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Biomedical subjects

M Silva

Publications and source records attributed to M Silva.

At least 19 recordsLinked to original sources
PubMed2006

Epidemiological survey of central nervous system germ cell tumors in Canadian children.

OBJECTIVES: To determine the incidence and characteristics of pediatric patients with central nervous system (CNS) germ cell tumors (GCT) in Canada. METHOD: A national retrospective review of hospital charts was done on all patients with CNS GCT diagnosed between 1990 and 2004. Patients had to be under age 18 years at the time of diagnosis of a CNS germ cell tumor and be a resident of Canada. Information extracted included age and year of diagnosis, pathological diagnosis, location of tumor, evidence of disseminated disease at time of diagnosis and biological markers. RESULTS: One hundred and twenty-one cases were identified (83 germinoma; 38 non-germinoma germ cell tumor). The mean annual incidence of CNS GCT was 1.06 per million children (0.7 per million for germinoma; 0.3 per million for NGGCT). Though yearly incidences varied, there was no clear trend to increased incidence. Male predominance was noted (2.4:1 for germinoma; 11:1 for NGGCT). The primary locations were the pineal and suprasellar regions. At the time of diagnosis, disseminated disease was not uncommon (22% germinoma; 32% NGGCT). Beta human gonadotrophin was elevated in the serum, cerebrospinal fluid (CSF) or both in 7% of patients with germinoma and 36% of patients with NGGCT. Elevation of alpha-fetoprotein in serum, CSF or both was seen in 34% of patients with NGGCT. CONCLUSION: The incidence of CNS germ cell tumors in Canadian children is similar to that observed in other Western countries.

Adolescent↗
PubMed2006

Disease progression in recently diagnosed patients with inherited marrow failure syndromes: a Canadian Inherited Marrow Failure Registry (CIMFR) report.

BACKGROUND: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. METHODS: The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. RESULTS: 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. CONCLUSIONS: IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.

Adolescent↗
PubMed2006

[Home ventilatory assistance in Chilean children: 12 years' experience].

OBJECTIVE: Home ventilatory support systems are a treatment option for patients with severe chronic respiratory failure. The objective of the present study was to characterize the children admitted to a home ventilatory assistance program. PATIENTS AND METHOD: The home ventilation program was created by our hospital to coordinate professional and technological support for chronic ventilator-dependent children. We revised and updated information on patient characteristics, type of assisted ventilation, respiratory morbidity, and equipment failures between 1993 and 2004. RESULTS: Follow-up of 35 children (18 male) was carried out by our hospital staff. Median age upon admission to the program was 12 months (range, 5 months to 14 years). Median length of time in the program was 21 months and we were able to wean 40% of patients from ventilators. Six patients died. The main indications for assisted ventilation were neuromuscular disease (12 cases), airway abnormality (11 cases), cardiopulmonary disease (7 cases), and hypoventilation syndrome (5 cases). The types of assisted ventilation used were continuous positive airway pressure (in 17 cases), bilevel positive pressure (in 8 cases), and synchronized intermittent mandatory ventilation (in 10 cases). Invasive ventilation via a tracheostomy was used in 26 cases. The use of noninvasive ventilation increased in the last 4 years. Respiratory morbidity (pneumonia and bacterial tracheitis) was the most frequent cause of hospitalization and the annual rate of such episodes was 1.6 per child. The annual rate of hospitalization due to equipment failures was 0.1 per child. CONCLUSION: The program provides safe and necessary home ventilatory assistance for children with severe chronic respiratory failure. The professional support that home hospitalization offers had a positive effect on outcome in these children. It is important to take our experience into account in creating a Chilean national home ventilatory assistance program.

Adolescent↗
PubMed2006

Lymphocyte volume and conductivity indices of the haematology analyser Coulter GEN.S in lymphoproliferative disorders and viral diseases.

