Executive dysfunction in children and adolescents with temporal lobe epilepsy: Is the Wisconsin Card Sorting Test enough?

The Wisconsin Card Sorting Test (WCST) is the gold standard in the evaluation of executive dysfunction (ED) in patients with temporal lobe epilepsy (TLE). We evaluated 35 children with TLE and 25 healthy controls with the WCST and with a more comprehensive battery. Among the children with TLE, 77.14% showed impairment on the WCST. On other tests (Wechsler Intelligence Scale for Children-Digit Forward, Matching Familiar Figures Test, Trail Making Test, Word Fluency, Finger Windows, and Number-Letter Memory), impairment was demonstrated in 94.29%. The authors concluded that the WCST is a good paradigm to measure executive impairment in children with TLE: however, it may be not enough. Evaluation performed only with the WCST not only underestimated the number of patients with ED, but also missed relevant information regarding the type of ED. (C) 2009 Elsevier Inc. All rights reserved.

A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms

Background: Little is known about the treatment of depression in older patients with heart failure. This Study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. Methods: We enrolled 72 older outpatients with ejection fraction < 50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. Results: A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05 + 9.74 vs 9.44 + 9.25, P = .082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. Conclusion: Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure. (C) 2009 Elsevier Inc. All rights reserved.

Failure of Imiquimod 5% Cream to Prevent Recurrence of Surgically Excised Trunk Keloids

Keloids are characterized by benign proliferation of fibroblasts in the setting of an altered cytokine profile, with a high recurrence rate after surgical treatment. Imiquimod is a topically applied immune-response modifier. Recently, auxiliary therapy using imiquimod 5% cream to prevent keloid recurrence after excisional surgery was reported to have had good results. To evaluate the efficacy of topical imiquimod 5% cream applied after surgical excision and primary closure of trunk keloids in the prevention of recurrence. Nine patients with a keloid lesion on the trunk were treated with surgical excision and primary closure. Daily application of imiquimod 5% cream for 8 weeks was initiated the night of surgery. The patients were evaluated 2, 4, 8, 12, and 20 weeks after. Keloid recurrence occurred in eight patients, seven of them 12 weeks after surgery. We lost track of one patient. The results of this study suggest that imiquimod 5% cream is not effective in preventing recurrence of trunk keloids after surgical excision. Although this is a small case series, results strongly discourage other studies using imiquimod 5% cream in the prevention of surgically excised trunk keloids. The authors have indicated no significant interest with commercial supporters.

Cavopulmonary anastomosis improves left ventricular assist device support in acute biventricular failure

Objective: Right ventricular failure during left ventricular assist device (WAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on right ventricular loading and WAD performance in a model of severe biventricular failure. Methods: LVAD support was performed by means of centrifugal pump implantation in 14 anesthetized dogs (20-30 kg) with severe biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to classical cavopulmonary anastomosis (Glenn shunt) or to control group and were maintained under WAD support for 2 h. Left and right atrial, right ventricular and systemic pressures were monitored, white total pulmonary flow was simultaneously recorded by transonic flowmeters located on the superior vena cava and pulmonary trunk. Blood gas and venous lactate determinations were also obtained. Results: Ventricular fibrillation maintenance resulted in acute WAD performance impairment after 90 min in the control group, while animals with Glenn circuit maintained normal WAD pump flow (55 +/- 13 ml kg(-1) min(-1) vs 21 +/- 4 ml kg(-1) min(-1), p < 0.001) and better peripheral perfusion (blood lactate of 29 +/- 10 pg/ml vs 46 +/- 9 pg/ml, p < 0.001). Left and right atrial pressures did not change significantly, while right ventricular pressure was tower in animals with Glenn circuit (13 +/- 3 mmHg vs 22 +/- 8 mmHg, p = 0.005). Right ventricular unloading with Glenn shunt also resulted in superior total pulmonary flow (59 +/- 13 ml kg(-1) min(-1) vs 17 +/- 3 ml kg(-1) min(-1), p < 0.001). Conclusion: The concomitant use of cavopulmonary anastomosis during LVAD support in a model of severe biventricular failure limited right ventricular overloading and resulted in better hemodynamic performance. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Assessment of a New Experimental Model of Isolated Right Ventricular Failure

