Colloidal systems for the delivery of cyclosporin A to the anterior segment of the eye.

Due to the eye's specific anatomical and physiological conformation, the treatment of eye diseases is a real challenge for pharmaceutical therapy. The presence of efficient protective barriers (i.e., the conjunctival and corneal membranes) and protective mechanisms (i.e., blinking and nasolachrymal drainage) makes this organ particularly impervious to local drug therapy. To overcome these issues, numerous strategies have been envisioned using pharmaceutical technology. Many formulations currently on the market or still under development are emulsions or colloidal systems intended to enhance precorneal residence time and corneal penetration, causing a consequent increase in drug bioavailability after instillation. After a review of some recent developments in the field of cyclosporin A formulations for the eye, a novel micellar formulation of cyclosporine A based on a diblock methoxy-poly(ethylene glycol)-hexysubstituted poly(lactides) (MPEG-hexPLA) is described.

Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease.

BACKGROUND: According to recent guidelines, patients with coronary artery disease (CAD) should undergo revascularization if significant myocardial ischemia is present. Both, cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) allow for a reliable ischemia assessment and in combination with anatomical information provided by invasive coronary angiography (CXA), such a work-up sets the basis for a decision to revascularize or not. The cost-effectiveness ratio of these two strategies is compared. METHODS: Strategy 1) CMR to assess ischemia followed by CXA in ischemia-positive patients (CMR + CXA), Strategy 2) CXA followed by FFR in angiographically positive stenoses (CXA + FFR). The costs, evaluated from the third party payer perspective in Switzerland, Germany, the United Kingdom (UK), and the United States (US), included public prices of the different outpatient procedures and costs induced by procedural complications and by diagnostic errors. The effectiveness criterion was the correct identification of hemodynamically significant coronary lesion(s) (= significant CAD) complemented by full anatomical information. Test performances were derived from the published literature. Cost-effectiveness ratios for both strategies were compared for hypothetical cohorts with different pretest likelihood of significant CAD. RESULTS: CMR + CXA and CXA + FFR were equally cost-effective at a pretest likelihood of CAD of 62% in Switzerland, 65% in Germany, 83% in the UK, and 82% in the US with costs of CHF 5'794, euro 1'517, £ 2'680, and $ 2'179 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. CONCLUSIONS: The CMR + CXA strategy is more cost-effective than CXA + FFR below a CAD prevalence of 62%, 65%, 83%, and 82% for the Swiss, the German, the UK, and the US health care systems, respectively. These findings may help to optimize resource utilization in the diagnosis of CAD.

Current Molecular Imaging of Spinal Tumors in Clinical Practice.

Energy metabolism measurements in spinal cord tumors, as well as in osseous spinal tumors/metastasis in vivo, are rarely performed only with molecular imaging (MI) by positron emission tomography (PET). This imaging modality developed from a small number of basic clinical science investigations followed by subsequent work that influenced and enhanced the research of others. Apart from precise anatomical localization by coregistration of morphological imaging and quantification, the most intriguing advantage of this imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, MI represents one of the key technologies in translational molecular neuroscience research, helping to develop experimental protocols that may later be applied to human patients. PET may help monitor a patient at the vertebral level after surgery and during adjuvant treatment for recurrent or progressive disease. Common clinical indications for MI of primary or secondary CNS spinal tumors are: (i) tumor diagnosis, (ii) identification of the metabolically active tumor compartments (differentiation of viable tumor tissue from necrosis) and (iii) prediction of treatment response by measurement of tumor perfusion or ischemia. While spinal PET has been used under specific circumstances, a question remains as to whether the magnitude of biochemical alterations observed by MI in CNS tumors in general (specifically spinal tumors) can reveal any prognostic value with respect to survival. MI may be able to better identify early disease and to differentiate benign from malignant lesions than more traditional methods. Moreover, an adequate identification of treatment effectiveness may influence patient management. MI probes could be developed to image the function of targets without disturbing them or as treatment to modify the target's function. MI therefore closes the gap between in vitro and in vivo integrative biology of disease. At the spinal level, MI may help to detect progression or recurrence of metastatic disease after surgical treatment. In cases of nonsurgical treatments such as chemo-, hormone- or radiotherapy, it may better assess biological efficiency than conventional imaging modalities coupled with blood tumor markers. In fact, PET provides a unique possibility to correlate topography and specific metabolic activity, but it requires additional clinical and experimental experience and research to find new indications for primary or secondary spinal tumors.

