Development of a clinically useful multi-segment kinetic foot model.

BACKGROUND: Traditionally, gait analysis studies record the foot as a single rigid segment, leaving movements and loads within the foot undetected. In addition, very few data of multi-segment foot kinetics have been represented in the literature due to measurement and equipment limitations. As a result, this study aims to develop a novel multi-segment kinetic foot model that is clinically feasible and enables both kinematic and kinetic analysis of large patient groups. RESULTS: Outcome measurements include rotation angles of intersegmental dorsi/plantar flexion, inversion/eversion, and internal/external rotation, joint moments, joint powers and the medial longitudinal arch (MLA) height/length ratio. Repeatability of joint motions was calculated using coefficients of multiple correlation. Most joint motions measured by this foot model showed strong within-subject reliability (R > 0.7) in healthy adults. Outcome measures were in agreement with other multi-segment foot models found in the biomechanics literature. CONCLUSIONS: This novel multi-segment foot model is able to quantify intersegmental foot kinematics and kinetics and can be a useful tool for research and assessments on clinical populations.

A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance.

BACKGROUND: MET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected with MET-amp at EGFR-TKI progression using next-generation sequencing. METHODS: Of the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed. RESULTS: The objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 vs. 2.3 vs. 2.9 months, p = 0.010), but overall survival was comparable (10.0 vs. 4.1 vs. 8.5 months, p = 0.088). TP53 mutation (58.5%) and EGFR-amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included EGFR-T790M (n = 2), EGFR-L718Q (n = 1), EGFR-S645C (n = 1), MET-D1228H (n = 1), BRAF-V600E (n = 1), NRAS-Q61H (n = 1), KRAS-amp (n = 1), ERBB2-amp (n = 1), CDK4-amp (n = 1), and MYC-amp (n = 1). CONCLUSION: Our study provides real-world clinical evidence from a large cohort that simultaneous inhibition of EGFR and MET could be a more effective therapeutic strategy for patients with MET-amp acquired from EGFR-TKI therapy.

Prognosis and Concurrent Genomic Alterations in Patients With Advanced NSCLC Harboring MET Amplification or MET Exon 14 Skipping Mutation Treated With MET Inhibitor: A Retrospective Study.

BACKGROUND: MET amplification or METex14 skipping mutations are uncommon oncogenic events in NSCLC patients. Clinicopathological characteristics, concurrent gene alterations, and prognosis of MET TKIs in these patients are yet to be elucidated. METHODS: We retrospectively analyzed the genomic profiles of 43 MET amplifications or 31 METex14 skipping mutations in NSCLC patients with no previous treatment with EGFR TKIs. Survival outcomes were analyzed in evaluable patients receiving MET TKI treatment: MET amplification cohort (n = 29) and METex14 skipping mutation cohort (n = 29). RESULTS: Among evaluable patients, a shorter PFS was observed in the MET amplification cohort than in the METex14 skipping mutation cohort (7.0 months vs. 11.0 months, P = 0.043). Concurrent mutations in both cohorts resulted in a statistically significant shorter PFS (MET amplification: 3.5 months versus 8.0 months, P = 0.038, METex14 skipping mutation: 7.0 versus NR months, P = 0.022). However, a statistically significant OS (17.0 months versus 20.0 months, P = 0.044) was only observed in the MET amplification cohort. TP53, the most common concurrent mutation in both cohorts, was associated with worse survival outcomes as compared to the wild type. The MET amplification cohort with a concurrent PIK3CA mutation exhibited primary resistance to MET TKIs and showed disease progression (80%). CONCLUSION: MET TKIs could be a better treatment option for patients with METex14 skipping mutations. Concurrent mutations may deteriorate the PFS of MET TKIs in NSCLC patients with MET amplification or METex14 skipping mutations. PIK3CA mutations may confer primary resistance to MET TKIs in patients with MET amplification.

Evaluation of the pharmacokinetic effects of itraconazole on alflutinib (AST2818): an open-label, single-center, single-sequence, two-period randomized study in healthy volunteers.

