10 results on '"Saben J"'
Search Results
2. Renal autotransplant as a definitive treatment for nutcracker syndrome: A multicenter retrospective study.
- Author
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Philip JL, Saben J, Meram E, Steinberg T, Lauer K, Malamon J, Pomfret E, Nydam T, Foley DP, and Pshak T
- Abstract
Objective: Nutcracker syndrome is a rare condition that involves mechanical compression of the left renal vein, leading to chronic and debilitating left flank pain. The etiology of the pain is misdiagnosed frequently, and patients usually require long-term opioid use to manage their pain. Multiple therapeutic options for nutcracker syndrome have been described in the literature but the reports are limited by small numbers of patients, and the lack of convincing data demonstrating consistently improved outcomes. Here we report the largest series to date of patients undergoing renal autotransplantation for the treatment of nutcracker syndrome., Methods: We performed a multicenter retrospective cohort review of patients 105 patients with nutcracker syndrome who underwent renal autotransplantation as a primary or salvage therapy., Results: During the overall study period, 93.1% of patients treated with autotransplantation had durable, complete flank pain relief at 12 months with both open and robotic surgical approach. After autotransplantation, a statistically significant decrease in the percentage of patients using opioids from 48.6% to 17.0% was demonstrated at 12 months. In those patients using opioids before autotransplantation, a statistically significant decrease in morphine milligram equivalents was demonstrated from an alarming 68.9 ± 15.0 per day to 25.0 ± 11.02 morphine milligram equivalents per day., Conclusions: Our findings suggest that renal autotransplantation, as a primary treatment or a salvage treatment, in patients with nutcracker syndrome provides durable pain relief and a marked decrease in chronic opioid use regardless of surgical approach., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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3. The Genomics of Elevated ALT and Adducts in Therapeutic Acetaminophen Treatment: a Pilot Study.
- Author
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Monte AA, Sonn B, Saben J, Rumack BH, Reynolds KM, Dart RC, and Heard KJ
- Subjects
- Adult, Female, Genetic Variation, Genome-Wide Association Study, Humans, Immune System, Male, Middle Aged, Pilot Projects, Young Adult, Acetaminophen therapeutic use, Acetaminophen toxicity, Analgesics, Non-Narcotic toxicity, Chemical and Drug Induced Liver Injury drug therapy, Chemical and Drug Induced Liver Injury genetics, Genetic Predisposition to Disease, Pain drug therapy
- Abstract
Introduction: Therapeutic acetaminophen (APAP) ingestion causes asymptomatic drug-induced liver injury in some patients. In most cases, elevations in alanine aminotransferase (ALT) are transient and return to the normal range, even with continued APAP ingestion, though ALT elevation persists in some patients unpredictably. The etiology of this liver injury or adaption is unclear. Our objective was to identify new pharmacogenomic variants associated with elevated ALT or elevated protein adduct concentrations in patients receiving therapeutic acetaminophen., Methods: We performed genome-wide sequencing analysis on eight patients using leftover blood samples from an observational study that administered four grams of acetaminophen for up to 16 days to all patients. Two patients with ALT elevations > two times the upper limit of normal, two patients with no adduct formation, and four control patients were sequenced. The genomes were aligned with the GRCh38 reference sequence, and variants with predicted low, moderate, or high impact on the subsequent proteins were first manually curated for biologic plausibility, then organized and examined in the REACTOME pathway analysis program., Results: We found 394 variants in 107 genes associated with elevated ALT. Variants associated with ALT elevation predominantly involved genes in the immune system (MHC class II complex genes), endoplasmic reticulum stress response (SEC23B and XBP1), oxidative phosphorylation (NDUFB9), and WNT/beta-catenin signaling (FZD5). Variants associated with elevated adducts were primarily in signal transduction (MUC20) and DNA repair mechanisms (P53)., Conclusions: While underpowered, genetic variants in immune system genes may be associated with drug-induced liver injury at therapeutic doses of acetaminophen.
- Published
- 2021
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4. Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites.
