Sergio Hassid

Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants

OBJECTIVE Sudden infant death syndrome has been related to both exposure to prenatal cigarette smoke and impaired arousability from sleep. We evaluated whether healthy infants born to mothers who smoked during pregnancy had higher auditory arousal thresholds than those born to mothers who did not smoke and whether the effects of smoking occurred before birth. STUDY DESIGN Twenty-six newborns were studied with polygraphic recordings for 1 night: 13 were born to mothers who did not smoke, and 13 were born to mothers who smoked (>9 cigarettes per day). Other infants with a median postnatal age of 12 weeks were also studied, 21 born to nonsmoking mothers and 21 born to smoking mothers. White noise of increasing intensity was administered during rapid eye movement sleep to evaluate arousal and awakening thresholds. RESULTS More intense auditory stimuli were needed to induce arousals in newborns (P =.002) and infants (P =. 044) of smokers than in infants of nonsmokers. Behavioral awakening occurred significantly less frequently in the newborns of smokers (P =.002) than of nonsmokers. CONCLUSIONS Newborns and infants born to smoking mothers had higher arousal thresholds to auditory challenges than those born to nonsmoking mothers. The impact of exposure to cigarette smoke occurred before birth.

Galectin-1 Is Overexpressed in Nasal Polyps under Budesonide and Inhibits Eosinophil Migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1–mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.

Extracellular nucleotides regulate CCL20 release from human primary airway epithelial cells, monocytes and monocyte-derived dendritic cells.

Extracellular nucleotides regulate ion transport and mucociliary clearance in human airway epithelial cells (HAECs) via the activation of P2 receptors, especially P2Y2. Therefore, P2Y2 receptor agonists represent potential pharmacotherapeutic agents to treat cystic fibrosis (CF). Nucleotides also modulate inflammatory properties of immune cells like dendritic cells (DCs), which play an important role in mucosal immunity. Using DNA‐microarray experiments, quantitative RT‐PCR and cytokine measurements, we show here that UTP up‐regulated ∼2‐ to 3‐fold the antimicrobial chemokine CCL20 expression and release in primary HAECs cultured on permeable supports at an air–liquid interface (ALI). Both P2Y2 (ATPγS, UTP, INS365) and P2Y6 (UDP, INS48823) agonists increased CCL20 release. UTP‐induced CCL20 release was insensitive to NF‐κB pathway inhibitors but sensitive to inhibitors of ERK1/2 and p38/MAPK pathways. Furthermore, UTP had no effect on interleukin‐(IL)‐8 release and reduced the release of both CCL20 and IL‐8 induced by TNF‐α and LPS. Accordingly, UTP reduced the capacity of basolateral supernatants of HAECs treated with TNF‐α or LPS to induce the chemoattraction of both CD4+ T lymphocytes and neutrophils. In addition, we show that, in monocyte‐derived DCs, ATPγS, and UDP but not UTP/INS365‐stimulated CCL20 release. Likewise, UDP but not ATPγS was also able to increase CCL20 release from monocytes. Pharmacological experiments suggested an involvement of P2Y11 or P2Y6 receptors through NF‐κB, ERK1/2, and p38/MAPK pathways. Altogether, our data demonstrate that nucleotides may modulate chemokine release and leukocyte recruitment in inflamed airways by acting on both epithelial and immune cells. Our results could be relevant for further clinical investigations in CF. J. Cell. Physiol. 211: 716–727, 2007.

Endoscopic treatment for Zenker's diverticulum: long-term results (with video)

BACKGROUND Diverticulotomy is a standard treatment for Zenkers diverticulum (ZD). This technique was adapted to flexible endoscopy. OBJECTIVE We report our long-term results of ZD treatment by using flexible endoscopy assisted by a soft diverticuloscope. DESIGN Follow-up study. SETTING Academic hospital. Tertiary-care referral center. PATIENTS A total of 150 patients with ZD were treated with the same technique from July 2002 to June 2011. INTERVENTION The procedure was performed by using a soft diverticuloscope to expose the septum, which was then cut with a needle-knife, and the procedure was completed by use of endoclip placement at the bottom of the section. MAIN OUTCOME MEASUREMENTS Symptoms were compared before and after the procedure, 1 month later, and at the end of follow-up. RESULTS The median size of the ZD was 3 cm (range 1-8 cm). The endoscopic incision was performed in one session (range 1-3 sessions). Clinical success at 1 month was 90.3%. Four adverse events (2.2%) occurred and were managed conservatively. Symptom evaluation at 1 month and at the end of follow-up was obtained in 103 and 134 patients, respectively. The dysphagia score dropped from 1.88 to 0.29 (P < .01) and 0.34 (P < .05) at 1 month and at the end of follow-up, respectively (median 43 months, range 13-121 months). Regurgitations and chronic cough dropped from 73% and 27% to 11% and 2% at the end of follow-up, respectively. Symptom recurrence occurred in 31 patients (23.1%); among them 23 had a second treatment, and only 5 required a third one. LIMITATIONS Retrospective study, single center. CONCLUSION Endoscopic incision of ZD by using a soft diverticuloscope and completed by endoclips is safe and efficient at short term and long term.

