Role of galectin-1 in the olfactory nervous system

The olfactory nervous system is responsible for the detection of odors. Primary sensory olfactory neurons are located in a neuroepithelial sheet lining the nasal cavity. The axons from these neurons converge on to discrete loci or glomeruli in the olfactory bulb. Each glomerulus consists of the termination of thousands of primary axons on the dendrites of second-order olfactory neurons. What are the molecular mechanisms which guide growing olfactory axons to select sites in the olfactory bulb? We have shown that subpopulations of these axons differentially express cell surface carbohydrates and that these different subpopulations target and terminate in particular regions of the olfactory bulb. Interestingly, the olfactory neurons and glial components in the olfactory pathway between the nose and brain express galectin-1. By using in vitro assays of neurite outgrowth we found that both galectin-1 and it's ligands were capable of specifically stimulating neurite elongation. Examination of the olfactory system in galectin-1 null mutants revealed that a subpopulation of axons failed to navigate to their target site in the olfactory bulb. This is the first phenotypic effect observed in galectin-1 null mutants and indicates that galectin-1 has a role in the growth and/or guidance of a subpopulation of axons in the olfactory system during development.

Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function

The level of fractional exhaled nitric oxide (FENO) is significantly elevated in uncontrolled asthma and decreases after anti-inflammatory therapy The aim of this prospective study was to analyze the behavior of FENO in the follow-up and management of the inflammation in asthmatic pediatric patients treated with inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins (IL), and pulmonary function. Twenty-six clinically stable asthmatic children aged from 6 to 18 years, previously treated or not with ICS were included. Following an international consensus (GINA), the patients were submitted to standard treatment with inhaled fluticasone for 3 months according to the severity of the disease. During this period, each patient underwent three assessments at intervals of approximately 6 weeks: Each evaluation consisted of the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13, and interferon gamma (INF-gamma), spirometry and cytological analysis of spontaneous or induced sputum. A significant reduction in mean FENO and IL-5, without concomitant changes in FEV1, was observed along the study. There was no significant correlation between FeNO and FEV1 in the three assessments. A significant correlation between FeNO and IL-5 levels was only observed in the third assessment (r = 0.499, P=0.025). In most patients, serum IL-10, IL-13, and INF-gamma concentrations were undetectable throughout the study Sputum samples were obtained spontaneously in 11 occasions and in 56 by induction with 3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them adequate for analysis. Only two of the 26 patients produced adequate samples in the three consecutive evaluations, which impaired the determination of a potential association between sputum cellularity and FeNO levels throughout the study. In conclusion, among the parameters of this study, it was difficult to perform and to interpret the serial analysis of spontaneous or induced sputum. Serum interleukins, which remained at very low or undetectable levels in most patients, were not found to be useful for therapeutic monitoring, except for IL-5 that seems to present some correlation with levels of FeNO exhaled. Monitoring of the mean FEV1 indicated no significant variations during the treatment, demonstrating that functional stability or the absence of obstruction may not reflect the adequate management of asthma. Serial measurement of FeNO seemed to best reflect the progressive anti-inflammatory action of ICS in asthma.

The central pathway of primary olfactory axons is abnormal in mice lacking the N-CAM-180 isoform