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

Improvements in the 6-Min Walk Test and Spirometry Following Thoracentesis for Symptomatic Pleural Effusions

Background: Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. Methods: Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV, were analyzed before and 48 h after the removal of large pleural effusions. Results: The mean fluid removed was 1,564 +/- 695 mL. After the procedure, values of FVC, FEV and 6-min walk distance increased (P<.001), whereas dyspnea decreased (P<.001). Statistical correlations (P<.001) between 6-min walk distance and FVC (r=0.725) and between 6-min walk distance and FEV, (r=0.661) were observed. Correlations also were observed between the deltas (prethoracentesis X postthoracentesis) of the 6-min walk test and the percentage of FVC (r=0.450) and of FEV, (r=0.472) divided by the volume of fluid removed (P<.05). Conclusion: In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities. CHEST 2011; 139(6):1424-1429

Percutaneous Laser Ablation of Sacrococcygeal Teratoma in a Hydropic Fetus with Severe Heart Failure - Too Late for a Surgical Procedure?

Sacrococcygeal teratoma (SCT) is the commonest solid fetal tumor. Perinatal prognosis is usually favorable, but sometimes it can be complicated by fetal hydrops being responsible for high risk of mortality. Fetal therapy in such cases has so far not been established. We report a case with a giant solid SCT associated with fetal hydrops and severe heart failure. 2D- and 3D-Doppler ultrasonography revealed great vessels originated from the medial sacral artery. Percutaneous laser ablation of these vessels was performed at 24 weeks of gestation. During the procedure, severe anemia was also diagnosed (hemoglobin 4.3 g/dl). Two days later, the fetus died and pathological examination revealed local tumor necrosis and blood hemorrhage inside the mass. We suggest that in such cases, fetal surgery may not be enough, being too late, and perhaps fetal clinical therapy for anemia and heart failure could be the best option at a gestational age of less than 28 weeks. Copyright (C) 2009 S. Karger AG, Basel

The epidemiology of acute respiratory failure in hospitalized patients: A Brazilian prospective cohort study

Purpose: The purpose of this study was to assess risk factors associated with the development of acute respiratory failure (ARF) and death in a general intensive care unit (ICU). Materials and Methods: Adults who were hospitalized at 12 surgical and nonsurgical ICUs were prospectively followed up. Multivariable analyses were realized to determine the risk factors for ARF and point out the prognostic factors for mortality in these patients. Results: A total of 1732 patients were evaluated, with an ARF prevalence of 57%. Of the 889 patients who were admitted without ARF, 141 (16%) developed this syndrome in the ICU. The independent risk factors for developing ARF were 64 years of age or older, longer time between hospital and ICU admission, unscheduled surgical or clinical reason for ICU admission, and severity of illness. Of the 984 patients with ARF, 475 (48%) died during the ICU stay. Independent prognostic factors for death were age older than 64 years, time between hospital and ICU admission of more than 4 days, history of hematologic malignancy or AIDS, the development of ARF in ICU, acute lung injury, and severity of illness. Conclusions: Acute respiratory failure represents a large percentage of all ICU patients, and the high mortality is related to some preventable factors such as the time to ICU admission. (C) 2011 Elsevier Inc. All rights reserved.

Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans

The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge-rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P) in macaques did not predict the human trial results. Ad5 vector -based vaccines did not protect macaques from infection after SHIV89.6P challenge but did cause a substantial reduction in viral load and a preservation of CD4(+) T cell counts after infection, findings that were not reproduced in the human trials. Although the SIV challenge model is incompletely validated, we propose that its expanded use can help facilitate the prioritization of candidate HIV-1 vaccines, ensuring that resources are focused on the most promising candidates. Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge.

