Long-term outcomes of urethral catheterisation injuries: a prospective multi-institutional study.

PURPOSE: There are no prospective data describing the incidence and spectrum of long-term complications associated with traumatic urethral catheterisation (UC). We prospectively monitored the long-term clinical outcomes and complications of patients with traumatic UC injuries. METHODS: A prospective study at two tertiary university hospitals was performed to record all referrals for iatrogenic urethral injuries caused by UC. Long-term follow-up was prospectively maintained by regular outpatient department visits and by monitoring all urological interventions and their outcomes from urinary catheter-related injuries. RESULTS: The incidence of traumatic UC was 13.4 per 1000 catheters inserted in male patients and 37 iatrogenic urethral injuries were recorded. The mean age was 74 ± 12 years and the mean length of follow-up was 37 ± 3.7 months. Urethral injuries were caused by inflating the catheter anchoring balloon in the urethra (n = 26) or by creating a false passage with the catheter tip (n = 11). In total, 29 patients (78%) developed urethral stricture disease during their follow-up; of which 11 have required at least one urethral dilation and two have required one urethrotomy. Three patients required long-term indwelling suprapubic catheter placement and seven patients opted for a long-term indwelling urethral catheter. There were eight patient mortalities; one of which was due to severe urosepsis resulting from catheter balloon inflation in the urethra. CONCLUSION: Catheter-related injuries are associated with significant long-term complications in this vulnerable patient cohort. In future, such injuries may be preventable if the safety profile of the urinary catheter is modified.

Precise auditory-vocal mirroring in neurons for learned vocal communication.

Brain mechanisms for communication must establish a correspondence between sensory and motor codes used to represent the signal. One idea is that this correspondence is established at the level of single neurons that are active when the individual performs a particular gesture or observes a similar gesture performed by another individual. Although neurons that display a precise auditory-vocal correspondence could facilitate vocal communication, they have yet to be identified. Here we report that a certain class of neurons in the swamp sparrow forebrain displays a precise auditory-vocal correspondence. We show that these neurons respond in a temporally precise fashion to auditory presentation of certain note sequences in this songbird's repertoire and to similar note sequences in other birds' songs. These neurons display nearly identical patterns of activity when the bird sings the same sequence, and disrupting auditory feedback does not alter this singing-related activity, indicating it is motor in nature. Furthermore, these neurons innervate striatal structures important for song learning, raising the possibility that singing-related activity in these cells is compared to auditory feedback to guide vocal learning.

In vivo vomeronasal stimulation reveals sensory encoding of conspecific and allospecific cues by the mouse accessory olfactory bulb.

The rodent vomeronasal system plays a critical role in mediating pheromone-evoked social and sexual behaviors. Recent studies of the anatomical and molecular architecture of the vomeronasal organ (VNO) and of its synaptic target, the accessory olfactory bulb (AOB), have suggested that unique features underlie vomeronasal sensory processing. However, the neuronal representation of pheromonal information leading to specific behavioral and endocrine responses has remained largely unexplored due to the experimental difficulty of precise stimulus delivery to the VNO. To determine the basic rules of information processing in the vomeronasal system, we developed a unique preparation that allows controlled and repeated stimulus delivery to the VNO and combined this approach with multisite recordings of neuronal activity in the AOB. We found that urine, a well-characterized pheromone source in mammals, as well as saliva, activates AOB neurons in a manner that reliably encodes the donor animal's sexual and genetic status. We also identified a significant fraction of AOB neurons that respond robustly and selectively to predator cues, suggesting an expanded role for the vomeronasal system in both conspecific and interspecific recognition. Further analysis reveals that mixed stimuli from distinct sources evoke synergistic responses in AOB neurons, thereby supporting the notion of integrative processing of chemosensory information.

An analysis of radiation dose reduction in paediatric interventional cardiology by altering frame rate and use of the anti-scatter grid.

