Wilma T. Anselmo-Lima

Gene expression profiling of mantle cell lymphoma cells reveals aberrant expression of genes from the PI3K-AKT, WNT and TGFbeta signalling pathways.

Microarray studies have revealed the differential expression of several genes in mantle cell lymphoma (MCL), but it is unknown which of these differences are dependent on the transformed MCL cell itself or on the tumour microenvironment. To investigate which genes and signalling pathways are aberrantly expressed in MCL cells we used oligonucleotide microarrays to perform gene expression profiling of both purified leukaemic MCL cells and their normal counterparts, the naive B cells. A total of 106 genes were differentially expressed at least threefold in MCL cells compared with naive B cells; 63 upregulated and 43 downregulated. To validate the microarray results in a larger set of samples, we selected 10 differentially expressed genes and quantified their expression by real‐time polymerase chain reaction in peripheral blood of MCL patients (n = 21), purified MCL cells (n = 6) and naive B cells (n = 4), obtaining fully concordant results. A computer‐assisted approach was used to procure specific molecular signalling pathways that were aberrantly expressed in MCL cells. Several genes related to apoptosis and to the PI3K/AKT, WNT and tumour growth factor β signalling pathways were altered in MCL cells when compared with naive B cells. These pathways may play a significant role in the pathogenesis of MCL and deserve further investigation as candidates for new therapeutic targets.

Muscular, functional and orthodontic changes in pre school children with enlarged adenoids and tonsils

INTRODUCTION Hypertrophy of the adenoids and palatine tonsils is the second most frequent cause of upper respiratory obstruction and, consequently, mouth breathing in children. Prolonged mouth breathing leads to muscular and postural alterations which, in turn, cause dentoskeletal changes. OBJECTIVE The aim of this study was to determine muscular, functional and dentoskeletal alterations in children aged 3-6 years. MATERIALS AND METHODS Seventy-three children, including 44 with tonsil hypertrophy and 29 controls, were submitted to otorhinolaryngologic, speech pathologic and orthodontic assessment. RESULTS Otorhinolaryngologic evaluation revealed a higher incidence of nasal obstruction, snoring, mouth breathing, apneas, nocturnal hypersalivation, itchy nose, repeated tonsillitis and bruxism in children with tonsils hypertrophy. Speech pathologic assessment showed a higher incidence of open lip and lower tongue position, and of hypotonia of the upper and lower lips, tongue and buccinator muscle in these children, accompanied by important impairment in mastication and deglutition. Orthodontic evaluation demonstrated a higher incidence of lower mandible position in relation to the cranial base, a reduction in lower posterior facial height, transverse atresia of the palate, and a dolicofacial pattern. CONCLUSION Postural and functional alterations anticipate dentoskeletal changes, except for the facial pattern. Postural alterations and the skeletal pattern seem to play an important role in infant dentofacial growth.

Dentofacial morphology of mouth breathing children

The relationship between dentofacial morphology and respiration has been debated and investigated from various approaches. The aim of this study was to verify the skeletal and dental relationship of mouth and nose breathing children. Thirty-five children, 7 to 10 years of age, were submitted to orthodontic and otorhinolaryngologic evaluations and were separated into 2 groups: 15 nose breathers and 20 mouth breathers. Each subject underwent a cephalometric radiograph analysis. Statistical analysis (Mann-Whitney U test) indicated that changed mode of breathing was associated with 1) maxillo-mandibular retrusion in relation to the cranial base in the mouth breathers; 2) the SNGoGn and NSGn angles were greater in the mouth breathing group; 3) incisor inclination in both jaws and the interincisal angle were not different between groups. There was no statistically significant difference in the maxillary and mandibular molar heights between the nose breathers and mouth breathers.

Cigarette smoke exposure impairs respiratory epithelial ciliogenesis.

Background Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation. Methods Mouse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity. Results CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 μg/mL, yielding >70% nonciliation and shorter cilia compared with control. No statistical difference on transepithelial resistance was evident. Conclusion CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduces the mucociliary clearance apparatus after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke.

High rates of detection of respiratory viruses in tonsillar tissues from children with chronic adenotonsillar disease.

Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.

Cephalometric evaluation of facial pattern and hyoid bone position in children with obstructive sleep apnea syndrome.

OBJECTIVES To assess the development of face and hyoid bone in children with obstructive sleep apnea syndrome (OSAS) through lateral cephalometries. MATERIALS AND METHODS Children aged 7-10 years with mixed dentition and with no previous otorhinolaryngologic, orthodontic or speech therapy treatments were studied. Twenty nasal breathers were compared to 20 mouth breathing children diagnosed as OSAS patients. All children underwent otorhinolaryngologic evaluation and cephalometries; children with OSAS also underwent nocturnal polysomnography in a sleep laboratory. RESULTS Children with OSAS presented increase in total and lower anterior heights of the face when compared to nasal breathers. In addition, children with OSAS presented a significantly more anterior and inferior position of the hyoid bone than nasal breathers. No significant differences in upper, anterior or posterior heights of the face were observed between groups. CONCLUSION The results suggest that there are evident and early changes in facial growth and development among children with OSAS, characterized by increased total and inferior anterior heights of the face, as well as more anterior and inferior position of the hyoid bone.

