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Objective: To compare binary metrics and Global Evaluative Assessment of Robotic Skills (GEARS) evaluations of training outcome assessments for reliability, sensitivity, and specificity., Background: GEARS-Likert-scale skills assessment are a widely accepted tool for robotic surgical training outcome evaluations. Proficiency-based progression (PBP) training is another methodology but uses binary performance metrics for evaluations., Methods: In a prospective, randomized, and blinded study, we compared conventional with PBP training for a robotic suturing, knot-tying anastomosis task. Thirty-six surgical residents from 16 Belgium residency programs were randomized. In the skills laboratory, the PBP group trained until they demonstrated a quantitatively defined proficiency benchmark. The conventional group were yoked to the same training time but without the proficiency requirement. The final trial was video recorded and assessed with binary metrics and GEARS by robotic surgeons blinded to individual, group, and residency program. Sensitivity and specificity of the two assessment methods were evaluated with area under the curve (AUC) and receiver operating characteristics (ROC) curves., Results: The PBP group made 42% fewer objectively assessed performance errors than the conventional group ( P < 0.001) and scored 15% better on the GEARS assessment ( P = 0.033). The mean interrater reliability for binary metrics and GEARS was 0.87 and 0.38, respectively. Binary total error metrics AUC was 97% and for GEARS 85%. With a sensitivity threshold of 0.8, false positives rates were 3% and 25% for, respectively, the binary and GEARS assessments., Conclusions: Binary metrics for scoring a robotic VUA task demonstrated better psychometric properties than the GEARS assessment., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To investigate the role of cytoreductive radical prostatectomy in addition to standard of care for patients with newly diagnosed metastatic prostate cancer., Materials and Methods: This multicentre, prospective study included asymptomatic patients from 2014 to 2018 (NCT02138721). Cytoreductive radical prostatectomy was offered to all fit patients with resectable tumours, resulting in 40 patients. Standard of care was administered to 40 patients who were ineligible or unwilling to undergo surgery. The primary endpoint was castration resistant cancer-free survival at the time point of ≥50% events. The secondary endpoint was local event-free survival. Kaplan-Meier and Cox regression analyses with propensity-score analysis were applied., Results: After a median (quartiles) follow-up of 35 (24-47) months, 42 patients became castration-resistant or died. The median castration resistant cancer-free survival was 53 (95% confidence interval [CI] 14-92) vs 21 (95% CI 15-27) months for cytoreductive radical prostatectomy compared to standard of care (P = 0.017). The 3-year estimates for local event-free survival were 83% (95% CI 71-95) vs 59% (95% CI 51-67) for cytoreductive radical prostatectomy compared to standard of care (P = 0.012). However, treatment group showed no significance in the multivariable models for castration resistant cancer-free survival (P = 0.5) or local event-free survival (P = 0.3), adjusted for propensity-score analysis. Complications were similar to the non-metastatic setting. Patients undergoing surgery were younger, with lower baseline prostate-specific antigen levels, alkaline phosphatase levels and metastatic burden., Conclusion: The present LoMP study was unable to show a difference between the two inclusion groups regarding castration resistant cancer-free survival for asymptomatic patients with newly diagnosed metastatic prostate cancer. These results validate previous evidence that, in well-selected and informed patients, cytoreductive radical prostatectomy is feasible and safe, with corresponding continence rates compared to the non-metastatic, high-risk setting. Whether cytoreductive radical prostatectomy could be a valuable option to achieve good local palliation needs to be further researched. Overall, the role of cytoreductive radical prostatectomy needs to be further explored in randomized studies to correct for potential bias., (© 2021 The Authors BJU International © 2021 BJU International.)

