Hereditary Cancer Clinics Improve Adherence to NCCN Germline Testing Guidelines for Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year overall survival rate of 10%. In November 2018, NCCN recommended that all patients with PDAC receive genetic counseling (GC) and germline testing regardless of family history. We hypothesized that patients with PDAC were more likely to be referred for testing after this change to the guidelines, regardless of presumed predictive factors, and that compliance would be further improved following the implementation of a hereditary cancer clinic (HCC). METHODS: We conducted a single-institution retrospective analysis of patients diagnosed with PDAC from June 2017 through December 2021 at University of California, Irvine. We compared rates of genetics referral among patients in different diagnostic eras: the 18-month period before the NCCN Guideline change (pre-NCCN era: June 2017 through November 2018), 14 months following the change (post-NCCN era: December 2018 through January 2020), and 18 months after the creation of an HCC (HCC era: June 2020 through December 2021). Family and personal cancer history, genetics referral patterns, and results of GC were recorded. Data were compared using chi-square, Fisher exact, and multivariate analyses. RESULTS: A total of 335 patients were treated for PDAC (123 pre-NCCN, 109 post-NCCN, and 103 HCC) at University of California, Irvine. Demographics across groups were comparable. Prior to the guideline changes, 30% were referred to GC compared with 54.7% in the post-NCCN era. After the implementation of the HCC, 77.4% were referred to GC (P<.0001). The odds ratio (OR) for referral to GC among patients with a positive family history of cancer progressively decreased following the change (pre-NCCN era: OR, 11.90 [95% CI, 3.00-80.14]; post-NCCN era: OR, 3.39 [95% CI, 1.13-10.76]; HCC era: OR, 3.11 [95% CI, 0.95-10.16]). CONCLUSIONS: The 2018 updates to the NCCN Guidelines for PDAC recommending germline testing for all patients with PDAC significantly increased GC referral rates at our academic medical center. Implementation of an HCC further boosted compliance with guidelines.

Intraoperative use of optical coherence tomography to differentiate normal and diseased thyroid and parathyroid tissues from lymph node and fat.

The purpose of this study is twofold: (1) to determine the feasibility of optical coherence tomography (OCT) to differentiate normal and diseased tissue of the neck region intraoperatively and (2) to evaluate how accurately a cohort of test subjects can identify various tissue types when shown a sample set of OCT images. In this in vivo, prospective, single institutional study, an OCT imaging system (Niris, Imalux, Cleveland, OH) was used to image parathyroid, thyroid, lymph node, and fat tissue in 76 patients during neck surgery. Biopsies were performed for comparison of OCT images with histology in select cases (n = 20). Finally, a group of either surgeons or scientists familiar with OCT (n = 17) were shown a sample of OCT images and asked to identify the tissue. A total of 437 OCT images were analyzed, and characteristic features of each tissue type were identified. OCT demonstrated distinct differences in structural architecture and signal intensity that allows differentiation between thyroid and parathyroid tissues, lymph nodes, and fat. OCT images were also compared with histology with good correlation. There was no difference in correctly identifying OCT-imaged tissue type between surgeons and scientists. This study is the first in vivo OCT imaging study to evaluate both normal and diseased tissues that may be encountered during neck surgery. OCT has the potential to become a valuable intraoperative tool to differentiate diseased and normal thyroid tissue intraoperatively to obtain an "optical biopsy" in real time without fixation, staining, or tissue resection.

Stimulation latency and comparison of cycling regimens in women using sacral neuromodulation.

AIMS: In this two-part study, we sought to define how long sacral neuromodulation users with overactive bladder should trial a new setting before attributing symptoms to that setting. Subsequently, we evaluated patient preferences of variable stimulation regimens. METHODS: In the initial phase of this prospective pilot study, participants' devices were turned off and later reactivated; time to symptom recurrence and resolution were recorded. In phase two, participants trialed four settings in a masked fashion with random order. After unmasking, participants chose their preferred setting and were followed 1 year. RESULTS: Twelve subjects completed phase one. With the device off, the mean time to symptom recurrence was 11.25 days. Mean time to symptom regression following reactivation was 6.42 days. Combined, the 90th percentile was 15 days for symptoms to reflect the device's new setting. Among 23 women completing part two, the most popular setting at the time of unmasking was a 1-hr on, 2-hr off cycled setting chosen by 7 (30%) participants. According to published estimates of battery longevity, 14 (61%) participants chose a more energy-conserving setting at the time of unmasking. The mean difference in estimated battery longevity between the chosen and baseline regimens was 14.5 months. These gains diminished in the following year with clinical changes in device settings by patients and providers. CONCLUSIONS: Sacral neuromodulation patients should allow a 2-week trial before attributing symptoms to a new setting. With additional information, many opt for energy-conserving settings. A 1-hr on, 2-hr off regimen warrants further study. Neurourol. Urodynam. 36:486-489, 2017. © 2016 Wiley Periodicals, Inc.

