Fractographic analysis of separated endodontic file designs.

Endodontic rotary files are cutting instruments used to perform root canal procedures within a tooth interior. Focusing on quantitative fractographic analysis increases necessary, clinical performance understanding of file separation failure. This research employed controlled, dynamic testing to failure of commercial rotary files, analyzing the fractographic, forensic characteristics in relation to Weibull reliability determination, considering: (1) design analysis; (2) stress concentrations; (3) times to failure; (4) number of cycles to failure (NCF). Ex vivo testing included three file designs, each having constant tip size (0.035 mm), taper (0.06 mm/mm), and length (25 mm). Files were individually tested using an electric, torque-controlled handpiece, rotating within a standardized, simulated canal until fracture separation occurred. Fractographic analysis, including critical measurements, was conducted using the scanning electron microscope (SEM) (PhenomProX, PhenomWorld, NL). Weibull statistical analysis established reliability factors per design group. Fractographic analysis identified separation fractures, processing inclusions, flexural-fatigue striations, and stress concentrations at flute pitches. Calculated NCF median values (1277-EE; 899-VB; 713-PI) demonstrated significant statistical differences among groups (p < 0.001). Separated apical fragments yielded statistically significant differences (p ≤ 0.05) for varying file design groups. Weibull moduli among groups were statistically equivalent. Fractographic analysis exposed a presence of multiple failure factors in addition to defect distribution, governing cyclic fatigue failure originating at stress concentration points irrespective of file design. Fractographic analysis indicated that a change in file design, specifically at the working edges, in addition to improved surface finish, has the potential of reducing failures by lowering points of stress concentration and reducing fracture initiating surface cracks.

miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215.

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. METHOD: We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis. RESULTS: We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis. CONCLUSION: Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.

A randomized, double-blind trial to compare shock wave frequencies of 60 and 120 shocks per minute for upper ureteral stones.

PURPOSE: Recent evidence demonstrates that decreasing shock wave frequency from the previous standard of 120 to 60 shocks per minute results in improved fragmentation of stones located within the renal collecting system. We report the first randomized trial to our knowledge to examine the effect of a slower shock wave frequency for shock wave lithotripsy on stones located in the proximal ureter. MATERIALS AND METHODS: A total of 163 patients with a previously untreated radiopaque calculus in the upper ureter measuring at least 5 mm underwent stratified block randomization according to stone size, and shock wave lithotripsy at 60 or 120 shocks per minute. Stone-free status at 3 months was confirmed with noncontrast computerized tomography or a plain abdominal x-ray and ultrasound study. RESULTS: Of the patients 77 were randomized to 60 shocks per minute and 86 were randomized to 120 shocks per minute. The groups were similar in gender, age, body mass index and initial stone area. At 3 months the 60 shocks per minute group had a higher overall stone-free rate (64.9% vs 48.8%, p = 0.039). Significantly fewer shocks were administered to patients treated at 60 shocks per minute (mean 2,680 vs 2,940, p <0.001). However, mean treatment times were longer (44.3 vs 24.5 minutes, p <0.001). Patients treated with 60 shocks per minute required fewer auxiliary procedures (29.9% vs 45.4%) (p = 0.031). CONCLUSIONS: Decreasing the rate of shock wave administration from 120 to 60 shocks per minute results in improved stone-free rates. A slower treatment rate of proximal ureteral stones reduces the need for additional shock wave lithotripsy or more invasive treatments to render patients stone-free, without any increase in morbidity, and with an acceptable increase in treatment time.

Effect of donor pneumoperitoneum on early allograft perfusion following renal transplantation in pediatric patients: an intraoperative Doppler ultrasound study.

Decreased perfusion and trauma during laparoscopic harvesting are proposed causative factors for DGF and rejection in children following renal transplantation with laparoscopic donor nephrectomy (LDN) allograft. We performed a retrospective review of 11 children who underwent LDN transplant and 11 preceding patients who underwent ODN transplant. Intraoperative DUS findings, creatinine values and clearance, time to nadir creatinine and AR episodes were compared. There were no significant differences in the BMI, vascular anatomy, side of nephrectomy, or warm ischemia time in the two groups. Mean follow-up duration was 11.4 and 30.4 months in LDN and ODN groups. DUS showed initial turbulent flow in five of the LDN and four of the ODN group with an average RI of 0.59 and 0.66 in the ODN and LDN groups, respectively (NS). Three patients in the ODN group had an abnormal RI compared to none in the LDN group (p = 0.034). The creatinine values, creatinine clearances (at 24 h, one, four wk and last follow-up) and AR episodes were similar in both groups. Pneumoperitoneum during LDN does not appear to have an adverse impact on early graft reperfusion.