Introduction: The addition of stereotactic ablative radiotherapy (SABR) to standard of care for patients with oligometastatic prostate cancer has the potential of improving survival and delaying further metastases. The primary aim of this analysis is to report survival outcomes and pattern of recurrence of patients with hormone-sensitive (HSPC) and castrate-resistant (CRPC) oligometastatic prostate cancer treated with SABR., Methods: This is a single-center retrospective study of patients with oligometastatic prostate cancer treated in Iridium Network between 2014 and 2018. All patients with oligometastatic (≤3 active lesions) HSPC and CRPC treated with SABR were included. Data were collected using electronic records. Patterns of first progression following SABR were reported. Kaplan-Meier methods were used to determine survival outcomes., Results: Eighty-seven men received SABR to 115 metastases. Nineteen patients were castrate-resistant and 68 hormone-sensitive at the time of SABR. Median follow-up was 41.6 months. In 25% of patients, no decline from baseline PSA was recorded. Median bPFS was 11.7 months (95% CI 7.6 - 18.3) for HSPC as well as CRPC (95% CI 6.4 - 24.0) (p=0.27). Median DMFS was 21.8 (95% CI 16.9 - 43.2) versus 17.6 months (95% CI 6.7 - 26.2) for HSPC versus CRPC, respectively (p=0.018). Median OS was 72.6 months (95% CI 72.6 - not reached) for HSPC and not reached for CRPC (95% CI 35.4 months - not reached) (p=0.026). For the subgroup of oligorecurrent HSPC, short-term androgen-deprivation therapy was associated with improved bPFS (median 6.0 vs. 18.3 months, HR 0.31, p<0.001) and DMFS (median 15.8 vs 29.6 months, HR 0.5, p=0.06). Information on pattern of relapse was retrieved for 79 patients: 45% (36/79) of these patients were long-term disease-free (>18 months), 28% (22/79) of patients wmere oligoprogressive (≤3 new lesions) and 27% (21/79) developed a polymetastatic relapse., Conclusion: In this cohort, oligometastatic HSPC showed potential benefit from SABR with a median DMFS of 21.8 months. Well-selected patients with oligometastatic CRPC may also benefit from SABR. For patients with metachronous and repeat oligorecurrent HSPC, combining SABR with short-term androgen-deprivation therapy was associated with improved bPFS and DMFS. Overall, 36/87 (41%) of patients were still free from clinical relapse at 18 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mercier, Claessens, De Troyer, Debacker, Fransis, Vandeursen, Ost and Dirix.)

The development of nephritis increases the risk of morbidity and mortality in systemic lupus erythematosus (SLE) patients. While standard induction therapies, such as mycophenolate mofetil (MMF) induce clinical remission (i.e., complete response) in approximately 50% of SLE patients with nephritis, many patients fail to respond. Therapeutic response is often not assessed until 6-12 months after beginning treatment. Those patients that fail to respond to treatment continue to accumulate organ damage, thus, there is a critical need to predict which patients will fail therapy before beginning treatment, allowing physicians to optimize therapy. Our previous studies demonstrated elevated urine, but not serum, glycosphingolipids (GSLs) in SLE patients with nephritis compared to SLE patients without nephritis, suggesting the urine GSLs were derived from the kidney. In this study, we measured the GSLs hexosylceramide and lactosylceramide in extracellular vesicles isolated from longitudinal urine samples of LN patients that were treated with MMF for 12 months. GSL levels were significantly elevated in the baseline samples (prior to treatment) of non-responders compared to complete responders. While a few other proteins measured in the whole urine were higher in non-responders at baseline, only GSLs demonstrated a significant ability to discriminate treatment response in lupus nephritis patients.

