Sigma metric analysis of quality indicators across the testing process as an effective tool for the evaluation of laboratory performance.

Background: Laboratories across the world are successfully using quality indicators (QIs) to monitor their performance. We aimed to analyze the effectiveness of using the peer group comparison and statistical tools such as sigma metrics for periodic evaluation of QIs and identify potential errors in the preanalytical, analytical, and postanalytical phases. Methods: We evaluated the monthly QIs for 1 year. A total of 11 QIs were evaluated across the three phases of the total testing process, using percentage variance, and sigma metric analysis. Results: Our study observed that based on sigma metric analysis, the performance was good for all the QIs except for the number of samples with the inappropriate specimen hemolyzed samples, clotted samples, and turnaround time (Sigma value < 3). The percentage variance of QIs in all the phases was plotted in a Pareto chart, which helped us in identifying turnaround time and internal quality control performance are the key areas that contribute to almost 80% of the errors among all the QIs. Conclusion: Laboratory performance evaluation using QIs and sigma metric analysis helped us in identifying and prioritizing the corrective actions in the key areas of the total testing process.

Clinical Outcomes of Patients With T1 Nested Variant of Urothelial Carcinoma Compared to Pure Urothelial Carcinoma of the Bladder.

PURPOSE: Evaluate oncologic outcomes of patients with cT1 nested variant (NV) of urothelial carcinoma (UC) and compare with cases of pure UC of the bladder. MATERIALS AND METHODS: We retrospectively identified 30 patients with NV who, between 1997 and 2012, underwent transurethral resection with T1 tumor stage, followed by restaging transurethral resection within 3 months confirming non-muscle-invasive disease. Radical cystectomy within 3 months of restaging transurethral resection was considered "early" treatment. We matched 3 patients with pure UC to each nested patient. RESULTS: Median follow-up for survivors was 4.3 years from T1-staged transurethral resection. Patients with NV had no statistically significant difference in metastasis-free survival (P = .2) and cancer-specific survival (P = .2) compared with patients with pure UC. However, it is concerning that the rate of upstaging to bladder and/or lymph nodes was 54% in patients with NV who underwent early radical cystectomy, even after rigorous restaging. CONCLUSIONS: Although NV UC may be diagnosed at a higher stage, when stage matched we have not seen any statistical evidence that it is more aggressive than typical UC. Because patients with NV UC who are cT1 on restaging transurethral resection appear to have a higher propensity to develop nodal metastatic disease and a higher rate of upstaging, patients with cT1 NV UC on restaging biopsy may benefit from "early" radical cystectomy, whereas patients with 

Effect of methysergide on pudendal inhibition of micturition reflex in cats.

The role of 5-HT2 and opioid receptors in pudendal inhibition of bladder activity induced by intravesical infusion of saline or 0.25% acetic acid (AA) was investigated in anesthetized cats using methysergide (a 5-HT2 receptor antagonist) and naloxone (an opioid receptor antagonist). AA irritated the bladder and significantly (P<0.0001) reduced bladder capacity to 27.0 ± 7.4% of saline control capacity. Pudendal nerve stimulation (PNS) at multiples of the threshold (T) intensity for inducing anal sphincter twitching restored bladder capacity to 60.1 ± 8.0% at 1-2T (P<0.0001) and 92.2 ± 14.1% at 3-4T (P=0.001) of the saline control capacity. Methysergide (0.03-1mg/kg, i.v.) suppressed low intensity (1-2T) PNS inhibition but not high intensity (3-4T) inhibition, and also significantly (P<0.05) increased control bladder capacity at the dosage of 0.3-1mg/kg. During saline infusion without AA irritation, PNS significantly increased bladder capacity to 150.8 ± 9.9% at 1-2T (P<0.01) and 180.4 ± 16.6% at 3-4T (P<0.01) of the saline control capacity. Methysergide (0.1-1 mg/kg) significantly (P<0.05) increased saline control bladder capacity and suppressed PNS inhibition at the dosage of 0.03-1mg/kg. After methysergide treatment (1 mg/kg), naloxone significantly (P<0.05) reduced control bladder capacity during AA infusion but had no effect during saline infusion. Naloxone also had no influence on PNS inhibition. These results suggest that 5-HT2 receptors play a role in PNS inhibition of reflex bladder activity and interact with opioid mechanisms in micturition reflex pathway. Understanding neurotransmitter mechanisms underlying pudendal neuromodulation is important for the development of new treatments for bladder disorders.

Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation.

