Novel FAM126A mutations in hypomyelination and congenital cataract disease.

Hypomyelination and congenital cataract (HCC, OMIM #610532) is a rare autosomal recessive disorder due to FAM126A mutations characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system. We have identified two novel mutations in three affected members of two unrelated families. Two sibs harbouring a microdeletion causing a premature stop in the protein showed the classical clinical and neuroradiologic HCC picture. The third patient carrying a missense mutation showed a relatively mild clinical picture without peripheral neuropathy. A residual amount of hyccin protein in primary fibroblasts was demonstrated by functional studies indicating that missense mutations are likely to have less detrimental effects if compared with splice-site mutations or deletions that cause the full-blown HCC phenotype, including peripheral nervous system involvement.

Early-onset absence epilepsy: SLC2A1 gene analysis and treatment evolution.

BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.

[Pharmaceutical care for older adults. Application of STOPP-START criteria]. / Atención farmacéutica de adultos mayores. Aplicación de los criterios STOPP-START.

INTRODUCTION: Drug-related problems can be caused by potentially inappropriate prescribing (PIP), one of the most used tools for its identification are the STOPP (Older Persons' potentially inappropriate Prescriptions) - START (Screening Tool to Alert doctors to Right Treatment) criteria. The objective of this study is to determine PIP in older adults who receive pharmaceutical care in the Pharmacotherapy Optimization Unit (POU)-Rosario. MATERIALS AND METHODS: Pharmacoepidemiological observational study, which evaluates the quality of medication use. Workplace: POU-Rosario. Population under study: adults over 60 years of age, who received pharmacotherapy follow-up during the period March 2017 to February 2018. PIPs were identified using the STOPP-START criteria, 2014 version; selecting the most appropriate criteria to assess outpatient pharmacotherapy. Prevalence of PIP and amount of PIP per active principle were estimated. RESULTS: 50 patients older than 60 years received pharmacotherapy follow-up in the POU; 47 patients (94.0%) had at least one PIP corresponding to a STOPP criterion; 17 STOPP criteria were found among the 41 initially selected, leading to 145 PIPs identified. And 7 START criteria among the 11 initially selected, leading to 50 PIPs identified. Medications with a higher amount of PIPs: benzodiazepines and proton pump inhibitors. CONCLUSIONS: This study allowed the identification of a high prevalence of PIP. The data obtained show the usefulness of these criteria. The STOPP-START criteria have been included to support decision making during pharmacotherapy follow-up to propose pharmaceutical interventions, in order to enhance pharmacotherapy. These activities contribute to patient safety, a dimension of health quality.

Structural Connectivity Analysis in Children with Segmental Callosal Agenesis.

BACKGROUND AND PURPOSE: Segmental callosal agenesis is characterized by the absence of the intermediate callosal portion. We aimed to evaluate the structural connectivity of segmental callosal agenesis by using constrained spherical deconvolution tractography and connectome analysis. MATERIALS AND METHODS: We reviewed the clinical-radiologic features of 8 patients (5 males; mean age, 3.9 years). Spherical deconvolution and probabilistic tractography were performed on diffusion data. Structural connectivity analysis, including summary network metrics, modularity analysis, and network consistency measures, was applied in 5 patients and 10 age-/sex-matched controls. RESULTS: We identified 3 subtypes based on the position of the hippocampal commissure: beneath the anterior callosal remnant in 3 patients (type I), beneath the posterior callosal remnant in 3 patients (type II), and between the anterior and posterior callosal remnants in 2 patients (type III). In all patients, the agenetic segment corresponded to fibers projecting to the parietal lobe, and segmental Probst bundles were found at that level. Ectopic callosal bundles were identified in 3 patients. Topology analysis revealed reduced global connectivity in patients compared with controls. The network topology of segmental callosal agenesis was more variable across patients than that of the control connectomes. Modularity analysis revealed disruption of the structural core organization in the patients. CONCLUSIONS: Three malformative subtypes of segmental callosal agenesis were identified. Even the absence of a small callosal segment may impact global brain connectivity and modularity organization. The presence of ectopic callosal bundles may explain the greater interindividual variation in the connectomes of patients with segmental callosal agenesis.

[Visceral leishmaniasis in infants without bioptic demonstration of the parasite. Presentation of 3 cases]. / Leishmaniosi viscerale del lattante senza dimostrazione bioptica del parassita. Presentazione di tre casi.

The Authors describe three infants with visceral leishmaniasis in whom bioptic research (in marrow, spleen and liver) has not demonstrated presence of leishmania. They remark this unusual aspect of visceral leishmaniasis in infant and debate the epidemiological, diagnostic, and therapeutic aspects of these cases.

[Acute bacterial enteritis in children. Etiological, clinical and epidemiological findings in a 5-year hospital case series]. / Le enteriti acute batteriche dell'infanzia. Rilievi etiologici, clinici ed epidemiologici su una casistica ospedaliera di 5 anni.

