Search

Study Design: Retrospective review., Objective: Determine clinical outcomes and cost utility of anterior cervical discectomy and fusion (ACDF) for the treatment of adjacent segment disease (ASD)., Summary of Background Data: The incidence of symptomatic ASD after ACDF has been estimated to occur in up to 26% of patients. Commonly, these patients will undergo an additional ACDF procedure. However, there are currently no studies available that adequately describe the clinical outcomes or cost utility of performing ACDF for ASD., Methods: A retrospective review of 40 patients undergoing ACDF for ASD was performed. Baseline and 2-year neck and arm pain (NRS-NP, NRS-AP), neck disability index (NDI), physical and mental quality of life (SF-12 PCS & MCS), and Zung depression score (ZDS) were assessed. Two-year total neck-related medical resource utilization, amount of missed work, and health-state values were determined. Quality-adjusted life years (QALYs) were calculated from EQ-5D assessments with US valuation. Comprehensive costs (indirect, direct, and total cost) and the value (cost-per-QALY gained) of performing ACDF for ASD were assessed., Results: Performing ACDF to treat ASD resulted in significant improvements (P<0.05) in NRS-NP, NRS-AP, NDI, SF-12 PCS, and ZDS outcome measures. Patient-reported health states also significantly improved, with a mean cumulative 2-year gain of 0.54 QALYs. The mean 2-year cost of surgery was $32,616 (direct cost: $25,391; indirect cost: $7225). ACDF for the treatment of ASD was associated with a mean 2-year cost per QALY gained of $60,526., Conclusions: Performing ACDF for ASD resulted in significant improvements in patient pain, disability, and quality of life. Further, the mean 2-year cost-per-QALY was determined to be $60,526, which suggests surgical intervention to be cost effective. This study is the first to provide evidence that performing an ACDF for ASD is both clinically and cost effective.

Unlabelled: To determine the accuracy of the pre-operative MRI-based diagnosis of soft tissue masses in the forearm, wrist, and hand, the records of 144 patients who underwent an MRI followed by excision of a soft tissue mass in the forearm, wrist, or hand were reviewed. The MRI-based diagnosis was compared to the histological diagnosis, which was considered the gold standard. The sensitivity, specificity, positive predictive value, and negative predictive value of the MRI-based diagnosis were calculated. A multivariate regression analysis was performed.While the accuracy of the MRI-based diagnosis varied widely, there was an overall sensitivity of 75 %. The most accurate diagnosis was an MRI-based diagnosis of ganglion cyst, which had a sensitivity of 94.7 % and a specificity of 94.4 %. Of particular concern was that the MRI-based diagnosis of a malignancy was only 66.7 % sensitive, with a positive predictive value of 44.4 %. On multivariate regression analysis, there was a trend towards improved accuracy in the wrist when compared to the finger, although this did not reach statistical significance.While pre-operative MRI remains a valuable tool for the evaluation of soft tissue masses in the distal upper extremity, caution is warranted when basing the diagnosis on MRI evidence alone., Level of Evidence: Level IV/Diagnostic.

Rationale: Zolpidem is a short-acting, non-benzodiazepine hypnotic that acts as a full agonist at α1-containing GABAA receptors. Overall, zolpidem purportedly has fewer instances of abuse and dependence than traditionally used benzodiazepines. However, several studies have shown that zolpidem may be more similar to benzodiazepines in terms of behavioral tolerance and withdrawal symptoms., Objectives: In the current study, we examined whether subchronic zolpidem or diazepam administration produced deficits in zolpidem's locomotor-impairing effects, anxiety-like behaviors, and changes in GABAAR subunit messenger RNA (mRNA)., Methods: Mice were given subchronic injections of either zolpidem (10 mg/kg), diazepam (20 mg/kg), or vehicle twice daily for 7 days. On day 8, mice were given a challenge dose of zolpidem (2 mg/kg) or vehicle before open field testing. Another set of mice underwent the same injection regimen but were sacrificed on day 8 for qRT-PCR analysis., Results: We found that subchronic zolpidem and diazepam administration produced deficits in the acute locomotor-impairing effects of zolpidem and increased anxiety-like behaviors 1 day after drug termination. In addition, we found that subchronic treatment of zolpidem and diazepam induced distinct but overlapping GABAAR subunit mRNA changes in the cortex but few changes in the hippocampus, amygdala, or prefrontal cortex. Levels of mRNA measured in separate mice after a single injection of either zolpidem or diazepam revealed no mRNA changes., Conclusions: In mice, subchronic treatment of zolpidem and diazepam can produce deficits in the locomotor-impairing effects of zolpidem, anxiety-like withdrawal symptoms, and subunit-specific mRNA changes.

Rationale: Zolpidem is a positive allosteric modulator of γ-aminobutyric acid (GABA) with preferential binding affinity and efficacy for α1-subunit containing GABA(A) receptors (α1-GABA(A)Rs). Over the last three decades, a variety of animal models and experimental procedures have been used in an attempt to relate the behavioral profile of zolpidem and classic benzodiazepines (BZs) to their interaction with α1-GABA(A)Rs., Objectives: This paper reviews the results of rodent and non-human primate studies that have evaluated the effects of zolpidem on motor behaviors, anxiety, memory, food and fluid intake, and electroencephalogram (EEG) sleep patterns. Also included are studies that examined zolpidem's discriminative, reinforcing, and anticonvulsant effects as well as behavioral signs of tolerance and withdrawal., Results: The literature reviewed indicates that α1-GABA(A)Rs play a principle role in mediating the hypothermic, ataxic-like, locomotor- and memory-impairing effects of zolpidem and BZs. Evidence also suggests that α1-GABA(A)Rs play partial roles in the hypnotic, EEG sleep, anticonvulsant effects, and anxiolytic-like of zolpidem and diazepam. These studies also indicate that α1-GABA(A)Rs play a more prominent role in mediating the discriminative stimulus, reinforcing, hyperphagic, and withdrawal effects of zolpidem and BZs in primates than in rodents., Conclusions: The psychopharmacological data from both rodents and non-human primates suggest that zolpidem has a unique pharmacological profile when compared with classic BZs. The literature reviewed here provides an important framework for studying the role of different GABA(A)R subtypes in the behavioral effects of BZ-type drugs and helps guide the development of new pharmaceutical agents for disorders currently treated with BZ-type drugs.

