Agbai O.,University of California at Davis |
Hamzavi I.,Ford Motor Company |
Jagdeo J.,University of California at Davis |
Jagdeo J.,Sacramento Veterans Affairs Medical Center |
Jagdeo J.,New York University
JAMA Dermatology | Year: 2017
IMPORTANCE Lasers are gaining interest as a treatment option for postinflammatory hyperpigmentation (PIH) but can pose a clinical dilemma given the risk for laser-induced or exacerbated PIH. OBJECTIVE To assess the clinical evidence for the use of lasers in the treatment of PIH. EVIDENCE REVIEW A systematic review was performed by searching PubMed databases from January 1, 1990, through May 31, 2016. Included studies involved laser treatment for PIH with the degree of pigmentation as a measure of outcome. The search was filtered to include only clinical studies written in the English language. Study methods were analyzed and the reproducibility of the studies was graded. Outcome measures varied from study to study and included concentration of melanin and hemoglobin, patient satisfaction questionnaires, clinical photography, subjective clinical improvement, light microscopy, melanin index, reflectance spectroscopy, and/or skin biopsy evaluated by a blinded dermatopathologist. FINDINGS Of 1295 results, 20 unique studies with 224 patients met the inclusion criteria. These studies included 1 randomized clinical observer-blinded study (6 patients), 4 nonrandomized clinical trials (133 patients), 1 cohort study (34 patients), 7 case series (44 patients), and 7 case reports (7 patients). Multiple lasers were studied; however,most of the studies were not methodologically rigorous. Some studies showed no improvement or worsening of PIH after laser treatment. The most extensively studied device was the Q-switched Nd:YAG laser, which has shown promising results based on multiple outcome measures as listed above. CONCLUSIONS AND RELEVANCE Some lasers may be beneficial in the treatment of PIH. The evidence suggests that additional studies would be required to determine the benefit of laser treatment of PIH. © 2017 American Medical Association.
Ishimaru T.,University of California at Davis |
Lau J.,University of California at Davis |
Jackson A.L.,University of Minnesota |
Modiano J.F.,University of Minnesota |
Weiss R.H.,Sacramento Veterans Affairs Medical Center
Journal of Urology | Year: 2010
Purpose We evaluated the effect of roscovitine (Sigma-Aldrich®), a pharmacological inhibitor of cyclin dependent kinase, on renal cell carcinoma cell lines in vitro. Materials and Methods We exposed several renal cell carcinoma cell lines to roscovitine and examined apoptotic signaling pathways using immunoblotting and immunohistochemistry. Results As expected, roscovitine caused dose and time dependent inhibition of cyclin dependent kinase 2 autophosphorylation, and of cyclin dependent kinase mediated Pol II phosphorylation in the ACHN (p53-wt) and 786-O (p53 inactive) renal cell carcinoma cell lines (ATCC®). Roscovitine also induced apoptosis in each cell line within a narrow concentration range (about 10 μg/ml). Apoptosis induction was more efficient in ACHN than in 786-O cells and at least partly due to p53 activity. In ACHN cells roscovitine induced apoptosis was associated with p21 induction, and decreased Akt1, XIAP and phospho-Rb expression. These changes also depended on p53 and were not present (p21) or showed a different dose pattern (Akt1, XIAP and phospho-Rb) in 786-O cells. Partial restoration of roscovitine induced apoptosis in 786-O cells by the Mdm-2 inhibitor nutlin-3 (Sigma-Aldrich) suggests that the inactivating mutation of VHL in these cells and its destabilizing effect on p53 are responsible for the decreased sensitivity to apoptosis. Conclusions Our data extend previous studies documenting the pro-apoptotic effect of roscovitine and to our knowledge show for the first time that this activity is restricted to a narrow dose range in renal cell carcinoma cells and partly depends on p53. Thus, roscovitine is a novel potential chemotherapy in a subset of patients with renal cell carcinoma if a narrow therapeutic window is used. These data also provide insight into the role of VHL mutation and p53 in the renal cell carcinoma response to therapeutic cyclin dependent kinase manipulation. © 2010 American Urological Association Education and Research, Inc.
Wang A.S.,University of California at Davis |
Barr K.L.,University of California at Davis |
Jagdeo J.,University of California at Davis |
Jagdeo J.,Sacramento Veterans Affairs Medical Center |
Jagdeo J.,SUNY Downstate Medical Center
Dermatology Online Journal | Year: 2013
Ingestion of raw or undercooked shiitake mushrooms is associated with a distinctive flagellate erythema. We describe a 61-year-old Caucasian man who presented with a pruritic, erythematous eruption of multiple linear streaks on the trunk and extremities starting 1 day after eating raw shiitake mushrooms. His symptoms and skin lesions resolved with minimal hyperpigmentation within approximately 1 week after treating with topical steroids and oral antihistamines. Skin biopsy showed non-specific findings, including a sparse perivascular and interstitial dermatitis as well as focal vacuolar interface changes. Our case illustrates that this condition is a visibly striking dermatitis with a self-limited course. The pathomechanism of the skin eruption remains unclear. © 2013 Dermatology Online Journal.
Nguyen D.-V.,University of California at Davis |
Nguyen D.-V.,Sacramento Veterans Affairs Medical Center |
Murin S.,University of California at Davis |
Murin S.,Sacramento Veterans Affairs Medical Center
Chest | Year: 2016
Bronchial thermoplasty has been found to be a safe and effective therapy for severe asthma. We report the case of amediastinal hematoma and hemothorax developing in a 66-year-old woman several days after an uneventful bronchial thermoplasty of the right lower lobe. Evaluation revealed a bleeding right bronchial artery pseudoaneurysm. Pseudoaneuryms have been reported in association with other procedures involving the therapeutic application of thermal energy, and a single case of hemoptysis requiring bronchial artery embolization occurred in a clinical trial of bronchial thermoplasty. However, bronchial artery pseudoaneurysm with hemomediastinum and hemothorax has not previously been reported after bronchial thermoplasty. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Taylor S.L.,University of California at Davis |
Ganti S.,University of California at Davis |
Bukanov N.O.,Genzyme |
Chapman A.,Emory University |
And 5 more authors.
American Journal of Physiology - Renal Physiology | Year: 2010
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and affects 1 in 1,000 individuals. Ultrasound is most often used to diagnose ADPKD; such a modality is only useful late in the disease after macroscopic cysts are present. There is accumulating evidence suggesting that there are common cellular and molecular mechanisms responsible for cystogenesis in human and murine PKD regardless of the genes mutated, and, in the case of complex metabolomic analysis, the use of a mouse model has distinct advantages for proof of principle over a human study. Therefore, in this study we utilized a urinary metabolomics-based investigation using gas chromatography-time of flight mass spectrometry to demonstrate that the cystic mouse can be discriminated from its wild-type counterpart by urine analysis alone. At day 26 of life, before there is serological evidence of kidney dysfunction, affected mice are distinguishable by urine metabolomic analysis; this finding persists through 45 days until 64 days, at which time body weight differences confound the results. Using functional score analysis and the KEGG pathway database, we identify several biologically relevant metabolic pathways which are altered very early in this disease, the most highly represented being the purine and galactose metabolism pathways. In addition, we identify several specific candidate biomarkers, including allantoic acid and adenosine, which are augmented in the urine of young cystic mice. These markers and pathway components, once extended to human disease, may prove useful as a noninvasive means of diagnosing cystic kidney diseases and to suggest novel therapeutic approaches. Thus, urine metabolomics has great diagnostic potential for cystic renal disorders and deserves further study. Copyright © 2005 by the American Physiological Society.
Inoue H.,University of California at Davis |
Kauffman M.,Karyopharm Therapeutics |
Shacham S.,Karyopharm Therapeutics |
Landesman Y.,Karyopharm Therapeutics |
And 4 more authors.
