Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization

Abstract Background: The high prevalence of atrial fibrillation (AF) in the postoperative period of myocardial revascularization surgery increases morbidity and mortality. Objective: To assess the efficacy of colchicine to prevent AF in the postoperative period of myocardial revascularization surgery, the impact of AF on hospital length of stay and death, and to identify its risk factors. Methods: Between May 2012 and November 2013, 140 patients submitted to myocardial revascularization surgery were randomized, 69 to the control group and 71 to the colchicine group. Colchicine was used at the dose of 1 mg orally, twice daily, preoperatively, and of 0.5 mg, twice daily, until hospital discharge. A single dose of 1 mg was administered to those admitted 12 hours or less before surgery. Results: The primary endpoint was AF rate in the postoperative period of myocardial revascularization surgery. Colchicine group patients showed no reduction in AF incidence as compared to control group patients (7.04% versus 13.04%, respectively; p = 0.271). There was no statistically significant difference between the groups regarding death from any cause rate (5.6% versus 10.1%; p = 0,363) and hospital length of stay (14.5 ± 11.5 versus 13.3 ± 9.4 days; p = 0.490). However, colchicine group patients had a higher infection rate (26.8% versus 8.7%; p = 0.007). Conclusion: The use of colchicine to prevent AF after myocardial revascularization surgery was not effective in the present study. Brazilian Registry of Clinical Trials number RBR-556dhr.

Miocardite no macaco Cebus após inoculações repetidas com Schizotrypanum cruzi

Transmission of Chagas disease is realized through contamination of ocular conjunctiva, mucosa or skin with infected dejections eliminated by the insect vectors of Schizotrypanum cruzi (Triatoma infestans, Panstrongylus megistus and Rhodnius prolixus). The triatomid bugs live in holes and craks in the walls, in beds, behind trunks, etc. Found in primitive mud huts covered with thatched roofs, and so the human dwellers have many chances to contract the disease, reinfections being reasonably more to expect than a single inoculation. Experimental work reproducing those natural conditions is welcomed as some important features in the pathologic picture of the disease such as the extensive myocardial fibrosis seen in chronic cases are still incompletely known. Microscopic changes were studied in the heart muscle of seven Cebus monkeys infected by S. cruzi. This animal survives the acute stage of the disease and so is particularly suited to experiments of long duration in which several inoculations of S. cruzi are performed. Three different strains of S. cruzi isolated from acute cases of Chagas' disease were employed. One monkey was injected in the skin with infected blood and necropsied after 252 days. Two monkeys were three times, and one, eight times infected in skin, one of them with contaminated blood, and two with contaminated blood and dejections from infected bugs. The necropsies were performed after 35, 95 and 149 days. One monkey was three times inoculated through the intact ocular conjunctiva (one time with infected blood, two times with dejections from infected bugs), and one time through the wounded buccal mucosa, and necropsied after 134 days. Another monkey was six times inoculated, four times through the intact ocular conjunctiva (one time with contaminated blood, three times with dejections from infected bugs) and two times injected in the skin with infected blood, and necropsied after 157 days. Finally, another monkey was nine times inoculated, four times through the intact ocular conjunctiva (one time with infected blood, and three times with dejections from infected bugs), and five times injected in the skin (four times with contaminated blood, and one time with dejections from infected bugs), and necropsied after 233 days. The microscopic picture was uniform presenting, however, considerable individual variations, and was represented by diffuse interstitial myocarditis, frequently more (marked in the right ventricle base of the heart), accompanied by lymphatic stasis. The infiltration consists of macrophages, plasma cells and lymphocytes, the cellular reaction having sometimes a perivascular distribution, involving the auriculo-ventricular system of conduction, endocardium, epicardium and cardiac sympathetic gangliae. The loss of cardiac muscle fibers was always minimal. Leishmanial forms of S. cruzi in myocardial fibers are scanty and, in two cases, absent. Fatty necrosis in the epicardium was noted in two cases. Obliterative changes of medium-sized branches of coronary arteries (hypersensitivity reaction?) and multiple infarcts of the myocardium was found in one instance. The diffuse myocarditis induced by S. cruzi in several species of monkeys of the genus Cebus observed after 233 days (several inoculations) and 252 days (single inoculation) is not associated with disseminated fibrosis such as is reported in chronic cases of Chagas' disease. Definite capacity of reversion is another characteristic of the interstitial myocarditis observed in the series of Cebus monkeys here studied. The impression was gained that repeated inoculation with S. cruzi may influence the myocardial changes differently according to the period between the reinoculations. A short period after the first inoculation is followed by more marked changes, while long periods are accompanied by slight changes, which suggests an active immunisation produced by the first inoculation. More data are required, however before a definite statement is made on this subject considering that individual variations, the natural capacity of reversion of the interstitial myocarditis and the employement of more than a species of Cebus monkeys probably exerts influence also in the results here reported.

