High-Sensitivity C-Reactive Protein as a Predictor of Cardiovascular Events after ST-Elevation Myocardial Infarction

Background: The association between high-sensitivity C-reactive protein and recurrent major adverse cardiovascular events (MACE) in patients with ST-elevation myocardial infarction who undergo primary percutaneous coronary intervention remains controversial. Objective: To investigate the potential association between high-sensitivity C-reactive protein and an increased risk of MACE such as death, heart failure, reinfarction, and new revascularization in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods: This prospective cohort study included 300 individuals aged >18 years who were diagnosed with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention at a tertiary health center. An instrument evaluating clinical variables and the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein was determined by nephelometry. The patients were followed-up during hospitalization and up to 30 days after infarction for the occurrence of MACE. Student's t, Mann-Whitney, chi-square, and logistic regression tests were used for statistical analyses. P values of ≤0.05 were considered statistically significant. Results: The mean age was 59.76 years, and 69.3% of patients were male. No statistically significant association was observed between high-sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high-sensitivity C-reactive protein was independently associated with 30-day mortality when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07-1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores. Conclusion: Although high-sensitivity C-reactive protein was not predictive of combined major cardiovascular events within 30 days after ST-elevation myocardial infarction in patients who underwent primary angioplasty and stent implantation, it was an independent predictor of 30-day mortality.

New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

AbstractBackground:Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity.Objectives:In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols.Methods:In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection.Results:Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001).Conclusions:The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome

Abstract Background: Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment. Objective: To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men. Methods One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay. Results: The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (psex < 0.01). Conclusions: Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.

Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test

Abstract Background: The kinetics of high-sensitivity troponin T (hscTnT) release should be studied in different situations, including functional tests with transient ischemic abnormalities. Objective: To evaluate the release of hscTnT by serial measurements after exercise testing (ET), and to correlate hscTnT elevations with abnormalities suggestive of ischemia. Methods: Patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty were referred for ET 3 months after infarction. Blood samples were collected to measure basal hscTnT immediately before (TnT0h), 2 (TnT2h), 5 (TnT5h), and 8 hours (TnT8h) after ET. The outcomes were peak hscTnT, TnT5h/TnT0h ratio, and the area under the blood concentration-time curve (AUC) for hscTnT levels. Log-transformation was performed on hscTnT values, and comparisons were assessed with the geometric mean ratio, along with their 95% confidence intervals. Statistical significance was assessed by analysis of covariance with no adjustment, and then, adjusted for TnT0h, age and sex, followed by additional variables (metabolic equivalents, maximum heart rate achieved, anterior wall STEMI, and creatinine clearance). Results: This study included 95 patients. The highest geometric means were observed at 5 hours (TnT5h). After adjustments, peak hscTnT, TnT5h/TnT0h and AUC were 59% (p = 0.002), 59% (p = 0.003) and 45% (p = 0.003) higher, respectively, in patients with an abnormal ET as compared to those with normal tests. Conclusion: Higher elevations of hscTnT may occur after an abnormal ET as compared to a normal ET in patients with STEMI.

Chromoblastomycosis murine model and in vitro test to evaluate the sensitivity of Fonsecaea pedrosoi to ketoconazole, itraconazole and saperconazole

An experimental model of murine chromoblastomycosis and in vitro tests with Fonsecaea pedrosoi were used to test the sensitivity of this fungus to three different antimycotics. The experimental model was standardized in BALB/c mice inoculated intraperitoneally with a 10(6) CFU/ml suspension of a F. pedrosoi isolate. Clinical infection was evident after 5 days of inoculation. Three groups of 27 mice each were used in the experiment. One group was treated with ketoconazole (KTZ), another with itraconazole (ITZ) and the other with saperconazole (SPZ). Antimycotic therapy was continued for 21 days. The control group consisted of 40 mice which were inoculated, but not treated. Infection was documented by macroscopic and microscopic examination of affected tissue in addition to culture of tissue macerates. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) for the F. pedrosoi strain used were done. The in vitro results showed that SPZ was the most active with MIC 0.01 mg/ml and MFC 0.1 mg/ml, followed by ITZ. SPZ was also the most effective in vivo since 63% of the treated animals (p=0.01) showed a curative effect after the observation period. We concluded that SPZ had the best in vitro and in vivo activity against F. pedrosoi.

Sensitivity of Leishmania spp. to Glibenclamide and 4-Aminopiridine: A Tool for the Study of Drug Resistance Development

We have demonstrated that Leishmania spp. grown as promastigotes, are sensitive to the K+ channel inhibitors 4-aminopyridine and glibenclamide. Their host cells, the macrophages, are not affected by similar concentrations of the drugs. We have also initiated the molecular characterization of the mechanisms involved in the development of drug resistance to glibenclamide by the parasite. Therefore, we have selected experimentally and begun to characterize the Venezuelan Leishmania (Leishmania) strain, NR resistant to glibenclamide [NR(Gr)]. The analysis of genomic DNA evidenced the existence of a fragment which apparently is amplified in NR(Gr). The fragment recognized by the pgpA probe, related to the Leishmania P-glycoprotein family and which was originally isolated from L. tarentolae, showed a size polymorfism between the sensitive and the resistant strain. These results suggest that the development of resistance to glibenclamide in the strain NR(Gr) might be associated with the amplification of the ltpgpA or related gene(s)

Quantitation of HIV-1 RNA Viral Load Using NASBA Methodology and Comparison with other Surrogate Markers for Disease Progression

In this study, HIV-1 viral load quantitation determined by Nucleic Acid Sequence Based Amplification (NASBA) was compared with other surrogate disease progression markers (antigen p24, CD4/CD8 cell counts and b-2 microglobulin) in 540 patients followed up at São Paulo, SP, Brazil. HIV-1 RNA detection was statistically associated with the presence of antigen p24, but the viral RNA was also detected in 68% of the antigen p24 negative samples, confirming that NASBA is much more sensitive than the determination of antigen p24. Regarding other surrogate markers, no statistically significant association with the detection of viral RNA was found. The reproducibility of this viral load assay was assessed by 14 runs of the same sample, using different reagents batches. Viral load values in this sample ranged from 5.83 to 6.27 log (CV = 36 %), less than the range (0.5 log) established to the determination of significant viral load changes.