Real-time MRI and articulatory coordination in speech.

This paper describes the real-time MRI technique and its use for the study of speech production. The two major problems, (i) the simultaneous recording of the MR images and the speech signal and (ii) the synchronisation of the images and of the speech signal, are addressed. Measurement accuracy on real-time images is evaluated by comparison with similar measurements on static MR images.

Correlation of Galectin-3/Galectin-3-Binding Sites with low Differentiation Status in Head and Neck Squamous Cell Carcinomas

The accurate determination of levels of differentiation is of prognostic value in human head and neck squamous cell carcinomas (HNSCCs). Because the deliberate selection of biochemical determinants accompanying certain stages of differentiation can refine the predictive power of histochemical assessments, the application of the quantitative evaluation of staining distribution and intensity by computer-assisted microscopy is one prerequisite to potential improvements. We used 2 innovative approaches with peanut agglutinin based on encouraging results with respect to common lectin-histochemistry. First, we used a custom-made neoglycoprotein to monitor the presence of Thomsen-Friedenreich (T) antigen-binding sites. Second, we measured the presence of 2 galectins immunohistochemically and, at the same time, measured lectin-histochemically the presence of accessible ligands for the endogenous lectins. We also monitored the presence of calcyclin, a protein with relevance to cell cycle progression or exocytosis. With 61 cases of HNSCC as their basis, including 31 oral, 20 laryngeal, and 10 hypopharyngeal lesions, the data show that the main modifications observed in connection with a loss of differentiation are related to a modification in the levels of both galectin-3/galectin-3-binding site and T-antigen/T-antigen-binding site expressions. The data obtained also suggest that galectin-3 could act as an acceptor site for the T antigen. Because the level of differentiation is known to be indicative of the recurrence rate in HNSCCs and our data clearly indicate that galectin-3 and the T antigen (and their respective binding sites) are involved in dedifferentiation processes, further investigation is warranted into the roles of galectins in HNSCC tumor progression and recurrence analysis.

Quantitative Glycohistochemistry Defines New Prognostic Markers for Cancers of the Oral Cavity

Histopathologic grading and clinical staging cannot provide a precise prognosis of oral cavity cancer patients. The use of glycohistochemical markers may improve the level of prognostic accuracy of such conventional classification systems.

Determination of the Levels of Expression of Sarcolectin and Calcyclin and of the Percentages of Apoptotic But Not Proliferating Cells to Enable Distinction Between Recurrent and Nonrecurrent Cholesteatomas

Objectives: To investigate in a series of cholesteatomas 1. whether subgroups of cholesteatomas with specific proliferative/apoptotic features exhibit distinct differentiation markers and 2. whether these different subgroups identified at the biological level relate to specific groups of clinically identified cholesteatomas.

Detection of Macrophage Migration Inhibitory Factor (MIF) in Human Cholesteatomas and Functional Implications of Correlations to Recurrence Status and to Expression of Matrix Metalloproteinases-3/9, Retinoic Acid Receptor-β, and Anti-apoptotic Galectin-3†

Objectives To investigate whether the expression of the macrophage migration inhibitory factor (MIF) 1) is detectable, 2) changes in relation to recurrence and infection status, and 3) relates to the levels of expression of growth regulators/differentiation markers, including galectin‐1, ‐3, and ‐8, retinoid acid receptors (RAR)]‐α, ‐β, and ‐γ, binding sites for sarcolectin, and invasion markers (cathepsins ‐B and ‐D, and matrix metalloproteinases [MMP]‐2, ‐3, and ‐9) in human cholesteatomas.

Lobular capillary haemangioma of the nasal cavity during pregnancy

OBJECTIVE We report a pregnant patient with a rapidly growing mass within the nasal cavity, which required pre-operative super-selective embolisation and subsequent removal under general anaesthesia after childbirth. We also discuss the clinical, radiological and histological characteristics of lobular capillary haemangioma, and its treatment. METHOD Case report and literature review. RESULTS Lobular capillary haemangioma is a benign lesion originating in the vascular tissue of skin, mucosa, muscles, glands and bone. These lesions grow rapidly. Nasal localisation is rare. Microtrauma and pregnancy are the most commonly proposed aetiological factors. Reported incidence during pregnancy ranges from less than 2 per cent to approximately 5 per cent. The management of a pregnant woman with such a lesion may be complex, and depends on the severity of symptoms and the status of the pregnancy. Complete surgical excision, with or without pre-operative embolisation, is the treatment of choice. CONCLUSION This uncommon lesion should be considered in any pregnant patient with a mass in the mouth or nasal cavity.