Tumor necrosis factor-α in human American tegumentary leishmaniasis

Tumor necrosis factor-alpha (TNF-α) is a cytokine produced by activated macrophages and other cells. In order to verify whether the serum levels of TNF-α in American tegumentary leishmaniasis patients are associated with the process of cure or aggravation of the disease, 41 patients were studied: 26 cases of cutaneous leishmaniasis (CL) and 15 of mucocutaneous leishmaniasis (MCL). During active disease the serum levels of TNF-α of MCL patients were significantly higher than those of CL patients and control subjects (healthy individuals and cutaneous lesions from other etiologies). The MCL patients had serum titers of TNF-α significantly lower at the end of antimonial therapy than before therapy. After a six-month follow-up, the MCL patients had serum levels of TNF-α similar to those observed at the end of the therapy as well as to those of CL patients and control subjects. No significant variation in the serum levels of TNF-α was observed in CL patients throughout the study period (before, at the end of therapy and after a six-month follow-up). The possible relationship between the high TNF-α serum levels and severity of the disease is discussed.

Detection of circulant tumor necrosis factor-alpha , soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever

Pro-inflammatory cytokines are believed to play an important role in the pathogenesis of dengue infection. This study reports cytokine levels in a total of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha (TNF-alpha) levels in sera which were statistically higher than those recorded for controls. In contrast, only one out of 16 patients with mild manifestations had elevated TNF-alpha levels. The levels of interleukin-6 (IL), IL-1beta tested in 24 samples and IL-12 in 30 samples were not significantly increased. Interferon-g was present in 10 out of 30 patients with dengue. The data support the concept that the increased level of TNF-alpha is related to the severity of the disease. Soluble TNF receptor p75 was found in most patients but it is unlikely to be related to severity since it was found with an equivalent frequency and levels in 15 patients with dengue fever and another 15 with dengue hemorrhagic fever.

Increased plasma levels of tumor necrosis factor-alpha in asymptomatic/"indeterminate" and Chagas disease cardiomyopathy patients

We compared plasma tumor necrosis factor-alpha (TNF-alpha) levels among asymptomatic/"indeterminate" Chagas disease patients (ASY) and patients across the clinical spectrum of chronic Chagas disease cardiomyopathy (CCC). Idiopathic dilated cardiomyopathy (DCM) patients and normal controls (NC) were included as controls. ASY Chagas disease patients had significantly higher plasma TNF-alpha levels than NC. TNF-alpha levels among severe CCC patients with significant left ventricular (LV) dysfunction were similar to those of DCM patients, showing average 2-fold higher levels than CCC patients without LV dysfunction and ASY patients, and 8-fold higher levels than NC. In Chagas disease, chronic TNF-a production prior to heart failure may play a role in CCC progression.

The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion

A major goal in the treatment of acute ischemia of a vascular territory is to restore blood flow to normal values, i.e. to "reperfuse" the ischemic vascular bed. However, reperfusion of ischemic tissues is associated with local and systemic leukocyte activation and trafficking, endothelial barrier dysfunction in postcapillary venules, enhanced production of inflammatory mediators and great lethality. This phenomenon has been referred to as "reperfusion injury" and several studies demonstrated that injury is dependent on neutrophil recruitment. Furthermore, ischemia and reperfusion injury is associated with the coordinated activation of a series of cytokines and adhesion molecules. Among the mediators of the inflammatory cascade released, TNF-alpha appears to play an essential role for the reperfusion-associated injury. On the other hand, the release of IL-10 modulates pro-inflammatory cytokine production and reperfusion-associated tissue injury. IL-1beta, PAF and bradykinin are mediators involved in ischemia and reperfusion injury by regulating the balance between TNF-alpha and IL-10 production. Strategies that enhance IL-10 and/or prevent TNF-alpha concentration may be useful as therapeutic adjuvants in the treatment of the tissue injury that follows ischemia and reperfusion.

Serial measurement of the circulating levels of tumour necrosis factor and its soluble receptors 1 and 2 for monitoring leprosy patients during multidrug treatment

Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host response to the aetiologic agent, Mycobacterium leprae . The induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, primarily through the action of cytokines. The purpose of the present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages of multidrug treatment (MDT) in comparison with non-infected individuals and to determine their role as putative biomarkers of the severity of leprosy or the treatment response. ELISA was used to measure the levels of these molecules in 30 healthy controls and 37 leprosy patients at the time of diagnosis and during and after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in infected individuals in comparison with controls. The levels of TNF-α, but not sTNF-R2, decreased with treatment. The current results corroborate previous reports of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the control of this cytokine during MDT.

Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

Tumour necrosis factor -308 and -238 promoter polymorphisms are predictors of a null virological response in the treatment of Brazilian hepatitis C patients

Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.

