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Biomedical subjects

A A Lopes

Publications and source records attributed to A A Lopes.

At least 19 recordsLinked to original sources

PCR screening for 22q11.2 microdeletion: development of a new cost-effective diagnostic tool.

BACKGROUND: Del22q11.2 syndrome is the most frequent known chromosomal microdeletion syndrome. Previous studies suggest that a substantial number of patients with congenital heart disease have a 22q11 deletion. The molecular diagnosis of Del22q11.2 is usually made by fluorescence in situ hybridization, an expensive and not widely available technique. We developed an efficient and cost-effective PCR SNP assay designed for the screening of 22q11.2 deletion through consecutive homozygosity. METHODS: Through the screening of dbSNP we have selected SNP markers located in the 22q11.2 microdeleted region. Population heterozygosities were determined in 213 normal individuals. Designed assays consisted of PCR amplification followed by restriction enzyme digestion. Fragments generated were visualized on agarose gel and genotyped. RESULTS: Selected markers were: rs5748411, rs2238778, rs4819523 and rs4680. All selected markers were localized in the 22q11.2 deleted region. Allele and genotype frequencies of all selected markers were under Hardy-Weinberg equilibrium. Selected SNPs were not in linkage disequilibrium. Predicted assay specificity was estimated to be 92.86% in the Brazilian population. CONCLUSIONS: The use of consecutive homozygosity in this SNP-based diagnostic test may be used as a cost-effective tool in reference molecular genetics laboratories.

Adult↗

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease.

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Adolescent↗

Knowledge about transplantation and attitudes toward organ donation: a survey among medical students in northeast Brazil.

During the registration for the second semester of 2002, 779 of the 1001 students from the Medical School, Federal University of Bahia, Brazil, answered an anonymous multiple-choice questionnaire including demographic variables, knowledge about transplantation issues, and willingness to donate organs. Mean age was 21.9 +/- 2.9 years (range: 17 to 51 years); 59.5% were men. Regarding the knowledge of which organs and tissues could be transplanted, 99.1% answered kidneys, 96.1% heart, 88.2% liver, 41.1% lung, 24.0% pancreas, 9% bowel, 98.3% corneas, 89.5% bone marrow, 38.1% heart valves, 47.7% skin, and 18.5% bone and tendons. Regarding the criteria of death, 82.4% answered that it is the lack of all brain activity, 8.2% cardiac arrest, 5.2% irreversible coma, and 4.2% did not know. As to the Brazilian transplantation law, 47.3% did not know, 51% had heard about it, and 1.7% answered that they knew the law in detail. As to the willingness to donate organs, 538 (69.2%) were donors. Of 239 nondonors, 51.1% answered the reason for not donating was the lack of confidence in the heath system, 14.3% had no knowledge of the matter, 17.7% were concerned about organ removal before brain death, and 1.7% for religious reasons. The percentage of those willing to donate organs was greater among spiritualists than among Catholics and Protestants. The results of this study support a greater emphasis on providing information regarding transplantation in medical schools to improve the knowledge of future heath care professionals about transplantation and organ donation issues.

Adult↗

Hypertension in black people: pathophysiology and therapeutic aspects.

Salt sensitivity is regarded as an important contributor to the higher risk of hypertension in black people as compared with whites. This finding is in agreement with a better response to diuretics than to monotherapy with angiotensin-converting enzyme (ACE) inhibitor in black subjects. It is important to remember that the hypotensive effect of ACE inhibitor is augmented in patients on a thiazide diuretic. Moreover, the antihypertensive response to a specific drug varies among black patients. Thus, ACE inhibitors should also be viewed as important options to treat hypertensive black subjects. Results from clinical trials support an emphasis on lifestyle modification and a more intensive blood pressure lowering by pharmacological interventions to reduce the large black-white gap in cardiovascular events and end-stage renal disease (ESRD) attributed to hypertension.

Black or African American↗

A mathematical framework for group analysis of von Willebrand factor multimeric composition following luminography.

