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Showing papers by "Medical University of South Carolina published in 2005"


Journal ArticleDOI
TL;DR: Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control (choice), and enhancing glutamatorgic drive in response to drug-associated stimuli.
Abstract: Objective: A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding. Method: Findings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking.

2,496 citations


Journal ArticleDOI
TL;DR: It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D in human subjects was performed and led to the definition of "normal" nutritional vitamin D status, i.e., vitamin D sufficiency, and current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation.
Abstract: It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D [25(OH)D] in human subjects was performed and led to the definition of "normal" nutritional vitamin D status, i.e., vitamin D sufficiency. Sampling human subjects, who appear to be free from disease, and assessing "normal" circulating 25(OH)D levels based on a Gaussian distribution of these values is now considered to be a grossly inaccurate method of identifying the normal range. Several factors contribute to the inaccuracy of this approach, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary intake recommendations for vitamin D. The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. We are now able to better identify sufficient circulating 25(OH)D levels through the use of specific biomarkers that appropriately increase or decrease with changes in 25(OH)D levels; these include intact parathyroid hormone, calcium absorption, and bone mineral density. Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D < or = 80 nmol or 32 microg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation.

1,170 citations


Journal ArticleDOI
22 Jun 2005-JAMA
TL;DR: Characteristics of patients with S aureus IE vary significantly by region, and further studies are required to determine the causes of regional variation.
Abstract: ContextThe global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown.ObjectivesTo document the international emergence of health care–associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE.Design, Setting, and ParticipantsProspective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003.Main Outcome MeasureIn-hospital mortality.ResultsS aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care−associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care−associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons).ConclusionsS aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.

1,101 citations


Journal ArticleDOI
TL;DR: In this 24-week randomized, open-label, noninferiority trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.
Abstract: Background Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. Methods We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. Results Of 140 patients recruited, 71 were randomly assigned to receive myco...

989 citations


Journal ArticleDOI
TL;DR: The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults.

767 citations


Journal ArticleDOI
03 Mar 2005-Neuron
TL;DR: A hypothesis is articulated that altered G protein signaling in the PFC focuses behavior on drug-associated stimuli, while dysregulated PFC-accumbens synaptic glutamate transmission underlies the unmanageable motivation to seek drugs.

644 citations


Journal ArticleDOI
TL;DR: This dissertation aims to provide a history of medical marijuana use in the United States and Canada over a 40-year period from 1989 to 2002, with a focus on the period up to and including the year ending in 2002.
Abstract: Hugh A. Sampson, MD, Anne Munoz-Furlong, BA, S. Allan Bock, MD, Cara Schmitt, MS, Robert Bass, MD, Badrul A. Chowdhury, MD, Wyatt W. Decker, MD, Terence J. Furlong, MS, Stephen J. Galli, MD, David B. Golden, MD, Rebecca S. Gruchalla, MD, Allen D. Harlor, Jr, MD, David L. Hepner, MD, Marilyn Howarth, MD, Allen P. Kaplan, MD, Jerrold H. Levy, MD, Lawrence M. Lewis, MD, Phillip L. Lieberman, MD, Dean D. Metcalfe, MD, Ramon Murphy, MD, Susan M. Pollart, MD, Richard S. Pumphrey, MD, Lanny J. Rosenwasser, MD, F. Estelle Simons, MD, Joseph P. Wood, MD, and Carlos A. Camargo, Jr, MD New York, NY, Fairfax and Charlottesville, Va, Boulder and Denver, Colo, Baltimore, Rockville, and Bethesda, Md, Rochester, Minn, Stanford, Calif, Dallas, Tex, Eugene, Ore, Boston, Mass, Philadelphia, Pa, Charleston, SC, Atlanta, Ga, St Louis, Mo, Cordova, Tenn, Scottsdale, Ariz, Manchester, United Kingdom, and Winnipeg, Manitoba, Canada

641 citations



Journal ArticleDOI
TL;DR: In rats, cymserine analogs caused long-term inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase, and improved the cognitive performance of aged rats.
Abstract: Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused long-term inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE inhibition augmented long-term potentiation. These compounds also improved the cognitive performance (maze navigation) of aged rats. In cultured human SK-N-SH neuroblastoma cells, intra- and extracellular β-amyloid precursor protein, and secreted β-amyloid peptide levels were reduced without affecting cell viability. Treatment of transgenic mice that overexpressed human mutant amyloid precursor protein also resulted in lower β-amyloid peptide brain levels than controls. Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease.

