Ketorolac effectively inhibits ureteral contractility in vitro

INTRODUCTION: The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range. MATERIALS AND METHODS: Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM-10 microM) for 90 minutes and compared with indomethacin (1 muM) and dimethyl sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time. RESULTS: Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1 nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 microM, 88.7%; and 10 microM, 98.3%. Ureteral contractility was significantly reduced by 1 microM ketorolac (39.0%; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 microM ketorolac was not significantly different at any time point from any of the higher doses studied. CONCLUSION: Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 microM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.     

Adult anterior urethral strictures: a national practice patterns survey of board certified urologists in the United States

PURPOSE: We determined the methods and patterns of the evaluation of and treatment for adult anterior urethral stricture disease by practicing urologists in the United States. MATERIALS AND METHODS: A nationwide survey of practicing members of the American Urological Association was performed by a mailed questionnaire. A total of 1,262 urologists were randomly selected from all 50 states, of whom 431 (34%) completed the questionnaire. RESULTS: Most urologists (63%) treat 6 to 20 urethral strictures yearly. The most common procedures used by those surveyed for urethral strictures were dilation (92.8%), optical internal urethrotomy (85.6%) and endourethral stent (23.4%). Minimally invasive procedures are used more frequently that any open urethroplasty technique. Furthermore, most urologists (57.8%) do not perform urethroplasty surgery. When used, the most common urethroplasty surgeries performed were end-to-end anastomotic urethroplasty, perineal urethrostomy and ventral skin graft urethroplasty. Few urologists (4.2%) performed buccal mucosa grafts. For a long bulbar urethral stricture or short bulbar urethral stricture refractory to internal urethrotomy 20% to 29% of respondents would refer to another urologist, while 31% to 33% would continue to manage the stricture by minimally invasive means despite predictable failure. Of the urologists 74% believed that the literature supports a reconstructive surgical ladder, in which urethroplasty is only performed after repeat failure of endoscopic methods. CONCLUSIONS: Most urologists in the United States have little experience with urethroplasty surgery. Most urologists erroneously believe that the literature supports a reconstructive surgical ladder for urethral stricture management. Unfamiliarity with the literature and inexperience with urethroplasty surgery have made the use of endoscopic methods inappropriately common.     

Complete cervical spinal cord injury above C6 predicts the need for tracheostomy

Background

Failed extubation and delayed tracheostomy contribute to poor outcomes in patients with a traumatic spinal cord injury (SCI). We determined if the level and completeness of SCI predict the need for tracheostomy.

Methods

Data from 256 patients with SCI between C1 and T3 with or without tracheostomy were retrospectively analyzed. Logistic regression identified predictors for tracheostomy. Data are presented as raw percentage or odds ratio (OR) with 95% confidence interval. P < .05 indicates significance.

Results

Complete spinal cord injuries were common in patients requiring tracheostomy (55% vs 18%, P < .05), and predicted the need for tracheostomy (OR: 6.4 (3.1 to 13.5), P < .05). An injury above C6 predicted the need for tracheostomy in patients with complete injury (OR: 3.7 (1 to 11.9), P < .05), but not incomplete injury (OR: .7 (.3 to 1.9); P = .53).

Conclusion

Tracheostomy is unlikely in patients with incomplete SCI, regardless of the level of injury. Patients with complete SCI above C6 are likely to require tracheostomy.     

Neuromuscular choristoma presenting with unilateral limb hypoplasia in a 3‐year‐old boy

Introduction: Neuromuscular choristomas (NMCs) are rare benign peripheral nerve lesions in which skeletal muscle tissue is admixed with nerve fascicles. Methods: We describe a case of sciatic nerve NMC presenting with unilateral limb hypoplasia, monoparesis, and equinovarus contracture in a pediatric patient. We outline the unique clinical presentation and diagnostic work‐up for our patient, including electromyographic and imaging studies. Results: MRI revealed fusiform enlargement of the sciatic nerve, <50% intralesional fat, and signal characteristics similar to those of muscle tissue. Ultrasound was utilized to characterize atrophy and fatty infiltration of affected muscles. The patient was treated conservatively with a customized physical therapy program and lower limb orthosis. Conclusions: Emerging diagnostic criteria are highlighted with the goal of distinguishing NMCs from more common peripheral nerve lesions. This can have important clinical consequences, as unnecessary biopsies are associated with aggressive fibromatosis, a potentially devastating complication. Muscle Nerve 54 : 797–801, 2016     