Long-Range Optical Coherence Tomography of the Neonatal Upper Airway for Early Diagnosis of Intubation-related Subglottic Injury.

RATIONALE: Subglottic edema and acquired subglottic stenosis are potentially airway-compromising sequelae in neonates following endotracheal intubation. At present, no imaging modality is capable of in vivo diagnosis of subepithelial airway wall pathology as signs of intubation-related injury. OBJECTIVES: To use Fourier domain long-range optical coherence tomography (LR-OCT) to acquire micrometer-resolution images of the airway wall of intubated neonates in a neonatal intensive care unit setting and to analyze images for histopathology and airway wall thickness. METHODS: LR-OCT of the neonatal laryngotracheal airway was performed a total of 94 times on 72 subjects (age, 1-175 d; total intubation, 1-104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records were reviewed retrospectively for extubation outcome. MEASUREMENTS AND MAIN RESULTS: Backward stepwise regression analysis demonstrated a statistically significant association between log(duration of intubation) and both laryngeal (P < 0.001; multiple r(2) = 0.44) and subglottic (P < 0.001; multiple r(2) = 0.55) airway wall thickness. Subjects with positive histopathology on LR-OCT images had a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer intubation time was found to be significantly associated with extubation failure. CONCLUSIONS: LR-OCT allows for high-resolution evaluation and measurement of the airway wall in intubated neonates. Our data demonstrate a positive correlation between laryngeal and subglottic wall thickness and duration of intubation, suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the early diagnosis of postintubation subglottic injury and help reduce the incidences of failed extubation caused by subglottic edema or acquired subglottic stenosis in neonates. Clinical trial registered with www.clinicaltrials.gov (NCT 00544427).

Intraoperative, real-time monitoring of blood flow dynamics associated with laser surgery of port wine stain birthmarks.

BACKGROUND AND OBJECTIVE: Port-wine stain (PWS) birthmarks affect ∼22 million people worldwide. After several treatment sessions, complete disappearance of the PWS occurs in only ∼10% of treated patients. There is a need to develop a new strategy to improve the efficacy of each treatment session and the overall treatment outcome. The study objective was to determine how intraoperative measurements of blood flow correlate with treatment response assessed several weeks post treatment. STUDY DESIGN/MATERIALS AND METHODS: We employed Laser Speckle Imaging (LSI) to measure intraoperative blood-flow dynamics. We collected data from 24 subjects undergoing laser therapy for facial PWS birthmarks. Photographs were taken before treatment and at a follow-up visit, and analyzed by two expert observers. RESULTS: Intraoperative LSI enables real-time monitoring of blood-flow dynamics in response to laser treatment and can inform clinicians on the need for focused re-treatment. The degree of PWS blanching achieved is positively correlated with the log-transformed acute blood-flow reduction (P = 0.022). CONCLUSION: LSI is a simple, intraoperative monitoring tool during laser therapy of PWS birthmarks. LSI provides a single value for blood flow that correlates well with the degree of blanching achieved with laser therapy.

Self-concept in children with Down syndrome.

Self-concept is a critical indicator of quality of life but few studies have examined this subject in children with Down syndrome (DS). In this study, we propose a novel methodology to assess the self-concept of children with DS by analyzing their responses towards two dolls, one with a "typically developing" (TD) appearance and one with the phenotypic features of DS. Fifty-four children with DS participated in play sessions with both dolls and were then interviewed to assess doll preference, resemblance, and attribution of positive qualities. We observed that children with DS: (i) exhibited a preference for the TD doll regardless of age, gender, IQ or self-awareness; (ii) attributed more positive qualities to the TD doll than the DS doll; and (iii) believed that they resembled the TD doll, rather than the more phenotypically accurate representation of themselves. Older participants were more likely to exhibit self-recognition by this technique. These findings contribute to current understandings of how people with DS view themselves and their disability.

Randomized prospective crossover study of interstim lead wire placement with curved versus straight stylet.

AIMS: To assess whether InterStim lead wire placement with the curved stylet achieves motor response at lower amplitudes compared to straight stylet use. METHODS: This was a prospective, randomized, crossover study of patients scheduled for InterStim lead wire placement. All patients underwent lead wire testing with both the curved and straight stylets. Patients were randomized to determine stylet order, and then crossed-over to the alternate. Intra-operatively, the amplitude achieving motor response at each electrode was recorded. The stylet with lowest overall amplitudes was used for final placement. Primary outcome measure was amplitude requirement in the two deepest (0 and 1) electrodes. Secondary outcomes included amplitudes at the number 2 and 3 electrodes, combined amplitudes, stylet order, and adverse outcomes. RESULTS: Forty-two patients were enrolled, 40 of whom were included in the final analysis. Mean age was 69 years (SD = 12.8) and mean BMI 27 (SD = 5.6). Indications for placement included: urge urinary incontinence (N = 26), urge/frequency (N = 25), non-obstructive urinary retention (N = 5), and fecal incontinence (N = 10). There were no significant differences between randomized groups. Regardless of order, the curved stylet achieved a motor response at lower amplitudes in the deepest electrodes (P < 0.001). Combined amplitudes of all electrodes were also significantly lower with the curved stylet (P < 0.001). Subsequently, 88% underwent final "optimal" placement with curved stylet (N = 35). CONCLUSIONS: The curved stylet for InterStim lead wire placement consistently achieved motor response at lower amplitudes. A brief intra-operative exchange of stylets represents a minor procedural alteration that could maximize Implantable Pulse Generator battery life and facilitate programming.

Endobronchial ultrasound skills and tasks assessment tool: assessing the validity evidence for a test of endobronchial ultrasound-guided transbronchial needle aspiration operator skill.

RATIONALE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming standard of care for the sampling of mediastinal adenopathy. The need for a safe, effective, accurate procedure makes EBUS-TBNA ideal for mastery training and testing. OBJECTIVES: The Endobronchial Ultrasound Skills and Tasks Assessment Tool (EBUS-STAT) was created as an objective competency-oriented assessment tool of EBUS-TBNA skills and knowledge. This study demonstrates the reliability and validity evidence of this tool. METHODS: The EBUS-STAT objectively scores the EBUS-TBNA operator's skills, including atraumatic airway introduction and navigation, ultrasound image acquisition and optimization, identification of mediastinal nodal and vascular structures, EBUS-TBNA sampling, and recognition of EBUS/computed tomography images of mediastinal structures. It can be administered at the bedside or using combination of low- and high-fidelity simulation platforms. Two independent testers administered the EBUS-STAT to 24 operators at three levels of EBUS-TBNA experience (8 beginners, 8 intermediates, and 8 experienced) at three institutions; operators were also asked to self-assess their skills. Scores were analyzed for intertester reliability, correlation with prior EBUS-TBNA experience, and association with self-assessments. MEASUREMENTS AND MAIN RESULTS: Intertester reliability between testers was very high (r = 0.9991, P < 0.00005). Mean EBUS-STAT scores for beginner, intermediate, and experienced groups, respectively, were 31.1, 74.9, and 93.6 out of 100 (F(2,21) = 118.6, P < 0.0001). Groups were nonoverlapping: post hoc tests showed each group differed significantly from the others (P < 0.001). Self-assessments corresponded closely to actual EBUS-STAT scores (r(2) = 0.81, P < 0.001). CONCLUSIONS: The EBUS-STAT can be used to reliably and objectively score and classify EBUS-TBNA operators from novice to expert. Its use to assess and document the acquisition of knowledge and skill is a step toward the goal of mastery training in EBUS-TBNA.

In vitro, ex vivo and in vivo isotherms for renal cryotherapy.