Diabetes results from an inadequate functional β cell mass, either due to autoimmune destruction (Type 1 diabetes) or insulin resistance combined with β cell failure (Type 2 diabetes). Strategies to enhance β cell regeneration or increase cell proliferation could improve outcomes for patients with diabetes. Research conducted over the past several years has revealed that factors regulating embryonic β cell mass expansion differ from those regulating replication of β cells post-weaning. This article aims to compare and contrast factors known to control embryonic and postnatal β cell replication. In addition, we explore the possibility that connective tissue growth factor (CTGF) could increase adult β cell replication. We have already shown that CTGF is required for embryonic β cell proliferation and is sufficient to induce replication of embryonic β cells. Here we examine whether adult β cell replication and expansion of β cell mass can be enhanced by increased CTGF expression in mature β cells.

Trigeminal sensory neurons develop from the neural crest and neurogenic placodes, and have been studied as a principal model of sensory neuron formation. While the Notch pathway has been extensively characterized in central nervous system development and other developmental processes, it has not been well characterized in sensory neurogenesis. Here we studied the functional role of Notch signaling in the trigeminal ophthalmic (opV) placode, a prime model of sensory neurogenesis. To establish a good spatiotemporal description of Notch pathway genes in the chick trigeminal placode, a stage-specific expression analysis was conducted, showing that expression of most Notch pathway genes and effectors are expressed in the placode, with expression primarily being confined to ectodermal cells. Expression was highest at stages of peak neuronal differentiation. To test the function of Notch signaling in opV placode cell differentiation, Notch receptor cleavage was blocked using the gamma-secretase inhibitor, DAPT, or signaling was activated by misexpression of the Notch intracellular domain (NICD). Notch activation resulted in a significant reduction in sensory neurogenesis. Cells remained in the ectoderm and did not differentiate. Expression of the opV specification marker Pax3 was also lost in targeted cells. DAPT exposure resulted in a dramatic increase in neurogenesis without increasing proliferation, where many differentiated cells were found in the mesenchyme and, surprisingly, within the ectoderm. This is the first result clearly showing prolific neuronal differentiation in the ectoderm of the trigeminal placodes after experimental manipulation of a molecular signaling pathway, thus identifying Notch signaling as a primary regulator of the sensory neuron fate in the opV placode., (Copyright 2010 Elsevier Inc. All rights reserved.)

Dissociation of the 10 S androgen receptor to 8, 6, and 4.5 S forms was dependent on temperature, the reducing and ionic environment, and the binding of androgen. The [3H]dihydrotestosterone-labeled 10 S receptor was observed at low ionic strength using rat Dunning prostate tumor cytosol freshly prepared in the absence of an exogenous sulfhydryl reducing agent. Addition of mercaptoethanol caused 10 S receptor dissociation to 8 S following incubation at 0 degrees C for 30 min, to 6 S after a 30-min incubation at 23 degrees C at low ionic strength, and to 4.5 S at high ionic strength. Mercaptoethanol-induced dissociation required binding of [3H]dihydrotestosterone. Treatment with cupric phenanthroline, a disulfide-forming reagent, stabilized the 10 S receptor in 0.4 M KCl, but the receptor remained sensitive to dissociation by mercaptoethanol. Zn2+ (25 microM) and sodium molybdate (10 mM) also stabilized the 10 S receptor. A Stokes radius of 96 +/- 5 A was determined for the 10 S receptor by Sepharose-6B chromatography, with a calculated Mr of 396,000. The 10 S receptor was not retained by DNA-Sepharose, while dissociated forms displayed binding affinity for DNA. It is proposed that the 10 S receptor represents the nontransformed androgen receptor, composed of the 4.5 S steroid binding units plus a nonsteroid binding protein, perhaps in a tetrameric configuration. Binding of dihydrotestosterone appears to sensitize the 10 S receptor to disulfide bond reduction, resulting in transformation by subunit dissociation.

Stated and measured patient heights and weights were compared, and the clinical importance of any differences was determined. A total of 112 health-clinic patients were interviewed for height and weight determinations. They were divided into four groups: men 21-35 years old; men 65 years and older; women 21-35 years old; and women 65 years and older. The stated and the actual heights and weights were analyzed for significant differences. Calculations of body surface area (BSA) and basal energy expenditure (BEE) were used to determine the clinical impact of any discrepancies. Patients in all groups tended to overestimate their height, but only the estimates of men differed significantly from the measured values. Differences between stated and measured heights for older women showed statistical differences from younger men and women but not from older men. All groups except young men overestimated their weight. Older men showed the greatest tendency towards overestimation of weight. In elderly men, the calculations of BSA and BEE were significantly different (p less than 0.002) when stated versus measured values were used. These differences were not considered clinically important. Overall, patients in all groups were well aware of their heights and weights.