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Biomedical subjects

J Morais

Publications and source records attributed to J Morais.

At least 19 recordsLinked to original sources
PubMed2006

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Aged↗
PubMed2002

Ecotoxicological assessment of leachates from MSWI bottom ashes.

In this paper, chemical and ecotoxicological data of leachates from bottom ashes collected in different Municipal Solid Waste Incinerators (MSWI) are shown. The bottom ashes were collected in Belgium (three incinerators--samples B1 to B3), France, Germany, Italy and United Kingdom (one incinerator in each country--samples F1, D1, I1 and UK1, respectively). Both chemical and ecotoxicological characterizations of leachates were done on the framework of the European Directive 91/689/EEC and the European Council Decision 94/904/EC. This work was carried out under the European project called Valomat, which was supported by the European Commission through Brite-Euram III program. Twenty-one inorganic parameters were analyzed. The ecotoxicological assays were done under standard laboratory conditions, using the bacterium Photobacterium phosphoreum, the freshwater alga Pseudokirchneriella subcapitata, the crustacean Daphnia magna and the vegetable Lactuca sativa. Chemical data varied from sample to sample. Similar results were obtained in biological assays. The samples can be classified as ecotoxic/hazardous according to the French proposal for a Criterion and Evaluation Methods of Waste Ecotoxicity (CEMWE) and the German regulation on Hazardous Waste Classification (HWC). However, samples B1, B2, B3 and D1 comply the maximum limits for direct valorization category defined in the French Classification of Bottom Ashes based on their Polluting Potential (CBAPP). Sample B1 presented the lowest level of ecotoxicity, being considered as the most interesting to be used in the development of new materials for civil engineering works.

Animals↗
PubMed2001

Influence of the interval between the administration of doxorubicin and paclitaxel on the pharmacokinetics of these drugs in patients with locally advanced breast cancer.

PURPOSE: The combination of bolus doxorubicin followed by a 3-h infusion of paclitaxel has high antitumor activity in patients with metastatic breast cancer, but is limited by unexpected cardiac toxicity. In contrast, the administration of the two drugs 16 h apart has similar antitumor activity but less cardiac toxicity. The purpose of this study was to compare the pharmacokinetics of these drugs when doxorubicin administration preceded paclitaxel by 30 min or by 24 h. PATIENTS AND METHODS: Women with locally advanced breast cancer were treated with doxorubicin (60 mg/m2 i.v. bolus) followed 24 h later by paclitaxel (200 mg/m2 i.v. over 3 h) for six cycles (four before and two after surgery). In one of the first two cycles doxorubicin preceded paclitaxel by 30 min instead of 24 h, with plasma sampling for pharmacokinetic analysis up to 48 h. Determination of drug levels in plasma was done by HPLC. RESULTS: A total of 28 patients were included. No clinical cardiac toxicity was observed but five patients discontinued doxorubicin-paclitaxel treatment after four cycles because of a decrease in LVEF of at least 15% from baseline or to less than 50%. While paclitaxel pharmacokinetics were not changed, there was a 30% and an 80% increase in the AUC0, 24h for doxorubicin and doxorubicinol, respectively, when the drugs were administered 30 min instead of 24 h apart. Even when paclitaxel was given 24 h after doxorubicin, there was a rebound 240% increase in the plasma concentration of doxorubicinol. CONCLUSIONS: Paclitaxel interferes with the pharmacokinetics of doxorubicin leading to higher systemic exposure to both doxorubicin and doxorubicinol, which is more evident when the plasma concentration of the anthracyclines is higher. This interference may explain the higher incidence of cardiac toxicity observed when the two drugs are administered within a short interval.

Adult↗
PubMed2001

[NiFe] hydrogenase from Desulfovibrio desulfuricans ATCC 27774: gene sequencing, three-dimensional structure determination and refinement at 1.8 A and modelling studies of its interaction with the tetrahaem cytochrome c3.

The primary and three-dimensional structures of a [NiFe] hydrogenase isolated from D. desulfitricans ATCC 27774 were determined, by nucleotide analysis and single-crystal X-ray crystallography. The three-dimensional structural model was refined to R=0.167 and Rfree=0.223 using data to 1.8 A resolution. Two unique structural features are observed: the [4Fe-4S] cluster nearest the [NiFe] centre has been modified [4Fe-3S-3O] by loss of one sulfur atom and inclusion of three oxygen atoms; a three-fold disorder was observed for Cys536 which binds to the nickel atom in the [NiFe] centre. Also, the bridging sulfur atom that caps the active site was found to have partial occupancy, thus corresponding to a partly activated enzyme. These structural features may have biological relevance. In particular, the two less-populated rotamers of Cys536 may be involved in the activation process of the enzyme, as well as in the catalytic cycle. Molecular modelling studies were carried out on the interaction between this [NiFe] hydrogenase and its physiological partner, the tetrahaem cytochrome c3 from the same organism. The lowest energy docking solutions were found to correspond to an interaction between the haem IV region in tetrahaem cytochrome c3 with the distal [4Fe-4S] cluster in [NiFe] hydrogenase. This interaction should correspond to efficient electron transfer and be physiologically relevant, given the proximity of the two redox centres and the fact that electron transfer decay coupling calculations show high coupling values and a short electron transfer pathway. On the other hand, other docking solutions have been found that, despite showing low electron transfer efficiency, may give clues on possible proton transfer mechanisms between the two molecules.

Amino Acid Sequence↗
PubMed2001

[Prognosis of postoperative aortic dissection. Assessment with magnetic resonance].