Antigenotoxicity and antimutagenicity of lycopene in HepG2 cell line evaluated by the comet assay and micronucleus test

Epidemiological studies have provided evidence that high consumption of tomatoes effectively reduces the risk of reactive oxygen species (ROS)-mediated diseases such as cancer. Tomatoes are rich sources of lycopene, a potent singlet oxygen-quenching carotenoid. In addition to its antioxidant properties, lycopene shows an array of biological effects including antimutagenic and anticarcinogenic activities. In the present study, the chemopreventive action of lycopene was examined on DNA damage and clastogenic or aneugenic effects of H2O2 and n-nitrosodiethylamine (DEN) in the metabolically competent human hepatoma cell line (HepG2 cells). Lycopene at concentrations of 10. 25, and 50 mu M, was tested under three protocols: before, simultaneously, and after treatment with the mutagen, using the comet and micronucleus assays. Lycopene significantly reduced the genotoxicity and mutagenicity of H2O2 in all of the conditions tested. For DEN, significant reductions of primary DNA damage (comet assay) were detected when the carotenoid (all of the doses) was added in the cell culture medium before or simultaneously with the mutagen. In the micronucleus test, the protective effect of lycopene was observed only when added prior to DEN treatment. In conclusion, our results suggest that lycopene is a suitable agent for preventing chemically-induced DNA and chromosome damage. (C) 2007 Elsevier Ltd. All rights reserved.

Western blotting method (TESAcruzi) as a supplemental test for confirming the presence of anti-Trypanosoma cruzi antibodies in finger prick blood samples from children aged 0-5 years in Brazil

Some Latin American countries have plans for total control and/or eradication of Chagas disease by the main vector (Triatoma infestans) and by blood transfusion. To achieve this, patients with Chagas disease must be identified. A Western blotting test, TESAcruzi, is described as a supplemental test for diagnosis of Chagas disease using samples collected from children <5 years living in different states of Brazil. Blood samples collected by finger prick on filter paper were sent to the test laboratory by a central laboratory to confirm results obtained previously. Ten percent of negative samples, all doubtful and all positive samples were received. Commercial reagents, IgG indirect immunofluorescence, enzyme immunoassay, and a recently introduced TESAcruzi test were used. From 8788 samples, 163 (1.85%) were reactive by IgG-ELISA and 312 (3.55%) by IgG IIF. From these, 77 (0.87%) were reactive in the TESAcruzi test. The results had high clinical value to identify those truly infected. (C) 2010 Elsevier B.V. All rights reserved.

Experimental tuberculosis: Designing a better model to test vaccines against tuberculosis

Experimental models of infection are good tools for establishing immunological parameters that have an effect on the host-pathogen relationship and also for designing new vaccines and immune therapies. In this work, we evaluated the evolution of experimental tuberculosis in mice infected with increasing bacterial doses or via distinct routes. We showed that mice infected with low bacterial doses by the intratracheal route were able to develop a progressive infection that was proportional to the inoculum size. In the initial phase of disease, mice developed a specific Th1-driven immune response independent of inoculum concentration. However, in the late phase, mice infected with higher concentrations exhibited a mixed Th1/Th2 response, while mice infected with lower concentrations sustained the Th1 pattern. Significant IL-10 concentrations and a more preeminent T regulatory cell recruitment were also detected at 70 days post-infection with high bacterial doses. These results suggest that mice infected with higher concentrations of bacilli developed an immune response similar to the pattern described for human tuberculosis wherein patients with progressive tuberculosis exhibit a down modulation of IFN-gamma production accompanied by increased levels of IL-4. Thus, these data indicate that the experimental model is important in evaluating the protective efficacy of new vaccines and therapies against tuberculosis. (C) 2010 Elsevier Ltd. All rights reserved.

Altered plasma response to zinc and iron tolerance test after Roux-en-Y gastric bypass

