RESUMEN
OBJECTIVES: The present study aimed to develop strategies for genotyping DO*HY (Dombrock system) and DI*A/DI*B (Diego system) alleles and to evaluate the impact of genomic and self-declared ancestry on rare donor screening in admixed populations. BACKGROUND: The antigens Hy and Dib demonstrate clinical importance. The lack of antisera for the serological evaluation of these antigens makes it necessary to develop molecular methods. In addition, considering that some rare red blood cell phenotypes present differences in frequency between ethnic groups, it is important to assess the applicability of self-declared ancestry in the search for rare donors in admixed populations. METHODS: DO*HY and DI*A/DI*B genotyping based on real-time polymerase chain reaction (PCR) was standardised. A total of 457 blood donors clustered by self-defined skin colour/race categories were genotyped. Furthermore, individual genomic ancestry was used in the analyses. RESULTS: The assays developed are reproducible and provide satisfactory results even at low concentrations of DNA, which make them useful in situations where the DNA is scarce, such as dried blood spots on filter paper, or when screening for pooled samples. No significant difference was observed in the frequencies of the DI*A, DI*B and DO*HY, comparing the self-declared White (branco) donors with those who are Black (preto) and Brown (pardo). CONCLUSION: Real-time PCR, especially using pooled samples, is a promising strategy to screen rare blood donors. Although both self-reported race/colour and some blood group phenotypes are associated with ancestry, the results point to a greater complexity in the application of self-declared race/colour in the screening of rare donors in admixed populations.
Asunto(s)
Donantes de Sangre , Antígenos de Grupos Sanguíneos/genética , Tipificación y Pruebas Cruzadas Sanguíneas , Selección de Donante , Etnicidad/genética , Técnicas de Genotipaje , Autoinforme , Femenino , Humanos , MasculinoRESUMEN
Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies.
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Presión Arterial , Hipertensión Pulmonar/complicaciones , Hipertrofia Ventricular Derecha/etiología , Arteria Pulmonar/fisiopatología , Disfunción Ventricular Derecha/etiología , Función Ventricular Derecha , Remodelación Ventricular , Adaptación Psicológica , Animales , Señalización del Calcio , Constricción , Modelos Animales de Enfermedad , Fibrosis , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/metabolismo , Hipertrofia Ventricular Derecha/patología , Hipertrofia Ventricular Derecha/fisiopatología , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Arteria Pulmonar/cirugía , Ratas Wistar , Factores de Tiempo , Disfunción Ventricular Derecha/metabolismo , Disfunción Ventricular Derecha/patología , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular IzquierdaRESUMEN
Previous environmental biomonitoring studies indicated higher environmental lead (Pb) pollution levels at the districts of Aveiro and Leiria (Portugal). In evaluating the risk for human health, which is associated with contaminated soils after oral uptake, total soil concentrations have generally been held against criteria established from toxicological studies based upon the assumption that the uptake of the contaminant is similar in the toxicological studies and from the soils assessed. This assumption is not always valid, as most toxicological studies are carried out with soluble forms of the contaminants, whereas many soil contaminants are or become embedded in the soil matrix and thus exhibit limited availability. This study intends to estimate the soluble fraction of Pb in the soils from central Portugal, and to assess the bioaccessibility of Pb and, hence, infer exposure and risk for human health. Yet, as the physical-chemical properties of the soil exert some control over the solubility of Pb in the surface environment, the relation between such soil properties and the estimated soluble and/or bioaccessible fractions of Pb is also investigated. Other objective, with a more practical nature, was to give some contribution to find a suitable in vitro mimetic of the gastrointestinal tract environment. The results indicate relatively low total metal concentrations in the soils, even if differences between regions were observed. The Aveiro district has the higher total Pb concentration and the metal is in more soluble forms, that is, geoavailable. Soils with higher concentrations of soluble Pb show higher estimates of bioaccessible Pb. Soil pH seems to influence human bioaccessibility of Pb.