619 citations


Journal ArticleDOI
TL;DR: A new role is suggested for adiponectin as an autocrine factor in adipose tissues: promoting cell proliferation and differentiation from preadipocytes into adipocytes, augmenting programmed gene expression responsible for adipogenesis, and increasing lipid content and insulin responsiveness of the glucose transport system in adipocytes.

598 citations


Journal ArticleDOI
TL;DR: The results from this population suggest that there is a bell-shaped distribution of pelvic organ support in a gynecologic clinic population and Advancing age, Hispanic race, increasing body mass index, and the increasing weight of the vaginally delivered fetus have the strongest correlations with prolapse.

Journal ArticleDOI
TL;DR: Although these results need to be validated in a large clinical trial, this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury.


Journal ArticleDOI
TL;DR: D dorsal hippocampus, basolateral amygdala, and dorsomedial prefrontal cortex play critical roles in contextual reinstatement of cocaine-seeking behavior and the involvement of the DH in explicit CS- and cocaine-induced reinstatement is investigated.


Journal ArticleDOI
TL;DR: The authors discuss the neurobiological interface between substance use Disorders and other psychiatric disorders with an emphasis on emerging data concerning four psychiatric disorders that commonly co-occur with substance use disorders: depression/mood disorders, posttraumatic stress disorder, attention deficit hyperactivity disorder, and schizophrenia.
Abstract: The high rate of co-occurrence of substance use disorders and other psychiatric disorders is well established. The population of people with co-occurring disorders is heterogeneous, and the prevalence of comorbidity differs by diagnostic group. One of the overarching issues in the area of comorbidity is the nature of the connection between psychiatric disorders and substance use disorders. The rapid development of technical advances in the neurosciences has led to a better understanding of the molecular biology, neurotransmitter systems, and neural circuitry involved in mental illness and substance use disorders. The authors discuss the neurobiological interface between substance use disorders and other psychiatric disorders with an emphasis on emerging data concerning four psychiatric disorders that commonly co-occur with substance use disorders: depression/mood disorders, posttraumatic stress disorder, attention deficit hyperactivity disorder, and schizophrenia. Better understanding of the connection between substance use disorders and psychiatric disorders could have a profound effect on prevention and treatment.

Journal ArticleDOI
TL;DR: This work examines data that are missing at random and nonignorable missing, and compares four common approaches for inference in generalized linear models with missing covariate data: maximum likelihood (ML), multiple imputation (MI), fully Bayesian (FB), and weighted estimating equations (WEEs).
Abstract: Missing data is a major issue in many applied problems, especially in the biomedical sciences. We review four common approaches for inference in generalized linear models (GLMs) with missing covariate data: maximum likelihood (ML), multiple imputation (MI), fully Bayesian (FB), and weighted estimating equations (WEEs). There is considerable interest in how these four methodologies are related, the properties of each approach, the advantages and disadvantages of each methodology, and computational implementation. We examine data that are missing at random and nonignorable missing. For ML, we focus on techniques using the EM algorithm, and in particular, discuss the EM by the method of weights and related procedures as discussed by Ibrahim. For MI, we examine the techniques developed by Rubin. For FB, we review approaches considered by Ibrahim et al. For WEE, we focus on the techniques developed by Robins et al. We use a real dataset and a detailed simulation study to compare the four methods.