Alflutinib (AST2818) is a newly developed third-generation EGFR tyrosine kinase inhibitor for the treatment of lung cancer patients with T790M-resistant mutations. It is metabolized mainly by the CYP3A4 enzyme. At the same time, it has the potential to induce CYP3A4. In this study, we aimed to estimate the effect of itraconazole (a strong inhibitor of CYP3A4) on the pharmacokinetics of alflutinib. For this aim, a single-center, open-label, single-sequence, two-period trial was designed. The pharmacokinetic parameters of AST2818 and its active metabolite AST5902 were established from blood concentration measurements, and adverse events (AEs) of two periods of treatment were documented. For AST2818, the Cmax, AUC0-t, and AUC0-∞ in period II (coadministration of itraconazole) increased by 6.5 ng/mL, 1263.0 h*ng/mL, and 1067.0 h*ng/mL, respectively. And the corresponding 90% CIs were 1.23 (1.14-1.32), 2.41 (2.29-2.54), and 2.22 (2.11-2.34), respectively. The Cmax, AUC0-t, and AUC0-∞ of AST5902 in period II decreased by 4.849 ng/mL, 415.60 h*ng/mL, and 391.4 h*ng/mL, respectively. Moreover, the corresponding 90% CIs were 0.09 (0.08-0.10), 0.18 (0.17-0.19), and 0.14 (0.13-0.15), respectively. Nonetheless, in period II, plasma concentrations of total active components (AST2818 and AST5902) changed marginally. The AUC0-∞ of total active components increased 60%, and the corresponding Cmax increased 8%. Possible treatment-related AEs assessed by investigators were fewer in period II (23.3% vs 36.7%). In conclusion, the total exposure of AST2818 and active metabolite AST5902 increased following the coadministration of itraconazole, but it was still safe and well-tolerated.

Clinicopathological and prognostic significance of PD-1/PD-L1 axis expression in patients with tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is more aggressive than other head and neck tumors, and the prognosis for patients with advanced TSCC is poor. At present, comprehensive treatment based on surgery as the main method is not effective for patients with advanced TSCC. The application of PD-1/PD-L1 immunocheckpoint inhibitor alone in patients with TSCC has not been reported. To explore the role of PD-1/PD-L1, we investigated the expression of PD-1 and PD-L1 in TSCC and analyzed the relationship between the expression of PD-1 and PD-L1 and the related clinicopathological parameters and survival prognosis. The expression of PD-1 was significantly associated with palindromia (p = .015) and maximum diameter (p = .043). The expression of PD-L1 in tumor cells was significantly associated with N stage (P = .024), chemotherapy (p = .032), and clinical stage (p = .019). The expression of PD-L1 in infiltrating lymphocytes was significantly associated with palindromia (p = .030). Univariate and multivariate Cox analyses for prognoses of patients showed significant prognostic factors of overall survival and relapse-free survival. The high expression of PD-L1 on infiltrating lymphocytes for OS and RFS was an independent protective factor for patients with TSCC. The high expression of PD-1 on infiltrating lymphocytes and clinical stage for OS and RFS were independent risk factors for patients with TSCC. The data provide a reference for clinical treatment of TSCC with immunotherapy.

A Randomized, Open, Single-Centre, Crossed Study of the Effect of Food on the Pharmacokinetics of One Oral Dose of Alflutinib Mesylate Tablets (AST2818) in Healthy Male Subjects.

The aim of the study was to study the PK of AST2818 tablets after one oral dose in healthy male subjects on an empty stomach and in a postprandial state and to evaluate the effect of food on AST2818 bioavailability. Sixteen healthy Chinese male subjects were randomly divided into two groups: a fasting-postprandial group and a postprandial-fasting group. The drug was administered once per evaluation at a dose of 80 mg, with an interval of 22 days between the two treatments. The LC-MS/MS method was used to determine the concentrations of AST2818 and its metabolite AST5902. Plasma pharmacokinetic parameters were calculated by noncompartmental analysis (NCA). WinNonlin® version 7.0 was used to analyse PK parameters, and SAS version 9.4 was used for statistical analyses. After a meal, the peak concentration of alflutinib increased by approximately 53%, and the AUC increased by approximately 32%; The peak concentration of its metabolite AST5902 decreased by approximately 20%, and the AUC decreased by approximately 8%. There was no significant change in peak time. The peak AST5902 concentration and AUC0-∞ were 27.4% and 71.4%, respectively, of that of alflutinib. None of the subjects experienced serious AEs, and both fasting and high-fat meal administration were safe. There was no statistically significant difference between groups in AEs (P = 0.102, RR = 1.40) or adverse reactions (P = 0.180, RR = 1.30). The effects of food may not need to be considered for the clinical use of alflutinib. No serious AEs occurred, and drug administration was safe and tolerable after fasting or a high-fat meal.

