Patient individual phase gating for stereotactic radiation therapy of early stage non-small cell lung cancer (NSCLC).

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw.

Helical tomotherapy: Comparison of Hi-ART and Radixact clinical patient treatments at the Technical University of Munich.

The helical tomotherapy (HT) Hi-ART system was installed at our department in April 2007. In July 2018 the first Radixact system in Germany has been launched for clinical use. We present differences, advantages and disadvantages and show future perspectives in patient treatment using two HT devices. We investigate patient characteristics, image quality, radiotherapy treatment specifications and analyze the time effort for treatments with the Hi-ART system from April 2010 until May 2017 and compare it to the data acquired in the first nine months of usage of the Radixact system. Comparing the Hi-ART and Radixact system, the unique option of integrated MVCT image acquisition has experienced distinct improvement in image quality. Time effort for irradiation treatment could be improved resulting in a mean beam on time for craniospinal axis treatment of 636.2 s for the Radixact system compared to 915.9 s for the Hi-ART system. The beneficial use of tomotherapy for complex target volumes is demonstrated by a head and neck tumor case and craniospinal axis treatment. With the Radixact system MVCT image quality has been improved allowing for fast and precise interfraction dose adaptation. The improved time effort for patient treatment could increase the accessibility for clinical usage.

Demographics and prevalence of positive QuantiFERON-TB Gold In-Tube test in renal transplant candidates.

BACKGROUND: Latent tuberculosis infection (LTBI) screening prior to solid organ transplantation is standard of care. QuantiFERON-TB Gold In-Tube (QFT-GIT) test is the preferred diagnostic test for renal transplant candidates (RTC). QFT-GIT reversions and the potential delay of living-donor kidney transplantation (LDKT) because of QFT-GIT positivity have not been examined previously in RTC. METHODS: We evaluated the prevalence of positive QFT-GIT in RTC from January 1 through December 31, 2011. In addition, we examined the demographic and renal disease data differences between QFT-GIT-positive and -negative patients, changes in QFT-GIT results, and positive QFT-GIT results reverting to negative. Lastly, we evaluated if QFT-GIT-positive patients were less likely to undergo LDKT within 6 months of QFT-GIT testing. RESULTS: In total, 722 RTC were analyzed, 16% of whom had positive QFT-GIT. The QFT-GIT-positive patients were more likely to be older and foreign-born, P < 0.0001. Haitians had the highest prevalence. Of the 119 QFT-GIT-positive patients, 25% had low/intermediate-positive results and were more likely to revert to negative, compared with patients with high-positive QFT-GIT results (50% vs. 0%, P = 0.01). A trend was seen toward fewer QFT-GIT-positive patients undergoing LDKT, compared with QFT-GIT-negative patients (0% vs. 3%, P = 0.09). CONCLUSIONS: Our high prevalence was likely a result of the high number of foreign-born RTC. Half of our small subset of low/intermediate-positive QFT-GIT patients reverted to negative. QFT-GIT-positive patients were more likely to have their LDKT delayed.

[Acute and overuse injuries of the shoulder in sports]. / Akutverletzungen und Überlastungsschäden der Schulter im Sport.

BACKGROUND: During sports the shoulder complex is exposed to considerable load especially where throwing is important and various pathological changes can occur. In the last two decades the shoulder in athletes has become a special term in clinical sports medicine METHODS: Selective literature review in PubMed and consideration of personal experience, research results as well as national and international recommendations RESULTS: In general acute lesions of the shoulder caused by sudden sport injuries, such as traumatic luxation, acromioclavicular (AC) joint disruption, traumatic tendon ruptures, labral lesions, cartilage defects and fractures have to be distinguished from chronic or long-standing pathologies due to recurrent microtrauma, such as overuse bursitis and tendinitis, as well as secondary forms of impingement along with rotator cuff tears and labral lesions. Besides common pathological changes that can be observed in almost all overhead-sports, there are also injuries that are more sport-specific due to the particular load profile in each sport. These injuries are especially common in racquet and throwing sports (e.g. golf, tennis, handball and volleyball) as well as in individual and artistic sports (e.g. swimming, gymnastics, dancing and rowing), contact and extreme sports (e.g. judo, mixed martial arts, bodybuilding, weightlifting, motocross and downhill mountain biking). CONCLUSION: Knowledge about sport-specific load profiles as well as about the variety of treatment options is crucial for successful treatment of these injuries.