The impact of training under different visual-spatial conditions on reverse-alignment laparoscopic skills development

Background  

Circumstances may arise during laparoscopic procedures in which alignment of the laparoscope and the instruments is off by 180°, creating a mirror image of the operative field. It has been shown that task performance is degraded under these reverse-alignment conditions, and that the magnitude of performance impairment is directly related to laparoscopic experience and skill. The aim of this study was to determine if reverse-alignment surgical skills could be developed through training.     

Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer

PURPOSE: The low rate of pelvic node metastasis in most contemporary series of patients undergoing radical prostatectomy for carcinoma of the prostate has been attributed to earlier and better patient selection than historical series. Alternatively, it has been suggested that the limited dissection commonly performed misses nodal metastasis in a substantial number of patients. To assess the value of an extended node dissection in detecting nodal metastasis, we performed a randomized prospective study. MATERIALS AND METHODS: A total of 123 patients undergoing radical prostatectomy were randomized to an extended node dissection on the right versus the left side of the pelvis with the other side being a limited dissection. The extended dissection included removal of all external iliac nodes to a point above the bifurcation of the common iliac artery, the obturator nodes and the presacral nodes. The limited dissection included only the nodes along the external iliac vein and obturator nerve. RESULTS: Mean patient age was 61 years. Clinical stage was T1c in 88 patients (72%), T2a in 26 (21%), T2b in 7 (6%) and T3 in 2 (1%). Mean preoperative prostate specific antigen was 7.4 ng./ml. Pelvic lymph node metastasis was histologically confirmed in 8 patients (6.5%). Positive nodes were found on the side of the extended dissection in 4 patients, on the side of the limited dissection in 3 and on both sides in 1. Complications possibly attributable to the node dissection included lymphocele in 4 patients, lower extremity edema in 5, deep venous thrombosis in 2, ureteral injury in 1 and pelvic abscess in 1. These complications occurred 3 times more often on the side of the extended dissection (p = 0.08). CONCLUSIONS: Extended node dissection in contemporary series of patients undergoing radical prostatectomy identifies few with nodal metastases not found by a more limited dissection. A trend toward an increased risk of complications attributable to the lymphadenectomy occurs with an extended dissection.     

Enhanced accumulation of A2E in individuals homozygous or heterozygous for mutations in BEST1 (VMD2)

Best vitelliform macular dystrophy (BMD) is an autosomal dominant inherited macular degenerative disease caused by mutations in the gene BEST1 (formerly VMD2). Prior reports indicate that BMD is characterized histopathologically by accumulation of lipofuscin in the retinal pigment epithelium (RPE). However, this accumulation has not been quantified and the chemical composition of lipofuscin in BMD has not been examined. In this study we characterize the histopathology of a donor eye from a rare individual homozygous for a mutation (W93C) in BEST1. We find that this individual's disease was not any more severe than has been described for heterozygotes. We then used this tissue to quantify lipofuscin accumulation by enriching intracellular granules from RPE cells on sucrose gradients and counting the granules in each density fraction. Granules from the homozygous donor eye as well as a donor eye from an individual heterozygous for the mutation T6R were compared with age-matched control eyes. Interestingly, the least dense fraction, representing classical lipofuscin granules was either not present or significantly diminished in the BMD donor eyes and the autoflourescence associated with lipofuscin had shifted to denser fractions. However, a substantial enrichment for granules in fractions of higher density was also noted in the BMD samples. Inspection of granules from the homozygous donor eye by electron microscopy revealed a complex abnormal multilobular structure. Analysis of granules by HPLC indicated a approximately 1.6- and approximately fourfold overall increase in A2E in the BMD eyes versus age-matched control eyes, with a shift of A2E to more dense granules in the BMD donor eyes. Despite the increase in A2E and total intracellular granules, the RPE in the homozygous donor eyes was relatively well preserved. Based on these data we conclude that the clinical and histopathologic consequences to the homozygous donor were not any more severe than has been reported previously for individuals who are established or presumptive heterozygotes. We find that A2E is a component of the lipofuscin accumulated in BMD and that it is more abundant than in control eyes suggesting that the etiology of BMD is similar to Stargardt's disease and Stargardt-like macular dystrophy. Finally, the changes we observe in the granules suggest that the histopathology and eventual vision loss associated with BMD may be due to defects in the ability of the RPE to fully degrade phagocytosed photoreceptor outer segments.     

