CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene.

BACKGROUND: Recently, mutations in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4) have been reported in Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in this same gene have been described in separate families with various skeletal dysplasias. Further clarification is needed of the different phenotypes associated with this gene. METHODS: We performed clinical evaluation, electrophysiology, and genetic analysis of the TRPV4 gene in 2 families with CMT2C. RESULTS: Two multigenerational families had a motor greater than sensory axonal neuropathy associated with variable vocal cord paresis. The vocal cord paresis varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One family with mild neuropathy also manifested pronounced short stature, more than 2 SD below the average height for white Americans. There was one instance of dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this family. The other family had a more severe, progressive, motor neuropathy with sensory loss, but less remarkable short stature and an R315W mutation in TRPV4. Third cranial nerve involvement and sleep apnea occurred in one subject in each family. CONCLUSION: CMT2C with axonal neuropathy, vocal cord paresis, and short stature is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result in highly variable orthopedic and neurologic phenotypes.

An in vitro comparison of possibly bioactive titanium implant surfaces.

The aim of the study was to compare Ca and P formation (CaP) and subsequent bone cell response of a blasted and four different possibly bioactive commercially pure (cp) titanium surfaces; 1. Fluoride etched (Fluoride), 2. Alkali-heat treated (AH), 3. Magnesium ion incorporated anodized (TiMgO), and 4. Nano HA coated and heat treated (nano HA) in vitro. Furthermore, to evaluate the significance of the SBF formed CaP coat on bone cell response. The surfaces were characterized by Optical Interferometry, Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS). CaP formation was evaluated after 12, 24 and 72 h in simulated body fluid (SBF). Primary human mandibular osteoblast-like cells were cultured on the various surfaces subjected to SBF for 72 h. Cellular attachment, differentiation (osteocalcin) and protein production (TGF-beta(1)) was evaluated after 3 h and 10 days respectively. Despite different morphological appearances, the roughness of the differently modified surfaces was similar. The possibly bioactive surfaces gave rise to an earlier CaP formation than the blasted surface, however, after 72 h the blasted surface demonstrated increased CaP formation compared to the possibly bioactive surfaces. Subsequent bone cell attachment was correlated to neither surface roughness nor the amount of formed CaP after SBF treatment. In contrast, osteocalcin and TGF-beta(1) production were largely correlated to the amount of CaP formed on the surfaces. However, bone response (cell attachment, osteocalcin and TGF-F production) on the blasted controls were similar or increased compared to the SBF treated fluoridated, AH and TiMgO surface.

Precipitation of calcium phosphate in the presence of albumin on titanium implants with four different possibly bioactive surface preparations. An in vitro study.

The aim of the present study was to compare the nucleating behaviour on four types of bioactive surfaces by using the simulated body fluid (SBF) model with the presence albumin. Titanium discs were blasted (B) and then prepared by alkali and heat treatment (AH), anodic oxidation (AO), fluoridation (F), or hydroxyapatite coating (HA). The discs were immersed in SBF with 4.5 mg/ml albumin for 3 days, 1, 2, 3 and 4 weeks and analysed with scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDX) and X-ray photoelectron spectroscopy (XPS). Topographic surface characterisation was performed with a contact stylus profilometer. The results demonstrated that the bioactive surfaces initiated an enhanced calcium phosphate (CaP) formation and a more rapid increase of protein content was present on the bioactive surfaces compared to the blasted control surface. The observation was present on all bioactive surfaces. The fact that there was a difference between the bioactive surfaces and the blasted control surface with respect to precipitation of CaP and protein content on the surfaces support the fact that there may be biochemical advantages in vivo by using a bioactive surface.

Bone tissue responses to Mg-incorporated oxidized implants and machine-turned implantsin the rabbit femur.

