Enhanced Morbidity of Pectoralis Major Myocutaneous Flap Used for Salvage after Previously Failed Oncological Treatment and Unsuccessful Reconstructive Head and Neck Surgery

Introduction. The reconstruction of complex cervicofacial defects arising from surgical treatment for cancer is a real challenge for head and neck surgeons, especially in salvage reconstruction surgery and/or failed previous reconstruction. The pectoralis major myocutaneous flap (PMMF) has been widely used in these specific situations due to its reliability and low rate of failure or complications. Objectives. Identify factors that determine complications and influence the final outcome of the reconstructions with PMMF in salvage cancer surgery or in salvage reconstruction. Methods. A cross-sectional study design was used to evaluate a sample including 17 surgical patients treated over a period of ten years that met the inclusion criteria. Results. Reconstruction was successful in 13 cases (76.5%), with two cases of partial flap loss and no case of total loss. Complications occurred in 13 cases (76.5%) and were specifically related to the flap in nine instances (52.9%). An association was identified between the development of major complications and reconstruction of the hypopharynx (P = 0.013) as well as in patients submitted to surgery in association with radiation therapy as a previous cancer treatment (P = 0.002). The former condition is also associated with major reconstruction failure (P = 0.018). An even lower incidence of major complications was noted in patients under the age of 53 (P = 0.044). Conclusion. Older patients, with hypopharyngeal defects and submitted to previous surgery plus radiation therapy, presented a higher risk of complications and reconstruction failure with PMMF.

Tank experiments with borehole self-potential data

Despite their importance in the evaluation of petroleum and gas reservoirs, measurements of self-potential data under borehole conditions (well-logging) have found only minor applications in aquifer and waste-site characterization. This can be attributed to lower signals from the diffusion fronts in near-surface environments because measurements are made long after the drilling of the well, when concentration fronts are already disappearing. Proportionally higher signals arise from streaming potentials that prevent using simple interpretation models that assume signals from diffusion only. Our laboratory experiments found that dual-source self-potential signals can be described by a simple linear model, and that contributions (from diffusion and streaming potentials) can be isolated by slightly perturbing the borehole conditions. Perturbations are applied either by changing the concentration of the borehole-filling solution or its column height. Parameters useful for formation evaluation can be estimated from data measured during perturbations, namely, pore water resistivity, pressure drop across the borehole wall, and electrokinetic coupling parameter. These are important parameters to assess, respectively, water quality, aquifer lateral continuity, and interfacial properties of permeable formations.

Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites

Background: Plasmodium has a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host. Methods: Using the fluorescence resonance energy transfer (FRET) peptide substrate Abz-AIKFFARQ-EDDnp and Fluo4/AM, the effects of extracellular ATP on triggering proteolysis and Ca2+ signalling in Plasmodium berghei and Plasmodium yoelii malaria parasites were investigated. Results: The protease activity was blocked in the presence of the purinergic receptor blockers suramin (50 mu M) and PPADS (50 mu M) or the extracellular and intracellular calcium chelators EGTA (5 mM) and BAPTA/AM (25, 100, 200 and 500 mu M), respectively for P. yoelii and P. berghei. Addition of ATP (50, 70, 200 and 250 mu M) to isolated parasites previously loaded with Fluo4/AM in a Ca2+-containing medium led to an increase in cytosolic calcium. This rise was blocked by pre-incubating the parasites with either purinergic antagonists PPADS (50 mu M), TNP-ATP (50 mu M) or the purinergic blockers KN-62 (10 mu M) and Ip5I (10 mu M). Incubating P. berghei infected cells with KN-62 (200 mu M) resulted in a changed profile of merozoite surface protein 1 (MSP1) processing as revealed by western blot assays. Moreover incubating P. berghei for 17 h with KN-62 (10 mu M) led to an increase in rings forms (82% +/- 4, n = 11) and a decrease in trophozoite forms (18% +/- 4, n = 11). Conclusions: The data clearly show that purinergic signalling modulates P. berghei protease(s) activity and that MSP1 is one target in this pathway.