Although N-CAM has previously been implicated in the growth and fasciculation of axons, the development of axon tracts in transgenic mice with a targeted deletion of the 180-kD isoform of the neural cell adhesion molecule (N-CAM-180) appears grossly normal in comparison to wild-type mice. We examined the organization of the olfactory nerve projection from the olfactory neuroepithelium to glomeruli in the olfactory bulb of postnatal N-CAM-180 null mutant mice. Immunostaining for olfactory marker protein revealed the normal presence of fully mature primary olfactory neurons within the olfactory neuroepithelium of mutant mice. The axons of these neurons form an olfactory nerve, enter the nerve fiber layer of the olfactory bulb, and terminate in olfactory glomeruli as in wild-type control animals. The olfactory bulb is smaller and the nerve fiber layer is relatively thicker in mutants than in wild-type mice. Previous studies have revealed that the plant lectin Dolichos biflorus agglutinin (DBA) clearly stains the perikarya and axons of a subpopulation of primary olfactory neurons. Thus, DBA staining enabled the morphology of the olfactory nerve pathway to be examined at higher resolution in both control and mutant animals. Despite a normal spatial pattern of DBA-stained neurons within the nasal cavity, there was a distorted axonal projection of these neurons onto the surface of the olfactory bulb in N-CAM-180 null mutants. In particular, DBA-stained axons formed fewer and smaller glomeruli in the olfactory bulbs of mutants in comparison to wild-type mice. Many primary olfactory axons failed to exit the nerve fiber layer and contribute to glomerular formation. These results indicate that N-CAM-180 plays an important role in the growth and fasciculation of primary olfactory axons and is essential for normal development of olfactory glomeruli. (C) 1997 John Wiley & Sons, Inc.

Regional Blood Flow Distribution and Oxygen Metabolism During Mesenteric Ischemia and Congestion

Background. Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. Methods. Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. Results. SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-p)CO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. Conclusions. SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology. (C) 2010 Elsevier Inc. All rights reserved.

Presence of novel N-CAM glycoforms in the rat olfactory system

The functional activity of the neural cell adhesion molecule N-CAM can be modulated by posttranslational modifications such as glycosylation. For instance, the long polysialic acid side chains of N-CAM alter the adhesion properties of the protein backbone. In the present study, we identified two novel carbohydrates present on N-CAM, NOC-3 and NOC-4. Both carbohydrates were detected on N-CAM glycoforms expressed by subpopulations of primary sensory olfactory neurons in the rat olfactory system. Based on the expression of NOC-3 and NOC-4 and the olfactory marker protein (OMP), four independent subpopulations of primary sensory olfactory neurons were characterized. These neurons expressed: both NOC-3 and NOC-4 but not OMP; both NOC-4 and OMP but not NOC-3; NOC-3, NOC-4, and OMP together; and OMP alone. The NOC-3- and NOC-4-expressing neurons were widely dispersed in the olfactory neuroepithelium lining the nasal cavity. The axons of NOC-4 expressing neurons innervated all glomeruli in the olfactory bulb, whereas the NOC-3 expressing axons terminated in a discrete subset of glomeruli scattered throughout the whole olfactory bulb. We propose that both NOC-3 and NOC-4 are part of a chemical code of olfactory neurons which is used in establishing the topography of connections between the olfactory neuroepithelium and the olfactory bulb. (C) 1997 John Wiley & Sons, Inc.

Sonographic Diagnosis of a Ureteral Inguinal Hernia in a Renal Transplant

Complications related to renal transplants have been widely reported in the literature. The most common complications include acute tubular necrosis, rejection, perirenal fluid collections, vascular complications, and urinary tract obstruction, which are promptly identified by imaging studies. Here we report a case of a patient with a rare cause of obstruction: a ureteral inguinal hernia. This is the sixth report of this condition, and, to our knowledge, no previous case has been reported in which sonography played an important role in promptly identifying the underlying condition and allowing additional less hazardous studies, therefore aiding case management.

Minimally Invasive Computer-Assisted Stereotactic Fenestration of an Aqueductal Cyst: Case Report

Introduction: Current advances in frame modeling and computer software allow stereotactic procedures to be performed with great accuracy and minimal risk of neural tissue or vascular injury. Case Report: In this report we associate a previously described minimally invasive stereotactic technique with state-of-the-art 3D computer guidance technology to successfully treat a 55-year-old patient with an arachnoidal cyst obstructing the aqueduct of Sylvius. We provide 1 detailed technical information and discuss how this technique deals with previous limitations for stereotactic manipulation of the aqueductal region. We further discuss current advances in neuroendoscopy for treating obstructive hydrocephalus and make comparisons with our proposed technique. Conclusion: We advocate that this technique is not only capable of treating this pathology but it also has the advantages to enable reestablishment of physiological CSF flow thus preventing future brainstem compression by cyst enlargement.

