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Biomedical subjects

D Pereira

Publications and source records attributed to D Pereira.

At least 19 recordsLinked to original sources

Prognostic value of E-cadherin immunoexpression in patients with primary ovarian carcinomas.

PURPOSE: To analyse the negative versus positive immunoexpression of E-cadherin in patients with primary ovarian carcinomas, and determine its significance in relation to clinicopathological features, overall and recurrence-free survival (RFS). PATIENTS AND METHODS: The protein expression of E-cadherin was immunohistochemically evaluated in formalin-fixed, paraffin-embedded samples in 104 patients with primary ovarian carcinomas. The clinicopathological factors studied were age, FIGO staging, histological type, tumour differentiation, the appearance of the ovarian capsule, peritoneal implants and residual tumour after cytoreductive surgery. Overall survival and RFS were evaluated using the Kaplan-Meier method, and multivariate analysis was completed using the Cox regression model. RESULTS: Of the 104 carcinomas, negative E-cadherin immunoexpression was observed in seven (7%) cases, and positive immunoexpression in 97 (93%). E-cadherin categorised into negative versus positive expression did not associate with any of the established clinicopathological parameters. However, negative E-cadherin expression significantly predicted a poorer overall survival when compared with positive expression (P=0.006). In the multivariate analyses, negative E-cadherin and the presence of residual tumour after cytoreductive surgery were independent prognostic factors for survival (P=0.014 and P=0.034, respectively). CONCLUSIONS: The presence of residual tumour after primary cytoreductive surgery and negative E-cadherin expression seem to be useful markers in patients with ovarian carcinomas likely to have an unfavourable clinical outcome. The assessment of E-cadherin immunoreactivity may be a useful prognostic indicator in ovarian cancer, complementary to established prognostic factors.

Adult↗

HER2 polymorphism and breast cancer risk in Portugal.

Breast cancer is a major public health problem around the world, and its carcinogenesis is not yet well understood. The human epidermal growth factor Receptor 2 (HER2) seems to play an important role in the development of this neoplasia, and genetic alterations in this gene, such as point mutations and polymorphisms have been detected in breast cancer patients. We analysed the frequency of a single nucleotide polymorphism in the HER2 gene in blood samples from 152 breast cancer patients and 146 healthy controls using the polymerase chain reaction methodology, followed by restriction fragment length polymorphism (PCR-RFLP). We found a twofold increase in risk of breast cancer in women who are carriers of a Val allele genotype-Ile/Val and Val/Val genotypes [odds ratio (OR)=2.00; 95% confidence interval (CI) 1.23-3.25; P=0.005]. Our results indicate an association between the presence of the Val allele in the HER2 polymorphism and the risk of breast cancer. Further studies are needed to evaluate the role of this polymorphism in the behaviour of breast cancer.

Breast Neoplasms↗

Cyclophosphamide, etoposide and G-CSF to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma.

We aimed to assess the effectiveness of cyclophosphamide, etoposide and G-CSF (C+E) to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma. A matched cohort study was performed comparing patients mobilized with C+E to patients mobilized with cyclophosphamide and G-CSF (C alone). Patients were matched for disease, prior radiotherapy and a chemotherapy score reflecting the amount and type of prior chemotherapy. Thirty-eight consecutive patients mobilized with C+E were compared with 38 matched controls. C+E was equivalent to C alone in terms of numbers of patients achieving a minimum threshold of > or =2 x 10(6)/kg CD34(+)cells (82% vs 79%, P = 0.74). C+E was superior, however, in terms of total CD34(+) yield (6.35 vs 3.3 x 10(6)/kg, P < 0.01), achieving a target graft of > or =5 x 10(6)/kg (55% vs 34%, P = 0.04) and obtaining both a minimum (61% vs 32%, P < 0.01) and target (45% vs 13%, P < 0.01) graft in one apheresis. This superiority was largely confined to patients with lower chemotherapy scores. There was no difference in neutrophil and platelet recovery or transfusion requirements for those who subsequently received high-dose therapy and stem cell transplantation. Thus, C+E improves the efficiency of peripheral blood stem cell collection, but does not increase the number of patients who can proceed to transplantation. Most of the benefit of the regimen was confined to patients who had not received extensive prior therapy. Novel strategies are required to increase the collection efficiency of 'hard to mobilize' patients.