The contribution of metabotropic glutamate receptors (mGluR) and opioid receptors to inhibition of bladder overactivity by tibial nerve stimulation (TNS) was investigated in cats under α-chloralose anesthesia using LY341495 (a group II mGluR antagonist) and naloxone (an opioid receptor antagonist). Slow infusion cystometry was used to measure the volume threshold (i.e., bladder capacity) for inducing a large bladder contraction. After measuring the bladder capacity during saline infusion, 0.25% acetic acid (AA) was infused to irritate the bladder, activate the nociceptive C-fiber bladder afferents, and induce bladder overactivity. AA significantly (P < 0.0001) reduced bladder capacity to 26.6 ± 4.7% of saline control capacity. TNS (5 Hz, 0.2 ms) at 2 and 4 times the threshold (T) intensity for inducing an observable toe movement significantly increased bladder capacity to 62.2 ± 8.3% at 2T (P < 0.01) and 80.8 ± 9.2% at 4T (P = 0.0001) of saline control capacity. LY341495 (0.1-5 mg/kg iv) did not change bladder overactivity, but completely suppressed the inhibition induced by TNS at a low stimulus intensity (2T) and partially suppressed the inhibition at high intensity (4T). Following administration of LY341495, naloxone (0.01 mg/kg iv) completely eliminated the high-intensity TNS-induced inhibition. However, without LY341495 treatment a 10 times higher dose (0.1 mg/kg) of naloxone was required to completely block TNS inhibition. These results indicate that interactions between group II mGluR and opioid receptor mechanisms contribute to TNS inhibition of AA-induced bladder overactivity. Understanding neurotransmitter mechanisms underlying TNS inhibition of bladder overactivity is important for the development of new treatments for bladder disorders.

Role of opioid and metabotropic glutamate 5 receptors in pudendal inhibition of bladder overactivity in cats.

PURPOSE: We determined the role of opioid and metabotropic glutamate 5 receptors in the pudendal inhibition of bladder overactivity. MATERIALS AND METHODS: Cystometrograms were performed in 11 cats under α-chloralose anesthesia by slowly infusing the bladder with saline or 0.25% acetic acid. Pudendal nerve stimulation at intensities of multiple times the threshold to induce observable anal twitching was applied during cystometrogram to inhibit the bladder overactivity induced by acetic acid irritation. Naloxone (0.1, 0.3 and 1 mg/kg intravenously) was administered to block opioid receptors, followed by MTEP (3 and 10 mg/kg intravenously) to block metabotropic glutamate 5 receptors. After each drug dose, pudendal inhibition of bladder overactivity was examined during cystometrogram. RESULTS: Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased mean ± SE bladder capacity to 23.6% ± 2.7% of saline control capacity. Pudendal nerve stimulation at 1 to 1.5 and 4 × threshold suppressed bladder overactivity and significantly increased mean capacity to 57.5% ± 8.1% (p = 0.0005) and 106% ± 15% (p = 0.0002), respectively, of saline control capacity. Naloxone had no effect on pudendal inhibition but MTEP eliminated the inhibition induced by low intensity stimulation and significantly decreased the inhibition induced by high intensity stimulation (p <0.05). Neither naloxone nor MTEP altered baseline bladder overactivity. CONCLUSIONS: Opioid receptors are not involved in pudendal inhibition of bladder overactivity but metabotropic glutamate 5 receptors are partially involved. Understanding neurotransmitter mechanisms could improve the efficacy of neuromodulation therapy for overactive bladder and identify molecular targets for developing new drugs for overactive bladder.

Toxicological effects of the antibiotic oxytetracycline to an Indian major carp Labeo rohita.

Oxytetracycline (OTC), an antibacterial agent, is extensively used in aquaculture practices all over the world. Despite its use, the toxicity of OTC to freshwater fish has been scarcely investigated. In this study, Labeo rohita were exposed to different concentrations (20, 40, 60, 80, 100, and 120 mg L(-1)) of OTC. Based on the survival-to-mortality ratio, an 80 mg L(-1) concentration was selected for sublethal toxicity analysis. Fish were exposed to the above-mentioned concentration for a period of 25 days, during which fish were killed at the end of every 5 days to analyse certain hematological and enzymological parameters. During the exposure period, a mixed trend was observed in hemoglobin (Hb), hematocrit, mean cell volume, mean cellular Hb, and mean cellular Hb concentration, whereas decreased red blood cell count and increased white blood cell was noted. A biphasic trend was observed in the enzymatic levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in the vital organs (gill, liver and muscle) of fish. The alterations of these parameters lead to the conclusion that these parameters may be used as biomarkers in monitoring OTC toxicity in aquaculture and fisheries farms.