The purpose of this work is to investigate removal of the anti-scatter grid and alteration of the frame rate in paediatric interventional cardiology (IC) and assess the impact on radiation dose and image quality. Phantom based experimental studies were performed in a dedicated cardiac catheterisation suite to investigate variations in radiation dose and image quality, with various changes in imaging parameters. Phantom based experimental studies employing these variations in technique identified that radiation dose reductions of 28%-49% can be made to the patient with minimal loss of image quality in smaller sized patients. At present, there is no standard technique for carrying out paediatric IC in the UK or Ireland, resulting in the potential for a wide variation in radiation dose. Dose reductions to patients can be achieved with slight alterations to the imaging equipment with minimal compromise to the image quality. These simple modifications can be easily implemented in clinical practice in IC centres.

Enhancement of transmission at the developing retinogeniculate synapse.

Axon terminals from retinal ganglion cells in the left and right eyes initially overlap with each other in the lateral geniculate nucleus of the neonatal ferret, then segregate into eye-specific layers via an activity-dependent process. Brain slices were used to show that, during this period of reorganization, retinal terminals within the lateral geniculate nucleus evoke excitatory postsynaptic currents composed of both NMDA and non-NMDA receptor-mediated currents. The amplitude of these currents could be enhanced for several tens of minutes to more than an hour by several bursts of high frequency synaptic stimulation, and the induction of enhancement appears to depend on NMDA receptor activation. Synaptic enhancement such as this could provide one of the physiological mechanisms by which retinal terminals segregate into eye-specific layers during development.

Thalamic relay of spontaneous retinal activity prior to vision.

Before vision, retinal ganglion cells produce spontaneous waves of action potentials. A crucial question is whether this spontaneous activity is transmitted to lateral geniculate nucleus (LGN) neurons. Using a novel in vitro preparation, we report that LGN neurons receive periodic barrages of postsynaptic currents from the retina that drive them to fire bursts of action potentials. Groups of LGN neurons are highly correlated in their firing. Experiments in wild-type and NMDAR1 knockout mice show that NMDA receptor activation is not necessary for firing. The transmission of the highly correlated retinal activity to the LGN supports the hypothesis that retinal waves drive retinogeniculate synaptic remodeling. Because LGN neurons are driven to fire action potentials, this spontaneous activity could also act more centrally to influence synaptic modification within the developing visual cortex.

Slow NMDA-EPSCs at synapses critical for song development are not required for song learning in zebra finches.

Birdsong, like human speech, is learned via auditory experience during a developmentally restricted sensitive period. Within projection neurons of two avian forebrain nuclei, NMDA receptor-mediated EPSCs (NMDA-EPSCs) become fast during song development, a transition posited to limit learning. To discover whether slow NMDA-EPSCs at these synapses are required for learning, we delayed song learning beyond its normal endpoint, post-hatch day (PHD) 65, by raising zebra finches in isolation from song tutors. At PHD45, before learning, isolation delayed NMDA-EPSC maturation, but only transiently. By PHD65, NMDA-EPSCs in isolates were fast and adult-like, yet isolates presented with tutors readily learned song. Thus song learning did not require slow NMDA-EPSCs at synapses critical for song development.

Characterisation of human urethral rupture thresholds for urinary catheter inflation related injuries.

Data on urethral catheter related injuries is sparse. In this study we aimed to characterise urethral diametric strain and urinary catheter inflation pressure thresholds that precede human urethral trauma during urethral catheterisation (UC). Human urethras were obtained from patients undergoing male to female gender reassignment surgery [(n = 9; age 40 ±â€¯13.13 (range: 18-58)) years]. 12Fr urinary catheters were secured in the bulbar urethra and the catheter's anchoring balloon was inflated with a syringe pump apparatus. Urethral diametric strain and balloon pressure were characterised with video extensometry and a pressure transducer respectively. Immunohistochemistry, Masson's trichrome and Verhoeff-Van Gieson stains evaluated urethral trauma microscopically. Morphological characterisation of the urethral lumen was performed by examining non-traumatised histological sections of urethra and recording luminal area, perimeter and major/minor axis length. Tearing (n = 3) and rupture (n = 3) of the urethra were observed following catheter balloon inflation. The threshold for human urethral rupture occurred at an external urethral diametric strain ≥ 27% and balloon inflation pressure ≥ 120kPa. Significant relationships were identified between urethral wall thickness and the level of trauma induced during catheter balloon inflation (p = 0.001) and between the pressure required to inflate the catheter balloon and the length of the major axis of the urethral lumen (p = 0.004). Ruptured urethras demonstrated complete transection of collagen, elastin and muscle fibres. In conclusion, urethral rupture occurs at an external urethral diametric strain ≥ 27% or with balloon inflation pressures ≥ 120 kPa. Incorporation of these parameters may be useful for designing a safety mechanism for preventing catheter inflation related urethral injuries.