Journal of Urology | Year: 2013
Purpose: Renal cell carcinoma often presents asymptomatically and patients are commonly diagnosed at the metastatic stage, when treatment options are limited and survival is poor. Since progression-free survival using current therapy for metastatic renal cell carcinoma is only 1 to 2 years and existing drugs are associated with a high resistance rate, new pharmacological targets are needed. We identified and evaluated the nuclear exporter protein CRM1 as a novel potential therapy for renal cell carcinoma. Materials and Methods: We tested the efficacy of the CRM1 inhibitors KPT-185 and 251 in several renal cell carcinoma cell lines and in a renal cell carcinoma xenograft model. Apoptosis and cell cycle arrest were quantified and localization of p53 family proteins was assessed using standard techniques. Results: KPT-185 attenuated CRM1 and showed increased cytotoxicity in renal cell carcinoma cells in vitro with evidence of increased apoptosis as well as cell cycle arrest. KPT-185 caused p53 and p21 to remain primarily in the nucleus in all renal cell carcinoma cell lines, suggesting that the mechanism of action of these compounds depends on tumor suppressor protein localization. Furthermore, when administered orally in a high grade renal cell carcinoma xenograft model, the bioavailable CRM1 inhibitor KPT-251 significantly inhibited tumor growth in vivo with the expected on target effects and no obvious toxicity. Conclusions: The CRM1 inhibitor protein family is a novel therapeutic target for renal cell carcinoma that deserves further intensive investigation for this and other urological malignancies. © 2013 American Urological Association Education and Research, Inc.
Leung F.W.,Research and Medical Services |
Leung F.W.,University of California at Los Angeles |
Leung J.W.,University of California at Davis |
Leung J.W.,Sacramento Veterans Affairs Medical Center |
And 6 more authors.
Endoscopy | Year: 2011
Failure of cecal intubation when using air insufflation during scheduled unsedated colonoscopy in veterans prompted a literature search for a less uncomfortable approach. Water-related maneuvers as adjuncts to air insufflation were identified as effective in minimizing discomfort, although medication requirement was not reduced and willingness to repeat unsedated colonoscopy was not addressed. These adjunct maneuvers were combined with turning the air pump off to avoid colon elongation during insertion. Warm water infusion in lieu of air insufflation was evaluated in observational studies. Subsequent refinements evolved into the water method a combination of air exclusion by aspiration of residual air to minimize angulations at flexures and a dynamic process of water exchange to remove feces in order to clear the view and aid insertion. In subsequent randomized controlled trials, the water method significantly reduced medication requirement, increased the proportion of patients in whom complete unsedated colonoscopy could be achieved, reduced patient recovery time burdens (sedation on demand), decreased abdominal discomfort during and after colonoscopy, enhanced cecal intubation, and increased willingness to repeat the procedure (scheduled unsedated). Supervised education of trainees and self-learning by an experienced colonoscopist were feasible. Lessons learned in developing the water method for optimizing patient-centered outcomes are presented. These proof-of-principle observations merit further research assessment in diverse settings. © Georg Thieme Verlag KGStuttgart, New York.
Leung J.,University of California at Davis |
Leung J.,Sacramento Veterans Affairs Medical Center |
Mann S.,University of California at Davis |
Mann S.,Sacramento Veterans Affairs Medical Center |
And 7 more authors.
Gastrointestinal Endoscopy | Year: 2011
Background: Sedation for colonoscopy discomfort imposes a recovery-time burden on patients. The water method permitted 52% of patients accepting on-demand sedation to complete colonoscopy without sedation. On-site and at-home recovery times were not reported. Objective To confirm the beneficial effect of the water method and document the patient recovery-time burden. Design Randomized, controlled trial, with single-blinded, intent-to-treat analysis. Setting Veterans Affairs outpatient endoscopy unit. Patients This study involved veterans accepting on-demand sedation for screening and surveillance colonoscopy. Intervention Air versus water method for colonoscope insertion. Main Outcome Measurements Proportion of patients completing colonoscopy without sedation, cecal intubation rate, medication requirement, maximum discomfort (0 = none, 10 = severe), procedure-related and patient-related outcomes. Results One hundred veterans were randomized to the air (n = 50) or water (n = 50) method. The proportions of patients who could complete colonoscopy without sedation in the water group (78%) and the air group (54%) were significantly different (P = .011, Fisher exact test), but the cecal intubation rate was similar (100% in both groups). Secondary analysis (data as Mean [SD]) shows that the water method produced a reduction in medication requirement: fentanyl, 12.5 (26.8) μg versus 24.0 (30.7) μg; midazolam, 0.5 (1.1) mg versus 0.94 (1.20) mg; maximum discomfort, 2.3 (1.7) versus 4.9 (2.0); recovery time on site, 8.4 (6.8) versus 12.3 (9.4) minutes; and recovery time at home, 4.5 (9.2) versus 10.9 (14.0) hours (P = .049; P = .06; P = .0012; P = .0199; and P = .0048, respectively, t test). Limitations Single Veterans Affairs site, predominantly male population, unblinded examiners. Conclusion This randomized, controlled trial confirms the reported beneficial effects of the water method. The combination of the water method with on-demand sedation minimizes the patient recovery-time burden. (Clinical trial registration number: NCT00920751.) © 2011 American Society for Gastrointestinal Endoscopy.
