Publications by authors named "Daniel S Han"

12 Publications

  • Page 1 of 1

A Cystic Renal Mass in the Setting of a Pneumothorax: More Than Meets the Eye?

Urology 2021 Feb 9. Epub 2021 Feb 9.

Department of Pediatric Urology, Children's Hospital Colorado, Aurora, CO.

DICER1 syndrome is a rare hereditary cancer predisposition syndrome that has relevance to pediatric urology providers due to its association with many various pediatric genitourinary malignancies. We describe the case of a pediatric patient who was eventually diagnosed with a pathogenic DICER1 germline variant after undergoing resection of a cystic nephroma and pleuropulmonary blastoma.
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http://dx.doi.org/10.1016/j.urology.2021.01.049DOI Listing
February 2021

Enhanced recovery after surgery and anesthetic outcomes in pediatric reconstructive urologic surgery.

Pediatr Surg Int 2021 Jan 7;37(1):151-159. Epub 2020 Nov 7.

Department of Pediatric Urology, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 E. 16th Ave, B-463, Aurora, CO, 80045, USA.

Purpose: Enhanced recovery after surgery (ERAS) is a perioperative management strategy to hasten postoperative recovery. We examined the effects of a pilot implementation of ERAS for pediatric patients on anesthetic outcomes.

Methods: We performed a prospective case-control study utilizing an ERAS protocol in patients aged < 18 years undergoing urologic reconstruction that included a bowel anastomosis. Protocol elements included: multimodal analgesia, opioid minimization, and routine nausea/vomiting prophylaxis. ERAS patients were propensity-matched with historical controls. Outcomes of interest included maximum PACU pain score, time to first opioid, opioid-free days, and need for opioids on day of discharge.

Results: A total of 13 ERAS patients and 26 historical controls were included, with median ages 9.9 years (IQR 9.1-11) and 10.4 years (IQR 8.0-12.4), respectively. ERAS increased the percentage of patients who did not receive any intraoperative or postoperative opioids (0% vs 15%, p = 0.046 for both) and reduced maximum PACU pain score (3 vs 0, p < 0.001). The use of postoperative supplemental oxygen was decreased in the ERAS group (85% vs 38%, p = 0.013).

Conclusions: The implementation of an ERAS protocol appears to decrease postoperative pain, opioid usage, and positively impact other anesthetic outcomes in children undergoing urologic reconstructive surgery utilizing a bowel anastomosis.
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http://dx.doi.org/10.1007/s00383-020-04775-0DOI Listing
January 2021

Reflux Timing Is a Predictor of Successful Endoscopic Treatment of Vesicoureteral Reflux.

Urology 2019 02 29;124:237-240. Epub 2018 Oct 29.

Pediatric Urology, University of California San Diego, Rady Children's Hospital, San Diego, CA.

Objective: To determine whether vesicoureteral reflux (VUR) that occurs during either the filling or voiding phase on voiding cystourethrogram (VCUG) has prognostic significance on successful endoscopic treatment.

Materials And Methods: A retrospective review was performed of 299 patients (438 ureters) with VUR who underwent endoscopic treatment with dextranomer/hyaluronic acid copolymer (Deflux) at a single institution from 2010 to 2013. Success was defined as absence of VUR on 3-month follow-up VCUG. Preoperative VCUGs were analyzed to determine whether the onset of VUR occurred during the filling or voiding phase. Predictor variables to determine success were analyzed, with a specific focus on VUR timing.

Results: Success rate was 319/438 (72.8%) by ureter and 202/299 (67.6%) by patient. Reflux was seen during the filling and voiding phases in 290 and 148 ureters, respectively. Success rate was 203/290 (78%) for filling VUR and 116/148 (70%) for voiding VUR. Univariable analysis revealed voiding VUR had significantly increased odds of success (odds ratio [OR] 3.2, P = .049), while high-grade reflux (OR 0.53, P = .005) had significantly decreased odds of success. Multivariable analysis showed that voiding VUR (OR 3.2, P = .005) had significantly higher odds of success while those with high grade reflux (OR 0.42, P = .017) had significantly decreased odds of success.

