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A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-β peptide of 40-42 amino acid residues (1). Prefibrillar, soluble oligomers of amyloid-β have been recognized to be early and key intermediates in Alzheimer's-disease-related synaptic dysfunction (2-9). At nanomolar concentrations, soluble amyloid-β oligomers block hippocampal long-term potentiation (7), cause dendritec spine retraction from pyramidal cells (5,8) and impair rodent spatial memory (2). Soluble amyloid-β oligomers have been prepared from chemical syntheses, transfected cell culture supernatants, transgenic mouse brain and human Alzheimer's disease brain (2,4,7,9). Together, these data imply a high-affinity cell-surface receptor for soluble amyloid-β oligomers on neurons-one that is central to the pathophysiological process in Alzheimer's disease. Here we identify the cellular prion protein ([PrP.sup.C]) as an amyloid-β-oligomer receptor by expression cloning. Amyloid-β oligomers bind with nanomolar affinity to [PrP.sup.C], but the interaction does not require the infectious [PrP.sup.Sc] conformation. Synaptic responsiveness in hippocampal slices from young adult PrP null mice is normal, but the amyloid-β oligomer blockade of long-term potentiation is absent. Anti-PrP antibodies prevent amyloid-β-oligomer binding to [PrP.sup.C] and rescue synaptic plasticity in hippocampal slices from oligomeric amyloid-β. Thus, [PrP.sup.C] is a mediator of amyloid-β-oligomer-induced synaptic dysfunction, and [PrP.sup.C]-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease., To characterize amyloid-β-oligomer-binding sites, we synthesized amyloid-β(1-42) peptide conjugated to biotin through the α amino group (biotin-Aβ42), and then denatured the peptide and allowed oligomers to form as described for [...]

I read with interest the article by Mark Crane ['Treating pain without fear,' July 4, 2008]. Mr. Crane points out the importance of regular immunoassay urine drug tests in the [...]

I read with interest the recent article by Mark Crane ["Treating pain without fear," July 4, 2008]. He points out the importance of regular immunoassay urine drug tests in the [...]

Background: Because the symptoms of drug misuse are nonspecific and difficult to detect, pain physicians have relied heavily on the results of urine drug tests to diagnose and treat chronic noncancer pain in patients who are prescribed controlled substances. However, changes in Medicare local carrier determinations for Medicare Part B providers in Connecticut, Indiana, Kentucky, and New York went into effect on July 1, 2009, whereby qualitative drug screening was no longer recognized as medically reasonable and necessary in the treatment of patients with chronic noncancer pain unless the patient presents with suspected drug overdose., Study Design: A retrospective review of urine drug testing services., Objective: To determine the extent of urine drug testing in patients with chronic noncancer pain in a large, Kentucky neuroscience practice offering pain management services combined with neurologic and neurosurgical services to better understand the potential effects of recent changes to Medicare benefits., Methods: An audit of services provided during 2007 was conducted using computer software., Outcome Measures: Outcome measures included the number of practice services, number of urine drug tests by payor, and the number of noncompliant patients by payor who self-released from care., Results: Urine drug tests represented approximately 18.2% of professional medical services rendered in 2007 to patients with a diagnosis of chronic noncancer pain. Of these, UDTs represented approximately 22.2% of services provided to Medicare patients and 24.6% of services provided to Medicaid patients. In 2007, 2,081 patients with noncompliant UDTs self released from the practice against medical advice. Of these, 23.1% were enrolled in Medicare and 47.5% were enrolled in Medicaid. Approximately 40% of patients were referred to the CARE Clinic on the basis of noncompliance as indicated by UDT and/or behavioral health issues. Of these, approximately 50% remained in treatment. Urine drug tests were also instrumental in revealing that 19.6% of patients showed signs of drug abuse or addiction. Of these patients, approximately 60% were government insured., Limitations: Not a prospective, double-blinded study. We approximated the proportion of patients potentially affected by drug abuse or addiction as the percentage of patients self releasing from medical care., Conclusion: In 2007, UDTs were used as an effective tool in adherence monitoring in a private neuroscience practice in Kentucky that offers pain management services combined with neurologic and neurosurgical services. UDTs were instrumental in referring 40% of patients for evaluation and treatment by behavioral health and addiction medicine specialists. UDTs were also instrumental in discovering signs of drug abuse or addiction in 19.6% of patients. Of these patients, approximately 60% were government insured. Should the objective and reliable sign offered by UDTs be eliminated from the physician's toolbox, the physician's ability to accurately diagnose and treat these patients could be impaired.

A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-beta peptide of 40-42 amino acid residues. Prefibrillar, soluble oligomers of amyloid-beta have been recognized to be early and key intermediates in Alzheimer's-disease-related synaptic dysfunction. At nanomolar concentrations, soluble amyloid-beta oligomers block hippocampal long-term potentiation, cause dendritic spine retraction from pyramidal cells and impair rodent spatial memory. Soluble amyloid-beta oligomers have been prepared from chemical syntheses, transfected cell culture supernatants, transgenic mouse brain and human Alzheimer's disease brain. Together, these data imply a high-affinity cell-surface receptor for soluble amyloid-beta oligomers on neurons-one that is central to the pathophysiological process in Alzheimer's disease. Here we identify the cellular prion protein (PrP(C)) as an amyloid-beta-oligomer receptor by expression cloning. Amyloid-beta oligomers bind with nanomolar affinity to PrP(C), but the interaction does not require the infectious PrP(Sc) conformation. Synaptic responsiveness in hippocampal slices from young adult PrP null mice is normal, but the amyloid-beta oligomer blockade of long-term potentiation is absent. Anti-PrP antibodies prevent amyloid-beta-oligomer binding to PrP(C) and rescue synaptic plasticity in hippocampal slices from oligomeric amyloid-beta. Thus, PrP(C) is a mediator of amyloid-beta-oligomer-induced synaptic dysfunction, and PrP(C)-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease.