The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction

OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators may be beneficial in heart failure due to their metabolic and antihypertrophic effects, but these agents can cause oedema. We hypothesized that, on balance, the PPARgamma activator rosiglitazone would be beneficial in heart failure post-myocardial infarction. METHODS AND RESULTS: Rosiglitazone (3 mg/kg/day p.o.) given to male Wistar rats for 14 days, caused a 31% increase in left ventricular (LV) dP/dt(max) (P<0.05 vs. placebo). A separate group of rats was subjected to sham (SH) or coronary artery ligation and randomised to: untreated (UT); rosiglitazone 3 mg/kg/day (R); captopril, 2 g/l in drinking water (C); captopril+rosiglitazone (C+R). Mean LV infarct sizes were similar for all groups at 40+/-2%. After 8 weeks, echocardiographic ejection fractions were 82+/-3, 40+/-3, 50+/-2*, 49+/-2, 50+/-3% for SH, UT, R, C and C+R groups, respectively (*P<0.05 vs. UT). Captopril prevented LV dilatation, but rosiglitazone did not. In vivo hemodynamics showed that only UT had significantly elevated LV end-diastolic pressures and reduced +dP/dt(max), with R partially, and C and C+R almost completely preventing the increase in LVEDP. Captopril, but not rosiglitazone, significantly reduced LV hypertrophy [LV/bw; 1.97+/-0.09 (SH), 2.15+/-0.04 (UT), 2.10+/-0.05 (R), 1.81+/-0.04* (C), 1.88+/-0.07 (C+R); *(P<0.05 vs. UT)]. Rosiglitazone increased 8-week mortality, which was 26% for R and 19% for C+R compared with 0% for UT and C (P=0.03 vs. UT). CONCLUSIONS: Rosiglitazone did not modulate LV remodeling, but was associated with increased mortality post-myocardial infarction (MI) in rats. The mechanisms require further study, but these results caution against use of PPARgamma activators in post-MI heart failure in non-diabetics.     

Factors associated with accurate self-reported adherence to HIV antiretrovirals

The purpose of this study was to determine the conditions in which self-reports provide an accurate assessment of adherence to HIV antiretrovirals. In a sample of 58 participants, self-reported and electronically monitored adherence to antiretroviral therapy were compared over a three-day period. Of the 16 who reported missed doses, only six (38%) accurately reported the number of doses they took, although the electronic monitoring data confirmed that all but one (94%) did in fact miss at least one dose. In contrast, 25 (60%) of the 42 participants who reported no missed doses were accurate. Nearly all (96%) participants who actually did take all their doses accurately reported their adherence compared to only 20% of those who missed at least one dose (P<0.001). Cognitive functioning was marginally associated with self-report accuracy, but all other baseline factors were not associated with accuracy. Our findings highlight the need for more effective self-report methodology and a better understanding of the circumstances in which self-reports are valid measures of adherence.     

Effectiveness of dexamethasone iontophoresis for temporomandibular joint involvement in juvenile idiopathic arthritis

Objective

Temporomandibular joint (TMJ) involvement is common in juvenile idiopathic arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low‐grade electric currents for transdermal dexamethasone delivery into deeper anatomic structures. The purpose of this study was to assess the safety and effectiveness of DIP for the treatment of TMJ involvement in JIA, and to delineate variables that are associated with improvement after DIP.

Methods

Medical records of all JIA patients who underwent DIP for TMJ involvement at a larger tertiary pediatric rheumatology center from 1997–2011 were reviewed. DIP was performed using a standard protocol. The effectiveness of DIP was assessed by comparing the maximal interincisor opening (MIO_TMJ) and the maximal lateral excursion (MLE_TMJ) before and after treatment.

Results

Twenty‐eight patients (ages 2–21 years) who received an average of 8 DIP treatment sessions per involved TMJ were included in the analysis. Statistically significant improvement in the median MIO_TMJ (P < 0.0001) was observed in 68%. The median MLE_TMJ (P = 0.03) improved in 69%, and resolution of TMJ pain occurred in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were transient site erythema (86%), skin blister (4%), and metallic taste (4%). Improvement in TMJ range of motion from DIP is associated with lower MIO_TMJ, lower MLE_TMJ, and absence of TMJ crepitus at baseline.

