Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Estudo comparativo da análise de ciclo de vida de concretos geopoliméricos e de concretos à base de cimento Portland composto (CP II)

A Análise de Ciclo de Vida (ACV) é um método que inclui a compilação e avaliação das entradas, saídas e dos impactos de um produto ao longo do seu ciclo de vida. Os resultados desta análise são utilizados para escolher alternativas favoráveis para uma aplicação específica. Este artigo utilizou as ferramentas de ACV, apoiada pelo software Umberto, para comparar o processo de obtenção de concretos de cimento Portland com o de concretos geopoliméricos, obtidos da ativação alcalina de aluminossilicatos. O impacto ambiental foi avaliado considerando 1 m³ de cada concreto, sendo (i) as emissões de CO2 (kg CO2/ m³) e (ii) a demanda energética (MJ/m³) as variáveis para determinar o potencial sustentável de ambos materiais. O objetivo principal foi avaliar se os concretos geopoliméricos são mais sustentáveis do que os concretos tradicionais. Os resultados obtidos mostraram que o consumo energético é reduzido em 45,8% na produção do concreto geopolimérico, quando comparado à produção do concreto de cimento Portland de desempenho mecânico equivalente. Com relação às emissões de CO2, o concreto geopolimérico reduz as emissões em 72,4%, em comparação ao concreto tradicional de cimento Portland CPII. Assim, o primeiro se mostra uma alternativa a ser considerada, na produção de materiais de construção de menor impacto ambiental

Long-term outcome of preterm infants treated with nasal continuous positive airway pressure

This study's aim was to assess neurodevelopmental and growth outcome until the age of 4 years of premature infants placed on early nCPAP, in the setting of the neonatal intensive care unit (NICU) and follow-up program of the Division of Neonatology of the Department of Pediatrics of the University Hospital, Lausanne, Switzerland. All consecutive inborn infants weighing <1500 g or <32 weeks of gestational age admitted to the NICU during two periods of 12 months-7.1996-6.1997 and 7.1998-6.1999-were compared before and after the systematic application of early nCPAP. Of 172 infants admitted to the NICU, 150 (87%) survived. 126 (84%) were tested at 6 months' corrected age, 121 (81%) at 18 months' corrected age, and 117 (78%) at the age of 4 years. Detailed perinatal data were collected. Follow-up included neurological examination, developmental testing and measurement of growth parameters. Statistical analyses were performed. Early application of nCPAP and avoidance of mechanical ventilation showed no adverse effects on neurodevelopment and growth. A significantly higher developmental quotient was found in the nCPAP group at 18 months' corrected age. Several trends were also noted in the nCPAP group with a decrease of intraventricular hemorrhage and in "abnormal neurodevelopment" at 6 months corrected age, a bigger head circumference at all different tested ages and a greater height at 6 and 18 months corrected ages. In conclusion, our study of developmental outcome documents the absence of any harmful effect of early application of nCPAP to treat respiratory failure in very low birthweight infants

Impact of infertility treatments on the health of newborns.

OBJECTIVE: To measure the use of infertility treatments in the general population and their association with neonatal health. DESIGN: Cross-sectional, population-based study. SETTING: Canton of Vaud, Switzerland; Etude du Developpement des Nouveau-nes (EDEN), a prospective study of chronic childhood conditions. PATIENT(S): Six thousand four hundred seventy-seven live newborns (6,379 pregnancies) delivered of residents of Vaud in the 19 maternity hospitals between 1993 and 1994. MAIN OUTCOME MEASURE(S): Neonatal morbidity, multiplicity, low birth weight, prematurity, intrauterine growth retardation, transfer to intensive care, and length of hospital stay. RESULT(S): Infertility treatments were reported for 2.1% of pregnancies (129 women, 148 newborns) and were associated significantly with adverse outcomes. Population-attributable risks varied from 3%-20%. The outcomes of twins did not differ regardless of whether their mother was treated for infertility. Among singletons, only low birth weight was significantly more frequent when infertility treatments were used. Unadjusted odds ratios for neonatal morbidity were significant only for multiple births (2.56; 95% confidence interval 1.21-5.42). This association was not influenced by maternal characteristics and it disappeared after controlling for sex, gestational age, and birth weight. CONCLUSIONS(S): An independent effect of infertility treatments on neonatal morbidity cannot be ruled out, but most of their impact appeared to be mediated by multiplicity and prematurity. Reducing the number of medically induced multiple pregnancies is the most effective prevention of neonatal morbidity related to infertility treatments. Follow-up studies are needed

Enrolment of a population-based cohort of newborns at higher risk of developing a chronic condition: the EDEN study.

OBJECTIVE: To describe the methods used at birth to recruit a population-based cohort of newborns of all birthweights at higher risk of having a chronic condition, and to present baseline results. METHODS: Screening of all newborns at hospital discharge for five non-exclusive criteria: (1) low birthweight (LBW), (2) congenital anomalies or genetic disease, (3) specified conditions associated with a high probability of chronicity, (4) referral to a neonatal intensive care unit (NICU), (5) or defined social problems. Calculation of Hobel risk scores for children satisfying > or = 1 criterion. SUBJECTS: All 6477 live births delivered in the 19 maternity hospitals of a geographically defined region (Vaud, Switzerland) to resident mothers in 1993-1994. RESULTS: Twelve per cent (n = 760) of newborns met > or = 1 criterion: 6.3% of all newborns had an LBW (criterion 1), 2.4% had a birth defect, 0.9% met criterion (3), 4.4% stayed in an NICU and 1.6% had serious social problems. Hobel prenatal score was high (> or = 10 points) for 41% of children with > or = 1 criterion, the intrapartum score for 87% and the neonatal score for 68%. CONCLUSIONS: Most newborns identified by the above simple criteria also had elevated perinatal risks. The validity of the criteria will later be tested against the results of the examinations of children with > or = 1 criterion at 18 months and 4 years of age, but the assessment at birth already shows that normal birthweight (NBW) children, in agreement with previous studies, contribute half the children at high risk perinatally

Cytomegalovirus fetal infection: prenatal diagnosis

We report the results of prenatal diagnosis in 15 cases of primary cytomegalovirus infection during pregnancy. Sixteen fetuses (one twin pregnancy) were examined by ultrasonography, amniocentesis, and fetal blood sampling. Prenatal diagnosis was positive in eight cases as evidenced by positive amniotic fluid cultures in eight, positive immunoglobulin M (IgM) in six, and abnormal ultrasound in two. Among infected fetuses, abnormal laboratory findings included anemia, thrombocytopenia, and elevated liver function tests. Three pregnancies were terminated because of ultrasound abnormality or abnormal laboratory indices. In cases of fetal infection with normal ultrasound and normal laboratory findings, the pregnancies were allowed to proceed, leading to the birth of four infants (three with subclinical infections, one with bilateral hearing loss). The relation between anemia, thrombocytopenia, altered liver function tests, and subsequent handicap remains unknown, but the abnormalities observed in utero correspond to those described at birth in cases of cytomegalic inclusion disease. Amniocentesis alone allowed the diagnosis of infection in all cases, but fetal blood sampling provided additional information about the fetal condition