Previous studies have demonstrated a significant improvement in the bone response to oxidized titanium implants. Little is known about the effects of specific oxide properties on the bone tissue responses to titanium implants. This study in-vestigated the bone tissue responses to magnesium (Mg)-incorporated oxidized titanium implants and machine-turned titani-um implants in the rabbit femur. The oxidized implants were prepared using micro arc oxidation (MAO) methods. Surface oxide properties were characterized by using various surface analytic techniques, involving scanning electron microscopy (SEM) equipped with energy dispersive spectrometer (EDS), X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS) and optical interferometry. Screw shaped titanium implants, 10 machine-turned implants (controls) and 10 Mg-incorporated im-plants (tests) were inserted in the femoral condyles of 10 New Zealand white rabbits. After a 6-week healing period, resonance frequency analyses and removal torque measurements of the Mg-incorporated oxidized implants demonstrated significant im-provements in implant integration with bone in comparison to machine-turned implants, p=0.007 and p=0.017, respectively. Bone growth in the pores of the oxidized implants was probably incomplete at a follow-up of 6 weeks, as indicated by SEM and EDS measurements. Mg-incorporated titanium implants significantly improved bone responses as compared with machine-turned control implants. Considering the differences and similarities of the surface oxide properties of controls and test im-plants, the enhanced bone responses to Mg-incorporated implants could be explained by the Mg surface chemistry of the test im-plants. (Journal of Applied Biomaterials and Biomechanics 2005; 3: 18-28).

The electrochemical oxide growth behaviour on titanium in acid and alkaline electrolytes.

Titanium implants have a thin oxide surface layer. The properties of this oxide layer may explain the good biocompatibility of titanium implants. Anodic oxidation results in a thickening of the oxide film, with possible improved biocompatability of anodized implants. The aim of the present study was twofold: (1) firstly, to characterize the growth behaviour of galvanostatically prepared anodic oxide films on commercially pure (c.p.) titanium and (2) secondly, to establish a better understanding of the electroche0mical growth behaviour of anodic oxide on commercially pure titanium (ASTM grade 1) after changes of the electrochemical parameters in acetic acid, phosphoric acid, calcium hydroxide, and sodium hydroxide under galvanostatic anodizing mode. The oxide thickness was measured by Ar sputter etching in Auger Electron spectroscopy (AES) and the colours were estimated by an L*a*b* system (lightness, hue and saturation) using a spectrophotometer. In the first part of our study, it was demonstrated that the interference colours were useful to identify the thickness of titanium oxide. It was also found that the anodic forming voltages with slope (dV/dt) in acid electrolytes were higher than in alkaline electrolytes. Each of the used electrolytes demonstrates an intrinsically specific growth constant (nm/V) in the range of 1.4--2.78 nm/V. In the second part of our study we found, as a general trend, that an increase of electrolyte concentration and electrolyte temperature respectively decreases the anodic forming voltage, the anodic forming rate (nm/s) and the current efficiency (nm.cm(2)/C), while an increase of the current density and the surface area ratio of the anode to cathode increase the anodic forming voltage, the anodic forming rate and the current efficiency. The effects of electrolyte concentration, electrolyte temperature, and agitation speed were explained on the basis of the model of the electrical double layer.

Oxidized implants and their influence on the bone response.

Surface oxide properties are regarded to be of great importance in establishing successful osseointegration of titanium implants. Despite a large number of theoretical questions on the precise role of oxide properties of titanium implants, current knowledge obtained from in vivo studies is lacking. The present study is designed to address two aspects. The first is to verify whether oxide properties of titanium implants indeed influence the in vivo bone tissue responses. The second, is to investigate what oxide properties underline such bone tissue responses. For these purposes, screw-shaped/turned implants have been prepared by electrochemical oxidation methods, resulting in a wide range of oxide properties in terms of: (i) oxide thickness ranging from 200 to 1000 nm, (ii) the surface morphology of barrier and porous oxide film structures, (iii) micro pore configuration - pore sizes<8 microm by length, about 1.27 microm2 to 2.1 microm2 by area and porosity of about 12.7-24.4%, (iv) the crystal structures of amorphous, anatase and mixtures of anatase and rutile type, (v) the chemical compositions of TiO2 and finally, (vi) surface roughness of 0.96-1.03 microm (Sa). These implant oxide properties were divided into test implant samples of Group II, III, IV and V. Control samples (Group I) were turned commercially pure titanium implants. Quantitative bone tissue responses were evaluated biomechanically by resonance frequency analysis (RFA) and removal torque (RT) test. Quantitative histomorphometric analyses and qualitative enzyme histochemical detection of alkaline (ALP) and acidic phosphatase (ACP) activities were investigated on cut and ground sections after six weeks of implant insertion in rabbit tibia. In essence, from the biomechanical and quantitative histomorphometric measurements we concluded that oxide properties of titanium implants, i.e. the oxide thickness, the microporous structure, and the crystallinity significantly influence the bone tissue response. At this stage, however, it is not clear whether oxide properties influence the bone tissue response separately or synergistically.