PURPOSE: Preoperative planning for renal cryotherapy is based on isotherms established in gel. We replicated gel isotherms and correlated them with ex vivo and in vivo isotherms in a porcine model. MATERIALS AND METHODS: PERC-17 CryoProbes (1.7 mm) and IceRods (1.47 mm) underwent trials in gel, ex vivo and in vivo porcine kidneys. Temperatures were recorded at 13 predetermined locations with multipoint thermal sensors. RESULTS: At the cryoprobe temperatures were not significantly different along the probe in any medium for either system (p = 0.0947 to 0.9609). However, away from the probe ex vivo and in vivo trials showed warmer temperatures toward the cryoprobe tip for each system (p = 0.0003 to 0.2141). Mean +/- SE temperature 5 mm distal to the cryoprobe tip in vivo was 19.2C +/- 16.1C for CryoProbes and 27.3C +/- 11.2C for IceRods. Temperatures were consistently colder with CryoProbes than with IceRods in gel (p <0.00005), ex vivo (p <0.00005) and in vivo (p = 0.0014). At almost all sites temperatures were significantly colder in gel and in ex vivo kidney than in in vivo kidney for CryoProbes (p = 0.0107 and 0.0008, respectively) and for IceRods (each p <0.00005). CONCLUSIONS: Gel and ex vivo isotherms do not predict the in vivo pattern of freezing. Thus, they should not be used for preoperative planning. The cryoprobe should be passed 5 mm beyond the tumor border to achieve suitably cold temperatures. Multipoint thermal sensor probes are recommended to record actual temperature during renal cryotherapy.

Sacrifice of accessory pudendal arteries in normally potent men during robot-assisted radical prostatectomy does not impact potency.

AIM: Whether or not sacrificing accessory pudendal arteries (APAs) during radical prostatectomy affects potency has been an ongoing source of concern. Herein, we present our potency results relative to sacrificing APAs in normally pre-potent men following robot-assisted radical prostatectomy (RARP). METHODS: The distribution of APAs and clinical characteristics were prospectively recorded in 200 consecutive patients undergoing RARP with a cautery-free technique. Sexual function was assessed using the International Index of Erectile Function 5-item questionnaire (IIEF-5). All APAs were sacrificed due to stapling the dorsal vein complex. MAIN OUTCOME MEASURES: Postoperatively, potency was defined by an affirmative answer to the following two questions: "Were erections adequate for penetration?" and "were the erections satisfactory?" Postoperative IIEF-5 scores and quality of erections (% of preoperative firmness: 0%, 25%, 50%, 75%, 100%) were also obtained. Subgroup analysis of patients age < or =65 years with IIEF-5 score of 22-25 was performed. RESULTS: Eighty patients (40%) had APAs. Preoperatively, there was no association with having an APA and normal/abnormal sexual function. Preoperatively, 58/200 were < or =65 years with self-administered IIEF-5 scores of 22-25. Postoperatively, 53/58 (91%) were potent at 24 months follow-up. Nineteen of 58 patients had a sacrificed APA; 39 patients had no APA. Eighteen of 19 (95%) patients with sacrificed APAs were potent vs. 35/39 (90%) with no APA present (P = 0.53). Multivariate analysis showed no significant correlation between sacrificing an APA and time of potency recovery, quality of postoperative erections (94% vs. 90% P = 0.80) or mean IIEF-5 score (22.4 vs. 20.8, P = 0.13). CONCLUSION: We found no correlation between the presence or absence of APAs and preoperative sexual function. Furthermore, after sacrificing all APAs, we found no correlation with potency return, time to return of potency, quality of erections, or mean IIEF-5 scores at 24 months.

Genetic Subtype-Phenotype Analysis of Growth Hormone Treatment on Psychiatric Behavior in Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a complex multisystemic condition caused by a lack of paternal expression of imprinted genes from the 15q11.2-q13 region. Limited literature exists on the association between molecular classes, growth hormone use, and the prevalence of psychiatric phenotypes in PWS. In this study, we analyzed nine psychiatric phenotypes (depressed mood, anxiety, skin picking, nail picking, compulsive counting, compulsive ordering, plays with strings, visual hallucinations, and delusions) recognized in PWS and investigated associations with growth hormone treatment (GHT), deletions (DEL) and uniparental disomy (UPD) in a cohort of 172 individuals with PWS who met the criteria for analysis. Associations were explored using Pearson chi-square tests and univariable and multivariable logistic regression analyses to control for confounding exposures. This observational study of the largest dataset of patients with PWS to date suggested the following genetic subtype and phenotype correlations in psychiatric behaviors: (1) skin picking was more frequent in those with DEL vs. UPD; (2) anxiety was more common in those with UPD vs. DEL; and (3) an increased frequency of anxiety was noted in the UPD group treated with GHT compared to the DEL group. No other significant associations were found between the genetic subtype or GHT including for depressed mood, nail picking, compulsive counting, compulsive ordering, playing with strings, and visual hallucinations. Further studies will be required before any conclusions can be reached.