Antineoplastic Combined Chemotherapy Protocols↗

Mortality and morbidity trends in ischemic heart disease in the autonomous region of Madeira in the ten-year period 1987-1996.

The increase in absolute number of deaths from ischemic heart disease (IHD) in the population aged > or = 65 years, in both sexes, in Madeira, when comparing the years 1987 and 1996, led to significant increases in the corresponding standardized death rates that go against the stabilization seen at national level. Significant increases in these rates for the same years were also seen in the district of Beja and in the Azores. The aim of this study was to ascertain the trends for the incidence, morbidity and mortality from acute myocardial infarction (AMI) in patients admitted in Madeira and its contribution to the increase in these rates, particularly in the population aged < 65 years of both sexes, which the number of deaths from ischemic heart disease did not increase. We studied 119 pts with AMI admitted in 1987 (year A), of whom 53 were aged < 65 years, and 186 pts with AMI admitted in 1996 (year B), of whom 72 were aged < 65 years, whose data were included in the Madeira Ischemic Heart Disease Register (RECIMA), an IHD hospital register that covers 1792 patients admitted with AMI in the Coronary Intensive Care Unit of the Department of Medical and Surgical Cardiology of Funchal Hospital over a period of 15 years (1984-1998). Mortality by the 28th day (fatal AMI admissions) in all ages fell slightly in both sexes in the two years studied (A = 19.3%; B = 16.1%). The number of fatal AMI admissions rose among females in the two age groups considered A = 11; B = 20; delta% = +45) and fell among males (A = 12; B = 10; delta% = -20). In males aged > or = 65 years, this number remained the same (A = 7; B = 7) and fell in males aged > or = 65 years (A = 5; B = 3; delta% = -40). The number of pts who survived to the 28th day (non-fatal AMI admissions) rose in all age groups for both sexes (A = 96; B = 156; delta% = +38.46), as did the ratios with deaths from IHD. These increases were roughly double in the group of patients aged 65 years compared to patients aged < 65 years. We found highly significant positive correlations in the population aged < 65 years between the number of non-fatal AMI admissions (morbidity data) and the number of deaths from IHD (mortality data) recorded in every year of the 10-year period 1987-96, these values being highly significant in both sexes (r = 0.89; p < 0.0001), in males (r = 0.87; p < 0.0001) and in females (r = 0.77; p < 0.0001). Since our study was carried out on an island on which all AMI cases are admitted to a single treatment center, we can conclude that these positive correlations represent a trend towards worsening of morbidity and mortality from IHD in Madeira in the population aged < 65 years, even though the number of deaths from IHD did not rise. The establishment of IHD registers similar to RECIMA in other regions of the country would help to identify trends in morbidity, mortality, and morbidity plus mortality in this population that would be useful in improving the orientation of resources allocated to the prevention and treatment of cardiovascular diseases.

Age Distribution↗

Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors.