Resonance metallic stents do not effectively relieve extrinsic ureteral compression in pediatric patients.

BACKGROUND AND PURPOSE: Use of metallic stents (Resonance) has been reported in the literature to be effective in relieving extrinsic obstruction in adults. Successful patency rates have been reported to be around 83.3%. The use of Resonance stents in children has not been reported. We present our experience with these stents in addressing extrinsic ureteral obstruction in the pediatric population. PATIENTS AND METHODS: We identified two patients who underwent placement of Resonance stents for extrinsic compression at the Children's Hospital of the University of Pittsburgh Medical Center. The first patient is a 12-year-old girl with a solitary left kidney who had a diagnosis of pelvic rhabdomyosarcoma; she was treated with surgery followed by adjuvant chemoradiation. Two years post-treatment, worsening renal function secondary to ureteral strictures developed. The second patient is a 14-year-old girl with a history of Gardner syndrome. Recurrent desmoid tumors developed in her pelvis and retroperitoneum that led to right ureteral obstruction, necessitating a nephrostomy tube. RESULTS: Both patients underwent successful technical placement of a Resonance stent. The time to failure for patient 1 was 3 months and for patient 2, 3 weeks. The first patient presented to the emergency department 3 months poststent in renal failure with a creatinine level of 13.7 mg/dL. This necessitated nephrostomy tube placement and hemodialysis. Ultimately, she needed an ileal ureter to preserve renal function. She is off hemodialysis and has a creatinine level of 2.2 mg/dL.The second patient, recurrent episodes of pyelonephritis, worsening hydronephrosis, and flank pain developed with just the Resonance stent in place. It was elected to remove the Resonance stent and replace the nephrostomy tube. She needed extensive ureterolysis, a right subtotal ureterectomy with a right to left ureteroureterostomy. CONCLUSION: We did not find the use of these stents to be effective in children. The time to failure was significantly shorter in children than those reported in the literature for adults.

Combination of foot stimulation and tramadol treatment reverses irritation induced bladder overactivity in cats.

PURPOSE: We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. MATERIALS AND METHODS: Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. RESULTS: Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. CONCLUSIONS: This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects.

Inhibition of micturition reflex by activation of somatic afferents in posterior femoral cutaneous nerve.

This study determined if activation of somatic afferents in posterior femoral cutaneous nerve (PFCN) could modulate the micturition reflex recorded under isovolumetric conditions in α-chloralose anaesthetized cats. PFCN stimulation inhibited reflex bladder activity and significantly (P <0.05) increased bladder capacity during slow infusion of saline or 0.25% acetic acid (AA). The optimal frequency for PFCN stimulation-induced bladder inhibition was between 3 and 10 Hz, and a minimal stimulation intensity of half of the threshold for inducing anal twitching was required. Bilateral pudendal nerve transection eliminated PFCN stimulation-induced anal twitching but did not change the stimulation-induced bladder inhibition, excluding the involvement of pudendal afferent or efferent axons in PFCN afferent inhibition.Mechanical or electrical stimulation on the skin surface in the PFCN dermatome also inhibited bladder activity. Prolonged (2 × 30 min) PFCN stimulation induced a post-stimulation inhibition that persists for at least 2 h. This study revealed a new cutaneous-bladder reflex activated by PFCN afferents. Although the mechanisms and physiological functions of this cutaneous-bladder reflex need to be further studied, our data raise the possibility that stimulation of PFCN afferents might be useful clinically for the treatment of overactive bladder symptoms.

Ureteral ectopia inserting into ipsilateral epididymis resulting in inflammatory paratesticular tumor.

An 8-year-old male with a history of VACTERL association was found to have a paratesticular mass. The patient was treated successfully with a radical orchiectomy and found to have ureteral ectopia inserting into the ipsilateral epididymis, resulting in this paratesticular mass caused by inflammation of the epididymis. This is the only reported case in the English literature of an ectopic ureter inserting into the epididymis and presenting as a paratesticular tumor. In unclear cases of paratesticular, inflammatory appearing masses, inguinal exploration is warranted.

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats.

Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3-7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50-60% of the saline control capacity. Tramadol administered alone in low doses (0.3-1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3-7 mg/kg) increased bladder capacity (50-60%). TNS in combination with tramadol (3-7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects.