Papers by BRIDGETT STANDRIDGE
Open forum infectious diseases, 2018
Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immun... more Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (= .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M;...
Southern Medical Journal, Feb 1, 2001
Studies have shown that aerosolized aminoglycosides represent a safe and effective means of treat... more Studies have shown that aerosolized aminoglycosides represent a safe and effective means of treating pneumonia due to Pseudomonas sp. Aerosolized aminoglycosides have been shown to improve clinical outcome, with less risk of nephrotoxicity relative to parenteral aminoglycosides. Apparently, less drug resistance is associated with the use of aerosolized aminoglycosides. Cost factors favor aerosolized delivery methods. The full recovery experienced by the patient in this case study suggests that aerosolized amikacin may be a safe, efficacious, and cost-effective means of treating pseudomonal pneumonia in geriatric patients. Controlled clinical trials should be conducted to further investigate this treatment regimen.
Family medicine
Pharmaceutical companies provide the majority of financial support for staging the American Acade... more Pharmaceutical companies provide the majority of financial support for staging the American Academy of Family Physicians (AAFP) Annual Scientific Assembly. In return they are allowed to dominate the physical and mental environment. The assembly is opulent and entertaining, but undoubtedly much of the expense is passed to the health care consumer in the form of high-priced brand-name prescription drugs. Additionally, public perception of such spectacles threatens the image that the AAFP has been careful to nurture--that family physicians are the ultimate advocates for our patients and, by extension, the health care-consuming public. Family physicians and our representative AAFP must recognize our complicity with and vulnerability to media forces. We must further adjust our role, not only to avoid the appearance of impropriety but to rededicate ourselves to our science, our intellectual basis, and ultimately our patients.
The Journal of family practice, 2005
American family physician, 2010
Urine drug screening can enhance workplace safety, monitor medication compliance, and detect drug... more Urine drug screening can enhance workplace safety, monitor medication compliance, and detect drug abuse. Ordering and interpreting these tests requires an understanding of testing modalities, detection times for specific drugs, and common explanations for false-positive and false-negative results. Employment screening, federal regulations, unusual patient behavior, and risk patterns may prompt urine drug screening. Compliance testing may be necessary for patients taking controlled substances. Standard immunoassay testing is fast, inexpensive, and the preferred initial test for urine drug screening. This method reliably detects morphine, codeine, and heroin; however, it often does not detect other opioids such as hydrocodone, oxycodone, methadone, fentanyl, buprenorphine, and tramadol. Unexpected positive test results should be confirmed with gas chromatography/mass spectrometry or high-performance liquid chromatography. A positive test result reflects use of the drug within the prev...
Southern Medical Journal, 2008
Alcoholism is the third leading cause of preventable mortality and morbidity in the United States... more Alcoholism is the third leading cause of preventable mortality and morbidity in the United States. Johnson et al have shown that topiramate can improve drinking outcomes among alcohol-dependent individuals. The mechanism is the latest in a series of efforts to translate the developing neuroscience of addiction into clinically beneficial interventions. The topiramate intervention offers real promise for a devastating disease that badly needs effective treatment measures.
American Journal of Hypertension, 2004
A key Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) conclu... more A key Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) conclusion is that thiazide diuretics should be preferred for first-step antihypertensive therapy. ALLHAT was not a monotherapy trial, and rational drug combinations were discouraged by study design in the lisinopril limb. The ALLHAT conclusion that recommends chlorthalidone for initial hypertension therapy seems unjustified because ALLHAT was not a trial that initiated therapy for hypertension. ALLHAT was not of sufficient length to detect the poorer outcomes that are inevitable with increased rates of diabetes in the chlorthalidone limb. The heart failure subset analysis was not prospectively established. ALLHAT was not designed to make the conclusions claimed by its authors.
Current Atherosclerosis Reports, 2005
By failing to recognize the heterogeneity of hypertension, the authors of the Antihypertensive an... more By failing to recognize the heterogeneity of hypertension, the authors of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study used a faulty premise to conduct a poorly designed clinical trial. By failing to control blood pressures equally across study drug groups, ALLHAT cannot be considered to be a definitive comparative trial. Being neither a monotherapy trial nor a trial that initiated therapy for blood pressure control, ALLHAT provided no data to recommend first-line therapy for hypertension, making the conclusions invalid. Thiazide-type diuretics increase angiotensin II and consequently promote atherosclerosis and arteriolarsclerosis. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers retard atherosclerosis and are nephroprotective. Multiple randomized controlled trials show beneficial clinical outcomes, including cardioprotection and nephroprotection, with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These agents, and not thiazide-type diuretics, should be used as first-line agents to retard the process of atherosclerosis and its clinical outcomes in the setting of arterial hypertension.
