Additional clinical value of voxel‐based morphometric MRI post‐processing for MRI‐negative epilepsies: a prospective study

Aims: Magnetic resonance imaging is of paramount importance in the presurgical evaluation of drug resistant epilepsy. Detection of a potentially epileptogenic lesion significantly improves seizure outcome after surgery. To optimize the detection of subtle lesions, MRI post‐processing techniques may be of essential help. Methods: In this study, we aimed to evaluate the detection rate of the voxel‐based morphometric analysis program (MAP) in a prospective trial. We aimed to study the MAP+ findings in terms of their clinical value in the decision‐making process of the presurgical evaluation. Results: We included, prospectively, 21 patients who had negative MRI by visual analysis. In a first step, results of the conventional non‐invasive presurgical evaluation were discussed, blinded to the MAP results, in multidisciplinary patient management conferences to determine the possible seizure onset zone and to set surgical or invasive evaluation plans. Thereafter, MAP results were presented, and the change of initial clinical plan was recorded. All MAP detections were reaffirmed by a neuroradiologist with epilepsy expertise. For the 21 patients included, mean age at the time of patient management conference was 26 years (SD 15 +/‐ years, range: 5–54 years). In total, 4/21 had temporal lobe epilepsy and 17/21 had extra‐temporal lobe epilepsy. MAP was positive in 10/21 (47%) patients and in 6/10 (60%) a diagnosis of focal cortical dysplasia was confirmed after neuroradiologist review, corresponding to a 28% detection rate. MAP+ findings had a clear impact on the initial management in 7/10 patients (7/21, 33% of all patients), which included an adaptation of the intracranial EEG plan (6/7 patients), or the decision to proceed directly to surgery (1/7 patients). Conclusion: MRI post‐processing using the MAP method yielded an increased detection rate of 28% for subtle dysplastic lesions in a prospective cohort of MRI‐negative patients, indicating its potential value in epilepsy presurgical evaluation.     

Comparison of serum selenium levels among hypertensive and normotensive pregnant women

Objective: To correlate serum selenium levels with hypertensive disorders of pregnancy (HDP) in a selected population and evaluate this mineral as a possible protective factor. Methods: This case–control study included 32 normotensive, 20 hypertensive (chronic and gestational hypertension), and 38 preeclamptic pregnant women. All patients were recruited from antenatal or obstetric admissions of a tertiary hospital in Brazil. Serum selenium was measured at the time of inclusion. Patients were followed up until hospital discharge after delivery. Results: Groups did not differ with regard to maternal age, ethnicity, educational attainment, parity, or smoking prevalence. Normotensive patients had lower body mass index and were included in the study earlier. These patients also had a higher prevalence of comorbidities other than hypertension. Continuous use of medication and a history of HDP in previous pregnancies were more common in preeclamptic patients. Serum selenium levels were not significantly different between groups, with an average of 56.4 ± 15.3?μg/L in the control group, 53.2 ± 15.2?μg/L in the hypertension group, and 53.3 ± 16.8?μg/L in the preeclampsia group (p?=?0.67). Among patients with preeclampsia, 52.6% had the severe form. Serum selenium levels in these patients also did not differ significantly from those of controls (p?=?0.77). Preeclampsia was associated with earlier termination of pregnancy and lower birth weight (p?<?0.05). There were no significant differences across groups in other outcomes of interest. Conclusion: Serum selenium levels did not differ significantly between groups. Thus, we could not establish whether selenium is a protective factor against these conditions.     

Inhibition of HIV-1 infection by monoclonal antibodies to carbohydrates of Schistosoma mansoni

Patients infected with HIV-1 develop a potent humoral immune response against the virus, but HIV-1 primary isolates are remarkably resistant to neutralizing antibodies. Considering that the envelope glycoprotein of HIV-1 (gp120/41) is heavily glycosylated, we investigated whether anti-carbohydrate antibodies could inhibit HIV-1 infection in vitro. We studied the neutralizing activity of three monoclonal antibodies (mAbs) raised to carbohydrates of Schistosoma mansoni, against seven primary isolates of HIV-1. Assays were performed infecting peripheral blood mononuclear cells from normal donors with viral isolates previously treated with mAbs. Viral strains used were tropic for the coreceptors CCR5, CXCR4, and dual-tropic ones. We found that the anti-glycan mAbs vigorously inhibited HIV-1 infection, regardless of the preferential coreceptor usage of the isolate, in a dose-response manner. Importantly, five isolates were resistant to neutralization by two HIV-1 antibody-positive human sera endowed with potent anti-HIV-1 inhibitory activity. Our findings suggest that carbohydrates of the HIV-1 viral envelope may be a target of an effective humoral immune response elicited by vaccination.The first two authors contributed equally to this work     

Gene analysis in patients with premature ovarian failure or gonadal dysgenesis: a preliminary study

OBJECTIVE: The aim of this study was to evaluate the presence of mutations in the coding region of the QM gene and fragile X in patients with premature ovarian failure and gonadal dysgenesis. METHODS: After approval by the local Ethics Committee, blood samples, in EDTA, of 100 normally ovulating women, 23 with premature ovarian failure (POF) and 14 with gonadal dysgenesis 46XX, aged less than 40 years, were screened for mutation in the QM gene coding region. All patients with POF have 46, XX karyotype and serum levels of follicle-stimulating hormone (FSH) over 30 mIU/mL. In addition, all samples from patients with premature ovarian failure underwent analysis for fragile X. RESULTS: The QM gene located at a hotspot region (Xq28) showed five points of mutations in a patient with premature ovarian failure. Four of them were able to change the amino acid sequence of the protein. None of our patients were diagnosed as having pre or mutant X fragile syndrome. CONCLUSION: Our study suggests that Xq28 (QM gene) may be involved in ovary failure. However, further studies are needed to confirm this hypothesis.     

