Late Auditory evoked potentials in individuals with tinnitus

Long latency auditory evoked potentials (LLAEP) alterations in individuals with tinnitus are suggestive of dysfunction in the central auditory pathways at a cortical level. Aim: to characterize the LLAEP in individuals with and without tinnitus exposed to occupational noise. Method: Cross-sectional contemporary cohort, prospective study. Sixty subjects exposed to occupational noise, ranging in age from 29 to 50 years underwent LLAEP assessment; 30 of them had tinnitus complaint and 30 did not have tinnitus. Results: we observed significant statistical difference regarding the mean values of latencies of waves N1 (p<0.001), P2 (p=0.002) and P300 (p=0.039) when we compared individuals with and without tinnitus. In individuals with tinnitus we also noticed a greater number of altered results concerning components N1 (60%) and P2 (66.7%), although only component P2 presented significant statistical difference (p=0.010). For the LLAEP, the latency increase was the only type of alteration found (p=1.000). We found a greater association between bilateral tinnitus and bilateral alteration for all components N1(73%), P2(73%) and P300(50%). Conclusion: It is relevant to study LLAEP in individuals with tinnitus exposed to high occupational sound pressure levels.

Case Report: Severe Rhabdomyolysis Caused by Plasmodium vivax Malaria in the Brazilian Amazon

Severe rhabdomyolysis (creatine phosphokinase = 29.400U/L) developed in a 16-year-old boy from Manaus. Brazil, after he started treatment with chloroquine for infection with Plasmodium vivax Treatment led to myoglobinuria and acute renal failure After hemodialysis. the patient improved and a muscle biopsy specimen showed no myophosphorylase or deaminase deficiency. This case of rhabdomyolysis associated with P vivax infection showed no comorbidities The pathogenesis is still unclear

Evaluation of inverted papilloma and squamous cell carcinoma by nasal contact endoscopy

Background: Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. This study described and compared the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma (SCC) and tested the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. Methods: The patients included in this study were divided into group A, patients diagnosed with inverted papilloma, and group B, patients diagnosed with SCC. CE results were compared among themselves. CE images were presented to examiners not experienced with the method. Results: Twenty-two patients were examined, 13 in group A and 9 in group B. The main relevant differences in CE findings between those two groups were corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. Conclusion: CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal SCC, which may enable better preoperative planning. (Am J Rhinol Allergy 24, 210-214, 2010; doi: 10.2500/ajra.2010.24.3467)

Assessment of immediate conservative breast surgery reconstruction: A classification system of defects revisited and an algorithm for selecting the appropriate technique

Background: Although various techniques have been used for breast conservation surgery reconstruction, there are few studies describing a logical approach to reconstruction of these defects. The objectives of this study were to establish a classification system for partial breast defects and to develop a reconstructive algorithm. Methods: The authors reviewed a 7-year experience with 209 immediate breast conservation surgery reconstructions. Mean follow-up was 31 months. Type I defects include tissue resection in smaller breasts (bra size A/B), including type IA, which involves minimal defects that do not cause distortion; type III, which involves moderate defects that cause moderate distortion; and type IC, which involves large defects that cause significant deformities. Type II includes tissue resection in medium-sized breasts with or without ptosis (bra size C), and type III includes tissue resection in large breasts with ptosis (bra size D). Results: Eighteen percent of patients presented type I, where a lateral thoracodorsal flap and a latissimus dorsi flap were performed in 68 percent. Forty-five percent presented type II defects, where bilateral mastopexy was performed in 52 percent. Thirty-seven percent of patients presented type III distortion, where bilateral reduction mammaplasty was performed in 67 percent. Thirty-five percent of patients presented complications, and most were minor. Conclusions: An algorithm based on breast size in relation to tumor location and extension of resection can be followed to determine the best approach to reconstruction. The authors` results have demonstrated that the complications were similar to those in other clinical series. Success depends on patient selection, coordinated planning with the oncologic surgeon, and careful intraoperative management.

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent-onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first-onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM-IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel-based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right-sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left-sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.

Increased rates of white matter hyperintensities in late-onset bipolar disorder

Objectives: Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset 60 years), early-onset BD subjects (EO-BD, illness onset < 60 years), and elderly healthy volunteers. Methods: T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. Results: There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). Conclusions: Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these. findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

White-matter hyperintensities in first-episode psychosis

Background White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies. Aims To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder. Method T-2-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. visual white-matter hyperintensity ratings were used for group and subgroup comparisons. Results There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms. Conclusions White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings. Declaration of interest None. Funding detailed in Acknowledgements.