Journal ArticleDOI
TL;DR: The coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.
Abstract: OBJECTIVE —The aim of this study was to evaluate the effect of depression on all-cause and coronary heart disease (CHD) mortality among adults with and without diabetes. RESEARCH DESIGN AND METHODS —We studied 10,025 participants in the population-based National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study who were alive and interviewed in 1982 and had complete data for the Center for Epidemiologic Studies Depression Scale. Four groups were created based on diabetes and depression status in 1982: 1 ) no diabetes, no depression (reference group); 2 ) no diabetes, depression present; 3 ) diabetes present, no depression; and i4) diabetes present, depression present. Cox proportional hazards regression models were used to calculate multivariate-adjusted hazard ratios (HRs) of death for each group compared with the reference group. RESULTS —Over 8 years (83,624 person-years of follow-up), 1,925 deaths were documented, including 522 deaths from CHD. Mortality rate per 1,000 person-years of follow-up was highest in the group with both diabetes and depression. Compared with the reference group, HRs for all-cause mortality were no diabetes, depression present, 1.20 (95% CI 1.03–1.40); diabetes present, no depression 1.88 (1.55–2.27); and diabetes present, depression present, 2.50 (2.04–3.08). HRs for CHD mortality were no diabetes, depression present, 1.29 (0.96–1.74); diabetes present, no depression 2.26 (1.60–3.21); and diabetes present, depression present, 2.43 (1.66–3.56). CONCLUSIONS —The coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.

Journal ArticleDOI
TL;DR: It is demonstrated that recombinant RPE65, when expressed in QBI-293A and COS-1 cells, has robust enzymatic activity of the previous unidentified isomerohydrolase, an enzyme converting all-trans retinyl ester to 11-cis retinol in the visual cycle.
Abstract: RPE65 is an abundant protein in the retinal pigment epithelium. Mutations in RPE65 are associated with inherited retinal dystrophies. Although it is known that RPE65 is critical for regeneration of 11-cis retinol in the visual cycle, the function of RPE65 is elusive. Here we show that recombinant RPE65, when expressed in QBI-293A and COS-1 cells, has robust enzymatic activity of the previous unidentified isomerohydrolase, an enzyme converting all-trans retinyl ester to 11-cis retinol in the visual cycle. The initial rate for the reaction is 2.9 pmol/min per mg of RPE65 expressed in 293A cells. The isomerohydrolase activity of RPE65 requires coexpression of lecithin retinol acyltransferase in the same cell to provide its substrate. This enzymatic activity is linearly dependent on the expression levels of RPE65. This study demonstrates that RPE65 is the long-sought isomerohydrolase and fills a major gap in our understanding of the visual cycle. Identification of the function of RPE65 will contribute to the understanding of the pathogenesis for retinal dystrophies associated with RPE65 mutations.

Journal ArticleDOI
TL;DR: Improved understanding of the molecular basis of cancer will provide new possibilities for: (1) earlier detection as well as better diagnosis and staging of disease with detection of minimal residual disease recurrences and evaluation of response to therapy; (2) prevention; and (3) novel treatment strategies.

Journal ArticleDOI
TL;DR: Having medications used as a threat or punishment, unwanted sexual advances in a psychiatric setting, inadequate privacy, and sexual assault by a staff member were associated with a history of exposure to sexual assault as an adult.
Abstract: OBJECTIVE: This study examined the frequency and associated distress of potentially traumatic or harmful experiences occurring within psychiatric settings among persons with severe mental illness who were served by a public-sector mental health system. METHODS: Participants were 142 randomly selected adult psychiatric patients who were recruited through a day hospital program. Participants completed a battery of self-report measures to assess traumatic and harmful events that occurred during the course of their mental health care, lifetime trauma exposure, and symptoms of posttraumatic stress disorder. RESULTS: Data revealed high rates of reported lifetime trauma that occurred within psychiatric settings, including physical assault (31 percent), sexual assault (8 percent), and witnessing traumatic events (63 percent). The reported rates of potentially harmful experiences, such as being around frightening or violent patients (54 percent), were also high. Finally, reported rates of institutional measures of...