Emerging data suggest that a subset of circulating human CD34(+) cells have phenotypic features of endothelial cells. Whether these cells are sloughed mature endothelial cells or functional circulating endothelial precursors (CEPs) is not known. Using monoclonal antibodies (MoAbs) to the extracellular domain of the human vascular endothelial receptor-2 (VEGFR-2), we have shown that 1.2 +/- 0.3% of CD34(+) cells isolated from fetal liver (FL), 2 +/- 0.5% from mobilized peripheral blood, and 1.4 +/- 0.5% from cord blood were VEGFR-2(+). In addition, most CD34(+)VEGFR-2(+) cells express hematopoietic stem cell marker AC133. Because mature endothelial cells do not express AC133, coexpression of VEGFR-2 and AC133 on CD34(+) cells phenotypically identifies a unique population of CEPs. CD34(+)VEGFR-2(+) cells express endothelial-specific markers, including VE-cadherin and E-selectin. Also, virtually all CD34(+)VEGFR-2(+) cells express the chemokine receptor CXCR4 and migrate in response to stromal-derived factor (SDF)-1 or VEGF. To quantitate the plating efficiency of CD34(+) cells that give rise to endothelial colonies, CD34(+) cells derived from FL were incubated with VEGF and fibroblast growth factor (FGF)-2. Subsequent isolation and plating of nonadherent FL-derived VEGFR-2(+) cells with VEGF and FGF-2 resulted in differentiation of AC133(+ )VEGFR-2(+) cells into adherent AC133(-)VEGFR-2(+)Ac-LDL(+ )(acetylated low-density lipoprotein) colonies (plating efficiency of 3%). In an in vivo human model, we have found that the neo-intima formed on the surface of left ventricular assist devices is colonized with AC133(+)VEGFR-2(+) cells. These data suggest that circulating CD34(+) cells expressing VEGFR-2 and AC133 constitute a phenotypically and functionally distinct population of circulating endothelial cells that may play a role in neo-angiogenesis.

AC133 Antigen↗

Thrombolytic therapy impact on prognosis after twelve months of first acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: Thrombolytic therapy is still widely used to restore antegrade flow in the infarct related artery (IRA), with unquestionable benefits in mortality reduction of such patients. The aim of this study was to evaluate early (< or = 28 days) and one-year mortality of patients with a first Q wave myocardial infarction (Q AMI), comparing those who underwent thrombolytic therapy with those who did not. POPULATION AND METHODS: A retrospective study was done on 907 patients (median age: 35 +/- 13 years, 66% male) admitted to a Coronary Unit with the diagnosis of first Q AMI, from January 1988 to December 1997, all in the same geographical area (minimum follow-up period of one year, mean follow-up 43 +/- 37 months). We compared demographics and clinical characteristics (coronary risk factors, previous history of angina, MI location and evolution, cardiac events, 28 day and one-year mortality) of patients who underwent thrombolysis (group T = 355) versus those who did not undergo reperfusion therapy (group NT = 552). RESULTS: Of these patients 39% underwent thrombolytic therapy. Group NT had a greater number of female patients (40% vs 25%; p < 0.001), a significantly higher mean age (67 +/- 12.2 vs 61 +/- 12; p < 0.001), and a higher percentage of diabetics (29% vs 19%; p < 0.001), in comparison to group T. The Q AMI developed into Killip class > or = 2 in 43% of patients in group NT and 23% in group T (p < 0.001). A higher number of AV block (NT-13% vs T-8%; p < 0.05) and higher in-hospital mortality (NT-14% vs T-9%; p < 0.05) was observed in patients not undergoing thrombolysis. The early (NT-22% vs T-12%; p < 0.001) and one-year (NT-33% vs T-16%; p < 0.001) mortalities were significantly higher in group NT than in group T, even after multivariate analysis. CONCLUSIONS: 1--Patients who did not undergo thrombolytic therapy initially had a profile of greater severity, and a higher early and one-year mortality rate. 2--Those who underwent thrombolytic therapy presented a significantly lower mortality, a benefit that was still observed after one year of follow-up and after multivariate correction.

Aged↗

Survival analysis within one year of first acute myocardial infarction: comparison between non-Q and Q wave myocardial infarction.