Community-Based Upper Gastrointestinal Cancer Screening in a Randomized Controlled Trial: Baseline Results in a Non-high-incidence Area.

A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat-egg-milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.

High methylation of ZNF582 in cervical adenocarcinoma affects radiosensitivity and prognosis.

BACKGROUND: Our previous study demonstrated hypermethylation of the ZNF582 gene in cervical cancer, but its prognostic value in cervical cancer, especially in cervical adenocarcinoma (CAC), remains unclear. The present study aimed to investigate the value of ZNF582 gene methylation for diagnosis and prediction of radiochemotherapy sensitivity and prognosis in CAC. METHODS: We first determined ZNF582 methylation levels using quantitative methylation-specific PCR in a training set. Disease-free survival and overall survival (DFS and OS) rates were estimated using the Kaplan-Meier method. A Cox regression model was used to assess the prognostic significance of ZNF582 gene methylation in CAC patients. Immunohistochemistry was used to test ZNF582 protein expression in CAC tissues, and an MTT assay evaluated the sensitivity of Hela cells (with or without ZNF582 transfection) to radiation and chemotherapy. RESULTS: The ZNF582 gene showed a higher level of methylation in the CAC group than in the noncancer group, and patients negative for ZNF582 methylation had worse prognoses. We also found that ZNF582 methylation levels were reduced in concomitant chemo-radio-therapy (NCRT) patients compared with that in non-NCRT patients. Methylation-negative status was correlated with high ZNF582 protein expression, and ZNF582 protein overexpression could increase resistance to radiation and chemotherapy in Hela cells. CONCLUSIONS: Aberrant high methylation of ZNF582 may be a potential biomarker for CAC detection and prognosis monitoring. Overexpression of ZNF582 protein could increase CAC chemoradiotherapy resistance.

Development and validation of two prognostic nomograms for predicting survival in patients with non-small cell and small cell lung cancer.

PURPOSE: This study aimed to construct two prognostic nomograms to predict survival in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using a novel set of clinical parameters. PATIENTS AND METHODS: Two nomograms were developed, using a retrospective analysis of 5384 NSCLC and 647 SCLC patients seen during a 10-year period at Xiang Ya Affiliated Cancer Hospital (Changsha, China). The patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to identify the prognostic factors needed to establish nomograms for the training cohort. The model was internally validated via bootstrap resampling and externally certified using the validation cohort. Predictive accuracy and discriminatory capability were estimated using concordance index (C-index), calibration curves, and risk group stratification. RESULTS: The largest contributor to overall survival (OS) prognosis in the NSCLC nomogram was the therapeutic regimen and diagnostic method parameters, and in the SCLC nomogram was the therapeutic regimen and health insurance plan parameters. Calibration curves for the nomogram prediction and the actual observation were in optimal agreement for the 3-year OS and acceptable agreement for the 5-year OS in both training datasets. The C-index was higher for the NSCLC cohort nomogram than for the TNM staging system (0.67 vs. 0.64, P = 0.01) and higher for the SCLC nomogram than for the clinical staging system (limited vs. extensive) (0.60 vs. 0.53, P = 0.12). CONCLUSION: Treatment regimen parameter made the largest contribution to OS prognosis in both nomograms, and these nomograms might provide clinicians and patients a simple tool that improves their ability to accurately estimate survival based on individual patient parameters rather than using an averaged predefined treatment regimen.

Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents.

Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 µM against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 µM, respectively).

Synthesis and in vitro cytotoxic activity evaluation of novel heterocycle bridged carbothioamide type isosteviol derivatives as antitumor agents.

Two series of novel carbothioamide-substituted pyrazole and isoxazolidine derivatives were facilely prepared by functional interconversions in ring D of the tetracyclic diterpene isosteviol. The in vitro cytotoxic activities against four human tumor cell lines were evaluated. Our results indicated that carbothioamide-substituted pyrazole derivatives exhibited noteworthy cytotoxic activities. Specifically, compound 12p (IC(50)=6.51 µM) had the most potent cytotoxicity against Raji cell, which may be exploitable as a lead compound for the development of potent antitumor agents.

