Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

[Short version of recommendations for enhanced recovery program (ERP) for cystectomy: Technical measures]. / Version courte des recommandations de la récupération ameliorée après chirurgie (RAAC) pour la cystectomie : mesures techniques.

INTRODUCTION: The enhanced recovery program (ERP) is a management mode whose objective is to reduce the risk of complications and allow the patient to recover more quickly all its functional capacities and to reintegrate at most quickly and safely in his usual environment. This intentionally synthetic document aims to disseminate in the urological community the main points of the ERP recommendations for cystectomy. This work, coordinated by AFU, involves several other partners. The full document is available on the "Urofrance" website. Another article will follow on organizational measures. METHOD: The development of the recommendations is based on the method "formalized consensus of experts" proposed by the HAS. The report is based on a systematic review of the literature (January 2006-May 2017), two rounds of iterative quotations and a national proofreading. Levels of proof of conclusions and gradation of recommendations are based on the HAS grid. RESULTS: The bibliographic strategy made it possible to retain 298 articles. Only the recommendations that obtained a strong agreement after the two rounds of iterative listing were retained. The recommendations presented here are in chronological form (before, during, after hospitalization). Twenty-six key points on the technical and organizational measures of ERP have been identified. CONCLUSION: The result of the literature review, supplemented by expert opinion, suggests a significant clinical interest in the application and dissemination of ERP for cystectomy, despite the limited data available for this indication.

[Morbi-mortality of transurethral resection of the prostate in patients aged 75 and over]. / Morbi-mortalité de la résection trans-urétrale de la prostate par courant monopolaire chez les patients âgés de 75 ans et plus.

INTRODUCTION: Monopolar transurethral resection of the prostate is one of standard surgical treatment of benign prostatic hyperplasia. The objective of this study was to evaluate early postoperative complications in patients aged 75 years old and more using a standardized classification. MATERIAL AND METHODS: We included all patients aged at least 75 on the day of surgery between 1 January 2008 and 31 December 2013. The reporting of complications was carried from the Clavien-Dindo classification. RESULTS: One hundred and seventy-six patients were included in this study. A total of 47.2% of patients experienced at least one complication. The majority of patients (79.5%) had complications grade 1 or 2 according to Clavien-Dindo classification. One patient died postoperatively at day 27. Most complications were urological (55%). A high Charlson score and low plasma hemoglobin levels have been identified as a risk factor for complications. CONCLUSION: Monopolar transurethral resection of the prostate is followed by significant morbidity in older patients, higher than in the general population. LEVEL OF EVIDENCE: 4.

Another case of "European hantavirus pulmonary syndrome" with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages.

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

A mouse model for Zellweger syndrome.

The cerebro-hepato-renal syndrome of Zellweger is a fatal inherited disease caused by deficient import of peroxisomal matrix proteins. The pathogenic mechanisms leading to extreme hypotonia, severe mental retardation and early death are unknown. We generated a Zellweger animal model through inactivation of the murine Pxr1 gene (formally known as Pex5) that encodes the import receptor for most peroxisomal matrix proteins. Pxr1-/- mice lacked morphologically identifiable peroxisomes and exhibited the typical biochemical abnormalities of Zellweger patients. They displayed intrauterine growth retardation, were severely hypotonic at birth and died within 72 hours. Analysis of the neocortex revealed impaired neuronal migration and maturation and extensive apoptotic death of neurons.

[Implementation of reperfusion therapy in ST segment elevation myocardial infarction (STEMI). A policy statement from the Belgian Society of Cardiology and its working group of acute cardiology and interventional cardiology]. / Mise en pratique du traitement de reperfusion dans les infarctus du myocarde avec élévation du segment ST.

Myocardial infarction remains a major healthcare problem. Reperfusion therapy has been shown to influence favourably short- and long-term patient survival. The authors reviewed the data of early recognition of STEMI (ST Elevation Myocardial Infarction), the reperfusion modalities including a flowchart management, as proposed by the Belgian working groups (BIWAC and BWGIC), and the lessons learned from European and American registries. Primary PCI often remains the treatment of choice. A national policy is still required to implement the guidelines and improve clinical practice for our STEMI patients.

[Implementation of reperfusion therapy in ST segment elevation myocardial infarction (STEMI). A policy statement from the Belgian Society of Cardiology and its working group of acute cardiology and interventional cardiology]. / Mise en pratique du traitement de reperfusion dans les infarctus du myocarde avec élévation du segment ST (STEMI). Recommandations actualisées de la Société Belge de Cardiologie et de ses groupes de travail: le Groupe Interdisciplinaire de Cardiologie Aiguë (BIWAC) et le Groupe de Cardiologie Interventionnelle (BWGIC).