Peri-insular hemispherotomy: potential pitfalls and avoidance of complications.

Techniques for cerebral hemispherectomy have progressively evolved towards more disconnection and less excision over the last 50 years. Peri-insular hemispherotomy (PIH), as described by the senior author, has the maximal ratio of disconnection to excision among all procedures for hemispheric epilepsy. In this study, we focus on surgical complications and intraoperative anatomical observations during PIH over the last 10 years. Based on this experience, the procedure has undergone some modifications, which we detail herein.

Gastroschisis - what should be told to parents?

Gastroschisis is a common congenital abdominal wall defect. It is almost always diagnosed prenatally thanks to routine maternal serum screening and ultrasound screening programs. In the majority of cases, the condition is isolated (i.e. not associated with chromosomal or other anatomical anomalies). Prenatal diagnosis allows for planning the timing, mode and location of delivery. Controversies persist concerning the optimal antenatal monitoring strategy. Compelling evidence supports elective delivery at 37 weeks' gestation in a tertiary pediatric center. Cesarean section should be reserved for routine obstetrical indications. Prognosis of infants with gastroschisis is primarily determined by the degree of bowel injury, which is difficult to assess antenatally. Prenatal counseling usually addresses gastroschisis issues. However, parental concerns are mainly focused on long-term postnatal outcomes including gastrointestinal function and neurodevelopment. Although infants born with gastroschisis often endure a difficult neonatal course, they experience few long-term complications. This manuscript, which is structured around common parental questions and concerns, reviews the evidence pertaining to the antenatal, neonatal and long-term implications of a fetal gastroschisis diagnosis and is aimed at helping healthcare professionals counsel expecting parents. © 2013 John Wiley & Sons, Ltd.

The different types of internal hernia after laparoscopic Roux-En-Y gastric by-pass for morbid obesity: MDCT features [C-419]

Learning Objectives: 1. To provide an overview of the different types of internal hernia (IH) occurring after laparoscopic Roux‑en‑Y gastric bypass (LRYGBP) for morbid obesity. 2. To describe correspondent MDCT features in relation with the underlying anatomical landmarks in order to differentiate their localisation and to direct the surgeon during following laparoscopic closure of mesenteric defects. Background: LRYGBP for morbid obesity is associated with less perioperative complications, shorter hospital stay and a more rapid recovery compared with the open surgical procedure. However, a relatively high incidence of IH is seen that may be due to the laparoscopic approach, but also caused by rapid weight loss with consecutive loosening of the mesenteric sutures. Procedure Details: After briefly reviewing the surgical procedure of LRYGBP (ante‑ versus retrocolic), we describe the exact anatomical landmarks of the different types of IH occurring at any time after operation: They are caused by surgical defects at the level of the transverse colon mesentery, at the Petersen's space, which represents an opening between the mesocolon and jejunal mesentery, or at the entero‑enterostomy site. Typical MDCT features of each IH type in axial and coronal planes as well as targeted vascular reconstructions are demonstrated. Conclusion: Exact knowledge about underlying pathophysiology and anatomical landmarks is essential for distinguishing the different types of IH occurring after LRYGBP on MDCT, since radiological features are difficult to recognize and may even overlap. The radiologist should be aware of the potential anatomic sites to ensure subsequent straightforward laparoscopic exploration.

Gerdy tubercle osteotomy in surgical approach of posterolateral corner of the knee.

Posterolateral corner (PLC) injuries of the knee are uncommon injury patterns that may result in significant degrees of functional disability. When surgery is necessary to address this injury a good knowledge of anatomy and a good surgical exposure is the mainstay. This report reviews the complex anatomy of the posterolateral corner (PLC) of knee and describes the osteotomy of Gerdy tubercle as a technical variant to approach this anatomical region. This surgical step allowing a good mobilisation of the multiple layers of ilio-tibial tract from distal to proximal makes an excellent exposure of the PLC structures with absence of morbidity.

