Intramyocardial Injection of Autologous Bone Marrow Cells as an Adjunctive Therapy to Incomplete Myocardial Revascularization - Safety Issues

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59&plusmn;5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3&plusmn;0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+=1.8&plusmn;0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6&plusmn;0.8 (baseline) to 1.2&plusmn;0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65&plusmn;0.14 (baseline) to 0.17&plusmn;0.05 (one year) (P=0.002), but also in the injected areas from 1.11&plusmn;0.20 (baseline) to 0.34&plusmn;0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial

Internal fit of two all-ceramic systems and metal-ceramic crowns

OBJECTIVES: The aim of this study was to investigate the internal fit (IF) of glass-infiltrated alumina (ICA - In-Ceram Alumina), yttria-stabilized tetragonal zirconia polycrystals (Y-TZP - IPS e.max ZirCAD), and metal-ceramic (MC - Ni-Cr alloy) crowns. MATERIAL AND METHODS: Sixty standardized resin-tooth replicas of a maxillary first molar were produced for crown placement and divided into 3 groups (n=20 each) according to the core material used (metal, ICA or Y-TZP). The IF of the crowns was measured using the replica technique, which employs a light body polyvinyl siloxane impression material to simulate the cement layer thickness. The data were analyzed according to the surfaces obtained for the occlusal space (OS), axial space (AS) and total mean (TM) using two-way ANOVA with Tukey s multiple comparison test (p<0.05). RESULTS: No differences among the different areas were detected in the MC group. For the Y-TZP and ICA groups, AS was statistically lower than both OS and TM. No differences in AS were observed among the groups. However, OS and TM showed significantly higher values for ICA and Y-TZP groups than MC group. Comparisons of ICA and Y-TZP revealed that OS was significantly lower for Y-TZP group, whereas no differences were observed for TM. CONCLUSIONS: The total mean achieved by all groups was within the range of clinical acceptability. However, the metal-ceramic group demonstrated significantly lower values than the all-ceramic groups, especially in OS

Appendectomy: comparative study between a public and a private hospital

OBJECTIVE: The aim of this study is to compare data of patients submitted to appendectomy for acute appendicitis at a public hospital and at a private hospital. METHODS: A total of 200 medical records of patients submitted to appendectomy for acute appendicitis at a public hospital (n=100) and at a private hospital (n=100), was reviewed retrospectively. RESULTS: Mean age and gender distribution were similar for patients of both hospitals. More patients had been previously evaluated by other physicians in the group of the public hospital (n=85) than of the private hospital (n=13) (pOBJETIVO:Comparar dados dos pacientes submetidos à apendicectomia por apendicite aguda em um hospital público e um privado. MÉTODOS: O total de 200 prontuários médicos de pacientes que foram submetidos à apendicectomia por apendicite aguda em um hospital público (n=100) e em um hospital privado (n=100) foi revisado retrospectivamente. RESULTADOS: A idade média e a distribuição dos pacientes por sexo foram similares entre os dois hospitais. Um número maior de pacientes foi previamente avaliado por outro médico no grupo operado no hospital público (n=85) do que no hospital privado (n=13) (p< 0,0001). Ultrassonografia foi realizada mais frequentemente no hospital público (n=56) do que no hospital privado (n=30) (p=0,0002). O tempo de internação hospitalar foi mais longo no hospital público (3,5±2,8 dias) do que no hospital privado (2,5±1,7 dias) (p=0,0024). Complicações pós-operatórias foram mais comuns no hospital público (n=36) do que no hospital privado (n=20) (p<0,0117). O tempo de retorno as atividades de rotina foi mais longo no hospital público (33.2±8.3 dias) do que no hospital privado (16.4±5.2 dias) (p<0,0001). A análise de regressão logística mostrou que a probabilidade estimada da apendicite complicada aumenta com o intervalo de tempo entre o início dos sintomas e a apendicectomia (p<0.001). O fator de risco independente associado com apendicite complicada foi o intervalo de tempo entre o início dos sintomas e a apendicectomia (odds ratio 41.65, 95% CI 2.90-597.49, p<0.0001) no hospital público. Não houve fatores de risco independente associados com apendicite complicada no hospital privado. CONCLUSÃO: Existem importantes diferenças no processo diagnóstico e nos resultados dos pacientes submetidos à apendicectomia por apendicite aguda entre hospital público e privado

Merozoite surface protein-1 genetic diversity in Plasmodium malariae and Plasmodium brasilianum from Brazil

Abstract\ud \ud Background\ud The merozoite surface protein 1 (MSP1) gene encodes the major surface antigen of invasive forms of the Plasmodium erythrocytic stages and is considered a candidate vaccine antigen against malaria. Due to its polymorphisms, MSP1 is also useful for strain discrimination and consists of a good genetic marker. Sequence diversity in MSP1 has been analyzed in field isolates of three human parasites: P. falciparum, P. vivax, and P. ovale. However, the extent of variation in another human parasite, P. malariae, remains unknown. This parasite shows widespread, uneven distribution in tropical and subtropical regions throughout South America, Asia, and Africa. Interestingly, it is genetically indistinguishable from P. brasilianum, a parasite known to infect New World monkeys in Central and South America.\ud \ud \ud Methods\ud Specific fragments (1 to 5) covering 60 % of the MSP1 gene (mainly the putatively polymorphic regions), were amplified by PCR in isolates of P. malariae and P. brasilianum from different geographic origin and hosts. Sequencing of the PCR-amplified products or cloned PCR fragments was performed and the sequences were used to construct a phylogenetic tree by the maximum likelihood method. Data were computed to give insights into the evolutionary and phylogenetic relationships of these parasites.\ud \ud \ud Results\ud Except for fragment 4, sequences from all other fragments consisted of unpublished sequences. The most polymorphic gene region was fragment 2, and in samples where this region lacks polymorphism, all other regions are also identical. The low variability of the P. malariae msp1 sequences of these isolates and the identification of the same haplotype in those collected many years apart at different locations is compatible with a low transmission rate. We also found greater diversity among P. brasilianum isolates compared with P. malariae ones. Lastly, the sequences were segregated according to their geographic origins and hosts, showing a strong genetic and geographic structure.\ud \ud \ud Conclusions\ud Our data show that there is a low level of sequence diversity and a possible absence of allelic dimorphism of MSP1 in these parasites as opposed to other Plasmodium species. P. brasilianum strains apparently show greater divergence in comparison to P. malariae, thus P. malariae could derive from P. brasilianum, as it has been proposed.We are grateful to Profª Luzia Helena Carvalho (Laboratório de Malária,\ud Centro de Pesquisas René Rachou – FIOCRUZ) for provision of P. brasilianum\ud sample (Peruvian III strain). We are also grateful to Prof Luis Fabio Silveira\ud (Museu de Zoologia da Universidade de São Paulo) for the provision of P169\ud sample and Dra. Sandra do Lago Moraes (Instituto de Medicina Tropical de\ud São Paulo da Universidade de São Paulo) for the provision of 23PA, 50PA,\ud 66PA samples. This research was funded by CNPq (475727/2007-0 - Edital\ud Universal) and FAPESP to Karin Kirchgatter. Lilian de Oliveira Guimarães has a\ud CAPES scholarship, and J.M.P. Alves is supported by grant #2013/14622-3,\ud São Paulo Research Foundation

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets