A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.

We report the identification of a new transthyretin (TTR) gene mutation and variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy, mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial biopsy revealed amyloid deposits in the heart of a patient who had no family history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum screening for a TTR variant by isoelectric focusing (IEF) was positive and prompted further studies to identify the genetic abnormality and to characterize the amyloidogenic protein. Direct DNA sequence analysis of all four coding regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts of guanine (G) and adenine (A) were observed at the second base position of codon 61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum showed the presence of both wild-type and variant proteins. The observed mass results for the wild-type and variant proteins were consistent with the predicted values calculated from the genetic analysis data.     

FMC pratique: où se former? Le compagnonnage vu par le CREGG

Acta Endoscopica - Les praticiens libéraux doivent être donc des collaborateurs actifs dans le processus d’enseignement et ce, par leur implication au quotidien dans les outils...     

Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Advanced image fusion algorithms for Gamma Knife treatment planning. Evaluation and proposal for clinical use.

Image fusion is a process of combining information from multiple sensors. It is a useful tool implemented in the treatment planning programme of Gamma Knife Radiosurgery. In this paper we evaluate advanced image fusion algorithms for Matlab platform and head images. We develop nine level grayscale image fusion methods: average, principal component analysis (PCA), discrete wavelet transform (DWT) and Laplacian, filter - subtract - decimate (FSD), contrast, gradient, morphological pyramid and a shift invariant discrete wavelet transform (SIDWT) method in Matlab platform. We test these methods qualitatively and quantitatively. The quantitative criteria we use are the Root Mean Square Error (RMSE), the Mutual Information (MI), the Standard Deviation (STD), the Entropy (H), the Difference Entropy (DH) and the Cross Entropy (CEN). The qualitative are: natural appearance, brilliance contrast, presence of complementary features and enhancement of common features. Finally we make clinically useful suggestions.     

Long-term outcomes evaluation after pars defect repair in adult low-grade isthmic spondylolithesis

Adult low-grade isthmic spondylolisthesis is often treated by posterolateral lumbar fusion (PLF), with a certain rate of complications and non-return to work. Alternatives to fusion, like pars defect repair (PDR), were used with encouraging results in young populations and athletes but their outcomes were rarely evaluated for adult patients. This retrospective study quantitatively analysed the long-term outcomes in adult isthmic spondylolisthesis patients treated by PLF or PDR. At a mean follow-up of 9 years, clinical, socio-professional, radiological data and Stauffer-Coventry score were available for 59 patients (39 cases treated by PLF and 20 treated by PDR). The overall clinical outcomes were comparable in both populations (88% in the PDR and 80% in PLF group 1), with a larger proportion of excellent results (56% vs. 10%) and of return to work in the PDR group. Radiological quantitative analysis highlighted stationary evolution and comparable outcomes for the two groups, except for vertebral slip evolution and adjacent level degeneration rate. Abnormal kinematic patterns outlined for PLF patients 20% of pseudarthrosis and 42% of adjacent levels hypermobility and for PDR ones low mobility for the levels adjacent to instrumented vertebra in 40% of cases. Quantified analysis of biomechanical parameters interpreted altogether with clinical outcome, complications and economic burden of the patient, provided accurate objective data for a better appreciation of global outcome, allowing for a preliminary view on long-term outcomes after PDR in adult low-grade isthmic spondylolisthesis, which were not presented in literature until now.     

Long-term survival after vinblastine, bleomycin, and cisplatin treatment in patients with germ cell tumors of the ovary: An update

Thirteen patients with a malignant germ cell tumor of the ovary have been treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). In 12 patients a complete remission was reached, which was maintained in 10 of these patients. One patient with large tumor residues and a partial remission became CR after surgery. The tumor recurred in 2 patients after 6 and 27 months. Overall, 11 of these patients are in long-term remission, from 14 to 84 months after the start of treatment. VBP is an effective treatment for malignant germ cell tumors of the ovary, even in patients with large tumor residuals.