The haematology analyser Coulter GEN.S gives a set of data -'positional parameters'- defining white blood cell (WBC) populations by mean of index values (mean and standard deviation of volume, conductivity and scatter, used to identify the WBC populations). The volume and conductivity parameters related to the lymphocytes were analysed at diagnosis in patients suffering from chronic B-lymphocytic leukaemia (B-CLL), other non-CLL lymphoproliferative disorders (OLPD) and viral diseases. The standard deviation of volume index (SDVI) is significantly higher in the three groups, whereas the mean volume index (MVI) is significantly lower in B-CLL, and increased in OLPD and viral diseases. These two groups could be distinguished by their mean conductivity index (MCI), which is significantly lower in viral disease group. Cut-offs were calculated for each parameter by the mean of Receiver Operating Characteristic (ROC) analysis. The study of the detection performances showed that the combination of lymphocyte count with SDVI, MVI and MCI could be used with a good sensitivity and specificity to discriminate between the most frequent lymphocyte pathologies, even in patients with normal lymphocyte count.

Electric Conductivity↗
PubMed2006

Factors influencing recent dental graduates' location and sector of employment in Victoria.

BACKGROUND: Recruitment and retention of dentists in the public sector and rural areas in Victoria has become increasingly difficult in recent years. There are little available data on the factors that influence the sector and location of practice of new dental graduates. The objective of this study was to investigate the factors considered by new graduates in determining the location and sector of employment after graduation, and influencing any early changes in career path. METHODS: Questionnaires were sent to dentists who Mgraduated from The Univrersity of Melbourne from graduated from The University of Melbourne from 2000-2003 who were currently practising in Victoria. There were 154 subjects to whom questionnaires were sent and 109 useable questionnaires were returned, a response rate of 74 per cent. RESULTS: Upon graduation, 53 per cent of the new graduates chose to work in the private sector only, compared to 15 per cent in public sector only and 33 per cent in both. At present, 71 per cent work in the private sector only, 17 per cent in the public sector only and 12 per cent in both. The most important factors for choosing to work in the private sector were receiving broad range of clinical experience, opportunities to familiarize with practice management and providing a continuity of care. The principal factors for practising in the public sector were clinical mentoring and advice, consolidating clinical skills and work environment. Initially, 48 per cent of the sample chose to work in metropolitan areas only, 39 per cent in rural areas only and 13 per cent in both. Factors that influenced the decision to work in rural areas were the broad range of clinical experience and remuneration, while the main factors for choosing to work in metropolitan areas were lifestyle and proximity to family and friends. CONCLUSIONS: This study found that a large proportion of new dental graduates initially chose to work in the public sector and rural areas on graduation primarily as a means of consolidating their clinical skills. However, retention of dentists in both these areas appears to be a problem, with less than 10 per cent of 2000-2001 graduates still than 10 per cent of 2000-2001 graduates still working in the public sector and only 20 per cent of 2000-2001 graduates still working in rural areas.

Attitude of Health Personnel↗
PubMed2006

Historical and current perspectives of neuroactive compounds derived from Latin America.

Plants and invertebrates in Latin America have contributed to a great extent in the use, discovery and development of novel neuroactive tools. Significantly, these neuroactive drugs have proven to be particularly important for our current understanding of the physiology and pharmacology of the nervous system. In addition, these discoveries have helped to build the modern and successful pharmacological business that we know today. For example, curare helped to introduce the use of muscle relaxing agents into modern surgical techniques. The discovery of cocaine from the leaves of Peruvian coca plants was instrumental in the discovery of local anesthetics. The search and discovery for useful neuroactive compounds derived from Latin America has also been ongoing in other areas and new applications for quinine, capsaicin and epibatidine were recently described. Besides these organic compounds, several peptides produced by spiders and other invertebrates to hunt their prey also induce effects in channels and membrane receptors at very low concentrations, indicating their high potency and selectivity. It is likely that new pharmaceutics will be developed from these molecules. The interest to renew the search for new compounds is timely, since largely unexplored lands, such as the Amazon and Patagonia, hold an important number of plants and animals that contain exciting new active compounds. With the introduction of new techniques to isolate, identify and characterize the molecular targets and actions of chemical entities, together with the need for more potent and selective compounds to treat neurological conditions, it is necessary to broaden the current exploratory effort in order to find more beneficial uses.