[Analysis of the incidence of short-term illness in four counties of Hunan Province].

OBJECTIVE: To determine the prevalence and incidence of illness of two-week duration, and the factors influencing these, among residents 15 years and older in four counties of Hunan Province. METHODS: Data were sampled from four counties of Hunan Province for the Fourth National Health Service Survey. Incidence and two-week prevalence of disease were used to assess the health service needs of residents. A non-conditional, stepwise logistic regression was employed to explore the influencing factors. RESULTS: The two-week prevalence and incidence were 11.5% and 3.9%, respectively, in four counties of Hunan. The three leading diseases of two-week prevalence were: respiratory diseases, digestive diseases, and musculoskeletal diseases. Non-conditional stepwise logistic regression showed that urban residents had 0.64 times the risk of two-week illness compared with the rural residents (P< 0.05); residents in the 45-59 year age group and the 60+ year age group had 1.69 and 2.62 times the risk of two-week illness compared with residents in the 15-44 year age group, respectively (P<0.05). The widowed had 1.91 times the risk of prevalence of two-week illness contrasted to singles (P<0.05); the students had 0.29 times the risk of two-week illness contrasted to the workers (P<0.05); urban residents had 0.63 times the risk of two-week illness compared with the rural (P<0.05); the widowed had 2.37 times the risk of incidence of two-week illness compared with singles (P<0.05). CONCLUSION: The majority of health service needs of residents of four counties is generated by three diseases: respiratory diseases, digestive diseases, and musculoskeletal diseases. Relatively, rural residents, the elderly, employed persons and the widowed have higher health service needs than others and deserve specific attention.

Health-related quality of life of doctors and nurses in China: findings based on the latest open-access data.

OBJECTIVE: To assess the health-related quality of life (QOL) of doctors and nurses using the recent free-access data. METHODS: The health-related QOL data of doctors and nurses came from a sub-survey of the Fourth National Health Services Survey (NHSS) of China in 2008, which used the European Quality of Life-5 Dimensions 3 level version (EQ-5D-3L) to measure the QOL. We used logistic regression to compare the percentage of respondents reporting any problems for each dimension of the EQ-5D-3L descriptive system between inhabitants aged 15-64 years and doctors and nurses. RESULTS: Fewer doctors and nurses reported problems in mobility (1.9%) than inhabitants aged 15-64 years (2.9%) (odds ratio = 0.65). No difference was detected in self-care problem. Compared with inhabitants aged 15-64 years, a relatively large proportion of doctors and nurses reported problems in usual activities (3.4% vs. 2.7%; odds ratio = 1.27), pain/discomfort (18.1% vs. 6.7%; odds ratio = 3.08), and anxiety/depression (24.6% vs. 5.1%; odds ratio = 6.07). The EQ-VAS score mean of doctors and nurses approached that of inhabitants aged 15-64 years (82 vs. 79). CONCLUSION: Compared with inhabitants aged 15-64 years, doctors and nurses have relatively poor health in usual activities, self-reporting pain/discomfort, and anxiety/depression.

[An epidemiological survey on the incidence of non-fatal injury and influencing factors among children under 5 years old in China].

OBJECTIVE: To determine the incidence of non-fatal injuries and related influencing factors among children under 5 years old in China. METHODS: Data involving 10 819 children under 5 years old was from the Fourth National Health Service Survey of China. Injury-related indicators include: history of ever having had an injury, its frequency, cause, location and severity of the injury. A two-level Poisson regression was used to examine the significance of related socio-economic variables. RESULTS: The overall incidence rate of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The first three leading causes of non-fatal injuries were falls, animal bite, fire/burn among children under 1 year old, with the rates as 3.9, 1.8 and 1.8 per 1000 population, respectively. For children aged 1 to 4 years old, the first three leading causes were animal bite, fall, fire/burn with rates as 6.5, 6.0 and 2.9 per 1000 population, respectively. 83.0% and 69.0% of last injuries occurred at home for the above said two age groups. No disability was found among children younger than 1 year old who suffered from a nonfatal injury while for the 1 - 4 age group, the disability accounted for 1.0% of injury-induced outcomes. After adjusting other variables, boys had 1.57 times the risk of injury compared with girls in the 1 - 4 age group (P < 0.05). The differences on the effects regarding ethnicity, per capita household income, and place were insignificant (P > 0.05). None of the socio-economic variables was found that significantly related to the non-fatal injury risk among children under 1 year old (P > 0.05). CONCLUSION: The incidence of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The three leading causes of injuries were animal bite, falls, fire/burn respectively. Home was the most common place that non-fatal injuries occurred. Boys had a higher risk of injury compared with girls among children aged 1 to 4 years old and the difference was significant.