Introduction: There is a gap between optimal and actual use of radiotherapy (RT) in muscle-invasive bladder cancer (MIBC). We investigated the opinions of radiation-oncologists, urologists, and medical oncologists on use of RT in different cases. Barriers and facilitators for applying guidelines were examined., Material and Methods: A web-based survey was developed at Ghent University Hospital and conducted from November 18, 2016 to July 17, 2017. The place of primary, adjuvant, and palliative RT was evaluated. Additional questions assessed the use of guidelines, barriers, and facilitators., Results: In total, 126 physicians (57 radiation oncologists, 41 urologists, and 28 medical oncologists) completed the survey. Significant differences in use of RT in the primary and adjuvant setting were observed between radiation oncologists and urologists. Younger age and presence of hydronephrosis are perceived as contraindications for RT in the primary setting. In the adjuvant setting, RT was mainly considered in case of positive surgical margins. All radiation oncologists and 96% of medical oncologists considered palliative RT for patients with painful bone metastases, whereas 21% of urologists did not (P < .001). Clinical decisions are mainly based on EAU guidelines. The most important reason for nonadherence to guidelines is external barriers (18%). One strategy to improve awareness of guidelines is a summary of guidelines on the website of national organizations (54%)., Conclusion: There is controversy regarding the place of RT in MIBC, with a clear variation between professionals. Barriers and facilitators to use RT should be addressed, seeing the gap in RT utilization and predicted increase in patients requiring RT for MIBC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Clean intermittent self-catheterization (CISC) is now considered the gold standard for the management of urinary retention. In the literature, several articles on patients' perspectives on CISC and adherence to this technique have been published. No studies have yet explored the points of view of professional caregivers, such as nurses and doctors. The aim of this study was to explore the opinions of urologists about CISC and to evaluate the need for dedicated nurses specialized in CISC through a self-administered questionnaire., Methods: A questionnaire was developed to explore the opinions of professional caregivers about self-catheterization and to evaluate the need to provide nurses with specialized education in CISC. Questionnaires were sent to 244 urologists through email. We received 101 completed questionnaires. The response rate was 41.4%., Results: Hand function, the presence or absence of tremor, and visual acuity were rated as the most important determinants for proposing CISC to a patient. Twenty-five percent of the urologists reported that financial remuneration would give them a greater incentive to propose CISC. The lack of dedicated nurses was reported by half of the urologists as a factor preventing them from proposing CISC. A meaningful number of urologists thought that patients perceive CISC as invasive and unpleasant. Although most urologists would choose CISC as a treatment option for themselves, almost 1 urologist out of 5 would prefer a permanent catheter., Conclusions: This questionnaire gave valuable insights into urologists' perceptions of CISC, and could serve as the basis for a subsequent broader international study. Further research should also focus on the opinions of nurses and other caregivers involved in incontinence management. Apart from financial remuneration, it is also clear that ensuring sufficient expertise and time for high-quality CISC care is important. This could be a potential role for dedicated nurses.

Purpose: The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors., Patients and Methods: All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2-3 years of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors., Results: Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25-87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17-1.54) and OS (HR 1.22, 95% confidence interval 1.10-1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%)., Conclusions: Patients with pN1 PCa treated with wpRT and 2-3 years ADT have an encouraging 5‑year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.

Objectives: PADUA score is a standardized anatomical classification of renal tumors proposed with the aim to objectivize the decision-making process of any urologist evaluating kidney tumors potentially suitable for nephron-sparing surgery. The system was proposed in a series of patients treated with open partial nephrectomy (PN) and was recently validated in a series of patients treated with either open or laparoscopic PN. The purpose of the present study was to validate the PADUA score in a series of consecutive patients who underwent robot-assisted PN (RPN)., Methods: We evaluated retrospectively all the MRI or CT images of 62 consecutive patients who underwent RPN for renal tumors at a nonacademic teaching institution by a single surgeon between September 2006 and November 2009., Results: PADUA score (6-7 vs. 8-11) was correlated with warm ischemia time (WIT) (P = 0.002), console time (P = 0.001), blood loss (P = 0.009), percentage of pelvicaliceal repair (P = 0.002), and overall complications (P = 0.02). PADUA score was the only variable able to predict the risk of the overall complications (P = 0.02). PADUA score turned out to be an independent predictor of WIT >20 min in multivariable analysis (OR 5.4; P = 0.002), once adjusted for surgeon's experience Finally, PADUA score was the only independent predictor of the need for pelvicaliceal repair (OR 3.7; P = 0.006)., Conclusions: PADUA classification was an effective tool to predict WIT and risk of perioperative complications also in patients who underwent RPN. This classification must be considered useful to improve patients counseling and selection for RPN.