The Authors carried out retrospective research into bacterial enteritis observed during the past 5 years (Jan. 1982-Dec. 1986) in Pediatric Clinic R of Palermo. The pathogenic agents more frequently isolated were minor salmonellas, followed by E. Coli and shigellas. The first ones showed an incidence almost constant during the five years, while the second and third ones presented epidemic tops in 1982 and 1985. Inside the salmonellas' group it was evidenced a prevalence of S.T. Murium (44.71%), of S. Corvallis (21.13%) and of S. Enteridis (11.38%) and inside the shigellas' group S. Sonnei was more evident (80.43%). A higher incidence of bacterial enteritis appeared: during the period summer-autumn, in patients under one year or undernourished, in those coming from lower social classes, not breast-fed or wrongly fed. An accurate analyses of symptoms has not allowed an aetiological diagnosis, and clinical course of illness was always favourable. The therapy more often used was rehydration, associated with antibiotics only in very serious cases.

[Patient safety: use of quality management to prevent medication errors in the hospital medication use cycle]. / Seguridad del paciente: aplicación de gestión de calidad para prevenir errores de medicación en el circuito de uso de medicamentos.

OBJECTIVES: To describe the medication errors in the medication use cycle in a general public hospital, and to identify intervention strategies in relation to the detection and prevention of these errors. METHODS: Descriptive study with cross-sectional design. General public hospital of 190 beds, in Rosario (Argentina). Daily and systematic data collection of the circuit of use of medicines during May 2009. Once the errors were identified and classified, an interdisciplinary group sequentially applied different quality management tools to recognize and weigh causes, and propose solutions. (Flowchart, Cause Effect Diagram, Brainstorming, Nominal Group and Matrix Decision). RESULTS: Information on 60 patients was retrieved during the study period, with 506 medication errors detected. The impact indicators showed the following values: 8.4 errors/patient and 88.6 errors/100 patients-day. From the causes identified, two were defined as relevant: "Double prescription" and "Lack of clear policy". Of the various solutions proposed, an intervention strategy was defined to include a differently designed form for "prescription/indication/administration" in the clinical history which could be updated daily, with a duplicate to Pharmacy for the distribution, as well as a Standard Operating Procedure to standardize this new way of working. CONCLUSION: This work achieved, through quality management, the commitment of a team of health professionals to seek and make changes for patient safety, and to improve the quality of services provided by the hospital.

[Acute enteritis and dietetic errors in the first 6 months of life]. / Enteriti acute ed errori dietetici nei primi 6 mesi di vita.

The dietary habits of 174 infants under 6 months old and suffering from enteritis were analysed revealing a high incidence of feeding errors (almost always feeding with artificial formulas, wrong concentration of milk powder, failure to sterilise the bottle and the water used to dilute the milk, too early administration of undiluted, unboiled bottled cow's milk, too early and incorrect weaning). Such mistakes appeared to be linked to the poor economic and sociocultural conditions of the families concerned. It is claimed that dietary errors conditioned by the poor economic and sociocultural conditions encountered may have favoured the onset of enteritis and that the adequate prophylaxis of acute infantile enteritis will depend on improving people's dietary habits and living conditions.

Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV).

BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide. The typical presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset (perinatal, congenital, juvenile, or adult) and severity. OBJECTIVE: To identify the molecular bases of different neuromuscular forms of GSD-IV and to establish possible genotype/phenotype correlations. METHODS: Eight patients with GBE deficiency had different neuromuscular presentations: three had fetal akinesia deformation sequence (FADS), three had congenital myopathy, one had juvenile myopathy, and one had combined myopathic and hepatic features. In all patients, the promoter and the entire coding region of the GBE gene at the RNA and genomic level were sequenced. RESULTS: Nine novel mutations were identified, including nonsense, missense, deletion, insertion, and splice-junction mutations. The three cases with FADS were homozygous, whereas all other cases were compound heterozygotes. CONCLUSIONS: This study expands the spectrum of mutations in the GBE gene and confirms that the neuromuscular presentation of GSD-IV is clinically and genetically heterogeneous.

Evaluación de normas de buenas prácticas de fabricación de mezclas de nutrición parenteral extemporánea / Evaluation of good standars practices of fabrication parenteral nutrition extemporaneous mixtures

Las buenas prácticas de fabricación (BPF) sistematizan un conjunto de recomendaciones cuya aplicación es, sin lugar a dudas el camino más eficaz para asegurar la calidad de los productos farmacéuticos. Su finalidad es doble: por un lado, proveer a la industria farmacéutica de una referencia para la evaluación y aplicación de procedimientos de fabricación adecuados, y por el otro, faciliar las tareas de fiscalización y control de las autoridades sanitarias, así como la armonización de las respectivas normativas nacionales. Las normas nacionales de BPF ofrecen un marco regulatorio para asegurar que las mezclas de nutrición parenteral extemporáneas preparadas sean adecuadas para el fin propuesto, garantizando que cumplan con los requisitos de calidad, seguridad, pureza y eficacia preestablecidos, así como también presentar evidencia documentada completa del cumplimiento de las buenas practicas de fabricación...