Preliminary study of virtual reality and model simulation for learning laparoscopic suturing skills.

PURPOSE: Repetitive practice of laparoscopic suturing and knot tying can facilitate surgeon proficiency in performing this reconstructive technique. We compared a silicone model and pelvic trainer to a virtual reality simulator in the learning of laparoscopic suturing and knot tying by laparoscopically naïve medical students, and evaluated the subsequent performance of porcine laparoscopic cystorrhaphy. MATERIALS AND METHODS: A total of 20 medical students underwent a 1-hour didactic session with video demonstration of laparoscopic suturing and knot tying by an expert laparoscopic surgeon. The students were randomized to a pelvic trainer (10) or virtual reality simulator (10) for a minimum of 2 hours of laparoscopic suturing and knot tying training. Within 1 week of the training session the medical students performed laparoscopic closure of a 2 cm cystotomy in a porcine model. Objective structured assessment of technical skills for laparoscopic cystorrhaphy was performed at the procedure by laparoscopic surgeons blinded to the medical student training format. A video of the procedure was evaluated with an objective structured assessment of technical skills by an expert laparoscopic surgeon blinded to medical student identity and training format. The medical students completed an evaluation questionnaire regarding the training format after the laparoscopic cystorrhaphy. RESULTS: All students were able to complete the laparoscopic cystorrhaphy. There was no difference between the pelvic trainer and virtual reality groups in mean +/- SD time to perform the porcine cystorrhaphy at 40 +/- 15 vs 41 +/- 10 minutes (p = 0.87) or the objective structured assessment of technical skills score of 8.8 +/- 2.3 vs 8.2 +/- 2.2 (p = 0.24), respectively. Bladder leak occurred in 3 (30%) of the pelvic trainer trained and 6 (60%) of the virtual reality trained medical student laparoscopic cystorrhaphy procedures (Fisher exact test p = 0.37). The only significant difference between the 2 groups was that 4 virtual reality trained medical students considered the training session too short compared to none of those trained on the pelvic trainer (p = 0.04). CONCLUSIONS: There is no significant difference between the pelvic trainer and virtual reality trained medical students in proficiency to perform laparoscopic cystorrhaphy in a pig model, although both groups require considerably more training before performing this procedure clinically. The pelvic trainer training may be more user-friendly for the novice surgeon to begin learning these challenging laparoscopic skills.

Diagnosis of subglottic stenosis in a rabbit model using long-range optical coherence tomography.

OBJECTIVES/HYPOTHESIS: Current imaging modalities lack the necessary resolution to diagnose subglottic stenosis. The aim of this study was to use optical coherence tomography (OCT) to evaluate nascent subglottic mucosal injury and characterize mucosal thickness and structural changes using texture analysis in a simulated intubation rabbit model. STUDY DESIGN: Prospective animal study in rabbits. METHODS: Three-centimeter-long sections of endotracheal tubes (ETT) were endoscopically placed in the subglottis and proximal trachea of New Zealand White rabbits (n = 10) and secured via suture. OCT imaging and conventional endoscopic video was performed just prior to ETT segment placement (day 0), immediately after tube removal (day 7), and 1 week later (day 14). OCT images were analyzed for airway wall thickness and textural properties. RESULTS: Endoscopy and histology of intubated rabbits showed a range of normal to edematous tissue, which correlated with OCT images. The mean airway mucosal wall thickness measured using OCT was 336.4 µm (day 0), 391.3 µm (day 7), and 420.4 µm (day 14), with significant differences between day 0 and day 14 (P = .002). Significance was found for correlation and homogeneity texture features across all time points (P < .05). CONCLUSIONS: OCT is a minimally invasive endoscopic imaging modality capable of monitoring progression of subglottic mucosal injury. This study is the first to evaluate mucosal injury during simulated intubation using serial OCT imaging and texture analysis. OCT and texture analysis have the potential for early detection of subglottic mucosal injury, which could lead to better management of the neonatal airway and limit the progression to stenosis. LEVEL OF EVIDENCE: NA Laryngoscope, 127:64-69, 2017.

Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma.