LIMB REPLANTATION AFTER AVULSION INJURIES: TECHNIQUES AND TACTICS FOR SUCCESS

Objectives: Retrospective evaluation of cases of limb replantation after avulsion injuries. Evaluation of the techniques and tactics used, that contributed to success and good functional results. Methods: Forty-three patients' records were assessed. All the cases had been submitted to limb replantation after avulsion injuries. Results: The majority of the cases were young men. The most common injury was to the thumbs. The surgical techniques and tactics used were: nerve grafting, vein grafting, transposition of the digital vessels, limb shortening, and heterotopic replantation. The most commonly used technique was vein graft. The limb survival rate was high (93%), as was patient satisfaction. Conclusion: Replantation after avulsion injury depends on the correct diagnosis of the limb viability and the use of appropriate surgical techniques and tactics for each case. The experience of the team of surgeons and a good hospital structure are essential for good results. There are few articles in medical literature about the indications, techniques and results of limb replantation after avulsion injuries. We believe that this retrospective evaluation can bring new information and contributions to the correct management of this highly complex situation. Level of evidence IV, Case Series.

Safety and efficacy of gemcitabine plus cisplatin combination in pretreated metastatic breast cancer patients

Metastatic breast cancers (MBC) previously treated with anthracyclines (A) and taxanes (T) have a complicated management. Gemcitabine (G)-cisplatin (C) combinations have been used as synergistic salvage therapy in MBC and are considered as another option for patients with important symptoms and aggressive visceral disease. We analyzed the safety and efficacy of GC in AT-pretreated MBC, as well as overall survival (OS) and time to progression (TTP). Forty-nine subjects received IV G 750 mg/m(2) and C 30 mg/m(2), both d1 and d8 every 3 weeks. Response evaluation was performed every second cycle and in the end of treatment. GC protocol was the first-line palliative chemotherapy in half of the cases, and median number of cycles/patient were 4(2-12). Lung (75.5%) was the most frequent site of metastasis. Most of the patients related clinical improvement with chemotherapy with minimal/mild tolerable collateral effects in 85.7% of cases. Following 34 months, mean OS/TTP was 13.12/6.6 months. Objective-responded patients (40.3%) were statistically associated with the improvement in symptoms after CT (P < 0.01), and OS was directly correlated with chemotherapy response (P < 0.01). HER-2 overexpression was a prognostic factor with reduced OS (P = 0.01). GC protocol was effective and tolerable in objective-responded patients.

Florística e fitossociologia em parcelas permanentes da Mata Atlântica do sudeste do Brasil ao longo de um gradiente altitudinal