Animals↗
PubMed2006

[Microbiological isolates in patients with febrile neutropenia and hematological neoplasias].

We studied the frequency of culture isolation, type of microorganism isolated and local pattern of resistance in 309 adult febrile neutropenic inpatients with hematological neoplasm, who were hospitalized between January 1998 and December 2003, in Caracas University Hospital (Hospital Universitario de Caracas), in Venezuela. There were 576 febrile neutropenic episodes. Organisms were isolated in 41% of 940 cultures. The most common organisms involved were gram-negative bacilli (48%), followed by gram-positive cocci (35.1%), fungal (11.5%) and other agents (5.4%). Coagulase-negative staphylococci (22.4%) and Escherichia coli (13.4%) were the most isolated; 58.5% of 479 agents isolated had an antibiogram; 62.2% of coagulase-negative staphylococci and 23.1% coagulase-positive staphylococci were oxacillin-resistant. We did not find any vancomycin-resistant organisms. The gram-negative antimicrobial sensitivity for imipenem was 96.2%, cefepime 81%, and ceftazidime 57.5%. Tazobactam-piperacillin and sulbactam-cefoperazone were tested in 26% of antibiograms and had activity of 57.1% and 77.5%, respectively. Fungi were not characterized. Betalactamases producing gram-negative bacilli were found. In general, micro-biological identification and local vigilance of antibacterial resistance pattern must be done routinely in these patients, in order to improve empiric therapy guidelines.

Adult↗
PubMed2005

Detection of hepatitis C virus RNA by in situ hybridization in paraformaldehyde fixed biopsies.

Fourteen hepatitis C virus (HCV) chronically infected patients were submitted to routine liver biopsy for histological evaluation. Liver samples were assayed to HCV-RNA by in situ hybridization, using digoxigenin labeled probe. HCV genotypes were found to be predominantly type 1 (71.4%), followed by genotype 3 (21.4%), and genotype 2 (7.2%). Alanine-aminotransferase levels were raised in 10 patients. The histopathological scores were minimal (21.4%), mild (57.2%), and moderate (21.4%). Viral RNA was detected in liver cells from nine patients (64.3%). ISH method provides localization and poor confirmation of HCV RNA in the liver tissue of HCV chronic patients.

Adult↗
PubMed2005

Antifungal susceptibility and pathogenic potential of environmental isolated filamentous fungi compared with colonizing agents in immunocompromised patients.

Infection is a major cause of morbidity and mortality in bone marrow transplant recipients and in patients with hematological malignancies. The source of infection is almost always endogenous flora or the hospital environment. The present study evaluated bone marrow transplant recipients and patients with hematological malignancies colonized and/or infected with filamentous fungi. During 1 year, environmental air samples were also taken from the bone marrow transplant unit by a modification of gravity air-setting plate (GASP) methodology. Fusarium spp. were the most prevalent genus in the fall and Cladosporium spp. in the winter. Clinically isolated strains grew better at 37 degrees C than environmental strains. According to NCCLS M-38P methods, environmental Aspergillus strains showed higher MICs to miconazol and itraconazol, and clinical Fusarium strains were less susceptible to fluconazole.

Air Microbiology↗
PubMed2005

Ribosomal DNA heterochromatin in plants.