Therapy, 2005
Evaluation of: Yip AG, Green RC, Huyck M et al. Nonsteroidal anti-inflammatory drug use and Alzhe... more Evaluation of: Yip AG, Green RC, Huyck M et al. Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study. BMC Geriatr. 5(1), 2 (2005). The Multi-Institutional Research in Alzheimer’s Genetic Epidemiology study data reveal an inverse association between nonsteroidal anti-inflammatory drugs (NSAIDs) and Alzheimer’s disease that is more robust among subjects who carried the apolipoprotein E e4 allele. Randomized trials of NSAIDs for the primary prevention of Alzheimer’s disease are unlikely to show effects with treatment until participants have been followed for several years. Inhibition of γ-secretase, as identififed in three Aβ-lowering NSAIDs, is an avenue of research likely to demonstrate preventive efficacy in prospective clinical trials. A subset of NSAIDs, or their analogs, will probably contribute to a combination-therapy approach targeted to different mechanisms of the neuropathology associated with the amyloid cascade.
Southern Medical Journal, 2008
Southern Medical Journal, 2001
Studies have shown that aerosolized aminoglycosides represent a safe and effective means of treat... more Studies have shown that aerosolized aminoglycosides represent a safe and effective means of treating pneumonia due to Pseudomonas sp. Aerosolized aminoglycosides have been shown to improve clinical outcome, with less risk of nephrotoxicity relative to parenteral aminoglycosides. Apparently, less drug resistance is associated with the use of aerosolized aminoglycosides. Cost factors favor aerosolized delivery methods. The full recovery experienced by the patient in this case study suggests that aerosolized amikacin may be a safe, efficacious, and cost-effective means of treating pseudomonal pneumonia in geriatric patients. Controlled clinical trials should be conducted to further investigate this treatment regimen.
Journal of the American Medical Directors Association, 2005
Background and Objective: The pharmacotherapy of Alzheimer's disease (AD) is evolving rapidly. Un... more Background and Objective: The pharmacotherapy of Alzheimer's disease (AD) is evolving rapidly. Unless new discoveries continue to emerge to facilitate prevention and effective treatment of the disease, the anticipated burden of this disease on caregivers and society at large will overwhelm resources. The objective of this paper is to review the state of development of approaches likely to yield effective interventional measures with regard to AD in the future. Design: A comprehensive systematic search of MED-LINE using focused search criteria, a search of reference lists from these studies and reviews, a review of the Cochrane Database of Systematic Reviews, and a hand search of relevant journals was conducted. Selection of articles was based on the clinical focus. Additional inclusion criteria preferentially selected key articles that contained higher-level evidence in accordance with explicit, validated criteria. Results: Pharmaceutical interventions are being developed and tested that confer neuroprotective benefits by targeting causative mechanisms. Conclusion: The paradigm that AD is pharmacologically unresponsive is shifting. Our understanding of the molecular mechanisms of neurodegeneration will soon allow us to more specifically target and interrupt the processes that contribute to this dementia.
Evidence-Based Mental Health, 2004
Clinical Therapeutics, 2004
Background: Alzheimer' s disease (AD), a progressive degenerative disorder of the brain, is the m... more Background: Alzheimer' s disease (AD), a progressive degenerative disorder of the brain, is the most common cause of cognitive impairment in the elderly. The pharmacotherapy of AD is evolving rapidly. Cholinergic stabilization with cholinesterase-inhibitor (ChEI) therapy implies neuroprotection and a resultant slowing of disability and disease progression. The moderate-affinity N-methyl-D-aspartate (NMDA)-receptor antagonist memantine may block neural excitotoxicity. Objective: The purpose of this review was to examine the evidence for the responsiveness to pharmacotherapy of established AD; specifically, the extent to which the benefits of therapy have been proved, the extent to which currently available ChEIs support cholinergic neurotransmission, and the extent to which currently available ChEIs and memantine provide neuroprotection. Methods: Relevant studies were identified through a comprehensive search of MEDLINE for articles published between January 1999 and February 2004 using the terms Alzheimer's pharmacotherapy, cholinesterase inhibitor therapy, Alzheimer's disease, donepezil, rivastigmine, galantamine, glutamatergic system modifiers, and memantine; a search of the reference lists of identified articles; and a manual search of pertinent journals. Articles were selected that contained higher-level evidence, based on explicit validated criteria. Results: ChEI therapy was associated with quality-of-life improvements that included enhanced performance of activities of daily living, reduced behavioral disturbances, stabilized cognitive impairment, decreased caregiver stress, and delay in the first dementia-related nursing home placement. In large clinical trials in moderate to severe AD (a stage that is associated with distress for patients and caregiver burden, and for which other treatments are not available), memantine showed an ability to delay cognitive and functional deterioration. The combination of memantine and ChEI therapy was significantly more efficacious than ChEI therapy alone (P < 0.001) and was well tolerated. Conclusions: The idea that AD is pharmacologically unresponsive appears to be changing. With the use of ChEI and NMDA-receptor antagonist therapy, the symptoms and outcomes of this devastating neurodegenerative disease can be improved and its course altered.