Journal ArticleDOI
TL;DR: Patients with psoriasis attending the University of Utah Dermatology Clinics were more likely to be obese and to smoke compared with non-psoriatic patients and more likelyto be obese compared with other large cohorts with Psoriasis.
Abstract: UPI. Thus, obesity appears to be the consequence of psoriasis and not a risk factor for onset of disease. We did not observe an increased risk for psoriatic arthritis in patients with obesity; furthermore, obesity did not positively or negatively affect the response or the adverse effects of topical corticosteroids, light-based treatments, and systemic medications. The prevalence of smoking in the UPI population was higher than in the general Utah population (37% vs 13%; P.001)andhigherthaninthenonpsoriaticpopulation(37% vs 25%; P.001). We found a higher prevalence of smokers in the obese population within the UPI than in the obese populationwithintheUtahpopulation(25%vs9%;P.001). Conclusions: Patients with psoriasis attending the University of Utah Dermatology Clinics were more likely to be obese and to smoke compared with nonpsoriatic patients and more likely to be obese compared with other large cohorts with psoriasis. Smoking appears to have a role in the onset of psoriasis, but obesity does not. The high prevalence of obesity and smoking in a psoriasis cohort has not been previously noted; if confirmed, it supports the prediction that a significant portion of patients with psoriasis will have the comorbid conditions and public health issues of those with obesity and smoke. Arch Dermatol. 2005;141:1527-1534


Journal ArticleDOI
TL;DR: It is demonstrated that nonsynaptic glutamate derived from xc- modulates synaptic glutamate release and thereby regulates cocaine-induced drug seeking.
Abstract: Withdrawal from chronic cocaine reduces extracellular glutamate levels in the nucleus accumbens by decreasing cystine/glutamate exchange (xc-). Activating xc- with N-acetylcysteine restores extracellular glutamate and prevents cocaine-induced drug seeking. It was hypothesized that the activation of xc- prevents drug seeking by increasing glutamatergic tone on presynaptic group II metabotropic glutamate receptors (mGluR2/3) and thereby inhibiting excitatory transmission. In the first experiment, the capacity of glutamate derived from xc- to regulate excitatory transmission via mGluR2/3 was determined. Physiological levels of cystine (100-300 nm) were restored to acute tissue slices from the nucleus accumbens or prefrontal cortex. Cystine increased glutamate efflux and decreased miniature EPSC (mEPSC) and spontaneous EPSC (sEPSC) frequency as well as evoked EPSC amplitude. These effects of cystine were presynaptic, because there was no change in mEPSC or sEPSC amplitude, and an increase in the evoked EPSC paired-pulse facilitation ratio. The cystine-induced reduction in EPSCs was reversed by blocking either xc- or mGluR2/3. In the second experiment, blocking mGluR2/3 prevented the ability of N-acetylcystine to inhibit the reinstatement of drug seeking in rats trained to self-administer cocaine. These data demonstrate that nonsynaptic glutamate derived from xc- modulates synaptic glutamate release and thereby regulates cocaine-induced drug seeking.

Journal ArticleDOI
TL;DR: The peroral endoscopic transgastric approach to ligation of the Fallopian tubes with long-term survival is technically feasible and safe in a porcine model and has potential for a wide array of diagnostic and therapeutic procedures.

Journal ArticleDOI
TL;DR: Patients being operated for NSCLC are elderly with significant comorbid conditions and Mediastinoscopy is infrequently performed and lymph nodes are biopsied in less than 50% of them, and positive surgical margins are too frequent.

Journal ArticleDOI
TL;DR: Results indicate that AICAR can be utilized as a therapeutic drug to inhibit cancer, and AMPK can be a potential target for treatment of various cancers independent of the functional tumor suppressor gene, LKB.

