Occurrence of noise in alumina-on-alumina total hip arthroplasty. A survey on 284 consecutive hips

SummaryBackgroundAlumina-on-alumina bearings have been accepted as a valuable alternative for young and active patients. Alumina fractures, and socket loosening were the main complications reported. But, with the increasing number of prostheses implanted, noise occurrence appeared as a new concern. The primary aim of the present study was to quantify the prevalence of noticing noise in a population having received alumina-on-alumina total hip arthroplasty as well as its eventual impact on outcome.Patients and methodsTwo hundred and eighty-four ceramic-on-ceramic hips were performed in 238 patients from January 2003 to December 2004. The average age was 52.4±13.4years (range, 13 to 74years). All the hips received the same prosthesis (Ceraver-Osteal™) with alumina bearing components (Ceraver-Osteal™): 32mm liners were used for cups of 50mm or larger and 28mm liners for cups smaller than 48mm; the minimal alumina thickness was 6mm. The acetabular component (Cerafit™) was hemispherical, coated with a hydroxyapatite layer and press-fit fixed. The stem (Cerafit™) was a straight tapered cementless stem, fully coated with a hydroxyapatite layer. Clearance between femoral head and liner was between 20 and 50 microns. A retrospective survey was conducted by an independent surgeon who did not participate to surgery in 2007. He conducted phone interviews of patients using a standard questionnaire. No suggestion was offered on how they could describe the noise and they felt free to use the word that they considered to be the most adapted. Satisfaction was evaluated. When the noise was present, X-rays were taken to assess if sign of bearings fracture was present.ResultsFour patients (six hips) died of unrelated causes during the follow-up period. Three patients (three hips) live outside France and could not be followed (1.3%). Nine patients (10 hips) could not be traced and were considered lost to follow-up (3.8%). Two hundred and twenty-two patients with 265 hips, therefore, were included (nine using bearing components in 28mm diameter and 265 in 32mm). Twenty-eight hips experienced noise generation (10.6%). It was defined as a snap for six patients, as a cracking sound by six, as rustling by six patients, as a squeaking by seven patients (2.6%), a tinkling by two patients, one patient was unable to define the sound she felt. No factor related to the patient influenced the occurrence of noise. Twelve patients were dissatisfied with the result of their hip prosthesis, five of them experienced noise (41.7%); 210 were satisfied or very satisfied, 23 of them experiencing noise (11%); this difference was significant (P=0.002).ConclusionThe origins of noise occurrence are unknown. Squeaking may be related to generation of stripe wear and absence of sufficient lubrication. Other types of noise can be due to microseparation, occult dislocation, impingement between the femoral neck and the acetabular rim.Level of evidenceLevel IV. Retrospective study

A MANBA mutation resulting in residual beta-mannosidase activity associated with severe leukoencephalopathy: a possible pseudodeficiency variant

<p>Abstract</p> <p>Background</p> <p>β-Mannosidosis (OMIM 248510) is a rare inborn lysosomal storage disorder caused by the deficient activity of β-mannosidase, an enzyme encoded by a single gene (<it>MANBA</it>) located on chromosome 4q22-25. To date, only 20 cases of this autosomal recessive disorder have been described and 14 different <it>MANBA </it>mutations were incriminated in the disease. These are all null mutations or missense mutations that abolish β-mannosidase activity. In this study, we characterized the molecular defect of a new case of β-mannosidosis, presenting with a severe neurological disorder.</p> <p>Methods</p> <p>Genomic DNA was isolated from peripheral blood leukocytes of the patient to allow <it>MANBA </it>sequencing. The identified mutation was engineered by site-directed mutagenesis and the mutant protein was expressed through transient transfection in HEK293T cells. The β-mannosidase expression and activity were respectively assessed by Western blot and fluorometric assay in both leukocytes and HEK293T cells.</p> <p>Results</p> <p>A missense disease-associated mutation, c.1922G>A (p.Arg641His), was identified for which the patient was homozygous. In contrast to previously described missense mutations, this substitution does not totally abrogate the enzyme activity but led to a residual activity of about 7% in the patient's leukocytes, 11% in lymphoblasts and 14% in plasma. Expression studies in transfected cells also resulted in 7% residual activity.</p> <p>Conclusion</p> <p>Correlations between MANBA mutations, residual activity of β-mannosidase and the severity of the ensuing neurological disorder are discussed. Whether the c.1922G>A mutation is responsible for a yet undescribed pseudodeficiency of β-mannosidase is also discussed.</p

Necdin Protects Embryonic Motoneurons from Programmed Cell Death

NECDIN belongs to the type II Melanoma Associated Antigen Gene Expression gene family and is located in the Prader-Willi Syndrome (PWS) critical region. Necdin-deficient mice develop symptoms of PWS, including a sensory and motor deficit. However, the mechanisms underlying the motor deficit remain elusive. Here, we show that the genetic ablation of Necdin, whose expression is restricted to post-mitotic neurons in the spinal cord during development, leads to a loss of 31% of specified motoneurons. The increased neuronal loss occurs during the period of naturally-occurring cell death and is not confined to specific pools of motoneurons. To better understand the role of Necdin during the period of programmed cell death of motoneurons we used embryonic spinal cord explants and primary motoneuron cultures from Necdin-deficient mice. Interestingly, while Necdin-deficient motoneurons present the same survival response to neurotrophic factors, we demonstrate that deletion of Necdin leads to an increased susceptibility of motoneurons to neurotrophic factor deprivation. We show that by neutralizing TNFα this increased susceptibility of Necdin-deficient motoneurons to trophic factor deprivation can be reduced to the normal level. We propose that Necdin is implicated through the TNF-receptor 1 pathway in the developmental death of motoneurons

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study

Background: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. Methods: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. Results: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Conclusions: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years