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Biomedical subjects

A Pereira

Publications and source records attributed to A Pereira.

At least 55 records · Page 3Linked to original sources
PubMed2001

Platelet-specific antibodies in HLA-immunized patients receiving chronic platelet support.

BACKGROUND: In HLA-alloimmunized patients, the unexpected failure of HLA-matched platelet transfusions usually raises the suspicion about concomitant platelet-specific antibodies. As the reported frequency of platelet-specific antibodies in multitransfused patients varies widely, the aim of this study was to determine the prevalence of such antibodies in a population of chronic thrombocytopenic patients with HLA antibodies. STUDY DESIGN AND METHODS: From 1985 to 1997, 11,777 determinations of HLA antibodies were performed in 1330 hematologic patients receiving chronic platelet support. Fifty-two patients with HLA alloimmunization that lasted more than 1 month were selected. The search for platelet-specific antibodies was performed by using a monoclonal antibody immobilization of platelet antigens assay, thus allowing the identification of platelet-specific antibodies directed against the platelet glycoproteins (GP) Ib/IX, GPIIb/IIIa, and GPIa/IIa. Specificity of the platelet-specific antibodies was further investigated by using a solid-phase assay with chloroquine-treated platelets. RESULTS: Only 2 (3.8%) of the 52 patients had platelet-specific antibodies. One antibody reacted with an epitope of the GPIIb/IIIa that was present in all the panel platelets, and that probably was an autoantibody. The other was an anti-HPA-5b. CONCLUSIONS: The prevalence of platelet-specific antibodies in patients with HLA alloimmunization is very small. The search for concomitant platelet-specific antibodies would be indicated only when other causes of refractoriness to HLA-matched platelets are ruled out.

HLA Antigens↗
PubMed2001

Health and economic consequences of HCV lookback.

BACKGROUND: Several countries have conducted or are considering campaigns of lookback on blood recipients who may have acquired posttransfusion HCV (PT-HCV) before the implementation of anti-HCV screening. There is, however, no estimation of the health and economic consequences of the medical interventions triggered by the lookback. STUDY DESIGN AND METHODS: This study used a Monte Carlo simulation of a Markov model representing the natural history of PT-HCV. Unadjusted and quality-adjusted life expectancy and lifetime medical costs were calculated for a cohort of patients in whom PT-HCV is diagnosed through the lookback, and these values were compared with those calculated for a similar cohort on whom lookback is not performed. RESULTS: The model predicts that 47 percent of people who received transfusions of HCV-infective blood 10 years ago are still alive, carry the infection, and have not yet progressed to end-stage liver failure. In this population, forthcoming complications of PT-HCV will reduce the remaining life expectancy by 1.75 years per patient. Medical interventions triggered by the diagnosis of PT-HCV would salvage 0.123 years of life expectancy, at a net cost of $921 per newly diagnosed patient. The health and economic impact of diagnosing a new case of PT-HCV through lookback was sensitive to the patient's age, the efficacy of antiviral therapies, the time elapsed from transfusion to lookback, and the future inflation of costs of treating end-stage liver disease. Under some plausible assumptions, the intervention could result in net financial savings for the health care system, but it may also produce a net health loss for the majority of patients who will be said to be HCV-positive without being offered an effective therapy. CONCLUSION: Diagnosis of PT-HCV through HCV lookback has a potential both to increase patients' life expectancy and to reduce health care costs. However, more effective antiviral therapies and a better knowledge of factors predicting the progression of PT-HCV are needed to attain those goals. Meanwhile, care should be taken to avoid pursuing a health gain for a minority that might result in a health loss for the majority.

Blood Transfusion↗
PubMed2001

Transfusing methylene blue-photoinactivated plasma instead of FFP is associated with an increased demand for plasma and cryoprecipitate.

