Secretory carcinoma of the sinonasal cavity and pharynx: A retrospective analysis of four cases and literature review.

Secretory carcinoma (SC) is a recently recognized type of salivary gland tumor characterized by t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. Most SCs are located in a main salivary gland, and primary sinonasal secretary carcinoma is rare. We describe three cases of primary SC in the sinonasal cavity with high-grade transformation (HGT) in one case, and the first case in the pharynx. All tumors comprised slightly atypical cells with solid, tubular, microcystic growth patterns. The case with HGT included two components with distinct sharp boundaries and comedo necrosis, high mitotic figures and obvious cellular atypia. Tumor cells were positive for vimentin, S100, and Gata-3 and negative for p63 and DOG-1. Three cases showed nuclear staining of pan-TRK and one showed cytoplasmic staining. All cases harbored ETV6 gene rearrangement, and ETV6-NTRK3 gene fusion was detected in three cases. Most patients were treated with radical resection and adjuvant therapy. After excision, all remained tumor-free for 65-164 months (medium 98.5 months). SC in the sinonasal cavity and pharynx is a low-grade malignant tumor with histologic features overlapping those of other salivary gland tumors. Immunohistochemical analysis and fluorescence in situ hybridization are useful techniques for its differential diagnosis.

Singlet oxygen generation in aerosol jet and on biological surfaces.

The paper presents steady-state and time-resolved experiments on photophysical processes associated with photodynamic inactivation of infections provided by nebulization of Radachlorin photosensitizer solution. As models of surfaces subjected to photodynamic inactivation we used glass, plant leaf, mushroom cap peel and superficial fascia of chicken and salmon skin flaps. The oxygen content in the photosensitizer solution was varied by blowing with atmospheric air and with pure oxygen. It was shown that singlet oxygen was generated efficiently in the aerosol jet and that its amount increased noticeably at higher oxygen concentrations. The kinetics of photosensitizer photobleaching on different surfaces were found to be significantly different with characteristic decay times varying from seconds for leaf and glass to minutes for fascial flaps. This observation was attributed to much faster oxygen depletion on rough crumbly surfaces of biological samples due to effective oxidation reactions occurred. The singlet oxygen generation and degradation times, and the relative quantum yield were determined on different surfaces by recording time-resolved phosphorescence at about 1270 nm under normoxic and hyperoxic conditions and analyzed on the basis of the set of master equations. The results obtained provide reference marks for choosing optimal irradiation durations for photodynamic inactivation of pathogenic infectious agents (bacteria, mycobacteria, fungi, viruses) on mucous membranes, including the tracheobronchial tree.

A Quality Improvement Project to Minimize COVID-19 Infections in Patients Receiving Haemodialysis and the Role of Routine Surveillance Using Nose and Throat Swabs for SARS-CoV-2 rRT-PCR and Serum Antibody Testing.

BACKGROUND: Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. OBJECTIVE: We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. METHODS: A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. RESULTS: Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, p < 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245-280). CONCLUSIONS: Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.

Application of Hi-throat/Hi-volume SPE technique in assessing organophosphorus pesticides and their degradation products in surface water from Tai Lake, east China.

Organophosphorus pesticides (OPPs) are among the most commonly used pesticides worldwide. However, these compounds pose a serious threat to aquatic environments. Here, thirty-seven pesticides and eight degradation products were determined in surface water samples from Tai Lake, East China, using a high-volume solid phase extraction technique (Hi-throat/Hi-volume SPE). Surface water was pumped in-situ through a portable sampler, and OPPs in the water retained on the Hi-volume SPE adsorption column, finally extracted for analysis. This technique efficiently reduced the detection limits to below 0.3 ng/L. In total, 40 out of 45 OPP congeners were detected, which far exceeded the amount of OPPs in previous studies. The total concentration of OPPs ranged between 101.4 and 1530 ng/L (median: 378.9 ng/L). Parathion exhibited the highest concentration (median: 112.0 ng/L), followed by paraoxon-methyl (median: 90.3 ng/L), as well as carbophenothion, fenthion, and mevinphos. Agricultural areas were more polluted than residential and industrial regions. However, degradation products persisted in residential and industrial waters. The ecological risks of OPPs in these areas were estimated based on the risk quotient index (RQ). Parathion, fenthion, carbophenothion, and tolclofos-methyl occurred at high-risk levels, and the levels of degradation products were also non-trivial. Our findings thus indicated that OPP degradation products pose a potential threat to natural environments and should therefore be closely monitored.

