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Biomedical subjects

Eduardo Rocha

Publications and source records attributed to Eduardo Rocha.

At least 19 recordsLinked to original sources
PubMed2006

A prospective observational study on the effectiveness and safety of bemiparin, first dose administered 6 h after knee or hip replacement surgery.

INTRODUCTION: Bemiparin has shown to be effective and safe in clinical trials in total knee or hip replacement. MATERIALS AND METHODS: We conducted a prospective, open, multicentre, uncontrolled study to audit the utilisation patterns of bemiparin 3,500 IU/day, first dose administered 6 h after surgery, in 1,009 patients undergoing total hip or knee replacement surgery in standard clinical practice. We analysed rates of documented symptomatic venous thromboembolism (VTE) [deep-vein thrombosis (DVT) and pulmonary embolism (PE)] confirmed by objective methods, major bleeding, death, thrombocytopaenia and other adverse events up to 6 weeks. RESULTS: Rate of documented symptomatic DVT was 0.3% (95% CI, 0.1-0.9%). No cases of documented PE were reported. There were 14 (1.4%) major bleedings (95% CI, 0.8-2.3%). Neuraxial anaesthesia was used in 937 (92.9%) patients. There were no cases of spinal haematoma, fatal bleeding or bleeding in critical organs. There were 6 (0.6%) cases of mild thrombocytopaenia, which did not require treatment discontinuation. No cases of severe type II heparin-induced thrombocytopaenia were observed. There were no deaths during bemiparin prophylaxis. The median length of hospitalisation was 9 days and 92.5% of patients continued prophylaxis post-hospitalisation for a total median time of 38 days. There were no thromboembolic or bleeding complications during post-hospitalisation prophylaxis. Postoperative start of prophylaxis with bemiparin permitted that 29.3% of patients could be admitted to hospital the same day of the intervention. CONCLUSION: Bemiparin prophylaxis, started 6 h after surgery and given for 5-6 weeks after total hip or knee replacement, was associated with low rates of VTE, major bleeding and other adverse events in normal clinical practice. Bemiparin thromboprophylaxis started 6 h after surgery makes neuraxial anaesthesia/analgesia procedures easier, without compromising efficacy.

Aged↗
PubMed2006

Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma.

BACKGROUND: Follicular lymphoma is considered incurable, although cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential remissions. A patient's second complete response is typically shorter than that patient's first complete response. Idiotype vaccines can elicit specific immune responses and molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven. METHODS: Thirty-three consecutive follicular lymphoma patients in first relapse received six monthly cycles of CHOP-like chemotherapy. Patients who achieved a second complete response were vaccinated periodically for more than 2 years with autologous lymphoma-derived idiotype protein vaccine. Specific humoral and cellular responses were assessed, and patients were followed for disease recurrence. Statistical tests were two-sided. RESULTS: Idiotype vaccine could be produced for 25 patients who had a second complete response. In 20 patients (80%), a humoral (13/20) and/or a cellular (18/20) idiotype-specific response was detected. The median duration of the second complete response has not been reached, but it exceeds 33 months (range = 20+ to 51+ months). None of the 20 responders relapsed while undergoing active vaccination. All responders with enough follow-up for the comparison to be made experienced a second complete response that was statistically significantly (P<.0001) longer than both their first complete response (18 of 18 patients) and than the median duration of a CHOP-induced second complete response, i.e., 13 months (20 of 20 patients). The five nonresponders all had a second complete response that was shorter (median = 10 months; range = 8-13 months) than their first complete response (median = 17 months; range = 10-39 months). CONCLUSIONS: Idiotypic vaccination induced a specific immune response in the majority of patients with follicular lymphoma. Specific immune response was associated with a dramatic and highly statistically significant increase in disease-free survival. This is the first formal demonstration of clinical benefit associated with the use of a human cancer vaccine.

Adult↗
PubMed2006

Histology of the digestive tract of the freshwater stingray Himantura signifer Compagno and Roberts, 1982 (Elasmobranchii, Dasyatidae).

We investigated the histology and histochemistry (of carbohydrates and proteins) of the digestive tract of the freshwater stingray Himantura signifier. The alimentary tract consists of a mouth, pharynx, esophagus, stomach (with a descending cardiac and ascending pyloric part), anterior intestine (with an initial portion and a spiral intestine) and posterior intestine, ending in a cloaca. Histologically, three layers--mucosa, muscularis and adventitia/serosa--were defined from the mouth to esophagus and in the posterior intestine, whereas in the stomach and anterior intestine four layers were present, including a submucosa. The epithelial lining of mouth, pharynx and cloaca was of the stratified cuboidal type, whereas that of the esophagus and posterior intestine was stratified columnar. The stomach and anterior intestine were lined by a simple columnar epithelium with microvilli. Goblet cells were observed along the alimentary tract, except in the stomach. In the descending cardiac portion of this organ, gastric glands composed of oxyntic, oxyntic-peptic and peptic cells were observed. The anterior intestine presented a spiral valve with 11 folds, formed by mucosa and submucosa. The posterior intestine was particular in displaying a three-layered muscularis. Mucosubstances secreted along the alimentary tract contained both neutral and acid mucins, but in the stomach only neutral mucins were detected. The stomach presented intense protein content in the epithelial lining of the gastric pits. Enteroendocrine cells were identified in the stomach and intestine. Overall, our data offer a baseline for comparative purposes and future detailed ultrastructural and immunohistochemical studies.

Animals↗
PubMed2006

[Venous thromboembolism in patients with cancer].

The association between neoplastic diseases and venous thromboembolism (VTE) is known since long time ago. The nature of this association is bidirectional. On one hand, cancer increases the incidence of venous thrombosis and, on the other hand, the hemostatic system does play a key role in the tumorigenesis process. However, despite recent advances in the field, prophylaxis and treatment of VTE in cancer patients is still a challenge, due to the complexity of this type of patients. This review is focused on some important points regarding management of VTE in cancer patients such as physiopathology, epidemiology, search for hidden malignancy, prognostic impact, prophylaxis in the medical and surgical setting, or initial and long-term treatment.

Anticoagulants↗
PubMed2006

Temperature and gender influences on the hepatic stroma (and associated pancreatic acini) of Nile tilapia, Oreochromis niloticus (Teleostei, Cichlidae): a stereological analysis by light microscopy.

The normal organ morphology and function in fishes varies according to several natural factors, and such variability is found in liver. Knowledge about the normal liver microanatomy is fundamental to pathological evaluation. Even though gender and temperature are important factors for modulating morphophysiological processes in fishes, their influences on liver stroma are virtually unknown. Because temperature- and gender-related changes exist in liver parenchyma, we predict both factors should also influence the normal stromal structure. Using Nile tilapia as a model, we undertook a study to: 1) establish baseline quantitative structural data on the hepatic stroma (and intimately associated pancreatic acini); 2) compare data with those available from other species, namely, salmonids that do not have a liver with pancreatic acini; and 3) test our hypothesis that, within normal healthy limits, the stroma and its structural components may vary significantly with temperature and gender. We used 1-year-old male and female specimens acclimated to 17 degrees C (breeding noncompatible) and 27 degrees C (breeding compatible) for 45 days. Basic morphometric fish parameters were recorded. After estimation of liver volume, the organ was sliced and pieces systematically sampled for light microscopy. Stereology allowed estimation of the relative volumes of organ components. The total volumes were computed by combining the relative volumes with the total liver volumes. Nile tilapia of both genders, held at 17 vs. 27 degrees C, showed structural quantitative differences in the relative volumes of stroma and most of its components, and in the total volumes of certain stromal elements. The total volume of the stroma and of associated pancreatic acini did not differ. We first established that, in fishes, the total amount (volume) of liver biliary ducts and of eosinophilic granule cells might significantly change (increase and decrease, respectively) with a higher acclimation temperature. Indeed, virtually all the stereological changes were, essentially, temperature- and not gender-related. At 27 degrees C, parallel changes in the parenchyma caused a decreased liver volume and hepatic-somatic index (HSI). The relative volumetric proportion of stroma vs. parenchyma in tilapia is higher than in salmonids. The differences found in this study could not be detected with a qualitative approach, thus stressing the importance of using stereology for analyzing histological patterns and for establishing reliable baseline values in healthy conditions. It was also anticipated that in experimental settings with fish the baseline liver stromal architecture may be different according to temperature and breeding status; in consequence, the effects of the tested variable may also diverge. Our data do not fully explain the lower liver volume and HSI at 27 degrees C, thus justifying studies on the parenchyma, particularly on cell size and number.

Animals↗
PubMed2006

Design-based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic antigen polyclonal antibodies.

