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Evaluation of safety is of paramount importance with adoption of novel surgical technology. Although robotic surgery has become widely used in oncologic surgery, analysis of safety is lacking in comparison to traditional techniques. Standardized assessment of robotic surgical outcomes and adverse events following oncologic surgery is necessary for quality improvement with innovative technology. Between 2003 and 2016, 10,013 unique robotic operations were performed in 9,858 patients. Our prospectively maintained database was retrospectively reviewed for hospital readmissions and Clavien–Dindo grade ≥ 2 complications within 30 days. Multivariable logistic regression was used to identify predictors of surgical complications and hospital readmissions. Cases were stratified by discipline: genitourinary (n = 8240), gynecologic (n = 857), thoracic (n = 457), gastrointestinal (n = 322), hepatobiliary (n = 60), ear/nose/throat (n = 44) and general (n = 33). Intraoperative complications occurred in 42 surgeries (0.4%). Postoperative complications occurred in 946 patients [9.4%, highest grade 2 (n = 574), 3 (n = 288), 4 (n = 72), 5 (n = 10)]. Most frequent complications were ileus (154, 16.3%), anemia (91, 9.6%), cardiac arrhythmia (62, 6.6%), deep vein thrombosis/pulmonary embolus (47, 5.0%), wound infection (45, 4.8%) and urinary leak (43, 4.5%). 405 patients (4.0%) required readmission. Most common causes for hospital readmission were ileus (44, 10.9%), urinary leak (23, 5.7%), urinary tract infection (23, 5.7%), intra-abdominal abscess/fluid collection (23, 5.7%), and small bowel obstruction (19, 4.7%). On multivariable analysis, longer operative time and older age predicted complications and readmissions (p ≤ 0.02). Robotic-assisted surgery appears a safe for oncologic surgery with acceptable hospital readmission and complication rates. Older age and longer operative time were associated with complications and readmission.

Introduction:Urologists partnered with anesthesiologists to implement a model of perioperative and postoperative care known as the multidisciplinary perioperative surgical home in order to ...

INTRODUCTION AND OBJECTIVE:Extended pelvic lymph node dissection (eLND) at the time of radical prostatectomy has a staging benefit over limited pelvic lymph node dissection (LLND) but an unclear th...

BACKGROUND: To identify novel myofibrillar components of the Drosophila flight muscles, we carried out a proteomic analysis of chemically demembranated flight muscle myofibrils, and characterized the knockdown phenotype of a novel gene identified in the screen, CG1674. RESULTS: The CG1674 protein has some similarity to vertebrate synaptopodin 2-like, and when expressed as a FLAG-tagged fusion protein, it was localized during development to the Z-disc and cytoplasm. Knockdown of CG1674 expression affected the function of multiple muscle types, and defective flight in adults was accompanied by large actin-rich structures in the flight muscles that resembled overgrown Z-discs. Localization of CG1674 to the Z-disc depended predominantly upon presence of the Z-disc component alpha-actinin, but also depended upon other Z-disc components, including Mask, Zasp52, and Sals. We also observed re-localization of FLAG-CG1674 to the nucleus in Alpha-actinin and sals knockdown animals. CONCLUSIONS: These studies identify and characterize a previously unreported myofibrillar component of Drosophila muscle, that is necessary for proper myofibril assembly during development.

