The turmoil around the drug-eluting stents

Of 141 hospital survivors after intracardiac repair of tetralogy of Fallot, eight died suddenly 6–23 years later. Compared with the other 133 patients, these eight were older at operation, with higher post-repair systolic right ventricular pressure and more often complete atrioventricular block; ventricular arrhythmia was diagnosed before death in three cases. In follow-up totalling 2255 patient years, the linearized rate of sudden death was 0.35%/year. The instantaneous risk of sudden death showed continuous increase with the length of follow-up. Of 80 survivors electrocardiographically evaluated 13–26 (median 20) years postoperatively, none had complete block, but 79 had complete right bundle branch block, including seven with left anterior hemiblock. Ventricular extrasystoles were recorded in 1% at rest, in 34% during exercise and in 83% during 24-hour ambulatory monitoring, with Lown Grade ≥II in 27%. Old age and possibly presence of fibrosis and/or fibroelastosis in right ventricular outflow tract muscle correlated independently with high Lown Grade. A patient with Lown grade III died suddenly 2 years after our follow-up. Old age at repair thus was associated with increased risk of late sudden death and with frequent ventricular arrhythmia in long-term survivors.     

Knee and hip radiographic osteoarthritis predict total hip bone loss in older adults: A prospective study

The relationship between osteoarthritis (OA) and osteoporosis remains controversial. This study was designed to determine the association between hip and knee radiographic OA and change in total hip bone mineral density (BMD) over 2.6 years. A total of 867 population‐based randomly selected subjects (mean age 62 years, range 51 to 80 years, and 49% female) were included. Hip and knee joint space narrowing (JSN, 0 to 3) and osteophytes (0 to 3) in both lower limbs was assessed using Altman's atlas. Total hip BMD was measured by dual‐energy X‐ray absorptiometry (DXA). We found that radiographic OA (score of JSN or osteophytes > 0) was common in this sample (hip 45%, knee 68%). In multivariable analyses, percentage change in total hip BMD per year was predicted by right and left hip axial JSN (β = –0.25% and –0.29% per grade, respectively, both p < .05), right hip superior femoral osteophytes (grades 2 and 3 versus 0: β = –1.60, p < .05), combined right and left knee tibiofemoral JSN (β = –0.06 per grade from grades 0 to 12, p < .05), and osteophytes (β = –0.06 per grade from grades 0 to 14, p < .05) independent of each other and joint pain. In conclusion, older subjects with radiographic hip and knee OA have higher total hip bone loss over 2.6 years regardless of symptoms, suggesting that consideration should be given to the monitoring of bone mass in these subjects. © 2010 American Society for Bone and Mineral Research.     

Staging of Hepatic Fibrosis: Comparison of Magnetic Resonance Elastography and Shear Wave Elastography in the Same Individuals

Objective

To cross-validate liver stiffness (LS) measured on shear wave elastography (SWE) and on magnetic resonance elastography (MRE) in the same individuals.

Materials and Methods

We included 94 liver transplantation (LT) recipients and 114 liver donors who underwent either MRE or SWE before surgery or biopsy. We determined the technical success rates and the incidence of unreliable LS measurements (LSM) of SWE and MRE. Among the 69 patients who underwent both MRE and SWE, the median and coefficient of variation (CV) of the LSM from each examination were compared and correlated. Areas under the receiver operating characteristic curve in both examinations were calculated in order to exclude the presence of hepatic fibrosis (HF).

Results

The technical success rates of MRE and SWE were 96.4% and 92.2%, respectively (p = 0.17), and all of the technical failures occurred in LT recipients. SWE showed 13.1% unreliable LSM, whereas MRE showed no such case (p < 0.05). There was moderate correlation in the LSM in both examinations (r = 0.67). SWE showed a significantly larger median LSM and CV than MRE. Both examinations showed similar diagnostic performance for excluding HF (Az; 0.989, 1.000, respectively).

