Romulus, MI, United States
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He S.,Bethesda University | Bausch S.B.,United Road Services | Bausch S.B.,Bethesda University
Neuropharmacology | Year: 2014

Chronic N-methyl-d-aspartate receptor (NMDAR) blockade with high affinity competitive and uncompetitive antagonists can lead to seizure exacerbation, presumably due to an imbalance in glutamatergic and GABAergic transmission. Acute administration of the moderate affinity NMDAR antagonist memantine in vivo has been associated with pro- and anticonvulsive properties. Chronic treatment with memantine can exacerbate seizures. Therefore, we hypothesized that chronic memantine treatment would increase glutamatergic and decrease GABAergic transmission, similar to high affinity competitive and uncompetitive antagonists. To test this hypothesis, organotypic hippocampal slice culture were treated for 17-21 days with memantine and then subjected to electrophysiological recordings. Whole-cell recordings from dentate granule cells revealed that chronic memantine treatment slightly, but significantly increased sEPSC frequency, mEPSC amplitude and mEPSC charge transfer, consistent with minimally increased glutamatergic transmission. Chronic memantine treatment also increased both sIPSC and mIPSC frequency and amplitude, suggestive of increased GABAergic transmission. Results suggest that a simple imbalance between glutamatergic and GABAergic neurotransmission may not underlie memantine's ictogenic properties. That said, glutamatergic and GABAergic transmission were assayed independently of one another in the current study. More complex interactions between glutamatergic and GABAergic transmission may prevail under conditions of intact circuitry.


Dacher M.,United Road Services | Nugent F.S.,United Road Services
Neuropharmacology | Year: 2011

Adaptive behaviors often require the learning of appropriate responses to rewarding stimuli, yet aberrant learning processes can lead to serious diseases such as addiction. Dopamine (DA) neurons of the ventral tegmental area (VTA) play an essential role in the treatment of rewarding stimuli, and they exhibit plasticity in response to such stimuli, but also to drugs of abuse. Previously we discovered a form of presynaptic nitric oxide (NO)-mediated long-term potentiation (LTP GABA) at GABAergic synapses onto VTA DA neurons that is prevented with morphine in vivo 24 h after exposure. Here we investigated whether the same GABAergic synapses are capable of exhibiting long-term depression (LTD in addition to LTP GABA) and its possible modulation by morphine in vivo. We found that indeed the efficacy of VTA GABAergic synapses can be down-regulated through induction of a novel form of LTD (i.e., LTD GABA) in response to synaptic stimulation. Paired pulse ratio (PPR) and coefficient of variance (CV) analyses of evoked IPSCs confirmed that this plasticity may be postsynaptic. Consistently, LTD GABA did not involve presynaptic cannabinoid CB 1receptors (CB 1Rs). Moreover, NMDAR activation was not necessary for LTD GABA. However, blockade of D 2 dopamine receptors (D 2R) significantly attenuated LTD GABA proposing a novel synaptic mechanism for the regulation of excitability of DA neurons by endogenous DA and D 2R activation. Interestingly, 24 h after a single in vivo exposure to morphine, LTD GABA was absent in slices from morphine-treated rats but unaffected in slices from saline-treated rats, confirming a bidirectional impact of morphine on GABAergic synaptic plasticity in the VTA. The control of bidirectional GABAergic plasticity by morphine in the VTA may represent the neural correlates necessary for the addictive properties of opiates. This article is part of a Special Issue entitled 'Synaptic Plasticity and Addiction'. © 2011 Elsevier Ltd. All rights reserved.


Objectives To audit the quality of written hospital discharge prescriptions and quantify and evaluate pharmacy contributions to ensuring discharge medication information is accurate and complete. Methods A tool was developed and piloted to audit discharge prescription information against best practice guidance. Simultaneously, pharmacist contributions to discharge prescription accuracy and completeness were recorded, classified and rated for potential clinical impact. Results were analysed according to four variables: care area; emergency or elective admission; type of prescription; place of screening. Results 2071 discharge prescriptions were audited in 45 trusts. 32% of prescriptions met the audit definition of legal and unambiguous. Pharmacists made an average of 1.4 contributions per audited prescription to ensure accuracy and completeness of information. 33% of these contributions were judged to have averted moderate or severe patient harm. Minor variations in error rates and potential for clinical impact were seen across the variables studied. Organisations using fully electronic prescribing systems had error and omission rates similar to those producing electronic discharge prescriptions from handwritten charts. Pharmacy-led medicines reconciliation at admission supported the identification of issues requiring resolution in 23% of audited prescriptions. Pharmacy departments screened prescriptions for approximately 50% of patients recorded as discharged. Conclusions Two-thirds of audited discharge prescriptions were inaccurate or incomplete prior to pharmacy screening. Clinical screening by pharmacists contributes significantly to patient safety and is supported by pharmacy-led medicines reconciliation at admission. Discharge prescriptions released without a pharmacy screen could pose a risk to the patient.


