A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease

Background Lysosomal storage disorders (LSDs), are a heterogeneous group of rare disorders caused by defects in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur at a frequency of about 1 in 5,000 live births, though recent neonatal screening suggests a higher incidence. New treatment options for LSDs demand a rapid, early diagnosis of LSDs if maximal clinical benefit is to be achieved. Methods Here, we describe a novel, highly specific and sensitive biomarker for Niemann-Pick Type C disease type 1 (NPC1), lyso-sphingomyelin-509. We cross-validate this biomarker with cholestane-3β,5α,6β-triol and relative lysosomal volume. The primary cohort for establishment of the biomarker contained 135 NPC1 patients, 66 NPC1 carriers, 241 patients with other LSDs and 46 healthy controls. Results With a sensitivity of 100.0% and specificity of 91.0% a cut-off of 1.4 ng/ml was established. Comparison with cholestane-3β,5α,6β-triol and relative acidic compartment volume measurements were carried out with a subset of 125 subjects. Both cholestane-3β,5α,6β-triol and lyso-Sphingomyelin-509 were sufficient in establishing the diagnosis of NPC1 and correlated with disease severity. Conclusion In summary, we have established a new biomarker for the diagnosis of NPC1, and further studies will be conducted to assess correlation to disease progress and monitoring treatment

Cementless total hip arthroplasty using the spongiosa-I fully coated cancellous metal surface : a minimum twenty-year follow-up

Background: We present the results of cementless total hip arthroplasty performed with use of an anatomically adapted femoral stem and hemispherical cup with a fully coated Spongiosa-I metal surface, which was designed to achieve a surface similar to human cancellous bone. The purpose of the present retrospective case series was to determine the long-term outcomes of this hip arthroplasty system after a minimum of twenty years of follow-up. Methods: Between 1983 and 1985, 209 consecutive total hip arthroplasty procedures (199 patients) were performed with use of the first-generation Spongiosa metal-surface chromium-cobalt total hip implant with an articulating surface consisting of a ceramic head and an ultra-high-molecular-weight polyethylene liner. We report the clinical and radiographic outcomes, the rates of and reasons for revision, and the influence of sex and age on outcome and complications. Results: At the time of the latest follow-up, twenty-seven patients had died and thirteen patients had been lost to follow-up; none of these forty patients had had revision surgery. The outcomes for 159 patients (169 prostheses) were reviewed. The mean duration of follow-up was 262 months (range, 242 to 275 months). There were nineteen revisions, including fourteen revisions of the femoral stem, two revisions of the acetabular cup, and three revisions of both components. The mean Harris hip score for patients who did not undergo revision surgery was 82 points. The probability of survival of both components at twenty years, with revision for any reason as the end point, was 97%. The probability of survival of the acetabular component was 98%, and the probability of survival of the femoral component only was 86%. The probability of component survival was significantly increased among older patients. Conclusions: The results of cementless hip arthroplasty with use of the first-generation Spongiosa implant were excellent at a minimum of twenty years of follow-up. The probability of survival of the acetabular component exceeded that of the femoral stem. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.6 page(s

Protocol and Methodology of the Stroke in Young Fabry Patients (sifap1) Study: A Prospective Multicenter European Study of 5,024 Young Stroke Patients Aged 18-55 Years

Background: Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients. Methods: We initiated the Stroke in Young Fabry Patients (sifap1) study as a multinational prospective European study of stroke patients aged 18-55 years and collected a broad range of clinical, laboratory, and radiological data using stringent standardized methods. All patients were tested for Fabry disease and blood was stored for future genetic testing. Results: We managed to enroll 5,024 eligible young stroke patients in 15 countries and 47 centers across Europe between April 2007 and January 2010. The median number of patients included per center was 98 with a range between 8 and 315. The average duration of patient recruitment per center was 22 months, ranging between 5 and 33 months. The database was closed in July 2010. This paper describes protocol and methodology of the sifap1 study. Conclusion: The sifap1 study included the largest series of young stroke patients so far and will allow for analyses on a large number of aspects of stroke in the young. Copyright (C) 2010 S. Karger AG, Base