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Background: Hypomyelination and congenital cataract (HCC) is a rare autosomal recessive white matter disorder characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system, caused by mutations in the FAM126A gene., Aims: To report three patients of two unrelated families segregating novel mutations., Methods: clinical, neurophysiological, neuroradiologic and molecular investigations were carried out., Results: All patients show bilateral congenital cataract and progressive neurological impairment with peripheral neuropathy. The clinical phenotype is consistent with the severe form of HCC. Brain magnetic resonance imaging show the combination of a diffuse hypomyelination with superimposed periventricular white matter signal abnormalities., Conclusions: this study describes three additional HCC patients indicating that this recently defined leukoencephalopathy should be included in the differential diagnosis of hypomyelination in childhood. The peculiar clinical and neuroradiologic findings are useful to properly address molecular investigations and allow the differential diagnosis between HCC and other hypomyelinating forms., (Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy., Design: Prospective cohort study., Setting: Epilepsy centers in Italy., Patients: Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization., Main Outcome Measures: Identification of copy number variations (CNVs) and gene enrichment., Results: Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = .03) and showed higher gene content (P = .02) than those in control subjects. The CNVs larger than 1 megabase (P = .002) and including more than 10 genes (P = .005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associated with emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P = .004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy., Conclusions: Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap between CNVs observed in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.

The purpose of this retrospective study was to review the role of chemotherapy in the treatment, management and outcome of children diagnosed with clival chordomas. The medical records of six pediatric chordoma patients diagnosed at Childrens Hospital Los Angeles between 1995 and 2005 were reviewed. Of the six patients reviewed, all underwent an initial surgical resection. Following resection, three received a combination of chemotherapy and radiation therapy, two received chemotherapy alone and one patient refused both forms of therapy; this patient expired of progressive tumor. One patient developed acute monoblastic leukemia (M5a subtype) and died of intracranial hemorrhage during induction chemotherapy, 39 months after initial diagnosis. MRI of brain and spine showed disease progression shortly before his death. Two patients who received chemotherapy only after surgery, one patient who received chemotherapy at relapse following irradiation and one patient who received irradiation followed by chemotherapy are alive with stable radiographic abnormalities at a median follow-up of 9 years from diagnosis (range: 6-13 years). Chemotherapeutic agents included ifosfamide and etoposide in all four surviving patients. Chemotherapy with ifosfamide and etoposide may have a role in the treatment of pediatric clival chordomas when used alone or in combination with irradiation.

In the paper, the practical problem of analysing in an integrated way the performance of provincial waste systems is approached, in the framework of the Strategic Environmental Assessment (SEA). In particular, the in itinere phase of SEA is analysed herein. After separating out a proper group of ambits, to which the waste system is supposed to determine relevant impacts, pertinent sets of single indicators are proposed. Through the adoption of such indicators the time trend of the system is investigated, and the suitability of each indicator is critically revised. The structure of the evaluation scheme, which is essentially based on the use of ambit issues and analytical indicators, calls for the application of the method of the Dashboard of Sustainability for the integrated evaluation of the whole system. The suitability of this method is shown through the paper, together with the possibility of a comparative analysis of different scenarios of interventions. Of course, the reliability of the proposed method strongly relies on the availability of a detailed set of territorial data. The method appears to represent a useful tool for public administration in the process of optimizing the policy actions aimed at minimizing the increasing problem represented by waste production in urban areas.

Caveolins are the principal protein components of caveolae, invaginations of the plasma membrane involved in cell signaling and trafficking. Caveolin-3 (Cav-3) is the muscle-specific isoform of the caveolin family and mutations in the CAV3 gene lead to a large group of neuromuscular disorders. In unrelated patients, we identified two distinct CAV3 mutations involving the same codon 78. Patient 1, affected by dilated cardiomyopathy and limb girdle muscular dystrophy (LGMD)-1C, shows an autosomal recessive mutation converting threonine to methionine (T78M). Patient 2, affected by isolated familiar hyperCKemia, shows an autosomal dominant mutation converting threonine to lysine (T78K). Cav-3 wild type (WT) and Cav-3 mutations were transiently transfected into Cos-7 cells. Cav-3 WT and Cav-3 T78M mutant localized at the plasma membrane, whereas Cav-3 T78K was retained in a perinuclear compartment. Cav-3 T78K expression was decreased by 87% when compared with Cav-3 WT, whereas Cav-3 T78M protein levels were unchanged. To evaluate whether Cav-3 T78K and Cav-3 T78M mutants behaved with a dominant negative pattern, Cos-7 cells were cotransfected with green fluorescent protein (GFP)-Cav-3 WT in combination with either mutant or WT Cav-3. When cotransfected with Cav-3 WT or Cav-3 T78M, GFP-Cav-3 WT was localized at the plasma membrane, as expected. However, when cotransfected with Cav-3 T78K, GFP-Cav-3 WT was retained in a perinuclear compartment, and its protein levels were reduced by 60%, suggesting a dominant negative action. Accordingly, Cav-3 protein levels in muscles from a biopsy of patient 2 (T78K mutation) were reduced by 80%. In conclusion, CAV3 T78M and T78K mutations lead to distinct disorders showing different clinical features and inheritance, and displaying distinct phenotypes in vitro.