Endourologic procedures such as percutaneous nephrolithotomy (PCNL) employ the use of foot pedals in low-light operating room (OR) settings. These pedals can be especially difficult to locate or distinguish when several pedals are present during a single operation. Improper instrument activation in the OR has led to serious complications ranging from unintentional electrocautery to patient burns and even an intraoperative explosion. This study evaluates the impact of color-coded illumination on speed and efficiency of foot pedal activation.During a simulated PCNL procedure, the foot pedals for a C-arm, laser, and ultrasonic lithotripter (USL) were placed in random positions. Ten participants performed pedal activation in a randomized sequence. Objective outcomes included time to instrument activation, number of attempted pedal presses, number of incomplete pedal presses, and number of incorrect pedal presses. Subjective preferences for pedal illumination were also determined. Data were analyzed using Mann-Whitney U, Wilcoxon signed-rank, and Chi-square tests with p 0.05 indicating statistical significance.Illuminated foot pedals were associated with decreases in the average activation time for all instruments collectively (3.95 seconds vs 6.49 seconds; p = 0.017) and individually (C-arm: 3.07 seconds vs 4.21 seconds; p = 0.006; laser: 13.04 seconds vs 15.18 seconds; p 0.001; USL: 3.28 seconds vs 4.91 seconds; p 0.001) compared with nonilluminated pedals. Illuminated pedals were associated with fewer attempted pedal presses (33.5 vs 39.5; p = 0.007) and incomplete pedal presses (1.5 vs 8.5; p = 0.002). The number of incorrect pedal presses decreased with illumination, but this did not reach statistical significance (0 vs 0.5; p = 0.08). Participants reported that illumination simplified pedal activation and recommended its use (p 0.01).Color-coded illumination improved the speed and efficiency of foot pedal activation during simulated PCNL. Participants subjectively preferred using illuminated foot pedals for endourologic procedures and felt that they improved safety and efficiency.

Purpose Intravesical electrical stimulation treatment (IVES) has been successfully used to treat neurogenic bladder. We report the results of an observational study regarding the use of IVES for women with overactive bladder syndrome (OAB) and/or urgency urinary incontinence (UUI). Materials and methods IVES was performed in women with OAB (defined by frequency ≥8/day, nocturia ≥2/night, or ≥3 episodes of UUI on 3-day voiding diary) who failed prior medical therapy. Subjects underwent 4 weeks of treatment with an 8-Fr Detruset™ IVES catheter. Primary outcome was Patient Global Impression of Improvement (PGI-I) at 3 months. Secondary outcomes included Visual Analog Scale (VAS), Short Form OAB Questionnaire (OAB-q SF), Pelvic Floor Distress Inventory (PFDI), Pelvic Floor Impact Questionnaire (PFIQ), reduction in frequency and UUI on voiding diary, and adverse effects. Analysis was done with paired t-tests and Wilcoxon signed rank tests. Results Seventeen subjects completed the study. At 4 weeks post-treatment, 15 improved on PGI-I (11 subjects: 'a little better', 2: 'much better', 2: 'very much better'). There were significant improvements in symptom bother and health-related quality of life as measured by OAB-q SF and pelvic organ prolapse and urinary distress as measured by PFDI. Frequency decreased from 10.3±4.3 at baseline to 8.9±2.3 (p=0.04) at 3 months. No pain was reported during treatment. There was one urinary tract infection during the study period. No other adverse events were reported. Conclusions IVES appears to be a safe and effective novel treatment for OAB. Larger comparative studies are needed to investigate its potential for long-term treatment.

Aims Translabial ultrasound (TUS) is a useful tool for identifying and assessing synthetic slings. This study evaluates the ability of urology trainees to learn basic pelvic anatomy and sling assessment on TUS. Methods Eight urology trainees (six residents and two medical students) received a lecture reviewing basic anatomy and sling assessment on TUS followed by review of two training cases. Next, they underwent a 126-question examination assessing their ability to identify anatomic planes and structures in those planes, identify the presence of slings, and assess the location and intactness of a sling. The correct response rate was compared to that of an attending radiologist experienced in reading TUS. Non-parametric tests (Fisher's exact, chi-squared tests, and Yates correction) were used for statistical analysis, with P

INTRODUCTION AND OBJECTIVES:Benign ureteroenteric strictures (UES) may occur after radical cystectomy with urinary diversion. Timely treatment is instrumental in preventing renal insufficiency. The...