Up-regulation of GAP-43 in the chinchilla ventral cochlear nucleus after carboplatin-induced hearing loss: correlations with inner hair cell loss and outer hair cell loss.

Inner ear damage leads to nerve fiber growth and synaptogenesis in the ventral cochlear nucleus (VCN). In this study, we documented the relationship between hair cell loss patterns and synaptic plasticity in the chinchilla VCN using immunolabeling of the growth associated protein-43 (GAP-43), a protein associated with axon outgrowth and modification of presynaptic endings. Unilateral round window application of carboplatin caused hair cell degeneration in which inner hair cells (IHC) were more vulnerable than outer hair cells (OHC). One month after carboplatin treatment (0.5-5 mg/ml), we observed varying patterns of cochlear hair cell loss and GAP-43 expression in VCN. Both IHC loss and OHC loss were strongly correlated with increased GAP-43 immunolabeling in the ipsilateral VCN. We speculate that two factors might promote the expression of GAP-43 in the VCN; one is the loss of afferent input through IHC or the associated type I auditory nerve fibers. The other occurs when the medial olivocochlear efferent neurons lose their cochlear targets, the OHC, and may as compensation increase their synapse numbers in the VCN.

Dosimetric consequences of tumour motion due to respiration for a scanned proton beam.

A method for simulating spot-scanned delivery to a moving tumour was developed which uses patient-specific image and plan data. The magnitude of interplay effects was investigated for two patient cases under different fractionation and respiratory motion variation scenarios. The use of volumetric rescanning for motion mitigation was also investigated. For different beam arrangements, interplay effects lead to severely distorted dose distributions for a single fraction delivery. Baseline shift variations for single fraction delivery reduced the dose to the clinical target volume (CTV) by up to 14.1 Gy. Fractionated delivery significantly reduced interplay effects; however, local overdosage of 12.3% compared to the statically delivered dose remained for breathing period variations. Variations of the tumour baseline position and respiratory period were found to have the largest influence on target inhomogeneity; these effects were reduced with fractionation. Volumetric rescanning improved the dose homogeneity. For the CTV, underdosage was improved by up to 34% in the CTV and overdosage to the lung was reduced by 6%. Our results confirm that rescanning potentially increases the dose homogeneity; however, it might not sufficiently compensate motion-induced dose distortions. Other motion mitigation techniques may be required to additionally treat lung tumours with scanned proton beams.

Relationship between noise-induced hearing-loss, persistent tinnitus and growth-associated protein-43 expression in the rat cochlear nucleus: does synaptic plasticity in ventral cochlear nucleus suppress tinnitus?

Aberrant, lesion-induced neuroplastic changes in the auditory pathway are believed to give rise to the phantom sound of tinnitus. Noise-induced cochlear damage can induce extensive fiber growth and synaptogenesis in the cochlear nucleus, but it is currently unclear if these changes are linked to tinnitus. To address this issue, we unilaterally exposed nine rats to narrow-band noise centered at 12 kHz at 126 dB sound pressure level (SPL) for 2 h and sacrificed them 10 weeks later for evaluation of synaptic plasticity (growth-associated protein 43 [GAP-43] expression) in the cochlear nucleus. Noise-exposed rats along with three age-matched controls were screened for tinnitus-like behavior with gap prepulse inhibition of the acoustic startle (GPIAS) before, 1-10 days after, and 8-10 weeks after the noise exposure. All nine noise-exposed rats showed similar patterns of severe hair cell loss at high- and mid-frequency regions in the exposed ear. Eight of the nine showed strong up-regulation of GAP-43 in auditory nerve fibers and pronounced shrinkage of the ventral cochlear nucleus (VCN) on the noise-exposed side, and strong up-regulation of GAP-43 in the medial ventral VCN, but not in the lateral VCN or the dorsal cochlear nucleus. GAP-43 up-regulation in VCN was significantly greater in Noise-No-Tinnitus rats than in Noise-Tinnitus rats. One Noise-No-Tinnitus rat showed no up-regulation of GAP-43 in auditory nerve fibers and only little VCN shrinkage, suggesting that auditory nerve degeneration plays a role in tinnitus generation. Our results suggest that noise-induced tinnitus is suppressed by strong up-regulation of GAP-43 in the medial VCN. GAP-43 up-regulation most likely originates from medial olivocochlear neurons. Their increased excitatory input on inhibitory neurons in VCN may possibly reduce central hyperactivity and tinnitus.

