The effect of shoulder variation on IMRT and SmartArc for Head and Neck Cancer

Purpose: First, to determine an average and maximum displacement of the shoulder relative to isocenter over the course of treatment. Second, to establish the dosimetric effect of shoulder displacements relative to correct isocenter alignment on the dose delivered to the target and the surrounding structures for head and neck cancer patients. Method and Materials: The frequency of shoulder shifts of various magnitudes relative to isocenter was assessed for 4 patients using image registration software. The location of the center of the right and left humeral head relative to isocenter (usually C2) was found daily from CT on rails scans, and was compared to the location of the humeral heads relative to isocenter on the initial simulation CT. Three Baseline head and neck IMRT and SmartArc plans were generated in Pinnacle based on simulation CTs. The CT datasets (external contour and boney structures) were then modified to represent shifts of the shoulder (relative to isocenter) between 3 mm and 15 mm in the SI, AP, and LR directions. The initial plans were recalculated on the image sets with shifted shoulders. Results: On average, shoulder variation was 2-5 mm in each direction, although displacements of over 1 cm in the inferior and posterior directions occurred. Shoulder shifts induced perturbations in the dose distribution, although generally only for large shifts. Most substantially, large, superior shifts resulted in coverage loss by the 95% isodose line for targets in the lower neck. Inferior shifts elevated the dose to the brachial plexus by 0.6-4.1 Gy. SmartArc plans showed similar loss of target coverage as IMRT plans. Conclusions: The position of the shoulder can have an impact on target coverage and critical structure dose. Shoulder position may need to be considered for setup of head and neck patients depending on target location.

Intracisternal application of endotoxin enhances the susceptibility to subsequent hypoxic-ischemic brain damage in neonatal rats.

Perinatal brain damage is associated not only with hypoxic-ischemic insults but also with intrauterine inflammation. A combination of antenatal inflammation and asphyxia increases the risk of cerebral palsy >70 times. The aim of the present study was to determine the effect of intracisternal (i.c.) administration of endotoxin [lipopolysaccharides (LPS)] on subsequent hypoxic-ischemic brain damage in neonatal rats. Seven-day-old Wistar rats were subjected to i.c. application of NaCl or LPS (5 microg/pup). One hour later, the left common carotid artery was exposed through a midline neck incision and ligated with 6-0 surgical silk. After another hour of recovery, the pups were subjected to a hypoxic gas mixture (8% oxygen/92% nitrogen) for 60 min. The animals were randomized to four experimental groups: 1) sham control group, left common carotid artery exposed but not ligated (n = 5); 2) LPS group, subjected to i.c. application of LPS (n = 7); 3) hypoxic-ischemic study group, i.c. injection of NaCl and exposure to hypoxia after ligation of the left carotid artery (n = 17); or 4) hypoxic-ischemic/LPS study group, i.c. injection of LPS and exposure to hypoxia after ligation of the left carotid artery (n = 19). Seven days later, neonatal brains were assessed for neuronal cell damage. In a second set of experiments, rat pups received an i.c. injection of LPS (5 microg/pup) and were evaluated for tumor necrosis factor-alpha expression by immunohistochemistry. Neuronal cell damage could not be observed in the sham control or in the LPS group. In the hypoxic-ischemic/LPS group, neuronal injury in the cerebral cortex was significantly higher than in animals that were subjected to hypoxia/ischemia after i.c. application of NaCl. Injecting LPS intracisternally caused a marked expression of tumor necrosis factor-alpha in the leptomeninges. Applying LPS intracisternally sensitizes the immature rat brain to a subsequent hypoxic-ischemic insult.

Endoscopically assisted decompression of the median nerve in the pronator and Kiloh-Nevin syndrome: Surgical technique

STATE OF THE ART The proximal median nerve compression syndrome includes the pronator teres and the Kiloh-Nevin syndrome. This article presents a new surgical technique of endoscopic assisted median nerve decompression. MATERIAL AND SURGICAL TECHNIQUE Endoscopic scissor decompression of the median nerve is always performed under plexus anaesthesia. It includes 6 key steps documented in this article. We review the indications and limitations of the surgical technique. RESULTS Since 2011, three clinical series have highlighted the advantages of this technique. Functional and subjective results are discussed. We also review the limitations of the technique and its potential for future development. CONCLUSION Although clinical results after endoscopic assisted decompression of the median nerve appear excellent they still need to be compared with conventional techniques. Clinical studies are likely to develop primarily due to the mini-invasive nature of this new surgical technique.

Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study

BackgroundNiemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.MethodsClinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013. We retrospectively evaluated diagnostic delays and period prevalence rates for neurological, psychiatric and visceral symptoms associated with NP-C disease. The NP-C suspicion index was calculated for the time of neurological disease onset and the time of diagnosis.ResultsThe shortest median diagnostic delay was noted for vertical supranuclear gaze palsy (2y). Ataxia, dysarthria, dysphagia, spasticity, cataplexy, seizures and cognitive decline displayed similar median diagnostic delays (4¿5y). The longest median diagnostic delay was associated with hepatosplenomegaly (15y). Highest period prevalence rates were noted for ataxia, dysarthria, vertical supranuclear gaze palsy and cognitive decline. The NP-C suspicion index revealed a median score of 81 points in nine patients at the time of neurological disease onset which is highly suspicious for NP-C disease. At the time of diagnosis, the score increased to 206 points.ConclusionA neurologic-psychiatric disease pattern represents the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Visceral manifestation such as isolated hepatosplenomegaly often fails recognition and thus highlights the importance of a work-up for lysosomal storage disorders. The NP-C suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile NP-C patients.

Autonomic angiotensinergic fibres in the human heart with an efferent sympathetic cophenotype

AIM The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.

Effects of microbeam radiation therapy on normal and tumoral blood vessels

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.

Brain barriers: Crosstalk between complex tight junctions and adherens junctions

Unique intercellular junctional complexes between the central nervous system (CNS) microvascular endothelial cells and the choroid plexus epithelial cells form the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB), respectively. These barriers inhibit paracellular diffusion, thereby protecting the CNS from fluctuations in the blood. Studies of brain barrier integrity during development, normal physiology, and disease have focused on BBB and BCSFB tight junctions but not the corresponding endothelial and epithelial adherens junctions. The crosstalk between adherens junctions and tight junctions in maintaining barrier integrity is an understudied area that may represent a promising target for influencing brain barrier function.

The importance of phrenic nerve preservation and its effect on long-term postoperative lung function after pneumonectomy

OBJECTIVES The importance of phrenic nerve preservation during pneumonectomy remains controversial. We previously demonstrated that preservation of the phrenic nerve in the immediate postoperative period preserved lung function by 3-5% but little is known about its long-term effects. We, therefore, decided to investigate the effect of temporary ipsilateral cervical phrenic nerve block on dynamic lung volumes in mid- to long-term pneumonectomy patients. METHODS We investigated 14 patients after a median of 9 years post pneumonectomy (range: 1-15 years). Lung function testing (spirometry) and fluoroscopic and/or sonographic assessment of diaphragmatic motion on the pneumonectomy side were performed before and after ultrasonographic-guided ipsilateral cervical phrenic nerve block by infiltration with lidocaine. RESULTS Ipsilateral phrenic nerve block was successfully achieved in 12 patients (86%). In the remaining 2 patients, diaphragmatic motion was already paradoxical before the nerve block. We found no significant difference on dynamic lung function values (FEV1 'before' 1.39 ± 0.44 vs FEV1 'after' 1.38 ± 0.40; P = 0.81). CONCLUSIONS Induction of a temporary diaphragmatic palsy did not significantly influence dynamic lung volumes in mid- to long-term pneumonectomy patients, suggesting that preservation of the phrenic nerve is of greater importance in the immediate postoperative period after pneumonectomy.

Incidence and outcomes of symptomatic neonatal arterial ischemic stroke.

BACKGROUND AND OBJECTIVES Neonatal arterial ischemic stroke (NAIS) is associated with considerable lifetime burdens such as cerebral palsy, epilepsy, and cognitive impairment. Prospective epidemiologic studies that include outcome assessments are scarce. This study aimed to provide information on the epidemiology, clinical manifestations, infarct characteristics, associated clinical variables, treatment strategies, and outcomes of NAIS in a prospective, population-based cohort of Swiss children. METHODS This prospective study evaluated the epidemiology, clinical manifestations, vascular territories, associated clinical variables, and treatment of all full-term neonates diagnosed with NAIS and born in Switzerland between 2000 and 2010. Follow-up was performed 2 years (mean 23.3 months, SD 4.3 months) after birth. RESULTS One hundred neonates (67 boys) had a diagnosis of NAIS. The NAIS incidence in Switzerland during this time was 13 (95% confidence interval [CI], 11-17) per 100,000 live births. Seizures were the most common symptom (95%). Eighty-one percent had unilateral (80% left-sided) and 19% had bilateral lesions. Risk factors included maternal risk conditions (32%), birth complications (68%), and neonatal comorbidities (54%). Antithrombotic and antiplatelet therapy use was low (17%). No serious side effects were reported. Two years after birth, 39% were diagnosed with cerebral palsy and 31% had delayed mental performance. CONCLUSIONS NAIS in Switzerland shows a similar incidence as other population-based studies. About one-third of patients developed cerebral palsy or showed delayed mental performance 2 years after birth, and children with normal mental performance may still develop deficits later in life.