The stabilizing effects of the acquired immunity on the schistosomiasis transmission modeling - the sensitivity Analysis

A mathematical model is proposed to analyze the effects of acquired immunity on the transmission of schistosomiasis in the human host. From this model the prevalence curve dependent on four parameters can be obtained. These parameters were estimated fitting the data by the maximum likelihood method. The model showed a good retrieving capacity of real data from two endemic areas of schistosomiasis: Touros, Brazil (Schistosoma mansoni) and Misungwi, Tanzania (S. haematobium). Also, the average worm burden per person and the dispersion of parasite per person in the community can be obtained from the model. In this paper, the stabilizing effects of the acquired immunity assumption in the model are assessed in terms of the epidemiological variables as follows. Regarded to the prevalence curve, we calculate the confidence interval, and related to the average worm burden and the worm dispersion in the community, the sensitivity analysis (the range of the variation) of both variables with respect to their parameters is performed.

Age-related worm load and worm fecundity patterns in human populations, as indicated by schistosome circulating antigens

Recently, our group determined the relationship between serum CAA levels and fecal egg counts in two foci with very intense Schistosoma mansoni transmission: Maniema (Zaire), an area endemic for S. mansoni since several decades, and Ndombo (Senegal), where transmission has only been established since a few years. The objective was to study and compare age-related worm load and worm fecundity patterns in these two different endemic settings. Here, we will summarize the most important findings and conclusions of this study.

Sensitivity of a Vacuum Aspiratory Culture Technique for Diagnosis of Localized Cutaneous Leishmaniasis in an Endemic Area of Leishmania (Viannia) braziliensis Transmission

Sixty eight patients with localized cutaneous leishmaniasis from an area with Leishmania (Viannia) braziliensis transmission had cultures performed with a modified Marzochi´s vacuum aspiratory puncture technique to establish sensitivity and contamination rate with this new method. Overall sensitivity of three aspirates was 47.1%; (CI95% 39.4; 59.4) significantly greater than the sensitivity of a single one aspirate. Fungal contamination was observed in 6/204 (2.9%) inoculated culture tubes. We recommend that this useful technique should be adopted as routine for primary isolation of L. (V.) braziliensis from localized cutaneous ulcers.

Sensitivity of Lymph Node Aspiration in Localized Cutaneous Leishmaniasis Due to Leishmania (Viannia) braziliensis

Twenty nine patients with localized cutaneous leishmaniasis had lymph node and skin ulcer aspirations for culture of Leishmania with the modified Marzochi´s vacuum aspiratory technique. Sensitivity of lymph node aspiration was 58.6% and 34.5% for skin ulcer aspiration (P=0.06). Combined sensitivity of the two methods was 79.3%. There was no agreement between methods (Kappa Index = -0.084; CI95% -0,45; 0,28) showing the potential complementary roles in diagnostic approach.

Worm load and septal fibrosis of the liver in Capillaria hepatica-infected rats

Inocula, varying from 15 to 1,000 embryonated Capillaria hepatica eggs, were administered to young adult rats by gastric tube, in an attempt to investigate the influence of worm load in the production of septal fibrosis of the liver. Low doses of 15, 30 or 50 eggs were sufficient to produce septal fibrosis, but it appeared with variable degrees of intensity and always with focal distribution. Septal fibrosis became diffuse, progressive with time, and already well developed 40 days after infection, when 100 eggs or more were administered. However, higher inocula (200, 500 and 1,000 eggs) did not intensify septal fibrosis, although the number of parasitic focal lesions proportionally augmented.

Changes on Schistosoma mansoni (Digenea: Schistosomatidae) worm load in Nectomys squamipes (Rodentia: Sigmodontinae) concurrently infected with Echinostoma paraensei (Digenea: Echinostomatidae)

The water rat, Nectomys squamipes, closely involved in schistosomiasis transmission in Brazil, has been found naturally infected simultaneously by Schistosoma mansoni and Echinostoma paraensei. Laboratory experiments were conducted to verify parasitic interaction in concurrent infection. It was replicated four times with a total of 42 water rats and essayed two times with 90 mice pre-infected with E. paraensei. Rodents were divided into three groups in each replication. A wild strain recently isolated from Sumidouro, RJ, and a laboratory strain of S. mansoni from Belo Horizonte (BH) was used. Rats infected with E. paraensei were challenged 4 weeks later with S. mansoni and mice 2 or 6 weeks after the infection with S. mansoni. Necropsy took place 8 weeks following S. mansoni infection. The N. squamipes treatment groups challenged with S. mansoni RJ strain showed a significant decrease (80 and 65%) in the S. mansoni parasite load when compared with their respective control groups. There was a significant change or no change in the hosts challenged with the BH strain. The persistence time of E. paraensei within host was extended in relation to control groups, with a consequent enhancement of the number of recovered worm. An E. paraensei strain-specific influence on S. mansoni parasitism is reported. This paper presents some experimental data about this interaction in N. squamipes and Mus musculus.