Photographic art and dealing with death

Recently, we were faced with a request from a student photographer who wanted to take pictures of bodies donated to our institute and used for dissection courses for medical students or for scientific purposes. Students are expressly forbidden to take pictures in the dissection hall; however, we allowed this student photographer to do her diploma work in our institute. The reason why she was proposing such a topic was that her brother died young and her parents donated his body to science. To overcome this loss of a loved one, she wanted to know what happens to the donated bodies. She followed the procedure of embalming and different dissections that took place during the summer semester and she took pictures throughout. The outcome of this work was a very nice photographic document, called 'dissection', a book with many pictures but no figure legends. The image document shows the different steps in the preparation and preservation of bodies and the work of an anatomist in the dissection hall. As we impose rules on our students, we had also to give directives in the use of the photographs taken, especially for a photographer who will use the most prominent pictures for exhibitions, i.e. that the pictures do not show names or are used for publication on the internet, or show identification numbers of cadavers, or give indication ofn the institution and are relatively anonymous. This story tells how one can deal with death and at the same time advance one's personal career. The author represents the Swiss Anatomical Society SGAHE and is supported by the Swiss Academy of Science, ScNat.

Accessory tendinous slips arising from the extensor carpi ulnaris (ECU) tendon: MRI appearance, prevalence and association with ECU tenosynovitis and tendinopathy

Purpose: To report the MRI features of ECU accessory tendinous slips, assess their observable prevalence and evaluate a potential link between this anatomical variation and ECU tenosynovitis or tendinopathy. Methods and materials: Institutional review board approved this retrospective study, with waiver of patient informed consent. One hundred sixty wrist MRI studies from 158 patients (85 females, 73 males, mean age 45.6 years, range 14-86) performed between March 2008 and February 2009 on a 1.5-T unit were included. MR images were analyzed by two radiologists in consensus. The observable prevalence of ECU accessory tendinous slips was assessed and their origin, diameter and insertion sites were noted. The presence of ECU tenosynovitis and/or tendinopathy was also evaluated. Results: The observable prevalence of ECU accessory tendinous slips was 21.9% (35/160). The origin was always seen: 8 were at the level of, and 27 distal to the ECU subsheath. The slip median diameter was 0.67 mm (range 0.43-0.88). The insertion was seen in 17.1% (6/35): 2 were on the fifth metacarpal bone, 4 on the extensor apparatus of the fifth finger. ECU tenosynovitis (20%), tendinopathy (5.7%) as well as concomitant tenosynovitis and tendinopathy (25.7%) were more frequently encountered in the patients with the anatomical variation than in the control patients group (0.8%, 3.2% and 9.6% respectively). Differences were statistically significant for tenosynovitis (p = 0.0001) and concomitant tenosynovitis and tendinopathy (p = 0.02) of the ECU. Conclusion: ECU accessory tendinous slips are frequent and visible on 1.5-T wrist MRI studies. ECU tenosynovitis and tendinopathy are more frequent in patients bearing this anatomical variation.

The Phantom Urine: An Unexpected Finding during a Routine Cesarean Section.

We present here an atypical finding during an elective repeat cesarean section. Despite urine flow through an indwelling bladder catheter, bladder remains distended during the whole procedure. Unexpected anatomical variations and malformations can make routine surgery challenging. Urinary tract anomalies should be suspected in cases of unexpected difficult bladder catheterization.