Journal ArticleDOI
TL;DR: It is proposed that zonula occludens (ZO)-1 controls the rate of Cx43 channel accretion at GJ peripheries, which, in conjunction with the rates of GJ turnover, regulates GJ size and distribution.
Abstract: Regulation of gap junction (GJ) organization is critical for proper function of excitable tissues such as heart and brain, yet mechanisms that govern the dynamic patterning of GJs remain poorly defined. Here, we show that zonula occludens (ZO)-1 localizes preferentially to the periphery of connexin43 (Cx43) GJ plaques. Blockade of the PDS95/dlg/ZO-1 (PDZ)-mediated interaction between ZO-1 and Cx43, by genetic tagging of Cx43 or by a membrane-permeable peptide inhibitor that contains the Cx43 PDZ-binding domain, led to a reduction of peripherally associated ZO-1 accompanied by a significant increase in plaque size. Biochemical data indicate that the size increase was due to unregulated accumulation of gap junctional channels from nonjunctional pools, rather than to increased protein expression or decreased turnover. Coexpression of native Cx43 fully rescued the aberrant tagged-connexin phenotype, but only if channels were composed predominately of untagged connexin. Confocal image analysis revealed that, subsequent to GJ nucleation, ZO-1 association with Cx43 GJs is independent of plaque size. We propose that ZO-1 controls the rate of Cx43 channel accretion at GJ peripheries, which, in conjunction with the rate of GJ turnover, regulates GJ size and distribution.

Journal ArticleDOI
TL;DR: The abstinence-based incentive procedure, which provided a mean of 203 dollars in prizes per participant, was efficacious in improving retention and associated abstinence outcomes.
Abstract: Context Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence are efficacious in improving outcomes in substance abusers, but these treatments have rarely been implemented in community-based settings. Objective To evaluate the efficacy of an abstinence-based contingency management intervention as an addition to usual care in community treatment settings. Design Random assignment to usual care or usual care plus abstinence-based incentives for 12 weeks. Setting Eight community-based outpatient psychosocial drug abuse treatment programs. Participants A total of 415 cocaine or methamphetamine users beginning outpatient substance abuse treatment. Intervention All participants received standard care, and those assigned to the abstinence-based incentive condition also earned chances to win prizes for submitting substance-free urine samples; the chances of winning prizes increased with continuous time abstinent. Main Outcome Measures Retention, counseling attendance, total number of substance-free samples provided, percentage of stimulant- and alcohol-free samples submitted, and longest duration of confirmed stimulant abstinence. Results Participants assigned to the abstinence-based incentive condition remained in treatment for a mean ± SD of 8.0 ± 4.2 weeks and attended a mean ± SD of 19.2 ± 16.8 counseling sessions compared with 6.9 ± 4.4 weeks and 15.7 ± 14.4 sessions for those assigned to the usual care condition ( P P Conclusion The abstinence-based incentive procedure, which provided a mean of $203 in prizes per participant, was efficacious in improving retention and associated abstinence outcomes.

Journal ArticleDOI
TL;DR: It is suggested that patients with chronic or recurrent, treatment-resistant depression may show long-term benefit when treated with VNS, and longer-term VNS was generally well tolerated.
Abstract: Background: Vagus nerve stimulation (VNS) had antidepressant effects in an initial open, acute phase pilot study of 59 participants in a treatment-resistant major depressive episode (MDE). We examined the effects of adjunctive VNS over 24 months in this cohort. Method: Adult outpatients (N = 59) with chronic or recurrent major depressive disorder or bipolar (I or II) disorder and experiencing a treatment-resistant, nonpsychotic MDE (DSM-IV criteria) received 2 years of VNS. Changes in psychotropic medications and VNS stimulus parameters were allowed only after the first 3 months. Response was defined as > or = 50% reduction from the baseline 28-item Hamilton Rating Scale for Depression (HAM-D-28) total score, and remission was defined as a HAM-D-28 score < or = 10. Results: Based on last observation carried forward analyses, HAM-D-28 response rates were 31% (18/59) after 3 months, 44% (26/59) after 1 year, and 42% (25/59) after 2 years of adjunctive VNS. Remission rates were 15% (9/59) at 3 months, 27% (16/59) at 1 year, and 22% (13/59) at 2 years. By 2 years, 2 deaths (unrelated to VNS) had occurred, 4 participants had withdrawn from the study, and 81% (48/59) were still receiving VNS. Longer-term VNS was generally well tolerated. Conclusion: These results suggest that patients with chronic or recurrent, treatment-resistant depression may show long-term benefit when treated with VNS.