Myocardial infarction remains a major healthcare problem. Reperfusion therapy has been shown to influence favourably short- and long-term patient survival. The authors reviewed the data of early recognition of STEMI (ST Elevation Myocardial Infarction), the reperfusion modalities including a flowchart management, as proposed by the Belgian working groups (BIWAC and BWGIC), and the lessons learned from European and American registries. Primary PCI often remains the treatment of choice. A national policy is still required to implement the guidelines and improve clinical practice for our STEMI patients.

Electron microscopic examination of subcellular fractions. I. The preparation of representative samples from suspensions of particles.

A method is described for preparing, by filtration on Millipore filters, very thin (about 10 micro) pellicles of packed particles. These pellicles can be embedded in Epon for electron microscopic examination. They are also suitable for cytochemical assays. The method was used with various particulate fractions from rat liver. Its main advantages over the usual centrifugal packing techniques are that it produces heterogeneity solely in the direction perpendicular to the surface of the pellicle and that sections covering the whole depth of the pellicle can be photographed in a single field. It thus answers the essential criterion of random sampling and can be used for accurate quantitative evaluations.

Basiliximab as an alternative to antithymocyte globulin for early immunosuppression in lung transplantation.

OBJECTIVE: Basiliximab (BAS), an interleukin-2 monoclonal antibody, has shown promising results as induction therapy in liver and kidney transplantation. We compared the efficacy and patient tolerability of BAS and antithymocyte globulin (ATG) in lung transplantation (LTx). PATIENTS AND METHODS: The study included 37 patients in two groups (ATG and BAS, respectively). The indication for LTx was emphysema in 62.6% of patients in group 1 and 57.1% of patients in group 2. Mean (SD) patient characteristics compared in the two groups included age (52.0 [9.8] vs 54 [10.6] years), height (172.0 [10.1] vs 169 [7.55] cm), and weight (73.9 [15.3] vs 64.4 [14.2] kg) (P = .049). Induction therapy after LTx in the two groups was as follows: in 16 transplantation procedures (eight single and eight bilateral) performed between April 1998 and December 2002, ATG, 3 mg/kg/d for 3 days, was administered, and in 21 transplantation procedures (15 single and 6 bilateral) performed between January 2003 and July 2005, BAS, 20 mg on days 0 and 4, was given. Dosages of cyclosporine, azathioprine, and steroids for maintenance therapy were equivalent in the two groups. We retrospectively compared patient tolerability, occurrence of acute rejection or infection (from bacteria, cytomegalovirus [CMV], or Aspergillus), and outcomes between the two groups during 2 years of follow-up. RESULTS: No cytokine-mediated reaction was observed in either group; however, there was a difference in hematologic effects. On day 2, mean (SD) platelet count was significantly lower in the ATG group at 113,500 (56,400)/mm(3) vs 151,900 (57,300)/mm(3) (P = .046). Because of severe thrombocytopenia, three patients could not be given ATG on day 3. The overall incidence of aspergillosis (18.8% vs 19.0%) and CMV infection (31% vs 57%) was similar in the two groups. However, when the recipient was CMV-positive and the donor was CMV-negative, the there was a clear trend (33.3% vs 88.9%). The number of acute rejection episodes was similar (43.8% vs 52.4%). Survival increased by 20% in the BAS group (P = .03). CONCLUSION: In LTx, safety of BAS use is as good as or better than that of ATG, with no difference in acute rejection episodes or infections, with the possible exception of increased reactivation of CMV infection. Thus, BAS could be an alternative to ATG as induction therapy in LTx; however, further studies are necessary.

Effects of curing sodium nitrite additive and natural meat fat on growth control of Listeria monocytogenes by the bacteriocin-producing Lactobacillus curvatus strain CWBI-B28.

In realistic model meat systems, the separate and combined effects of fat content and sodium nitrite on the antilisterial activity of the bacteriocin of Lactobacillus curvatus CWBI-B28 were studied. In laboratory fermentations where Listeria monocytogenes was co-cultured at 4 degrees C with bacteriocin-producing CWBI-B28 in lean pork meat (fat content: 13%) without added nitrite, a strong antilisterial effect was observed after one week. The effect was maintained for an additional week, after which a slight and very gradual rebound was observed. Both added nitrite (20 ppm) and a high-fat content (43%) were found to antagonise this antilisterial effect, the Listeria cfu count reached after six weeks being 200 times as high in high-fat meat with added nitrite than in lean meat without nitrite. This antagonism could not be attributed to slower growth of the bacteriocin-producing strain, since CWBI-B28 grew optimally in fat-rich meat with 20 ppm sodium nitrite. Bacteriocin activity was also measured in the samples. The observed activity levels are discussed in relation to the degree of antilisterial protection conferred.