PLoS One, 2010
Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated... more Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4 + counts compared to no therapy. Methodology: Participants not on continuous ART with $300 CD4 + cells/mm 3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly.
Southern Medical Journal, 1994
Adding to the growing awareness of medications that can cause pancreatitis is a small but signifi... more Adding to the growing awareness of medications that can cause pancreatitis is a small but significant number of reports implicating the angiotensin converting enzyme (ACE) inhibitors. In this report, I describe the case of a patient who had no risk factors for pancreatitis and who was taking no medications known to cause pancreatitis other than lisinopril. The abruptness, severity, and fulminant course of this case of probable ACE inhibitor-induced pancreatitis are unprecedented in the medical literature. Possible mechanisms underlying the induction of pancreatitis by ACE inhibitors are discussed. The medical literature concerning pancreatitis and articles reviewing ACE inhibitors do not make note of the relationship between the two. Greater awareness of this association will promote a higher index of suspicion in appropriate clinical settings. Further reporting of cases and clinical research into the cause and prevention of drug-induced pancreatitis appears to be indicated.
Current Alzheimer Research, 2006
Rigorous scientific research has identified multiple interactive mechanisms that parallel and are... more Rigorous scientific research has identified multiple interactive mechanisms that parallel and are likely causative of the development of Alzheimer&#39;s disease (AD). Causative mechanisms include genomics, the creation of amyloid beta (Abeta), factors inhibiting the Abeta removal process, the transformation of Abeta to its toxic forms (various forms of Abeta aggregation), and lastly the oxidative, inflammatory, and other effects of toxic Abeta. Fibrillar beta-amyloid peptide, a major component of senile plaques in AD brain, is known to induce microglial-mediated neurotoxicity under certain conditions, but some recent studies support the notion that Abeta oligomers are the primary neurotoxins. Abeta-42 oligomers that are soluble and highly neurotoxic, referred to as Abeta-derived diffusible ligands (ADDLs), assemble under conditions that block fibril formation. These oligomers bind to dendrite surfaces in small clusters with ligand-like specificity and are capable of destroying hippocampal neurons at nanomolar concentrations. Evidence is presented that AD is triggered by these soluble, neurotoxic assemblies of Abeta rather than the late stage pathology landmarks of amyloid plaques and tangles. The premise is that AD symptoms stem from aberrant nerve cell signaling and synaptic failure rather than nerve cell death, which nevertheless follows and exacerbates the initial pathologies of AD. The defective clearance of amyloid leads to amyloid angiopathy that in turn perpetuates hypoperfusion that affects formation as well as absorption of CSF thereby altering clearance of amyloid and promoting vascular and parenchymal deposition[1]. Hypoperfusion, the defective clearance of amyloid, and resultant increase in amyloid deposition thus represent a vicious cycle. Chronic vascular hypoperfusion-induced mitochondrial failure results in oxidative damage, which drives caspase 3-mediated Abeta peptide secretion and enhances amyloidogenic APP processing. Intracellular Abeta accumulation in turn promotes a significant oxidative and inflammatory mechanism that generates a vicious cycle of Abeta generation and oxidation, each accelerating the other. Abeta activates astrocytes that add to the oxidative imbalance, upregulate the expression of APP via TGF-beta, and are capable of expressing BACE1. Each of these 3 actions accelerates the larger cycle of cholinergic neuron destruction. As oxidative stress induces lesions of cholinergic nuclei producing a reduction in cholinergic neurotransmission, a subsequent increase in cortical APP involving PKCepsilon leads to accelerated amyloidogenic APP metabolism. The linkage of cholinergic activation and APP metabolism completes an additional feedback loop wherein the damage wrought by Abeta accelerates further Abeta production. A comprehensive vision of the neuropathophysiologic mechanisms that result in AD reveals several vicious cycles within a larger vicious cycle, that is to say, a number of interactive systems that each, once set in motion, amplify their own processes, thus accelerating the development of AD.
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Papers by BRIDGETT STANDRIDGE