Kirsh K.,United Road Services
Journal of pain & palliative care pharmacotherapy | Year: 2012

Prescription opioids are prescribed increasingly for the management of chronic pain, and this has been accompanied by a dramatic rise in opioid-related abuse, addiction, and overdose deaths. Reports of abuse involving nonoral administration (e.g., snorting, injecting) of prescription opioids are increasing, although the epidemiology of oral versus nonoral abuse is not well understood. Available data indicate that oral abuse is far more common,with 72% to 97% of opioid abusers perferring oral administration. Factors associated with nonoral administration include longer duration of opioid abuse, male gender, and rural setting. Extended-release opioids, because of their relatively high drug load, may be attractive to experienced abusers seeking to manipulate the formulation to facilitate a rapid onset of effect. Putative abuse-deterrent formulations have been developed to decrease the likelihood or consequences of nonoral abuse. In addition, Risk Evaluation and Mitigation Strategies (REMS) are now required for prescribed extended-release/long-acting opioids by the US Food and Drug Administration, although their effectiveness in reducing the risk of abuse, addiction, and overdose has not been evaluated. Physicians should remain vigilant when prescribing opioids and should exercise appropriate patient selection, perform risk analysis and stratification, and maintain continuous patient monitoring to ensure the benefits outweigh these important risks.


Williams W.W.,United Road Services
MMWR. Morbidity and mortality weekly report | Year: 2012

In the United States, annual influenza epidemics typically occur during the late fall through early spring. During these epidemics, rates of serious illness and death are highest among adults aged ≥65 years, children aged <2 years, and persons of any age who have medical conditions that increase their risk for complications from influenza. Adults aged 50-64 years who have underlying medical conditions have a substantially increased risk for hospitalization during the influenza season. Influenza illness among healthy adults aged 18-64 years typically is not as severe as the illness among adults aged ≥65 years, pregnant women, or persons with chronic medical conditions and less frequently results in hospitalization. However, influenza among healthy adults aged 18-49 years is an important cause of outpatient medical visits and worker absenteeism. An economic analysis estimated an annual average of approximately 5 million illnesses, 2.4 million outpatient visits, 32,000 hospitalizations, and 680 deaths from influenza among adults aged 18-49 years who did not have a medical condition that increased their risk for influenza complications. In this analysis, adults aged 18-49 years accounted for 10% of the total economic cost from influenza, or approximately $8.7 billion.


Watts N.B.,United Road Services
Endocrine Practice | Year: 2013

Objective: To review information pertinent to bone health and osteoporosis in men.Methods: A review of pertinent literature was conducted.Results: Osteoporosis affects approximately 2 million men in the US and accounts for an estimated 600,000 fractures each year. There are significant differences in skeletal size and structure between men and women that account for differences in fracture incidence, location, and outcomes. Bone density testing is appropriate for men age 70 and older and younger men (50-69) who have risk factors for osteoporosis. Lifestyle management, including adequate calcium and vitamin D intake, appropriate physical activity, and avoidance of tobacco and heavy alcohol use, is appropriate for all men. Pharmacologic therapy to reduce fracture risk is advisable for men with a clinical diagnosis of osteoporosis (a spine or hip fracture) or a T-score of -2.5 or below in the spine, femoral neck, total hip or 1/3 radius; however, the majority of men at high risk will only be identified using a fracture risk assessment tool, such as FRAX. Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options.Conclusions: Osteoporosis in men presents an important public health problem with significant morbidity and mortality. There are recommended strategies for identifying men at high risk of fracture, and effective agents are available for treatment. © 2013 AACE.


Elder R.W.,United Road Services
American Journal of Preventive Medicine | Year: 2012

The Community Preventive Services Task Force recommends person-to-person interventions intended to modify adolescents' risk and protective behaviors by improving their caregivers' parenting skills, on the basis of sufficient evidence of effectiveness in reducing adolescent risk behaviors. These interventions, conducted face-to-face or by telephone, occur outside of clinical settings.


Delany J.R.,United Road Services
MMWR. Surveillance summaries : Morbidity and mortality weekly report. Surveillance summaries / CDC | Year: 2011

These guidelines for biosafety laboratory competency outline the essential skills, knowledge, and abilities required for working with biologic agents at the three highest biosafety levels (BSLs) (levels 2, 3, and 4). The competencies are tiered to a worker's experience at three levels: entry level, midlevel (experienced), and senior level (supervisory or managerial positions). These guidelines were developed on behalf of CDC and the Association of Public Health Laboratories (APHL) by an expert panel comprising 27 experts representing state and federal public health laboratories, private sector clinical and research laboratories, and academic centers. They were then reviewed by approximately 300 practitioners representing the relevant fields. The guidelines are intended for laboratorians working with hazardous biologic agents, obtained from either samples or specimens that are maintained and manipulated in clinical, environmental, public health, academic, and research laboratories.


Edwards T.A.,United Road Services
Veterinary Clinics of North America - Food Animal Practice | Year: 2010

Vaccines and antibiotics are still relied upon as the standard methods of bovine respiratory disease (BRD) prevention, control, and therapy. Success in building disease resistance begins with genetic selection and continues with colostrum management and reducing pathogen exposure. Purchasing single-source cattle with a history of pre- and post-weaning procedures will minimize pathogen exposure and enhance immunity. Using cattle-handling techniques and facilities that promote low stress will allow host immune defenses to remain effective against bacterial and viral colonization. Lastly, controlling BRD must be managed through a comprehensive herd health immunization and management program that effectively addresses disease challenges common to the operation. © 2010 Elsevier Inc.


Watts N.B.,United Road Services
Nature Reviews Endocrinology | Year: 2014

GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ‰ 55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX ® (upper arm, forearm, hip and clinical vertebral fractures) account for >40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases. © 2014 Macmillan Publishers Limited.

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