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Plomo/análisis , Contaminantes del Suelo/análisis , Suelo/química , Humanos , Concentración de Iones de Hidrógeno , Plomo/química , Modelos Biológicos , Portugal , Medición de Riesgo , Contaminantes del Suelo/química , SolubilidadRESUMEN
Lycotoxin I and Lycotoxin II are natural anti-microbial peptides that were identified in the venom of the Wolf Spider Lycosa carolinensis. These peptides were found to be potent growth inhibitors for bacteria (Escherichia coli) and yeast (Candida glabrata) at micromolar concentrations. Recently, shortened analogues of LycoI and LycoII have been reported to have decreased haemolytic effects. A shorter Lyco-I analogue studied, LycoI 1-15 (H-IWLTALKFLGKHAAK-NH2), was active only above 10 microM, but was also the least haemolytic. On the basis of these findings, we became interested in obtaining a deeper insight into the membrane activity of LycoI 1-15, as this peptide may represent the first major step for the future development of selective, i.e. non-haemolytic, Lycotoxin-based antibiotics. The interaction of this peptide with liposomes of different composition was studied by microcalorimetry [differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC)] and CD. The results obtained from the calorimetric and spectroscopic techniques were jointly discussed in an attempt to further understand the interaction of this peptide with model membranes.
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Péptidos Catiónicos Antimicrobianos/química , Venenos de Araña/química , Secuencia de Aminoácidos , Péptidos Catiónicos Antimicrobianos/síntesis química , Rastreo Diferencial de Calorimetría , Dicroismo Circular , Liposomas/química , Datos de Secuencia Molecular , Fosfolípidos/química , Venenos de Araña/síntesis química , Termodinámica , Factores de TiempoRESUMEN
UNLABELLED: Linezolid, an oxazolidinone-class antimicrobial agent, is a new drug; its use has frequently been questioned due to its high price. However, recent trials have demonstrated that the use of linezolid in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (VAP-MRSA) may be justified due to its improved efficacy compared to vancomycin. Price and cost have different magnitudes, and clinical efficacy should always be considered in the decision-making process. Our objective was to determine whether linezolid treatment was more cost-effective than vancomycin for treating VAP-MRSA. METHODOLOGY: Elaboration of an economic model from a metanalysis of previous clinical trials comparing both drugs, through a cost-effectiveness analysis. Costs of the treatments were calculated using Brazilian parameters and were compared to the results obtained in the metanalysis. In order to compare the results with real life conditions, costs were calculated for both name brand and for generic vancomycin. RESULTS: The cost (May/2004) per unit (vial, ampoule or bag) was R$ 47.73 for the name-brand vancomycin, R$ 14.45 for generic vancomycin and R$ 214.04 for linezolid. Linezolid's efficacy in VAP-MRSA according to the metanalysis was 62.2% and vancomycin's efficacy was 21.2%. The total cost per cured patient was R$ 13,231.65 for the name-brand vancomycin, R$ 11,277.59 for generic vancomycin and R$ 7,764.72 for linezolid. CONCLUSION: Despite the higher price per unit, linezolid was more cost-effective than vancomycin.
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Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Oxazolidinonas/uso terapéutico , Neumonía Estafilocócica/tratamiento farmacológico , Vancomicina/uso terapéutico , Acetamidas/economía , Antibacterianos/economía , Análisis Costo-Beneficio , Infección Hospitalaria/economía , Infección Hospitalaria/etiología , Costos de los Medicamentos , Humanos , Linezolid , Resistencia a la Meticilina/efectos de los fármacos , Oxazolidinonas/economía , Neumonía Estafilocócica/microbiología , Respiración Artificial/efectos adversos , Staphylococcus aureus/efectos de los fármacos , Vancomicina/economíaRESUMEN
Linezolid, an oxazolidinone-class antimicrobial agent, is a new drug; its use has frequently been questioned due to its high price. However, recent trials have demonstrated that the use of linezolid in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (VAP-MRSA) may be justified due to its improved efficacy compared to vancomycin. Price and cost have different magnitudes, and clinical efficacy should always be considered in the decision-making process. Our objective was to determine whether linezolid treatment was more cost-effective than vancomycin for treating VAP-MRSA. METHODOLOGY: Elaboration of an economic model from a metanalysis of previous clinical trials comparing both drugs, through a cost-effectiveness analysis. Costs of the treatments were calculated using Brazilian parameters and were compared to the results obtained in the metanalysis. In order to compare the results with real life conditions, costs were calculated for both name brand and for generic vancomycin. RESULTS: The cost (May/2004) per unit (vial, ampoule or bag) was R$ 47.73 for the name-brand vancomycin, R$ 14.45 for generic vancomycin and R$ 214.04 for linezolid. Linezolid's efficacy in VAP-MRSA according to the metanalysis was 62.2 percent and vancomycin's efficacy was 21.2 percent. The total cost per cured patient was R$ 13,231.65 for the name-brand vancomycin, R$ 11,277.59 for generic vancomycin and R$ 7,764.72 for linezolid. CONCLUSION: Despite the higher price per unit, linezolid was more cost-effective than vancomycin.
