Timothy Harrah

PURPOSE: To develop a physical understanding of ureterorenoscopy irrigation, we derive mathematical models from basic physical principles and compare these predictions with the results of benchtop experiments. Mathematical modeling can be used to understand the role of inlet pressure, tip deflection, the presence of working tools, geometric properties of the instruments used, and material properties of the irrigation fluid on resulting flow rate. MATERIALS AND METHODS: We develop theoretical models to describe irrigation flow in an idealized setup and compare with benchtop experiments for flow through a straight scope, a scope with a deflected tip, and a scope with a working tool inserted. The benchtop experiments were performed using Boston Scientific LithoVue ureteroscope and a variety of Boston Scientific working tools. Standard ureteroscope working channels have circular cross sections, but using theoretical models we investigate whether modifications to the cross-sectional geometry can enhance flow rates. RESULTS: The theoretical flow predictions are confirmed by experimental results. Tip deflection is shown to have a negligible effect on flow rate, but the presence of working tools decreases flow significantly (for a fixed driving pressure). Flow rate is predicted to improve when tools are placed at the edge of the channel, rather than the center, and modifying the cross-sectional shape from a circle to an ellipse can further increase flow rate. CONCLUSIONS: A mathematical framework is formulated and shown to accurately predict the properties of ureteroscope irrigation flow. The theoretical approach has significant potential in quantifying irrigation flow and improving ureteroscope design.

The distal-half tail fiber of bacteriophage T4 is made of three gene products: trimeric gp36 and gp37 and monomeric gp35. Chaperone P38 is normally required for folding gp37 peptides into a P37 trimer; however, a temperature-sensitive mutation in T4 (ts3813) that suppresses this requirement at 30 degrees C but not at 42 degrees C was found in gene 37 (R. J. Bishop and W. B. Wood, Virology 72:244-254, 1976). Sequencing of the temperature-sensitive mutant revealed a 21-bp duplication of wild-type gene 37 inserted into its C-terminal portion (S. Hashemolhosseini et al., J. Mol. Biol. 241:524-533, 1994). We noticed that the 21-amino-acid segment encompassing this duplication in the ts3813 mutant has a sequence typical of a coiled coil and hypothesized that its extension would relieve the temperature sensitivity of the ts3813 mutation. To test our hypothesis, we crossed the T4 ts3813 mutant with a plasmid encoding an engineered pentaheptad coiled coil. Each of the six mutants that we examined retained two amber mutations in gene 38 and had a different coiled-coil sequence varying from three to five heptads. While the sequences varied, all maintained the heptad-repeating coiled-coil motif and produced plaques at up to 50 degrees C. This finding strongly suggests that the coiled-coil motif is a critical factor in the folding of gp37. The presence of a terminal coiled-coil-like sequence in the tail fiber genes of 17 additional T-even phages implies the conservation of this mechanism. The increased melting temperature should be useful for "clamps" to initiate the folding of trimeric beta-helices in vitro and as an in vivo screen to identify, sequence, and characterize trimeric coiled coils.

Laser lithotripsy is now the preferred treatment option for urolithiasis over Shock wave lithotripsy (SWL) for renal stones smaller than 1.5 cm due to shorter operation times and a better stone-free rates (from the retrospective study by E. B. Cone et al). Nonetheless, the detailed mechanism of calculus disintegration by laser pulse remains relatively unclear. One of the fundamental parameters for laser stone interaction is the ablation threshold. Richard L. Blackmon, et. al. have studied the ablation threshold for Ho: YAG and the thulium fiber lasers (TFL) in terms of the laser energy density. However, an ablation threshold in terms of peak power density would be more universally applicable. In this study, two commercially available Ho: YAG lasers were used as the laser pulse source. The fibers used in the investigation are SureFlexTM fibers, (Models S-LLF273 and S-LLF365) with 273 and 365 μm core diameters, respectively. Calculus phantoms were made of the Bego stone material with various degrees of hardness. These stone phantoms were ablated with the Ho: YAG lasers at different peak power densities. The laser pulse width was measured utilizing a 2 μm photodiode (Thorlabs DET10D), and the laser-induced crater volumes were evaluated with a 3-D digital microscope (Keyence VHX-900F). In this way, we determined the ablation threshold as a function of peak power density for the Bego stone phantoms with 3 different hardness values. Additional investigations of the ablation threshold of other stone types will be conducted in a future study.

Holmium:YAG laser has been the lithotrite of choice for around 30 years in kidney stone surgery. Lasers have evolved over the years to offer higher power, increased pulse frequencies and longer pulse durations. The drivers for change have been to improve stone ablation and to minimise retropulsion. We report on a new prototype Holmium laser that fires multiple “micro-pulses” in “pulse packets” and discuss the stone phantom ablation rate results utilizing a bench model. The prototype laser demonstrated impressive stone ablation rates in our bench testing across a range of power settings. We will discuss the details of these results supporting that pulse-modulation with packets of micro-pulses are a promising technological development. (Disclaimers: Bench Test results may not necessarily be indicative of clinical performance. The testing was performed by or on behalf of BSC.