BACKGROUND: Photodynamic virus inactivation of plasma with methylene blue significantly decreases the recovery of fibrinogen and coagulation factors V and VIII. Because an adequate supply of fibrinogen is essential for the therapeutic efficacy of transfused plasma in many clinical settings, it was plausible that transfusing photoinactivated plasma (PIP) instead of FFP would result in an increased demand for plasma and cryoprecipitate. STUDY DESIGN AND METHODS: The study involved a retrospective analysis of the use of plasma at a university hospital (Barcelona, Spain) over three 1-year periods: one before the implementation of PIP therapy and two after. Blood components transfused to plasma recipients were listed by broad diagnostic categories based on the Diagnosis-Related Group classification. RESULTS: During the period under study, 2,967 patients were given plasma in this hospital. They received 27,434 units of plasma, 1,660 of cryoprecipitate, 10,079 of platelets, and 24,607 of packed RBCs. Patients undergoing surgical procedures accounted for 74 percent of all transfused plasma. In 71 percent of patient admissions, packed RBCs were transfused in addition to plasma. Diagnostic categories with the greatest requirement for plasma were cardiac valve surgery, liver transplant, wounds and traumatic injuries, and bowel surgery. The use of PIP was associated with a 56-percent increase in the aggregated demand for plasma, whereas the transfusion of non-virus-inactivated cryoprecipitate increased twofold the first year and threefold the second year. The growth in the use of plasma took place in all the diagnostic categories. In those categories that include patients with liver disease, a partial substitution of PIP for cryoprecipitate was observed during the second year after PIP therapy implementation. CONCLUSION: The use of PIP was associated with a marked increase in the demand for plasma and cryoprecipitate, which probably was due to the low hemostatic quality of the new component. It is possible that such an increase overrode the potential health benefits derived from transfusing virus-inactivated plasma.

Aged↗
PubMed2001

New indole alkaloids from Sarcocephalus latifolius.

Phytochemical investigation of the root extract of Sarcocephalus latifolius has led to the isolation of the new indole alkaloids 21-O-methylstrictosamide aglycone and 21-O-ethylstrictosamide aglycone, together with strictosamide, angustine, nauclefine, angustidine, angustoline, 19-O-ethylangustoline, naucleidinal, 19-epi-naucleidinal, quinovic acid-3 beta-O-beta-D-fucopyranoside, quinovic acid-3 beta-O-alpha-L-rhamnopyranoside, scopoletin, and beta-sitosterol. Strictosamide displayed moderate antiplasmodial activity against Plasmodium falciparum.

Alkaloids↗
PubMed2001

Magnetic resonance markers of ischaemia: their correlation with vasodilatory reserve in patients with carotid artery stenosis and occlusion.

OBJECTIVES: Better methods of identifying patients with asymptomatic carotid artery stenosis who are at high risk of stroke are required. It has been suggested that proton magnetic resonance spectroscopy (MRS) may allow the identification of ongoing ischaemia in this patient group by the detection of a potentially reversible reduction of N-acetyl aspartate (NAA), a presumed marker of neuronal integrity, and the presence of lactate, a marker of anaerobic metabolism. Previous studies have reported metabolite ratios rather than absolute concentrations. This study was performed to determine if NAA was reduced ipsilateral to carotid stenosis or occlusion, and if its concentration was related to carbon dioxide reactivity, a marker of cerebrovascular reserve. METHODS: Twenty one patients with unilateral carotid stenosis (>70%) or occlusion were studied. Single voxel proton MRS was performed in the ipsilateral and contralateral hemispheres, with the voxel positioned in the arterial borderzone region between the middle and anterior cerebral artery territories. Absolute quantification of metabolite concentrations was performed. Cerebrovascular reactivity to 6% carbon dioxide was determined in both middle cerebral artery territories using transcranial Doppler ultrasonography. RESULTS: Mean (SD) cerebrovascular reactivity was significantly lower in the stenosed compared with the contralateral hemisphere (13.3 (7.7) v 19.2 (8.2)%/kPa, p=0.002). There were no significant differences in the absolute concentrations of NAA, choline, or creatine between the ipsilateral and contralateral hemispheres (for example, NAA 10.1 (1.1) v 10.5 (1.1) mmol/l, p=0.1). No lactate peak was seen in any spectra. For each metabolite measured, there was no correlation between the absolute concentration and cerebrovascular reactivity for either hemisphere. CONCLUSIONS: In patients with carotid stenosis and occlusion we found no evidence that chronic hypoperfusion is associated with a reduction in NAA or the presence of lactate. Magnetic resonance spectroscopy is unlikely to help in the selection of patients with asymptomatic carotid stenosis for endarterectomy.