Introduction: Localized prostate cancer is increasingly treated by robot-assisted radical prostatectomy (RARP). We evaluated the introduction of RARP following a training program at a high-volume robotic center., Materials and Methods: Before starting RARP, a young urologist followed a 6-month training program. The outcome of his first 50 RARPs was compared with the last 50 open radical prostatectomies (ORPs) performed by an experienced urologist at the same institution. Tumor characteristics were similar in both groups. Median follow-up was 12 (RARP) and 31 (ORP) months (p < 0.001)., Results: RARP was associated with more nerve sparing (82 vs. ORP 46%, p < 0.001), longer operation time [median 205 (range 120-310) vs. ORP 180 (85-280) min, p = 0.001], lower decline of postoperative hemoglobin [RARP -2.1 (0.1-4.5) vs. ORP -4.0 (1.0-7.0) g/dl, p < 0.001] and shorter catheter stay [6 (5-47) vs. ORP 14 (9-43) days, p < 0.001]. Complication rates were similar. Overall and pT2-positive surgical margin rate was 8 vs. 24% (p = 0.054) and 0 vs. 11.8% (p = 0.114) for RARP vs. ORP, respectively. One-year urinary continence rate was 76.7 (RARP) and 75.8% (ORP, p = 0.833)., Conclusions: RARP was safely introduced after a training program in a high-volume robotic center, both surgically, oncologically and functionally., (© 2013 S. Karger AG, Basel.)

Aims: The aim of the study was to evaluate feasibility, efficacy, and safety of the AdVance male sling in neuropathic male patients with intrinsic sphincter deficiency., Methods: We evaluated 20 consecutive male neuropathic patients (12 menigomyelocele and 8 lower spinal cord injured), age 23 ± 13 years (range 6-52 years) with urodynamically proven sphincter deficiency and stress urinary incontinence. In all patients an AdVance male sling was implanted from June 2007 to September 2009. Patients were evaluated with the number of pads per day (PPD), visual analogue scale (VAS) for continence and the International Consultation on Incontinence-Short Form (ICIQ-SF). Cure was defined as a 10 on VAS or using no pads for urinary leakage, improvement as >5 and failure as ≤5., Results: Positive effect in 13 of 20 patients (65%) at 1-year follow-up: 8 patients were cured, 5 improved, and 7 failed. VAS score increased from baseline 2.6 (SD 2.0) to 7.2 (SD 3.5) at 12 months (P < 0.001). ICIQ-SF decreased from 14 (SD 4.2) to 4 (SD 4.1) (P < 0.001). Friedman and Wilcoxon tests revealed at 1, 3, 6, 9, and 12 months significant improvement compared to baseline (P = 0.008)., Conclusions: Implantation of the AdVance male sling is feasible in both adult and pediatric patients. A promising cure/improvement rate was achieved as well as a low complication rate., (Copyright © 2012 Wiley Periodicals, Inc.)

