Oxidative stress biomarkers and otoacoustic emissions in humans exposed to styrene and noise

Objective: Evaluating the correlation between otoacoustic emission levels, styrene exposure, and oxidative stress biomarkers concentration in styrene-exposed subjects, to investigate the role of oxidative stress in outer hair cell damage. Design: Distortion product otoacoustic emissions were measured in the exposed workers and in a control group. Separation between the distortion and reflection otoacoustic components was performed by time-frequency-domain filtering. The urinary concentration of the DNA and RNA oxidation products, namely 8-oxo-7,8-dihydroguanine (oxoGua), 8-oxo-7,8-dihydro-2′-deoxyguanosine (oxodGuo), and 8-oxo-7,8-dihydroguanosine (oxoGuo), were evaluated. Study sample: Nine subjects exposed to styrene in a fiberglass factory, eight control subjects. The two groups were statistically equivalent in mean age. Results: Statistically significant differences were found in the distortion component levels between the exposed and the control group. High levels of the oxidative damage biomarkers were found in the workers exposed to high levels of styrene. Significant negative correlation was found between the otoacoustic emission distortion component levels and the concentration of the oxoGuo biomarker. Conclusions: Exposure-induced damage of the cochlear amplifier is shown in the mid-frequency range, confirming animal experiments, in which hair cells in the cochlear middle turn were damaged. Hearing damage is consistent with the outer hair cell apoptosis pathway associated with oxidative stress.     

Combination of ketanserin and verapamil or propranolol in patients with alcoholic cirrhosis: search for an additive effect

Drugs reported to reduce portal pressure through different mechanisms were combined in the hope of either additive portal hypotensive effects in "responders," or inducing a portal hypotensive effect in "nonresponders" to the initial drug. Seven patients with alcoholic cirrhosis received verapamil, 10 mg i.v., and, 60 min later, ketanserin, 5 mg i.v. Verapamil decreased heart rate and increased free hepatic venous pressure but had no effect on hepatic venous pressure gradient or azygos blood flow. When combined with verapamil, ketanserin significantly diminished wedged hepatic venous pressure and hepatic venous pressure gradient. Ten other patients with alcoholic cirrhosis received propranolol, 15 mg i.v., and 45 min later, ketanserin, 5 mg i.v. In all patients, heart rate, cardiac index and azygos blood flow significantly decreased after propranolol. After propranolol alone, however, wedged hepatic venous pressure decreased in only five patients, responders. In five other patients, defined as nonresponders, propranolol did not decrease this pressure. The addition of ketanserin to propranolol induced further significant reduction in wedged hepatic venous pressure, hepatic venous pressure gradient and azygos blood flow. Among the five nonresponders, three had a reduced wedged hepatic venous pressure after ketanserin was combined. We conclude that verapamil does not reduce portal pressure or collateral blood flow in patients with alcoholic cirrhosis. The splanchnic hemodynamic effects of propranolol and ketanserin appear to be independent and additive, without significant systemic alteration.     

Cerebral atrophy and white matter disruption in chronic schizophrenia

Several magnetic resonance imaging (MRI) studies have shown cerebral atrophy in established schizophrenia, although not in all reports. Discrepancies may mostly be due to population and post-processing differences. Recently, disruption of cortical white matter integrity has also been reported in chronic patients with schizophrenia. In this study we explored tridimensional (3D) cerebral volumes and white matter microstructure in schizophrenia with structural and diffusion magnetic resonance. Twenty-five patients with established schizophrenia and 25 1:1 matched normal controls underwent a session of MRI using a Siemens 1.5T-scanner. 3D brain volume reconstruction was performed with the semi-automatic software Amira (TGS, San Diego, CA), whereas the apparent diffusion coefficients (ADCs) of cortical white matter water molecules were obtained with in-house developed softwares written in MatLab (The Mathworks-Inc., Natick, MA). Compared to controls, patients with schizophrenia had significantly smaller gray matter intracranium and total brain volumes, increased 4th ventricle volumes, and greater temporal and occipital ADCs. Patients treated with typical antipsychotic medication (N = 9) had significantly larger right lateral and 4th ventricles compared to those on atypical antipsychotic drugs. Intracranial volumes significantly inversely correlated with left temporal ADC in patients with schizophrenia. Also, age correlated directly with right, left, and 3rd ventricle volumes and inversely with gray matter intracranium volumes in individuals with schizophrenia. This study confirmed the presence of cortical atrophy in patients with schizophrenia, especially in those on typical antipsychotic drugs, and the existence of white matter disruption. It also suggested that physiological aging effects on brain anatomy may be abnormally pronounced in schizophrenia.     

