Search

Background: The association of behavioural phenotype assessment with cytogenomic characterisation may provide a better comprehension of genotype–phenotype correlations in syndromes caused by chromosomal abnormalities, such as 18p deletion syndrome. Method: We report on four Brazilian patients with 18p deletion syndrome characterised by cytogenomic techniques and detailed neuropsychological evaluation. Intellectual, adaptive and behavioural characteristics were assessed through the Wechsler's Scales, the Vineland‐II Scale and the Child Behaviour Checklist, respectively. Socio‐economic measures including main caretaker educational level and family income as defined by Brazilian criteria for social class classification were also collected to evaluate a possible contribution of environmental factors in neurocognitive variability. Results: Two out of four patients showed intellectual disability (IQ < 70). Wechsler's scale results suggest that in our sample, interpretation of social situations based on observation of non‐verbal behaviour constitute a cognitive strength while judgement of social rules and language skills associated with word knowledge and verbal fluency may be a cognitive weakness. Concerning adaptive behaviour, motor and socialisation domains showed to better develop than communication and daily living skills on the Vineland‐II Scale. Only one patient presented internalising behavioural problems based on the Child Behaviour Checklist. Our results also suggested that socio‐economic status may contribute to overall patient development. Conclusion: Our results suggest that some 18p deletion syndrome patients may present average intellectual performance and that the segment deletion size and some families' socio‐economic conditions may influence cognitive development. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis ( CRS) can be classified into CRS with nasal polyps ( CRSw NP) and CRS without nasal polyps ( CRSs NP). CRSw NP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS ( ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. Methods This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis ( JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery ( ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. Results We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography ( CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. Conclusion We subdivided CRSw NP in non- ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy. [ABSTRACT FROM AUTHOR]

Many different surgical procedures have been described to alleviate nasal obstruction due to turbinate hypertrophy in patients with allergic rhinitis (AR) who continuously have chronic nasal congestion. The goal of surgical procedures should be ‘optimal reduction of volume and secretion with preservation of function’. For a period of about 25 years, laser surgery of the inferior turbinate has been considered a simple and effective surgical treatment with a low complication rate that has been in widespread use by many ENT surgeons. Various trials have demonstrated the clinical effectiveness of a series of different laser systems including carbon dioxide, Nd:YAG, potassium-titanyl-phosphate, and diode laser. Laser surgery generally induces significant increases of the total volume of the nasal cavity. Several studies have provided evidence that the expression degree of local inflammatory cytokines and chemical mediators can be attenuated by the treatment. The mucociliary function of the inferior turbinate seems to be preserved after CO2 laser intervention. A breakthrough in the surgical procedures available for allergic patients who severely suffer from both intractable hypertrophic inferior turbinates and unregulated nasal secretion was introduced in Japan. Posterior nasal neurectomy is a novel alternative method in which neural bundles are selectively cut or cauterized from the sphenopalatine foramen. Resection of the posterior nasal nerve at this point enables surgeons to inhibit the parasympathetic nerve function of the nasal mucosa with no troublesome complications such as decrease of lacrimal secretion. The procedure simultaneously provides interruption of the somatic afferent innervation to the turbinate mucosa. Herein we assess the clinical effectiveness of this surgical procedure based on objective and measurable monitoring parameters and discuss the underlying therapeutic mechanisms. [ABSTRACT FROM AUTHOR]

Different patterns of β-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome Aims: The cadherin–catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally β-catenin (β-ct) can also take part in signal transduction and nuclear β-ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of β-ct is still uncertain, we investigated the expression pattern of β-ct as well as the possible prognostic role. Methods and results: β-catenin expression was immunohistochemically investigated in a retrospective series of 401 R0-resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous β-ct expression similar to that in normal gastric mucosa. In 80 tumours β-ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous β-ct expression was found. Additionally, in 53 tumours, a strong β-ct expression could be observed in the cytoplasm with a simultaneous nuclear β-ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunoreactivity without cytoplasmic staining. There were no significant correlations between the degree of membranous β-ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E-cadherin, irrespectively of the different β-ct staining pattern. Univariate analysis revealed no influence on survival, either for membranous or for cytoplasmic/nuclear β-ct expression. Conclusion: Our data on 401 tumours suggest that activation of the Wnt/β-catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/nuclear β-ct expression nor the reduction or loss of membranous β-ct expression is correlated with a specific histological tumour type, tumour progression or prognosis. [ABSTRACT FROM AUTHOR]