Behavioral learning. The illuminated songbird.

Recent studies of the neural mechanisms of avian song learning suggest that pathways for adult song production are distinct from those essential to juvenile song development.

Bird communication: two voices are better than one.

How do emperor penguins find their mates on a featureless ice flow, packed at densities of ten animals per square meter? A recent study has revealed how use of their 'two-voice' calls enables emperor penguins to locate their mates and chicks under some of nature's most extreme conditions.

Bird song: of tone and tempo in the telencephalon.

Songbirds learn a new song by matching the sound they produce to a memorized model. A distributed central pattern-generating circuit has now been identified that governs song production; the new results have important implications for the way songs are learned.

Can an old bird change his tune?

The stereotyped courtship songs of 'age-limited' songbirds, which learn their songs during a specific early period of their lives, were once thought immutable, but recent studies suggest that their maintenance may actually rely on subtle cues provided by auditory feedback.

Architecture of a transcribing-translating expressome.

DNA transcription is functionally coupled to messenger RNA (mRNA) translation in bacteria, but how this is achieved remains unclear. Here we show that RNA polymerase (RNAP) and the ribosome of Escherichia coli can form a defined transcribing and translating "expressome" complex. The cryo-electron microscopic structure of the expressome reveals continuous protection of ~30 nucleotides of mRNA extending from the RNAP active center to the ribosome decoding center. The RNAP-ribosome interface includes the RNAP subunit α carboxyl-terminal domain, which is required for RNAP-ribosome interaction in vitro and for pronounced cell growth defects upon translation inhibition in vivo, consistent with its function in transcription-translation coupling. The expressome structure can only form during transcription elongation and explains how translation can prevent transcriptional pausing, backtracking, and termination.

Sensitive periods and circuits for learned birdsong.

Experience influences the development of certain behaviors and their associated neural circuits during a discrete period after birth. Songbirds, with their highly quantifiable vocal output and well-delineated vocal control circuitry, provide an excellent context in which to examine the neural mechanisms regulating sensitive periods for learning. Recent discoveries indicate that auditory input to the vocal control circuitry in songbirds is dynamically modulated and show that neural circuitry previously thought to be used only in plastic juvenile song may also actively maintain stable adult song. These findings provide important clues to how sensitive periods for auditory feedback and vocal plasticity are regulated during song development.

Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines.

