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An integrated safety analysis of intravenous ibuprofen (Caldolor(Â®)) in adults. - Journal of pain research
Intravenous (IV) nonsteroidal anti-inflammatory drugs such as IV ibuprofen are increasingly used as a component of multimodal pain management in the inpatient and outpatient settings. The safety of IV ibuprofen as assessed in ten sponsored clinical studies is presented in this analysis. Overall, 1,752 adult patients have been included in safety and efficacy trials over 11 years; 1,220 of these patients have received IV ibuprofen and 532 received either placebo or comparator medication. The incidence of adverse events (AEs), serious AEs, and changes in vital signs and clinically significant laboratory parameters have been summarized and compared to patients receiving placebo or active comparator drug. Overall, IV ibuprofen has been well tolerated by hospitalized and outpatient patients when administered both prior to surgery and postoperatively as well as for nonsurgical pain or fever. The overall incidence of AEs is lower in patients receiving IV ibuprofen as compared to those receiving placebo in this integrated analysis. Specific analysis of hematological and renal effects showed no increased risk for patients receiving IV ibuprofen. A subset analysis of elderly patients suggests that no dose adjustment is needed in this higher risk population. This integrated safety analysis demonstrates that IV ibuprofen can be safely administered prior to surgery and continued in the postoperative period as a component of multimodal pain management.
Activation of exogenous fatty acids to acyl-acyl carrier protein cannot bypass FabI inhibition in Neisseria. - The Journal of biological chemistry
Neisseria is a Gram-negative pathogen with phospholipids composed of straight chain saturated and monounsaturated fatty acids, the ability to incorporate exogenous fatty acids, and lipopolysaccharides that are not essential. The FabI inhibitor, AFN-1252, was deployed as a chemical biology tool to determine if Neisseria can bypass the inhibition of fatty acid synthesis by incorporating exogenous fatty acids. Neisseria encodes a functional FabI that was potently inhibited by AFN-1252. AFN-1252 caused a dose dependent inhibition of fatty acid synthesis in growing Neisseria, a delayed inhibition of growth phenotype and minimal inhibition of DNA, RNA, and protein synthesis showing that its mode of action is through inhibiting fatty acid synthesis. Isotopic fatty acid labeling experiments showed that Neisseria encodes the ability to incorporate exogenous fatty acids into its phospholipids by an acyl-acyl carrier protein dependent pathway. However, AFN-1252 remained an effective antibacterial when Neisseria are supplemented with exogenous fatty acids. These results demonstrate that extracellular fatty acids are activated by an acyl-acyl carrier protein synthetase (AasN) and validate type II fatty acid synthesis (FabI) as a therapeutic target against Neisseria.Copyright Â© 2015, The American Society for Biochemistry and Molecular Biology.
Current Food Classifications in Epidemiological Studies Do Not Enable Solid Nutritional Recommendations for Preventing Diet-Related Chronic Diseases: The Impact of Food Processing. - Advances in nutrition (Bethesda, Md.)
To date, observational studies in nutrition have categorized foods into groups such as dairy, cereals, fruits, and vegetables. However, the strength of the association between food groups and chronic diseases is far from convincing. In most international expert surveys, risks are most commonly scored as probable, limited, or insufficient rather than convincing. In this position paper, we hypothesize that current food classifications based on botanical or animal origins can be improved to yield solid recommendations. We propose using a food classification that employs food processes to rank foods in epidemiological studies. Indeed, food health potential results from both nutrient density and food structure (i.e., the matrix effect), both of which can potentially be positively or negatively modified by processing. For example, cereal-based foods may be more or less refined, fractionated, and recombined with added salt, sugars, and fats, yielding a panoply of products with very different nutritional values. The same is true for other food groups. Finally, we propose that from a nutritional perspective, food processing will be an important issue to consider in the coming years, particularly in terms of strengthening the links between food and health and for proposing improved nutritional recommendations or actions.Â© 2015 American Society for Nutrition.