Individual patient variation and inter-rater reliability of lower calyceal infundibular width on routine intravenous pyelography.

OBJECTIVE: To standardise infundibular width (IFW) measurement, to determine patient variability, and to determine inter-rater variability on intravenous pyelography (IVP). PATIENTS AND METHODS: Fifty outpatient IVP films were randomly drawn from two hospitals between 1 July 1998 and 31 August 1999, and examined to measure the lower calyceal IFW on the 5, 10 and 20 min films with compression, and after voiding. Kidneys with previous renal surgery, hydronephrosis or renal anatomical anomalies were excluded; in all, 81 kidneys from 50 patients were examined. The IFW was measured at the narrowest point along the infundibulum. All 50 films were then reviewed by two urologists unaware of their origin, to determine the inter-rater reliability of the infundibular measurements. RESULTS: Analysis of variance (anova) with posthoc analysis showed a significant difference in IFW at each phase of the IVP (repeated measures anova, P < 0.001). The mean (95% confidence interval) IFW was greatest on the compression film, at 4.4 (2.6) mm, and least on the postvoid film, at 1.6 (2.1) mm. Overall inter-rater reliability was 0.9780 (intraclass correlation coefficient), and the Pearson correlation between each rater for the IFW at each phase of the IVP was >/= 0.886. CONCLUSIONS: There is wide variability in lower calyceal IFW among the various IVP films in a given study. Thus any predictive value of the IFW must be standardized for the timing and IVP film type (compression, postvoid, etc.). The inter-rater reliability of IFW is high, suggesting that if used correctly it may be more useful in predicting the outcome after shock wave lithotripsy.

Predicting conversion in laparoscopic colorectal surgery. Fellowship training may be an advantage.

BACKGROUND: Laparoscopic colorectal surgery has clear advantages over open surgery; however, the effectiveness of the approach depends on the conversion rate. The objective of this work was to prospectively validate a model that would predict conversion in laparoscopic colorectal surgery. METHODS: A simple clinical model for predicting conversion in laparoscopic colorectal surgery was previously developed based on a multivariable logistic regression analysis of 367 procedures. This model was applied prospectively to a follow-up group of 248 procedures by the same team, including 54 procedures performed by one new fellowship-trained surgeon. RESULTS: Patients in the follow-up group were more likely to have cancer (56% vs 44%, p = 0.007) and were more obese (median, 71.0 vs 66.0 kg; p < 0.001). The rate of conversion in the follow-up group was unchanged (8.9% vs 9.0%, p > 0.05). Despite expected trends toward increasing risk of conversion with weight level (<60 kg, 6.8%; 60-<90 kg, 9.0%; >90 kg, 12.1%; p > 0.05) and malignancy (10.1% vs 7.3%, p > 0.05), the model did not distinguish well between groups at risk for conversion. Contrary to the model, however, the fellowship-trained surgeon had a conversion rate that was not higher than that of the other, more experienced surgeons (7.3% vs 9.3%, p > 0.05) even though he was less experienced, and operating on patients who were more obese (median, 75.0 vs 70 kg; p = 0.02) and more likely to have cancer (59% vs 55%, p > 0.05). Recalculated conversion scores that excluded the inexperience point for the fellowship-trained surgeon showed a good fit for the model. Considering the original and follow-up experience together (615 cases), the model clearly stratifies patients into low (0 points), medium (1-2 points), and high risk (3-4 points) for conversion, with respective rates of 2.9%, 8.1%, and 20% ( p = 0.001). CONCLUSION: This model appears to be a valid predictor of conversion to open surgery. Fellowship training may provide sufficient experience so that learning curve issues are redundant in early practice. This model now requires validation by other centers.

Laparoscopic versus open donor nephrectomy.

BACKGROUND: As compared with open donor nephrectomy (OpenDN), laparoscopic donor nephrectomy (LapDN) offers donors more rapid recovery and recipients equivalent graft function, but LapDN costs remain greater. This study compared LapDN and OpenDN with cost-utility analysis. METHODS: Utilities were assessed with time trade-off, probabilities derived from systematic review of the literature and the costs derived from 27 OpenDN and 34 LapDN patients treated contemporaneously. A societal perspective was taken. Lost employment costs were included. An incremental cost-effectiveness ratio (ICER) was calculated with best- and worst-case scenarios for confidence intervals. Sensitivity analyses assessed robustness. RESULTS: LapDN costs are lower (11,170.71 dollars vs 12,631.91 dollars), whereas quality of life (QOL) is superior (0.7247 vs 0.6585 quality-adjusted life years [QALY], rendering LapDN a dominant strategy. The model was robust to all variables, and LapDN remained dominant from a payer perspective. In a worst-case scenario, the ICER for LapDN was at most 2,231.61 dollars per QALY. CONCLUSIONS: LapDN offers improved QOL at lower costs, despite the fact that this analysis included patients treated during the learning curve of LapDN at our institution. By potentially increasing organ donor rates, LapDN may be further cost saving by decreasing the number of patients receiving dialysis.