Background: Ischemia is thought to contribute to benign ureteroenteric stricture (UES) after radical cystectomy with urinary diversion (RCUD). Our institution adopted the use of ureteral perfusion assessment during all RCUDs using real-time indocyanine green angiography using the SPY fluorescence imaging platform (Stryker Corp., Kalamazoo, MI, USA). This guides the location of ureteral transection prior to ureteroenteric anastomosis. We sought to compare UES rates before and after adoption of SPY. Methods: A retrospective chart review was undertaken for the first 47 consecutive cases of RCUD using SPY as well as the previous 47 consecutive cases, which were performed without SPY. Fisher’s exact and Wilcoxon rank-sum tests were used to compare benign UES rates and the length of ureter excised during anastomosis. A p < 0.05 indicated statistical significance. Results: Median follow up was 12.0 months for SPY cases and 24.3 months for non-SPY cases. The UES rate for SPY RCUDs was 0% (0/93 ureters) compared with 7.5% (7/93 ureters) for non-SPY RCUDs ( p = 0.01). Amongst SPY RCUDs, 86 ureters had no hydronephrosis and 7 had mild hydronephrosis with reflux on loopogram. A total of 34.4% of ureters (32/93) had poor distal perfusion, requiring a more proximal anastomosis. The median length excised for ureters with poor distal perfusion was 3.8 cm, compared with 2.2 cm for ureters with good distal perfusion ( p < 0.0001). No complications attributable to the use of SPY were noted. Conclusion: Use of SPY to assess ureteral perfusion was associated with a decrease in the UES rate after RCUD. A total of 34.4% of ureters demonstrated poor distal perfusion, requiring a significantly more proximal ureteroenteric anastomosis.

INTRODUCTION AND OBJECTIVES:Radical cystectomy during multi-visceral resection for locally advanced pelvic malignancy requires urinary diversion. Outcomes with incontinent and continent urinary div...

INTRODUCTION AND OBJECTIVES:A minority of patients undergoing trimodality therapy for bladder cancer will go on to require salvage cystectomy. We report the outcomes in a small cohort of open and m...

Introduction: Volume of renal parenchymal loss is known to affect postoperative renal function after partial nephrectomy (PN). We utilize a novel comparison using donor nephrectomy (DN) pa...

Objective To introduce a grading system (kidney, ureter, and bladder [KUB]) to identify encrusted stents that may require multiple surgeries, multimodal surgery, and operative time > 180 minutes for successful removal. Methods One hundred ten retained encrusted ureteral stents were retrospectively scored using the KUB grading system and this score was correlated with operative time, need for multiple surgeries or multimodal surgery, and stone-free rate. Data analysis was performed with t test, Mann-Whitney U test, and chi-square tests. A P value of Results Average indwelling stent time was 17.2 months (0.7-139.0). There were 83.6% of stents removed in a single surgery, with 63.0% of these requiring multimodal surgery. K score ≥ 3 was associated with multiple surgeries (odds ratio [OR] 3.59, P = .006), multimodal surgery (OR 2.44, P = .04), operative time > 180 minutes (OR 3.80, P = .001), and lower stone-free rate (OR 0.23, P = .02). U score ≥ 3 was associated with operative time > 180 minutes (OR 3.28, P = .003). B score ≥ 3 was associated with lower stone-free rate (OR 0.23, P = .020). Total score ≥ 9 was associated with multiple surgeries (OR 4.19, P = .001), operative time > 180 minutes (OR 3.45, P = .002), and lower stone-free rate (OR 0.13, P = .001). Conclusion The KUB system identifies stents at risk for requiring multiple surgeries, multimodal surgery, and operative time > 180 minutes. It also correlates with stone-free rate. This grading system can help surgeons manage patient expectations and predict surgical complexity.

Background Translabial ultrasound (TUS) can provide an inexpensive alternative imaging modality for evaluating pelvic floor structures and synthetic slings as mesh can be difficult to identify on pelvic exam or cystoscopy, patients may be unable to provide an accurate history of previous pelvic surgery, and cross-sectional imaging with computed tomography and magnetic resonance imaging can be inadequate for evaluating synthetic slings. Objective To demonstrate the use of TUS in the evaluation of female pelvic floor structures and mesh. Methods Translabial ultrasound can be used in the Urology clinic or intraoperative setting using a curvilinear transducer. Following identification of anatomic landmarks in the various planes of the pelvic floor, TUS can evaluate for pelvic floor disorders and the type and location of synthetic mesh material. Artifacts, such as air pockets in the vagina or rectum and the hypoechoic pubic symphysis, are also considered. Results Real-time imaging allows for dynamic examination of pelvic organ prolapse and urethral hypermobility that can contribute to pelvic exam findings. Bladder ultrasound can help evaluate for lesions, calculi, and even mesh erosion. Translabial ultrasound can also be used to differentiate hyperechoic retropubic and transobturator slings by identifying the position of sling arms and the appearance of the sling at different planes. Evaluation with TUS can demonstrate sling disruption, folding, urethral impingement, and erosion into pelvic floor structures. This can be particularly useful in patients presenting with pain, recurrent infections, or voiding dysfunction in which problems with mesh may not be easily identified on pelvic exam or cystoscopy. This imaging modality can complement a patient's history, aid in preoperative planning, and enable intraoperative identification of mesh slings. Conclusion Translabial ultrasound provides a quick, readily available, and easy-to-learn imaging modality for evaluating pelvic floor structures and mesh in the office or intraoperative setting.