Este trabalho resume os dados de florística e fitossociologia de 11, das 14 parcelas de 1 ha, alocadas ao longo do gradiente altitudinal da Serra do Mar, São Paulo, Brasil. As parcelas começam na cota 10 m (Floresta de Restinga da Praia da Fazenda, município de Ubatuba) e estão distribuídas até a cota 1100 m (Floresta Ombrófila Densa Montana da Trilha do rio Itamambuca, município de São Luis do Paraitinga) abrangendo os Núcleos Picinguaba e Santa Virgínia do Parque Estadual da Serra do Mar. Na Restinga o solo é Neossolo Quartzarênico francamente arenoso, enquanto que na encosta o solo é um Cambisolo Háplico Distrófico argilo-arenoso, sendo que todas as parcelas apresentaram solo ácido (pH 3 – 4) com alta diluição de nutrientes e alta saturação de alumínio. Na Restinga e no sopé da encosta o clima é Tropical/Subtropical Úmido (Af/Cfa), sem estação seca, com precipitação média anual superior a 2.200 mm e temperatura média anual de 22 °C. Subindo a encosta mantêm-se a média de precipitação, mas há um gradativo resfriamento, de forma que a 1.100 m o clima é Subtropical Úmido (Cfa/Cfb), sem estação seca, com temperatura média anual de 17 °C. Destaca-se ainda que, quase diariamente, a parte superior da encosta, geralmente acima de 400 m, é coberta por uma densa neblina. Nas 14 parcelas foram marcados, medidos e amostrados 21.733 indivíduos com DAP ≥ 4,8 cm, incluindo árvores, palmeiras e fetos arborescentes. O número médio de indivíduos amostrados nas 14 parcelas foi de 1.264 ind.ha–1 (± 218 EP de 95%). Dentro dos parâmetros considerados predominaram as árvores (71% FOD Montana a 90% na Restinga), seguidas de palmeiras (10% na Restinga a 25% na FOD Montana) e fetos arborescentes (0% na Restinga a 4% na FOD Montana). Neste aspecto destaca-se a FOD Terras Baixas Exploradas com apenas 1,8% de palmeiras e surpreendentes 10% de fetos arborescentes. O dossel é irregular, com altura variando de 7 a 9 m, raramente as árvores emergentes chegam a 18 m, e a irregularidade do dossel permite a entrada de luz suficiente para o desenvolvimento de centenas de espécies epífitas. Com exceção da FOD Montana, onde o número de mortos foi superior a 5% dos indivíduos amostrados, nas demais fitofisionomias este valor ficou abaixo de 2,5%. Nas 11 parcelas onde foi realizado o estudo florístico foram encontradas 562 espécies distribuídas em 195 gêneros e 68 famílias. Apenas sete espécies – Euterpe edulis Mart. (Arecaceae), Calyptranthes lucida Mart. ex DC. e Marlierea tomentosa Cambess (ambas Myrtaceae), Guapira opposita (Vell.) Reitz (Nyctaginaceae), Cupania oblongifolia Mart. (Sapindaceae) e as Urticaceae Cecropia glaziovii Snethl. e Coussapoa microcarpa (Schott) Rizzini – ocorreram da Floresta de Restinga à FOD Montana, enquanto outras 12 espécies só não ocorreram na Floresta de Restinga. As famílias com o maior número de espécies são Myrtaceae (133 spp), Fabaceae (47 spp), 125 Fitossociologia em parcelas permanentes de Mata Atlântica http://www.biotaneotropica.org.br/v12n1/pt/abstract?article+bn01812012012 http://www.biotaneotropica.org.br Biota Neotrop., vol. 12, no. 1 Introdução A Mata Atlântica sensu lato (Joly et al. 1999) é a segunda maior floresta tropical do continente americano (Tabarelli et al. 2005). A maior parte dos Sistemas de Classificação da vegetação brasileira reconhece que no Domínio Atlântico (sensu Ab’Saber 1977) esse bioma pode ser dividido em dois grandes grupos: a Floresta Ombrófila Densa, típica da região costeira e das escarpas serranas com alta pluviosidade (Mata Atlântica – MA – sensu stricto), e a Floresta Estacional Semidecidual, que ocorre no interior, onde a pluviosidade, além de menor, é sazonal. Na região costeira podem ocorrer também Manguezais (Schaeffer-Novelli 2000), ao longo da foz de rios de médio e grande porte, e as Restingas (Scarano 2009), crescendo sobre a planície costeira do quaternário. No topo das montanhas, geralmente acima de 1500 m, estão os Campos de Altitude (Ribeiro & Freitas 2010). Em 2002, a Fundação SOS Mata Atlântica em parceria com o INPE (Instituto..., 2002) realizaram um levantamento que indica que há apenas 7,6% da cobertura original da Mata Atlântica (s.l.). Mais recentemente Ribeiro et al. (2009) refinaram a estimativa incluindo fragmentos menores, que não haviam sido contabilizados, e concluíram que resta algo entre 11,4 e 16% da área original. Mesmo com esta fragmentação, o mosaico da Floresta Atlântica brasileira possui um dos maiores níveis de endemismos do mundo (Myers et al. 2000) e cerca da metade desses remanescentes de grande extensão estão protegidos na forma de Unidades de Conservação (Galindo & Câmara 2005). Entre os dois centros de endemismo reconhecidos para a MA (Fiaschi & Pirani 2009), o bloco das regiões sudeste/sul é o que conserva elementos da porção sul de Gondwana (Sanmartin & Ronquist 2004), tido como a formação florestal mais antiga do Brasil (Colombo & Joly 2010). Segundo Hirota (2003), parte dos remanescentes de MA está no estado de São Paulo, onde cerca de 80% de sua área era coberta por florestas (Victor 1977) genericamente enquadradas como Mata Atlântica “sensu lato” (Joly et al. 1999). Dados de Kronka et al. (2005) mostram que no estado restam apenas 12% de área de mata e menos do que 5% são efetivamente florestas nativas pouco antropizadas. Nos 500 anos de fragmentação e degradação das formações naturais, foram poupadas apenas as regiões serranas, principalmente a fachada da Serra do Mar, por serem impróprias para práticas agrícolas. Usando o sistema fisionômico-ecológico de classificação da vegetação brasileira adotado pelo IBGE (Veloso et al. 1991), a Floresta Ombrófila Densa, na área de domínio da Mata Atlântica, foi subdividida em quatro faciações ordenadas segundo a hierarquia topográfica, que refletem fisionomias de acordo com as variações das faixas altimétricas e latitudinais. No estado de São Paulo, na latitude entre 16 e 24 °S temos: 1) Floresta Ombrófila Densa das Terras Baixas - 5 a 50 m de altitude; 2) Floresta Ombrófila Densa Submontana – no sopé da Serra do Mar, com cotas de altitude variando entre 50 e 500 m; 3) Floresta Ombrófila Densa Montana – recobrindo a encosta da Serra do Mar propriamente dita, em altitudes que variam de 500 a 1.200 m; 4) Floresta Ombrófila Densa Altimontana – ocorrendo no topo da Serra do Mar, acima dos limites estabelecidos para a formação montana, onde a vegetação praticamente deixa de ser arbórea, pois predominam os campos de altitude. Nas últimas três décadas muita informação vem sendo acumulada sobre a composição florística e a estrutura do estrato arbóreo dos remanescentes florestais do estado, conforme mostram as revisões de Oliveira-Filho & Fontes (2000) e Scudeller et al. (2001). Em florestas tropicais este tipo de informação, assim como dados sobre a riqueza de espécies, reflete não só fatores evolutivos e biogeográficos, como também o histórico de perturbação, natural ou antrópica, das respectivas áreas (Gentry 1992, Hubbell & Foster 1986). A síntese dessas informações tem permitido a definição de unidades fitogeográficas com diferentes padrões de riqueza de espécies e apontam para uma diferenciação, entre as florestas paulistas, no sentido leste/oeste (Salis et al. 1995, Torres et al. 1997, Santos et al. 1998). Segundo Bakker et al. (1996) um método adequado para acompanhar e avaliar as mudanças na composição das espécies e dinâmica da floresta ao longo do tempo é por meio de parcelas permanentes (em inglês Permanent Sample Plots –PSPs). Essa metodologia tem sido amplamente utilizada em estudos de longa duração em florestas tropicais, pois permite avaliar a composição e a estrutura florestal e monitorar sua mudança no tempo (Dallmeier 1992, Condit 1995, Sheil 1995, Malhi et al. 2002, Lewis et al. 2004). Permite avaliar também as consequências para a floresta de problemas como o aquecimento global e a poluição atmosférica (Bakker et al. 1996). No Brasil os projetos/programas que utilizam a metodologia de Parcelas Permanentes tiveram origem, praticamente, com o Projeto Rubiaceae (49) e Lauraceae (49) ao longo de todo gradiente da FOD e Monimiaceae (21) especificamente nas parcelas da FOD Montana. Em termos de número de indivíduos as famílias mais importantes foram Arecaceae, Rubiaceae, Myrtaceae, Sapotaceae, Lauraceae e na FOD Montana, Monimiaceae. Somente na parcela F, onde ocorreu exploração de madeira entre 1960 e 1985, a abundância de palmeiras foi substituída pelas Cyatheaceae. O gradiente estudado apresenta um pico da diversidade e riqueza nas altitudes intermediárias (300 a 400 m) ao longo da encosta (índice de Shannon-Weiner - H’ - variando de 3,96 a 4,48 nats.indivíduo–1). Diversas explicações para este resultado são apresentadas neste trabalho, incluindo o fato dessas altitudes estarem nos limites das expansões e retrações das diferentes fitofisionomias da FOD Atlântica durante as flutuações climáticas do Pleistoceno. Os dados aqui apresentados demonstram a extraordinária riqueza de espécies arbóreas da Floresta Ombrófila Densa Atlântica dos Núcleos Picinguaba e Santa Virgínia do Parque Estadual da Serra do Mar, reforçando a importância de sua conservação ao longo de todo o gradiente altitudinal. A diversidade desta floresta justifica também o investimento de longo prazo, através de parcelas permanentes, para compreender sua dinâmica e funcionamento, bem como monitorar o impacto das mudanças climáticas nessa vegetação.