The aim of this review is to integrate earlier results and recent findings to present the current state-of-the-art vision concerning the dynamic behavior of the ribosomal DNA (rDNA) fraction in plants. The global organization and behavioral features of rDNA make it a most useful system to analyse the relationship between chromatin topology and gene expression patterns. Correlations between several heterochromatin fractions and rDNA arrays demonstrate the heterochromatic nature of the rDNA and reveal the importance of the genomic environment and of developmental controls in modulating its dynamics.

DNA, Plant↗
PubMed2005

Screening of Leishmania APRT enzyme inhibitors.

Adenine phosphoribosyltransferase (APRT) enzyme from Leishmania tarentolae has been proposed as a target for the rational search of new leishmanicidal drugs. In this paper, we describe the evaluation of the inhibitory activity on L. tarentolae APRT enzyme of 46 crude extracts of Meliaceae and Rutaceae plants, besides three furoquinolone alkaloids. The results showed that 21 extracts were able to decrease the APRT enzymatic activity (IA% > or = 50). The methanolic extracts from roots and leaves of Cedrela fissilis and from fruits, branches and leaves of Cipadessa fruticosa have showed strong activities. Therefore, these species could be a promising source of lead compounds for the rational design of new leishmanicidal drugs. The phytochemical investigation of an active fraction from Almeidea rubra afforded the alkaloids isodutaduprine, isoskimmianine and isokokusagine, which showed low to moderate activity on APRT.

Adenine Phosphoribosyltransferase↗
PubMed2004

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes.

Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 microM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.

Animals↗
PubMed2004

Crystal structure of adenine phosphoribosyltransferase from Leishmania tarentolae: potential implications for APRT catalytic mechanism.

The three-dimensional structure of Leishmania tarentolae adenine phosphoribosyltransferase (APRT) in complex with adenosine-5-monophosphate (AMP) and a phosphate ion has been solved. Refinement against X-ray diffraction data extending to 2.2-A resolution led to a final crystallographic R factor of 18.3%. Structural comparisons amongst this APRT enzyme and other 'type I' PRTases whose structures have been determined reveal several important features of the PRTases catalytic mechanism. Based on structural superpositions and molecular interaction potential calculations, it was possible to suggest that the PRPP is the first substrate to bind, while the AMP is the last product to leave the active site, in accordance to recent kinetic studies performed with the Leishmania donovani APRT.

Adenine Phosphoribosyltransferase↗
PubMed2004

Fetal cardiac dysfunction in preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (PROM) is associated with one-third of preterm births. In about 50% of preterm PROM cases, the fetuses will elicit a fetal inflammatory response syndrome (FIRS). FIRS is associated with the impending onset of preterm labor, periventricular leukomalacia, neonatal sepsis, and long-term handicap, including the development of bronchopulmonary dysplasia and cerebral palsy. The fetal myocardium is a potential target organ of proinflammatory cytokines released during FIRS. The objective of this study was to determine whether preterm PROM is associated with functional changes in the fetal heart, as determined by fetal echocardiography. METHODS: A retrospective study was conducted to assess the diastolic function of fetuses with preterm PROM with documented microbial invasion of the amniotic cavity (n = 25), preterm PROM without microbial invasion of the amniotic cavity (n = 42), and fetuses from normal pregnancies (control group = 150). Pregnancies with multiple gestation, fetal distress, fetuses that were small for gestational age, and major congenital anomalies were excluded. Fetal echocardiography studies were performed with two-dimensional ultrasound, color Doppler imaging and pulsed Doppler ultrasound. Non-parametric statistics were used for comparisons. A p value of < 0.05 was considered significant. RESULTS: The prevalence of positive amniotic fluid cultures for micro-organisms in patients with preterm PROM was 35.8% (24/67). Ureaplasma urealyticum was the most frequent isolate, either alone (41.7%; 10/24) or with other micro-organisms (29.2%; 7/24). Fetuses with preterm PROM had a higher delta early diastolic filling/atrial contraction (E/A) peak velocity ratio, a higher delta E/A velocity-time integral (VTI) ratio, a lower delta A peak velocity, a lower delta A VTI, and a lower A VTI/total VTI ratio in the mitral valve compared to those with uncomplicated pregnancies. The delta E/A peak velocity ratio was significantly higher and the delta A VTI significantly lower in fetuses with preterm PROM and microbial invasion of the amniotic cavity than in those with preterm PROM without microbial invasion of the amniotic cavity. CONCLUSIONS: Preterm PROM is associated with changes in fetal cardiac function consistent with increased left ventricular compliance. These observations were also noted in fetuses with microbial invasion of the amniotic cavity. Our findings suggest that fetal cardiac function is altered in preterm PROM and, in particular, in cases with intra-amniotic infection.

