Baclofen-induced disinhibition in area CA1 of rat hippocampus is resistant to extracellular Ba

The mechanism of disinhibition produced by (±)-baclofen was studied using intracellular recording in area CA1 of rat hippocampal slices. Baclofen reversibly depressed monosynaptic IPSPs evoked by direct activation of interneurons in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) andd,l-2amino-5-phosphonovalerate (APV). Ba²⁺ prevented baclofen-induced hyperpolarization of pyramidal neurons but not depression of monosynaptic IPSPs by baclofen. Baclofen reversibly depressed monosynaptic IPSPs when applied close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that baclofen disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating receptors on the terminals of inhibitory neurons that are coupled to a Ba²⁺-insensitive effector mechanism.     

Evaluation of the MagNA Pure LC used with the TRUGENE HBV Genotyping Kit.

BACKGROUND: The current manual sample processing method recommended for use with the TRUGENE HBV Genotyping Kit (TRUGENE HBV; Bayer HealthCare LLC, Tarrytown, NY) is labor-intensive and may be prone to specimen cross-contamination. Recent evaluations of the MagNA Pure LC (MP; Roche Applied Science, Indianapolis, IN) suggest that it is suitable for automated, contamination-free extraction and purification of viral nucleic acids from large-volume (1.0 mL) serum or plasma specimens. OBJECTIVES: We evaluated the MP Total Nucleic Acid Isolation Kit--Large Volume (Roche Applied Science) in conjunction with TRUGENE HBV to establish the analytical sensitivity (threshold titer) of the assay, in HBV DNA International Units (IU)/mL, for obtaining consistent, interpretable sequence data from TRUGENE HBV. STUDY DESIGN: HBV analytical standards, prepared as 10 replicates (1.0 mL each) at each of the following concentrations: 200, 1000, 5000, and 10,000 IU/mL, were processed by MP and analyzed by TRUGENE HBV according to manufacturer's instructions. Performance of TRUGENE HBV used in conjunction with MP sample processing was evaluated further using 22 clinical serum specimens containing low titers of HBV DNA. RESULTS: All replicates of HBV analytical standards at 1000, 5000, and 10,000 IU/mL yielded interpretable TRUGENE HBV sequences, whereas interpretable sequences were obtained in 90% (9 of 10) of the replicates at 200 IU/mL. TRUGENE HBV sequences were interpretable in 86% (19 of 22) of the clinical specimens studied. CONCLUSIONS: MP sample processing is efficient and suitable for use with TRUGENE HBV. When combined with MP sample processing, TRUGENE HBV yielded interpretable sequences from HBV analytical standards and clinical serum specimens with HBV DNA titers of > or =200 IU/mL.     

Computerized tomography diagnosis of diffuse intraperitoneal metastases after retroperitoneal lymphadenectomy for testicular carcinoma

We report 2 cases of diffuse intraperitoneal metastases from testicular carcinoma following transabdominal retroperitoneal lymphadenectomy. This is an unusual pattern of metastasis for nonseminomatous germ cell tumors and it is believed to be the result of direct seeding from lymphatic leakage secondary to surgery. The value of computerized tomography in diagnosing this entity is emphasized.     

Combining Vaccines with Conventional Therapies for Cancer

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.     

Predicting outcome in severe heart failure. Who will benefit from device therapy (CRT)?

Dyssynchronous ventricular contraction in severe heart failurecontributes to low cardiac output, worsening symptoms, and poorprognosis. Recognition of the effect of dyssynchrony in heartfailure, and the possibility of manipulating the sequence ofelectrical cardiac activation to improve the efficiency of mechanicalevents, led Cazeau et al. to attempt four-chamber pacing in1994.¹ This early system could stimulate both atria and bothventricles extrinsically, and could dictate the temporal relationshipbetween atrial systole and ventricular systole, and the ventriculo-ventricularrelationship. Modern cardiac resynchronization therapy (CRT),involving pacing of the right and left ventricles, with rightatrial pacing to optimize atrio-ventricular delay, has evolvedrapidly from this beginning. Left bundle branch block (LBBB) on the surface electrocardiogram(ECG) has been considered a marker of mechanical dyssynchronyas it represents a delay in conduction of depolarization tothe left ventricle, with the greatest delay usually being in     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.