Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

Background

Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.

Methods

Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.

Results

Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10^-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10^-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10^-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).

Conclusions

We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.     

Defining the cost of the Egyptian lymphatic filariasis elimination programme

BACKGROUND: Ultrasonography (USG) is known to be a suitable tool for diagnosis in lymphatic filariasis as the adult filarial nematode Wuchereria bancrofti in scrotal lymphatic vessels of infected men can be detected by the characteristic pattern of movement, the Filaria Dance Sign. In onchocerciasis, moving adult worms have not yet been demonstrated by USG. In addition the verification of drug effects on living adult Onchocerca volvulus filariae in trials is hampered by the lack of tools for longitudinal observation of alterations induced by potentially macrofilaricidal drugs in vivo. The present study was carried out to determine the frequency of detection of moving adult filariae of O. volvulus by USG. METHODS: In an endemic region for onchocerciasis in Ghana, 61 patients infected with onchocerciasis were recruited by palpation and onchocercomas examined by USG using an ultrasound system equipped with a 7.5 - 10 MHz linear transducer. Onchocercomas were recorded on videotape and evaluated with regard to location, number and size, as well as to movements of adult filariae. RESULTS: In the 61 patients 303 onchocercomas were found by palpation and 401 onchocercomas were detected by USG. In 18 out of 61 patients (29.5%), altogether 22 nodules with moving adult O. volvulus filariae were detected and are presented in animated ultrasound images as mp-4 videos. CONCLUSION: Ultrasonographical examinations of onchocercomas where living adult filariae can be displayed may serve as a new tool for the longitudinal observation in vivo of patients with onchocerciasis undergoing treatment and as an adjunct to histological evaluation.     

Evidence for an early evolutionary emergence of γ-type carbonic anhydrases as components of mitochondrial respiratory complex I

Background  

The complexity of mitochondrial complex I (CI; NADH:ubiquinone oxidoreductase) has increased considerably relative to the homologous complex in bacteria. Comparative analyses of CI composition in animals, fungi and land plants/green algae suggest that novel components of mitochondrial CI include a set of 18 proteins common to all eukaryotes and a variable number of lineage-specific subunits. In plants and green algae, several purportedly plant-specific proteins homologous to γ-type carbonic anhydrases (γCA) have been identified as components of CI. However, relatively little is known about CI composition in the unicellular protists, the characterizations of which are essential to our understanding of CI evolution.     

The Ontogeny of Apomorphine-Induced Alterations of Neostriatal Dopamine Release: Effects on Spontaneous Release

The effects of apomorphine (0.05, 0.1, and 1.0 mg/kg, s.c.) on the extracellular levels of dopamine and the dopamine metabolite 3, 4-dihydroxyphenylacetic acid were studied through the use of in vivo microdialysis in the neostriatum of developing and adult rats. Fifteen-minute samples were collected from urethane-anesthetized rats 5, 10–11, 21–22, and 35–36 days old and adults and quantified by HPLC with electrochemical detection. Apomorphine attenuated extracellular levels of dopamine in all age groups, suggesting that the dopamine autoreceptor modulating release in the neostriatum is functional by 5 days of age. A dose-response effect of apomorphine on extracellular dopamine was observed in all age groups except at 10–11 days of age. Extracellular levels of 3, 4-dihydroxyphenylacetic acid were also significantly decreased in all age groups, consistent with the hypothesis that synthesis-modulating dopamine autoreceptors in the neostriatum are functional by 5 days of age. Apomorphine had a significantly greater effect on extracellular 3, 4-dihydrpxyphenylacetic acid levels at the 0.05 and 0.1 mg/kg doses in the 5- and 10–11-day-old age groups compared with the other ages. Absolute levels of extracellular dopamine were significantly attenuated at 5 days of age compared with the other ages, and absolute levels of extracellular 3, 4-dihydroxyphenylacetic acid monotonically increased with age.