[Investigation of traffic law violations among middle school students in Hunan province and the influencing factors].

OBJECTIVE: To determine the incidence of traffic law violations among middle school students of Hunan province and to identify the influencing factors. METHODS: Stratified sampling and cluster sampling were used to randomly select students from 96 classes of 16 middle schools. Road traffic law violations were measured through recalling the occurrence of 5 common violations in the prior year. Most of influencing factors were collected by self-designed questionnaire except for family support function and parenting that were measured by the family assessment device (FAD) and the parenting locus of control scale (PLOC), respectively. Kruskal Wallis H test and multinomial logistic regression were used to analyze the data. RESULTS: The overall incidence rate of five common traffic law violations among middle school students in Hunan province fell between 16.6%-43.3%. Except for running against traffic light or not using pedestrian crossings (8.2%), students with the other 4 traffic law violations merely accounted for less 4%. The rates of students with 1, 2, 3, 4 and 5 kinds of traffic law violations were 25.3%, 17.8%, 10.2%, 6.2% and 3.4%, respectively. Logistic regression showed that there were 3 factors (area, junior or senior high school, and single child or not), 5 factors (area, junior or senior high school, sex, single child or not, and class leader or not) and 6 factors (type of school, junior or senior high school, sex, class leader or not, family support function, and type of family education) significantly associating with the occurrence of 1, 2, and 3 or more traffic law violations, respectively. CONCLUSION: Only a small proportion of students often or almost always break traffic law or break several traffic laws at the same time. Students with serious traffic law violations should be targeted by school safety education and intervention.

Digoxin derivatives substituted by alkylidene at the butenolide part.

A series of digoxin derivatives containing the gamma-alkylidene butenolide moiety were synthesised by way of stereoselective vinylogous aldol reaction of the unactivated butenolide in simple conditions. The structures of compounds synthesised were characterised by infrared (IR), nuclear magnetic resonance (NMR) and HR-MS. Preliminary bioassay shows that some of them have cardiac functions, especially compound 2g that induced a marked increase in myocardial contractility at 10ngml(-1) and 20ngml(-1) concentrations without digitalis toxicity.

In vitro comparison of fragmentation efficiency of flexible pneumatic lithotripsy using 2 flexible ureteroscopes.

PURPOSE: Pneumatic lithotripsy has been shown to be an effective and safe intracorporeal lithotripsy modality for renal and ureteral calculi, capable of fragmenting stones of all compositions. We determined the in vitro stone fragmentation abilities of the 0.5 mm flexible pneumatic lithotripsy probe when inserted through the working channel of 2, 7.5Fr flexible ureteroscope designs (straight working channel and offset working channel at approximately 30 degrees from the long axis of the endoscope). The velocity and displacement of the pneumatic probe tip were also evaluated with the probe inserted through each endoscope. MATERIALS AND METHODS: The 0.5 mm (1.5Fr) stainless steel probe was tested at 5 deflection angles, namely 0, 12, 24, 33 and 48 degrees, at a pneumatic pressure of 2.5 bar when inserted through the offset and straight working channel ureteroscopes. A noncontact optical laser system was used to measure or calculate the displacement and velocity of the 0.5 mm probe tip at each angle of deflection with the 2 ureteroscopes. Fragmentation at all deflection angles was assessed using plaster of Paris stone phantoms with the pneumatic device on continuous mode at 2.5 bar pressure for 30 seconds. Stones were weighed after each fragmentation cycle and the percent weight lost was determined. Comparisons were made between the 2 ureteroscopes at each angle. RESULTS: Probe tip displacement was significantly better through the straight channel ureteroscope with 30% improvement at all angles tested compared to the offset channel. Moreover, a substantial decrement in tip displacement was noted as the angle of deflection increased regardless of the endoscope used. Conversely tip velocity was relatively unchanged throughout the study and it was equivalent from straight to offset channel measurements. Phantom stone fragmentation correlated inversely with the severity of the deflection angle. An approximately 80% loss of fragmentation ability was noted as the angle increased from 0 to 48 degrees. Although the pneumatic device performed better through the straight channel scope, a similar percent loss in fragmentation from 0 to 48 degrees was seen when using either endoscope. CONCLUSIONS: The flexible pneumatic 0.5 mm lithotripsy probe appears to be best used through a straight channel flexible ureteroscope, out performing use through the offset channel scope at all angles of deflection. Tip displacement and fragmentation ability were inversely related to the degree of active deflection as the angle increased from 0 to 48 degrees. Use of the flexible pneumatic probe to aid in managing renal or proximal ureteral calculi may be limited until an improved probe can be developed, allowing complete and unencumbered fragmentation throughout all angles of deflection.