Structural and kinetic studies of Schistosoma mansoni adenylate kinases

The human parasite Schistosoma mansoni is totally dependent on the purine salvage pathway in order to supply large quantities of purine precursors for its energy and DNA biosynthetic needs. Adenylate kinase (ADK) is responsible for the conversion of AMP (produced by the adenosine kinase reaction) into ADP, which is subsequently converted into ATP by nucleoside diphosphate kinase (NDPK). ADK and NDPK are the most active enzymes of the pathway, probably reflecting an evolutionary adaptation due to the intense use of the branch in which they participate. However, notwithstanding their importance very little information has been accumulated found regarding these enzymes. In this work two adenylate kinases from S. mansoni were cloned and heterologously expressed in Escherichia coil. The purified products were utilized in activity assays, and displayed kinetic parameters similar to the corresponding human orthologous proteins. The cytosolic S. mansoni ADK was crystallized and its structure solved allowing us to detect a difference in the nucleotide binding site when compared with the human ortholog. (C) 2012 Elsevier B.V. All rights reserved.

Identification of a new translocation that disrupts the RUNX1 gene in a patient with de novo acute myeloid leukemia

Translocation (8;21)(q22;q22)/RUNX1-RUNX1T1 is a molecular marker that is usually associated with a favorable outcome in both pediatric and adult patients with acute myeloid leukemia (AML). The present report describes the results of hematologic, cytogenetic, and fluorescence in situ hybridization analysis of a case of AML with maturation in a 23-year-old woman. Cytogenetic analysis revealed a balanced translocation involving chromosomal band 21q22, which disrupts the RUNX1 gene, and 10q22, with the following karyotype: 45,X,-X,t(10;21)(q24;q22)[cp16]/46,XX [4]. Interphase FISH showed, in 67% of the 300 interphase nuclei analyzed, three signals for RUNX1 and two RUNX1T1, but no signals corresponding to RUNX1-RUNX1T1 fusion gene. These results were corroborated by RT-PCR, which revealed negative results for the amplification of RUNX1-RUNX1T1 fusion gene. The patient was refractory to conventional and salvage chemotherapy regimens and early relapsed after unrelated donor bone marrow transplantation (BMT), dying of pneumonia, acute respiratory failure, and sepsis on day +80 after BMT, 1 year after diagnosis.

FOLLOW-UP OF TREATED OSTEOSARCOMA PATIENT

Objective: To evaluate the value of post-treatment follow-up in osteosarcoma patients. Methods: Data were collected through a clinical record, with socio-demographic and clinical data, and information relating to the medical appointment. Descriptive analysis of the data was carried out. The Chi-squared test was used to associate the independent variables with attendance at scheduled follow-up appointments. Results: We found a recurrence in 59.6% of cases, of which 58% were lung related; 44% presented clinical complaints and arrived on the scheduled date of the appointment. There was no statistically significant association between the demographic characteristics and early attendance of follow-up visits. 81.3% of the cases who came for the appointment earlier than originally scheduled presented complaints compared to those who did not (p=0.005). Of the cases who presented recurrence, 12.9% attended an appointment late and those who did not present recurrence, 47.6% were late for the appointment (p=0.006). Conclusion: It is seen that the patients who came for an earlier appointment presented more complaints and were associated with the positive result of the exams carried out. The patients who had recurrence and came for an earlier appointment did not present a statistically significant difference in recurrence-free survival. It was observed that distance was not a predominant factor in late attendance at appointments. Level of Evidence II, Retrospective Study.