BACKGROUND: Non-Q wave Myocardial Infarction (non-Q AMI) is related pathophysiologically to Q wave AMI, as each represents different stages of plaque rupture and thrombosis. Post-hospital re-infarction and recurrent angina are more frequent in non-Q AMI than in Q wave AMI, offsetting the higher early risk with Q wave AMI, with one-year survival rates similar in the two types of MI. OBJECTIVES: 1--Evaluation of early (< or = 28 days) and one-year total mortality from first non-Q AMI in comparison to QMI. 2--Analysis of recurrent acute ischaemic events (non-fatal reinfarction and unstable angina) in both types of MI in the same periods of time. POPULATION AND METHODS: A retrospective study of 1146 patients, mean age 65 +/- 13 years, 65% male, admitted at CCU with a first MI, from January 1988 to December 1997 (minimum follow-up period of one year, mean follow-up 42 +/- 37 months). We compared the baseline demographics and clinical characteristics (coronary risk factors, previous angina, MI evolution, recurrent cardiac events, 28 day mortality and one year mortality) of patients with non-Q AMI (NQ group = 239) and Q wave AMI (Q group = 907). RESULTS: The NQ group patients were significantly older (mean age: 67 +/- 12.6 vs 65 +/- 12.5 years; p < 0.05), included fewer smokers (29% vs 43%; p < 0.001) and were more symptomatic before the index infarction (stable angina: 40% vs 30%; p < 0.05; unstable angina: 16% vs 6%; p < 0.001), when compared to the Q group patients. There were no significant differences in MI evolution, in Killip-Kimbal class > or = 2, recurrent angina and in-hospital mortality (Q-12% vs NQ-9%; ns), although there was a higher combined risk of arrhythmias and AV conduction disturbances in patients with QMI (Q-34% vs NQ-26%; p < 0.05). The combined risk of unstable angina and reinfarction at one year was significantly higher in group NQ (NQ-13% vs Q-8.1%; p < 0.05). The NQ group showed no significant difference in 28 day total mortality (NQ-14% vs Q-17%; ns) or at one year follow-up (NQ-24% vs Q-26%; ns) when compared to the Q group. CONCLUSION: 1--Despite a lower severity of non-Q AMI in the acute phase, 28 day and one year total mortality were similar in the two groups. 2--Patients with non-Q AMI showed a higher incidence of recurrent ischemic events at one year follow-up.

Aged↗

Mice with disrupted midsized and heavy neurofilament genes lack axonal neurofilaments but have unaltered numbers of axonal microtubules.

Mammalian neurofilaments are assembled from the light (NF-L), midsized (NF-M), and heavy (NF-H) neurofilament proteins. While NF-M and NF-H cannot self-assemble into homopolymers, the data concerning NF-L has been more contradictory. In vitro bovine, porcine, and murine NF-L can homopolymerize in the absence of other subunits. However, in vivo studies suggest that neither rat nor mouse NF-L can form filaments when transfected alone into cells lacking endogenous intermediate filaments. By contrast, human NF-L forms homopolymers in similar cell lines. Recently we generated mice with null mutations in the NF-M and NF-H genes. To determine if mouse NF-L can homopolymerize in mouse axons, NF-M and NF-H null mutants were bred to create a line of double mutant animals. Here we show that axons in NF-M/H double mutant animals are largely devoid of 10-nm filaments. Instead, the axoplasm is transformed to a microtubule-based cytoskeleton-although the lack of any increase in tubulin levels per unit length of nerve or of increases in microtubule numbers relative to myelin sheath thickness argues that microtubules are not increased in response to the loss of neurofilaments. Thus in vivo rodent neurofilaments are obligate heteropolymers requiring NF-L plus either NF-M or NF-H to form a filamentous network.

Animals↗

[Influence of the equality of ventricular pressure in the echocardiographic determination of the ejection fraction of the left ventricle].

