Citations

Object In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. Methods The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme–linked electrode to measure glutamate; and 3) a multiple enzyme–linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig. Results The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA. Conclusions By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery.

ABSTRACT Purpose. The purpose of this report is to describe acute myopia as an ocular adverse reaction to topiramate (Topamax, Ortho‐McNeil, Raritan, NJ) and discuss the importance of recognizing this syndrome. Methods. Retrospective case report and brief review of the literature. Results. A 27‐year‐old female patient developed decreased vision in both eyes due to acute myopia 2 weeks of after initiating therapy with topiramate. Emergency department evaluation revealed visual acuities of 20/400 right eye and 20/200 left eye. Intraocular pressures were 33 mm Hg right eye and 26 mm Hg left eye. The anterior chambers were shallow. Retinal striae were present in the maculae. The patient stated no previous need for optical correction. However, after initiating treatment with topiramate, she refracted to approximately −5.00 D bilaterally. Ultrasound testing revealed that the patient had suprachoroidal effusions in both eyes. The symptoms and clinical findings resolved completely with discontinuation of topiramate, administration of topical atropine 1% and prednisolone acetate 1%. Conclusions. An acute myopic shift may be the presenting sign of an idiosyncratic drug reaction that can include secondary bilateral angle closure glaucoma. This condition can occur in patients who do not have a history of anterior chamber abnormalities. Recognizing this condition and discontinuing the use of the causative drug may prevent angle closure and associated vision loss.

Between 1976 and 2004, 38 revision arthroplasties (35 patients) were performed for aseptic loosening of the humeral component. The mean interval from primary arthroplasty to revision was 7.1 years (0.4 to 16.6). A total of 35 shoulders (32 patients) were available for review at a mean follow-up of seven years (2 to 19.3). Pre-operatively, 34 patients (97%) had moderate or severe pain; at final follow-up, 29 (83%) had no or only mild pain (p < 0.0001). The mean active abduction improved from 88° to 107° (p < 0.01); and the mean external rotation from 37° to 46° (p = 0.27). Excellent or satisfactory results were achieved in 25 patients (71%) according to the modified Neer rating system. Humeral components were cemented in 29, with ingrowth implants used in nine cases. There were 19 of standard length and 17 were longer (two were custom replacements and are not included). Bone grafting was required for defects in 11 humeri. Only two glenoid components were left unrevised. Intra-operative complications included cement extrusion in eight cases, fracture of the shaft of the humerus is two and of the tuberosity in four. There were four re-operations, one for recurrent humeral loosening, with 89% survival free of re-operations at ten years. Revision surgery for aseptic loosening of the humeral component provides reliable pain relief and modest improvement of movement, although there is a substantial risk of intra-operative complications. Revision to a total shoulder replacement gives better results than to a hemiarthroplasty.

Abstract Poor growth in early life is associated with numerous adverse outcomes later in life. In 123 adolescents 16–18 yr of age, the previous findings of a positive relation between size in early life and later bone mass was confirmed. These associations were mediated by the current height and weight, but it was not confirmed that alterations of the GH–IGF axis cause this. Introduction: Numerous studies have found associations between low birth weight and disease later in life, including decreased bone mass. Materials and Methods: A longitudinal cohort of 16- to 19-year-old adolescents (n = 123) with data on third trimester fetal growth velocity (FGV) was assessed by serial ultrasound measurements, birth weight (BW), and weight at 1 yr. A follow-up study included DXA scan, anthropometric measurements, and measurements of the growth hormone (GH) –IGF-I axis in a representative subpopulation (n = 30). Results: BW and weight at 1 yr were positively associated with whole body BMC (p = 0.02 and p &lt; 0.0001, respectively), lumbar spine BMC (p = 0.001 and p = 0.03, respectively), and lumbar spine BMD (p = 0.04). After correction for adolescent height and weight, no association remained significant. There was no relation between IGF-I and IGF binding protein 3 (IGFBP-3) levels in adolescence and size in early life or bone mass. In the subpopulation, GH secretion (median, 2.58 versus 4.05), GH pulse mass (median, 10.7 versus 19.4 mU/liter), and total GH (median, 74.9 versus 108.8 mU/liter/12 h) were decreased in the small for gestational age (SGA) group compared with the appropriate for gestational age (AGA) group; this did not reach statistical significance. Likewise, there were no differences in IGF-I, IGF-II, and IGFBP-1, −2, and −3 levels between the SGA and AGA groups. A statistically significant positive association between FGV and adolescent IGF-II was found (B = 199.9, p = 0.006). Significant negative associations between GH measurement and BMC, as well as BMD, were found (B = −0.008, p = 0.005 and B = −0.008, p = 0.006, respectively). Conclusions: This study confirms the previous findings of a positive relation between size in early life and later BMC, an association apparently independent of the distal part of the GH/IGF-I axis. However, this association may be mediated mainly by postnatal growth determining size of the skeletal envelope rather than an effect of fetal programming on bone mass per se.

In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating leukemic blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors, not only for achieving remission but also for relapse-free survival (RFS). However, in acute myeloid leukemia (AML) parameters of chemosensitivity have been restricted mainly to the rapidity of achievement of complete remission (CR) or the assessment of residual leukemic bone marrow blasts during aplasia. We hypothesized that the time to circulating peripheral blood blast clearance, as a potential surrogate for in vivo chemosensitivity, would have prognostic relevance in AML also. In a retrospective analysis of a cohort of 86 adult patients with AML receiving uniform induction and consolidation chemotherapy, we demonstrate that the time to clearance of circulating blasts during induction chemotherapy is an independent prognostic marker of RFS, superseding other known or established risk factors, including karyotype and number of inductions to achieve CR.