The objective of the present study was to establish a method for quantitative analysis of von Willebrand factor (vWF) multimeric composition using a mathematical framework based on curve fitting. Plasma vWF multimers from 15 healthy subjects and 13 patients with advanced pulmonary vascular disease were analyzed by Western immunoblotting followed by luminography. Quantitative analysis of luminographs was carried out by calculating the relative densities of low, intermediate and high molecular weight fractions using laser densitometry. For each densitometric peak (representing a given fraction of vWF multimers) a mean area value was obtained using data from all group subjects (patients and normal individuals) and plotted against the distance between the peak and IgM (950 kDa). Curves were constructed for each group using nonlinear fitting. Results indicated that highly accurate curves could be obtained for healthy controls and patients, with respective coefficients of determination (r2) of 0.9898 and 0.9778. Differences were observed between patients and normal subjects regarding curve shape, coefficients and the region of highest protein concentration. We conclude that the method provides accurate quantitative information on the composition of vWF multimers and may be useful for comparisons between groups and possibly treatments.

Adolescent↗

Race and glomerulonephritis in patients with and without hepatosplenic Schistosomiasis mansoni.

BACKGROUND/AIMS: United States investigators have shown evidence of higher susceptibility to focal segmental glomerulosclerosis (FSGS) in blacks than in whites. This association between race and FSGS has not been assessed outside the US. The present study assesses the association between race and type of glomerulonephritis in a sample of Brazilian patients, taking into account the presence of the hepatosplenic form of Schistosomiasis mansoni (HSM). METHODS: Eighty patients with focal segmental glomerulosclerosis (FSGS) were compared to 50 with membranoproliferative glomerulonephritis (MPGN). The association between race (i.e. black versus white) and type of glomerulonephritis was adjusted for age, gender and HSM by logistic regression. RESULTS: Blacks were more likely than whites to have FSGS (as compared to MPGN), both among patients with HSM (odds ratio (OR) = 2.67; 95% confidence interval (CI) = 0.81 - 8.81) and without HSM (OR = 2.19; 95% CI = 0.79 - 6.05). After adjustment for age, gender and HSM, the odds of FSGS remained significantly greater for blacks (OR = 2.49; 95% CI = 1.05 - 5.95). CONCLUSION: The increased likelihood of FSGS in Brazilian blacks is consistent with findings from US patients. The association between race and type of glomerulonephritis was similar between patients with and without HSM. Future investigations should focus on the mediators factors that might explain these findings.

Adolescent↗

Community acquired pneumonia among pediatric outpatients in Salvador, Northeast Brazil, with emphasis on the role of pneumococcus.

Pneumonia is one of the leading causes of hospitalization and death among children in developing countries, and mortality due to pneumonia has been associated with S. pneumoniae infection. This investigation was designed to describe the antimicrobial susceptibility and serotype patterns of pneumococcal strains recovered from the blood of children with community-acquired pneumonia (CAP) and to assess the clinical findings of pneumococcal bacteremic patients with pneumonia. In a 26 month prospective study, blood cultures were obtained as often as possible from children (<16 years of age) diagnosed with CAP in two emergency rooms. Antimicrobial drug susceptibility tests and serotyping were performed when pneumococcus was identified. We studied 3,431 cases and cultured blood samples from 65.5% of those. Pneumococcus was recovered from 0.8% of the blood samples. The differences in age, somnolence, wheezing and hospitalization among children with and without pneumococcal bacteremia were statistically significant. Pneumococcal bacteremia was age-related (mean 1.63 +/- 1.55; median 0.92) and associated with somnolence and hospitalization among children with CAP. One strain was recovered from pleural fluid. Penicillin resistance was detected in 21.0% (4/19) of the strains at an intermediate level, whereas 63.0% of the strains were resistant to trimethoprim-sulfamethoxazole. The most common serotypes were 14 and 6B, and these serotypes included the resistant strains. Eight of our 18 isolates from blood were of types included in the heptavalent conjugate pneumococcal vaccine, recently licensed in the USA.

Adolescent↗

Differential effects of enzymatic treatments on the storage and secretion of von Willebrand factor by human endothelial cells.