Conclusion

MRE and SWE show moderate correlation in their LSMs, although SWE shows higher incidence of unreliable LSMs in cirrhotic liver.     

A DNA resequencing array for genes involved in Parkinson's disease

Parkinson's disease (PD) is aetiologically complex with both familial and sporadic forms. Familial PD results from rare, highly penetrant pathogenic mutations whereas multiple variants of low penetrance may contribute to the risk of sporadic PD. Common variants implicated in PD risk appear to explain only a minor proportion of the familial clustering observed in sporadic PD. It is therefore plausible that combinations of rare and/or common variants in genes already implicated in disease pathogenesis may help to explain the genetic basis of PD. We have developed a CustomSeq Affymetrix resequencing array to enable high-throughput sequencing of 13 genes (44 kb) implicated in the pathogenesis of PD. Using the array we sequenced 269 individuals, including 186 PD patients and 75 controls, achieving an overall call rate of 96.5% and 93.6%, for two respective versions of the array, and >99.9% accuracy for five samples sequenced by capillary sequencing in parallel. We identified modest associations with common variants in SNCA and LRRK2 and a trend suggestive of an overrepresentation of rare variants in cases compared to controls for several genes. We propose that this technology offers a robust and cost-effective alternative to targeted sequencing using traditional sequencing methods, and here we demonstrate the potential of this approach for either routine clinical investigation or for research studies aimed at understanding the genetic aetiology of PD.     

Magnetoencephalography is more successful for screening and localizing frontal lobe epilepsy than electroencephalography

PURPOSE: The diagnosis of frontal lobe epilepsy may be compounded by poor electroclinical localization, due to distributed or rapidly propagating epileptiform activity. This study aimed at developing optimal procedures for localizing interictal epileptiform discharges (IEDs) of patients with localization related epilepsy in the frontal lobe. To this end the localization results obtained for magnetoencephalography (MEG) and electroencephalography (EEG) were compared systematically using automated analysis procedures. METHODS: Simultaneous recording of interictal EEG and MEG was successful for 18 out of the 24 patients studied. Visual inspection of these recordings revealed IEDs with varying morphology and topography. Cluster analysis was used to classify these discharges on the basis of their spatial distribution followed by equivalent dipole analysis of the cluster averages. The locations of the equivalent dipoles were compared with the location of the epileptogenic lesions of the patient or, if these were not visible at MRI with the location of the interictal onset zones identified by subdural electroencephalography. RESULTS: Generally IEDs were more abundantly in MEG than in the EEG recordings. Furthermore, the duration of the MEG spikes, measured from the onset till the spike maximum, was in most patients shorter than the EEG spikes. In most patients, distinct spike subpopulations were found with clearly different topographical field maps. Cluster analysis of MEG spikes followed by dipole localization was successful (n = 14) for twice as many patients as for EEG source analysis (n = 7), indicating that the localizability of interictal MEG is much better than of interictal EEG. CONCLUSIONS: The automated procedures developed in this study provide a fast screening method for identifying the distinct categories of spikes and the brain areas responsible for these spikes. The results show that MEG spike yield and localization is superior compared with EEG. This finding is of importance for the diagnosis and preoperative evaluation of patients with frontal lobe epilepsy.     

The effect of levodopa on respiration and word intelligibility in people with advanced Parkinson's disease