Echocardiography↗
PubMed2004

Evaluation of the coulter LH 750 haematology analyzer compared with flow cytometry as the reference method for WBC, platelet and nucleated RBC count.

The Coulter LH 750 is a new haematology analyser with several new features: a count of nucleated red blood cells (NRBCs), automated WBC correction in presence of a flag indicating a cellular interference and a lower incidence of platelet or WBC interference flags when compared with the GEN.S, our current instrument. We had three main goals in our study: evaluating the LH 750 WBC counts when a GEN.S flag suggests a risk of WBC interference, ascertaining whether the platelet counts not flagged by the LH 750 were accurately assessed in samples flagged by the GEN.S and evaluating the NRBC assay provided by the LH 750. Flow cytometry, using CD45 and CD41, respectively for WBC and platelet labelling, was used as a reference method to assess the accuracy of the LH 750 counts. NRBC were identified by double labelling with propidium iodide (PI) and CD45, NRBCs being CD45-/PI+. A significant relationship was found between LH 750 and flow cytometric WBC counts, whether a WBC correction was made by the LH 750 (r = 0.9809, n = 54) or not (r = 0.9901, n = 23). A highly significant relationship was observed for platelets not only in the range from 0 to 450 x 10(9)/l (r = 0.981, n = 108) but also in cases of thrombocytopenia (range: 0-80 x 10(9)/l; r = 0.956, n = 51). In samples with NRBCs, the NRBC percentages given by the LH 750 and by flow cytometry were highly correlated (r = 0.977, n = 60) and WBC counts were accurate. In conclusion, the reduction in flagging by the LH 750, the accuracy of the results, and the availability of a NRBC count, constitute major advantages.

Antigens, Surface↗
PubMed2003

Platelet chimerism by polymerase chain reaction (PCR) utilizing variable number of tandem repeats (VNTR) in allogeneic stem cell transplant in children: a new novel approach to full chimerism analysis.

Evaluation of chimerism following allogeneic transplantation has been performed traditionally focusing on two cellular compartments, namely lymphoid and myeloid. However, none has been described so far to evaluate platelet chimerism. In order to achieve full chimerism in all three cellular compartments, we prospectively obtained 138 samples of peripheral blood in 55 patients at different post transplant periods following allogeneic hematopoietic transplantation. Evaluation of chimerism was performed utilizing tests of variable number of tandem repeat (VNTR) and sex determination by quantitative polymerase chain reaction (PCR). Tests for platelet chimerism using platelet-rich plasma were simultaneously analyzed with samples for T-cell lymphoid and myeloid compartments. Complete donor chimerism was noted in 49 of 55 patients (89%), while the remaining six have split chimerism ranging from 34 to 98%. There is significant difference (P=0.0004) between the percentages of donor DNA in all three cellular compartments comparing the means+/-s.e.m. (myeloid 95.60+/-0.9, T-cell lymphocytes 87.6+/-1.9, and the platelets 90.8+/-1.5); however, comparison between the medians is not statistically significant. This study represents an additional step towards achieving full chimerism and the observation may help reduce the number of unnecessary platelet transfusions once chimerism is noted in that cellular compartment.

Adolescent↗
PubMed2003

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

DNA Primers↗