Noise trauma impairs neurogenesis in the rat hippocampus.

The hippocampus, a major site of neurogenesis in the adult brain, plays an important role in memory. Based on earlier observations where exposure to high-intensity noise not only caused hearing loss but also impaired memory function, it is conceivably that noise exposure may suppress hippocampal neurogenesis. To evaluate this possibility, nine rats were unilaterally exposed for 2 h to a high-intensity, narrow band of noise centered at 12 kHz at 126 dB SPL. The rats were also screened for noise-induced tinnitus, a potential stressor which may suppress neurogenesis. Five rats developed persistent tinnitus-like behavior while the other four rats showed no signs of tinnitus. Age-matched sham controls showed no signs of hearing loss or tinnitus. The inner ear and hippocampus were evaluated for sensory hair cell loss and neurogenesis 10 weeks post-exposure. All noise exposed rats showed severe loss of sensory hair cells in the noise-exposed ear, but essentially no damage in the unexposed ear. Frontal sections from the hippocampus were immunolabeled for doublecortin to identify neuronal precursor cells, or Ki67 to label proliferating cells. Noise-exposed rats showed a significant reduction of neuronal precursors and fewer dividing cells as compared to sham controls. However, we could not detect any difference between rats with behavioral evidence of tinnitus versus rats without tinnitus. These results show for the first time that high intensity noise exposure not only damages the cochlea but also causes a significant and persistent decrease in hippocampal neurogenesis that may contribute to functional deficits in memory.

Central auditory plasticity after carboplatin-induced unilateral inner ear damage in the chinchilla: up-regulation of GAP-43 in the ventral cochlear nucleus.

Inner ear damage may lead to structural changes in the central auditory system. In rat and chinchilla, cochlear ablation and noise trauma result in fiber growth and synaptogenesis in the ventral cochlear nucleus (VCN). In this study, we documented the relationship between carboplatin-induced hair cell degeneration and VCN plasticity in the chinchilla. Unilateral application of carboplatin (5mg/ml) on the round window membrane resulted in massive hair cell loss. Outer hair cell degeneration showed a pronounced basal-to-apical gradient while inner hair cell loss was more equally distributed throughout the cochlea. Expression of the growth associated protein GAP-43, a well-established marker for synaptic plasticity, was up-regulated in the ipsilateral VCN at 15 and 31 days post-carboplatin, but not at 3 and 7 days. In contrast, the dorsal cochlear nucleus showed only little change. In VCN, the high-frequency area dorsally showed slightly yet significantly stronger GAP-43 up-regulation than the low-frequency area ventrally, possibly reflecting the high-to-low frequency gradient of hair cell degeneration. Synaptic modification or formation of new synapses may be a homeostatic process to re-adjust mismatched inputs from two ears. Alternatively, massive fiber growth may represent a deleterious process causing central hyperactivity that leads to loudness recruitment or tinnitus.

Mechanical testing of 3.5 mm locking and non-locking bone plates.

Locking plate technologies are being developed in order to provide the surgeon with advantages over previous bone plate systems (both locking and non-locking). Locking plate systems possess inherent biological advantages in fracture fixation by preserving the periosteal blood supply, serving as internal fixators. It is important to consider the strength of each orthopaedic implant as an important selection criterion while utilizing the reported advantages of locking plate systems to prevent catastrophic fracture failure. Mechanical testing of orthopaedic implants is a common method used to provide a surgeon with insight on mechanical capabilities, as well as to form a standardized method of plate comparison. The purpose of this study was to demonstrate and to quantify observed differences in the bending strength between the LCP (Limited Contact Plate), LC-DCP, 3.5 mm Broad LC-DCP (Limited Contact Dynamic Compression Plate), and SOP (String of Pearls) orthopaedic bone plates. The study design followed the ASTM standard test method for static bending properties of metallic bone plates, which is designed to measure mechanical properties of bone plates subjected to bending, the most common loading encountered in vivo. Single cycle four point bending was performed on each orthopaedic implant. The area moment of inertia, bending stiffness, bending strength, and bending structural stiffness were calculated for each implant. The results of this study demonstrated significant differences (p<0.001) in bending strength and stiffness between the four orthopaedic implants (3.5 Broad LC-DCP>SOP>LCP=LC-DCP). The 3.5 mm LCP should be expected to provide in vivo strength and stiffness similar to a comparable LC-DCP. The SOP should provide strength and stiffness that is greater than a comparable LC-DCP but less than a 3.5 mm Broad LC-DCP.