Background: The duodenum and proximal jejunum are excluded after Roux-en-Y gastric bypass but these intestinal sites are where iron and zinc are most absorbed. Therefore, they are among the nutrients whose digestive and absorptive process can be impaired after surgery. The aim of the present study was to investigate the iron and zinc plasma response to a tolerance test before and after bariatric surgery. The study was performed at Sao Paulo University School of Medicine of Ribeirao Preto, Brazil. Methods: In a longitudinal paired study, 9 morbidly obese women (body mass index >= 40 kg/m(2)) underwent an iron and zinc tolerance test before and 3 months after surgery. The iron and zinc levels were determined at 0, 1, 2, 3, and 4 hours after a physiologic unique oral dose. The mineral concentrations in die plasma and 24-hour urine sample were assayed using an atomic absorption spectrophotometer. The anthropometric measurements and 3-day food record were also evaluated. A linear mixed model was used to compare the plasma concentration versus interval after the oral dose, before and after surgery. Results: The pre- and postoperative test results revealed a significantly lower plasma zinc response (P <.01) and a delayed response to iron intake after surgery. The total plasma iron concentration area, during the 4 hours, was not different after surgery (P >.05). The 24-hour urinary iron and zinc excretion did not differ between the pre- and postoperative phases. Conclusion: The present data showed a compromised response to the zinc tolerance test after gastric bypass surgery, suggesting an impaired absorption of zinc. More attention must be devoted to zinc nutritional status after surgery. (Surg Obes Relat Dis 2011;7:309-314.) (C) 2011 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Heart failure disease management program experience in 4,545 heart failure admissions to a community hospital

Background Disease management programs (DMPs) are developed to address the high morbi-mortality and costs of congestive heart failure (CHF). Most studies have focused on intensive programs in academic centers. Washington County Hospital (WCH) in Hagerstown, MD, the primary reference to a semirural county, established a CHF DMP in 2001 with standardized documentation of screening and participation. Linkage to electronic records and state vital statistics enabled examination of the CHF population including individuals participating and those ineligible for the program. Methods All WCH inpatients with CHF International Classification of Diseases, Ninth Revision code in any position of the hospital list discharged alive. Results Of 4,545 consecutive CHF admissions, only 10% enrolled and of those only 52.2% made a call. Enrollment in the program was related to: age (OR 0.64 per decade older, 95% CI 0.58-0.70), CHF as the main reason for admission (OR 3.58, 95% CI 2.4-4.8), previous admission for CHF (OR 1.14, 95% CI 1.09-1.2), and shorter hospital stay (OR 0.94 per day longer, 95% CI 0.87-0.99). Among DMP participants mortality rates were lowest in the first month (80/1000 person-years) and increased subsequently. The opposite mortality trend occurred in nonenrolled groups with mortality in the first month of 814 per 1000 person-years in refusers and even higher in ineligible (1569/1000 person-years). This difference remained significant after adjustment. Re-admission rates were lower among participants who called consistently (adjusted incidence rate ratio 0.62, 95% CI 0.52-0.77). Conclusion Only a small and highly select group participated in a low-intensity DMP for CHF in a community-based hospital. Design of DMPs should incorporate these strong selective factors to maximize program impact. (Am Heart J 2009; 15 8:459-66.)

Influence of Glomerular Filtration Rate on the Pharmacokinetics of Cyclophosphamide Enantiomers in Patients With Lupus Nephritis

The pharmacokinetics of cyclophosphamide (CYC) enantiomers were evaluated in patients with lupus nephritis distributed in 2 groups according to creatinine clearance: group 1 (90.6-144.6 mL/min/1.73 m(2)) and group 2 (42.8-76.4 mL/min/ 1.73 m(2)). All patients were treated with 0.75 to 1.3 g of racemic CYC as a 2-hour infusion and with 1 mg intravenous midazolam as a drug-metabolizing marker. CYC enantiomers and midazolam concentrations in plasma were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The following differences (Wilcoxon test, P <= .05) were observed between the (S)-(-) and (R)-(+) enantiomers: AUC(0-infinity) 152.41 vs 129.25 mu g.h/mL, CL 3.28 vs 3.89 L/h, Vd 31.38 vs 29.74 L, and t(1/2) 6.79 vs 5.56 h for group 1 and AUC(0-infinity) 167.20 vs 139.08 mu g.h/mL, CL 2.99 vs 3.59 L/h, and t(1/2) 6.15 vs 4.99 h for group 2. No differences (Mann test, P <= .05) were observed between groups 1 and 2 in the pharmacokinetic parameters of both enantiomers. No significant relationship was observed between midazolam clearance (2.92-16.40 mL/min.kg) and clearance of each CYC enantiomer. In conclusion, CYC kinetic disposition is enantioselective, resulting in higher exposures of the (S)-(-) enantiomer in lupus nephritis patients, and the pharmacokinetic parameters of both enantiomers are not altered by the worsening of renal condition.