OBJECTIVES: Limited data have been reported concerning the influence of right ventricular systolic overload on the accuracy of the 2D echocardiographic (echo) determination of left ventricular (LV) ejection fraction (EF). The normal newborn at birth (high pulmonary peak systolic pressure) and just after the fall of pulmonary pressure, represent an in vivo model to study this influence. This study compares the LVEF determined by recommended 2D echocardiographic algorithms with that by 3D echo, in newborns at birth and just after the normal fall of right ventricular systolic pressure. METHODS: 100 echocardiographic studies (50 at 2 to 6 hours after birth--group I; and 50 at 7 to 14 days old--control group) were performed in 82 normal newborns, to determine LVEF by 4 geometric models (cylinder hemiellipsoid; ellipsoid biplane; single plane area length, in 4- and 2-chamber view; biplane method of discs) and visual estimation, using 3D echocardiography as the reference method. RESULTS: In group I, the correlation between 3D echo and cylinder hemiellipsoid was r = 0.62 (SEE = 4.5%); ellipsoid biplane, r = 0.69 (SEE = 4.1%); single plane area length, 4 chambers, r = 0.66 (SEE = 5.1%) and, 2 chambers, r = 0.72 (SEE = 4.0%); biplane method of discs, r = 0.83 (SEE = 3.6%), and, visual estimation, r = 0.78 (SEE = 3.5%). In the control group, the correlation between 3D echo and cylinder hemiellipsoid was r = 0.70 (SEE = 3.4%); ellipsoid biplane, r = 0.63 (SEE = 3.4%); single plane area length, 4 chambers, r = 0.79 (SEE = 3.5%) and, 2 chambers, r = 0.76 (SEE = 4.1%); biplane method of discs, r = 0.90 (SEE = 2.3%), and, visual estimation, r = 0.64 (SEE = 3.9%). IN CONCLUSION: These data suggest that the biplane method of discs and single plane area length using 2-chamber view allows a more accurate LVEF determination when significant right ventricular pressure overload is present.

Algorithms↗

Nutritional control of pregnant women on chronic hemodialysis.

The authors describe their experience in the follow-up of four patients with chronic renal failure who became pregnant while being treated with chronic hemodialysis. The outcomes were successful and each gave birth to healthy babies. The adequate nutritional condition previous to the pregnancies added more safety to their management. Special dedication to the nutritional control enabled a good outcome of their pregnancies. It stressed the importance of the intervention of the nutritionist-dietitian in the follow-up of nephrologic patients and the integration of a multidisciplinary staff.

Adult↗

Comparison of left ventricular ejection fraction in congenital heart disease by visual versus algorithmic determination.

Two-dimensional (2D) echocardiographic visual estimation of left ventricular (LV) ejection fraction (EF) in patients with acquired heart disease yields results that are comparable to those obtained by recommended algorithms. However, there is no information concerning its accuracy in congenital heart disease. This study compares applicability, accuracy, and reproducibility of LVEF by visual estimation with that by currently used algorithms (cylinder hemiellipsoid, ellipsoid biplane, and biplane method of disks) in 92 consecutive patients with congenital heart disease but unrepaired complete atrioventricular septal defect, univentricular heart, and hypoplastic left ventricle, using 3D echocardiography as the reference method. Visual estimation of LVEF could be applied in all cases. Because of technically inadequate 2D echocardiographic images for volume measurement, analysis for comparison could be performed in 71 patients (77%), aged 1 day to 47 years. The correlation between 3D echocardiographic and visual estimation was 0.91 (SEE 3.3%), cylinder hemiellipsoid, 0.86 (SEE 3.9%), ellipsoid biplane 0.87 (SEE 3.9%), and biplane method of disks 0.93 (SEE 3.2%). Intraobserver variability was similar for all 2D echo methods. Interobserver variability was greater for visual estimation. In conclusion, visual estimation of LVEF is applicable to most patients with congenital heart disease, yielding results that are comparable to those obtained by currently used 2D echocardiographic algorithms.

Adolescent↗

Is mitral valve prolapse a congenital or acquired disease?

The prevalence of mitral valve prolapse (MVP) at birth was studied in 1,734 consecutive newborns without congenital structural heart disease. We have not identified any case of an unequivocal pattern of MVP using auscultatory and echocardiographic diagnostic criteria. Our data argue for the concept that MVP is an acquired disease.

Echocardiography↗

Diaspirin crosslinked hemoglobin (DCLHb) polymerization.

By employing proprietary polymerization agents possessing specific binding groups and by completing diaspirin crosslinked hemoglobin (DCLHb) polymerization under specific conditions, we have selectively achieved the following objectives: (1) the P50 was adjusted to the physiologic range or left- or right-shifted; (2) the surface of DCLHb was modified ("decorated"); (3) DCLHb was polymerized but not decorated; (4) DCLHb was polymerized and decorated; or (5) DCLHb was site-specifically modified and polymerized.

Amino Acids, Diamino↗