutation. Objective. HHT, also known as Osler-Weber-Rendu syndrome, comprises different expressions depending on genetic type and mutation type. The influence of HHT type on HR-QOL has not been established and is addressed in this paper. Patients and methods. A total of 94patients with confirmed diagnoses of HHT (Curaçao criteria) participated in this study. EDTA (ethylene diamine tetraacetic acid) blood samples of 24patients were sequenced genetically into genotype HHT1 (ENG) vs HHT2 (ALK-1) and mutation type missense vs nonsense. HR-QOL was assessed with the German Short Form 36Health Survey (SF-36). Results. HHT2 patients (genotype ALK-1) demonstrated significantly higher physical component scores than HHT1 patients (effect size d=0.62). Patients with genotype ENG (HHT1) with nonsense mutations showed significantly higher mental component scores than patients with missense mutations (effect size=0.79).     

Use of Context in Pragmatic Language Comprehension by Children with Asperger Syndrome or High-Functioning Autism

Utilizing relevance theory, this study investigated the ability of children with Asperger syndrome (AS) and high-functioning autism (HFA) to use context when answering questions and when giving explanations for their correct answers. Three groups participated in this study: younger AS/HFA group (age 7–9, n = 16), older AS/HFA group (age 10–12, n = 23) and a normally functioning control group (age 7–9, n = 23). The results indicated that the younger AS/HFA group did less well when answering contextually demanding questions compared to the control group, and the performance of the older AS/HFA group fell in between the younger AS/HFA group and the control group. Both AS/HFA groups had difficulties explaining their correct answers, suggesting that they are not always aware of how they have derived answers from the context.     

An epidemiological and diagnostic study of Asperger syndrome according to four sets of diagnostic criteria

OBJECTIVE: This study evaluated the diagnostic process and prevalence rates of Asperger syndrome (AS) according to the DSM-IV, ICD-10, and criteria developed by Gillberg and Gillberg and by Szatmari and colleagues and clarified confusion about AS. METHOD: An epidemiological study of 5,484 eight-year-old children in Finland, 4,422 (80.6%) of whom rated on the high-functioning Autism Spectrum Screening Questionnaire by parents and/or teacher, 125 of them screened and 110 examined by using structured interview, semistructured observation, IQ measurement, school day observation, and patient records. Diagnoses were performed by following the DSM-IV, ICD-10, and criteria developed by Gillberg and Gillberg and by Szatmari and colleagues in detail. RESULTS: The prevalence rates per 1,000 were 2.5 according to the DSM-IV, 2.9 to ICD-10, 2.7 to Gillberg and Gillberg's criteria, and 1.6 to the criteria of Szatmari et al. CONCLUSIONS: The results emphasize the need to reconsider the diagnostic criteria of AS. The importance of multi-informant sources came up, and the need of several informants was highlighted, especially when diagnosing the broader pervasive developmental disorders.     

Mechanisms of Particle-Induced Pulmonary Inflammation in a Mouse Model: Exposure to Wood Dust

Repeated airway exposure to wood dust has long been known tocause adverse respiratory effects such as asthma and chronicbronchitis and impairment of lung function. However, the mechanismsunderlying the inflammatory responses of the airways after wooddust exposure are poorly known. We used a mouse model to elucidatethe mechanisms of particle-induced inflammatory responses tofine wood dust particles. BALB/c mice were exposed to intranasallyadministered fine (more than 99% of the particles had a particlesize of 5 µm, with virtually identical size distribution)birch or oak dusts twice a week for 3 weeks. PBS, LPS, and titaniumdioxide were used as controls. Intranasal instillation of birchor oak dusts elicited influx of inflammatory cells to the lungsin mice. Enhancement of lymphocytes and neutrophils was seenafter oak dust exposure, whereas eosinophil infiltration washigher after birch dust exposure. Infiltration of inflammatorycells was associated with an increase in the mRNA levels ofseveral cytokines, chemokines, and chemokine receptors in lungtissue. Oak dust appeared to be a more potent inducer of theseinflammatory mediators than birch dust. The results from ourin vivo mouse model show that repeated airway exposure to wooddust can elicit lung inflammation, which is accompanied by inductionof several proinflammatory cytokines and chemokines. Oak andbirch dusts exhibited quantitative and qualitative differencesin the elicitation of pulmonary inflammation, suggesting thatthe inflammatory responses induced by the wood species may risevia different cellular mechanisms.     

Evaluation of hydroxyimine as cytochrome P450-selective prodrug structure

Hydroxyimine derivatives of ketoprofen (1) and nabumetone (2) were synthesized and evaluated in vitro and in vivo as cytochrome P450-selective intermediate prodrug structures of ketones. 2 released nabumetone in vitro in the presence of isolated rat and human liver microsomes and in different recombinant human CYP isoforms. Bioconversion of 2 to both nabumetone and its active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), was further confirmed in rats in vivo. Results indicate that hydroxyimine is a useful intermediate prodrug structure for ketone drugs.     