Endophthalmitis: A Rare but Devastating Metastatic Bacterial Complication of Hemodialysis Catheter-Related Sepsis

There are many infectious complications related to vascular access in patients undergoing maintenance hemodialysis. We report two cases of endophthalmitis as a metastatic infection associated with a tunneled catheter and a temporary dual lumen catheter. Both patients were diabetic. A 61-year-old female on maintenance hemodialysis by a jugular tunnelized catheter during the past year was receiving parenteral antibiotics for catheter salvage due to fever episodes in the last 3 months. She was admitted to the hospital presenting pain, proptosis, conjunctival hyperemia, corneal infiltrate, and visual acuity of no light perception (NLP). A 51-year-old male recently undergoing hemodialysis by a temporary dual lumen catheter presented fever. His catheter was removed, but he was admitted to the hospital presenting fever, decreased vision, edema, and pain in his left eye. On examination, eyelid edema, conjunctival hyperemia, purulent secretion, hypopyon in the pupils, and visual acuity of NLP were verified. A diagnosis of endogenous endophthalmitis was made in both patients on clinical grounds and computed tomography. Evisceration of the left eye was the first option of treatment for both patients due to poor vision. Cultures of the eviscerated ocular globes showed Staphylococcus hemolyticus and Staphylococcus aureus, respectively. After evisceration, both patients received treatment, had a good outcome, and were discharged to continue their hemodialysis program. Metastatic bacterial endophthalmitis is a rare complication of dialysis catheter-related bacteremia. When suspected, urgent ophthalmologic evaluation and treatment are needed to reduce the risk of losing vision in the affected eye.

Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase

Abstract Background Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (EC 2.4.2.8) is a central enzyme in the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida cannot synthesize purines de novo and use the salvage pathway to synthesize purine bases, making this an attractive target for antiparasitic drug design. Results The glycosomal HGPRT from Leishmania tarentolae in a catalytically active form purified and co-crystallized with a guanosine monophosphate (GMP) in the active site. The dimeric structure of HGPRT has been solved by molecular replacement and refined against data extending to 2.1 Å resolution. The structure reveals the contacts of the active site residues with GMP. Conclusion Comparative analysis of the active sites of Leishmania and human HGPRT revealed subtle differences in the position of the ligand and its interaction with the active site residues, which could be responsible for the different reactivities of the enzymes to allopurinol reported in the literature. The solution and analysis of the structure of Leishmania HGPRT may contribute to further investigations leading to a full understanding of this important enzyme family in protozoan parasites.

Biosynthesis of vitamins and cofactors in bacterium-harbouring trypanosomatids depends on the symbiotic association as revealed by genomic analyses

Some non-pathogenic trypanosomatids maintain a mutualistic relationship with a betaproteobacterium of the Alcaligenaceae family. Intensive nutritional exchanges have been reported between the two partners, indicating that these protozoa are excellent biological models to study metabolic co-evolution. We previously sequenced and herein investigate the entire genomes of five trypanosomatids which harbor a symbiotic bacterium (SHTs for Symbiont-Haboring Trypanosomatids) and the respective bacteria (TPEs for Trypanosomatid Proteobacterial Endosymbiont), as well as two trypanosomatids without symbionts (RTs for Regular Trypanosomatids), for the presence of genes of the classical pathways for vitamin biosynthesis. Our data show that genes for the biosynthetic pathways of thiamine, biotin, and nicotinic acid are absent from all trypanosomatid genomes. This is in agreement with the absolute growth requirement for these vitamins in all protozoa of the family. Also absent from the genomes of RTs are the genes for the synthesis of pantothenic acid, folic acid, riboflavin, and vitamin B6. This is also in agreement with the available data showing that RTs are auxotrophic for these essential vitamins. On the other hand, SHTs are autotrophic for such vitamins. Indeed, all the genes of the corresponding biosynthetic pathways were identified, most of them in the symbiont genomes, while a few genes, mostly of eukaryotic origin, were found in the host genomes. The only exceptions to the latter are: the gene coding for the enzyme ketopantoate reductase (EC:1.1.1.169) which is related instead to the Firmicutes bacteria; and two other genes, one involved in the salvage pathway of pantothenic acid and the other in the synthesis of ubiquinone, that are related to Gammaproteobacteria. Their presence in trypanosomatids may result from lateral gene transfer. Taken together, our results reinforce the idea that the low nutritional requirement of SHTs is associated with the presence of the symbiotic bacterium, which contains most genes for vitamin production.