A pharmacoeconomical model for choice of a treatment for pregnant women with gestational diabetes

This study discusses two main questions: the direct medical costs and the clinical effectiveness of the hospital treatment with insulin of pregnant women with gestational diabetes (GD). A prospective study that includes 50 women with GD is performed. The pregnant women are divided into 2 groups: Group I (n=30) — pregnant women treated only with a diet; and Group II (n=20) — pregnant women treated with diet and insulin. We found that the metabolite compensation degree is improved after the applied treatment with insulin. The coefficient cost/effectiveness is 6954 lv./100 women. The analysis decision tree confirms in a very convenient way the fact that insulin treatment is a clinically more effective and financially more profitable strategy.     

FOXL2 copy number changes in the molecular pathogenesis of BPES: unique cohort of 17 deletions

Blepharophimosis Syndrome (BPES) is an autosomal dominant developmental disorder of the eyelids with or without ovarian dysfunction caused by FOXL2 mutations. Overall, FOXL2deletions represent 12% of all genetic defects in BPES. Here, we have identified and characterized 16 new and one known FOXL2 deletion combining multiplex ligation‐dependent probe amplification (MLPA), custom‐made quantitative PCR (qPCR) and/or microarray‐based copy number screening. The deletion breakpoints could be localized for 13 out of 17 deletions. The deletion size is highly variable (29.8 kb ‐ 11.5 Mb), indicating absence of a recombination hotspot. Although the heterogeneity of their size and breakpoints is not reflected in the uniform BPES phenotype, there is considerable phenotypic variability regarding associated clinical findings including psychomotor retardation (8/17), microcephaly (6/17), and subtle skeletal features (2/17). In addition, in all females in whom ovarian function could be assessed, FOXL2 deletions proved to be associated with variable degrees of ovarian dysfunction. In conclusion, we present the largest series of BPES patients with FOXL2 deletions and standardized phenotyping reported so far. Our genotype‐phenotype data can be useful for providing a prognosis (i.e. occurrence of associated features) in newborns with BPES carrying a FOXL2 deletion. © 2010 Wiley‐Liss, Inc.     

Relationship between spinal mobility measures and quality of life in patients with ankylosing spondylitis

The aim of this study was to assess spinal mobility status and Quality of life (QoL) of patients with ankylosing spondylitis (AS) and determine the relationship between spinal mobility and measures of clinical condition including QoL. A total of 74 patients with AS were included in this study. Disease specific instruments Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were applied, and mobility testing: occiput-wall distance and chest expansion. QoL was assessed by the Short Form-36 (SF-36). The mean age was 48.5 years; there were significant correlations between BASMI score and age (P < 0.001), disease duration (P < 0.001), symptoms duration (P < 0.001) and BASFI (P < 0.001). BASMI was negatively correlated with SF-36 physical function subscale (P < 0.001) and general health subscale (P = 0.029). In multivariate regression analysis, BASFI score (P < 0.001) was independently associated factor with physical function domain of SF-36. This study showed that in AS spinal mobility measures are associated with physical function, general health, emotional role and mental health domains of QoL.     

Geometric considerations when planning an asymmetric genioplasty

The sliding osteotomy of the inferior border of the mandible, otherwise known as genioplasty, has often been described in the world literature with regard to diagnosis and treatment planning. However, the treatment of the asymmetric chin has received little attention. Moreover, diagnosis and treatment planning of asymmetric chins with concomitant orthognathic surgery is completely lacking from the literature. The complexity of surgically correcting asymmetric chins, compounded with complex, bimaxillary orthognathic surgery, is an extremely challenging task. This article looks at geometric considerations when planning the surgical correction of an asymmetric chin following a protocol of data collection, model surgery, diagnosis, and treatment planning. Clinical experience in the form of a case presentation will demonstrate the millimetric precision that can be achieved when planning corrective genioplasty in an asymmetric patient undergoing concomitant orthognathic surgery.     

Reversible brain damage following acute poisoning with an organic solvent determined by magnetic resonance

INTRODUCTION: Acute exposure to the effects of volatile solvents is characterized by the abrupt onset of symptoms and signs of poisoning, and relatively fast recovery in the majority of cases. CASE REPORT: We report a 24-year-old patient with an acute, accidental poisoning with a mixture of volatile organic solvents (most probably toluene, styrene and xylene), which led to the development of upward gaze paresis, diplopia, hemiparesis, ataxic gate, and the late onset truncal ataxia episodes. After 6 weeks, he recovered completely, while his extensive brain MRI lesions in the caudate nuclei, laterobasal putaminal regions, bilateral anterior insular cortex, central midbrain tegmental area) withdrew completely after 4 months. CONCLUSION: Acute toxic encephalopathy should be a part of the differential diagnosis in any patient with acute neurobehavioral and neurological deficit.     

Mutant p53 is constitutively phosphorylated at Serine 15 in UV-induced mouse skin tumors: involvement of ERK1/2 MAP kinase

Upon DNA damage, phosphorylation and nuclear translocation of wild-type p53 tumor suppressor protein signals its functional activation. However, very little is known about phosphorylation and localization of mutant p53. We found that mutant p53 protein in UV-induced murine primary skin tumors and cultured cell lines was constitutively phosphorylated at serine 15 residue and localized in the cell's nuclei. To investigate the mechanism of constitutive phosphorylation of mutant p53, we tested the involvement of a wide range of protein kinases and found that ERK1/2 mitogen-activated protein kinase was physically associated with mutant p53 in the nucleus. Addition of active recombinant ERK2 kinase protein in vitro to immunoprecipitated mutant p53 resulted in increased phosphorylation at serine 15. Furthermore, ERK1/2 activity was higher in tumor cells than normal cells, suggesting that phosphorylation of mutant p53 at serine 15 depends on the level of ERK1/2 activation. Interestingly, accumulation of mutant p53 in tumor cells was paralleled by low levels of Murine Double Minute 2 protein (MDM2) expression. However, when MDM2 was overexpressed, the fraction of mutant p53 that was phosphorylated at serine 15 resisted degradation, whereas the level of total p53 decreased, suggesting that phosphorylation at serine 15 and downregulation of MDM2 protein may both contribute to stabilization of mutant p53 in tumor cells.     

Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal multisystem degeneration that is associated with widespread oligodendroglial alpha-synuclein (alpha-SYN) inclusions. Presently no animal model completely replicates the specific neuropathology of MSA. Here we investigated the behavioral and pathological features resulting from oligodendroglial alpha-SYN overexpression in transgenic mice exposed to mitochondrial inhibition by 3-nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy. Widespread astrogliosis and microglial activation were also observed in the presence of alpha-SYN in oligodendrocytes. Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies.     

Subacute systemic 3-nitropropionic acid intoxication induces a distinct motor disorder in adult C57Bl/6 mice: behavioural and histopathological characterisation

Data on motor behavioural disorders induced by systemic 3-nitropropionic acid, an irreversible inhibitor of mitochondrial succinate dehydrogenase and their histopathological correlates in mice, are sparse. We thus further characterised the subacute 3-nitropropionic-acid-induced motor disorder and its time course in C57Bl/6 mice using standard behavioural tests, histopathological correlates and in vivo magnetic resonance imaging. Firstly, we studied two intoxication paradigms (340 and 560 mg 3-nitropropionic acid/kg, 7 days) compared to controls. The low-dose regimen induced only slight motor changes (reduced hindlimb stride length and rearing). The high-dose regimen induced significant (P<0.05) behavioural and sensorimotor integration deficits (pole test, rotarod, stride length, open-field spontaneous activity) but with 37.5% lethality at week one. The clinical motor disorder consisted of hindlimb clasping and dystonia, truncal dystonia, bradykinesia and impaired postural control. Histopathologically, there were discrete lesions of the dorsolateral striatum in 62.5% of mice together with a 32% reduction (P<0.0001) of the striatal volume, reduced caldbindin-D28K immunoreactivity in the lateral striatum, and met-enkephalin and substance P in the striatal output pathways. There was also a significant (P<0.05) 30-40% dopaminergic cell loss within the substantia nigra pars compacta. Secondly, we validated a semi-quantitative behavioural scale to describe the time course of the motor deficits and to predict the occurrence of striatal damage. We sought to determine whether it could also be disclosed in vivo by magnetic resonance imaging. The scale correlated with the striatal volume reduction (r(2)=0.57) and striatal cell loss (r(2)=0.87) but not with the loss of striatal dopaminergic terminals (dopamine transporter binding). Increased T2-signal intensity within the striatal lesion correlated with the cell loss (r(2)=0.66).We conclude that systemic administration of 3-nitropropionic acid in C57Bl/6 mice induces a distinct motor disorder and dose-dependent striatonigral damage, which are potentially useful to model human diseases of the basal ganglia.