Application of Hi-throat/Hi-volume SPE technique in analyzing occurrence, influencing factors and human health risk of organophosphate esters (OPEs) in drinking water of China.

Organophosphate esters (OPEs) are typical industrial additives widely applied in various industrial and household products, but they may pollute drinking water. In the present study, the occurrence of OPEs in drinking water was analyzed. For this purpose, 25 drinking water samples were collected from households in 25 cities in China. The concentrations of OPEs were accurately determined according to a high-throughput organic analysis testing combined with high-volume solid phase extraction (Hi-throat/Hi-volume SPE) technique. Through this technique, nine OPEs were detected, with spiked recoveries from 77% to 101%, and their total concentrations (ΣOPEs) ranging from 46.8 to 251 (average 126) ng L-1. The detection frequencies of the selected OPEs determined via Hi-throat/Hi-volume SPE were 88.0%-100%, which are much higher than those previously reported. The limit of detections of the OPEs was low at < 0.01 ng L-1, which could be mainly attributed to the high volume of accumulated drinking water (>20 L). OPEs in drinking water presented a decreasing trend from cities in coastal provinces to inland cities of China. Redundancy analysis showed that the concentrations of OPEs in drinking water were significantly influenced by economic-demographic influencing factors. The non-carcinogenic and lifetime carcinogenic risks (non-CR and CR) of the analyzed OPEs in drinking water were negligible for urban residents in China.

Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial.

BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.

Negative viral nucleic acid test of induced sputum: an additional criteria for COVID-19 patient's discharge.

OBJECTIVE: Concerns have been raised that patients with Coronavirus Disease 2019 (COVID-19) are still infectious with a re-positive nucleic acid test of the pharyngeal swab after hospital discharge. The aim of this study was to investigate the clinical relevance of induced sputum as an additional indicator for the current clinical discharge criteria of COVID-19 patients to prevent virus recurrence. PATIENTS AND METHODS: Twenty-one COVID-19 patients who met the national clinical discharge criteria were discharged from the hospital and tested daily for the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleic acid in their pharyngeal swabs and every other day for the presence of SARS-CoV-2 in their induced sputum. Once the patient's induced sputum was negative after two consecutive tests, testing was discontinued. RESULTS: Among 21 discharged patients from COVID-19, the first pharyngeal swab and induced sputum tests for viral nucleic acid were positive in 3 (14.3%) and 8 (38.1%) patients respectively. Induced sputum was significantly more positive than pharyngeal swab (p < 0.05). In our cohort, all pharyngeal swabs became negative at day 7, and all induced sputa turned negative at day 11 after discharge. Interestingly, patients with negative pharyngeal swabs experienced viral relapse, whereas patients with negative induced sputum did not revert to positivity. CONCLUSIONS: The detection rate of positive viral nucleic acid in induced sputum was high. Patients with negative induced sputum nucleic acid tests did not have a relapse of SARS-COV-2, indicating that viral nucleic acid testing of induced sputum should be used as an additional criterion for patients with national clinical discharge criteria COVID-19.

Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min.

The outbreak of SARS-CoV-2 is posing serious global public health problems. Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide.

Histochemical detection of free thiols in glandular cells and tissues of different marine Polychaeta.

Either through differentiated glands or specialised individual cells, the coating epithelia of soft-bodied marine invertebrates are responsible for the secretion of a broad span of peptidic substances, from protective mucins to biocides. These secretions are characterised by the presence of cysteine-rich proteins and peptides, rendering a distinct histochemical signature of secretory epithelia. Through a histochemical procedure for fluorescence microscopy in paraffin sections, we performed a comparative assessment of the distribution of thiol-rich compounds in multiple epithelia of different species of intertidal Polychaeta, which revealed distinctive patterns of distribution that closely relate to ecology, morphoanatomy and physiology. The presence of free thiols was notorious in mucocytes and enzyme-plus toxin-secreting cells. Consequently, strong signals were recorded in the mucocytes of the parapodia of Nereis splendida, the epidermis and pharynx epithelium of Mysta picta and the venom glands of Glycera alba. The findings show an investment in mucus secretion in foragers such as Nereis and Mysta, especially the latter, which is not a native burrower, as a protective response and as lubricant for locomotion. Additionally, nereidids are believed to secret integumentary toxins for defence. On the other hand, Glycera is an ambush predatorial burrower whose behaviour entirely revolves around the delivery of venom making use of its four jaws. The results showed that the detection of thiol-rich compounds in histological sections can be a tool to identify potential toxin secretion and delivery structures, with important consequences for the bioprospecting of novel bioreactives from marine invertebrates for the purpose of drug discovery.