- Author
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Brocker CN, Velenosi T, Flaten HK, McWilliams G, McDaniel K, Shelton SK, Saben J, Krausz KW, Gonzalez FJ, and Monte AA
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- Adult, Aged, Aged, 80 and over, Bacteria growth & development, Bacteria metabolism, Blood Pressure, Female, Humans, Hypertension drug therapy, Hypertension microbiology, Hypertension urine, Male, Middle Aged, Prospective Studies, Antihypertensive Agents therapeutic use, Bacteria drug effects, Gastrointestinal Microbiome, Hypertension metabolism, Metabolome drug effects, Metoprolol therapeutic use, Urinalysis methods
- Abstract
Introduction: Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. Metabolomics, the study of end-stage metabolites of upstream biologic processes, yield insight into mechanisms of drug effectiveness and safety. Our aim was to determine metabolomic profiles associated with metoprolol effectiveness for the treatment of hypertension., Methods: We performed a prospective pragmatic trial (NCT02293096) that enrolled patients between 30 and 80 years with uncontrolled HTN. Patients were started on metoprolol succinate at a dose based upon systolic blood pressure (SBP). Urine and blood pressure measurements were collected weekly. Individuals with a 10% decline in SBP or heart rate (HR) were considered responsive. Genotype for the CYP2D6 enzyme, the primary metabolic pathway for metoprolol, was evaluated for each subject. Unbiased metabolomic analyses were performed on urine samples using UPLC-QTOF mass spectrometry., Results: Urinary metoprolol metabolite ratios are indicative of patient CYP2D6 genotypes. Patients taking metoprolol had significantly higher urinary levels of many gut microbiota-dependent metabolites including hydroxyhippuric acid, hippuric acid, and methyluric acid. Urinary metoprolol metabolite profiles of normal metabolizer (NM) patients more closely correlate to ultra-rapid metabolizer (UM) patients than NM patients. Metabolites did not predict either 10% SBP or HR decline., Conclusion: In summary, urinary metabolites predict CYP2D6 genotype in hypertensive patients taking metoprolol. Metoprolol succinate therapy affects the microbiome-derived metabolites.
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- 2020
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5. Acute Illness Associated with Cannabis Use, by Route of Exposure: An Observational Study.
- Author
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Monte AA, Shelton SK, Mills E, Saben J, Hopkinson A, Sonn B, Devivo M, Chang T, Fox J, Brevik C, Williamson K, and Abbott D
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- Cardiovascular Diseases etiology, Colorado epidemiology, Emergency Service, Hospital organization & administration, Humans, Marijuana Abuse epidemiology, Marijuana Abuse physiopathology, Mental Disorders etiology, Retrospective Studies, Vomiting etiology, Administration, Inhalation, Marijuana Abuse complications
- Published
- 2019
6. Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy.
- Author
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Boudoures AL, Saben J, Drury A, Scheaffer S, Modi Z, Zhang W, and Moley KH
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- Animals, Antimycin A toxicity, Cells, Cultured, Female, Gene Dosage drug effects, Hydrazones toxicity, Membrane Potential, Mitochondrial drug effects, Mice, Mice, Inbred C57BL, Obesity pathology, Autophagy physiology, DNA, Mitochondrial genetics, Gene Dosage genetics, Membrane Potential, Mitochondrial physiology, Mitochondria pathology, Mitophagy physiology, Oocytes metabolism
- Abstract
Mitochondria are the most prominent organelle in the oocyte. Somatic cells maintain a healthy population of mitochondria by degrading damaged mitochondria via mitophagy, a specialized autophagy pathway. However, evidence from previous work investigating the more general macroautophagy pathway in oocytes suggests that mitophagy may not be active in the oocyte. This would leave the vast numbers of mitochondria - poised to be inherited by the offspring - vulnerable to damage. Here we test the hypothesis that inactive mitophagy in the oocyte underlies maternal transmission of dysfunctional mitochondria. To determine whether oocytes can complete mitophagy, we used either CCCP or AntimycinA to depolarize mitochondria and trigger mitophagy. After depolarization, we did not detect co-localization of mitochondria with autophagosomes and mitochondrial DNA copy number remained unchanged, indicating the non-functional mitochondrial population was not removed. To investigate the impact of an absence of mitophagy in oocytes with damaged mitochondria on offspring mitochondrial function, we utilized in vitro fertilization of high fat high sugar (HF/HS)-exposed oocytes, which have lower mitochondrial membrane potential and damaged mitochondria. Here, we demonstrate that blastocysts generated from HF/HS oocytes have decreased mitochondrial membrane potential, lower metabolites involved in ATP generation, and accumulation of PINK1, a mitophagy marker protein. This mitochondrial phenotype in the blastocyst mirrors the phenotype we show in HF/HS exposed oocytes. Taken together, these data suggest that the mechanisms governing oocyte mitophagy are fundamentally distinct from those governing somatic cell mitophagy and that the absence of mitophagy in the setting of HF/HS exposure contributes to the oocyte-to-blastocyst transmission of dysfunctional mitochondria., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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7. Maternal pregravid obesity changes gene expression profiles toward greater inflammation and reduced insulin sensitivity in umbilical cord.
- Author
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Thakali KM, Saben J, Faske JB, Lindsey F, Gomez-Acevedo H, Lowery CL Jr, Badger TM, Andres A, and Shankar K
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- Adiposity physiology, Adult, Analysis of Variance, Anthropometry, Blotting, Western, Cell Adhesion Molecules metabolism, DNA Primers genetics, Early Growth Response Protein 1 metabolism, Female, Gene Expression Profiling, Human Umbilical Vein Endothelial Cells, Humans, Insulin blood, Leptin blood, Microarray Analysis, Proto-Oncogene Proteins c-fos metabolism, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Umbilical Cord metabolism, Gene Expression Regulation physiology, Inflammation physiopathology, Insulin Resistance physiology, Maternal Nutritional Physiological Phenomena physiology, Obesity physiopathology, Umbilical Cord physiopathology
- Abstract
Background: Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC)., Methods: UCs from 12 lean (pregravid BMI < 24.9) and 10 overweight/obese (pregravid BMI ≥ 25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays. Metabolic parameters were assayed in mother's plasma and cord blood., Results: Although offspring birth weight and adiposity (at 2 wk) did not differ between groups, expression of 232 transcripts was affected in UC from overweight/obese compared with those of lean mothers. Gene-set enrichment analysis revealed an upregulation of genes related to metabolism, stimulus and defense response, and inhibitory to insulin signaling in the overweight/obese group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from overweight/obese mothers, while endothelin receptor B, KLF10, PEG3, and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST, and SOCS1 were positively correlated (P < 0.05) with mother's first-trimester body fat mass (%)., Conclusion: Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life.
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- 2014
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8. Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity.
- Author
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Saben J, Zhong Y, Gomez-Acevedo H, Thakali KM, Borengasser SJ, Andres A, and Shankar K
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- Activating Transcription Factor 3 immunology, Activating Transcription Factor 3 metabolism, Cell Line, Early Growth Response Protein 1 genetics, Early Growth Response Protein 1 metabolism, Female, Humans, Infant, Newborn, Interleukin-6 genetics, Interleukin-6 immunology, Interleukin-6 metabolism, Interleukin-8 genetics, Interleukin-8 immunology, Interleukin-8 metabolism, Lipid Metabolism genetics, MAP Kinase Signaling System drug effects, MAP Kinase Signaling System immunology, Male, Palmitates pharmacology, Placenta cytology, Pregnancy, Serum Response Factor immunology, Serum Response Factor metabolism, Transcriptome drug effects, Transcriptome immunology, Trophoblasts cytology, Trophoblasts immunology, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha pharmacology, Early Growth Response Protein 1 immunology, Lipid Metabolism immunology, Obesity immunology, Placenta immunology, Pregnancy Complications immunology
- Abstract
Obesity is associated with low-grade chronic inflammation, which contributes to cellular dysfunction promoting metabolic disease. Obesity during pregnancy leads to a proinflammatory milieu in the placenta; however, the underlying causes for obesity-induced placental inflammation remain unclear. Here, we examine the mechanisms by which saturated fatty acids and inflammatory cytokines induce inflammation in placental trophoblasts. We conducted global transcriptomic profiling in BeWo cells following palmitate and/or TNFα treatment and gene/protein expression analyses of MAPK pathways and characterized downstream transcription factors directly regulating inflammatory cytokines. Microarray analysis revealed increased expression of genes regulating inflammation, stress response, and immediate early response in cytotrophoblasts in response to palmitic acid (PA), TNFα, or a combination of both (PA + TNFα). Both gene ontology and gene set enrichment analysis revealed MAPK and EGR-1 signaling to be upregulated in BeWo cells, which was confirmed via immunoblotting. Importantly, activation of JNK signaling was necessary for increased proinflammatory cytokine (IL-6, TNFα, and IL-8) and EGR1 mRNA. Consistent with the requirement of JNK signaling, ChIP analysis confirmed the recruitment of c-Jun and other MAPK-responsive immediate early factors on the EGR1 promoter. Moreover, recruitment of EGR-1 on cytokine promoters (IL-6, TNFα, and IL-8) and an impaired proinflammatory response following knockdown of EGR-1 suggested it as a central component of the mechanism facilitating inflammatory gene expression. Finally, akin to in vitro findings, term placenta from obese women also had both increased JNK and p38 signaling and greater EGR-1 protein relative to lean women. Our results demonstrate that lipotoxic insults induce inflammation in placental cells via activation of JNK/EGR-1 signaling.
- Published
- 2013
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9. I'm a doctor ... and I played one on TV.
- Author
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Saben J
- Subjects
- Anecdotes as Topic, Communication Barriers, Humans, Public Relations, Uncertainty, Family Practice education, Informed Consent, Internship and Residency, Physician-Patient Relations, Television
- Published
- 2003
10. A day in the life...perspectives by a family practice intern.
- Author
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Saben J
- Subjects
- Anecdotes as Topic, Humans, Physician-Patient Relations, United States, Workload, Family Practice education, Internship and Residency, Physician's Role
- Published
- 2001
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