Health-related quality of life after laparoscopic and open nephrectomy.

BACKGROUND: Postoperative recovery often is assessed with parameters (pain and return to work) susceptible to bias. This study sought objectively to compare postoperative health-related quality of life (HRQL) after laparoscopic and open nephrectomy with the Postoperative Recovery (PRS) (a validated questionnaire designed to assess pain), activities of daily living (ADL), and HRQL in postoperative patients. METHODS: Patients undergoing contemporaneous laparoscopic and open nephrectomy received the PRS pre- and postoperatively. The results were analyzed with analysis of covariance (ANCOV) and survival analysis. RESULTS: The 33 open nephrectomy and 38 laparoscopic patients in this study were comparable in age, gender, body mass index (BMI) and employment. Laparoscopic operative time was longer (p = 0.015), and the hospital stay was shorter (p<0.001). Laparoscopic patients had higher HRQL scores from postoperative days 3 to 365 (p<0.001), and they returned to preoperative HRQL faster (p<0.001). CONCLUSIONS: An objective HRQL instrument confirms that laparoscopic nephrectomy patients recover faster and with a higher HRQL than open surgery patients. The PRS can be modified for use after other abdominal procedures, and may prove useful for comparisons of other minimally invasive surgical techniques.

CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans.

Galectin-1 induces death of immature thymocytes and activated T cells. Galectin-1 binds to T cell-surface glycoproteins CD45, CD43, and CD7, although the precise roles of each receptor in cell death are unknown. We have determined that CD45 can positively and negatively regulate galectin-1-induced T cell death, depending on the glycosylation status of the cells. CD45(+) BW5147 T cells lacking the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) were resistant to galectin-1 death. The inhibitory effect of CD45 in C2GnT(-) cells appeared to require the CD45 cytoplasmic domain, because Rev1.1 cells expressing only CD45 transmembrane and extracellular domains were susceptible to galectin-1 death. Moreover, treatment with the phosphotyrosine-phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate(V) enhanced galectin-1 susceptibility of CD45(+) T cell lines, but had no effect on the death of CD45(-) T cells, indicating that the CD45 inhibitory effect involved the phosphatase domain. Expression of the C2GnT in CD45(+) T cell lines rendered the cells susceptible to galectin-1, while expression of the C2GnT in CD45(-) cells had no effect on galectin-1 susceptibility. When CD45(+) T cells bound to galectin-1 on murine thymic stromal cells, only C2GnT(+) T cells underwent death. On C2GnT(+) cells, CD45 and galectin-1 co-localized in patches on membrane blebs while no segregation of CD45 was seen on C2GnT(-) T cells, suggesting that oligosaccharide-mediated clustering of CD45 facilitated galectin-1-induced cell death.

Mechanical percussion, inversion and diuresis for residual lower pole fragments after shock wave lithotripsy: a prospective, single blind, randomized controlled trial.

PURPOSE: We compare the effectiveness of mechanical percussion and inversion with observation for eliminating lower caliceal fragments 3 months after shock wave lithotripsy. MATERIALS AND METHODS: At 3 months after shock wave lithotripsy 69 patients with residual lower caliceal fragments 4 mm. or less were randomized to receive either mechanical percussion and inversion or observation for 1 month. The observation group then received crossover mechanical percussion and inversion if fragments persisted. All patients were followed with plain film of the kidneys, ureters and bladder to assess the stone area and stone-free status, and renal tomography or noncontrast spiral computerized tomography to confirm stone-free status. A blinded radiologist reviewed all films. Patients were treated with a mechanical chest percussor applied to the flank while inverted to greater than 60 degrees after receiving 20 mg. furosemide. RESULTS: A total of 35 patients were randomized to receive immediate mechanical percussion and inversion therapy and 34 observation. Of the patients in the observation group 28 subsequently received mechanical percussion and inversion after completing the observation period. The groups were not different in gender, body mass index, side affected, stone location or renal anatomical features. The mechanical percussion and inversion group had a substantially higher stone-free rate than the observation group (40% versus 3%, respectively, p <0.001). The mechanical percussion and inversion group also had a greater improvement in total stone area than controls (-63.3% versus +2.7%, respectively, p <0.001). No significant adverse effects were noted in the mechanical percussion and inversion group. CONCLUSIONS: Mechanical percussion and inversion is a safe and effective treatment option for residual lower caliceal fragments 3 months after shock wave lithotripsy. Nearly 50% of patients become stone-free, and stone burden is decreased by 50% in the remainder.