E-Racer

The E-Racer was made for a young boy with cerebral palsy. The client cannot use his legs and control in his left arm is very limited. The client's family expressed a desire for an electric go-kart, and also for the go-kart to resemble a "normal" go-kart. To that end, the E-Racer has been outfitted with both steering wheel and joystick modes so the client can choose which control system he would like to use depending on what he is comfortable with. The E-Racer is a stock go-kart which was modified in several key ways. The electronics were drastically modified to accommodate the two controls systems. In addition, both the steering and braking systems were modified so they could be controlled electrically rather than mechanically. Finally, several modifications were made to the go-kart to improve the rider's comfort and safety.

The role of deregulated E2F1 expression in brain tumors

Mutations disabling the retinoblastoma (Rb) pathway are among the most common in human cancers, including brain cancer. These mutations promote tumor development through deregulated control of the E2F family of transcription factors. E2F1 belongs to a class of E2F's identified as transcriptional activators and involved in the G1/S phase transition of the cell. However, E2F-1 presents with a paradox as it is considered to have membership in two gene classes, functioning as both an oncogene and a tumor suppressor. This unusual trait generates a degree of uncertainty on the role that E2F1 plays in the development or maintenance of any given tumor. Here we show that E2F1 functions as an oncogene in brain tumors through the generation of mice engineered to overexpress E2F1 specifically within glial cells and neuronal progenitors as directed by the GFAP promoter. Mice carrying the transgene develop with high penetrance a phenotype characterized by neurological deficits including paresia, ataxia, head tilt and seizures. MRI imagining of the tgE2F1 mice reveals a low incidence of mild hydrocephalus, and most notably, histological analysis demonstrates that 25% of tgE2F1 mice present with the spontaneous formation of malignant brain tumors. Overall these neoplasms show histological features from a wide range of aggressive brain cancers including medulloblastoma, choroid plexus carcinoma, primary neuroectodermic tumor and malignant gliomas. Isolation and characterization of astrocytes from the tgE2F1 animal reveals a highly proliferative population of cells with 55% ± 2.5 of the tgE2F1astrocytes, 35% ± 3.4 normal mouse astrocytes in S-phase and the acquired capacity to grow in anchorage independent conditions. Additionally tgE2F1 astrocytes show an aberrant phenotype with random chromosomal fusions and nearly all cells demonstrating polyploidy. Taken together, this model forces a comparison to human brain tumor formation. Mouse age as related to tumoral mimics the human scenario with juvenile tgE2F1 mice presenting embryonal tumors typically identified in children, and older tgE2F1 mice demonstrating gliomas. In this regard, this study suggests a global role for E2F1 in the formation and maintenance of multilineage brain tumors, irrefutably establishing E2F1 as an oncogene in the brain. ^

Neogene planktonic foraminifera of ODP Site 130-806

The Neogene biostratigraphy presented here is based on the study of 230 samples through 737 m of pelagic sediment in Hole 806B. Sediment accumulation is interrupted only once in the uppermost lower Miocene (Zone N6), apparently coincident with a widespread deep-sea hiatus. Preservation of planktonic foraminifers through the section ranges from good to moderately poor. One hundred and ten species of planktonic foraminifers were identified; taxonomic notes on most species are included. All of the standard low-latitude Neogene foraminiferal zones are delineated, with the exceptions of Zones N8 and N9 because of a high first occurrence of Orbulina, and Zones N18 and N19 because of a high first occurrence of Sphaeroidinella dehiscens. Good agreement exists between the published account of the variation in planktonic foraminiferal species richness and the rates of diversification and turnover, and measurements of these evolutionary indexes in the record of Hole 806B. The global pattern of change in tropical/transitional species richness is paralleled in Hole 806B, with departures caused by either ecological conditions peculiar to the western equatorial Pacific or by inexactness in the estimation of million-year intervals in Hole 806B. Temporal changes in the relative abundance of taxa in the sediment assemblages, considered in light of their depth habitats, reveal a detailed picture of historical change in the structure of the upper water column over the Ontong Java Plateau. The dominance of surface dwellers (Paragloborotalia kugleri, P. mayeri, Dentoglobigerina altispira, Globigerinita glutinata, and Globigerinoides spp.) throughout the lower and middle Miocene is replaced by a more equitable distribution of surface (D. altispira and Globigerinoides spp.), intermediate (Globorotalia menardii plexus), and deep (Streptochilus spp.) dwellers in the late Miocene, following the closing of the Indo-Pacific Seaway and the initiation of large-scale glaciation in the Antarctic. The shoaling of the thermocline along the equator engendered by these climatic and tectonic events persisted through the Pliocene, when initial increases in the abundance of a new set of shallow, intermediate, and deep dwelling species of planktonic foraminifers coincide with the closing of the Panamanian Seaway.