Central and Cortical Gray Mater Segmentation of Magnetic Resonance Images of the Fetal Brain

Motivation. The study of human brain development in itsearly stage is today possible thanks to in vivo fetalmagnetic resonance imaging (MRI) techniques. Aquantitative analysis of fetal cortical surfacerepresents a new approach which can be used as a markerof the cerebral maturation (as gyration) and also forstudying central nervous system pathologies [1]. However,this quantitative approach is a major challenge forseveral reasons. First, movement of the fetus inside theamniotic cavity requires very fast MRI sequences tominimize motion artifacts, resulting in a poor spatialresolution and/or lower SNR. Second, due to the ongoingmyelination and cortical maturation, the appearance ofthe developing brain differs very much from thehomogenous tissue types found in adults. Third, due tolow resolution, fetal MR images considerably suffer ofpartial volume (PV) effect, sometimes in large areas.Today extensive efforts are made to deal with thereconstruction of high resolution 3D fetal volumes[2,3,4] to cope with intra-volume motion and low SNR.However, few studies exist related to the automatedsegmentation of MR fetal imaging. [5] and [6] work on thesegmentation of specific areas of the fetal brain such asposterior fossa, brainstem or germinal matrix. Firstattempt for automated brain tissue segmentation has beenpresented in [7] and in our previous work [8]. Bothmethods apply the Expectation-Maximization Markov RandomField (EM-MRF) framework but contrary to [7] we do notneed from any anatomical atlas prior. Data set &Methods. Prenatal MR imaging was performed with a 1-Tsystem (GE Medical Systems, Milwaukee) using single shotfast spin echo (ssFSE) sequences (TR 7000 ms, TE 180 ms,FOV 40 x 40 cm, slice thickness 5.4mm, in plane spatialresolution 1.09mm). Each fetus has 6 axial volumes(around 15 slices per volume), each of them acquired inabout 1 min. Each volume is shifted by 1 mm with respectto the previous one. Gestational age (GA) ranges from 29to 32 weeks. Mother is under sedation. Each volume ismanually segmented to extract fetal brain fromsurrounding maternal tissues. Then, in-homogeneityintensity correction is performed using [9] and linearintensity normalization is performed to have intensityvalues that range from 0 to 255. Note that due tointra-tissue variability of developing brain someintensity variability still remains. For each fetus, ahigh spatial resolution image of isotropic voxel size of1.09 mm is created applying [2] and using B-splines forthe scattered data interpolation [10] (see Fig. 1). Then,basal ganglia (BS) segmentation is performed on thissuper reconstructed volume. Active contour framework witha Level Set (LS) implementation is used. Our LS follows aslightly different formulation from well-known Chan-Vese[11] formulation. In our case, the LS evolves forcing themean of the inside of the curve to be the mean intensityof basal ganglia. Moreover, we add local spatial priorthrough a probabilistic map created by fitting anellipsoid onto the basal ganglia region. Some userinteraction is needed to set the mean intensity of BG(green dots in Fig. 2) and the initial fitting points forthe probabilistic prior map (blue points in Fig. 2). Oncebasal ganglia are removed from the image, brain tissuesegmentation is performed as described in [8]. Results.The case study presented here has 29 weeks of GA. Thehigh resolution reconstructed volume is presented in Fig.1. The steps of BG segmentation are shown in Fig. 2.Overlap in comparison with manual segmentation isquantified by the Dice similarity index (DSI) equal to0.829 (values above 0.7 are considered a very goodagreement). Such BG segmentation has been applied on 3other subjects ranging for 29 to 32 GA and the DSI hasbeen of 0.856, 0.794 and 0.785. Our segmentation of theinner (red and blue contours) and outer cortical surface(green contour) is presented in Fig. 3. Finally, torefine the results we include our WM segmentation in theFreesurfer software [12] and some manual corrections toobtain Fig.4. Discussion. Precise cortical surfaceextraction of fetal brain is needed for quantitativestudies of early human brain development. Our workcombines the well known statistical classificationframework with the active contour segmentation forcentral gray mater extraction. A main advantage of thepresented procedure for fetal brain surface extraction isthat we do not include any spatial prior coming fromanatomical atlases. The results presented here arepreliminary but promising. Our efforts are now in testingsuch approach on a wider range of gestational ages thatwe will include in the final version of this work andstudying as well its generalization to different scannersand different type of MRI sequences. References. [1]Guibaud, Prenatal Diagnosis 29(4) (2009). [2] Rousseau,Acad. Rad. 13(9), 2006, [3] Jiang, IEEE TMI 2007. [4]Warfield IADB, MICCAI 2009. [5] Claude, IEEE Trans. Bio.Eng. 51(4) (2004). [6] Habas, MICCAI (Pt. 1) 2008. [7]Bertelsen, ISMRM 2009 [8] Bach Cuadra, IADB, MICCAI 2009.[9] Styner, IEEE TMI 19(39 (2000). [10] Lee, IEEE Trans.Visual. And Comp. Graph. 3(3), 1997, [11] Chan, IEEETrans. Img. Proc, 10(2), 2001 [12] Freesurfer,http://surfer.nmr.mgh.harvard.edu.