In this review, we examine the evolution and application of various diagnostic modalities for varicoceles starting with venography, scintigraphy, and thermography and their role in the evaluation of a varicocele patient. Some of these methods have been supplanted by less invasive and more easily performed diagnostic modalities, especially ultrasound and Doppler examination of the scrotum. Advances in ultrasound and magnetic resonance imaging hold the potential to expand the role of imaging beyond that of visual confirmation and characterization of varicoceles. The ability to identify the early indicators of testicular dysfunction based on imaging findings may have implications for the management of varicoceles in the future.

Percutaneous nephrolithotomy (PCNL) is associated with significant variability in postoperative pain and subsequent narcotic use. The purpose of this study was to determine the factors associated with high narcotic use following PCNL.A single-center retrospective review of patients undergoing initial PCNL between 2004 and 2014 was performed. Preoperative, intraoperative and postoperative factors associated with postoperative narcotic usage were analyzed. The primary outcome variable was mean narcotic usage, standardized to intravenous morphine-equivalents. Patients in the lowest 75th percentile were compared to those in the highest 25th percentile. Univariate and multivariate statistical analyses were performed, with p0.05 considered significant.When the 243 patients were compared from lowest to highest quartile, total narcotic use during the first 48 hour period was 2.3, 8.4, 15.6, and 41.7 mg of morphine-equivalents. On univariate analysis, predictors of high narcotic use included age 20-39 (p0.001), preoperative narcotic use (p0.001), presence of a postoperative complication (p = 0.044), and high stone burden (p = 0.002). Age20 (p0.001) and60 years (p = 0.014) were associated with low narcotic use. On multivariate analysis, age 20-39 (OR 6.87, 95% CI 2.22-21.23, p = 0.001), male gender (OR 2.47, CI 1.05-5.81, p = 0.037), and preoperative narcotic use (OR 3.27, CI 1.41-7.60, p = 0.006) were associated with higher opioid requirement.Patients who were aged 20-39, males, and those with prior narcotic exposure used the highest doses of narcotics postoperatively. Knowledge of the factors predictive of high narcotic usage may allow better preoperative management of patient expectations and more effective postoperative care to prevent the complications of high narcotic usage.

Retrograde ejaculation is a relatively rare cause of male infertility. Yet, as one of the few pathologies in male infertility that can in some cases be successfully treated with medications, it is important for the clinician to be able to diagnose and treat this entity. Recent studies have demonstrated findings pertaining to the cause and mechanism of retrograde ejaculation that run contrary to classical teaching. This chapter will examine these findings and review the causes, workup, diagnosis, and treatment for retrograde ejaculation. A clinical vignette of a common presentation of retrograde ejaculation is presented and workup, diagnosis, and treatment are discussed.