Middle Turbinate Headache Syndrome

The middle turbinate and nasal septum are innervated by the anterior ethmoidal nerve, a branch of the ophthalmic division of the trigeminal nerve. As reported in the classical work of Wolff (1948), stimulation of these regions causes pain in the medial canthus of the supraorbital region. Periorbital pain due to middle turbinate compression against the septum or the lateral wall of the nose may be due to congestion of the nasal mucosa or to pneumatization of the middle turbinate (concha bullosa). The diagnosis is made by exclusion and requires a high index of suspicion, anterior rhinoscopy, computerized tomography (CT), and confirmation by the lidocaine test. We present five cases of middle turbinate headache syndrome, all with contha bullosa. Four were treated surgically by partial middle turbinectomy and septoplasty more than 1 year ago, with excellent results. One patient refused surgical treatment which was suggested after failure of medical treatment with antihistamines, decongestants, and a topical corticosteroid, and continues to be symptomatic. Despite the small number of cases studied, the authors conclude that the procedure used was effective for the resolution of headache.

Prognosis of acute invasive fungal rhinosinusitis related to underlying disease.

BACKGROUND Acute invasive fungal rhinosinusitis (AIFRS) is a rare disease with high morbidity and mortality rates. The objective of this study was to correlate the initial clinical features of AIFRS to the prognosis after surgery. METHODS Thirty-two patients with AIFRS were evaluated retrospectively. The correlation of underlying disease, fungus isolated, and extent of the disease to the clinical outcome of AIFRS was also evaluated. RESULTS The most common underlying disease was hematological malignancy and aplasia (n=20). Aspergillus (n=13) and Mucoraceae (n=11) were the main fungi found in AIFRS. Mucosal biopsy confirmed fungal invasion to the nasal mucosa in all cases. Computed tomography and endoscopic findings showed a predominance of unilateral disease, with various stages of nasal involvement. All patients underwent surgical debridement and systemic antifungal therapy immediately after diagnosis. Sixteen patients died (50%) due to AIFRS. A poor prognosis was related to the extensiveness of AIFRS and to the underlying disease (patients with aplastic anemia and diabetes had the worst outcomes), but not to the fungus isolated. CONCLUSIONS Early medical and surgical treatment is essential to improve the prognosis of AIFRS patients. A poorer prognosis was associated with underlying disease and extensiveness of AIFRS, but not to the fungus isolated.

Does rapid maxillary expansion increase nasopharyngeal space and improve nasal airway resistance

OBJECTIVE To evaluate the effect of rapid maxillary expansion (RME) on the dimension of the nasopharyngeal space and its relation to nasal airway resistance. METHODS Twenty-five school-age children (from 7 to 10 year-old) with mouth and/or mixed breathing, with mixed dentition and uni- or bilateral posterior crossbite involving the deciduous canines and the first permanent molars, were evaluated. RME was placed and remained during 90 days. Rhinomanometry and orthodontic documentation were performed at four different times, i.e., before (T(1)), immediately after (T(2)), 90 days (T(3)) and 30 months (T(4)) after RME. RESULTS Differences in nasopharyngeal area and in nasal airway resistance were observed only 30 months after RME, and could be explained by facial growth, and not because of the orthodontic procedure. CONCLUSION RME does not influence on nasopharyngeal area or nasal airway resistance in long-term evaluation.

Endoscopic Revision of External Dacryocystorhinostomy

OBJECTIVES: To observe the benefit of endoscopic surgery for the treatment of lacrimal duct obstruction in revisional surgeries after external dacryocystorhinostomy. STUDY DESIGN AND SETTING: Retrospective nonrandomized study. Eleven cases of recurrent lacrimal duct obstruction after external dacryocystorhinostomy were submitted to endoscopic dacryocystorhinostomy. RESULTS: The rate of success after revisional surgery was 90.9%. The major causes of failure of the external approach were the presence of granulation tissue, septal deviations and synechiae near the opening of the fistula, inadequate removal of the bony wall adjuvant the lacrimal sac, technical error in the localization of the lacrimal sac, and excessive perioperative bleeding that impaired the surgical field. CONCLUSION: Endoscopic dacryocystorhinostomy in revisional cases proved to be a safe technique of low morbidity, permitting effective resolution of the lacrimal obstructions. SIGNIFICANCE: Endoscopic surgery allows greater visibility of the lacrimal sac and its neighbor anatomic alterations and leads to better results.