Sphenoid sinus symmetry and differences between sexes

Objectives: To evaluate the anatomic variations of neurovascular structures adjacent to the sphenoid sinus and their agreement between right and left sides as well as differences between sexes. Methods: Forty-five cadavers were dissected (24 men, and differences between sexes and agreement of anatomic variations of the sphenoid sinus between sides were analyzed. Results: The mean distance from the sphenoid sinus ostium to the anterior nasal spine was greater in males than in females by an average of 3.0 mm (p = 0.001) while the mean difference of distances between the right and left side was -1.1 +/- 3.1 mm. Female cadavers had a greater frequency of optic-carotid recess (p = 0.04) and dehiscence over the maxillary nerve (p = 0.02), as well as greater relative risk of optic nerve protrusion (p < 0.001), and dehiscence over the internal carotid artery (ICA) (p = 0.002). In male cadavers the intersinus septum was inserted on the course of the ICA 3.5 times more often than in female (p = 0.02). Agreement of anatomic variations between sides ranged from moderate to almost perfect depending on the structures evaluated. Conclusions: There are anatomic differences of the sphenoid sinus between sexes and between right and left sides, and these differences should be taken into consideration during surgery.

Craniofacial morphology and otitis media with effusion in children

Otitis media with effusion (OME) affects 28-38% of pre-school children, and it occurs due to the dysfunction of the auditory tube. Anatomical development of the auditory tube depends on the craniofacial growth and development. Deviations of normal. craniofacial. morphology and growth using cephatometric studies, may predict the evolution of otitis. Our goal in this paper is to determine if there are differences in craniofacial morphology between children with adenoid enlargement, with and without otitis media with effusion. This is a prospective study in which the sample consisted of 67 children (mate and female) from 5 to 10 years old. All patients presented chronic upper airway obstruction due to tonsil. and adenoid enlargement (>80% degree of obstruction). Thirty-three patients presented otitis media with effusion, for more than 3 months and 34 did not. The tatter composed the control group. Standardized lateral head radiographs were obtained for all. subjects. Radiographs were taken with patient positioned by a cephalostat and stayed with mandibles in centric occlusion and Lips at rest. Radiographs were digitalized and specific Landmarks were identified using a computer program Radiocef 2003, 5th edition. Measurements, angles and tines were taken of the basicranium, maxilla and mandible according to the modified Ricketts analysis. In addition, facial height and facial axis were determined. Children with otitis media with effusion present differences in the morphology of the face, regarding these measures: N-S (anterior cranial base length), N-ANS (upper facial height), ANS-PNS (size of the hard palate), Po-Or.N-Pog (facial depth), Ba-N.Ptm-Gn (facial axis), Go-Me (mandibular Length) and Vaia--Vaip (inferior pharyngeal airway). (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Comparison of the GDx VCC scanning laser polarimeter and the stratus optical coherence tomograph in the detection of band atrophy of the optic nerve

Aim To compare the ability of scanning laser polarimeter (SLP) with variable corneal compensation (GDx VCC) and optical coherence tomograph (Stratus OCT) to discriminate between eyes with band atrophy (BA) of the optic nerve and healthy eyes. Methods The study included 37 eyes with BA and temporal visual field (VF) defects from chiasmal compression, and 29 normal eyes. Subjects underwent standard automated perimetry (SAP) and retinal nerve fibre layer (RNFL) scans using GDx VCC and Stratus OCT. The severity of the VF defects was evaluated by the temporal mean defect (TMD), calculated as the average of 22 values of the temporal total deviation plot on SAP. Receiver operating characteristic (ROC) curves were calculated. Pearson`s correlation coefficients were used to evaluate the relationship between RNFL thickness parameters and the TMD. Results No significant difference was found between the ROC curves areas (AUCs) for the GDx VCC and Stratus OCT with regard to average RNFL thickness (0.98 and 0.99, respectively) and the superior (0.94; 0.95), inferior (0.96; 0.97), and nasal (0.92; 0.96) quadrants. However, the AUC in the temporal quadrant (0.77) was significantly smaller (P < 0.001) with GDx VCC than with Stratus OCT (0.98). Lower TMD values were associated with smaller RNFL thickness in most parameters from both equipments. Conclusion Adding VCC resulted in improved performance in SLP when evaluating eyes with BA, and both technologies are sensitive in detecting average, superior, inferior, and nasal quadrant RNFL loss. However, GDx VCC still poorly discriminates RNFL loss in the temporal quadrant when compared with Stratus OCT.