While IGF-1 plays a role in early B-cell development, little is known of insulin and insulin-like growth factor-1 (IGF-1) action in post-marrow B-cells. Recently, our laboratory demonstrated that mouse and human multiple myeloma (MM) cell lines possess functional insulin receptors (IRs) and IGF-1 receptors (IGF-1Rs). In this study, we show that responsiveness to insulin and IGF-1 is more developed in human MM cell lines than in human B-lymphoblastoid cell lines. Two human MM cell lines (U266 and RPMI 8226) were compared to three B-lymphoblastoid cell lines [Epstein-Barr virus immortalized B-cells (EBV), a Burkitt lymphoma cell line (Ramos), and a non-EBV lymphoblastoid cell line (HS Sultan)]. Surface IR and IGF-1R expression, measured by flow cytometry, demonstrated that the MM cell lines expressed more IRs and IGF-1Rs than did the EBV, Ramos, or HS Sultan cell lines. In vitro receptor kinase activity of affinity-purified receptors showed that the MM cells had more phosphorylated receptors than did the EBV, Ramos, or HS Sultan cells. Intracellular receptor signaling was also markedly different between the two cell groups. Whole cell phosphorylation studies showed that MM cells possessed not only hormone-dependent receptor autophosphorylation (M(r) 97,000) but also substrate phosphorylation (M(r) 185,000; 60,000). The lymphoblastoid cells, while demonstrating receptor autophosphorylation (IR autophosphorylation in the EBV cell line at 200 nM hormone was similar to MM receptor phosphorylation at 2 nM), lacked hormone-responsive substrates. The MM cell lines contained significantly more hormone-stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity than the B-lymphoblastoid cell lines. In the MM cells, PI 3-kinase was activated by at least 10-fold, but, in the B-lymphoblastoid cell lines, it was activated by no more than 2-fold. Hormone-responsive glucose metabolism was also greater in the MM cell lines. In the U266 cells, insulin increased lactate production 62 +/- 9 and 101 +/- 12% (mean +/- SE) at concentrations of 2 nM and 200 nM, respectively. IGF-1 produced 72 +/- 9 and 99 +/- 13% increases at similar concentrations. In the 8226 cells, insulin increased lactate production 4 +/- 4 and 36 +/- 15% at 2 and 200 nM, respectively. IGF-1 produced a 13 +/- 6 and 70 +/- 18% increase. In the EBV and Ramos cells, neither hormone increased lactate production by more than 10 +/- 3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic transformations underlying highly selective auditory representations of learned birdsong.

Stimulus-specific neuronal responses are a striking characteristic of several sensory systems, although the synaptic mechanisms underlying their generation are not well understood. The songbird nucleus HVC (used here as a proper name) contains projection neurons (PNs) that fire temporally sparse bursts of action potentials to playback of the bird's own song (BOS) but are essentially silent when presented with other acoustical stimuli. To understand how such remarkable stimulus specificity emerges, it is necessary to compare the auditory-evoked responsiveness of the afferents of HVC with synaptic responses in identified HVC neurons. We found that inactivating the interfacial nucleus of the nidopallium (NIf) could eliminate all auditory-evoked subthreshold activity in both HVC PN types, consistent with NIf serving as the major auditory afferent of HVC. Simultaneous multiunit extracellular recordings in NIf and intracellular recordings in HVC revealed that NIf population activity and HVC subthreshold responses were similar in their selectivity for BOS and that NIf spikes preceded depolarizations in all HVC cell types. These results indicate that information about the BOS as well as other auditory stimuli is transmitted synaptically from NIf to HVC. Unlike HVC PNs, however, HVC-projecting NIf neurons fire throughout playback of BOS as well as non-BOS stimuli. Therefore, temporally sparse BOS-evoked firing and enhanced BOS selectivity, manifested as an absence of suprathreshold responsiveness to non-BOS stimuli, emerge in HVC. The transformation to a sparse auditory representation parallels differences in NIf and HVC activity patterns seen during singing, which may point to a common mechanism for encoding sensory and motor representations of song.

Lesions of an avian forebrain nucleus that disrupt song development alter synaptic connectivity and transmission in the vocal premotor pathway.

The avian forebrain nucleus, the lateral magnocellular nucleus of the anterior neostriatum (LMAN), is necessary for normal song development because LMAN lesions made in juvenile birds disrupt song production but do not disrupt song when made in adults. Although these age-limited behavioral effects implicate LMAN in song learning, a potential confound is that LMAN lesions could disrupt normal vocal motor function independent of any learning role by altering LMAN's premotor target, the song nucleus, the robust nucleus of the archistriatum (RA). To date, however, no studies have examined directly the effects of LMAN lesions on the circuitry of the RA. We report here that juvenile LMAN lesions rapidly and profoundly affect RA, altering synaptic connectivity within this nucleus, including descending inputs from the song nucleus HVc. Specifically, morphological assays of the dendritic spines of RA projection neurons and axon terminal boutons arising from HVc show a numerical decline in the density of connections in RA in LMAN-lesioned juveniles compared with controls. Concurrently, LMAN lesions alter excitatory transmission within the juvenile RA: after LMAN lesions, the stimulus-response relationship between HVc fibers and RA neurons steepens, and the amplitude of spontaneous monophasic EPSCs increases. Rather than arresting RA in a juvenile state, LMAN lesions transform the structure and function of RA and its connections, such that it is distinct from that of the normal juvenile. In many ways, RA circuitry in LMAN-lesioned juveniles resembles that of normal adults, suggesting that LMAN lesions induce a premature maturation of the vocal motor pathway, which may lead to a loss of behavioral plasticity and abnormal song development.