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306C>T and g.-735C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306C>T and g.-735C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306C>T and g.-735C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined.     

Implants,Mechanical Devices,and Vascular Surgery for Erectile Dysfunction

IntroductionThe field of erectile dysfunction (ED) is evolving and there is a need for state-of-the-art information in the area of treatment.AimTo develop an evidence-based, state-of-the-art consensus report on the treatment of erectile dysfunction by implants, mechanical devices, and vascular surgery.MethodsTo provide state-of-the-art knowledge concerning treatment of erectile dysfunction by implant, mechanical device, and vascular surgery, representing the opinions of 7 experts from 5 countries developed in a consensus process over a 2-year period.Main Outcome MeasureExpert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.ResultsThe inflatable penile prosthesis (IPP) is indicated for the treatment of organic erectile dysfunction after failure or rejection of other treatment options. Comparisons between the IPP and other forms of ED therapy generally reveal a higher satisfaction rate in men with ED who chose the prosthesis. Organic ED responds well to vacuum erection device (VED) therapy, especially among men with a suboptimal response to intracavernosal pharmacotherapy. After radical prostatectomy, VED therapy combined with phosphodiesterase type 5 therapy improved sexual satisfaction in patients dissatisfied with VED alone. Penile revascularization surgery seems most successful in young men with absence of venous leakage and isolated stenosis of the internal pudendal artery following perineal or pelvic trauma. Currently, surgery to limit venous leakage is not recommended.ConclusionsIt is important for the future of the field that patients be made aware of all treatment options for erectile dysfunction in order to make an informed decision. The treating physician should be aware of the patient's medical and sexual history in helping to guide the decision. More research is needed in the area of revascularization surgery, in particular, venous outflow surgery. Hellstrom WJG, Montague DK, Moncada I, Carson C, Minhas S, Faria G, and Krishnamurti S. Implants, mechanical devices, and vascular surgery for erectile dysfunction.     

Effects of Exercise Training in Patients with Chronic Heart Failure and Sleep Apnea

Study Objectives:

To test the effects of exercise training on sleep and neurovascular control in patients with systolic heart failure with and without sleep disordered breathing.

Design:

Prospective interventional study.

Setting:

Cardiac rehabilitation and exercise physiology unit and sleep laboratory.

Patients:

Twenty-five patients with heart failure, aged 42 to 70 years, and New York Heart Association Functional Class I-III were divided into 1 of 3 groups: obstructive sleep apnea (n = 8), central sleep apnea (n = 9) and no sleep apnea (n = 7).

Interventions:

Four months of no-training (control) followed by 4 months of an exercise training program (three 60-minute, supervised, exercise sessions per week).

Measures and Results:

Sleep (polysomnography), microneurography, forearm blood flow (plethysmography), peak VO_2, and quality of life were evaluated at baseline and at the end of the control and trained periods. No significant changes occurred in the control period. Exercise training reduced muscle sympathetic nerve activity (P < 0.001) and increased forearm blood flow (P < 0.01), peak VO₂(P < 0.01), and quality of life (P < 0.01) in all groups, independent of the presence of sleep apnea. Exercise training improved the apnea-hypopnea index, minimum O₂ saturation, and amount stage 3-4 sleep (P < 0.05) in patients with obstructive sleep apnea but had no significant effects in patients with central sleep apnea.

Conclusions.

The beneficial effects of exercise training on neurovascular function, functional capacity, and quality of life in patients with systolic dysfunction and heart failure occurs independently of sleep disordered breathing. Exercise training lessens the severity of obstructive sleep apnea but does not affect central sleep apnea in patients with heart failure and sleep disordered breathing.

Citation:

Ueno LM; Drager LF; Rodrigues ACT; Rondon MUPB; Braga AMFW; Mathias W; Krieger EM; Barretto ACP; Middlekauff HR; Lorenzi-Filho G; Negrão CE. Effects of exercise training in patients with chronic heart failure and sleep apnea. SLEEP 2009;32(5):637-647.     

Onset of promiscuous gene expression in murine fetal thymus organ culture

T-cell differentiation and induction of tolerance to self-antigens occurs mainly in the thymus. Thymic stromal cells, specifically medullary thymic epithelial cells, express a diverse set of genes encoding parenchymal organ-specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has been implicated in preventing organ-specific autoimmunity by inducing T-cell tolerance to self antigens. Early thymopoiesis and the critical factors involved in T-cell differentiation can be reproduced in vitro by murine fetal thymus organ culture (FTOC), which mimics the natural thymic microenvironment. To evaluate the occurrence of PGE in FTOC, gene expression profiling during in vitro thymic development in BALB/c mice was performed using a set of nylon cDNA microarrays containing 9216 sequences. The statistical analysis of the microarray data (sam program) revealed the temporal repression and induction of 57 parenchymal and seven lymphoid organ-specific genes. Most of the genes analysed are repressed during early thymic development (15-17 days post-coitum). The expression of the autoimmune regulator (AIRE) gene at 16 days post-coitum marks the onset of PGE. This precedes the induction of parenchymal organ genes during the late developmental phase at 20 days post-coitum. The mechanism of T-cell tolerance induction begins during fetal development and continues into adulthood. Our findings are significant because they show a fine demarcation of PGE onset, which plays a central role in induction of T-cell tolerance.