OBJECTIVES: Hypokinetic dysarthria is commonly encountered in Parkinson's disease (PD). Although the etiology of this dysarthria is multifactorial, disorders of respiration may strongly contribute to it. The aim of this study was to evaluate the effects of levodopa on measures of respiration and intelligibility. PATIENTS AND METHODS: Vital capacity (VC), sustained vowel phonation (SVP) and phonation quotient (PQ) were determined with and without medication in 25 patients suffering from idiopathic PD. Intelligibility was evaluated by three independent speech pathologists using the word subtest protocol of the Yorkston and Beukelman "Assessment of intelligibility of dysarthric speech" (AIDS). RESULTS: VC was abnormal in 18/25 patients in the off-condition and 15/25 in the on-condition. SVP was normal in 22/25 patients in the off-state and in all patients in the on-state. PQ was normal in all patients in the off- and on-condition. All three respiratory parameters, as well as intelligibility, improved significantly following administration of levodopa. There were significant differences between men and women for VC and PQ, with men having the highest values for both parameters in both conditions. In none of the two conditions a correlation between respiratory parameters and intelligibility could be demonstrated. CONCLUSION: This study suggests that thoracic mobility is decreased in PD, and that pharmacological treatment results in improvement, but not in normalization. Moreover, it remains unclear to what extent dyskinesias negatively influence respiratory control. Our results also demonstrate improvement of intelligibility after pharmacological treatment of PD. However, this improvement is not solely the consequence of respiratory changes. Further research on the effects of different characteristics on intelligibility is necessary.     

Astrocytes derived from fetal neural progenitor cells as a novel source for therapeutic adenosine delivery

PurposeIntracerebral delivery of anti-epileptic compounds represents a novel strategy for the treatment of refractory epilepsy. Adenosine is a possible candidate for local delivery based on its proven anti-epileptic effects. Neural stem cells constitute an ideal cell source for intracerebral transplantation and long-term drug delivery. In order to develop a cell-based system for the long-term delivery of adenosine, we isolated neural progenitor cells from adenosine kinase deficient mice (Adk^?/?) and compared their differentiation potential and adenosine release properties with corresponding wild-type cells.MethodsFetal neural progenitor cells were isolated from the brains of Adk^?/? and C57BL/6 mice fetuses and expanded in vitro. Before and after neural differentiation, supernatants were collected and assayed for adenosine release using liquid chromatography–tandem mass spectrometry (LC–MS/MS).ResultsAdk^?/? cells secreted significantly more adenosine compared to wild-type cells at any time point of differentiation. Undifferentiated Adk^?/? cells secreted 137 ± 5 ng adenosine per 10⁵ cells during 24 h in culture, compared to 11 ± 1 ng released from corresponding wild-type cells. Adenosine release was maintained after differentiation as differentiated Adk^?/? cells continued to release significantly more adenosine per 24 h (47 ± 1 ng per 10⁵ cells) compared to wild-type cells (3 ± 0.2 ng per 10⁵ cells).ConclusionsFetal neural progenitor cells isolated from Adk^?/? mice – but not those from C57BL/6 mice – release amounts of adenosine considered to be of therapeutic relevance.     

Opinion of Belgian neurologists on antiepileptic drug treatment in 2006: Belgian study on epilepsy treatment (BESET‐2)

Objectives – (i) To describe the medical treatment of epilepsy in Belgium in 2006, (ii) to detect the presence or absence of consensus in epilepsy treatment and (iii) to analyze the evolution of the neurologists’ opinion between 2003 and 2006. Materials and methods – In December 2006, 100 neurologists were interviewed with a structured questionnaire, based on ordinal four‐point scales. The questionnaire contained questions on treatment choices in adult patients with epilepsy. The results of this survey were compared with results of a previous one done in 2003. Results – Initial monotherapy was the preferred treatment strategy. Valproate was first choice in idiopathic generalized epilepsy. Carbamazepine and oxcarbazepine were first choice in focal epilepsy with partial seizures. Valproate was also first choice in focal epilepsy with secondarily generalized seizures. New antiepileptic drugs were recommended in second line. However, in special treatment situations, they were considered first‐line, e.g. lamotrigine in case of women in childbearing age. In comparison with 2003, there was a trend of using earlier the new antiepileptic drugs. Conclusions – In end 2006, carbamazepine, valproate and oxcarbazepine were considered to be first choice drugs, whereas other newer drugs, like lamotrigine, levetiracetam and topiramate were predominantly prescribed in second line.