Background Nitric oxide (NO) is believed to participate in the regulation of airway clearance and non-specific cellular immunity. Recent studies have suggested that airway epithelial cells of allergic and non-allergic individuals may differ in their ability to produce this molecule. Objective The aim of this study was to detect the difference in NO production in human nasal epithelial cells between normal subjects and patients with perennial allergic rhinitis (AR), and to assess the relationship between the expression of nitric oxide synthase (NOS) isoforms and the severity of the disease. Methods Nasal epithelial cells were obtained from the inferior turbinate. The expression of mRNAs encoding constitutive endothelial NOS (eNOS) and inducible NOS (iNOS) was studied by reverse transcription-polymerase chain reaction (RT-PCR). Direct NO production in living cells was visualized and quantified by a fluorescent indicator, DAF-2 DA. Results RT-PCR analysis demonstrated that AR patients with a RAST score of 5 or 6 showed significant increases in the levels of iNOS mRNA and slight reductions in those of eNOS mRNA. Patients with a RAST score of 2–4 also revealed the same tendency however, the difference was not significant. DAF-2 DA imaging demonstrated that epithelial cells, especially the ciliated cells, produced a larger amount of NO than non-epithelial inflammatory cells. Preincubation with L-NAME resulted in an approximate 40% decrease in both groups. Conclusion These results directly indicate that nasal epithelial cells of AR patients overall produce higher levels of NO through the concomitant expression of different NOS isoforms. Continuous NO production by the epithelial cells in normal subjects further support the hypothesis that NO derived from epithelium may play dual roles in the regulation of nasal airway clearance and in the host defense. In addition, the use of DAF-2 DA provides a reliable method to visualize and quantify the direct NO production of living cells. [ABSTRACT FROM AUTHOR]

The article describes a case of severe congestive heart failure and acute gastric mucosal necrosis in a 51-year-old man who complained of vomiting, epigastric pain and hematemesis. Topics discussed include the patient's medical history, a description of the findings of his enhanced computed tomography, and the surgical procedure underwent by the patient for his acute gastric necrosis (AGN).

The following are the abstracts from the autumn meeting held in London, October 1996. [ABSTRACT FROM AUTHOR]

Objectives: To examine the clinical usefulness of transoral ultrasonography (US) in determining the invasion depth of superficial pharyngeal carcinoma (SPC). Determining the invasion depth of SPC is crucial for transoral surgery including determining treatment strategy. This study aimed to examine the usefulness of transoral US in determining the invasion depth of SPC., Methods: Forty-six patients with 51 lesions who underwent both magnifying endoscopy with narrow-band imaging (ME-NBI) and transoral US were included. The primary outcomes were the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of ME-NBI and transoral US findings for pathological tumor depth in SPCs., Results: The accuracy (82.4%), sensitivity (85.2%), PPV (82.1%), and NPV (82.6%) rates of US for subepithelial propria (SEP) were higher than those of ME-NBI and macroscopic classification, indicating that transoral US is superior to ME-NBI in determining the invasion depth. All cases where the SEP was clearly invaded (SEP deep) could be diagnosed as SEP by transoral US., Conclusions: Transoral US may be useful in determining the invasion depth of SPCs., Level of Evidence: 3 Laryngoscope, 133:2192-2197, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The human monoclonal antibody dupilumab blocks interleukin (IL)-4 andIL-13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS-52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS-52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy., Methods: Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund-Mackay score assessed by CT (LMK-CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm., Results: Dupilumab significantly improved NPS, NC, and LMK-CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non-/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK-CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups., Conclusion: Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives/hypothesis: Dupilumab, which blocks the shared receptor component for interleukin-4 and interleukin-13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers., Methods: Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co-primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund-Mackay CT (LMK-CT) scores. Symptoms, sense of smell, health-related quality of life, and safety were assessed during the 52-week treatment period., Results: Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: -3.1, P < .0001; Arm B: -2.1, P = .0011); NC score (Arm A: -1.2, P < .0001; Arm B: -0.9, P < .0001); and LMK-CT (Arm A: -5.1, P = .0005; Arm B: -2.8, P = .0425). The most common treatment-emergent adverse event in dupilumab and placebo-treated patients was nasopharyngitis., Conclusion: Dupilumab provided rapid, significant, and clinically meaningful improvements for patients with CRSwNP in Japan. Dupilumab was well tolerated, and safety and efficacy were consistent with the overall study population., Level of Evidence: 2 Laryngoscope, 131:E1770-E1777, 2021., (© 2020 Sanofi. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

We present clinical and cytogenetic data on a family with a t(4;13)(p16;q11) translocation present in four generations. The balanced translocation resulted in one individual with monosomy 4p and one individual with trisomy 4p, due to 3:1 segregation. The male patient with trisomy 4p was fertile and transmitted the extra chromosome to his daughter., (Copyright 2004 Wiley-Liss, Inc.)