BACKGROUND/AIMS: Hepatocytes (HEP) have been the major target for structural quantification in the liver, but an estimation of their total number (N), their percentage in relation to the global number of liver cells and the evaluation of the percentage of binucleated hepatocytes (BnHEPs) have never been performed with modern design-based stereological techniques. The establishment of sound technical guidelines and baseline quantitative data in non-pathological conditions are relevant to properly evaluate HEP hyperplasia and BnHEP responses. METHODS: In this study, we combined immunocytochemistry with sound design-based stereology for estimating the N of HEP and the N of non-hepatocytic cells (NHCs). For obtaining systematic uniform random sections (30 microm thick), a smooth fractionator sampling scheme was applied to the liver of five male Wistar rats (3 month old). Those sections were immunostained with polyclonal antibodies against carcinoembryonic antigen. Because biliary canaliculi were then marked, an unequivocal counting of mononucleated hepatocytes (MnHEP) and BnHEP was allowed. RESULTS: The N of HEP was estimated to be 1.93 x 10(9), with a coefficient of error (CE) of 0.02, corresponding to 129 x 10(6) HEP/g of liver. BnHEP represented 26% of total HEP number. The N of NHC was estimated as 1.31 x 10(9) (CE=0.02). CONCLUSION: The strategy here presented provides a reliable method for accessing the N of HEP (distinguishing MnHEP from BnHEP) in situations in which these parameters are relevant, namely for evaluating the magnitude of an hyperplastic liver response from its very early onset.

Animals↗
PubMed2006

Cost effectiveness of bemiparin sodium versus unfractionated heparin and oral anticoagulants in the acute and long-term treatment of deep vein thrombosis.

INTRODUCTION: Low-molecular-weight heparins (LMWHs) are at least as effective and well tolerated as unfractionated heparin (UFH) in the treatment of deep vein thrombosis (DVT), offering easier administration and obviating the need for anticoagulant monitoring, but have a higher acquisition cost than UFH. OBJECTIVE: To quantify the potential economic impact of two regimens of subcutaneous bemiparin 115 IU/kg/day for 7-10 days (plus oral anticoagulants [OAC] or followed by long-term bemiparin 3500IU) versus dose-adjusted intravenous UFH for 7 days plus OAC for 3 months in the acute and long-term treatment of DVT. The representative patient was a 62-year-old, 77 kg male with proximal DVT of the lower limbs. METHODS: A cost-effectiveness analysis was performed using a decision-tree modelling approach. The results were expressed in terms of costs (euro, 2002 values) and incremental cost effectiveness. The treatment costs (hospital stay, physician services, drug administration) and costs incurred due to complications (pulmonary embolism, recurrent DVT, bleeding events, thrombocytopenia and deaths) during the 3-month study period were considered for the primary analysis. Life expectancy and QALYs were considered for the secondary analysis. The study was performed in the setting of the Spanish National Health System. RESULTS: Bemiparin plus OAC or long-term bemiparin for 3 months provided net cost savings of euro 769 and euro 908 per patient, respectively, compared with UFH plus OAC (UFH plus OAC euro 4128 vs bemiparin plus OAC euro 3359 vs long-term bemiparin euro 3220). Bemiparin plus OAC and long-term bemiparin for 3 months were calculated to avoid 27 and 7 additional VTE events, respectively, per 1000 patients treated. Bemiparin plus OAC or long-term bemiparin increased quality-adjusted life expectancy by approximately 1.72 and 0.74 years, respectively, compared with UFH plus OAC. The univariate sensitivity analysis supported the cost effectiveness of bemiparin in all the ranges tested for complications and costs. CONCLUSIONS: Our model suggests that bemiparin plus OAC or long-term bemiparin for 3 months may be dominant strategies over UFH plus OAC in the treatment of DVT from the Spanish National Health System perspective, offering better outcomes and cost savings. Long-term bemiparin may be a cost-neutral alternative to bemiparin plus OAC.

Administration, Oral↗
PubMed2005

[New strategies in the secondary prevention of relapsing venous thromboembolism].

Treatment of venous thromboembolism includes an acute phase treatment, followed by a secondary prophylaxis period. Oral anticoagulants have been the usual treatment for secondary prophylaxis of VTE. However, some issues regarding oral anticoagulant treatment (OAT), such as length or intensity are controversial. The appropriate duration of OAT depends on the individual risk of both, thrombotic recurrence and hemorrhagic complications. Recent studies suggest that full-dose OAT is more effective and as safe as low-dose OAT. On the other hand, low-molecular-weight heparins are an alternative for the secondary prophylaxis of VTE, being the treatment of choice in patients with cancer or during pregnancy. Probably, new antithrombotic drugs such as idraparinux or ximelagatran, will be considered as another therapeutic alternative in a near future.

Anticoagulants↗
PubMed2005

Identification and organ expression of peroxisome proliferator activated receptors in brown trout (Salmo trutta f. fario).