We report somatic mutations in three genes (CSNK1 epsilon, encoding the Ser/Thr kinase casein kinase I epsilon; DLG1, encoding a membrane-associated putative scaffolding protein; and EDD/hHYD, encoding a progestin induced putative ubiquitin-protein ligase) in mammary ductal carcinoma. These genes were suspected of playing a role in cancer because loss-of-function mutations in their Drosophila homologues cause excess tissue growth. Using DNA from 82 laser-microdissected tumor samples, followed by microsatellite analysis, denaturing HPLC and direct sequencing, we found multiple somatic point mutations in all three genes, and these mutations showed significant association with loss of heterozygosity of closely linked polymorphic microsatellite markers. For CSNK1 epsilon and DLG1, most of the mutations affected highly conserved residues, some were found repetitively in different patients, and no synonymous mutations were found, indicating that the observed mutations were selected in tumors and may be functionally significant. Immunohistochemical reactivity of each protein was reduced in poorly differentiated tumors, and there was a positive association between altered protein reactivity, loss of heterozygosity, and somatic mutations. There was a statistically significant association of hDlg staining with p53 and Ki67 reactivity, whereas CSK1 epsilon and EDD/hHYD staining levels were associated with progesterone receptor status. The results provide strong indications for a role of all three genes in mammary ductal carcinoma. They also justify additional studies of the functional significance of the changes, as well as a search for additional changes in these and other genes identified from studies on model systems.

Development of a Tool to Assess Basic Competency in the Performance of Rigid Bronchoscopy.

RATIONALE: Rigid bronchoscopy is increasingly used by pulmonologists for the management of central airway disorders. However, an assessment tool to evaluate the competency of operators in the performance of this technique has not been developed. We created the Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) to serve as an objective, competency-oriented assessment tool of basic rigid bronchoscopic skills, including rigid bronchoscopic intubation and central airway navigation. OBJECTIVES: To assess whether RIGID-TASC scores accurately distinguish the basic rigid bronchoscopy skills of novice, intermediate, and expert operators, and to determine whether RIGID-TASC has adequate interrater reliability when used by different independent testers. METHODS: At two academic medical centers in the United States, 30 physician volunteers were selected in three categories: 10 novices at rigid bronchoscopy (performed at least 50 flexible, but no rigid, bronchoscopies), 10 operators with intermediate experience (performed 5-20 rigid bronchoscopies), and 10 experts (performed ≥100 rigid bronchoscopies). Participants included pulmonary and critical care fellows, interventional pulmonology fellows, and faculty interventional pulmonologists. Each subject then performed rigid bronchoscopic intubation and navigation on a manikin, while being scored independently by two testers, using RIGID-TASC. MEASUREMENTS AND MAIN RESULTS: Mean scores for three categories (novice, intermediate, and expert) were 58.10 (±4.6 [SE]), 78.15 (±3.8), and 94.40 (±1.1), respectively. There was significant difference between novice and intermediate (20.05, 95% confidence interval [CI] = 7.77-32.33, P = 0.001), and intermediate and expert (16.25, 95% CI = 3.97-28.53, P = 0.008) operators. The interrater reliability (intraclass correlation coefficient) between the two testers was high (r = 0.95, 95% CI = 0.90-0.98). CONCLUSIONS: RIGID-TASC showed evidence of construct validity and interrater reliability in this setting and group of subjects. It can be used to reliably and objectively score and classify operators from novice to expert in basic rigid bronchoscopic intubation and navigation.

Fluoroquinolone therapy in Mycobacterium chelonae keratitis after lamellar keratectomy.

PURPOSE: To characterize a rabbit model of Mycobacterium chelonae keratitis after lamellar keratectomy and assess the effectiveness of fluoroquinolone therapy. SETTING: University Laboratory, University of California, Irvine, California, USA. METHODS: Twenty-eight New Zealand white rabbits had unilateral lamellar keratectomy with placement of 2.5 x 10(5) colony-forming units of log-phase M chelonae under each flap. Eyes (7 per group) were randomized and treated with sterile balanced salt solution, gatifloxacin 0.3%, ciprofloxacin 0.3%, or levofloxacin 0.5% 4 times daily. Two masked observers examined all eyes on days 2, 5, and 7 and weekly for 4 weeks. Severity of disease and bacterial culture results were the main outcomes measured. The means and standard deviations were calculated, and differences between the groups were statistically analyzed. RESULTS: All eyes developed clinical disease. At the time the rabbits were killed, eyes treated with balanced salt solution, ciprofloxacin, levofloxacin, and gatifloxacin were culture positive in 6 (85.7%), 7 (100%), 6 (85.7%), and 3 (42.9%) of 7 eyes per group, respectively. Frequency of positive culture and the severity of clinical disease in gatifloxacin-treated eyes were significantly less (P < .05) than in the other groups combined. CONCLUSIONS: The rabbit model of M chelonae keratitis was successfully developed in our study. A fourth-generation quinolone (gatifloxacin) showed the best performance among the fluoroquinolones tested in our experimental approach. The fourth-generation fluoroquinolone, gatifloxacin, could be effectively used for the treatment of mycobacterial keratitis.