Conclusion

In this pilot study, DIP appeared to be an effective and safe initial treatment of TMJ involvement in JIA, especially among patients with decreased TMJ measurements. Prospective controlled studies are needed.     

Insecticide resistance status of Aedes aegypti in 10 localities in Colombia

Insecticide resistance is one of the major threats to the effectiveness of vector control programs. In order to establish a baseline susceptibility profile of Aedes aegypti in the southwest of Colombia, 10 localities in four Departments (States) were evaluated. Standardized WHO bioassay, CDC bottle bioassay and microplate biochemical assays of non-specific β-esterase (NSE), mixed function oxidases (MFO) and acetylcholinesterase were used. Cross resistance was evaluated with field collected mosquitoes that underwent selection pressure in the laboratory from DDT, propoxur and lambdacyhalothrin during three alternate generations. Mosquitoes with mortality rates below 80% in bioassays were considered resistant. Insecticide resistance varied geographically. Insecticide resistance was observed in 100% of localities in which mosquitoes were exposed to DDT, bendiocarb and temephos using both assays. WHO bioassays showed susceptibility to pyrethroids in all the localities evaluated, however CDC bottle bioassays showed decreases in susceptibility especially with lambdacyhalothrin. All localities showed susceptibility to the organophosphate malathion. Mosquitoes from eight regions with evidence of resistance to any of the insecticide evaluated were also evaluated biochemically. Mosquitoes from five of these regions had increased levels of NSE and two regions had increased levels of MFO. Increase levels of NSE explain partially the low susceptibility to temephos found in all the localities. However, the biochemical mechanisms evaluated do not explain all the resistance observed. Cross resistance was observed between the DDT-selected strain and lambdacyhalothrin, and between the lambdacyhalothrin-selected strain and propoxur and vice versa. The selected strains do not show changes in the biochemical assays evaluated, therefore the observed cross-resistance suggests different biochemical mechanisms. This study shows that Ae. aegypti from Colombia can develop resistance to most of the insecticide classes in the market. Periodic surveillance of insecticide resistance is necessary in order to maintain effective interventions. This study helped to establish the National Network for the surveillance of the insecticide resistance in Colombia.     

Modulation of aldosterone release by epidural analgesia impacts brain natriuretic peptide: a link to stress cardiomyopathy? Pilot study

Objective Data pertaining to whether stress‐induced aldosterone release is associated with cardiac disorders are lacking. This study was designed to compare whether the modulation of intra‐operative aldosterone release by epidural analgesia had an effect on the brain natriuretic peptide (BNP) levels. Design, Patients, Measurements A study was pilot prospective, open label randomized one. Patients were randomized to one of two anaesthesia protocols: group 1 included 13 patients who received general anaesthesia, and group 2 included 12 patients who received combined general anaesthesia and epidural analgesia. Study protocol was by completed 25 male patients, median age 56 years, without significant comorbidities, who underwent radical cystectomy because of urinary bladder tumour. Serum aldosterone, BNP, cortisol (measured by radioimmunoassay), adrenocorticotropine hormone (ACTH) (by solid‐phase ELSA), blood chemistry, complete blood count and vital signs were compared preoperatively, intra‐operatively and at postoperative days (POD) 1 and 7. Results Hemodynamics was stable in both groups. Group 1 showed threefold serum aldosterone, (P = 0·001) 20‐fold ACTH (P = 0·003) and twofold cortisol (P = 0·001) increases intra‐operatively, unlike group 2. Both groups had a twofold BNP increase in POD 1 that remained above normal on POD 7 only in group 1 (P = 0·02; P = 0·019 vs group 2). Conclusion Alleviation of aldosterone release by epidural analgesia modulated the postoperative serum BNP pattern in patients with a low risk for cardiac diseases who underwent noncardiac surgery.     