Silverberg J.I.,St Lukes Roosevelt Hospital Center |
Patel M.,New York University |
Brody N.,New York University |
Jagdeo J.,New York University |
And 2 more authors.
Journal of Drugs in Dermatology | Year: 2012
Oxidative damage by reactive oxygen species (ROS) plays a major role in aging and carcinogenesis. Little is known about either the effects of acute ROS in necrosis and inflammation of skin or the therapeutic agents for prevention and treatment. Previously, our laboratory identified caffeine as an inhibitor of hydrogen peroxide (H 2O2)-generated lipid peroxidation products in human skin fibroblasts. Here, we study effects of caffeine on acute ROS-mediated necrosis. Human skin fibroblasts were incubated with caffeine, followed by H2O2 challenge. Flow cytometry was used to analyze cell morphology, counts, apoptosis and necrosis, and ROS. We found that caffeine protects from H2O2 cell damage at lower (0.01 mM) and intermediate (0.1 mM) doses. The beneficial effects of caffeine appear to be mediated by a mechanism other than antioxidant function. Copyright © 2012 Journal of Drugs in Dermatology.
Chun K.C.,Sacramento Veterans Affairs Medical Center |
Teng K.Y.,Sacramento Veterans Affairs Medical Center |
Chavez L.A.,University of California at Davis |
Van Spyk E.N.,Sacramento Veterans Affairs Medical Center |
And 5 more authors.
Annals of Vascular Surgery | Year: 2014
Background An active abdominal aortic aneurysm (AAA) screening program at a regional Veterans Affairs (VA) health system identifies patients at risk for AAA. The purpose of this study is to evaluate unique risk factors associated with the AAA diagnosis upon AAA screening examination to identify the most at risk patients for AAA. Methods Data were extracted from a regional VA health care system to identify patients who underwent AAA screening within a 3-year period. An aortic diameter ≥3.0 cm was defined as an AAA. Patient risk factors included age, body mass index, total cholesterol, estimated glomerular filtration rate (eGFR), statin use, and active smoking status; the presence of hypertension, diabetes, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), or peripheral vascular disease (PVD) was also evaluated. Risk factors were compared in a multivariate analysis between patients with AAA and patients with a normal aorta. Results A total of 6,142 patients (mean ± SD age: 72.7 ± 5.3 years) were screened for AAA between January 2007 and December 2009. A total of 469 patients (7.6%) with AAA were identified. The following risk factors were significantly associated with a diagnosis of AAA: age >75 years (39.6% vs. 28.9%; P < 0.001), prevalence of CAD (43.1% vs. 28.5%; P < 0.001), COPD (26% vs. 11.4%; P < 0.001), PVD (37.3% vs. 7.7%; P < 0.001), eGFR <60 mL/min (36.7% vs. 24.3%; P < 0.001), and current smoking (23.2% vs. 15.3%; P < 0.001). The risk factors significantly associated with normal aortic size were the presence of diabetes (18.6% vs. 27.4%; P < 0.001) and total cholesterol ≥200 mg/dL (10.4% vs. 15%; P = 0.04). Conclusions The diagnosis of AAA in a large screening study is typically identified in patients who are at high risk for cardiovascular disease. The presence of diabetes is a major cardiovascular risk factor that is more associated with normal aorta when compared to patients with the AAA diagnosis. Total cholesterol ≥200 mg/dL was associated with decreased AAA risk, and renal insufficiency was associated with increased AAA risk. © 2014 by Elsevier Inc. All rights reserved.