Overview of transparent optical ceramics for high-energy lasers at NRL. - Applied optics
In this review, we present our recent research progress at the Naval Research Laboratory in the development of highly transparent and rugged ceramic window materials such as MgAl2O4 spinel and Î²-SiC; high-power solid-state laser gain materials based on sesquioxide such as Yb3+:Y2O3, Yb3+:Lu2O3, and Ho3+:Lu2O3; and composite ceramics in the application for high-energy lasers. Various powder synthesis/purification methods and powder post-process techniques necessary to create high-purity powders are described. Ceramic fabrication processes and chemical, morphological, and optical properties of the ceramics developed at the Naval Research Laboratory (NRL) are highlighted. We also report high-efficiency lasing from a hot-pressed rare-earth sesquioxide single layer and composite ceramics made from coprecipitated powder.
Development of the My Medicines and Me (M3Q) side effect questionnaire for mental health patients: a qualitative study. - Therapeutic advances in psychopharmacology
The objective of this study was to assess the acceptability, content validity and usability of the My Medicines and Me (M3Q) self-report side effect questionnaire.Eight focus groups consisting of mental health patients, carers, general practitioners, psychiatrists, mental health nurses and pharmacists were conducted, involving 78 participants. Two researchers independently examined the transcriptions and analysed the data thematically using an inductive method.The findings supported changes to the formatting, length and phrasing of questions in the original version of the questionnaire. Although the groups provided differing views on the usability of the M3Q in clinical practice, the patient and carer groups were unconditionally in favour of such a tool to be used systematically to describe patients' subjective experiences with side effects.The differing contribution made by all groups involved in the administration and completion of the M3Q assisted with content validity of the questionnaire. The acceptability and usability of this novel side effect questionnaire was also explored, with many participants agreeing it was a necessary tool for a patient centred approach to treatment. Following implementation of the changes to the current format of the questionnaire, investigation into the uptake and use in clinical practice should be carried out.
Genome analysis of orf virus isolates from goats in the Fujian Province of southern China. - Frontiers in microbiology
Orf virus (ORFV), a species of the genus Parapoxvirus of the family Poxviridae, causes non-systemic, highly contagious, and eruptive disease in sheep, goat, and other wild and domestic ruminants. Our previous work shows orf to be ubiquitous in the Fujian Province of China, a region where there is considerable heterogeneity among ORFVs. In this study, we sequenced full genomes of four Fujian goat ORFV strains (OV-GO, OV-YX, OV-NP, and OV-SJ1). The four strains were 132-139 kb in length, with each containing 124-132 genes and about 64% G+C content. The most notable differences between the four strains were found near the genome termini. OV-NP lacked seven and OV-SJ1 lacked three genes near the right terminus when compared against other ORFVs. We also investigated the skin-virulence of the four Fujian ORFVs in goats. The ORFVs with gene deletions showed low virulence while the ORFVs without gene deletions showed high virulence in goats suggesting gene deletion possibly leads to attenuation of ORFVs. Gene 134 was disrupted in OV-NP genome due to the lack of initial code. The phylogenetic tree based on complete Parapoxviruse genomes showed that sheep originated and goat originated ORFVs formed distinctly separate branches with 100% bootstrap. Based on the single gene phylogenetic tree of 132 genes of ORFVs, 47 genes can be easily distinguished as having originated from sheep or goats. In order to further reveal genetic variation presented in goat ORFVs and sheep ORFVs, we analyzed the deduced amino acid sequences of gene 008, multiple alignment of amino acid sequences of gene 008 from the genome of five goat ORFVs and four sheep ORFVs revealed 33 unique amino acids differentiating it as having sheep or goats as host. The availability of genomic sequences of four Fujian goat ORFVs aids in our understanding of the diversity of orf virus isolates in this region and can assist in distinguishing between orf strains that originate in sheep and goats.
Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy. - Molecular genetics and metabolism
Coenzyme A (CoA) is a ubiquitous cofactor involved in numerous essential biochemical transformations, and along with its thioesters is a key regulator of intermediary metabolism. Pantothenate (vitamin B5) phosphorylation by pantothenate kinase (PanK) is thought to control the rate of CoA production. Pantothenate kinase associated neurodegeneration is a hereditary disease that arises from mutations that inactivate the human PANK2 gene. Aryl phosphoramidate phosphopantothenate derivatives were prepared to test the feasibility of using phosphopantothenate replacement therapy to bypass the genetic deficiency in the Pank1(-/-) mouse model. The efficacies of candidate compounds were first compared by measuring the ability to increase CoA levels in Pank1(-/-) mouse embryo fibroblasts. Administration of selected candidate compounds to Pank1(-/-) mice corrected their deficiency in hepatic CoA. The PanK bypass was confirmed by the incorporation of intact phosphopantothenate into CoA using triple-isotopically labeled compound. These results provide strong support for PanK as a master regulator of intracellular CoA and illustrate the feasibility of employing PanK bypass therapy to restore CoA levels in genetically deficient mice.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Cancer Prevention: Obstacles, Challenges and the Road Ahead. - Journal of the National Cancer Institute
Approaches to reduce the global burden of cancer include two major strategies: screening and early detection and active preventive intervention. The latter is the topic of this Commentary and spans a broad range of activities. The genetic heterogeneity and complexity of advanced cancers strongly support the rationale for early interruption of the carcinogenic process and an enhanced focus on prevention as a priority strategy to reduce the burden of cancer; however, the focus of cancer prevention management should be on individuals at high risk and on primary localized disease in which screening and detection should also play a vital role. The timing and dose of (chemo-)preventive intervention also affects response. The intervention may be ineffective if the target population is very high risk or already presenting with preneoplastic lesions with cellular changes that cannot be reversed. The field needs to move beyond general concepts of carcinogenesis to targeted organ site prevention approaches in patients at high risk, as is currently being done for breast and colorectal cancers. Establishing the benefit of new cancer preventive interventions will take years and possibly decades, depending on the outcome being evaluated. We also propose that comparative effectiveness research designs and the value of information obtained from large-scale prevention studies are necessary in order for preventive interventions to become a routine part of cancer management.Â© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
A clinical communication tool for the assessment of psychotropic medication side effects. - Psychiatry research
The primary aim was to assess usability of the My Medicines and Me Questionnaire (M3Q) as a self-reported questionnaire for mental health patients to subjectively express side effects experienced with their psychotropic medications. The secondary aim was to evaluate patients' attitudes towards treatment and psychotropic medications following dialogue with their clinicians about side effects. Questionnaires were administered at six adult mental health facilities. A total of 205 participants were divided into intervention (facilitated dialogue) and non-intervention groups (no facilitated dialogue). The mean completion time for the M3Q was 15min (SD=6.5) with only 11 (5%) patients requiring assistance. The most commonly reported side effect was sedation (77%) and weight gain was ranked as the most bothersome (23%). The previously validated M3Q provided patients with the opportunity to express the impact these effects had on their lives. Side effects were the most common reason given for non-adherence. There were no significant changes in patient attitudes towards treatment and medications in the intervention group, mainly due to the logistical challenges in the clinicians' ability to view the questionnaire for the subsequent meeting with the patient. The M3Q demonstrated its usability in allowing patients to easily express their subjective experiences with side effects.Copyright Â© 2015 Elsevier Ireland Ltd. All rights reserved.
Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors. - Breast cancer research and treatment
Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5Â % (pÂ <Â 0.0001) and 3.7 versus 1.3Â % (pÂ <Â 0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25-45Â kg/m(2)) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, -3.45 (95Â % Confidence Interval [CI] -6.10, -0.79, pÂ =Â 0.0109) and 0.10 (95Â %CI 0.04, 0.16, pÂ =Â 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm -2.72 (95Â % CI -5.45, 0.01, pÂ =Â 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, -1.64 (95Â % CI -3.13, -0.15, pÂ =Â 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time.
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650 S Cherry St Ste 1015 Denver, CO 80246
4521 E Virginia Ave Bsmt 100
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