Aged↗
PubMed2001

Longitudinal left ventricular function in a population of healthy adults: a tissue Doppler imaging study.

BACKGROUND: Longitudinal left ventricular function is a major determinant of global ventricular function and is probably more sensitive than radial function in the detection of disease. Tissue Doppler imaging of the mitral annulus allows the study of longitudinal left ventricular function. METHODS: Forty-five healthy volunteers divided into two groups (younger and older than 45 years) were studied with pulsed tissue Doppler imaging of the 4 sides of the mitral annulus (septal, lateral, inferior, anterior) in 4 and 2 apical chamber views. In each wave (systolic-s, rapid filling-e, atrial contraction-a) we analyzed velocities, time intervals and velocity-time integrals, as well as heterogeneity and asynchrony indexes. Data were compared between the different sides in each group, between groups and with conventional Doppler data. RESULTS: In contrast to the septal side, the lateral side of the annulus shows higher velocities and velocity-time integrals of the s and e waves, with non-significantly shorter isovolumic relaxation time and shorter time to peak e. There is functional agreement between the lateral and inferior sides versus the septal and anterior sides of the annulus. Most systolic parameters remained unchanged with aging; however, aging was associated with decreased e velocity, increased a velocity and inverted e/a ratio. The relation between s and fractional shortening also did not change with aging. Annular isovolumic contraction time and isovolumic relaxation time were shorter than their respective global time intervals. CONCLUSIONS: This study shows that there are physiological differences in velocities, time intervals and velocity-time integrals between the 4 sides of the mitral annulus, reflecting physiological heterogeneity and asynchrony, and that some of these parameters are age dependent. These data also contribute to a better understanding of longitudinal left ventricular function and may be useful in future studies as reference values in control groups.

Adult↗
PubMed2000

The barrel field of the adult mouse SmI cortex as revealed by NADPH-diaphorase histochemistry.

The main goal of the present work was to investigate the pattern of NADPH-diaphorase activity in the somatosensory cortex of the adult mouse. Our results show that this enzyme, which is responsible for the production of the neuronal messenger nitric oxide, is abundant within the neuropil of SmI cortex, revealing the complete pattern of barrel fields. A previous study, however, had reported that NADPH-diaphorase reactivity within the barrels was transient, disappearing after the second postnatal week. We hypothesize that the massive occurrence of NADPH-diaphorase in the barrel fields of the adult mouse brain is related to the potential for plastic changes in the somatosensory cortex that is maintained throughout maturity.

Aging↗
PubMed2000

Target selected insertional mutagenesis on chromosome IV of Arabidopsis using the En-I transposon system.

Reverse genetics using insertional mutagenesis is an efficient experimental strategy for assessing gene functions. The maize Enhancer-Inhibitor (En-I) transposable element system was used to develop an effective reverse genetics strategy in Arabidopsis based on transposons. To generate insertion mutations in a specific chromosomal region we developed a strategy for local transposition mutagenesis. A small population of 960 plants, containing independent I transpositions was used to study local mutagenesis on chromosome IV of Arabidopsis. A total of 15 genes, located on chromosome IV, were tested for I insertions and included genes identified by the European ESSA I sequencing programme. These genes were of particular interest since homologies to other genes and gene families were identified, but their exact functions were unknown. Somatic insertions were identified for all genes tested in a few specific plants. Analysis of these progeny plants over several generations revealed that the ability to generate somatic insertions in the target gene were heritable. These genotypes that show high levels of somatic insertions can be used to identify germinal insertions in the progeny.

Arabidopsis↗
PubMed2000

Cortical and subcortical influences on the nucleus of the optic tract of the opossum.