Overweight And Obesity Repercussion In The Postoperative Of Myocardial Revascularization Surgery

This is a descriptive, retrospective study with cross-sectional quantitative approach, which aimed to relate the body mass index with events in the postoperative period of the myocardial revascularization surgery with use of extracorporeal circulation. The data collection period was between April and June/2012. Patients were divided according to the body mass index and classified as without excess of weight, overweight or obese. The data analysis was based on the descriptive statistics. The patients without excess of weight had more complications, especially those related to the lungs. Among overweight and obese individuals, the cardiovascular complications stood out. The obese subjects had the worse prognostic. Obesity and overweight did not have statistically significant association with a higher frequency of postoperative complications, in spite of the occurrence of cardiovascular complications in this group. The patients without excess of weight had higher risks of developing neurological events.


Arterial hypertension and associated factors in patients submitted to myocardial revascularization

OBJECTIVE To identify the prevalence of arterial hypertension and associated factors in patients submitted to myocardial revascularization. METHOD Cross-sectional study using the database of a hospital in São Paulo (SP, Brazil) containing 3010 patients with coronary artery disease submitted to myocardial revascularization. A multiple logistic regression was performed to identify variables independently associated with hypertension (statistical significance: p<0.05). RESULTS Prevalence of hypertension was 82.8%. After the variables were adjusted, the associated factors were as follows: age, odds ratio (OR): OR=1.01; 95% confidence interval (CI): CI:1.00-1.02; female gender: (OR=1.77;CI:1.39-2.25); brown-skin race: (OR=1.53;CI:1.07-2.19); obesity: (OR=1.53;CI:1.13-2.06); diabetes: (OR=1.90;CI:1.52-2.39); dyslipidemia: (OR=1.51;CI:1.23-1.85); and creatinine>1.3: (OR=1.37;CI:1.09-1.72). CONCLUSION A high prevalence of arterial hypertension and association with both non-modifiable and modifiable factors was observed.

Selection of shrimp breeders free of white spot syndrome and infectious hypodermal and hematopoietic necrosis

The objective of this work was to select surviving breeders of Litopenaeus vannamei from white spot syndrome virus (WSSV) outbreak, adapted to local climatic conditions and negatively diagnosed for WSSV and infectious hypodermal and hematopoietic necrosis virus (IHHNV), and to evaluate if this strategy is a viable alternative for production in Santa Catarina, Brazil. A total of 800 males and 800 females were phenotypically selected in a farm pond. Nested-PCR analyses of 487 sexually mature females and 231 sexually mature males showed that 63% of the females and 55% of the males were infected with IHHNV. Animals free of IHHNV were tested for WSSV, and those considered double negative were used for breeding. The post-larvae produced were stocked in nine nursery tanks for analysis. From the 45 samples, with 50 post-larvae each, only two were positive for IHHNV and none for WSSV. Batches of larvae diagnosed free of virus by nested-PCR were sent to six farms. A comparative analysis was carried out in growth ponds, between local post-larvae and post-larvae from Northeast Brazil. Crabs (Chasmagnathus granulata), blue crabs (Callinectes sapidus), and sea hares (Aplysia brasiliana), which are possible vectors of these viruses, were also evaluated. The mean survival was 55% for local post-larvae against 23.4% for post-larvae from the Northeast. Sea hares showed prevalence of 50% and crabs of 67% of WSSV.

Myocardial perfusion scintigraphy in the detection of silent ischemia in asymptomatic diabetic patients

OBJECTIVE: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1) and type 2 diabetes mellitus (DM2) without previous diagnoses of coronary artery disease (CAD) or cerebral infarction. MATERIALS AND METHODS: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2) underwent myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS). They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. RESULTS: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). CONCLUSION: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia.

Optimization of OSEM parameters in myocardial perfusion imaging reconstruction as a function of body mass index: a clinical approach

AbstractObjective:The present study is aimed at contributing to identify the most appropriate OSEM parameters to generate myocardial perfusion imaging reconstructions with the best diagnostic quality, correlating them with patients' body mass index.Materials and Methods:The present study included 28 adult patients submitted to myocardial perfusion imaging in a public hospital. The OSEM method was utilized in the images reconstruction with six different combinations of iterations and subsets numbers. The images were analyzed by nuclear cardiology specialists taking their diagnostic value into consideration and indicating the most appropriate images in terms of diagnostic quality.Results:An overall scoring analysis demonstrated that the combination of four iterations and four subsets has generated the most appropriate images in terms of diagnostic quality for all the classes of body mass index; however, the role played by the combination of six iterations and four subsets is highlighted in relation to the higher body mass index classes.Conclusion:The use of optimized parameters seems to play a relevant role in the generation of images with better diagnostic quality, ensuring the diagnosis and consequential appropriate and effective treatment for the patient.