Validation of an analytical method to quantify the permeation and penetration of flurbiprofen into human pharynx tissue.

The aim of this investigation was to develop receiver and extraction fluids, and subsequently validate an analytical method to quantify the permeation and penetration of flurbiprofen into human pharynx tissue using a Franz diffusion cell. The solubility and stability of flurbiprofen in a suitable receiver fluid, and a suitable extraction method and fluid to recover and quantitate flurbiprofen from human pharynx tissue, were investigated using high-performance liquid chromatography (HPLC). The potential interference of human pharynx tissue in the receiver fluid was also investigated. The HPLC analytical method was successfully validated according to current guidelines. The final receiver fluid demonstrated sufficient solubility and stability, and the extraction method and fluid resulted in >95% recovery of flurbiprofen following exposure to human pharynx tissue. The lower limit of quantitation of flurbiprofen was 0.045 µg/mL in both the receiver and extraction fluids. There was no interference of the human pharynx tissue with the HPLC method. This investigation validated an analytical method for quantitating flurbiprofen, and determined a suitable receiver fluid and extraction method and fluid, which can be used to investigate the permeation and penetration of flurbiprofen through human pharynx tissue using the Franz diffusion cell method.

Structural model, functional modulation by ivermectin and tissue localization of Haemonchus contortus P-glycoprotein-13.

Haemonchus contortus, one of the most economically important parasites of small ruminants, has become resistant to the anthelmintic ivermectin. Deciphering the role of P-glycoproteins in ivermectin resistance is desirable for understanding and overcoming this resistance. In the model nematode, Caenorhabditis elegans, P-glycoprotein-13 is expressed in the amphids, important neuronal structures for ivermectin activity. We have focused on its ortholog in the parasite, Hco-Pgp-13. A 3D model of Hco-Pgp-13, presenting an open inward-facing conformation, has been constructed by homology with the Cel-Pgp-1 crystal structure. In silico docking calculations predicted high affinity binding of ivermectin and actinomycin D to the inner chamber of the protein. Following in vitro expression, we showed that ivermectin and actinomycin D modulated Hco-Pgp-13 ATPase activity with high affinity. Finally, we found in vivo Hco-Pgp-13 localization in epithelial, pharyngeal and neuronal tissues. Taken together, these data suggest a role for Hco-Pgp-13 in ivermectin transport, which could contribute to anthelmintic resistance.

[Ryan index for detection of laryngopharyngeal reflux diseases].

Objective: To explore the utility of pharyngeal pH monitoring which positive standard is Ryan index in diagnosis of laryngopharyngeal reflux disease. Methods: In a retrospective study, clinical data of 590 patients who had symptoms laryngopharyngeal reflux disease from February 2016 to March 2017 were analyzed. All patients were received electronic laryngoscopy, assessment of reflux symptom index(RSI) and reflux finding score(RFS), and pharyngeal pH monitoring. SPSS 19.0 software was used to analyze the date. Results: There were 94 patients whose Ryan index were positive(15.93%). Among the 94 patients, 70 were positive during upright, 12 during supine and 12 during both upright and supine. There were 40 patients(6.78%)with pH decline events related to symptoms, while those Ryan index were normal. There were 536(90.85%), 417(70.68%), 233(39.49%) and 117(19.83%) patients with pH<6.5, pH<6.0, pH<5.5 and pH<5.0 events respectively. The positive rate of RSI, RFS, RSI and RFS, RSI or RFS were 44.24%, 16.78%, 7.12%, 53.90% respectively. The RFS score in Ryan index positive group was higher than that in Ryan index negative group[(8.2±2.4) vs (4.0±2.9), u=5.424, P<0.05], while the RSI score in Ryan index positive group was not statistically different from that in Ryan index negative group[(11.3±6.2) vs (12.7±5.8), t=1.247, P=0.167]. Conclusions: Pharyngeal pH monitoring is an objective and non-invasive method which can reflect laryngopharyngeal reflux directly. However, with the Ryan index as a criterion for the diagnosis of laryngopharyngeal reflux disease, partial patients may be missed. Further studies are needed to obtain more accurate and objective laryngopharyngeal pH statistical index for diagnosis of laryngopharyngeal reflux disease.