Reconnecting neuronal networks in the auditory brainstem following unilateral deafening.

When we disturbed the auditory input of the adult rat by cochleotomy or noise trauma on one side, several substantial anatomical, cellular, and molecular changes took place in the auditory brainstem. We found that: (1) cochleotomy or severe noise trauma both lead to a considerable increase of immunoreactivity of the growth-associated protein GAP-43 in the ventral cochlear nucleus (VCN) of the affected side; (2) the expression of GAP-43 in VCN is restricted to presynaptic endings and short fiber segments; (3) axon collaterals of the cholinergic medial olivocochlear (MOC) neurons are the path along which GAP-43 reaches VCN; (4) partial cochlear lesions induce the emergence of GAP-43 positive presynaptic endings only in regions tonotopically corresponding to the extent of the lesion; (5) judging from the presence of immature fibers and growth cones in VCN on the deafened side, at least part of the GAP-43 positive presynaptic endings appear to be newly formed neuronal contacts following axonal sprouting while others may be modified pre-existing contacts; and (6) GAP-43 positive synapses are formed only on specific postsynaptic profiles, i.e., glutamatergic, glycinergic and calretinin containing cell bodies, but not GABAergic cell bodies. We conclude that unilateral deafening, be it partial or total, induces complex patterns of reconnecting neurons in the adult auditory brainstem, and we evaluate the possibility that the deafness-induced chain of events is optimized to remedy the loss of a bilaterally balanced activity in the auditory brainstem.

Cell death or survival: molecular and connectional conditions for olivocochlear neurons after axotomy.

We aimed to determine whether rat olivocochlear neurons survive axotomy inflicted through cochlear ablation, or if they degenerate. To estimate their intrinsic potential for axonal regeneration, we investigated the expression of the transcription factor c-Jun and the growth-associated protein-43 (GAP43). Axonal tracing studies based on application of Fast Blue into the cochlea and calcitonin gene-related peptide immunostaining revealed that many, but not all, lateral olivocochlear neurons in the ipsilateral lateral superior olive degenerated upon cochleotomy. A decrease of their number was noticed 2 weeks after the lesion, and 2 months postoperative the population was reduced to approximately one quarter (27-29%) of its original size. No further reduction took place at longer survival times up to 1 year. Most or all shell neurons and medial olivocochlear neurons survived axotomy. Following cochleotomy, 56-60% of the lateral olivocochlear neurons in the ipsilateral lateral superior olive were found to co-express c-Jun and GAP43. Only a small number of shell and medial olivocochlear neurons up-regulated c-Jun expression, and only a small number of shell neurons expressed GAP43. Up-regulation of c-Jun and GAP43 in lateral olivocochlear neurons upon axotomy suggests that they have an intrinsic potential to regenerate after axotomy, but cell counts based on the markers Fast Blue and calcitonin gene-related peptide indicate that this potential cannot be exploited and degeneration is induced instead. The survival of one quarter of the axotomized lateral olivocochlear neurons and of all, or almost all, shell and medial olivocochlear neurons appeared to depend on connections of these cells to other regions than the cochlea by means of axon collaterals, which remained intact after cochleotomy.

In vivo axial dynamization of canine tibial fractures using the Securos external skeletal fixation system.

Bilateral transverse mid-shaft tibial osteotomies, with a 4-mm gap, were performed in purpose-bred research dogs and stabilized using a Securos Type 2 external skeletal fixotor (ESF). Full (100%) axial dynamization of one randomly selected ESF in each dog was performed at 31 days postoperatively. Caudo-cranial radiographs were obtained at weekly intervals, which were qualitatively and quantitatively evaluated (densitometry and ImageJ analysis). The dogs were euthanatized 13 weeks postoperatively, at which time dual energy x-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), mechanical testing in torsion, and qualitative histological analysis were performed. A two-tailed paired Student's t-test was performed for statistical analysis of all parameters of interest, with significance set at p < 0.05. Three of five dynamized bones bridged quicker, and four of five dynamized bones appeared to have greater callus formation, however, statistically significant differences could not be definitively determined. Statistically significant differences were not found with densitometry (any time frame), DEXA, pQCT, torsional stiffness or maximum torque. Despite the lack of statistically relevant data, trends were observed with larger callus size and density in the dynamized tibiae. The dynamized tibiae appeared to fracture more consistently outside of the area of the healing callus as compared to the control tibiae. Histological evaluation showed greater remodelling in four of five control limbs when compared to the dynamized limb. Dynamization at 31 days post-operatively may delay bone remodelling, despite a trend towards a larger callus size. The results of this study failed to show a definitive role for early full axial dynamization.