Enhancement of leukemia rejection by mice successfully treated for L1210 leukemia due to low dose compared to high dose VP-16.

We have earlier shown that VP-16 combined with Cyclosporin A (CsA) produces tumor specific immunity to L1210 leukemia in BDF/1 mice [Slater LM, Sweet P, Stupecky M, Reynolds JT. Cyclosporin A/VP-16 produced immunity to L1210 leukemia: the participation of cytotoxic CD(8) T-lymphocytes, Clin Immunol Immunopathol 1995;75:239-45]. Our current studies, designed to determine the role of VP-16 independently of CsA in this effect show that increased dose intensity of VP-16, in the absence of CsA, improves the frequency of 60 day survival of treated mice but impairs the ability of 60 day surviving mice to reject L1210 leukemia challenge. This impairment is associated with progressive diminution of mitogen responses by spleen cells harvested from tumor free VP-16 treated mice.

Association between promyelocyte protein and small ubiquitin-like modifier protein and the progression of cervical neoplasia.

OBJECTIVE: To examine the association between the size and number of promyelocyte protein-containing nuclear bodies, their colocalization with the small ubiquitin-like modifier protein, and existing histopathologic staging of cervical neoplasia progressing toward squamous cell carcinoma. METHODS: Fluorescence-based immunodetection of the promyelocyte protein and the small ubiquitin-like modifier protein was performed on paraffin-embedded and histopathologically graded human uterine cervical tissues. Quantitative measurements of the size and number of the promyelocyte protein-containing nuclear bodies were made and statistically analyzed. RESULTS: We found that promyelocyte protein-containing nuclear bodies exhibit changes in both size and number throughout the continuum of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. An increase in number and size of the bodies occurs with progression from normal to CIN I/CIN II. In CIN III, two new subcategories of nuclear body are present with distinctly different promyelocyte protein patterns, with the type B CIN III losing the small ubiquitin-like modifier protein partnership. In squamous cell carcinoma, we see the loss of this colocalization in both well and poorly differentiated tumors, with a distinctly different promyelocyte protein pattern. Well-differentiated tumors have bigger nuclear bodies that are more numerous than those of the poorly differentiated tumors. CONCLUSION: These data support the use of promyelocyte and small ubiquitin-like modifier proteins as a cytodiagnostic marker that parallels cervical cancer progression.

Corneal lenticule harvest using a microkeratome and an artificial anterior chamber system at high intrachamber pressure.

PURPOSE: To evaluate the safety and accuracy of a manual microkeratome and an artificial anterior chamber used at high intrachamber pressure to harvest corneal lenticules for lamellar keratoplasty. SETTING: Department of Ophthalmology, University of California, Irvine, California, USA. METHODS: Forty-seven human eye-bank corneoscleral rims were mounted on an artificial anterior chamber. A manual microkeratome was used to perform lamellar keratectomy at a mean intrachamber pressure of 95.8 mm hg +/- 4.8 (sd). Two thicknesses (300 microm and 360 microm microkeratome heads) and diameters (8.0 mm and 9.0 mm) were attempted, and the resultant lenticules were analyzed by pachymetry and digital photography. RESULTS: In the 9.0 mm/360 microm group, corneal perforation occurred in 12 of 17 lenticules (71.2%). Except for this group, 24 of 30 corneas (80.0%) showed a less than 0.5 mm deviation from the expected diameter. Neither the horizontal nor the vertical diameter differences were statistically significant (P >.05). The difference between the horizontal and vertical diameters was within +/-0.2 mm in 23 corneas (76.7%). Three (10.0%) corneal beds contained a slightly uneven keratectomy margin. CONCLUSIONS: This system provided accurate and smooth lenticules for lamellar keratoplasty. The precision and accuracy of the obtained corneal lenticules were better than those in previous reports. However, the 9.0 mm diameter/360 microm thickness head with high intrachamber pressure should not be applied in the clinical setting without further testing. In this laboratory study, a minimal corneal thickness of 588 microm was required to avoid perforation.