Potentially pathogenic, slow-growing mycobacteria released into workplace air during the remediation of buildings

Construction workers' exposure to airborne viable mycobacteria was studied during the remediation of three moldy and two nonmoldy buildings. Furthermore, the concentrations of airborne fungal and actinobacterial spores were determined. The samples for the microbial analyses were collected using a six-stage impactor and an all-glass impinger sampler, and by filter sampling. Specific mycobacteria media and nonselective media were used for the cultures. The samples were cultured for the total numbers of rapidly growing and slow-growing mycobacteria, and the isolates obtained were identified to the genus or species level. Mycobacteria were recovered from the air during the remediation of two of the moldy buildings and one nondamaged building. Concentrations of mycobacteria up to 160 cfu/m3 were detected. A total of 43 mycobacterial isolates was recovered. Most of the isolates were slow-growers, only two rapid-growing strains being detected. The 38 identified isolates belonged to potentially pathogenic species, including Mycobacterium avium complex, M. scrofulaceum, and M. fortuitum, and to saprophytic species, including M. nonchromogenicum and M. terrae. Mycobacteria were the most often detected in samples taken with a six-stage impactor. They were found in buildings with both high and low concentrations of fungi. In conclusion, mycobacteria, both potentially pathogenic and saprophytic species, may be released into the indoor air during the remediation of buildings.     

Anal incontinence: diagnosis by endoanal US or endovaginal MRI

Preoperative evaluation was made of the diagnostic value of endoanal ultrasound (EAUS) and endovaginal magnetic resonance imaging (EVMRI) in diagnosing anal sphincter defects as the cause of anal incontinence. Nineteen female individuals with anal incontinence were examined clinically with EAUS and with EVMRI at 1.5 T using a prostatic coil. The findings were evaluated independently and compared with findings at surgery. In diagnosing external anal sphincter defects, EAUS and EVMRI showed almost similar agreement with surgical findings, 12 (63%) out of 19 vs 11 (58%), respectively. Internal anal sphincter defects were equally detected by EAUS and EVMRI as compared with surgical diagnosis. There was considerable variation between radiologists in diagnosing defects by EVMRI. EAUS and EVMRI are equal in diagnosing anal sphincter defects.Abbreviations IAS Internal anal sphincter - EAS External anal sphincter - EAUS Endoanal ultrasound - MR Magnetic resonance - PPV Positive predictive value - NPV Negative predictive value - EVMRI Endovaginal magnetic resonance imaging - EAMRI Endoanal magnetic resonance imaging     

The influence of ambulation time on the incidence of transient neurologic symptoms after lidocaine spinal anesthesia

The cause of transient neurologic symptoms (TNSs) after lidocaine spinal anesthesia remains unclear. It has been proposed that early ambulation after spinal anesthesia contributes to the development of TNSs. We evaluated the influence of ambulation time on the occurrence of TNSs after spinal anesthesia with 50 mg of 2% plain lidocaine for knee arthroscopy. One-hundred-twenty patients undergoing knee arthroscopy (ASA physical status 1-2) were randomized into 3 groups, i.e., early (Group E), 6-h (Group 6-h), or late ambulation (Group L) groups. In Group E, ambulation was allowed as early as possible after regression of spinal block (on average 229 +/- 21 min; range, 135-247 min). In Group 6-h, the patients remained in bed for approximately 6 h after the block and in Group L until the next morning. The patient groups were comparable with respect to demographic, anesthetic, and surgical variables. The overall incidence of TNSs was 16%. TNSs occurred in 3 patients of Group E (7.5%), in 11 patients of Group 6-h (28%), and in 5 patients of Group L (13%). No significant differences were detected between the patients with and without TNSs. Early ambulation was not found to be a risk factor for TNSs after spinal anesthesia with 50 mg of 2% lidocaine. IMPLICATIONS: This study shows that early ambulation time does not increase the incidence of transient neurologic symptoms after spinal anesthesia with 50 mg of 2% lidocaine for elective knee arthroscopy.     

Myometrial inflammation in human delivery and its association with labor and infection

The presence of inflammation in decidual and myometrial samples as defined by histopathologic examination and the association between the myometrial inflammation and different maternal infectious morbidity and labor-related clinical variables were evaluated in 648 consecutive women who underwent cesarean section at various gestational periods. Altogether, 1,205 histologic (559 decidual and 646 myometrial) samples were studied. In normal pregnancies, myometrial inflammatory lesions were detected rarely before parturition, indicating their abnormality in these cases. After ruptured fetal membranes with advanced cervical dilatation and in patients with clinical chorioamnionitis, myometrial samples commonly were infiltrated by leukocytes, up to moderate and marked densities. Moderate to marked myometrial inflammation showed no diagnostic value in high-risk term parturients for the prediction of postoperative endometritis. Our study is the first to show the frequency of myometrial inflammation in nonselected consecutive pregnant women and, thus, is important for better understanding the myometrial inflammatory response during human parturition.