Analyzing the Area Under the Curve of Pharyngeal pH Probes in the Diagnosis of Reflux Disease.

OBJECTIVES: To analyze the area under the curve (AUC) from 24-hour pharyngeal pH probes and evaluate this parameter as a predictor of disease severity for laryngopharyngeal reflux. METHODS: Eighty patients met inclusion criteria of a completed 24-hour pharyngeal pH probe and Reflux Symptom Index (RSI) questionnaire. The AUC was calculated below a pH threshold of 5.5 using the trapezoidal rule. The RSI and RYAN scores were correlated with AUC values, and nonparametric tests were used for comparisons. RESULTS: The median AUC value was 18 007 pH-seconds with an interquartile range (IQR) of 63 156, the median RSI score was 21 (IQR = 16), and the median RYAN score was 15.3 (IQR = 78). There was a Spearman's correlation of .36 between the RSI scores and AUC values ( P = .001) and a moderate correlation between AUC values and RYAN scores (0.58, P < .001). An insignificant correlation of .19 between RYAN scores and RSI scores was observed ( P = .09). CONCLUSIONS: The AUC may be a useful objective value in establishing the diagnosis of laryngopharyngeal reflux. Prospective studies with larger patient populations are necessary to validate these findings and determine standardized thresholds for symptomatic patients.

Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas.

IMPORTANCE: The prognostic significance of p16 in squamous cell carcinoma (SCC) of the hypopharynx (HP) and nasopharynx (NP) and relationship between human papillomavirus (HPV) and p16 is unclear. OBJECTIVES: To evaluate the prognostic significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and assess the relationship between HPV and p16 in the HP and NP. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of 172 patients with SCC of the pharynx treated with definitive radiation therapy from 2002 to 2013 at a university tertiary referral center, with tissue available for immunohistochemical analysis. The median follow-up was 30.1 months. INTERVENTIONS: A total of 118 patients were treated with chemoradiation, and 54 patients were treated with radiation alone. Immunohistochemical analysis for p16 was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using in situ hybridization, and NP tumors were tested for Epstein-Barr virus. MAIN OUTCOMES AND MEASURES: Overall survival, locoregional control, and disease-free survival were analyzed according to p16, HPV, and Epstein-Barr virus status. RESULTS: Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16 Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14% in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and NP tumors. p16 Status was a significant predictor of all clinical outcomes for patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes. CONCLUSIONS AND RELEVANCE: p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ hybridization when p16 positive.

A huge nodular fasciitis in parapharygneal space in a 7-year-old girl: a case report and review of literature.

Nodular fasciitis (NF) is a benign and reactive fibroblastic growth extending from the superficial fascia into the subcutaneous tissue or muscle, with a morbidity of less than 20% in children. We report a case of a 7-year-old girl presented with a 3-month history of snore and mouth breathing. Image findings demonstrated a large soft-tissue mass in the right parapharyngeal space. The lesion was successfully eradicated by surgical removal. Pathological analysis established NF as the final diagnosis. Histopathological findings were notable for a reactive spindle-cell process composed of proliferative fibroblasts with extravasated red blood cells and interstitial edema. Immunohistochemical stains showed that the lesional cells were positive for smooth muscle actin (SMA), muscle-specific actin (HHF35), and epithelial membrane antigen (EMA), and negative for S100 protein. No clinical evidence of recurrence was noticed after 2 months of follow-up. Being the first report of NF in the parapharyngeal space of a child, this rare pediatric case points out the importance for otolaryngologists to keep NF in mind for differential diagnosis to avoid unnecessary wide resection.

Mapping the pharyngeal and intestinal pH of Caenorhabditis elegans and real-time luminal pH oscillations using extended dynamic range pH-sensitive nanosensors.

