Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study.

Background: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications.

Modeling Binaural Unmasking of Speech Using a Blind Binaural Processing Stage.

The equalization cancellation model is often used to predict the binaural masking level difference. Previously its application to speech in noise has required separate knowledge about the speech and noise signals to maximize the signal-to-noise ratio (SNR). Here, a novel, equalization cancellation model is introduced that can use the mixed signals.

Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity.

Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions.

Use of oxcarbazepine for treatment of refractory status epilepticus.

Purpose: Oxcarbazepine (OXC) is an effective anticonvulsant used for treatment of partial and secondarily generalized seizures. However, there is almost no data regarding its effectiveness and tolerability when used for treatment of status epilepticus (SE).

Methods: We retrospectively identified all patients who received OXC for treatment of SE in our hospital between July 2008 and December 2010 in our hospital and analyzed all available data.

Intravenous lacosamide or phenytoin for treatment of refractory status epilepticus.

Objectives: To compare intravenous phenytoin (PHT) and intravenous lacosamide (LCM) for treatment of status epilepticus after failure of the first and second drug.

Methods: We retrospectively identified patients from a large community hospital in northern Germany who had been diagnosed with SE between August 2008 and December 2010. Patients who had failed to respond to the first two drugs were selected for this analysis.

Coaligned dual-channel STED nanoscopy and molecular diffusion analysis at 20 nm resolution.

We report on a fiber laser-based stimulated emission-depletion microscope providing down to ∼20 nm resolution in raw data images as well as 15-19 nm diameter probing areas in fluorescence correlation spectroscopy. Stimulated emission depletion pulses of nanosecond duration and 775 nm wavelength are used to silence two fluorophores simultaneously, ensuring offset-free colocalization analysis. The versatility of this superresolution method is exemplified by revealing the octameric arrangement of Xenopus nuclear pore complexes and by quantifying the diffusion of labeled lipid molecules in artificial and living cell membranes.

Nanoscopy in a living mouse brain.

We demonstrated superresolution optical microscopy in a living higher animal. Stimulated emission depletion (STED) fluorescence nanoscopy reveals neurons in the cerebral cortex of a mouse with <70-nanometer resolution. Dendritic spines and their subtle changes can be observed at their relevant scales over extended periods of time.

Intravenous lacosamide for treatment of status epilepticus.

Objectives: Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment.

Intravenous levetiracetam as treatment for status epilepticus.

There are established drugs for the treatment of status epilepticus (SE) but their potentially hazardous side-effects are well known. Levetiracetam (LEV) is a novel anticonvulsant available for intravenous (i.v.

Intravenous lacosamide as successful treatment for nonconvulsive status epilepticus after failure of first-line therapy.

Treatment of status epilepticus usually requires intravenous anticonvulsant therapy. Lacosamide is a novel anticonvulsant drug that is available as infusion solution. We describe a patient with nonconvulsive status epilepticus who was successfully treated with intravenous lacosamide.

Pharmacokinetics of ethambutol in children and adults with tuberculosis.

Setting: Five hospitals in the United States.

Objective: To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB).

Design: Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens.

Modulation of Xenopus laevis Ca-activated Cl currents by protein kinase C and protein phosphatases: implications for studies of anesthetic mechanisms.

Ca-activated Cl currents (I(Cl(Ca))) are used frequently as reporters in functional studies of anesthetic effects on G protein-coupled receptors using Xenopus laevis oocytes. However, because anesthetics affect protein kinase C (PKC), they could indirectly affect I(Cl(Ca)) if this current is regulated by phosphorylation. We therefore studied the effect of modulation of either PKC or protein phosphatases PP1alpha and PP2A on I(Cl(Ca)) stimulated either by lysophosphatidate (LPA) signaling or by microinjection of Ca.

Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases.

Aminoglycoside use is limited by ototoxicity and nephrotoxicity. This study compared the incidences of toxicities associated with 2 recommended dosing regimens. Eighty-seven patients with tuberculosis or nontuberculous mycobacterial infections were prospectively randomized by drug to receive 15 mg/kg per day or 25 mg/kg 3 times per week of intravenous streptomycin, kanamycin, or amikacin.

Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis.

Background: Antihistamines are among the most frequently used medications in the United States. Despite dramatically higher cost, second-generation antihistamines are replacing diphenhydramine because of the perception that they are not constrained by its sedating effects.

Objective: We sought to examine, through meta-analytic procedures, the collective evidence regarding the sedating and performance-impairing effects of diphenhydramine relative to placebo and second-generation antihistamines.

Population pharmacokinetics of ethionamide in patients with tuberculosis.

Setting: Three US referral hospitals.

Objective: Determine the population pharmacokinetic (PK) parameters of ethionamide (ETA) following multiple oral doses.

Design: Fifty-five patients with tuberculosis (TB) participated.

Ofloxacin population pharmacokinetics in patients with tuberculosis.

Setting: Two tuberculosis hospitals in the United States.

Objective: To determine the population pharmacokinetic (PK) parameters of ofloxacin following multiple oral doses.

Design: A total of 73 patients with tuberculosis (TB) participated in the study.

Population pharmacokinetic modeling of pyrazinamide in children and adults with tuberculosis.

Study Objective: To determine population pharmacokinetic parameters of pyrazinamide after multiple oral doses given to children and adults with tuberculosis.

Design: Prospective, multiple-dose population pharmacokinetic study.

Setting: Five hospitals in the United States.

Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis.

Study Objectives: To determine population pharmacokinetic parameters of streptomycin after administration of multiple intramuscular and intravenous doses.

Design: Prospective, unblinded clinical study.

Setting: Two medical centers in Denver, Colorado.

The inhibitory effect of bupivacaine on prostaglandin E(2) (EP(1)) receptor functioning: mechanism of action.

Prostaglandin E(2) receptors, subtype EP(1) (PGE(2)EP(1)) have been linked to several physiologic responses, such as fever, inflammation, and mechanical hyperalgesia. Local anesthetics modulate these responses, which may be due to direct interaction of local anesthetics with PGE(2)EP(1) receptor signaling. We sought to characterize the local anesthetic effects on PGE(2)EP(1) signaling and elucidate mechanisms of anesthetic action.

The role of fluoroquinolones in tuberculosis today.

Tuberculosis is a growing international health concern; it is the leading infectious cause of death in the world today. The fluoroquinolones are the most recent class of drugs offering hope in the fight against this disease. Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin are currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.

Novel treatment of meningitis caused by multidrug-resistant Mycobacterium tuberculosis with intrathecal levofloxacin and amikacin: case report.

We report the case of a 25-year-old HIV-negative man with disseminated multidrug-resistant tuberculosis (MDRTB), who-on a retreatment regimen-experienced total resolution of TB miliary disease, but progressive TB meningitis. Therefore, intrathecal treatment with amikacin and levofloxacin was instituted, with successful clinical and microbiological results.

Potential interaction between itraconazole and clarithromycin.

Three patients negative for human immunodeficiency virus infection were admitted for pulmonary Mycobacterium avium complex (MAC) and aspergillosis infections. They were treated with different drug combinations, but all regimens included clarithromycin for MAC and itraconazole for aspergillosis. All patients experienced an increase in clarithromycin concentrations and clarithromycin: 14-OH-clarithromycin ratio compared with expected range values.

Multidrug-resistant tuberculosis meningitis: clinical problems and concentrations of second-line antituberculous medications.

Objective: [corrected] To describe a case of culture-proven multidrug-resistant tuberculous (MDR-TB) meningitis, in which the patient survived long enough for clinicians to adjust antituberculous therapy to second-line therapeutic agents.

Design: Case report.

Setting: Tertiary care hospital.

Therapeutic drug monitoring in patients with cystic fibrosis and mycobacterial disease.

Cystic fibrosis (CF) patients require higher dosages of many antibiotics. The relapse of tuberculosis in one CF patient, and the repeated growth of Mycobacterium avium-intracellulare in another, despite conventional therapy, raised the question of whether the serum levels of the antimycobacterial drugs were adequate. Antimycobacterial drug serum concentrations were assayed in 10 CF patients with pulmonary mycobacterial disease.