Reduction of tissue injury in shock-wave lithotripsy by using an acoustic diode.

An acoustic diode (AD) was constructed of two acoustic transparent membranes with good initial contact to allow the transmission of the positive pressure of lithotripter shock wave at an almost unaltered level, yet attenuate significantly its negative pressure, was fabricated. It was evaluated systematically on a Dornier HM-3 lithotripter to assess its application potential to reduce vascular injury without compromising stone fragmentation efficiency during shock-wave lithotripsy. By inserting the AD, the maximum compressive pressure, maximum tensile pressure and tensile duration of the lithotripter shock wave were formed to drop from 49.7 to 47.8 MPa, -7.5 to -7.0 MPa and 6.0 to 5.1 micros, respectively. Damage of a 0.2-mm inner diameter vessel phantom (cellulose hollow fiber) was reduced from rupture after 31 +/- 11 shocks to no rupture after 100 shocks. Maximum bubble size in free-field, maximum dilation of the vessel phantom wall and bubble collapse time became smaller with the use of the AD. However, stone fragmentation showed similar results without a statistically significant difference between the case with and without the AD. All these evidences suggest that the use of an acoustic diode may be a feasible approach to reduce tissue injury without compromising stone comminution in shock-wave lithotripsy.

The role of stress waves and cavitation in stone comminution in shock wave lithotripsy.

Using an experimental system that mimics stone fragmentation in the renal pelvis, we have investigated the role of stress waves and cavitation in stone comminution in shock-wave lithotripsy (SWL). Spherical plaster-of-Paris stone phantoms (D = 10 mm) were exposed to 25, 50, 100, 200, 300 and 500 shocks at the beam focus of a Dornier HM-3 lithotripter operated at 20 kV and a pulse repetition rate of 1 Hz. The stone phantoms were immersed either in degassed water or in castor oil to delineate the contribution of stress waves and cavitation to stone comminution. It was found that, while in degassed water there is a progressive disintegration of the stone phantoms into small pieces, the fragments produced in castor oil are fairly sizable. From 25 to 500 shocks, clinically passable fragments (< 2 mm) produced in degassed water increases from 3% to 66%, whereas, in castor oil, the corresponding values are from 2% to 11%. Similar observations were confirmed using kidney stones with a primary composition of calcium oxalate monohydrate. After 200 shocks, 89% of the fragments of the kidney stones treated in degassed water became passable, but only 22% of the fragments of the kidney stones treated in castor oil were less than 2 mm in size. This apparent size limitation of the stone fragments produced primarily by stress waves (in castor oil) is likely caused by the destructive superposition of the stress waves reverberating inside the fragments, when their sizes are less than half of the compressive wavelength in the stone material. On the other hand, if a stone is only exposed to cavitation bubbles induced in SWL, the resultant fragmentation is much less effective than that produced by the combination of stress waves and cavitation. It is concluded that, although stress wave-induced fracture is important for the initial disintegration of kidney stones, cavitation is necessary to produce fine passable fragments, which are most critical for the success of clinical SWL. Stress waves and cavitation work synergistically, rather than independently, to produce effective and successful disintegration of renal calculi in SWL