Atypical focal MRI lesions in a case of juvenile Alexander's disease

We present a juvenile case of Alexander's disease with atypical focal magnetic resonance imaging-detected lesions and elevated levels of lactate in cerebrospinal fluid. The diagnosis was based on the neuropathological finding of a diffuse accumulation of Rosenthal fibers within the brain and the spinal cord. The diagnosis was confirmed by detection of a mutation in exon 1 at nucleotide position 249 of glial fibrillary acidic protein cDNA, a finding previously reported in cases of infantile Alexander's disease.     

Obesity Treatment Using a Bioenterics Intragastric Balloon (BIB)—Preliminary Croatian Results

Aim of Study  

This study aims to assess the effectiveness, tolerance, safety, and patient satisfaction of obesity treatments using the Bioenterics intragastric balloon (BIB).     

Soluble adhesion molecules in acute ischemic stroke

BACKGROUND: Inflammatory adhesion molecules play a key role in the development of ischemic lesions. Elevated plasma concentrations of soluble adhesion molecules are reported in stroke patients, but data are still controversial. Our aim was to explore the potential association of plasma levels of soluble (s) intercellular and vascular cellular adhesion molecules-1 (sICAM-1 and sVCAM-1), sE-selectin and sL-selectin with acute ischemic stroke. METHODS: At our university hospital in Zagreb, Croatia, we prospectively enrolled 67 subjects with acute ischemic stroke, as well as 76 consecutive healthy individuals as controls who were visiting the centre for reasons unrelated to stroke. Serum concentrations of the molecules of interest were determined by means of quantitative sandwich enzyme immunoassay. RESULTS: Mean levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.034) and sE-selectin (p < 0.002) were higher in patients than in controls, whereas sL-selectin was lower in patients (p = 0.043). In patients, levels of soluble adhesion molecules were independent of age and sex except for sL-selectin, which was inversely correlated with age (r = -0.260, p = 0.034) and higher in women (p = 0.006) and diabetics (n = 14; p = 0.004). Serum levels did not differ significantly with respect to carotid atherosclerotic disease, smoking status, hypertension or hypercholesterolemia. As well as correlating with each other, concentrations of soluble adhesion molecules in patients correlated with traditional biochemical markers of inflammation: total leukocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein level. Concentrations of sICAM-1 and high-density lipoprotein-cholesterol and ESR were identified as significant independent predictors/indicators of acute ischemic stroke. CONCLUSIONS: Acute ischemic stroke is associated with elevated plasma levels of sICAM-1, sVCAM-1 and sE-selectin, independent of age, sex and other recognized risk factors for stroke. Decreased levels of sL-selectin are associated with acute stroke. The observed changes in serum concentrations of adhesion molecules indicate inflammatory process occurring during acute cerebral ischemia.     

Oxidative stress increases susceptibility of Mycobacterium tuberculosis to isoniazid

Isoniazid is a first-line antibiotic used in the treatment of infections caused by Mycobacterium tuberculosis. Isoniazid is a prodrug requiring oxidative activation by the catalase-peroxidase hemoprotein, KatG. Resistance to isoniazid can be obtained by point mutations in the katG gene, with one of the most common being a threonine-for-serine substitution at position 315 (S315T). The S315T mutation is found in more than 50% of isoniazid-resistant clinical isolates and results in an approximately 200-fold increase in the MIC of isoniazid compared to that for M. tuberculosis H37Rv. In the present study we investigated the hypothesis that superoxide plays a role in KatG-mediated isoniazid activation. Plumbagin and clofazimine, compounds capable of generating superoxide anion, resulted in a lower MIC of isoniazid for M. tuberculosis H37Rv and a strain carrying the S315T mutation. These agents did not cause as great of an increase in isoniazid susceptibility in the mutant strain when the susceptibilities were assessed by using the inhibitory concentration that causes a 50% decrease in growth. These results provide evidence that superoxide can play a role in isoniazid activation. Since clofazimine alone has antitubercular activity, the observation of synergism between clofazimine and isoniazid raises the interesting possibility of using both drugs in combination to treat M. tuberculosis infections.     