To compare the outcomes between laparoendoscopic single-site (LESS) and a novel percutaneous externally assembled laparoscopic (PEAL) nephrectomy in an in vivo porcine model.Ten female farm pigs were randomized to LESS nephrectomy (5) or PEAL nephrectomy (5). Operative times, estimated blood loss, and intraoperative and postoperative complications were compared. The surgeons used a Likert scale to grade difficulty of peritoneal access, port placement, tool assembly, hilar dissection, closure, and overall difficulty of surgery. Scar assessment was performed by a blinded plastic surgeon using the Vancouver Scar Scale. Descriptive statistics were reported as median and range. The Mann-Whitney U test was used for continuous and ordinal variables. A p value0.05 was considered significant.Median operative time was significantly shorter in the PEAL group vs the LESS group (85 minutes vs 127 minutes, p = 0.03). Median Likert scores showed overall hilar dissection and nephrectomy to be significantly easier using PEAL compared with LESS (2 vs 9, p 0.01 for both). The PEAL instruments left no visible scar at 5 feet in any animal, and only 1 out of 10 scars could be identified on physical examination.The PEAL surgical paradigm demonstrates nearly scarless outcomes while providing shorter operative times and easier performance than LESS nephrectomy in a porcine model.

Traditional techniques for obtaining percutaneous renal access utilize continuous fluoroscopy. In an attempt to minimize radiation exposure, we describe a novel laser direct alignment radiation reduction technique (DARRT) for percutaneous access and test it in a bench-top model.In this randomized-controlled bench-top study, 20 medical personnel obtained renal accesses using both the conventional bullseye technique and the laser DARRT. The primary endpoint was total fluoroscopy time. Secondary endpoints included insertion time, puncture attempts, course corrections, and subjective procedural difficulty. In the laser DARRT, fluoroscopy was used with the C-arm positioned with the laser beam at a 30° angle. The access needle and hub were aligned with the laser beam. Effective caliceal puncture was confirmed with fluoroscopy and direct vision. The Paired samples Wilcoxon signed rank test was used for statistical analysis with significance at p 0.05.A total of 120 needle placements were recorded. Fluoroscopy time for needle access using the laser DARRT was significantly lower than the bullseye technique in all groups as follows: attendings (7.09 vs 18.51 seconds; p 0.001), residents (6.55 vs 13.93 seconds; p = 0.001), and medical students (6.69 vs 20.22 seconds; p 0.001). Students rated the laser DARRT easier to use (2.56 vs 4.89; p 0.001). No difference was seen in total access time, puncture attempts, or course corrections between techniques.The laser DARRT reduced fluoroscopy time by 63%, compared with the conventional bullseye technique. The least experienced users found the laser DARRT significantly easier to learn. This novel technique is promising and merits additional testing in animal and human models.

RESULTS: Two hundred two patients were evaluated with CTU for AMH. GU malignancy was documented in 2 patients (0.99%), both renal masses suspicious for renal cell carcinoma (RCC). Sixty patients were found to have kidney stones, of which 26 had stones 1⁄4 5mm. Incidental extra-urinary findings were found in 150 (74.3%) patients, requiring further imaging costs of $17242 or $85.35 per patient screened. Twelve patients required a total of 20 procedures for a cost of $13898.57, resulting in 28 inpatient days and a hospital-adjusted expense of $41608. The total cost related to extra-urinary findings was $75122 or $371.89 per initial patient screened. CONCLUSIONS: The incidental extra-urinary findings detected on CTU can lead to expensive and invasive testing and treatment. Use of RUS in place of CTU to screen the upper tracts in patients with AMH could avoid costs and morbidity associated with these incidental findings, while still adequately evaluating the upper urinary tract. Those with positive findings on RUS, such as renal masses or stones, could then go on to CTU.