Conclusion: The timing of VUR on preoperative VCUG appears to be an important independent predictor of successful endoscopic treatment of VUR. This has important clinical considerations when selecting VUR patients who would be best candidates for endoscopic treatment.
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http://dx.doi.org/10.1016/j.urology.2018.09.034DOI Listing
February 2019

Outpatient Percutaneous Nephrolithotomy: The UC San Diego Health Experience.

J Endourol 2018 05 10;32(5):394-401. Epub 2018 Apr 10.

1 Department of Urology, UC San Diego Health , La Jolla, California.

Introduction: Outpatient percutaneous nephrolithotomy (PCNL) has been described for highly selected patients. We sought to assess the safety and feasibility of outpatient PCNL in a tertiary referral stone center without strict patient selection criteria.

Materials And Methods: We reviewed all PCNLs performed at our institution from September 2015 to October 2016. Of the 97 eligible cases, 60 patients underwent planned outpatient PCNL. Primary outcome was complication rate, and secondary outcome determined predictor variables of inpatient admission.

Results: Thirty-seven inpatient and 60 planned outpatient (one bilateral) PCNLs were performed with 65% and 44% American Society of Anesthesiologists (ASA) score ≥3, respectively. The 30-day overall complication rate for the inpatient and planned outpatient groups was 27% and 20%, respectively (p = 0.43) [70% and 92% Clavien grades I-II]. Emergency department presentation within 30 days was 19% and 18% (p = 0.94), and unplanned hospital readmission rate was 3% and 10% (p = 0.05). The 37 inpatient PCNL patients had larger total stone burden than outpatient cases (40.7 vs 25.8 mm, p = 0.0014); more often required two or more punctures into the kidney during the procedure (73% vs 45%, p = 0.025); and more often had supracostal access (20% vs 7%, p = 0.05). For the outpatient PCNL cohort, 72% patients were discharged same day, 28% were observed overnight for refractory symptoms or social reasons. Outpatient cohort radiographic stone-free rate by CT (no stones) was 67%.

Conclusion: Outpatient PCNL has been safely and effectively performed within our institution in moderate-sized stones almost regardless of comorbidity status. We suggest that this approach is a potential algorithmic change in centers with sufficient case volume.
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http://dx.doi.org/10.1089/end.2018.0056DOI Listing
May 2018

Synthesis, characterization, and in vivo efficacy of shell cross-linked nanoparticle formulations carrying silver antimicrobials as aerosolized therapeutics.

ACS Nano 2013 Jun 4;7(6):4977-87. Epub 2013 Jun 4.

Department of Pediatrics, Division of Pulmonary and Vascular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2-4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag(+) delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence.
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http://dx.doi.org/10.1021/nn400322fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287418PMC
June 2013

Ureteral calculi detection using low dose computerized tomography protocols is compromised in overweight and underweight patients.

J Urol 2012 Jul 12;188(1):124-9. Epub 2012 May 12.

Department ofUrology and Radiology, Loma Linda University Medical Center, Loma Linda, California 92354, USA.

Purpose: Low dose computerized tomography protocols have demonstrated a reduction in radiation exposure while maintaining excellent sensitivity and specificity in the detection of stones in patients of average size. Low dose computerized tomography protocols have not yet been evaluated in subjects in the extremes of weight. We evaluated the effect of body weight when using low dose protocols to detect ureteral calculi.

Materials And Methods: Three cadavers of increasing weight (55, 85 and 115 kg) were prepared by inserting 721 calcium oxalate stones (range 3 to 7 mm) in 33 random configurations into urinary tracts. Cadavers were then scanned using a GE LightSpeed® at 7 radiation settings. An independent, blinded review by a radiologist was conducted to generate ROC curves, with areas under the curve compared using a 1-way ANOVA (α = 0.05).

Results: Sensitivity and specificity were significantly lower in the low and high weight cadavers compared to the medium weight cadaver at 5 mAs (p <0.001) and 7.5 mAs (p = 0.048). Differences in sensitivity and specificity at radiation settings of 15 mAs or greater were not significant.