Asunto(s)
Humanos , Acetamidas/uso terapéutico , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Oxazolidinonas/uso terapéutico , Neumonía Estafilocócica/tratamiento farmacológico , Vancomicina/uso terapéutico , Acetamidas/economía , Antibacterianos/economía , Análisis Costo-Beneficio , Infección Hospitalaria/economía , Infección Hospitalaria/etiología , Costos de los Medicamentos , Resistencia a la Meticilina/efectos de los fármacos , Oxazolidinonas/economía , Neumonía Estafilocócica/economía , Neumonía Estafilocócica/etiología , Respiración Artificial/efectos adversos , Staphylococcus aureus , Vancomicina/economíaRESUMEN
INTRODUCTION: Adjuvant antibiotic therapy for acute abdominal conditions is widely used. Its timing, duration, dose and spectrum, however, are not homogeneous amongst surgeons and prolonged courses are often used despite the unproven benefits of this practice. OBJECTIVE: To evaluate use and compare duration of antibiotic treatments in acute abdominal surgery. METHODS: Retrospective cohort study. The medical records of 290 patients who underwent operations for acute abdomen from July 1998 to July 1999 in a teaching hospital were reviewed. The pattern of antibiotic use and rates of postoperative complications were evaluated, along with surgical diagnosis, degree of contamination/infection, and incidence of postoperative complications. The patients were stratified according to the degree of contamination/infection noted during the operation. The study population was divided in two groups according to the duration of antibiotic use (cut-off point at the median antibiotic use in days, for each group of contamination/infection degree), and outcomes were compared. RESULTS: The degree of contamination/infection was significantly associated with an increased risk of wound infection, intra-abdominal abscess, postoperative infective complications and overall postoperative complications (p < 0.001). A long course of antibiotics was not associated with lower infective complication rates. CONCLUSIONS: Shorter courses of antibiotic therapy based on the degree of contamination/infection seem to be safe. A prospective study should confirm this hypothesis.
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Abdomen Agudo/cirugía , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Infecciones Bacterianas/prevención & control , Complicaciones Posoperatorias , Adulto , Anciano , Profilaxis Antibiótica , Apendicitis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
It i an accepted fact that, in many countries, pharmacies are the predominat source of medical advice over-the-counter drugs, and supplies of "prescription-only" drugs for sale without a prescription. To assess the activities conducted by pharmacists or pharmacy counter assistants in response to a common health problem, a cross-sectional study was done at 114 pharmacies in Porto Alegre, Brazil. A fictitious case-history of cough was used by trained personnel entering the pharmacy and the subsequent activities by the pharmacist or pharmacy counter assistant were analyzed. Some kind of medication was provided in 101 (88.5 percent)of the pharmacies. Pharmacists gave medication in 80 percent of pharmacies, and pharmacy assistants in 95.5 percent (p<0.03). The class of medication most frequently dispensed was the expectorants (97 times, 92.4 percent), however, systemic antibiotics were provided in 11 pharmacies (10.5 percent). Of note, the pharmacists provided antibiotics more frequently than did pharmacy assistants (p=0.016). We conclude that pharmacy advice and symptomatic medical care (expectorants) are very common and that pharmacy assistants are more likely than pharmacists to provide medication. Of concern, when pharmacists were the drug dispensers of antibiotics which should be provided by prescription only, drugs were provided without proper diagnosis, and often incorrect dosages. This reflects a pontentially dangerous practice in need of careful evaluation, education and supervision.
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Antibacterianos , Antitusígenos/uso terapéutico , Tos/tratamiento farmacológico , Expectorantes/uso terapéutico , Medicamentos sin Prescripción/administración & dosificación , Medicamentos sin Prescripción/efectos adversos , Prescripciones de Medicamentos , Autoadministración , Monitoreo de Drogas/normas , Farmacias/normasRESUMEN
Vários estudos têm demonstrado a existência de achados oftálmicos na Sídrome de Imunodeficiência em pacientes adultos. Entretanto, em pacientes pediátricos, näo existe ainda um padräo oftálmico bem definido para esta patologia. Nesta série, estudamos 8 pacientes HIV positivos. Foi realizado exame oftálmico completo em cada paciente. Um paciente apresentava microftalmia e leucocoria decorrente de sua doença de base (hemofilia). Um paciente apresentava coriorretinite toxoplásmica. Näo foi estabelecido um padräo oftálmico neste grupo