Hypotension caused by therapeutic doses of venlafaxine: case report and proposed pathophysiological mechanisms

Although venlafaxine is usually associated with modest increases in blood pressure and not so often clinical hypertension, there are a few reported cases of hypotension related to overdoses of this specific antidepressant. The case study of a young female patient with a history of Major Depressive Disorder who initiated treatment with venlafaxine 75 mg/day and developed hypotension when the dosage was titrated up to 225 mg/day is described. The patient did not present comorbid diseases nor use other medication. A temporal association and a dose-dependent relationship between the hypotension and the use of venlafaxine is shown. To the best of the knowledge of the authors, this is the first case report that specifically associates regular doses of venlafaxine with the presence of hypotension. A pathophysiological mechanism is proposed, involving the participation of presynaptic alpha2-adrenergic receptors and the presence of a possible genetic polymorphism of cytochrome P4502D6, which is associated with lower drug metabolization, to explain the relationship between venlafaxine in regular dosage and development of hypotension.

Evaluation of the genotoxicity of treated urban sludge in the Tradescantia micronucleus assay

The sludge produced in sewage treatment plants can contain toxic substances. Among these, the genotoxic substances are of great concern. The present paper aimed at evaluating the genotoxicity of treated sludge samples collected at four different sewage treatment plants (STP) located in the State of Sao Paulo Brazil, using the Trad-MN assay. Another objective of the study was to compare the responses of the Clone #4430 with the Tradescantia pallida. Sludge samples mixed with reference soil in concentrations of 10, 25 and 50% (v/v) were tested in experiments with 3 months exposure in the field. Negative and positive controls (arsenic trioxide) were also tested with both plants. In Clone #4430 two sludge samples induced genotoxicity while in T pallida three were positive, although no clear dose-response were observed for both plants. Results with the negative and positive controls suggest that T pallida presented similar results when compared to the Clone #4430. The protocol using plants chronically exposed to sludge mixed with soil seems to be a promising tool to assess the genotoxicity of sludge although time consuming. (C) 2008 Elsevier B.V. All rights reserved.

Statins withdrawal, vascular complications, rebound effect and similitude

Hahnemann considered the secondary action of medicines to be a law of nature and reviewed the conditions under which it occurs. It is closely related to the rebound effects observed with many modern drugs. I review the evidence of the rebound effect of statins that support the similitude principle. In view of their indications in primary and secondary prevention of cardiovascular diseases, statins are widely prescribed. Besides reducing cholesterol biosynthesis, they provide vasculoprotective effects (pleiotropic effects), including improvement of endothelial function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory and thrombogenic responses, stabilisation of atherosclerotic plaques, and others. Recent studies suggest that suspension of statin treatment leads to a rebound imparing of vascular function, and increasing morbidity and mortality in patients with vascular diseases. Similarly to other classes of modern palliative drugs, this rebound effect is the same as a secondary action or vital reaction described by Samuel Hahnemann, and used in homeopathy in a therapeutic sense. Homeopathy (2010) 99, 255-262.

Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein

The microtubule-associated protein Tau promotes the assembly and stability of microtubules in neuronal cells. Six Tau isoforms are expressed in adult human brain. All six isoforms become abnormally hyperphosphorylated and form neurofibrillary tangles in Alzheimer disease (AD) brains. In AD, reduced activity of phospholipase A(2) (PLA(2)), specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), was reported in the cerebral cortex and hippocampus, which positively correlated with the density of neurofibrillary tangles. We previously demonstrated that treatment of cultured neurons with a dual cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser(214) site. The aim of this study was to conduct a preliminary investigation into the effects of in vivo infusion of MAFP into rat brain on PLA(2) activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA(2) activity in the frontal cortex and hippocampus. The reactivity to the antibody revealed three Tau protein bands with apparent molecular weight of close to 40, 43 and 46 kDa in both brain areas. MAFP decreased the 46 kDa band intensity in the frontal cortex, and the 43 and 46 kDa band intensities in the hippocampus. The results indicate that in vivo PLA(2) inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings.

Inhibition of motor cortex excitability with 15 Hz transcranial alternating current stimulation (tACS)

There remains a lack of solid evidence showing whether transcranial stimulation with weak alternating current (transcranial alternating current stimulation, tACS) can in fact induce significant neurophysiological effects. Previously, a study in which tACS was applied for 2 and 5 min with current density = 0.16-0.25 A/m(2) was unable to show robust effects on cortical excitability. Here we applied tACS at a significantly higher current density (0.80 A/m(2)) for a considerably longer duration (20 min) and were indeed able to demonstrate measurable changes to cortical excitability. Our results show that active 15 Hz tACS of the motor cortex (electrodes placed at C3 and C4) significantly diminished the amplitude of motor evoked potentials and decreased intracortical facilitation (ICF) as compared to baseline and sham stimulation. In addition, we show that our method of sham tACS is a reliable control condition. These results support the notion that AC stimulation with weak currents can induce significant changes in brain excitability; in this case, 15 Hz tACS led to a pattern of inhibition of cortical excitability. We propose that tACS may have a dampening effect on cortical networks and perhaps interfere with the temporal and spatial summation of weak subthreshold electric potentials. (C) 2010 Elsevier Ireland Ltd. All rights reserved.