Oxidative stress,NOx/l-arginine ratio and glutathione/glutathione S-transferase ratio as predictors of ‘sterile inflammation’ in patients with alcoholic cirrhosis and hepatorenal syndrome type II

Continuous intake of alcohol leads to liver cirrhosis because of imbalance of oxidative stress/antioxidative defense and chronic ‘sterile inflammation’. Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis. The aim of our study was to assess: (1) the oxidative stress/antioxidative defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with cirrhosis without HRS (32 patients), and a control group (40 healthy blood donors). All the patients with cirrhosis and HRS had type II HRS. MDA concentration was significantly higher in the groups with cirrhosis with and without HRS. Significant positive correlation was documented between the MDA level and de Ritis coefficient (AST/ALT), a marker of liver damage severity; between MDA and inflammation (CRP); between MDA and NOx concentration in the groups with cirrhosis with and without HRS. The correlation between MDA and creatinine level was significant in the group with HRS. The levels of GSH and GST were significantly lower in the groups with cirrhosis with and without HRS. The results of the study revealed that an increase in MDA and NOx concentration, along with decreased values of antioxidative defense and L-arginine, may indicate that liver damage can have an influence on progression to renal failure.     

Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS)

OBJECTIVE: The purpose of this study was to examine the effects of methylphenidate (MPH) on functional outcomes, including children's social skills, classroom behavior, emotional status, and parenting stress, during the 4-week, double-blind placebo controlled phase of the Preschoolers with Attention Deficit/Hyperactivity Disorder (ADHD) Treatment Study (PATS). METHODS: A total of 114 preschoolers who had improved with acute MPH treatment, were randomized to their best MPH dose (M = 14.22 mg/day; n = 63) or placebo (PL; n = 51). Assessments included the Clinical Global Impression-Severity (CGI-S), parent and teacher versions of the Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale (SCS), Social Skills Rating System (SSRS), and Early Childhood Inventory (ECI), and Parenting Stress Index (PSI). RESULTS: Medication effects varied by informant and outcome measure. Parent measures and teacher SWAN scores did not differentially improve with MPH. Parent-rated depression (p < 0.02) and dysthymia (p < 0.001) on the ECI worsened with MPH, but scores were not in the clinical range. Significant medication effects were found on clinician CGI-S (p < 0.0001) and teacher social competence ratings (SCS, p < 0.03). CONCLUSIONS: Preschoolers with ADHD treated with MPH for 4 weeks improve in some aspects of functioning. Additional improvements might require longer treatment, higher doses, and/or intensive behavioral treatment in combination with medication.     

Preparation of novel apigenin‐enriched,liposomal and non‐liposomal,antiinflammatory topical formulations as substitutes for corticosteroid therapy

Two oil‐in‐water formulations, containing equal amounts of apigenin‐enriched chamomile flower extracts, for potential use as topical antiinflammatory agents, were prepared and their physicochemical properties evaluated. A pilot clinical study was then carried out to assess patient acceptability and efficacy. The creams were either non‐liposomal or liposomal. The liposomal formulations were more viscous, thus producing superior release characteristics in vitro. The clinical study also showed that the liposomal creams were, as antiinflammatory agents, slightly more effective in vivo than the non‐liposomal formulations. These results suggest that there is scope for the further development of even more effective and safer alternatives to corticosteroids. Copyright © 2010 John Wiley & Sons, Ltd.     

Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: a retrospective claims database analysis

Background: Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP). Objective: This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient setting. Methods: This was a retrospective analysis of claims data from a large US health plan. Patients were aged >/=18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged >/=50 and >/=65 years. Results: Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged >/=50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and >/=65 years (OR = 0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged >/=65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxa-cin and macrolide recipients. Conclusions: Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged >/=50 and >/=65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitali-zations and costs did not differ significantly between the 2 treatment groups.     

An additional motor-related field in the lateral frontal cortex of squirrel monkeys

Our earlier efforts to document the cortical connections of the ventral premotor cortex (PMv) revealed dense connections with a field rostral and lateral to PMv, an area we called the frontal rostral field (FR). Here, we present data collected in FR using electrophysiological and anatomical methods. Results show that FR contains an isolated motor representation of the forelimb that can be differentiated from PMv based on current thresholds and latencies to evoke electromyographic activity using intracortical microstimulation techniques. In addition, FR has a different pattern of cortical connections compared with PMv. Together, these data support that FR is an additional, previously undescribed motor-related area in squirrel monkeys.