A comparison of patient-controlled sedation using either remifentanil or remifentanil-propofol for shock wave lithotripsy.

UNLABELLED: Patient-controlled sedation (PCS) has been used for extracorporeal shock wave lithotripsy (SWL) because it allows for rapid individualized titration of anesthetics. Because of its sedating effects, the addition of propofol to remifentanil may improve patient tolerance of SWL with PCS. One hundred twenty patients were randomly assigned to receive remifentanil 10 microg or remifentanil 10 microg plus propofol 5 mg for PCS with zero-lockout interval. Nine patients in the Remifentanil group and three patients in the Remifentanil-Propofol group required additional sedatives to complete their SWL (P = 0.128). Compared with the Remifentanil group, the Remifentanil-Propofol group required less remifentanil, had a decreased incidence of postoperative nausea and vomiting, and had a better overall satisfaction level. However, they had an increased incidence of transient apnea and oxygen desaturation. The incidence of apnea was 15% in the Remifentanil group and 52% in the Remifentanil-Propofol group (P < 0.001). All patients were able to move themselves to the stretcher at the end of SWL, and median time to home discharge was <70 min in both groups. Both remifentanil and remifentanil-propofol were useful for PCS during SWL. IMPLICATIONS: The addition of propofol to remifentanil improves patient satisfaction and decreases postoperative nausea and vomiting. However, it causes more respiratory depression than remifentanil alone. When remifentanil-propofol is used with patient-controlled sedation, appropriate monitoring and a minimum 1-2 min lockout interval is required.

Low success rate of repeat shock wave lithotripsy for ureteral stones after failed initial treatment.

PURPOSE: We determined the number of shock wave lithotripsy treatments that should be given for a single ureteral stone before alternate modalities are used. MATERIALS AND METHODS: We compared the stone-free rate of initial shock wave lithotripsy for ureteral calculi with that of subsequent treatments. We evaluated 1,593 ureteral stones treated with the Dornier MFL 5000 lithotriptor* from January 1, 1994 to September 1, 1999 using various parameters associated with treatment outcome. RESULTS: The stone-free rate after initial treatment was 68% (1,086 of 1,593 stones), which decreased to 46% (126 of 273) after re-treatment 1. We observed a further decrease in the stone-free rate after re-treatment 2 to 31% (19 of 61 stones, p = 0.001). The cumulative stone-free rate increased to 76% (1,212 of 1,593 stones) after 2 treatments and to 77% (1,231 of 1593) after 3. The stone-free rate for stones 10 mm. or less was significantly better than that of stones 11 to 20 mm. initially (64% versus 43%) and after re-treatment (49% versus 37%). A ureteral stent decreased the stone-free rate of initial treatment and re-treatment 1 by 12% and 14%, respectively (p = 0.001). After initial treatment the stone-free rate of the upper and mid ureter was significantly higher than that of the lower ureter. Patient weight had no significant impact on success in either group. CONCLUSIONS: The stone-free rate of re-treating ureteral calculi with shock wave lithotripsy decreases significantly after the initial treatment. These findings imply that ureteroscopic management of ureteral stones may be better than shock wave lithotripsy after initial shock wave lithotripsy fails.

CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death.

Galectin-1, an endogenous lectin expressed in lymphoid organs and immune-privileged sites, induces death of human and murine thymocytes and T cells. Galectin-1 binds to several glycoproteins on the T cell surface, including CD7. However, the T cell surface glycoprotein receptors responsible for delivering the galectin-1 death signal have not been identified. We show that CD7 is required for galectin-1-mediated death. This demonstrates a novel function for CD7 as a death trigger and identifies galectin-1/CD7 as a new biologic death signaling pair.

Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1.