Pinpointing the neural signatures of single-exposure visual recognition memory

Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys’ behavior was largely contrast invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those that are of lower contrast. However, the monkeys’ behavioral patterns were well predicted by a linearly decodable variant in which the total spike count was corrected for contrast modulation. These results suggest that the IT neural activity pattern that best aligns with single-exposure visual recognition memory behavior is not RS but rather sensory referenced suppression: reductions in IT population response magnitude, corrected for sensory modulation.

Under the right conditions, we are very good at remembering the images that we have seen: we can remember thousands of images after viewing each only once and only for a few seconds (1, 2). How our brains support this remarkable ability, often called “visual recognition memory” (3), is not well understood. The most prominent proposal to date suggests that memories about whether images have been encountered before are signaled in high-level visual brain areas such as inferotemporal cortex (IT) and perirhinal cortex via adaptation-like reductions of the population response to repeated as compared to novel stimuli, a phenomenon referred to as repetition suppression (RS) (4–9). Repetition suppression exhibits the primary attributes needed to account for the vast capacity of single-exposure visual memory behavior: response decrements in subsequent exposures are selective for image identity (even after viewing an extensive sequence of other images), and last for several minutes to hours (5, 6, 10). RS has also been shown to account for behavior in an image recognition memory task: a linear decoder with positive weights can predict single-exposure visual recognition memory behavior from neural responses in IT cortex (10).Despite the fact that the RS hypothesis is consistent with available evidence, it seems likely to be too simplistic an explanation for visual recognition memory encoding. In particular, it is well known that sensory neurons such as those of IT cortex are modulated not only by image memory, but also by stimulus properties such as image contrast (11). It is thus unclear whether and how these stimulus-induced effects interfere with judgments of whether images are novel or have been encountered before, and if they do not, how image memory can be decoded from neural responses in a way that disambiguates it from changes in these stimulus properties. To investigate this, we measured behavioral and neural responses of monkeys trained to report whether images were novel or repeated while disregarding image contrast (Fig. 1A).Open in a separate windowFig. 1.Visual memory behavior. (A) The contrast-invariant, single-exposure visual memory task. The monkeys viewed a sequence of images and reported whether they were novel (never seen before) or repeated (seen exactly once) while ignoring randomized changes in contrast. Monkeys were trained to saccade to one of two response targets to indicate their choice (red arrows). Images were repeated with a randomly chosen delay between the first and repeated presentation (“n-back”). (B) Images were displayed at one of two contrast levels, yielding two conditions for novel images, high (H) and low (L), and four conditions for repeated images: HH (repeated H preceded by novel H), LL (repeated L preceded by novel L), HL (repeated L preceded by novel H), and LH (repeated H preceded by novel L). The four repeated conditions were organized into same-contrast and mixed-contrast groups depending on whether the initial and repeated presentations were at the same or different contrasts, respectively. (C) Behavioral performance for the data pooled across monkeys in the task, where small black dots indicate average performance for an individual session and large colored dots indicate the average performance across sessions. A measure of contrast invariance, I, was computed as the ratio of the variance across contrast conditions and the variance with respect to the maximally contrast-modulated pattern after taking overall performance into account, subtracted from 1 (SI Appendix, SI Methods). Insets illustrate the expected behavioral pattern with minimal (I = 0) and maximal (I = 1) contrast invariance.