Citations

Object Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain. Methods The FSCV study consisted of a triangle wave scanned between −0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 μm) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by ~ 100 μm. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system. Results The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer); 2) Bluetooth transceiver; 3) microprocessor; and 4) direct-current battery. A Windows-XP laptop computer running custom software and equipped with a Universal Serial Bus–connected Bluetooth transceiver served as the base station. Computer software directed wireless data acquisition at 100 kilosamples/second and remote control of FSCV operation and adjustable waveform parameters. The WINCS provided reliable, high-fidelity measurements of dopamine and other neurochemicals such as serotonin, norepinephrine, and ascorbic acid by using FSCV at CFM and by flow injection analysis. In rats, the WINCS detected subsecond striatal dopamine release at the implanted sensor during high-frequency stimulation of ascending dopaminergic fibers. Overall, in vitro and in vivo testing demonstrated comparable signals to a conventional hardwired electrochemical system for FSCV. Importantly, the WINCS reduced susceptibility to electromagnetic noise typically found in an operating room setting. Conclusions Taken together, these results demonstrate that the WINCS is well suited for intraoperative neurochemical monitoring. It is anticipated that neurotransmitter measurements at an implanted chemical sensor will prove useful for advancing functional neurosurgery.

Abstract Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610–6)

ABSTRACT A retrospective examination of quantitation standard growth curves associated with 1,000 unique clinical serum specimens tested by a laboratory-developed TaqMan hepatitis C virus analyte-specific reagent-based assay revealed anomalous growth curves associated with 0.40% (95% confidence interval, 0.11% to 1.00%) of these specimens.

AbstractWhile it is generally accepted that most partial and isolated medial collateral ligament (MCL) injuries can be treated non‐operatively, ideal treatment of the MCL in multi‐ligament knee injuries remains controversial. High failure rates with repair of the posterolateral corner in the multi‐ligament injured knee have been recently reported, favoring reconstruction instead. The same maybe true for MCL injuries, however evidence‐based treatment recommendations are lacking in the current orthopedic literature. The purpose of this study was to perform an evidence‐based systematic review of the operative management (repair and/or reconstruction) of the MCL in the setting of multi‐ligament knee injuries. A comprehensive search of MEDLINE and the Cochrane databases for all relevant articles published in English from 1978 to 2008 on the outcomes of surgical management (repair and/or reconstruction) of the MCL in the setting of combined ligament injuries was performed. Inclusion criteria included articles published in (1) English, (2) on human subjects, (3) between the years of 1978 and 2008, (4) had minimum 12‐month follow‐up, with a mean of at least 24 months, (5) on surgical management of MCL injuries, (6) associated with multi‐ligament injuries (three or more ligaments) and/or knee dislocation, and (7) reported objective outcome data on the respective patient cohorts. Exclusion criteria consisted of technique papers, case reports, studies that included fractures associated with MCL injury and those that included pediatric patients. The review identified eight relevant studies. Five articles focused on MCL repair, while three articles focused on MCL reconstruction. No prospective studies compared MCL repair or reconstruction with non‐operative treatment or directly compared MCL reconstruction with MCL repair. Currently there is a paucity of objective data on the outcomes regarding surgical management of MCL tears in the combined ligament injured knee. This systematic review demonstrated satisfactory results in both repair and reconstruction groups. Future objective outcome‐based studies as well as comparative studies are needed to further evaluate the optimal treatment modality before evidence‐based recommendations can be made. Therefore, individual treatment decisions for each patient should be based on the characteristics and nature of the injury.

Background. Hepatitis C virus (HCV) nondetectability in the liver may predict a sustained viral response (SVR) in patients with an end of treatment response. HCV RNA can be detected in liver tissue by in situ hybridization (ISH).Aim. To determine if HCV nondetectability in liver allografts by ISH can predict SVR in patients who cleared virus serologically on treatment.Methods. Twenty five patients with undetectable serum HCV on Interferon/Ribavirin therapy for HCV recurrence post liver transplant (LT) were studied. All had biopsies at 4 months post LT (baseline) and follow up with HCV ISH analysis performed.Results. 10 were ISH positive (group 1); 15 were ISH negative (group 2). Groups 1 and 2 had similar patient, donor, and viral characteristics at LT, as well as treatment duration at the time of the ISH assayed liver biopsy (13±16versus10±4monthsP= .24). However, group 1 had longer total treatment duration (24±10versus14±5months,P= .001). Eight (80%) group 1 and 9 (60%) group 2 patients achieved SVR. Mean grade and stage (modified Ishak score) were similar at 4 months, however, group 1 had higher grade (3±1.7versus1.6±1.3,P= .039) and stage (1.4±1.4versus0.5±0.6,P= .084) on the ISH assayed biopsy, after similar post LT intervals (23±10versus24±12months,P= .91).Conclusion. Allograft HCV ISH nondetectability does not predict SVR in treatment responsive HCV recurrence, but is associated with less severe histologic disease.