Potential barriers and facilitators for implementation of an integrated care pathway for hearing-impaired persons: an exploratory survey among patients and professionals

Background  

Because of the increasing costs and anticipated shortage of Ear Nose and Throat (ENT) specialists in the care for hearing-impaired persons, an integrated care pathway that includes direct hearing aid provision was developed. While this direct pathway is still under investigation, in a survey we examined expectations and potential barriers and facilitators towards this direct pathway, of patients and professionals involved in the pathway.     

Warifteine,a bisbenzylisoquinoline alkaloid,induces relaxation by activating potassium channels in vascular myocytes

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Familial amyloidotic polyneuropathy with severe renal involvement in association with transthyretin Gly47Glu in Dutch,British and American-Finnish families

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder associated with more than 80 different transthyretin (TTR) mutations. The clinical features of FAP are broad and variable, but knowledge of the pattern and natural history of disease associated with particular mutations nevertheless offers the best guidance for management of individual patients, including the role and timing of treatment by orthotopic liver transplantation. FAP in association with TTR Gly47Glu has been described previously in an Italian kindred, and we report here its phenotype in 7 additional patients from Dutch, British, and American (Finnish) families. Characteristic clinical features included amyloid cardiomyopathy and autonomic failure but, unusually, moderate to severe renal failure was present in more than half of the cases. Only four patients were deemed to be sufficiently fit to undergo orthotopic liver transplantation, and clinical deterioration was generally rapid. These observations support early intervention with orthotopic liver transplantation in patients with FAP associated with TTR Gly47Glu.     

Influence of dental materials on dental MRI

Objectives:

To investigate the potential influence of standard dental materials on dental MRI (dMRI) by estimating the magnetic susceptibility with the help of the MRI-based geometric distortion method and to classify the materials from the standpoint of dMRI.

Methods:

A series of standard dental materials was studied on a 1.5 T MRI system using spin echo and gradient echo pulse sequences and their magnetic susceptibility was estimated using the geometric method. Measurements on samples of dental materials were supported by in vivo examples obtained in dedicated dMRI procedures.

Results:

The tested materials showed a range of distortion degrees. The following materials were classified as fully compatible materials that can be present even in the tooth of interest: the resin-based sealer AH Plus^® (Dentsply, Maillefer, Germany), glass ionomer cement, gutta-percha, zirconium dioxide and composites from one of the tested manufacturers. Interestingly, composites provided by the other manufacturer caused relatively strong distortions and were therefore classified as compatible I, along with amalgam, gold alloy, gold–ceramic crowns, titanium alloy and NiTi orthodontic wires. Materials, the magnetic susceptibility of which differed from that of water by more than 200 ppm, were classified as non-compatible materials that should not be present in the patient’s mouth for any dMRI applications. They included stainless steel orthodontic appliances and CoCr.

Conclusions:

A classification of the materials that complies with the standard grouping of materials according to their magnetic susceptibility was proposed and adopted for the purposes of dMRI. The proposed classification can serve as a guideline in future dMRI research.     

Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver,skeletal muscle and adipose tissue in an in vivo rat model

Cyclosporin A (CsA) and sirolimus (SRL) are immunosuppressive agents (IAs) associated with dyslipidemia, insulin resistance and new onset diabetes after transplantation (NODAT). However, the molecular mechanisms involved are not fully understood. We investigated the effects of six-week treatment of either CsA or SRL on glucose and lipid metabolism in Wistar rats. The results show that, compared with vehicle-treated rats, SRL-treated rats were significantly lighter starting at week 5. CsA or SRL caused glucose intolerance, increased storage of lipids in the liver and skeletal muscle, and decreased the insulin-stimulated glucose uptake in isolated adipocytes. Furthermore, these agents significantly decreased genes involved in insulin action and glucose uptake, such as, IRS-1, Glut4 and Glut1, and increased genes and/or proteins involved in hepatic lipogenesis and gluconeogenesis, while decreasing them in adipose tissue. After either treatment PGC1α gene expression was down regulated in skeletal muscle, an important player in fatty acid oxidation. Moreover, there was an increase in IL-6 gene expression in adipose tissue in the SRL-treated rats, suggesting stimulation of lipolysis. The results of the present study suggest that CsA and SRL lead to metabolic alterations in liver, muscle and adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.     

Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation

Although the majority of factor VII (FVII) circulates in the zymogen form, low levels of activated factor VII (FVIIa) have been postulated to exist in plasma and to serve a priming function for triggering of the clotting cascade. However, direct measurement of plasma FVIIa has not previously been possible. We have quantified plasma FVIIa levels using a novel, highly sensitive assay that is free from interference by FVII. Specificity of this clot-based assay results from the use of a mutant tissue factor that is selectively deficient in promoting FVII activation, but retains FVIIa cofactor function. In normal adults, FVIIa was found to be present in plasma (mean: 3.6 ng/mL) with considerable variation between individuals (range: 0.5 to 8.4 ng/mL). FVIIa levels were only loosely correlated with FVII coagulant activity, but were elevated in pregnancy and reduced with oral anticoagulant therapy. Incubation of plasma on ice in glass containers (cold activation) resulted in substantial FVIIa generation. Measurement of plasma forms of factor VII is of potential clinical importance because elevated FVII coagulant activity has been implicated as a significant risk predictor for ischemic heart disease. Clinically, this new assay will now permit direct assessment of the role of plasma FVIIa in thrombotic disorders.