Conclusions: The sensitivity and specificity for the detection of ureteral calculi on computerized tomography were decreased for underweight and overweight subjects when using extremely low dose radiation settings (less than 1 mSv). Low dose protocols of 15 mAs (2 mSv) can still be used for these subjects without jeopardizing the ability to identify ureteral stones.
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http://dx.doi.org/10.1016/j.juro.2012.02.2568DOI Listing
July 2012

A dynamic model of membrane-bound phospholipase Cβ2 activation by Gβγ subunits.

Mol Pharmacol 2011 Sep 21;80(3):434-45. Epub 2011 Jun 21.

Department of Physiology and Biophysics, Weill Cornell Medical College, Cornell University, New York, New York, USA.

Phospholipase C (PLC) β2, a well studied member of the family of enzymes that catalyze the hydrolysis of the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP₂) into secondary messengers, can be activated by the Gβγ subunits of heterotrimeric G-proteins in a manner that depends on the presence and composition of the associated phospholipid membrane surface. The N-terminal pleckstrin homology (PH) domain of PLCβ2 mediates both the response to Gβγ and membrane binding, but how these interactions are coupled to yield an activated catalytic core remains unknown. Here we propose a mechanism based on molecular models of truncated PLCβ2 in its activated form complexed with Gβγ and in the catalytically inactive/membrane-bound form, obtained with the application of protein-protein docking algorithms and coarse-grained molecular dynamics simulations. These models were probed experimentally, and the inferences were confirmed by results from a combination of molecular biology and fluorescence assays. Results from the dynamic simulations of the molecular models and their interactions with various lipid bilayers identify the determinants of PLCβ2-PH domain specificity for Gβγ and lipid membranes and suggest a mechanism for the previously reported dependence of Gβγ activation on the associated membrane composition. Together, these findings explain the roles of the different activators in terms of their effect on the orientations of the PH and catalytic core domains relative to the lipid membranes.
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http://dx.doi.org/10.1124/mol.111.073403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164327PMC
September 2011

Hybrid transureteral natural orifice translumenal endoscopic nephrectomy: a feasibility study in the porcine model.

J Endourol 2011 Feb 8;25(2):245-50. Epub 2010 Nov 8.

Department of Urology, Loma Linda University School of Medicine, Loma Linda, California, USA.

Background And Purpose: Natural orifice approaches for nephrectomy have included access via the stomach, vagina, bladder, and rectum. The use of the ureter as a natural orifice for natural orifice translumenal endoscopic surgery (NOTES) nephrectomy has not been previously reported. The purpose of this study is to test the feasibility of transureteral laparoscopic NOTES nephrectomy.

Materials And Methods: Three female farm pigs (29.2-30.8 kg) were placed into the lithotomy position. A cystoscopically placed extra-stiff guidewire was used to place a prototype dilating sheath into the left ureter. After dilation of the ureter and urethra, the sheath was exchanged for a 12-mm bariatric laparoscopic trocar. A 10.5-inch long 10-mm offset operating laparoscope with an internal 5-mm working port was used for the nephrectomy. One 2-mm and one 2/3-mm port were placed transabdominally to facilitate in situ morcellation. The kidney was cut into slices using the bipolar device and extracted via the ureteral port using the housing of a 12-mm bariatric stapling device.

Results: All three transureteral nephrectomies were successfully completed. The total mean operative time was 220 minutes (range 113-346 min). Component portions of the procedure were: Ureteral access (mean 21 min), nephrectomy (mean 70 min), and kidney morcellation (mean 103 min). Mean estimated blood loss was 20 mL (range 5-50 mL). There were no intraoperative complications.

Conclusions: This nonsurvival porcine feasibility study demonstrates the successful performance of transureteral nephrectomy. This approach shows promise as a way to decrease the invasiveness of NOTES nephrectomy by using the ureteral orifice as an access site.
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http://dx.doi.org/10.1089/end.2010.0311DOI Listing
February 2011

A theobromine derived silver N-heterocyclic carbene: synthesis, characterization, and antimicrobial efficacy studies on cystic fibrosis relevant pathogens.