Enzymatic treatment used for passaging of endothelial cells may induce release of von Willebrand factor (vWF). Decreased ability to replenish intracellular stores results in decreased secretion of vWF in later passages of cells. Since both trypsin and pancreatin complex have been used for passaging endothelial cells, we analyzed the effects of successive passaging with these two enzyme preparations on the storage and secretion of vWF by human umbilical vein endothelial cells (HUVECs). Measurements were performed after the second to fifth passages. Cytoplasmic vWF was analyzed by indirect immunofluorescence and secreted vWF was measured in the supernatant of cultured HUVECs by ELISA. In trypsin-passaged cells, secreted vWF decreased progressively from passages 2 to 5. Respective concentrations were 355.0 +/- 30.4, 201.0 +/- 84.5, 150.0 +/- 1.4 and 120.5 +/- 38.9 ng vWF/10(5) cells. Comparatively, pancreatin-passaged cells secreted even less vWF protein (P = .001) at passages 4 and 5 (108.5 +/- 12.0 and 100.0 +/- 4.2 ng/10(5) cells, respectively) and had less vWF-positive cytoplasmic granules per cell. Thus, in experiments involving measurements of endothelial vWF, the use of low passage cells is recommendable and passaging with a pure trypsin preparation appears to be more appropriate.

Cell Culture Techniques↗

Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study.

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: </=90 (n=6264); </=85 (n=6264); </=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure</=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure </=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of </=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of </=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels </=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure </=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

Aged↗

Chest radiograph abnormalities in patients hospitalized with leptospirosis in the city of Salvador, Bahia, Brazil.

This study was designed to estimate the prevalence of pulmonary radiograph abnormalities and describe the distribution of the patterns of radiographic alterations among patients hospitalized with leptospirosis. Chest radiographs of 139 patients hospitalized with leptospirosis in Couto Maia Hospital, in Salvador, Bahia, Brazil, between July, 1997, and July, 1999, were analyzed. The radiographs were requested soon after hospital admission, independent of the clinical manifestations of the patients. Only the first radiograph was considered. Pulmonary radiograph alterations were recorded in 35/139 patients (25.2%); 95% mid-point confidence interval = 18.5% to 32.9%. Among the patients with radiograph alterations, alveolar infiltrate was seen in 26/35 (74.3%). The lesions were bilateral in 54.3% and located in the inferior lobes in 45.5%. Pleural effusion, represented by blunting of the costo-phrenic angle, was detected in 8.6% of the patients. The pattern of the pulmonary alterations, predominantly bilateral alveolar infiltrates, is consistent with the evidence that the basic pulmonary alteration in leptospirosis is a generalized capillaritis.

Adolescent↗

Comparative study of bacterial infection prevalence between cirrhotic patients with and without upper gastrointestinal bleeding.

Bacterial infection is a frequent complication in patients with chronic liver disease, mainly during the advanced stages. There is evidence that the main factors that contribute to a predisposition to infection in cirrhotic patients are related to hepatic failure with consequent immunodeficiency. Invasive procedures (diagnostic or therapeutic) can predispose to bacterial infections, and upper gastrointestinal bleeding (UGB) is considered a potentially important risk factor. A group of cirrhotic patients (child B and C Pugh groups) were evaluated retrospectively by chart reviews regarding the prevalence of bacterial infection during hospitalization to determine whether UGB was a risk factor. An infection was considered present if a specific organ system was identified or if fever (> 38(o)C) persisted for more than 24 hours with associated leukocytosis. Spontaneous bacterial peritonitis was based on classical criteria. Eighty-nine patients were evaluated. Fourty-six patients presented with UGB, and 43 patients had no UGB (control). There were infections recorded in 25/46 (54%) patients with UGB, and 15/43 (35%) in those without UGB (p=0.065). The ratio of the number of infections/admitted patients, was significantly larger in the group with UGB (0.78 +/- 0.89 vs. 0.39 +/- 0.62; p=0.028) since patients had more than one infection. In the UGB group compared to non UGB group, ascites was more frequent (67% vs. 42%; p=0.027); they were more likely to have undergone endoscopic procedures (p<0.001) and the mean +/- SD for platelets count was smaller (96,114 +/- 57,563 vs 145,674 +/- 104,083; p=0.007). The results show that UGB is an important contribution to bacterial infection among Child B and C cirrhotic patients.