Galectin-1 induces apoptosis of human thymocytes and activated T cells by an unknown mechanism. Apoptosis is a novel function for a mammalian lectin; moreover, given the ubiquitous distribution of the oligosaccharide ligand recognized by galectin-1, it is not clear how susceptibility to and signaling by galectin-1 is regulated. We have determined that galectin-1 binds to a restricted set of T cell surface glycoproteins, and that only CD45, CD43, and CD7 appear to directly participate in galectin-1-induced apoptosis. To determine whether these specific glycoproteins interact cooperatively or independently to deliver the galectin-1 death signal, we examined the cell surface localization of CD45, CD43, CD7, and CD3 after galectin-1 binding to human T cell lines and human thymocytes. We found that galectin-1 binding resulted in a dramatic redistribution of these glycoproteins into segregated membrane microdomains on the cell surface. CD45 and CD3 colocalized on large islands on apoptotic blebs protruding from the cell surface. These islands also included externalized phosphatidylserine. In addition, the exposure of phosphatidylserine on the surface of galectin-1-treated cells occurred very rapidly. CD7 and CD43 colocalized in small patches away from the membrane blebs, which excluded externalized phosphatidylserine. Receptor segregation was not seen on cells that did not die in response to galectin-1, including mature thymocytes, suggesting that spatial redistribution of receptors into specific microdomains is required for triggering apoptosis.

The urology work force in Ontario for the 21st century: feast or famine?

OBJECTIVE: To address the issues of work-force planning and modelling in the 21st century for the specialty of urology in the Province of Ontario. DESIGN: Data (from 1991 to 1995) regarding urology physician resources were gathered from Health Canada, the Royal College of Physicians and Surgeons of Canada, the Ontario Physician Human Resources Data Centre, the Canadian Post-M.D. Education Registry, the System for Health Area Resource Planning (SHARP) database, the Canadian Institute for Health Information and the National Physician Database. Specifically, the age and gender breakdown of currently active Ontario urologists, measures of urologist clinical activity (from Ontario Hospital Insurance Plan billings and questionnaires), inputs into and exits from the active urologist population were gathered, and estimates of future needs for urologist services, based on current population and demographic models, were made. A model to predict the balance between future needs for urology services and future supply of urologists was then created and validated against data drawn from the SHARP database. RESULTS: The model revealed that there will be a significant shortage of urologists in Ontario in the immediate and long-term future; by the year 2010 there will be a shortfall of 101 urologists in Ontario, or 51% of the total needed. CONCLUSIONS: Enlarging the urology training programs in Ontario would help to minimize the estimated shortfall. Systematic modelling of physician work-force needs for the future is necessary for the optimal allocation of health care resources. The methodology of the urology work-force model is generalizable to physician work-force planning for other specialty groups on a provincial or national basis.

Profound natriuresis, extracellular fluid volume contraction, and hypernatremia with hypertonic losses following trauma.

A young male sustained very serious head and soft tissue injuries in a motor vehicle accident (MVA). Three interesting problems developed in the sodium (Na) and water area in the second week in hospital. First, on day 11 after the MVA, his urine output increased to 3 liters per day; the urine osmolality was 1000 mOsm/kg H2O and Na and Cl were the principal urine osmoles. There appeared to be a salt wasting syndrome because he had a very large natriuresis (close to 900 mmol/24 hr) at a time when his central venous pressure was low. To help identify the nephron site responsible for a natriuresis with a high urine osmolality, additional studies were carried out in normal volunteers who took a loop or a thiazide diuretic on different occasions while ADH was acting. The pattern of natriuresis in the patient was similar to that after the thiazide but not the loop diuretic. The second problem concerned his hypernatremia (153 mM) because his urine was hypertonic and his intravenous therapy was isotonic saline. To explain hypernatremia while receiving more electrolyte-free water, we speculated that there was a water shift into cells resulting from particles generated and retained in his intracellular fluid. Given the large shift of water required, a lesion in muscle was suspected, a form of rhabdomyolysis. The third problem concerned the rate of catabolism of lean body mass. The metabolic consequences of generating these intracellular particles and the large amount of urea that was excreted could reflect a large degree of protein catabolism.

Apoptosis of T cells mediated by galectin-1.

Galectin-1, a member of the family of beta-galactoside binding proteins, has growth regulatory and immunomodulatory activities. We report here that galectin-1, expressed by stromal cells in human thymus and lymph nodes, is present at sites of cell death by apoptosis during normal T-cell development and maturation. Galectin-1 induced apoptosis of activated human T cells and human T leukaemia cell lines. Resting T cells also bound galectin-1, but did not undergo apoptosis. Human endothelial cells that expressed galectin-1 induced apoptosis of bound T cells. Galectin-1-induced apoptosis required expression of CD45, and was decreased when N-glycan elongation was blocked by treatment of the cells by swainsonine, whereas inhibition of O-glycan elongation potentiated the apoptotic effect of galectin-1. Induction of apoptosis by an endogenous mammalian lectin represents a new mechanism for regulating the immune response.