The objective of the present review was to evaluate the effect of population-based screening on the incidence of prostate cancer, prostate cancer tumor stage and grade, prostate cancer mortality, and overall mortality. A systematic review was carried out in April 2011, searching the Medline and Web of Science databases. The records were reviewed to identify comparative and randomized controlled trials evaluating the effect of screening on prostate cancer. Eight trials were identified containing personalized data on a screened versus a non-screened cohort. Prostate-specific antigen and digital rectal examination were the main screening tools. Prostate-specific antigen threshold and screening interval was not uniform among the different trials. Screening was associated with a significant increase in prostate cancer detection (relative risk 1.55; P=0.002), and a significant shift towards more localized (relative risk 1.81; P=0.01) and more low-grade tumors (relative risk 2.32; P=0.001). In overall analysis, no significant effect on prostate cancer mortality (relative risk 0.88; P=0.18) and overall mortality (relative risk 0.90; P=0.27) in favor of screening was observed. An adjusted analysis excluding papers with short follow up, high prostate-specific antigen contamination in the non-screening group and low participation in the screening group was able to show a significant reduction in prostate cancer mortality of 24%. The ideal screening strategy is unclear. Screening is associated with better PC detection and this in a more localized stage and of less aggressive tumors. Excluding the main shortcomings in screening studies (short follow up, high prostate-specific antigen contamination in non-screening group and low participation in screening group), screening is able to reduce prostate cancer mortality., (© 2011 The Japanese Urological Association.)