Bacterial Infections↗

Use of oral antihypertensive medication preceding blood pressure elevation in hospitalized patients.

OBJECTIVE: To evaluate the frequency of oral antihypertensive medication preceding the increase in blood pressure in patients in a university hospital, the drug of choice, and the maintained use of antihypertensive medication. METHODS: Data from January to June 1997 from the University Hospital Professor Edgard Santos Pharmacy concerning the prescriptions of all inpatients were used. Variables included in the analysis were: antihypertensive medication prescription preceding increase in blood pressure, type of antihypertensive medication, gender, clinical or surgical wards, and the presence of maintained antihypertensive medication. RESULTS: The hospital admitted 2,532 patients, 1,468 in surgical wards and 818 in medical wards. Antihypertensive medication prescription preceding pressure increase was observed in 578 patients (22.8%). Nifedipine was used in 553 (95.7%) and captopril in 25 (4.3%). In 50.7% of patients, prescription of antihypertensive medication was not associated with maintained antihypertensive medication. Prescription of antihypertensive drugs preceding elevation of blood pressure was significantly (p<0.001) more frequent on the surgical floor (27.5%; 405/1468) than on the medical floor (14.3%; 117/818). The frequency of prescription of antihypertensive drugs preceding elevation of blood pressure without maintained antihypertensive drugs and the ratio between the number of prescriptions of nifedipine and captopril were greater in surgical wards. CONCLUSION: The use of antihypertensive medication, preceding elevation of blood pressure (22.8%) observed in admitted patients is not supported by scientific evidence. The high frequency of this practice may be even greater in nonuniversity hospitals.

Administration, Oral↗

Two novel anti-von Willebrand factor monoclonal antibodies.

Von Willebrand Factor is a multimer produced by endothelial cells and megakaryocytes, being stored in intracellular organelles, such as the Weibel-Palade bodies and alpha-granules in endothelial cells and platelets, respectively. This molecule acts as a carrier protein for factor VIIIc, involved in the intrinsic pathway of blood coagulation maintaining its stability in circulation. Von Willebrand Factor also plays an important role in platelet aggregation and adhesion to injured vessel wall. It interacts with platelets through two distinct glycoproteins, GPIb and GPIIb/IIIa. We raised two monoclonal antibodies, ECA-3 and ECA-4, against human umbilical vascular endothelial cells that recognize and immunoprecipitate von Willebrand Factor. Interestingly, ECA-4 monoclonal antibody is able to completely inhibit platelet agglutination induced by ristocetin, suggesting that it binds to von Willebrand Factor close to platelet GPIb binding site. The use of monoclonal antibodies to identify von Willebrand Factor binding regions to factor VIII or platelets has been reported by others. In pulmonary hypertension, abnormalities have been detected on the multimeric structure of the molecule as well as on its proteolytic fragments, by using monoclonal antibodies. Moreover, monoclonal antibodies raised against specific regions of von Willebrand Factor molecule may allow studies of functional abnormalities of this protein in inherited and acquired disorders like subtypes of von Willebrand's disease.

Animals↗

Endothelial cell dysfunction correlates differentially with survival in primary and secondary pulmonary hypertension.