OBJECTIVE: To evaluate operated type A aortic dissection by Magnetic Resonance Imaging (MRI), in order to detect long-term complications and identify prognostic indexes of evolution. DESIGN: Prospective study with a three-year period of follow-up. Prognosis evaluation. SETTINGS: Outpatient Clinic at Hospital de Santa Maria and Magnetic Resonance Imaging Center at Hospital da Cruz Vermelha. PATIENTS: A sample of 37 patients submitted to type A aortic dissection surgery, included sequentially, after exclusion of those with contraindication to MRI. METHODS: Initial evaluation (clinical and MRI study) at 3 to 4 months and at 1, 2 and 3 years after surgery. The mean follow-up time was 39.3 +/- 2.9 months. We evaluated the following complications over the aorta (aortic graft and five segments of residual aorta) and the aortic valve: aneurysm, pseudoaneurysm, rupture, re-dissection, progressive aortic valve regurgitation, reoperation and death. The prognostic indexes analysed were: presence of residual flap; false lumen patency; presence of re-entry points; false lumen to aorta dimension ratio; initial aortic dimension; increase of aortic dimension. RESULTS: All patients, with the exception of three that died, remained asymptomatic. COMPLICATIONS: Aneurysm was detected in 45.9% of patients, located in one or more segments; rupture occurred in three patients, preceded by aneurysm and pseudoaneurysm development; moderate or severe aortic regurgitation was detected in 47.8% of patients. Prognostic indexes: 1. Aneurysm development in each segment yeilded a significant association with: presence of residual flap in the same and other segments; higher initial dimension of the same and other segments, with the exception of the abdominal segment; higher increase in dimension of the same and other segments, with the exception of the abdominal segment; 2. Moderate or severe aortic regurgitation development showed a tendency to association with higher increase in dimension of proximal ascending aorta. 3. No association was found between aneurysm and aortic regurgitation development. CONCLUSIONS: Patients operated for type A aortic dissection had a high incidence of late complications which lead to reoperation and in some cases death. The presence of a residual flap, increased aortic dimensions and higher increase rate of aortic dimensions were associated with a complicated evolution. MRI was a very useful technique for long-term monitoring and to identify prognostic indexes of evolution.

Aortic Dissection↗
PubMed2001

Pulmonary transvalvular and venous flows in the estimation of left ventricular diastolic pressures. A comparative Doppler-catheterization study.

OBJECTIVES: To evaluate the association between patterns of pulmonary transvalvular and venous flows in patients with ischemic heart disease, assessed by Doppler echocardiography, and invasive measurements of left ventricular (LV) diastolic pressures. POPULATION: Thirty-seven patients with clinical diagnosis or suspicion of coronary heart disease and referred for coronary angiography; all were in sinus rhythm, and had no known valvular heart or chronic pulmonary disease. METHODS: The following were recorded during transthoracic Doppler echocardiography: acceleration time (AT) and total ejection time (ET) of right ventricular outflow; duration of the flow at atrial contraction (a duration) and duration of the "A" wave of mitral inflow (A duration). These data were correlated with the values of LV filling pressures previously obtained by cardiac catheterization. RESULTS: We found a significant correlation of LV end-diastolic pressures with the difference a-A duration (r = 0.75; p < 0.001) and also with the ratio AT/ET (r = -0.73;.

Adult↗
PubMed2000

Atomic transport and chemical stability during annealing of ultrathin Al2O3 films on Si.

Ultrathin films of Al2O3 deposited on Si were submitted to rapid thermal annealing in vacuum or in oxygen atmosphere, in the temperature range from 600 to 800 degrees C. Nuclear reaction profiling with subnanometric depth resolution evidenced mobility of O, Al, and Si species, and angle-resolved x-ray photoelectron spectroscopy revealed the formation of Si-Al-O compounds in near-surface regions, under oxidizing atmosphere at and above 700 degrees C. Under vacuum annealing all species remained essentially immobile. A model is presented based on diffusion-reaction equations capable of explaining the mobilities and reproducing the obtained profiles.

Journal Article↗
PubMed2000

Effect of acarbose on insulin sensitivity in elderly patients with diabetes.

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.

Acarbose↗
PubMed2000

[Transient cortical blindness after cardiac catheterization in a post-surgical coronary patient].

Transient cortical blindness is a known complication after cerebral and vertebral angiography although is a rare complication following cardiac catheterization. In this report, we describe a seventy-six-year-old male patient who had cortical blindness after coronary bypass graft angiography. The development of cortical blindness, in this setting, appears to be an osmotic disruption of the blood-brain barrier which is selective for the occipital cortex. Other hypotheses, such as an immunological reaction to the contrast agent or a direct injection of dye into the vertebral artery system, were considered. The clinical outcome is usually favourable, with vision completely restored within 24-48 hours, as was the case of the patient described in the present report.

Aged↗
PubMed1999

Crystallization and preliminary diffraction data analysis of both single and pseudo-merohedrally twinned crystals of rubredoxin oxygen oxidoreductase from Desulfovibrio gigas.

Crystals of rubredoxin oxygen oxidoreductase have been obtained and characterized. They belong to space group P2(1)2(1)2, with unit-cell dimensions a = 88.24 (15), b = 101.25 (7), c = 90.80 (3) A. The homodimer (86 kDa) in the asymmetric unit is related by a non-crystallographic twofold rotation axis parallel to the ab 'diagonal' direction, as shown by the self-rotation maximum in the section with chi = 180 degrees. This pseudo-crystallographic symmetry element was also found to be the twinning axis of pseudo-merohedrally twinned crystals, leading to apparent pseudo-tetragonal P42(1)2 crystal symmetry.

Cold Temperature↗