Background: Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70 Gy might result in improved outcome., Objective: To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD)., Design, Setting, and Participants: Between 1999 and 2008, 136 patients were referred for HD-SIMRT with or without AD. The median follow-up was 5 yr. Indications for HD-SIMRT were persisting prostate-specific antigen (PSA) or a rising PSA following RP. All patients were irradiated at a single, tertiary, academic centre. AD was initiated on the basis of seminal vesicle invasion, preprostatectomy PSA >20 ng/ml, Gleason score ≥ 4+3 (n=43), or personal preference of the referring urologist (n=54)., Intervention: A median 76-Gy dose was prescribed to the RP bed using intensity-modulated radiotherapy (IMRT) in all patients. AD consisted of a luteinising hormone-releasing hormone analogue for 6 mo., Measurements: Univariate and multivariate analyses were used to examine the influence of patient- and treatment-related factors on late toxicity, biochemical relapse-free survival (bRFS), and clinical relapse-free survival (cRFS)., Results and Limitations: The 5-yr actuarial bRFS and cRFS were 56% and 86%, respectively. On multivariate analysis, the presence of perineural invasion at RP (hazard ratio [HR]: 6.19, p=0.001) and an increasing pre-SRT PSA (PSA 0.5 ng/ml: HR: 1; PSA 1-1.5 ng/ml: HR: 1.60, p=0.30; and PSA >1 ng/ml: HR: 2.70, p=0.02) were independent factors for a decreased bRFS. The addition of AD improved bRFS (HR: 0.33, p=0.005). On multivariate analysis, none of the variables was a predictor of cRFS. The 5-yr risk of grade 2-3 toxicity was 22% and 8% for genitourinary and gastrointestinal symptoms, respectively., Conclusions: IMRT allows for safe dose escalation to 76Gy with good bRFS., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: It is unclear whether immediate adjuvant radiotherapy for high-risk disease at prostatectomy (capsule perforation, seminal vesicle invasion, and/or positive surgical margins) is equivalent to delayed salvage radiotherapy at biochemical recurrence. We performed a matched case analysis comparing high-dose adjuvant intensity modulated radiotherapy (A-IMRT) with salvage IMRT (S-IMRT)., Methods and Materials: One hundred forty-four patients with high-risk disease at prostatectomy were referred for A-IMRT, and 134 patients with high-risk disease were referred at biochemical recurrence (rising prostate-specific antigen [PSA], following prostatectomy, above 0.2 ng/ml) for S-IMRT. Patients were matched in a 1:1 ratio according to preoperative PSA level, Gleason score, and pT stage. Median doses of 74 Gy and 76 Gy were prescribed for A-IMRT and S-IMRT, respectively. We report biochemical relapse free survival (bRFS) rates using the Kaplan-Meier method. Univariate and multivariate analyses were used to examine tumour- and treatment-related factors., Results: A total of 178 patients were matched (89:89). From the end of radiotherapy, the median follow-up was 36 months for both groups. The 3-year bRFS rate for the A-IMRT group was 90% compared to 65% for the S-IMRT group (p < 0.05). On multivariate analysis, S-IMRT, Gleason grades of ≥ 4+3, perineural invasion, preoperative PSA level of ≥ 10 ng/ml, and omission of androgen deprivation (AD) were independent predictors for a reduced bRFS (p < 0.05). From the date of surgery, the median follow-up was 43 and 60 months for A-IMRT and S-IMRT, respectively. The 3-year bRFS rate for A-IMRT was 91% compared to 79% for S-IMRT (p < 0.05). On multivariate analysis, Gleason grades of ≥ 4+3, perineural invasion, and omission of AD were independent predictors for a reduced bRFS (p < 0.05). S-IMRT was no longer an independent prognostic factor (p = 0.08)., Conclusions: High-dose A-IMRT significantly improves 3-year bRFS compared to S-IMRT. Gleason grades of ≥ 4+3, perineural invasion, and omission of AD were independent prognostic factors for a decreased bRFS, both from the dates of surgery and from radiotherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To assess the long-term outcome of continent diversion in children with structural or neurogenic cause of incontinence, with special interest in differences between closed and open bladder neck procedures., Patients and Methods: A cohort of 63 children with intractable incontinence treated with continent diversion between January 1998 and January 2008 were reviewed for underlying disease, type of surgery, complications and outcome., Results: Forty patients had a continent diversion with open bladder neck (group 1) and 23 patients had their bladder neck closed (group 2: 11 primarily closed; 12 secondarily closed). There was no difference between the two groups in terms of patient characteristics, surgical re-interventions and stone formation. The continence rate however was significantly better in group 2 (95.6% vs 77.5%)., Conclusion: Bladder neck closure with continent diversion as primary or salvage procedure in children with intractable incontinence does not result in extra morbidity and has a high success rate. Thorough urodynamic evaluation of bladder function is the key to success in therapy planning for these children, to minimize the need for re-intervention., (Copyright © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: We determined the current etiology of urethral stricture disease in the developed world and whether there are any differences in etiology by patient age and stricture site., Material and Methods: Between January 2001 and August 2007 we prospectively collected a database on 268 male patients with urethral stricture disease who underwent urethroplasty at a referral center. The database was analyzed for possible cause of stricture and for previous interventions. Subanalysis was done for stricture etiology by patient age and stricture site., Results: The most important causes were idiopathy, transurethral resection, urethral catheterization, pelvic fracture and hypospadias surgery. Overall iatrogenic causes (transurethral resection, urethral catheterization, cystoscopy, prostatectomy, brachytherapy and hypospadias surgery) were the etiology in 45.5% of stricture cases. In patients younger than 45 years the main causes were idiopathy, hypospadias surgery and pelvic fracture. In patients older than 45 years the main causes were transurethral resection and idiopathy. In cases of penile urethra hypospadias surgery idiopathic stricture, urethral catheterization and lichen sclerosus were the main causes, while in the bulbar urethra idiopathic strictures were most prevalent, followed by strictures due to transurethral resection. The main cause of multifocal/panurethral anterior stricture disease was urethral catheterization, while pelvic fracture was the main cause of posterior urethral strictures., Conclusions: Of strictures treated with urethroplasty today iatrogenic causes account for about half of the urethral stricture cases in the developed world. In about 1 of 3 cases no obvious cause could be identified. The etiology is significantly different in younger vs older patients and among stricture sites.