Siliceous microfossils in middle Eocene sediments of ODP Holes 120-748B and 120-749B

The Middle Eocene Climatic Optimum (MECO) is a major transient warming event that occurred at ~ 40 Ma and reversed a long-term cooling trend through the early and middle Eocene. We report the results of a high-resolution, quantitative study of siliceous microfossils at Ocean Drilling Program Sites 748 and 749 (Southern Kerguelen Plateau, Southern Ocean, ~ 58°S) across a ~ 1.4 myr interval spanning the MECO event. At both sites, a significant increase in biosiliceous sedimentation is associated with the MECO event. Rich siliceous planktonic microfossil assemblages in this interval are unusual in that they are dominated by ebridians, with radiolarians as a secondary major component. Silicoflagellates and diatoms comprise only a minor fraction of the assemblage, in contrast to siliceous microfossil assemblages that characterize modern Southern Ocean sediments. Based on our new siliceous microfossil records, we interpret two ~ 300 kyr periods of elevated nutrient availability in Southern Ocean surface waters which span the peak warming interval of the MECO and the post-MECO cooling interval. A diverse assemblage of large silicoflagellates belonging to the Dictyocha grandis plexus is linked to the rapid rise in sea-surface temperatures immediately prior to peak warmth, and a pronounced turnover is observed in both ebridian and silicoflagellate assemblages at the onset of peak warming. The interval of peak warmth is also characterized by high abundance of cosmopolitan ebridians (e.g., Ammodochium spp.) and silicoflagellates (e.g., Naviculopsis spp.), and increased abundance of tropical and subtropical diatom genera (e.g., Asterolampra and Azpeitia). These observations confirm the relative pattern of temperature change interpreted from geochemical proxy data at multiple Southern Ocean sites. Furthermore, rapid assemblage changes in both autotrophic and heterotrophic siliceous microfossil groups indicate a reorganization of Southern Ocean plankton communities in response to greenhouse warming during the MECO event.

Toxina botulínica para la secreción descontrolada de saliva : presentación de un caso

La neurotoxina botulínica es producida por la bacteria anaerobia Clostridium botulinum (NTBo). Bloquea la transmisión neuromuscular por lo cual es utilizada para el tratamiento de enfermedades con hiperactividad muscular, bloqueando la liberación de acetilcolina y así la transmisión sináptica en la unión neuromuscular, lo que lleva al debilitamiento y atrofia de los músculos. Este mecanismo de acción motivó el uso de la toxina botulínica en las enfermedades con elevado tono muscular, como la distonía y la espasticidad, por lo cual también ha revolucionado la opción de tratamiento de los trastornos autónomos de hipersecreción. La sialorrea es un síntoma común en diversas enfermedades neurológicas. Las inyecciones de toxina botulínica, guiadas por ultrasonidos en las glándulas salivales, produce una disminución de la salivación excesiva en niños con deficiencias neurológicas como parálisis cerebral. La utilización de la toxina botulínica tipo A ha sido sugerida como tratamiento de la sialorrea en pacientes con parálisis cerebral (PC). Esta recomendación ha sido hecha por el efecto anticolinérgico de esta sustancia, principalmente por su capacidad para bloquear la liberación de acetilcolina a nivel de las membranas pre-sinápticas Aunque la respuesta al tratamrento es distinta en cada niño, en general se ha observado que cuanto más a menudo se utiliza la toxlna botulínica y más alta es la dosis utilizada, los resultados son mejores. Los expertos consideran conveniente el procedimiento porque muchos de estos pacientes están utilizando la toxina botulínica para sus problemas musculares y las distrntas condiciones pueden ser tratadas al mismo tiempo Se reporta la descripción de la aplicación de toxina botulínica en una paciente niña que concurre al Instituto de Rehabilitación Infantil TELETON de la ciudad de Valparaíso, Chile, con un trastorno motor severo y con salivación incontrolada persistente que provoca enfermedades respiratorias a repetición