Sequence and functional characterization of the terminal exon of the human insulin receptor gene.

We present 5.1 kb of the 3' noncoding region sequence of the human insulin receptor gene and identification of four functional polyadenylation domains responsible for 3'-end processing of the 5.4, 6.9, 8.0 and 9.4 kb human insulin receptor mRNA, respectively. The insulin receptor gene contains five putative polyadenylation sites (P1-P5), located 5160, 6502, 7488, 8945 and 8957 base pairs (bp) downstream from the translational initiation site. All putative polyadenylation sites are flanked by upstream AU rich and downstream GU rich regions which regulate mRNA stability and mRNA cleavage, respectively. Also, two RNA stem-loop structures have been identified. To determine its role on gene expression, a reporter gene was constructed containing various lengths of the insulin receptor 3' UTR and transiently transfected into COS 7 cells. A 539 bp fragment (4897-5436 bp downstream from the IR translational initiation site) inhibited CAT expression by 5-6 fold. Further downstream addition of 1169 bp of the insulin receptor 3' untranslated region enhanced gene expression by 2-fold. These studies provide evidence that the insulin receptor 3' untranslated region can modulate gene expression.

Dissociation of PTPase levels from their modulation of insulin receptor signal transduction.

Protein tyrosine phosphatases have been implicated in the regulation of receptor tyrosine kinase signalling pathways, including that of the insulin receptor. Here, cell density-dependent changes in PTPase expression have been exploited to investigate the relationship between cellular PTPase levels and the insulin receptor signal transduction pathway. Increasing cell density (20%, 50%, and >90%) in the rat McA-RH7777 hepatoma cell line resulted in increased protein expression of the receptor-like PTPase LAR (14-fold), and the nonreceptor PTPases PTP1B (11-fold) and SHP2 (10-fold). Each of these PTPases has previously been implicated in regulating insulin receptor signal transduction. Despite these marked increases, maximum insulin receptor autophosphorylation as well as receptor expression actually increased 2-fold. MAP kinase also increased approximately 2-fold as a function of cell density and paralleled increases in expression levels. Neither sensitivity nor maximum responsiveness to insulin were decreased at increasing cell densities as assessed by activation of PI 3-kinase. Duration of response was also unimpaired. These results suggest that expression levels of relevant PTPases are not the primary determinant in their modulation of insulin receptor kinase activity. Restricted accessibility at the molecular level or involvement of accessory proteins may be more critical parameters.

Attitudes among junior doctors towards improving the transurethral catheterisation process.

OBJECTIVES: To evaluate the subjective opinions of junior doctors on their adequacy of training and confidence levels for performing transurethral catheterisation (TUC) and to investigate their subjective interest in a 'safety mechanism' that would eliminate the potential for urethral trauma during TUC. METHODS: An anonymous online survey was emailed to all interns that had a documented email address on the Royal College of Surgeons Ireland registry (2012-2013). The survey consisted of eight questions pertaining to TUC of male patients. RESULTS: The survey was delivered to 252 email addresses and the response rate was 52% (130/252). The vast majority (99%; n = 128) of interns felt confident inserting a transurethral catheter independently and 73% (n = 95) subjectively received appropriate training for catheterising male patients. The incidence of trauma after mistakenly inflating the catheter's anchoring balloon in the urethra was 3% (n = 4). The majority (90%; n = 116) of respondents were interested in a safety mechanism for preventing urethral trauma and 71% (n = 92) felt that a safety mechanism for urethral trauma prevention should be compulsory for all transurethral catheterisation among male patients. CONCLUSION: Despite pre-emptive training programmes, it appears that iatrogenic urethral trauma secondary to TUC remains a persistent morbidity in healthcare settings. Designing a safer transurethral catheter may be necessary to eliminate the risk of unnecessary urethral trauma in patients.