Homolonto: generating homology relationships by pairwise alignment of ontologies and application to vertebrate anatomy.

MOTIVATION: The anatomy of model species is described in ontologies, which are used to standardize the annotations of experimental data, such as gene expression patterns. To compare such data between species, we need to establish relations between ontologies describing different species. RESULTS: We present a new algorithm, and its implementation in the software Homolonto, to create new relationships between anatomical ontologies, based on the homology concept. Homolonto uses a supervised ontology alignment approach. Several alignments can be merged, forming homology groups. We also present an algorithm to generate relationships between these homology groups. This has been used to build a multi-species ontology, for the database of gene expression evolution Bgee. AVAILABILITY: download section of the Bgee website http://bgee.unil.ch/

The Body Action and Posture Coding System (BAP): Development and Reliability

Several methods are available for coding body movement in nonverbal behavior research, but there is no consensus on a reliable coding system that can be used for the study of emotion expression. Adopting an integrative approach, we developed a new method, the Body Action and Posture (BAP) coding system, for the time-aligned micro description of body movement on an anatomical level (different articulations of body parts), a form level (direction and orientation of movement), and a functional level (communicative and self-regulatory functions). We applied the system to a new corpus of acted emotion portrayals, examined its comprehensiveness and demonstrated intercoder reliability at three levels: a) occurrence, b) temporal precision and c) segmentation. We discuss issues for further validation and propose some research applications.

Distribution and genesis of the RFRP-producing neurons in the rat brain: comparison with melanin-concentrating hormone- and hypocretin-containing neurons.

Prepro-RFRP-containing neurons have recently been described in the mammalian brain. These neurons are only found in the tuberal hypothalamus. In this work, we have provided a detailed analysis of the distribution of cells expressing the RFRP mRNA, and found them in seven anatomical structures of the tuberal hypothalamus. No co-expression with melanin-concentrating hormone (MCH) or hypocretin (Hcrt), that are also described in neurons of the tuberal hypothalamus, was observed. Using the BrdU method, we found that all RFRP cell bodies are generated between E13 and E14. Thus, RFRP neurons form a specific cell population with a complex distribution pattern in the tuberal hypothalamus. However, they are generated in one peak. These observations are discussed with data concerning the distribution and genesis of the MCH and Hcrt cell populations that are also distributed in the tuberal hypothalamus.

Multi-segment foot kinematics after total ankle replacement and ankle arthrodesis during relatively long-distance gait.

This study aimed to investigate the influence of ankle osteoarthritis (AOA) treatments, i.e., ankle arthrodesis (AA) and total ankle replacement (TAR), on the kinematics of multi-segment foot and ankle complex during relatively long-distance gait. Forty-five subjects in four groups (AOA, AA, TAR, and control) were equipped with a wearable system consisting of inertial sensors installed on the tibia, calcaneus, and medial metatarsals. The subjects walked 50-m twice while the system measured the kinematic parameters of their multi-segment foot: the range of motion of joints between tibia, calcaneus, and medial metatarsals in three anatomical planes, and the peaks of angular velocity of these segments in the sagittal plane. These parameters were then compared among the four groups. It was observed that the range of motion and peak of angular velocities generally improved after TAR and were similar to the control subjects. However, unlike AOA and TAR, AA imposed impairments in the range of motion in the coronal plane for both the tibia-calcaneus and tibia-metatarsals joints. In general, the kinematic parameters showed significant correlation with established clinical scales (FFI and AOFAS), which shows their convergent validity. Based on the kinematic parameters of multi-segment foot during 50-m gait, this study showed significant improvements in foot mobility after TAR, but several significant impairments remained after AA.