and uterus predisposes to this lesion during many gynecological and obstetric procedures. This kind of complication is increasing due to the widespread of cesarian deliveries. The aim of this video is to highlight the technique of vesicouterine fistula repair using vaginal approach. METHODS: A 38-year-old female was admitted to hospital with ciclic hematuria, amenorrhea and no incontinence. She had three previous cesarian deliveries, last one with bladder trauma 3 months before admission. Magnetic Resonance has shown a vesicouterine fistula above cervix. Patient intended to have future pregnancies so a vaginal correction of the vesicouterine fistula without hysterectomy was performed. The patient was prepared and draped in a modified dorsal lithotomy position. Initially, cystoscopy was done with identification of the fistula tract at anterior bladder wall. Uterine cavity was inspected though fistula tract. Next, ureteral catheters were introduced for safety during the procedure. Methylene blue was injected into the bladder to demonstrate the localisation of the fistula in the vaginal wall. A Pozzi clamp was applied to the uterine cervix for good exposure. Next, a supracervical incision was made and dissection was carried out until fistulous tract was identified. A T-clamp was applied to the vaginal wall and the inked fistulous tract was identified and dissected. An Hegar bougie was introduced into the cervical canal facilitating the procedure. Then the bladder wall was dissected in order to allow a tension-free closure of the bladder defect. Both ureters were identified before the vaginal wall was closed. After the closure of the bladder, uterus was closed with interrupted sutures over the Hegar bougie. Finally, vaginal wall was closed and ureteral catheters are removed. RESULTS: Patient was discharged home 1 day after surgery. Urethral catheter was maintained for 14 days. After four months, patient keeps without hematuria, neither incontinence and recovered her normal menstrual cycle. CONCLUSIONS: Vesicouterine fistula is a dreaded complication after cesarian deliveries. Its correction is usually performed through abdominal approach, however, vaginal approach is feasible, safe and less invasive. It may always be considered, mainly if procedure is made early after delivery, when uterus is still movable.

INTRODUCTION AND OBJECTIVES: We designed a novel technique of suctioning flexible ureteroscopy with automatic control of renal pelvic pressure (RPP) by a patented system including a pressuremeasuring ureteral access sheath (UAS) and an irrigation and suctioning platform. We sought to compare RPP values measured by the irrigation and suctioning platform and a nephrostomy catheter at different phases of flexible ureteroscopy when flow rate was set at 100 mL/min. METHODS: Eight young female pigs with a total of 16 macroscopically normal upper urinary tract systems were included .Via a subcostal incision a 6-F catheter was placed into the renal pelvis for RPP measurement by connecting to a pressure monitor. We then introduced the patented UAS (12-15F) retrogradely into the renal pelvis, through which the pressure was measured by the platform. RPP was measured at baseline period, irrigation and suctioning period, and therapeutic period. RESULTS: Twelve renal pelves were successfully established animal models for flexible ureteroscopy and pressure-measuring. Baseline RPP was 26.9 3.8mm Hg in the platform group and 26.3 5.2mm Hg in the nephrostomy group ( p 1⁄4 0.44). There was no significant difference on RPP between the 2 pressure measuring methods either at irrigation and suctioning period (-5.21+/-2.11 vs. -3.59+/-1.45, p1⁄40.42) or therapeutic period (-5.81+/-2.47 vs. -3.73+/-2.19, p1⁄40.39). CONCLUSIONS: Renal pelvic pressure can be accurately and effectively monitored and controlled using the irrigation and suctioning platform with function of pressure feedback and suctioning UAS with function of pressure-measuring.

We have developed an innovative method to remove albumin from plasma/serum samples for the LC-MS/MS quantitation of therapeutic proteins. Different combinations of organic solvents and acids were screened for their ability to remove albumin from plasma and serum samples. Removal efficiency was monitored by two signature peptides (QTALVELVK and LVNEVTEFAK) from albumin. Isopropanol with 1.0% trichloroacetic acid was found to be the most effective combination to remove albumin while retaining the protein of interest. Our approach was compared with a commercial albumin depletion kit on both efficiency of albumin removal and recovery of target proteins. We have demonstrated that our approach can remove 95% of the total albumin in human plasma samples while retaining close to 100% for two of three therapeutic proteins tested, with the third one at 60-80%. The commercial kit removed 98% of albumin but suffered at least 50% recovery loss for all therapeutic proteins when compared to our approach. Using BMS-C as a probe compound, the incorporation of the albumin removal approach has improved both assay sensitivity and ruggedness, compared to the whole plasma protein digestion approach alone. An LC-MS/MS method was developed and validated based on this new approach for the analysis of BMS-C in monkey serum. This assay was successfully applied to a toxicological study. When the albumin removal method was used in another clinical LC-MS/MS method, the sensitivity improved 10-fold to 50 ng/mL LLOQ comparing to a typical pellet digestion method.