In the present work we propose a new phylogenetic hypothesis for the role played by cortical and subcortical afferents to the nucleus of the optical tract, the main visual relay station of the horizontal optokinetic reflex in mammals. The hypothesis is supported by anatomical and physiological data obtained in the South American opossum (Didelphis aurita) using the following experimental approaches: (i) single-unit recordings in the nucleus of the optic tract and simultaneous electrical stimulation of the contralateral nucleus of the optic tract; (ii) single-unit recordings in the nucleus of the optic tract and simultaneous electrical stimulation of the ipsilateral striate cortex; (iii) injection of cholera toxin subunit B into the striate cortex and subsequent immunohistochemical reaction to reveal the presence of the marker in the thalamus and mesencephalon; and (iv) single-unit recordings in the nucleus of the optic tract both before and after ablation of the ipsilateral visual cortex. The main results are: (i) there is a strong inhibitory reciprocal effect upon the nucleus of the optic tract following stimulation of its contralateral counterpart; (ii) electrophysiological and anatomical data imply that the visual cortex does not project directly to the nucleus of the optic tract. Rather, cortical terminals seem to target the nearby anterior and posterior pretectal nuclei and orthodromic latencies in the nucleus of the optic tract following stimulation of the visual cortex were twice as large as in the superior colicullus; and (iii) ablation of the entire visual cortex did not have any effect upon binocularity of cells in the nucleus of the optic tract. These results strengthen the model proposed here for the role of the interactions between the nuclei of the optic tract under optokinetic stimulation. The hypothesis in the present work is that the cortical influences upon the nucleus of the optical tract, in addition to the subcortical ones, appeared only recently in phylogenesis. In more primitive mammals, such as the opossum, subcortical interactions are thought to play a relatively important role. With the emergence of retinal specializations, such as the fovea, one might suppose that there followed the appearance of new ocular movements, such as the smooth pursuit and certain types of saccades, that came to join the pre-existent optokinetic reflex.

Animals↗
PubMed2000

A transgenic perspective on plant functional genomics.

Transgenic crops are very much in the news due to the increasing public debate on their acceptance. In the scientific community though, transgenic plants are proving to be powerful tools to study various aspects of plant sciences. The emerging scientific revolution sparked by genomics based technologies is producing enormous amounts of DNA sequence information that, together with plant transformation methodology, is opening up new experimental opportunities for functional genomics analysis. An overview is provided here on the use of transgenic technology for the functional analysis of plant genes in model plants and a link made to their utilization in transgenic crops. In transgenic plants, insertional mutagenesis using heterologous maize transposons or Agrobacterium mediated T-DNA insertions, have been valuable tools for the identification and isolation of genes that display a mutant phenotype. To discover functions of genes that do not display phenotypes when mutated, insertion sequences have been engineered to monitor or change the expression pattern of adjacent genes. These gene detector insertions can detect adjacent promoters, enhancers or gene exons and precisely reflect the expression pattern of the tagged gene. Activation tag insertions can mis-express the adjacent gene and confer dominant phenotypes that help bridge the phenotype gap. Employment of various forms of gene silencing technology broadens the scope of recovering knockout phenotypes for genes with redundant function. All these transgenic strategies describing gene-phenotype relationships can be addressed by high throughput reverse genetics methods that will help provide functions to the genes discovered by genome sequencing. The gene functions discovered by insertional mutagenesis and silencing strategies along with expression pattern analysis will provide an integrated functional genomics perspective and offer unique applications in transgenic crops.

Crops, Agricultural↗
PubMed2000

The role of HLA antigens in the development of paracoccidioidomycosis.

BACKGROUND: Paracoccidioidomycosis is a systemic granulomatous disease that involves primarily the lungs and may disseminate to other organs and systems. It is caused by Paracoccidioides brasiliensis, a fungus that exhibits reversible thermal dimorphism and whose natural habitat is presently unknown. There are two main clinical forms: the acute (subacute) juvenile form and the chronic adult form. The former runs a more rapid course and is more severe than the latter. This mycosis is found throughout Latin America. Brazil accounts for 80% of reported cases. Presumably P. brasiliensis thrives in humid and hot places, especially near forests or farms. The infection is endemic in certain areas, especially in Brazil, Colombia and Venezuela, where nearly 100% of the population show cutaneous paracoccidioidina positive skin tests, indicating previous contact with the fungus, although a small percentage show clinical manifestations of the disease. METHODS: We compared the expression of HLA class I antigens in a healthy group (control) and in a group of patients with paracoccidioidomycosis (chronic adult form) using the Terasaki lymphocytotoxicity test modified by Amos for HLA antigen analysis. AIMS: To discover indications of whether or not individual susceptibility to P. brasiliensis might depend on some specific immunological defect. RESULTS: There is no evidence of association between a specific HLA antigen and paracoccidioidomycosis in the subjects studied. Further investigations are recommended.

Adult↗
PubMed2000

A model of the health and economic impact of posttransfusion hepatitis C: application to cost-effectiveness analysis of further expansion of HCV screening protocols.

BACKGROUND: Cost-effectiveness analyses are needed to decide the value of further expansion of the screening protocols for HCV in blood donors. However, such analyses are hampered by imperfect knowledge of the health and economic repercussions of posttransfusion hepatitis C (PTHC). STUDY DESIGN AND METHODS: A Monte Carlo simulation of a Markov model representing the outcomes of patients transfused with HCV-infective blood was used to estimate the health and economic impact of PTHC and to calculate the cost-effectiveness ratio of various HCV screening methods. RESULTS: Median survival for hypothetical patients with PTHC and for controls without hepatitis was 11.25 and 11.75 years, respectively. Overall, 12.3 percent of patients receiving HCV-infective blood will develop chronic hepatitis, 9.3 percent will progress to liver failure, and 9. 25 percent will eventually die of liver disease after a median time of 20.75 years (range, 6-70). Ninety-one percent of the infected blood recipients had no reduction in life expectancy due to PTHC, and the average loss per patient was 0.754 years. The present value of the lifetime health costs incurred by patients with PTHC is $6330 per case. HCV antibody testing increases the patients' life expectancy by 20.4 hours per blood collection tested, and it results in net savings by decreasing the number of patients that will require treatment for liver disease in the future. Adding HCV NAT increases the patients' life expectancy by 0.08 hours per blood collection tested, at a cost-effectiveness ratio of $1,829,611 per QALY gained. CONCLUSION: PTHC has low health benefits because of the advanced age of many blood recipients. Testing donors for HCV antibodies results in net savings for the health care system, despite low health benefits. Adding HCV NAT would produce little additional gain at a very high cost.

Blood Transfusion↗
PubMed2000

Sensitization to individual allergens as risk factors for lower FEV1 in young adults. European Community Respiratory Health Survey.

BACKGROUND: Atopy may impair ventilatory function, but results are controversial. We assess the association between individual reactivity to allergens and the level of baseline maximal one-second forced expiratory volume (FEV1), by smoking and respiratory symptoms. METHODS: The 1472 participants (response 44.5%) of the five Spanish areas of the European Community Respiratory Health Survey (ECRHS) who performed respiratory function tests, skin prick tests and/or specific IgE against common aeroallergens (e.g. mites, pets, mould, pollens) are included. Bronchial hyperreactivity (BHR) was measured with a methacholine challenge. RESULTS: After adjusting for BHR and smoking, in addition to the other allergens, skin reactivity to Alternaria (-208 ml; 95% CI :-451, 35) and IgE antibodies against cat (-124 ml; 95% CI:-269, 21) and Timothy grass (-115 ml, 95% CI:-190, -40) were associated with a decrease in FEV1 in females. Among males, skin reactivity to olive showed the strongest association (-111 ml; 95% CI: -261, 38). The associations were stronger in females. Smoking modifies the association for Alternaria and cat (P for interaction < 0.05). While cat is associated with a decrease in FEV1 in current smokers (-190 ml), Alternaria (-336 ml) was associated among never smokers. The exclusion of subjects with asthma symptoms, or adjustment for respiratory symptoms, led to similar results. CONCLUSIONS: We conclude that immunoresponse to individual allergens (particularly outdoor) is associated with the level of FEV1, and this association occurred independently of asthma, and in smokers and non-smokers, which may be of interest in natural history of chronic obstructive pulmonary disease (COPD).

Adult↗