Ubiquitin associated protein 1 is a risk factor for frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (FTLD) is now recognised as a common form of early onset dementia. Up to 40% of patients have a family history of disease demonstrating a large genetic component to its etiology. Linkage to chromosome 9p21 has recently been reported in families with this disorder.

Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP.

Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65 years) Alzheimer's disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early-onset AD (mean age at onset of 52.9 years; range 31-64).

TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis.

Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS.

Methodology/principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease.

Novel progranulin mutation: screening for PGRN mutations in a Portuguese series of FTD/CBS cases.

Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD) in many families. Different frequencies of these genetic changes have been reported in diverse populations leading us to determine if these mutations were a major cause of FTD in the Portuguese population. The entire coding sequence plus exon 0 of PGRN were sequenced in a consecutive series of 46 FTD/CBS Portuguese patients.

Whole genome analysis in a consanguineous family with early onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a clinically and genetically heterogeneous condition in which the typical features appear significantly earlier in life (before 65 years). Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in autosomal dominant forms of EOAD. However, in about 50% of Mendelian cases and in most of the sporadic EOAD patients, no mutations have been found.

Genotype, haplotype and copy-number variation in worldwide human populations.

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations.

DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA.

Background: Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved.

Methods: We identified two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism.

Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2.

Background: Mutations in the genes PRKN and LRRK2 are the most frequent known genetic lesions among Parkinson's disease patients. We have previously reported that in the Portuguese population the LRRK2 c.6055G > A; p.

Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal.

Mutations in the gene encoding beta-glucocerebrosidase, a lysosomal degrading enzyme, have recently been associated with the development of Parkinson disease. Here we report the results found in a cohort of Portuguese Parkinson disease patients and healthy age-matched controls for mutations in the aforementioned gene. This screening was accomplished by sequencing the complete open-reading frame, as well as intron/exon boundaries, of the glucocerebrosidase gene, in a total of 230 patients and 430 controls.

Peripheral inflammatory cytokines as biomarkers in Alzheimer's disease and mild cognitive impairment.

Background: Several lines of evidence in the literature have shown that inflammation is involved in the pathogenesis of Alzheimer's disease (AD). However, the results from the evaluation of serum inflammatory markers in AD patients have been controversial.

Objective: To determine if any differences exist in the monocytic secretion pattern of IL-1beta, IL-6, IL-12 and TNF-alpha from mild cognitive impairment (MCI) and AD patients, when compared with healthy age-matched controls.

Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort.

Background: Pathological brain iron deposition has been implicated as a source of neurotoxic reactive oxygen species in Alzheimer (AD) and Parkinson diseases (PD). Iron metabolism is associated with the gene hemochromatosis (HFE Human genome nomenclature committee ID:4886), and mutations in HFE are a cause of the iron mismetabolism disease, hemochromatosis. Several reports have tested the association of HFE variants with neurodegenerative diseases, such as AD and PD with conflicting results.

G2019S dardarin substitution is a common cause of Parkinson's disease in a Portuguese cohort.

LRRK2 mutations have recently been described in families with Parkinson's disease. Here we show that one of them (G2019S) is present in 6% (7 of 124) unrelated cases of disease in a clinic-based sample series from central Portugal, but not present in 126 controls from the same population. Thus, LRRK2 mutations appear to be a common cause of typical Parkinson's disease and as such will alter clinical practice.

[Mechanical ventilation near large centers. The experience of a perinatal care unit].

A retrospective study of the newborns who were submitted to mechanical ventilation at the Neonatal Intermediate Care Unit was made between July 1991 and June 1994. Mechanical ventilation in such a unit should be transitory and not exceed 24 hours. Information concerning pregnancy, labour, neonates, type of ventilation and its problems was gathered.

Ambroxol plus amoxicillin in the treatment of exacerbations of chronic bronchitis.

Twenty-three patients with exacerbations of chronic bronchitis were divided in two groups in a randomized fashion receiving either amoxicillin 1500 mg/d (n = 13) or amoxicillin 1500 mg/d associated with the mucolytic drug ambroxol 90 mg/d (n = 10). The improvement in cough, expectoration difficulties and sputum purulence was statistically more evident and occurred earlier in the ambroxol + amoxicillin group than in the amoxicillin only group. Although amoxicillin plasma and sputum levels were similar in both groups, the differences in daily sputum volume, which was also statistically greater in patients receiving ambroxol, suggests that this drug favours the bronchial mucus clearance of the antibiotic which could be related to the more favourable clinical evolution.

Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid.

Amoxicillin levels were measured in bronchoalveolar lavage (BAL) fluid samples obtained from patients who after randomization were treated in double-blind fashion either with amoxicillin 1000 mg p.o.t.

Influence of ambroxol on lung tissue penetration of amoxicillin.

Lung amoxicillin levels were assessed in tissue obtained from 16 patients who underwent lung resection due to different pulmonary diseases. In this double-blind placebo controlled study patients were allocated to two groups in randomized order; one group received amoxicillin 1000 mg t.i.

Experimental findings on the estrogenic activity of estradiol enantate.

In a first attempt to find out the estrogenic activity of the monthly injectable contraceptive composed of dihydroxyprogesterone acetophenide 150 mg + estradiol enantate 10 mg (Perlutal, Topasel), estradiol enantate (estra-1,3,5(10)-triene-3-ol-17 beta-heptanoat), estradiol benzoate and ethinylestradiol were compared in rats of the Chbb: THOM species. Estradiol benzoate potency was significantly higher than that of estradiol enantate: 20.34 (15.