Severe Posterior Epistaxis-Endoscopic Surgical Anatomy

Objective: To describe the anatomy of the sphenopalatine foramen (SPF) region and possible anatomical variations. Study Design: Prospective study accomplished from September, 2006, to January, 2007. Methods: The sphenopalatine foramen (SPF) of 61 cadavers were carefully dissected. Presence of the ethmoidal crest, location of sphenopalatine and accessory foramens, and the number of arterial branches emerging through foramens were observed. Data were analyzed in relation to gender, racial group, and symmetry of the cadaver. Prediction of the presence of accessory foramen was evaluated. Results: Mixed race cadavers prevailed in 122 nasal fossae dissected (75% males). Ethmoidal crest was present in 100% of the cadavers, being anterior to the SPF in 98.4% of the cases. The most frequent SPF location was the transition of the middle and superior meatus (86.9%). Mean distance from the SPF and accessory foramen to anterior nasal spine was 6.6 cm and 6.7 cm, respectively. Accessory foramen was present in 9.83% of the cases. A single arterial stem emerged through the SPF in 67.2% of the cases, and 100% through accessory foramens. The prevalence analyses showed no differences that were statistically significant (P > 0.05) between gender and racial group. The symmetry analyses showed a strong conformity (P < 0.01) between nasal fossae in relation to the SPF location. There was no statistically significant conformity between nasal fossae and accessory foramen (P = 0.53). None of the variables of interest presents any statistically significant (P > 0.05) association with the presence of the accessory foramen. Conclusions: There are anatomical variations in the lateral nose wall that should be considered for successful endoscopic surgical treatment of severe epistaxis.

The efficacy of functional endoscopic sinus surgery in the evolution of fever of unknown origin in ICU patients

Conclusion: Functional endoscopic sinus surgery (FESS) was found to be effective in treating fever of unknown origin (FUO) in intensive care unit (ICU) patients with rhinosinusitis, with 62% of patients showing improvement within 5 days of the procedure. Objective: To correlate improvement in FUO with FESS drainage of the paranasal sinuses. Methods: Fifty patients that developed FUO during ICU stay, with CT findings suggestive of rhinosinusitis, and showed no improvement in fever after clinical treatment underwent FESS for drainage of the paranasal sinuses and were evaluated for postoperative improvement of fever. Results: The study sample consisted of 50 patients (74% of whom were male, mean age 48.1 years). The most frequent diagnoses at ICU admission were tetanus, pulmonary disease, and cardiovascular disease. In all, 68% of patients underwent nasogastric or enteral intubation. CT scanning most commonly showed involvement of the sphenoid sinus. In 54% of cases, sinusitis was bilateral and extended throughout the maxillary, ethmoidal, and sphenoidal sinuses. Sinusectomy was performed in all patients, and pathological secretion in the paranasal sinuses was seen in 52% of patients during surgery. Gram-negative bacteria were the most commonly isolated organisms, followed by Gram-positive bacteria and fungi. Improvement of fever was found in 82% of patients after FESS; 38% of these improved within the first 48 h post-procedure, and the remaining 62% within the first 5 postoperative days.