The formation and fragmentation of a series of metal complexes containing polyether ionophores were studied using electrospray ionization (ESI) methods. Dissociation pathways were analyzed using both collision activated dissociation (CAD) and infrared multiphoton photodissociation (IRMPD) techniques. A number of structurally diagnostic fragment ions were observed, and in many cases the same types of pathways were observed for the alkali, transition, and alkaline earth metal complexes. The dominant fragmentation pathways included dehydration and cleavage across carbon–carbon bonds to produce either type-F or type-A fragments. Energy-resolved CAD and IRMPD experiments, along with double resonance SWIFT, were performed to evaluate the genealogy of fragmentation pathways.

Post-column addition of a metal salt and an auxiliary chelating ligand via a sheath flow offers an alternative strategy for promoting electrospray ionization of analytes via metal cationization. In the present study, a high-performance liquid chromatography (HPLC) mass spectrometer interface that incorporates a modified ionspray source that allows either online metal cationization or protonation is reported. The analytical utility of metal complexation is evaluated relative to protonation as a means for efficient ionization and generation of structurally diagnostic ions during HPLC separation. To improve metal cationization, an auxiliary chelating ligand is added to the sheath flow to coordinate the metal and stabilize the resulting complexes. The methodology was verified using a series of quinolone antibiotics as model analytes. Relative reaction efficiencies were compared for the protonation vs. metal complexation modes, and it was found that metal complexation with an auxiliary chelating ligand gave a three to five times better detection limit than protonation for the quinolones. Detector linearity and optimal reaction conditions are also reported.

The formation of a series of doubly charged pyridyl ngand-polyether-transition metal complexes was studied using electrospray ionization (ESI) methods. Both doubly charged mixed-ligand dimer and trimers were observed. Differences in the electronic structures of the metal ions and the nature of the polyether and pyridyl ligands influence the types of complexes formed. Despite the large differences in the solution binding constants of pyridyl and polyether ligands, mixed-ligand complexes were efficiently formed, suggesting that the ESI process itself may enhance the formation of certain types of complexes that might not be favored in solution. Charge reduction of the metal ion within the mixed-ligand complexes was not observed, although charge reduction of Cu 2+ occurred for the singleligand polyether and pyridyl complexes.

The formation, ligand exchange reactions, and dissociation of various types of mixed ligand/metal complexes are studied in a quadrupole ion trap. The monopositive complexes are generated by ion-molecule association reactions between the polydentate organic ligands and laser-desorbed monopositive metal ions (M+) and incorporate at least one polyether or at least one pyridyl ligand bound to a transition metal ion. Ligand exchange and collisional activated dissociation (CAD) techniques are used to investigate the nature of the binding interactions and the relative binding free energies of the various ligands. There are two dominant influences on the strength of the binding interactions in the complexes. First, the number of coordination sites of each ligand and its flexibility or ability to participate in cooperative binding interactions are reflected in the relative coordination capabilities of the ligands. Second, the ability of a ligand to approach the metal ion and successfully adopt a favorable binding conformation differs greatly when the metal is already bound to one versus two ligands. For example, when the metal is bound to two pyridyl ligands, the ability of a large flexible polyether with multiple oxygen binding sites to displace even one of the pyridyl ligands is greatly reduced relative to the case when the metal is only bound to a single pyridyl ligand. In addition to these two trends, the electronic configuration of the metal ion also plays a subtle role in terms of influencing the stabilities of certain monomer (pyridyl ligand + M+) and heterodimer (pyridyl ligand + M+ + polyether) complexes. However, the nature of the metal ion does not appear to change the trends in relative binding free energies of the various ligands; it simply influences the formation of certain types of complexes based on the optimum coordination number and favored coordination geometry of the metal ion.