[When should the pulmonologist consider lung transplantation? Criteria for referral and transplantation in COPD and idiopathic pulmonary fibrosis]. / Quand le pneumologue doit-il envisager la transplantation pulmonaire pour un de ses patients? Critères d'inscription en liste d'attente. BPCO, fibrose pulmonaire idiopathique.

INTRODUCTION: The definition of the optimal timing of referral for lung transplantation in cases of chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis remains a difficult question. BACKGROUND: The decision is based on the balance between the risk of death associated with the transplant procedure on one hand and, on the other, the risk of death associated with the natural course of the disease and/or the severity of the disability. It is not surprising, therefore, that the selection criteria take into account the main prognostic factors identified in both diseases. Recommendations for the selection criteria based on these prognostic indices have been published recently by a panel of international experts. In case of chronic obstructive pulmonary disease, the main indication for lung transplantation worldwide, the decision is not simple. The course of the individual patient is not easy to determine as, on an individual basis, some patients have a prolonged survival. In the case of idiopathic pulmonary fibrosis, the survival benefit provided by lung transplantation is well documented and it is therefore recommended to refer the patient to a transplantation centre once the diagnosis is established. This evaluation for lung transplantation does not prevent the subsequent inclusion of the patients in therapeutic protocols. CONCLUSION: International guidelines assist the pulmonologist to define the optimal moment of referral but these guidelines are not absolute and therefore, in case of doubt, physicians should not hesitate to refer the patient to a transplant centre.

Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain.

Excitotoxic damage may be a critical factor in the formation of brain lesions associated with cerebral palsy. When injected at birth, the glutamatergic analog ibotenate induces mouse brain lesions that strikingly mimic human microgyria. When ibotenate is injected at postnatal day 5, it produces transcortical necrosis and white matter cysts that mimic human perinatal hypoxic-like lesions. Vasoactive intestinal peptide (VIP) has potent growth-related actions and neuroprotective properties that influence mitosis and neuronal survival in culture. The goal of this study was to assess the protective role of VIP against excitotoxic lesions induced by ibotenate in developing mouse brain. VIP cotreatment reduced ibotenate-induced microgyric-like cortical lesions and white matter cysts by up to 77 and 85%, respectively. VIP protective effects were reproduced by a peptide derived from activity-dependent neurotrophic factor (ADNF), a trophic factor released by VIP-stimulated astrocytes, and by stearyl norleucine VIP, a specific VIP agonist that does not activate adenylate cyclase. Neither forskolin, an adenylate cyclase activator, nor pituitary adenylate cyclase-activating peptide, provided VIP-like protection. VIP and neurotrophic analogs, acting through a cAMP-independent mechanism and inducing ADNF release, could represent new avenues in the understanding and prevention of human cerebral palsy.

Nociceptin/orphanin FQ exacerbates excitotoxic white-matter lesions in the murine neonatal brain.

Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white-matter lesions, mimicking brain lesions that occur in human preterm infants. Nociceptin (NC), also called orphanin FQ, is the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor and does not bind classical high-affinity opioid receptors. In the present study, administration of NC exacerbated ibotenate-induced white-matter lesions while coadministration of ibotenate with either of two NC antagonists reduced excitotoxic white-matter lesions by up to 64%. Neither ibotenate plus endomorphin I (a selective mu receptor agonist), nor ibotenate plus naloxone (a classical opioid receptor antagonist) modulated the excitotoxic lesion. Pretreatment with antisense oligonucleotides targeting the NC precursor peptide mRNA significantly reduced ibotenate-induced white-matter damage. Finally, high doses of fentanyl, which stimulates both classical mu-opioid receptors and ORL1, exacerbated excitotoxic white-matter lesion. This toxic effect was blocked by inhibiting ORL1 but not classical opioid receptors. Together, these findings show that endogenous or exogenous stimulation of the ORL1 receptor can be neurotoxic and that blocking NC signaling protects the white matter against excitotoxic challenge. These data point to potential new avenues for neuroprotection in human preterm infants at high risk of brain lesions.

Air pollution and ST-elevation myocardial infarction: A case-crossover study of the Belgian STEMI registry 2009-2013.

BACKGROUND: Previous studies have shown that air pollution particulate matter (PM) is associated with an increased risk for myocardial infarction. The effects of air pollution on the risk of ST-elevation myocardial infarction (STEMI), in particular the role of gaseous air pollutants such as NO2 and O3 and the susceptibility of specific populations, are still under debate. METHODS: All patients entered in the Belgian prospective STEMI registry between 2009 and 2013 were included. Based on a validated spatial interpolation model from the Belgian Environment Agency, a national index was used to address the background level of air pollution exposure of Belgian population. A time-stratified and temperature-matched case-crossover analysis of the risk of STEMI was performed. RESULTS: A total of 11,428 STEMI patients were included in the study. Each 10µg/m3 increase in PM10, PM2.5 and NO2 was associated with an increased odds ratio (ORs) of STEMI of 1.026 (CI 95%: 1.005-1.048), 1.028 (CI 95%: 1.003-1.054) and 1.051 (CI 95%: 1.018-1.084), respectively. No effect of O3 was found. STEMI was associated with PM10 exposure in patients ≥75y.o. (OR: 1.046, CI 95%: 1.002-1.092) and with NO2 in patients ≤54y.o. (OR: 1.071, CI 95%: 1.010-1.136). No effect of air pollution on cardiac arrest or in-hospital STEMI mortality was found. CONCLUSION: PM2.5 and NO2 exposures incrementally increase the risk of STEMI. The risk related to PM appears to be greater in the elderly, while younger patients appear to be more susceptible to NO2 exposure.

Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery.

OBJECTIVES: The present study was aimed to evaluate the efficacy of a specific algorithm with continuous atrial dynamic overdrive pacing to prevent atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. BACKGROUND: Atrial fibrillation occurs in 30% to 40% of patients after cardiac surgery with a peak incidence on the second day. It still represents a challenge for postoperative prevention and treatment and may have medical and cost implications. METHODS: Ninety-six consecutive patients undergoing CABG for severe coronary artery disease and in sinus rhythm without antiarrhythmic therapy on the second postoperative day were randomized to have or not 24 h of atrial pacing through temporary epicardial wires using a permanent dynamic overdrive algorithm. Holter ECGs recorded the same day in both groups were analyzed to detect AF occurrence. RESULTS: No difference was observed in baseline data between the two study groups, particularly for age, male gender, history of AF, ventricular function, severity of coronary artery disease, preoperative beta-adrenergic blocking agent therapy or P-wave duration. The incidence of AF was significantly lower (p = 0.036) in the paced group (10%) compared with control subjects (27%). Multivariate analysis showed AF incidence to increase with age (p = 0.051) but not in patients with pacing (p = 0.078). It decreased with a better left ventricular ejection fraction only in conjunction with atrial pacing (p = 0.018). CONCLUSIONS: We conclude that continuous atrial pacing with an algorithm for dynamic overdrive reduces significantly incidence of AF the second day after CABG surgery, particularly in patients with preserved left ventricular function.

Is the management of hepatitis C patients appropriate? A population-based study.

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.

Left thoracoscopic thymectomy in children.

BACKGROUND: In the management of autoimmune myasthenia, thymectomy is recognized as effective surgical therapy. The necessity of complete radical thymectomy to achieve maximal improvement has been emphasized. Video-assisted thoracoscopic surgery has been successfully used for thymectomy in adults, and more recently in children, and has been described as achieving the same radicality and functional improvement as median sternotomy or as transcervical thymectomy. The aim of this work is to report our first thoracoscopic experience in this indication. METHODS: Patients with myasthenia gravis on anticholinesterase drugs and/or steroids are discussed for surgery in case of clinical deterioration despite increasing doses of medication or in case of no improvement. We decided to perform thoracoscopic thymectomies by a left-sided approach. Preoperative localization of thymic tissue is done by a thoracic CT exam. Patients are placed on their right side with a thoracic tilt under the thorax. Four thoracoscopic ports are used, a 10-mm for the camera and three 5-mm operating ports. The left lung was collapsed by selective intubation (double-lumen endotrachial intubation). RESULTS: Two boys, 7.5 and 14 years old, were addressed by the department of neurology for radical thymectomy. They presented an ocular myasthenia gravis for 2 years and a mild general myasthenia gravis for 7 years. The operative times were 120 and 240 min. There was no intraoperative or postoperative complication. Duration of thoracic drainage was 2 days. The children were discharged on the third postoperative day. For the second procedure, an ultrasound exam during surgery was necessary to localize the thymus exactly, thus enabling its complete resection without the need for a conversion. The follow-up is 19 and 7 months with a clinical improvement enabling the diminution of medication for both children, the end of ptosis for the first child, and the general improvement of muscle strength for the second. CONCLUSIONS: Thoracoscopic thymectomy in children with juvenile myasthenia gravis seems to offer a complete surgical resection, as do open techniques. In case of difficulties in finding the thymus, an ultrasound exam is feasible to enable complete resection. The left-sided thoracoscopic approach gives a good mediastinal and cervical exposition. Furthermore, being less painful in the postoperative period, it presents a less pronounced impairment of pulmonary function, and it presents good cosmetic effect.