[Diagnostic utility of capsule endoscopy in occult gastrointestinal bleeding]. / Diagnostik okkulter Blutungen des oberen Gastrointestinaltraktes durch die Videokapselendoskopie.

BACKGROUND AND OBJECTIVE: The video-capsule endoscopy (CE) of the small intestine is a novel innovative procedure for outpatient use that can detect even small lesions of the mucosa of the small intestine. Aim of this retrospective clinical study was to evaluate the diagnostic value of CE in a clinical routine setting. PATIENTS AND METHODS: Between July 2001 and October 2002 we investigated 42 patients with suspected gastrointestinal bleeding by CE. In all patients, the previous upper and lower endoscopy work-up was normal. In some cases additional procedures such as bloodpool scintigraphy, angiography, small-bowel enteroclysis or push-enteroscopy were performed. RESULTS: CE detected relevant pathological findings in 23 out of 42 Patients (55 %). The majority of findings in the CE consisted of angiodysplasia (n = 16), ulcer and haemorrhagical erosions (n = 10), one Ulcus Dieulafoy and additional polyps of the small intestine (n = 2). In 4 cases an inflammatory small-bowel disease was detected. These findings could be confirmed by Re-endoscopy. The information provided was helpful to direct further diagnostic and treatment options. In 14 cases (33 %) CE-findings steered additional diagnostic and therapeutic steps. We conclude that CE is safe and has a high diagnostic yield. CONCLUSION: M2A video CE is likely to become an integral part of the algorithm of diagnostic of occult gastrointestinal bleeding after exclusion of other causes of anemia and negative upper and lower endoscopy work-up.

Endoscopically assisted video capsule endoscopy of the small bowel in patients with functional gastric outlet obstruction.

Since the introduction in 2001 of M2A video capsule imaging of the small bowel in humans, this technique has been used increasingly in patients with disorders of the small bowel. In particular the assessment of small obscure gastrointestinal bleeding sources and the detection of shallow inflammatory lesions in the small bowel, have been greatly facilitated by this novel imaging procedure. We report two cases of patients with obscure gastrointestinal bleeding, in whom normal passage of the capsule through the antroduodenal junction was inhibited. This was because of delayed gastric emptying in both patients, which was presumably caused by functional impairment of pyloric motility. To facilitate capsule transport into the small bowel, after swallowing the capsule each patient underwent unsedated upper gastrointestinal endoscopy during which the capsule was grasped with a polypectomy snare, directly transported through the pylorus, and finally released upon arrival in the second portion of the duodenum. Capsule recordings revealed the source of bleeding in both patients and their medical or surgical treatment was subsequently escalated. Capsule imaging of the small bowel facilitated by esophagogastroduodenoscopy (EGD) is safe, and can be applied when patients have functional disorders of pyloric motility.

Transcription factor modulation and expression in the rat auditory brainstem following electrical intracochlear stimulation.

Neuronal activity in sensory organs elicited by adequate or electrical stimulation not only invokes fast electrical responses but may also trigger complex molecular changes inside central neurons. Following electrical intracochlear stimulation with a cochlear implant under urethane anesthesia, we observed changes in the phosphorylation state of the cAMP response element binding protein (CREB) and the expression of the immediate-early genes c-fos and egr-1, molecules known to act as transcription factors, in a tonotopically precise pattern in central auditory neurons. These neurons resided in the posteroventral and anteroventral cochlear nucleus, the dorsal cochlear nucleus, the lateral superior olive, the medial nucleus of the trapezoid body, the dorsal and ventral nucleus of the lateral lemniscus, and the central nucleus of the inferior colliculus. Moreover, effects of electrical stimulation were identified in the medial vestibular nucleus and the lateral parabrachial nucleus. Regionally, CREB was dephosphorylated wherever immediate-early gene expression went up. These massive stimulation-dependent modulations of transcription factors in the ascending auditory system are indicative of ongoing changes that modify the chemistry and structure of the affected cells and, consequently, their response characteristics to subsequent stimulation of the inner ear.