BACKGROUND: Plasma von Willebrand factor antigen (vWF:Ag) has been used as a marker of endothelial perturbation in a number of vascular disorders. In this study, vWF:Ag was determined as an attempt to evaluate the severity of endothelial cell dysfunction in primary pulmonary hypertension (PPH) and congenital heart disease-associated pulmonary hypertension (CHD-PH) comparatively and to determine its impact on short-term survival. METHODS AND RESULTS: Clinical, hemodynamic, and biochemical data were obtained from 11 patients with PPH and 24 with CHD-PH. Patient groups were similar in terms of age and pulmonary artery pressure. vWF:Ag was measured by electroimmunodiffusion. Patients were followed up for 1 year and at that time, data collected at the beginning of the study were subjected to univariate and multivariate analyses. vWF:Ag was increased in patients (normal reference value 87% +/- 23% activity, mean +/- SD), with higher levels in the PPH group (231% +/- 89%) in comparison with the CHD-PH group (127% +/- 68%) (P <.001). Multivariate analysis showed that survival was influenced by the underlying cause of pulmonary hypertension and vWF:Ag levels but not by patient age, sex, or pulmonary artery pressure. Seven of 10 nonsurvivors but only 4 of 25 survivors had PPH (P =.007). vWF:Ag was 255% +/- 90% in the nonsurvivor group and 121% +/- 54% in the survivors (P <.001). CONCLUSIONS: Our findings suggest that short-term survival is related to the severity of endothelial cell dysfunction in pulmonary hypertension. In addition, exceedingly high vWF:Ag levels in PPH might reflect a particular pattern of endothelial cell dysfunction that could be associated with decreased short-term life expectancy in this disorder compared with secondary forms of pulmonary hypertension.

Adolescent↗

Inverse association between skin response to aeroallergens and Schistosoma mansoni infection.

BACKGROUND: Helminthic infections and allergic disease are highly prevalent in many areas of the world. It is known that IgE antibodies are involved in the pathogenesis of both helminthiasis and atopy. However, the consequences of the presence of helminthic infections in atopic patients are still not completely understood. METHODS: Subjects infected by Schistosoma mansoni with more than 200 eggs/g of feces (n = 42) and uninfected subjects (n = 133) were selected from an endemic area of schistosomiasis. The history of allergy and results of the immediate hypersensitivity prick tests with inhalant allergen extracts were registered. Total IgE and IgE specific to S. mansoni and aeroallergens were measured in serum by ELISA. RESULTS: The proportion of individuals with a positive skin test to allergens was higher in the uninfected group (24.3%) than in the group with more than 200 eggs/g of feces (4.8%). The odds of atopy (defined as a positive test for at least one of the antigens) were 5 times higher (odds ratio = 7.0; 95% confidence interval = 1.6-31.1%; p = 0.01) in the uninfected group, after taking into account the potential influence of gender and age. While there was a tendency for higher total and S. mansoni-specific IgE levels in infected patients, an opposite trend, that is higher aeroallergen-specific IgE, was observed in uninfected subjects. CONCLUSIONS: There was a strong and statistically significant inverse association between the immediate skin test response to common aeroallergens and infection by S. mansoni. The results indicate that immediate hypersensitivity reactions may be suppressed in S. mansoni-infected individuals.

Adolescent↗

Mortality attributed to myocardial infarction in the male and female population of Salvador, BA, between 1981 and 1996.

OBJECTIVE: To describe according to gender the trend in mortality attributed to myocardial infarction (MI) in the population of Salvador, Bahia between 1981 and 1996. METHODS: This study was on mortality due to MI estimates by period and gender of the city of Salvador, Bahia. Data from 1981 to 1996 were stratified by quadrienia, and the percentage reduction in death rate due to MI relative to the preceding period (PRR) was determined. Comparisons between genders were expressed by the male/female death ratio (DR) based on the gender-related PPR. RESULTS: An overall increase of approximately 8% was observed in the death rate attributed to MI for the period 1985-1988 (89.2/10 5 individuals / year) versus the period 1981-1984 (82.1/10(5)/ year). In the subsequent periods, overall reductions of 10% and 20.3% were observed for the periods 1989-1992 and 1993-1996, respectively. For men, the PPRs were 11.1 in the period 1989-1992 and 22.7% in the period 1993-1996. The PPRs in women were lower: 8.6% and 17.4% between 1989 and 1992, and 1993 and 1996, respectively. Death rate reduction was greater for men than women, then the male/female DR decreased from 1.66 in 1981-1984 to 1.35 in 1993-1996. CONCLUSION: The results indicate a trend towards a reduction in the death rate attributed to myocardial infarction in the city of Salvador from the second half of the 1980s onwards, striking in men.

Adult↗