A randomized, controlled clinical trial was performed with patients with acute respiratory distress syndrome (ARDS) to compare the effect of conventional therapy or inhaled nitric oxide (iNO) on oxygenation. Patients were randomized to either conventional therapy or conventional therapy plus iNO for 72 h. We tested the following hypotheses: (1) that iNO would improve oxygenation during the 72 h after randomization, as compared with conventional therapy; and (2) that iNO would increase the likelihood that patients would improve to the extent that the FI(O2) could be decreased by > or = 0.15 within 72 h after randomization. There were two major findings. First, That iNO as compared with conventional therapy increased Pa(O2)/FI(O2) at 1 h, 12 h, and possibly 24 h. Beyond 24 h, the two groups had an equivalent improvement in Pa(O2)/FI(O2). Second, that patients treated with iNO therapy were no more likely to improve so that they could be managed with a persistent decrease in FI(O2) > or = 0.15 during the 72 h following randomization (11 of 20 patients with iNO versus 9 of 20 patients with conventional therapy, p = 0.55). In patients with severe ARDS, our results indicate that iNO does not lead to a sustained improvement in oxygenation as compared with conventional therapy.

Attentional modulation of the startle reflex was studied in 16 unmedicated schizophrenia patients and 15 control individuals during the 18F-2-deoxyglucose uptake period for positron emission tomography. In a task involving attended, ignored, and novel tones that served as prepulses, control individuals showed greater prepulse inhibition (PPI) at 120 ms and greater prepulse facilitation at 4,500 ms during attended than during ignored prepulses; the amount of PPI and facilitation during novel prepulses was intermediate. In contrast, patients failed to show differential PPI at 120 ms and tended to show greater facilitation at 4,500 ms during novel prepulses. For control individuals, greater PPI was associated with higher relative metabolic activity rates in prefrontal (Brodmann Areas 8, 9, and 10 bilaterally) and lower in visual cortex. Patients showed this relationship only for Area 10 on the left. Patients also had low metabolism in superior, middle, and inferior prefrontal cortex. Consistent with animal models, our results demonstrate the importance of the functional integrity of prefrontal cortex to PPI modulation.

Shock, a common and frequently fatal manifestation of gas gangrene caused by Clostridium perfringens, is probably mediated by extracellular toxins. Previous studies implicating alpha-toxin as the major lethal factor were frequently done with preparations contaminated with a second lethal factor, theta-toxin. We purified alpha- and theta-toxins from C. perfringens and demonstrated that both were lethal to mice. We investigated the effects of these purified toxins on cardiovascular function in intact rabbits; both toxins caused profound hypotension and bradycardia within 40 min. Reduced cardiac output preceded the development of hypotension and bradycardia. Purified alpha-toxin produced a dose-dependent reduction in myocardial function in isolated rabbit atrial preparations. Purified theta-toxin did not directly inhibit myocardial function. Shock induced by alpha-toxin may be partly mediated by direct depression of myocardial function. theta-Toxin reduced cardiac output in intact animals but had no direct effects on isolated heart preparations at concentrations that induced shock in intact animals. These data suggest that theta-toxin-induced shock could be mediated by an endogenous myocardial depressant factor.

Differences in Estimated Breeding Values expressed in dollars were compared by simulation of two, 100-cow, closed herds. One herd practiced normal intensity of female selection. The other herd generated various herd replacements by embryo transfer by varying 1) selection rate of embryo transfer dams and 2) numbers of daughters per dam from which embryos were transferred, while varying the merit of mates of embryo transfer dams. Estimated Breeding Value dollars were compounded each generation and regressed to remove age adjustments and added feed and health costs. Beginning values in both herds included a standard deviation of 55 Cow Index dollars, herd average of -23 Cow Index dollars, and a 120 Predicted Difference dollars for mates of dams not embryo transferred. Average merit of all sires used increased $12 per year. Herd calving rate (.70), proportion females (.5), calf loss (.15), and heifer survival rate (.83) were used. Breakeven cost per embryo transfer cow entering the milking herd was computed by Net Present Value analysis using a 10% discount rate over 10 and 20 yr. Breakeven cost or the maximum expense that would allow a 10% return on the expenditure ranged from $135 to $510 per surviving cow, $24 to $125 per transfer, $47 to $178 per pregnancy, and $81 to $357 per female calf born. As the number of replacements resulting from embryo transfer increased, breakeven cost per embryo transfer cow decreased due to diminishing return.