Although widely studied in mammals, little information about fish peroxisome proliferator activated receptors (PPARs) is yet available. As a baseline for future studies, the three PPAR isotypes were identified in brown trout (Salmo trutta f. fario) and their organ distribution pattern was established. The cDNA fragments encoding PPARs alpha, beta and gamma were amplified by PCR, and the deduced sequences of the correspondent peptides were compared with other species sequences. Both the 183 amino acid sequence from PPARalpha and the 103 amino acid sequence from PPARbeta shared high levels of homology with the correspondent peptides of other fishes and terrestrial vertebrates, whereas PPARgamma 108 amino acid sequence showed much less similarity with non-fish PPARgamma. According to both semi-quantitative RT-PCR and real-time RT-PCR, PPARalpha mRNA predominates in white muscle, heart and liver and PPARbeta is more expressed in testis, heart, liver, white muscle and trunk kidney. PPARgamma was only detected in trunk kidney and liver by real-time RT-PCR and also in spleen by semi-quantitative RT-PCR. PPARbeta seems to be the most strongly expressed isotype, whereas PPARgamma shows a much weaker global expression.

Amino Acid Sequence↗
PubMed2005

[Decreased transfusion requirements in acquired severe bleeding with recombinant activated factor VII].

BACKGROUND AND OBJECTIVE: Patients with severe and persistent bleeding have high mortality rates despite standard therapy, including blood transfusion support. The aim of the study was to evaluate the role of rFVIIa in the management of severe bleeding, refractory to other treatments. PATIENTS AND METHODS: All cases with severe bleeding and failure of previous treatments who received rFVIIa (n = 21) at one single center were retrospectively included in the study. RESULTS: A response after the administration of rFVIIa was reported in 16 of 21 patients (76.2%). Hemorrhage was completely halted in 14 cases, and 12 patients (57.1%) were alive 30 days after treatment. The use of rFVIIa was associated with a normalization of coagulation tests, especially the prothrombin time (p = 0.001). A marked reduction in blood requirements, red cell units (p = 0.003), fresh frozen plasma (p = 0.009) and platelets (p = 0.017) was also observed. CONCLUSIONS: rFVIIa may have an important role in the achievement of an adequate hemostasis and reduces blood requirements in patients with severe bleeding, emerging as an alternative to blood transfusion.

Adult↗
PubMed2005

How essential are nonessential genes?

Gene essentiality in bacteria has been identified in silico, focusing on gene persistence, or experimentally, focusing on the growth of knockouts in rich media. Comparing 55 genomes of Firmicutes and Gamma-proteobacteria to identify the genes which, while persistent among genomes, do not lead to a lethal phenotype when inactivated, we show that the characteristics of persistence, conservation, expression, and location are shared between persistent nonessential (PNE) genes and experimentally essential genes. PNE genes show an overrepresentation of genes related to maintenance and stress response. This outlines the limits of current experimental techniques to define gene essentiality and highlights the essential role of genes implicated in maintenance which, although dispensable for growth, are not dispensable from an evolutionary point of view. Firmicutes and Gamma-proteobacteria are mostly differing in the construction of the cell envelope, DNA replication and proofreading, and RNA degradation. In addition to suggesting functions for persistent genes that had until now resisted identification, we show that these genes have many characters in common with experimentally identified essential genes. They should then be regarded as truly essential genes.

Codon↗
PubMed2005

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells.

BACKGROUND: Apoptotic death of renal proximal tubular epithelial cells (RPTECs) is a feature of acute and chronic renal failure. RPTECs are directly damaged by ischemia, inflammatory, and cytotoxic mediators but also contribute to their own demise by up-regulating proinflammatory nuclear factor-kappaB (NF-kappaB)-dependent proteins. In endothelial cells, the Bcl family member A1 and the zinc finger protein A20 have redundant and dual antiapoptotic and anti-inflammatory effects. We studied the function(s) of A1 and A20 in human RPTECs in vitro. METHODS: Expression of A1 [reverse transcription-polymerase chain reaction (RT-PCR) and A20 (Northern and Western blot analysis)] in RPTECs was evaluated. A1 and A20 were overexpressed in RPTECs by recombinant adenoviral-mediated gene transfer. Their effect upon inhibitor of NFkappaB alpha (IkappaBalpha) degradation (Western blot), NF-kappaB nuclear translocation [electrophoretic mobility shift assay (EMSA)], up-regulation of intercellular adhesion molecule-1 (ICAM-1) [fluorescence-activated cell sorter (FACS)] and monocyte chemoattractant protein-1 (MCP-1) (Northern blot) and apoptosis [terminal deoxynucleotiddyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)] and FACS analysis of DNA content) was determined. RESULTS: A1 and A20 were induced in RPTECs as part of the physiologic response to tumor necrosis factor (TNF). A20, but not A1, inhibited TNF-induced NF-kappaB activation by preventing IkappaBalpha degradation, hence subsequent up-regulation of the proinflammatory molecules ICAM-1 and MCP-1. Unexpectedly, A20 did not protect RPTECs from TNF and Fas-mediated apoptosis while A1 protected against both stimuli. Coexpression of A1 and A20 in RPTECs achieved additive anti-inflammatory and antiapoptotic cytoprotection. CONCLUSION: A1 and A20 exert differential cytoprotective effects in RPTECs. A1 is antiapoptotic. A20 is anti-inflammatory via blockade of NF-kappaB. We propose that A1 and A20 are both required for optimal protection of RPTECs from apoptosis (A1) and inflammation (A20) in conditions leading to renal damage.