Cardiac hepatopathy: clinical,hemodynamic, and histologic characteristics and correlations

Cardiac hepatopathy, hepatic injury caused by cardiac dysfunction, is a common entity but has been characterized incompletely, particularly the relationship between hemodynamics and histology. We aimed to describe the clinical, biochemical, hemodynamic, and histologic characteristics of this disorder. Eighty-three patients from 2 tertiary referral centers were studied. Patients were divided into 3 groups based on the duration of cardiac dysfunction: (1) acute (n = 12); (2) chronic (n = 53); and (3) acute on chronic (n = 18). Results showed that serum aminotransferase levels were increased typically, particularly in the acute group (median aspartate aminotransferase level was 30.2 times the upper limit of normal [range, 1-100]; P <.0001 vs. the chronic group). The most salient hemodynamic features were elevated right atrial (14 mm Hg [range, 1-29]), and hepatic venous pressures (wedged: 18 mm Hg [range, 5-35]; free: 15 mm Hg [range, 2-30]). The hepatic venous pressure gradient was normal in most (81%), correlated moderately with the aminotransferase levels (aspartate aminotransferase level: r =.59; P <.0001), and associated with the presence of centrilobular necrosis and inflammation, periportal necrosis, and stainable hepatic iron (P <.05 for all comparisons), but not fibrosis. Sinusoidal dilatation was associated with higher right atrial (P =.047) and free hepatic venous pressures (P =.06). Although cirrhosis was rare (n = 1), centrilobular fibrosis was common (74%) and not associated with any hemodynamic measurement. In conclusion, cardiac hepatopathy has diverse clinical, hemodynamic, and histologic manifestations that vary with the temporal course of cardiac dysfunction. Hepatic fibrosis is common, but does not correlate with systemic or hepatic hemodynamics.     

Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in awake portal hypertensive rats

The effects of increasing doses of propranolol were studied in awake portal hypertensive rats in order to elucidate the relative effects of the beta-blocker on systemic and splanchnic circulation. Hemodynamic responses to 0.1, 0.2 and 0.4 mg per min infusions of propranolol were compared with placebo in awake rats with portal hypertension due to portal vein stenosis. Heart rate significantly and progressively decreased from 356 +/- 13 to 293 +/- 10 beats per min (mean +/- S.E.). Cardiac output significantly decreased from 54 +/- 3 to 42 +/- 3 ml per min per 100 gm body weight at the highest dose. Significant decrease in portal tributary blood flow from 27 +/- 1 to 18 +/- 1 ml per min, at 0.4 mg per min dose, was due not only to the decrease in cardiac output but also to a significant increase in portal tributary vascular resistance from 269 +/- 17 to 368 +/- 31 dyne per sec per cm5 x 10(3). However, portal pressure showed only an insignificant decrease from 14.9 +/- 1.1 to 14.1 +/- 1.4 mmHg. The reduction in portal pressure being minimal, in spite of a significant decrease in portal tributary blood flow, is explained by an increase in combined hepatic and collateral resistance from 44 +/- 2 to 66 +/- 4 dyne per sec per cm5 x 10(3), p less than 0.05, at 0.4 mg per min dose. We conclude that the systemic and splanchnic effects of propranolol show discrepancy at two levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of pegylated interferon alpha-related diabetic ketoacidosis: can this complication be avoided?

We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNα) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN α plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNα, as well as with standard IFNα. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening.     

EEG-fMRI as an useful tool to detect epileptic foci associated with secondary bilateral synchrony

IntroductionTailoring the epileptic cortex is the key issue in the pre-surgical work-up of patients with pharmacoresistant focal epilepsy. Not always, however, the conventional MRI and the scalp EEG are able to provide the information needed to address this issue since the imaging may be normal (criptogenetic epilepsy) and the EEG, even ictal, poorly localizing.Patient and methodsWe present a case of focal criptogenetic epilepsy with speech arrest seizures and bilateral synchronous spike and wave scalp EEG pattern (secondary bilateral synchrony). The patient underwent an EEG-fMRI continuous co-registration.ResultsThe EEG-fMRI showed a clear cut activation of a BOLD signal during the epileptic discharge over the left Supplementary Motor Area (SMA) and, on lesser degree, over the homolateral motor strip.DiscussionKnowledge and expertise about this technique has greatly increased over the last few years making it an useful tool for localizing purposes specially in patients with ambiguous scalp EEG and normal MRI just like the one we presented.