The competitive proton-binding abilities of a series of pyridyl and polyether ligands were examined by application of ligand-exchange and collisionally activated dissociation (CAD) methods. Many of the ligands of interest are multidentate, thus giving them enhanced capabilities for coordinating the proton, and they also may undergo a substantial loss of entropy, predominantly in rotational and vibrational modes of freedom, when binding a proton because the electrostatic interactions between donor atoms and the proton create a degree of organization of the ligand. The presence of dominant mixed-dimer complexes formed during the ligand-exchange reactions provides key evidence that multiple hydrogen-bond formation is operative for one or both ligands. Although CAD provides some insight into the factors which influence proton-binding strengths of the ligands in dimers, several general issues emerge when applying the CAD (i.e. the kinetic method) to estimate proton affinities of multidentate ligands. Owing to the severe impact of entropic effects upon dissociation of the dimers involving multidentate ligands, the ratio of product ions does not reflect the order of proton affinities of the ligands involved in the dimer. The CAD experiments give the order of gas-phase basicities at a higher temperature in which the entropy term is much more significant. This effect is especially significant when one of the ligands is floppy and multidentate and the other is rigid or monodentate. © 1998 John Wiley & Sons, Ltd.

The analysis of hydantoin and succinimide anticonvulsants was carried out using techniques of chemical ionization and collision activated dissociation (CAD) in a quadrupole ion trap. Dimethyl ether was used as the chemical ionization reagent gas to generate [M + H] + and [M + 13] + products, with the objective of determining whether the protonation and methylene substitution reactions occurred at the same site and whether the products provided the same structural information. CAD, including MS 3 , SWIFT double resonance experiments and deuterium-labeling studies suggest that protonation occurs on a nitrogen atom or carbonyl oxygen while methylene substitution occurs predominantly on the phenyl substituents. Both [M + H] + and [M + 13] + ions dissociate by similar pathways in which typically the attached proton or methylene group remains a spectator.

Although several lines of evidence implicate gray matter abnormalities in the prefrontal cortex and anterior cingulate cortex in patients with bipolar disorder, findings have been largely inconsistent across studies. Differences in patients' medication status or mood state or the application of traditional volumetric methods that are insensitive to subtle neuroanatomical differences may have contributed to variations in findings. The authors used MRI in conjunction with cortical pattern matching methods to assess cortical thickness abnormalities in euthymic bipolar patients who were not receiving lithium treatment.Thirty-four lithium-free euthymic patients with bipolar I disorder and 31 healthy comparison subjects underwent MRI scanning. Data were processed to measure cortical gray matter thickness. Thickness maps were spatially normalized using cortical pattern matching and were analyzed to assess illness effects and associations with clinical variables.Relative to healthy comparison subjects, euthymic bipolar patients had significantly thinner gray matter in the left and right prefrontal cortex (Brodmann's areas 11, 10, 8, and 44) and the left anterior cingulate cortex (Brodmann's areas 24/32). Thinning in these regions was more pronounced in patients with a history of psychosis. No areas of thicker cortex were detected in bipolar patients relative to healthy comparison subjects.Using a technique that is highly sensitive to subtle neuroanatomical differences, significant regional cortical thinning was found in lithium-free euthymic patients with bipolar disorder.

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-codedrvalue at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

Infrared multiphoton photodissociation (IRMPD) is combined with stored wave form inverse Fourier transforms (SWIFT) to effect dissociation and ion ejection in a quadrupole ion trap mass spectrometer. The application of IRMPD to the structural characterization of biochemical ions generated by chemical ionization and electrospray ionization and the feasibility of utilizing infrared photons for the activation of laser-desorbed metal ion-crown ether complexes was examined. The effect of helium pressure on the dissociation efficiency and relative dissociation rate constants for systems with well-known thermochemistry was evaluated. The helium pressure is not detrimental to the IRMPD experiment when nominal pressures lower than 2 x 10(-5) Torr are used. At pressures close to nominally 8 x 10(-5) Torr of helium, collisonal deactivation dominates. Results show conventional CAD is a more selective dissociation technique; however, the amount of fragment ion information generated depends highly on the qz value. IRMPD, on the other hand, is independent of the value of qz such that low rf storage values can be utilized during the irradiation period. Thus, under these conditions, informative lower mass fragment ions are trapped and detected. A larger number of structurally informative fragments is generated upon irradiation with infrared photons relative to the CAD method because of the further excitation of primary fragment ions upon photoabsorption. SWIFT wave forms are successfully utilized to determine the extent of excitation of primary fragment ions as well as prove/disprove dissociation pathways of a variety of ions such as macrolide antibiotics and hydrogen-bonded complexes.