Apoptosis↗
PubMed2005

Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies.

The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens.

Anticoagulants↗
PubMed2004

[Pharmacological alternatives to blood transfusion: what is new about?].

Pharmacological approaches to reduce blood transfusion include the protease inhibitor aprotinin, lysine-analogue antifibrinolytics synthetic arginine-vasopressin derivatives (DDAVP) and recombinant factor VII (rfVIIa). These agents are known to prevent the need for blood after major surgery (cardiac, hepatic, and orthopaedic). Among the nonhemostatic agents erythropoietin (EPO) may be effective to reduce blood requirements in medical and surgical patients. Aprotinin is consistently effective in reducing blood transfusion in cardiac and hepatic surgical procedures, but there is little data to support its use in elective orthopaedic surgery. Antifibrinolytics show no evidence of efficacy in cardiac and hepatic surgery and its use is not warranted in orthopaedic surgery. Limited data suggest that DDAVP may be effective when a defect in platelet function is demonstrated. rFVIIa emerges as a promising haemostatic agent with proven benefit to reduce bleeding in haemophiliacs with inhibitors but might also be effective in patients with thrombocytopenia and thrombopathy, as well as in life-threatening hemorrhage in postsurgical patients. Ongoing studies will established its role a possible "universal haemostatic agent". Hematopoietic cytokines, such as EPO, may have a place to avoid blood transfusion in a variety of clinical conditions, including cancer and critically ill patients.

Antifibrinolytic Agents↗
PubMed2004

Positron emission tomography using 18F-fluorodeoxyglucose for the evaluation of residual Hodgkin's disease mediastinal masses.

Given its obvious prognostic implications, the correct interpretation of the significance of any residual mediastinal mass following Hodgkin's disease (HD) treatment keeps maintaining its paramount importance. In this respect, 18F-fluorodeoxyglucose positron emission tomography (PET) is proving very effective for both active disease detection and relapse prediction. Twenty-nine consecutive HD patients, in whom computed tomography (CT) scan performed after therapy completion had documented a residual mediatinal mass of at least 2 cm, prospectively entered the study and underwent PET within 1 week from CT scan. With a median follow-up of 28 months from PET execution, no relapse was recorded among the 17 patients presenting with a negative PET. On the contrary, 9 of the 12 patients presenting with a positive PET relapsed/progressed within one year from PET execution. PET's negative and positive predictive values at 1 year were 100% and 75%, respectively. A negative PET seems to possibly exclude relapse in HD patient with a residual mediastinal mass. On the contrary, a positive PET result indicates a significantly higher risk of relapse. However, due to possible false positive results, a closer follow-up for all and a pathologic study in few selected patients is warranted.

False Negative Reactions↗
PubMed2004

Effects of customized bicarbonate buffered solutions for continuous renal replacement therapies on polymorphonuclear leukocytes function and viability.

It has previously been shown that the mixture of bicarbonate and calcium in the solutions used for continuous renal replacement therapy led to crystallization and significant changes in calcium concentration and pH. The aim of this study was to investigate the impact of bicarbonate/calcium and lactate/calcium solutions for Continuous Renal Replacement Therapies (CRRT) on the viability and function of polymorphonuclear cells (PMN). We tested four customized bicarbonate buffered solutions: single bag (bicarbonate and calcium mixed 24 h before testing), double bag (mixed immediately before testing), filtered single bag and double bag solutions, and a commercial lactate buffered solution. Blood from 6 volunteers was incubated with the solutions for 30 min followed by PMN isolation. After overnight incubation, viability, phagocytosis, and peroxide production by PMN were determined by flow cytometry. There was no difference between the test solutions with respect to PMN viability and function. Therefore, the presence of microcrystals and the consequent changes in electrolyte concentrations do not seem to impair PMN function.

Analysis of Variance↗