Two‐year evolution of latent rheumatic heart disease in Malawi

Background: In asymptomatic children, screening echocardiography has been used to attempt to diagnose rheumatic heart disease (RHD) at an early stage (latent RHD). World Heart Federation guidelines have standardized categorization of “definite,” “borderline,” or no RHD by echo findings. The progression of RHD diagnosed through echo screening is not known. In 2014, we screened 1450 schoolchildren in Malawi.
Objective: Our objective was to evaluate 2‐year RHD evolution among those diag‐nosed through screening.
Methods: Two‐year follow‐up echocardiograms of those diagnosed with latent RHD were read by a primary, secondary, then third reader if there was disagreement. Progression or regression of both definite and borderline groups were tabulated. Penicillin adherence, age, gender, number in home, and household income were com‐pared between those with definite RHD who regressed to borderline and those that stayed definite. We utilized the local system used to track HIV defaulters in order to bring participants back into care. Comparisons were made using Fisher’s exact and Wilcoxon rank‐sum tests.
Results: Of the 39 with borderline RHD, 1 was lost to follow‐up (2.6%), 1 progressed to definite (2.6%), 19 remained borderline (48.7%), 17 (43.6%) regressed to normal, and 1 was reclassified as mitral valve prolapse (2.6%). Of the 11 with definite RHD, 6 (54.5%) remained definite, 4 regressed to borderline (36.4%), and 1 regressed to nor‐mal (9.1%). Two of 11 with definite RHD had penicillin adherence above 80% for the 2‐year follow‐up period. There were no differences in adherence, gender, age, house‐hold income, or number in household between those with definite RHD that re‐gressed to borderline and those who did not (P > .19).
Conclusions: Borderlines had a very low progression rate to definite RHD. A strength of our study was a high retention rate (98%). Longer follow‐up is needed to determine expected disease evolution.     

Fibromyxoid sarcoma of the kidney. A case report

Low grade fibromyxoid sarcoma is an uncommon soft tissue tumor. We present the case of a 83-year-old female who developed large mass in the right kidney. A nephrectomy was performed. The tumor measured 18,5x17,5x11,5 cm and on pathology evaluation was diagnosed as low grade fibromyxoid sarcoma. Currently, the patient is doing well without evidence of local recurrence and distant metastasis. Low grade fibromyxoid sarcoma of the Kidney is a very rare tumor. The metastasizing potential is high. Sometimes long interval between tumor presentation and metastasis is observed. The treatment of choice is surgery. The role of radiotherapy and chemotherapy is uncertain.     

Leukotriene B4 in exhaled breath condensate and sputum supernatant in patients with COPD and asthma

STUDY OBJECTIVES: Some patients with COPD present with significant reversibility of airflow limitation after receiving bronchodilation therapy. Leukotriene B(4) (LTB(4)) has been implicated in the pathophysiology of both COPD and asthma. We tested the hypothesis that COPD patients with airflow reversibility and asthmatic patients who smoke might have similar levels of LTB(4) in exhaled breath condensate (EBC) and sputum supernatant. The repeatability and stability of LTB(4) measurements were additionally studied. DESIGN: Prospective, cross-sectional study. PATIENTS OR PARTICIPANTS: We studied 30 patients with COPD (15 smokers [FEV(1), 56% predicted; SD, 6% predicted]; 15 patients with significant reversibility in airway obstruction after bronchodilation [FEV(1), 14% predicted; SD, 2% predicted]). Fifteen asthmatic patients who smoked, with similar FEV(1) and reversibility were also studied. Ten healthy smokers served as control subjects. SETTING: A hospital research laboratory. INTERVENTIONS: Spirometry and reversibility testing were performed on the first visit. On the following day, EBC was collected for the measurement of LTB(4), and induced sputum was collected for differential cell counts and LTB(4) measurement in the sputum supernatant. MEASUREMENTS AND RESULTS: LTB(4) levels in EBC [mean (SD)] were increased in COPD patients (mean, 86.7 pg/mL; SD, 19 pg/mL) and asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL) compared to control subjects (mean, 32.3 pg/mL; SD, 10 pg/mL; p < 0.0001 for both groups). COPD patients with airflow reversibility (mean, 99.8 pg/mL; SD, 12 pg/mL) had values similar to those of asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL; p = 0.2) and higher than those of COPD patients without airflow reversibility (mean, 73.7 pg/mL; SD, 17 pg/mL; p = 0.002). Similar results were observed in the sputum supernatant. Measurements of LTB(4) in EBC and sputum were repeatable on two consecutive days, but measurements in the frozen samples of EBC and sputum were not stable after 3 weeks. CONCLUSIONS: Patients with asthma and reversible COPD presented with higher LTB(4) values compared to patients with nonreversible COPD and healthy smokers. This difference may be mainly attributed to the presence of reversibility in airway obstruction, probably as part of a common underlying inflammatory process.