[Aicardi-Goutieres syndrome: an oft unrecognised familial early-onset encephalopathy]. / Le syndrome d'Aicardi-Goutières: une maladie neurologique infantile, à transmission familiale, encore méconnue.

INTRODUCTION: Aicardi-Goutieres syndrome, first described in 1984, is a progressive infantile familial encephalopathy featuring cerebral calcifications, mainly of the basal ganglia, cerebral white matter abnormalities and cerebrospinal fluid lymphocytosis. Most of the patients present with severe developmental retardation, microcephaly, abnormal eye movements, pyramidal tract signs, and prominent dystonic movements. An elevated level of interferon-alpha in the CSF is a constant feature, particularly during the first stages of the disease course. One locus has been mapped on chromosome 3p21 in about half of the families so far studied. PATIENTS: and results. We report two new French cases and discuss the limits of the clinical syndrome, the differential diagnosis and issues raised by the pathophysiological mechanisms involved. The major concern is to separate this condition from intrauterine infections because of the genetic and therapeutic consequences. A number of other questions remain unanswered. For example, we still do not know today at what age the absence of features like CSF lymphocytosis, and possibly absence of calcifications, rules out the diagnosis of the condition. The origin of the vasculitis lesions is not known, but seems to be related to dysregulation of interferon production and secretion. CONCLUSION: Currently about 75 patients have been reported, even though many more probably exist. The study of this syndrome can contribute to the understanding of some mechanisms of CNS calcification and in a broader perspective to that of chronic encephalopathies with dysregulation of immune mechanisms.

Genotype determination at the survival motor neuron locus in a normal population and SMA carriers using competitive PCR and primer extension.

Precise quantitation of SMN1 copy number is of great interest in many clinical applications such as direct detection of SMA carriers or detection of an SMA-affected patient with a hemizygous deletion of the SMN1 gene. We describe a method that combines two independent nonradioactive PCR assays: determination of the relative ratio of the SMN1 and SMN2 genes using a primer extension assay and of the total SMN copy number using competitive PCR. Consistency of the results of two independent approaches ensures the reliability of the deduced genotype and thus avoids false interpretation of borderline results that can occur in quantitative assays. In all, 135 subjects were tested, including 91 normal controls and 44 SMA-affected children or SMA carriers. Two main genotypes were observed in controls: 2T/2C (45%) and 2T/1C (32%). A wide variability at the SMN locus is observed with nine different genotypes and up to six SMN genes. SMA carriers showed three frequent genotypes, 1T/2C (50%), 1T/3C (29%), and 1T/1C (18%). Normal chromosomes with two SMN1 genes per chromosome are not infrequent and thus, about 3% of SMA carriers are not detected using SMN1 copy number quantitation. Finally, as this method does not detect point mutations (4% of SMN1 gene mutations), reliability ranges from 93% to 100% depending on data available from the propositus.

Topographical and cytological evolution of the glial phase during prenatal development of the human brain: histochemical and electron microscopic study.

An ultrastructural analysis of prenatal gliogenesis and neuronal-glial relationships in the developing fetal brain was carried out using reduced osmium and periodic acid-thiocarbohydrazide-silver proteinate to stain selectively the glycogen content of the glial population. Gliophilic neuronal migration was confirmed in the human fetus, with radial glial fibers (RGF) acting as obligatory corridors for neuronal migration in the prospective neocortex and underlying intermediate zone (IZ). With this method, the entire glial phase was differentiated from neuronal elements; this permitted a description of the evolutionary distribution pattern of RGF: in the cortical plate, glial fascicles fully dissociate by 18 weeks gestation, whereas in the IZ, they remain grouped in fascicles until their transformation into astrocytes. The most conspicuous and constant developmental feature observed in the maturing glial cytoplasm between 21 and 30 weeks gestation was a radical enhancement in the abundance and activity of the lysosomal apparatus and autophagic vacuoles observed in the RGF, a cytological basis for the transformation of radial glial cells into astrocytes. These data have implications for the understanding of the ontogenesis of the neocortical vertical modules in the human brain and for the phylogenetic analysis of the vertical cortical units in terms of comparative mammalian anatomy.