Background: Diagnosing asthma cannot be always easy. It is important to consider the validity of the diagnostic tests, and/or how much more commonly they are positive in patients with asthma compared to healthy subjects and, particularly, to patients with asthma-like symptoms., Objective: To evaluate the validity of diagnostic tests for asthma, in terms of sensitivity, specificity, positive and negative predictive values, in patients with bronchial asthma compared to patients affected by gastro-oesophageal reflux disease (GERD) with asthma-like symptoms, and healthy control subjects without asthma and gastro-oesophageal reflux (GER)., Design: Single-center, cross-sectional, observational study., Patients: We studied 60 patients with mild asthma, 30 patients with GERD and asthma-like symptoms and 25 healthy control subjects., Measurements: We measured provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in 1s (MCh PC(20)/FEV(1)), the amplitude percent mean of peak expiratory flow (A%M of PEF), derived from twice-daily readings for >2 weeks, the FEV(1)/forced vital capacity (FEV(1)/FVC) ratio, the eosinophil count in blood and in induced sputum and the serum eosinophil cationic protein (ECP) levels., Results: FEV(1)/FVC ratio, A%M of PEF, blood eosinophils counts and serum ECP levels were less sensitive and specific when the reference population was composed of patients with asthma-like symptoms by GER. While, MCh PC(20)/FEV(1) and induced sputum eosinophils count were the most sensitive (both 90%) and specific (89% and 92%, respectively) tests., Conclusion: Our findings demonstrate that MCh PC(20)/FEV(1) and the induced sputum eosinophil count are the most useful objective tests in patients with mild asthma. All patients with asthma presented both an MCh PC(20)/FEV(1) <1500 microg and eosinophils count in the induced sputum >1%.

Purpose: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis., Methods: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models., Results: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity., Conclusions: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.

In this report, we have developed a novel method to identify compounds that rescue the dystrophin-glycoprotein complex (DGC) in patients with Duchenne or Becker muscular dystrophy. Briefly, freshly isolated skeletal muscle biopsies (termed skeletal muscle explants) from patients with Duchenne or Becker muscular dystrophy were maintained under defined cell culture conditions for a 24-h period in the absence or presence of a specific candidate compound. Using this approach, we have demonstrated that treatment with a well-characterized proteasome inhibitor, MG-132, is sufficient to rescue the expression of dystrophin, beta-dystroglycan, and alpha-sarcoglycan in skeletal muscle explants from patients with Duchenne or Becker muscular dystrophy. These data are consistent with our previous findings regarding systemic treatment with MG-132 in a dystrophin-deficient mdx mouse model (Bonuccelli G, Sotgia F, Schubert W, Park D, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, and Lisanti MP. Am J Pathol 163: 1663-1675, 2003). Our present results may have important new implications for the possible pharmacological treatment of Duchenne or Becker muscular dystrophy in humans.

Genetic testing of Duchenne and Becker muscular dystrophies (DMD/BMD) is a difficult task due to the occurrence of deletions or duplications within dystrophin (DMD) gene that requires dose sensitive tests. We developed three multiplex quantitative real-time PCR assays for dystrophin exon 5, 45, and 51 within two major hotspots of deletion/duplication. Each exon was co-amplified with a reference X-linked gene and the copy number of the target fragment was calculated by comparative threshold cycle method (delta deltaC(t)). We compared the performance of this method with previously described end-point PCR fluorescent analysis (EPFA) by studying 24 subjects carrying DMD deletions or duplications. We showed that Q-PCR is an accurate and sensitive technique for the identification of deletions and duplications in DMD/BMD. Q-PCR is a valuable tool for independent confirmation of EPFA screening, particularly when deletions/duplications of single exons occur or for rapid identification of known mutations in at risk carriers.

Objective: To compare structures, procedures and results of the pharmaceutical management of institutional pharmacies in the city of Rosario (Argentina), to define the current situation and thus recommend changes., Method: Descriptive study, using a questionnaire and quality indicators of an Accreditation Program of Hospital Pharmacies. Evaluated dimensions: selection, acquisition, reception, storage and stock control of drugs and medical devices. Data was collected for a one-year-period in order to obtain indicators. After tabulation, data was discussed in meetings with all the pharmacists that participate in this study, in order to evaluate the situation and propose changes for the Pharmacies, as well as to evaluate the Program based on usefulness of these indicators., Results: The general results illustrate how each institution has different health policies. 43.2% of indicators were answered, 67.6% reached standard values., Conclusions: This work allowed for an exhaustive analysis of the current situation. The pharmacists made proposals and unified criteria in order to obtain an improved use of the economic resources of each institution.

We report a novel nonsense mitochondrial cytochrome b mutation (G15170A) in a 40-year-old woman with progressive exercise intolerance and lactic acidosis. Muscle biopsy showed several cytochrome c oxidase-positive ragged-red fibers, and reduced activities of respiratory chain complexes I and III. This mutation, resulting in the loss of 228 amino acids of the protein, was very abundant in the patient's muscle, but undetectable in lymphocytes and fibroblasts. Clinical and laboratory data indicate that this defect is the primary cause of the disease, thus adding a new mutation in the cytochrome b gene among the growing number of patients with exercise intolerance and lactic acidosis.

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.

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.

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.