Pulmonary eosinophilia in a murine model of allergic inflammation is attenuated by small molecule alpha4beta1 antagonists.

Inhibition of alpha4beta1/vascular cell adhesion molecule-1 (VCAM-1) interactions have therapeutic potential in treating allergic airway disease because of the importance of these adhesion molecules in the trafficking of eosinophils, lymphocytes, and monocytes. We examined several small molecule inhibitors of alpha4beta1/VCAM-1 interactions with in vitro potencies (IC(50) values) ranging from 0.52 nM (CP-664511; 3-[3-(1-[2-[3-methoxy-4-(3-O-tolyl-ureido)phenyl]-acetylamino]-3-methyl-butyl)isoxazol-5-yl]-propionic acid) to 38.5 nM (CP-609643; 3-[3-methyl-1-[2-[4-(3-O-tolyl-ureido)-phenyl]-acetylamino]-butyl)-isoxazol-5-yl]-propionic acid). The same compounds were evaluated in vivo using a murine model of ovalbumin-induced pulmonary eosinophilia. In this model, systemic administration of antibodies against alpha4 reduced bronchoalveolar lavage (BAL) eosinophilia approximately 60%. Small molecule alpha4beta1 antagonists were administered by intratracheal instillation and demonstrated dose-dependent inhibition of BAL eosinophil numbers and achieved a maximum inhibition of approximately 60%. In general, the rank order of potency for these compounds in vitro was consistent with that observed in vivo, which confirms that their efficacy is likely via blockade of alpha4beta1/VCAM-1 interactions. The most potent compound, CP-664511, also inhibited BAL eosinophilia following s.c. administration (1-10 mg/kg, s.c.). These data support the utility of small molecule alpha4beta1 antagonists in the treatment of relevant diseases, such as asthma.

Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha(4)beta(1) integrin antagonists.

A series of isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives derived from LDV was found to be a potent antagonist of the alpha(4)beta(1) integrin. The synthesis and SAR leading up to 3-[3-(1-[-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino]-3-methyl-butyl)-isoxazol-5-yl]-propionic acid (22) are reported. In an allergic mouse model, compound 22 was efficacious delivered systemically (58% inhib @ 10 mg/kg, sc) as well as by intra-tracheal instillation (ED(50)=2 microg/kg).

Plasticity of the superior olivary complex.

The superior olivary complex (SOC) is part of the auditory brainstem of the vertebrate brain. Residing ventrally in the rhombencephalon, it receives sensory signals from both cochleae through multisynaptic pathways. Neurons of the SOC are also a target of bilateral descending projections. Ascending and descending efferents of the SOC affect the processing of auditory signals on both sides of the brainstem and in both organs of Corti. The pattern of connectivity indicates that the SOC fulfills functions of binaural signal integration serving sound localization. But whereas many of these connectional features are shared with the inferior colliculus (with the important exception of a projection to the inner ear), cellular and molecular investigations have shown that cells residing in SOC are unique in several respects. Unlike those of other auditory brainstem nuclei, they specifically express molecules known to be involved in development, plasticity, and learning (e.g., GAP-43 mRNA, specific subunits of integrin). Moreover, neurons of the SOC in adult mammals respond to various kinds of hearing impairment with the expression of plasticity-related substances (e.g., GAP-43, c-Jun, c-Fos, cytoskeletal elements), indicative of a restructuring of auditory connectivity. These observations suggest that the SOC is pivotal in the developmental and adaptive tuning of binaural processing in young and adult vertebrates.

Surgical stapling technique for radical hysterectomy: survival, recurrence, and late complications.

OBJECTIVE: The aim of this study was to conduct a long-term follow-up of the surgical stapling technique of radical hysterectomy to determine survival, recurrence, and late complications. METHODS: One hundred consecutive eligible patients treated with the surgical stapling technique of radical hysterectomy were prospectively evaluated. RESULTS: Median operative time was 3.2 h. Median blood loss was 500 ml. There was an 18% acute postoperative complication rate and a 10% long-term complication rate. There was a 6% recurrence rate and a 92% disease-free survival. CONCLUSION: The surgical stapling technique of radical hysterectomy results in acceptable survival, recurrence, and complication rates, which appear similar to those of the traditional type of radical hysterectomy, while operative time and blood loss appear to be reduced.