Objectives: A panel of cytokines has been found to be important for eosinophil accumulation and activation in nasal polyps. The aims of this study were to ascertain whether the activation of nuclear factor-kappa B (NF-kappaB) occurred in the polyp epithelium, and to examine the relationship between the degree of activation and local cytokine gene expression., Study Design/methods: Nasal polyp specimens were obtained from 26 untreated patients. The proportion of nuclear translocation of the NF-kappaB p50 subunit in the polyp epithelium was quantitatively analyzed by a combination of fluorescent immunohistochemistry and a laser scanning confocal microscope image system. The levels of GM-CSF, IL-5, IL-8, IL-16, and eotaxin mRNA expression in the same speci-mens were measured using reverse transcription-polymerase chain reaction., Results: Both cytoplasmic and nuclear localization of the p50 subunit was observed mainly in the epithelial layer in all specimens. The percentages of epithelial cells with nuclear translocation ranged from 4.5% to 40.5% (median, 18%). Significant correlations were observed between the degree of epithelial NF-kappaB activation and the levels of IL-8, IL-16, and eotaxin mRNA expression (r = 0.468, 0.47, and 0.739, respectively)., Conclusion: The activation of NF-kappaB in the nasal polyp epithelium is responsible for the recruitment of inflammatory cells, particularly eosinophils, through the initiation of the transcriptional pathway of the related cytokines. The increased NF-kappaB activity in the polyp epithelium may reflect hypersensitivity to unknown stimuli.

Objectives/hypothesis: Laser surgery of the inferior turbinates has become a popular surgical treatment for patients with allergic rhinitis, particularly for those who have persistent nasal obstruction and do not respond well to pharmacological therapy. The aim of this study was to investigate the effects of the laser surgery on local cytokine gene expression at the mucosal surface in relation to the improvement of nasal symptoms., Study Design: A prospective analysis of 25 patients with allergic rhinitis caused by the house dust mite who underwent laser surgery twice with a 1-month interval on an outpatient basis. Fifteen healthy volunteers served as normal control subjects., Methods: Improvement of the nasal symptoms was evaluated on a graded scale. Nasal mucosal cells were obtained by brushing from the inferior turbinate at each visit. The expression of messenger RNA (mRNA) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, RANTES (regulated on activation, normal T-cell expressed and secreted), and eotaxin was semiquantitatively analyzed by reverse transcription-polymerase chain reaction (RT-PCR)., Results: Two months after treatment, the nasal symptom scores significantly decreased from baseline. The decrease was most apparent in nasal obstruction. RT-PCR analysis revealed that a significant decrease in IL-8 and RANTES expression (P < .001 and P = .012, respectively) was observed after successive laser treatment, and the reduction in these cytokines was significantly correlated. On the other hand, mRNA expression of GM-CSF, IL-6, and eotaxin remained unchanged., Conclusions: This study provided evidence that the expression of local inflammatory cytokines can be attenuated in part by CO2 laser treatment, which may be closely related to the clinical effectiveness of this procedure.

The development of human nasal mucosa was studied in 20 fetal heads between 8 and 24 weeks of gestation. Initially the nasal cavity is lined by a single layer of flattened cells, which produces two to three layers of undifferentiated spherical cells. Olfactory epithelium lines the cranial portion of the human fetal nasal cavity at 8 weeks of gestation. Pseudostratified ciliated cuboidal or columnar epithelium appears at 9 weeks of gestation in the nasal cavity and between 14 and 16 weeks of gestation in the primitive ethmoid sinuses and maxillary sinus infundibulum. Goblet cells and glandular acini appear between 12 and 14 weeks of gestation. Initially these goblet cells/glands are found predominantly in the anterior nasal cavity but are more evenly distributed at 24 weeks of gestation. The epithelial development of the nasal septum generally precedes that of the lateral nasal wall. This study documents nasal mucosal maturation and associated anatomic development in the human fetus.

Carboplatin is a second-generation platinum antineoplastic agent. It has biological activity similar to cisplatin and is currently recommended for the treatment of ovarian cancer. In clinical use, carboplatin appears less ototoxic than cisplatin. This paper reports the ototoxic effects of carboplatin, in doses equivalent to the clinical use of the drug, in the chinchilla. Intravenous carboplatin 200 to 400 mg/m2 by bolus injection caused significant ototoxicity in this model as revealed by brainstem evoked responses (ABR audiometry). The cochlear pathology as seen by scanning electron microscopy revealed predominantly inner hair cell (IHC) stereocilia damage. Furthermore, the extent (grade) of the morphological lesions appears to be well correlated with the auditory brainstem response pattern of threshold elevation.

The uncinate process (UP) has become a familiar anatomical landmark to otolaryngologists due to the increasing popularity of functional endoscopic sinus surgery (FESS) in recent years. This study examines the histological and morphological features of UPs removed from a group of patients undergoing FESS operations for chronic sinusitis. The structure of the UP by light microscopy (LM) is reported. A relatively high proportion of goblet cells and seromucous glands was noted. Scanning electron microscopy (SEM) identified four surface cell types on the UP. Furthermore, four categories of surface morphology were noted. The most common appearance was of predominantly ciliated cells. A nonciliated surface ultrastructure is associated with a longer history of sinonasal symptoms and a higher incidence of surgical intervention.