Dalton Trans 2009 Sep 6(35):7308-13. Epub 2009 Aug 6.

Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.

The increasing incidence of multidrug-resistant (MDR) pulmonary infections in the cystic fibrosis (CF) population has prompted the investigation of innovative silver based therapeutics. The functionalization of the naturally occurring xanthine theobromine at the N(1) nitrogen atom with an ethanol substituent followed by the methylation of the N(9) nitrogen atom gives the N-heterocyclic carbene precursor 1-(2-hydroxyethyl)-3,7,9-trimethylxanthinium iodide. The reaction of this xanthinium salt with silver acetate produces the highly hydrophilic silver carbene complex SCC8. The in vitro antimicrobial efficacy of this newly synthesized complex was evaluated with excellent results on a variety of virulent and MDR pathogens isolated from CF patients. A comparative in vivo study between the known caffeine derived silver carbene SCC1 and SCC8 demonstrated the ability of both complexes to improve the survival rates of mice in a pneumonia model utilizing the clinically isolated infectious strain of Pseudomonas aeruginosa PA M57-15.
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http://dx.doi.org/10.1039/b907726jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867067PMC
September 2009

The antimicrobial efficacy of sustained release silver-carbene complex-loaded L-tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo studies.

Biomaterials 2009 Aug 23;30(22):3771-9. Epub 2009 Apr 23.

Department of Chemistry, University of Akron, Akron, OH 44325-3601, USA.

The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver-carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into L-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.
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http://dx.doi.org/10.1016/j.biomaterials.2009.03.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801440PMC
August 2009

Active state-like conformational elements in the beta2-AR and a photoactivated intermediate of rhodopsin identified by dynamic properties of GPCRs.

Biochemistry 2008 Jul 18;47(28):7317-21. Epub 2008 Jun 18.

Department of Physiology and Biophysics, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10021, USA.

G-Protein-coupled receptors (GPCRs) adopt various functionally relevant conformational states in cell signaling processes. Recently determined crystal structures of rhodopsin and the beta 2-adrenergic receptor (beta 2-AR) offer insight into previously uncharacterized active conformations, but the molecular states of these GPCRs are likely to contain both inactive and active-like conformational elements. We have identified conformational rearrangements in the dynamics of the TM7-HX8 segment that relate to the properties of the conserved NPxxY(x)5,6F motif and show that they can be used to identify active state-like conformational elements in the corresponding regions of the new structures of rhodopsin and the beta 2-AR.
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http://dx.doi.org/10.1021/bi800442gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664832PMC
July 2008

Membrane localization is critical for activation of the PICK1 BAR domain.

Traffic 2008 Aug 8;9(8):1327-43. Epub 2008 May 8.

Department of Neuroscience and Pharmacology, Molecular Neuropharmacology Group, Center for Pharmacogenomics, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark.

The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redistribution to clusters colocalizing with markers of recycling endosomal compartments. A similar clustering was observed both upon truncation of a short putative alpha-helical segment in the linker between the PDZ and the BAR domains and upon coexpression of PICK1 with a transmembrane PDZ ligand, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit, the GluR2 C-terminus transferred to the single transmembrane protein Tac or the dopamine transporter C-terminus transferred to Tac. In contrast, transfer of the GluR2 C-terminus to cyan fluorescent protein, a cytosolic protein, did not elicit BAR domain-dependent clustering. Instead, localizing PICK1 to the membrane by introducing an N-terminal myristoylation site produced BAR domain-dependent, but ligand-independent, PICK1 clustering. The data support that in the absence of PDZ ligand, the PICK1 BAR domain is inhibited through a PDZ domain-dependent and linker-dependent mechanism. Moreover, they suggest that unmasking of the BAR domain's membrane-binding capacity is not a consequence of ligand binding to the PDZ domain per se but results from, and coincides with, recruitment of PICK1 to a membrane compartment.
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http://dx.doi.org/10.1111/j.1600-0854.2008.00761.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622726PMC
August 2008