Endoscopic ligation of the anterior ethmoidal artery: a cadaver dissection study

Anterior ethmoidal artery (AEA) ligation may be necessary in cases of severe epistaxis not controllable with traditional therapy. Endoscopic endonasal ligation of the AEA is not used frequently; there are few studies in the literature for standardization of the endoscopic technique for this vessel. Aim: To demonstrate the feasibility of periorbital AEA ligation in a transethmoidal endoscopic approach. Methods: A prospective study where 50 nasal cavities were dissected. After anterior ethmoidectomy and partial removal of lamina papyracea, the periorbital area was carefully dissected along a subperiosteal plane to identify the AEA. The vessel was exposed within the orbit and dissected. Results: Data on technical difficulties, complications, the learning curve and anatomical variations were gathered. Conclusion: An endonasal endoscopic approach to the AEA within the orbit was shown to be feasible. Identifying the artery is not difficult, and this technique avoids external incisions. This approach appears to be an excellent alternative for approaching the AEA. Further clinical studies are needed to demonstarte the benefits of this technique.

Model-Predicted Performance of Second-Trimester Down Syndrome Screening With Sonographic Prenasal Thickness

Objective. The purpose of this study was to estimate the Down syndrome detection and false-positive rates for second-trimester sonographic prenasal thickness (PT) measurement alone and in combination with other markers. Methods. Multivariate log Gaussian modeling was performed using numerical integration. Parameters for the PT distribution, in multiples of the normal gestation-specific median (MoM), were derived from 105 Down syndrome and 1385 unaffected pregnancies scanned at 14 to 27 weeks. The data included a new series of 25 cases and 535 controls combined with 4 previously published series. The means were estimated by the median and the SDs by the 10th to 90th range divided by 2.563. Parameters for other markers were obtained from the literature. Results. A log Gaussian model fitted the distribution of PT values well in Down syndrome and unaffected pregnancies. The distribution parameters were as follows: Down syndrome, mean, 1.334 MoM; log(10) SD, 0.0772; unaffected pregnancies, 0.995 and 0.0752, respectively. The model-predicted detection rates for 1%, 3%, and 5% false-positive rates for PT alone were 35%, 51%, and 60%, respectively. The addition of PT to a 4 serum marker protocol increased detection by 14% to 18% compared with serum alone. The simultaneous sonographic measurement of PT and nasal bone length increased detection by 19% to 26%, and with a third sonographic marker, nuchal skin fold, performance was comparable with first-trimester protocols. Conclusions. Second-trimester screening with sonographic PT and serum markers is predicted to have a high detection rate, and further sonographic markers could perform comparably with first-trimester screening protocols.

Primary ciliary dyskinesia: evaluation using cilia beat frequency assessment via spectral analysis of digital microscopy images

Olm MA, Kogler JE Jr, Macchione M, Shoemark A, Saldiva PH, Rodrigues JC. Primary ciliary dyskinesia: evaluation using cilia beat frequency assessment via spectral analysis of digital microscopy images. J Appl Physiol 111: 295-302, 2011. First published May 5, 2011; doi:10.1152/japplphysiol.00629.2010.-Ciliary beat frequency (CBF) measurements provide valuable information for diagnosing of primary ciliary dyskinesia (PCD). We developed a system for measuring CBF, used it in association with electron microscopy to diagnose PCD, and then analyzed characteristics of PCD patients. 1 The CBF measurement system was based on power spectra measured through digital imaging. Twenty-four patients suspected of having PCD (age 1-19 yr) were selected from a group of 75 children and adolescents with pneumopathies of unknown causes. Ten healthy, nonsmoking volunteers (age >= 17 yr) served as a control group. Nasal brush samples were collected, and CBF and electron microscopy were performed. PCD was diagnosed in 12 patients: 5 had radial spoke defects, 3 showed absent central microtubule pairs with transposition, 2 had outer dynein arm defects, 1 had a shortened outer dynein arm, and 1 had a normal ultrastructure. Previous studies have reported that the most common cilia defects are in the dynein arm. As expected, the mean CBF was higher in the control group (P < 0.001) and patients with normal ultrastructure (P < 0.002), than in those diagnosed with cilia ultrastructural defects (i.e., PCD patients). An obstructive ventilatory pattern was observed in 70% of the PCD patients who underwent pulmonary function tests. All PCD patients presented bronchial wall thickening on chest computed tomography scans. The protocol and diagnostic techniques employed allowed us to diagnose PCD in 16% of patients in this study.