Browsing by Author "Williams, James"

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    Comparative Analyses and Ablation Efficiency of Thulium Fiber Laser by Stone Composition
    (Wolters Kluwer, 2024) Johnson, Jeffrey; Lee, Justin; Movassaghi, Miyad; Han, David; Pingle, Srinath-Reddi; Williams, James; Schulster, Michael; Gorroochurn, Prakash; Shao, Yinming; Shah, Ojas; Anatomy, Cell Biology and Physiology, School of Medicine
    Purpose: There are limited data on ablation effects of thulium fiber laser (TFL) settings with varying stone composition. Similarly, little is known surrounding the photothermal effects of TFL lithotripsy regarding the chemical and structural changes after visible char formation. We aim to understand the TFL's ablative efficiency across various stone types and laser settings, while simultaneously investigating the photothermal effects of TFL lithotripsy. Materials and methods: Human specimens of calcium oxalate monohydrate, calcium oxalate dihydrate, uric acid, struvite, cystine, carbonate apatite, and brushite stones were ablated using 13 prespecified settings with the Coloplast TFL Drive. Pre- and postablation mass, ablation time, and total energy were recorded. Qualitative ablative observations were recorded at 1-minute intervals with photographs and gross description. Samples were analyzed with Fourier-transform infrared spectroscopy pre- and postablation and electron microscopy postablation to assess the photothermal effects of TFL. Results: Across all settings and stone types, 0.05 J × 1000 Hz was the best numerically efficient ablation setting. When selected for more clinically relevant laser settings (ie, 10-20 W), 0.2 J × 100 Hz, short pulse was the most numerically efficient setting for calcium oxalate dihydrate, cystine, and struvite stones. Calcium oxalate monohydrate ablated with the best numerical efficiency at 0.4 J × 40 Hz, short pulse. Uric acid and carbonate apatite stones ablated with the best numerical efficiency at 0.3 J × 60 Hz, short pulse. Brushite stones ablated with the best numerical efficiency at 0.5 J × 30 Hz, short pulse. Pulse duration impacted ablation effectiveness greatly with 6/8 (75%) of inadequate ablations occurring in medium or long pulse settings. The average percent of mass lost during ablation was 57%; cystine stones averaged the highest percent mass lost at 71%. Charring was observed in 36/91 (40%) specimens. Charring was most often seen in uric acid, cystine, and brushite stones across all laser settings. Electron microscopy of char demonstrated a porous melting effect different to that of brittle fracture. Fourier-transform infrared spectroscopy of brushite char demonstrated a chemical composition change to amorphous calcium phosphate. Conclusions: We describe the optimal ablation settings based on stone composition, which may guide urologists towards more stone-specific care when using thulium laser for treating renal stones (lower energy settings would be safer for ureteral stones). For patients with unknown stone composition, lasers can be preset to target common stone types or adjusted based on visual cues. We recommend using short pulse for all TFL lithotripsy of calculi and altering the settings based on visual cues and efficiency to minimize the charring, an effect which can make the stone refractory to further dusting and fragmentation.
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    Mechanisms of human kidney stone formation
    (Springer, 2015-01) Evan, Andrew P.; Worcester, Elaine M.; Coe, Fredric L.; Williams, James; Lingeman, James E.; Department of Anatomy and Cell Biology, IU School of Medicine
    The precise mechanisms of kidney stone formation and growth are not completely known, even though human stone disease appears to be one of the oldest diseases known to medicine. With the advent of the new digital endoscope and detailed renal physiological studies performed on well phenotyped stone formers, substantial advances have been made in our knowledge of the pathogenesis of the most common type of stone former, the idiopathic calcium oxalate stone former as well as nine other stone forming groups. The observations from our group on human stone formers and those of others on model systems have suggested four entirely different pathways for kidney stone formation. Calcium oxalate stone growth over sites of Randall's plaque appear to be the primary mode of stone formation for those patients with hypercalciuria. Overgrowths off the ends of Bellini duct plugs have been noted in most stone phenotypes, do they result in a clinical stone? Micro-lith formation does occur within the lumens of dilated inner medullary collecting ducts of cystinuric stone formers and appear to be confined to this space. Lastly, cystinuric stone formers also have numerous small, oval, smooth yellow appearing calyceal stones suggestive of formation in free solution. The scientific basis for each of these four modes of stone formation are reviewed and used to explore novel research opportunities.
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    Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents with Eosinophilic Esophagitis
    (Wolters Kluwer, 2022-06) Gupta, Sandeep K.; Hill, Malcolm; Vitanza, Joanne M.; Farber, Robert H.; Desai, Nirav K.; Williams, James; Song, Ivy H.; Pediatrics, School of Medicine
    The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE)(MPI 101-01/NCT00762073). Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2–9 or 10–18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution versus bodyweight and body mass index were also evaluated. Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post-dose and the half-life of budesonide was 3.3–3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.
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    Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis
    (Wolters Kluwer, 2023) Mukkada, Vincent A.; Gupta, Sandeep K.; Gold, Benjamin D.; Dellon, Evan S.; Collins, Margaret H.; Katzka, David A.; Falk, Gary W.; Williams, James; Zhang, Wenwen; Boules, Mena; Hirano, Ikuo; Desai, Nirav K.; Pediatrics, School of Medicine
    Objectives: The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE). Methods: This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined. Results: Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo. Conclusions: BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.
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    Validation of a Real Time PCR Assay for the Detection of Ureaplasma urealyticum
    (Office of the Vice Chancellor for Research, 2015-04-17) Fortney, Sarah; Ermel, Aaron; Williams, James; Fife, Kenneth
    Ureaplasma urealyticum (UU) is a bacterium that occurs naturally in the genital flora of sexually active men and women. In high concentrations this bacterium can become pathogenic causing urethritis. Detection of UU by nucleic acid amplification is not widely practiced in the US, and culture isolation requires a specialized lab. The aim is to validate an assay utilizing a Real Time PCR (RT-PCR) for the detection of UU in our laboratory, and to determine the prevalence of UU in men and women attending a local STI clinic. A previously published RT-PCR assay was utilized to amplify a 152 base pair fragment of a highly conserved region of UU. The 152 base pair fragment of UU was amplified from an isolate and cloned into a TOPO-PCRII plasmid. The plasmid was used to develop quantitative standards of known concentrations; then to optimize and confirm the assay parameters, and determine the limit of detection for the assay. Assay performance in clinical matrix by spiked clinical specimens will be used to confirm the limit of detection when using residual samples. The UU fragment was successfully cloned and purified into a plasmid, which was verified by restriction enzyme digestion and PCR followed by gel electrophoresis. The plasmid containing the UU fragment was quantified using spectrophotometry and contained 7.27x1010 copies/μL. This plasmid was utilized in optimizing the RT-PCR assay, including primer concentrations and annealing temperature. Standards were developed through a dilution series of the purified plasmid from 1x1010-1x101 copies/μL. An increase in reaction efficiency was noted when the probe concentration was decreased from 0.2μM to 0.15 μM. Preliminary results show that the assay can detect down to ~10 copies/μl using purified plasmid. Thus far the assay has been optimized for our laboratory, and a set of standards to determine the limit of detection is being developed.