Extended dynamic range pH-sensitive ratiometric nanosensors, capable of accurately mapping the full physiological pH range, have been developed and used to characterize the pH of the pharyngeal and intestinal lumen of Caenorhabditis elegans in real-time. Nanosensors, 40 nm in diameter, were prepared by conjugating pH-sensitive fluorophores, carboxyfluorescein (FAM) and Oregon Green (OG) in a 1:1 ratio, and a reference fluorophore, 5-(and-6)-carboxytetramethylrhodamine (TAMRA) to an inert polyacrylamide matrix. Accurate ratiometric pH measurements were calculated through determination of the fluorescence ratio between the pH-sensitive and reference fluorophores. Nanosensors were calibrated with an automated image analysis system and validated to demonstrate a pH measurement resolution of ±0.17 pH units. The motility of C. elegans populations, as an indicator for viability, showed nematodes treated with nanosensors, for concentrations ranging from 50.00 to 3.13 mg/mL, were not statistically different to nematodes not challenged with nanosensors up to a period of 4 days (p < 0.05). The nanosensors were also found to remain in the C. elegans lumen >24 h after nanosensor challenge was removed. The pH of viable C. elegans lumen was found to range from 5.96 ± 0.31 in the anterior pharynx to 3.59 ± 0.09 in the posterior intestine. The pharyngeal pumping rate, which dictates the transfer of ingested material from the pharynx to the intestine, was found to be temperature dependent. Imaging C. elegans at 4 °C reduced the pharyngeal pumping rate to 7 contractions/min and enabled the reconstruction of rhythmic pH oscillations in the intestinal lumen in real-time with fluorescence microscopy.

Normal values of pharyngeal and esophageal 24-hour pH impedance in individuals on and off therapy and interobserver reproducibility.

BACKGROUND & AIMS: Combined pH and impedance monitoring can detect all types of reflux episodes within the esophageal lumen and the pharynx. We performed a multicenter study to establish normal values of pharyngeal and esophageal pH-impedance monitoring in individuals on and off therapy and to determine the interobserver reproducibility of this technique. METHODS: We collected ambulatory 24-hour pH-impedance recordings from 46 healthy subjects by using a bifurcated probe that allowed for detection of reflux events in the distal and proximal esophagus and pharynx. Data were collected when subjects had not received any medicine (off therapy) and after receiving 40 mg esomeprazole twice daily for 14 days (on therapy). The interobserver agreement for the detection of reflux events was determined in 20 subjects off and on therapy. Results were expressed as median (interquartile range). RESULTS: Off therapy, subjects had a median of 32 reflux events (17-45) in the distal esophagus and 3 (1-6) in the proximal esophagus; they had none in the pharynx. On therapy, subjects had a median number of 21 reflux events (6-37) in the distal esophagus and 2 (0-5) in the proximal esophagus; again, there were none in the pharynx. Interobserver agreement was good for esophageal reflux events but poor for pharyngeal events. CONCLUSIONS: We determined normal values of pharyngeal and gastroesophageal reflux events by 24-hour pH-impedance monitoring of subjects receiving or not receiving esomeprazole therapy. Analyses of esophageal events were reproducible, but analyses of pharyngeal events were not; this limitation should be taken into account in further studies.

Expression of different carbohydrate tumour markers and galectins 1 and 3 in normal squamous and malignant epithelia of the upper aaerodigestive tract.

AIM: Tumour markers hold a great relevance in the diagnosis and the follow-up treatment of different kinds of human carcinoma. Although head and neck cancer occurs frequently, there is still lack of appropriate tumour markers. Our investigation on the expression of sialyl Lewis A (CA19-9) in laryngeal carcinomas, consists of systematical analysis of oncofetal carbohydrates and of galectins 1 and 3 in different normal and malignant tissues of the aerodigestive tract. MATERIALS AND METHODS: Paraffin-embedded sections of normal tongue, vocal cord, larynx, pharynx and epiglottis, representing normal control tissue and laryngeal cancer tissue were incubated with monoclonal antibodies against sialyl Lewis A and X (sLeA and X), Lewis Y (LeY), the Thomsen-Friedenreich (TF) antigen and galectin 1 and 3 (Gal-1 and -3). A staining reaction was carried out with ABC-peroxidase and diaminobenzidine (DAB). Tissue of breast cancer was used as a positive control. Mouse IgM, as isotype control antibody, was used as a negative control. Semi quantitative evaluation was carried out double-blinded, by two independent investigators, including a pathologist. RESULTS: Squamous epithelia of all investigated normal tissues of the aerodigestive tract show nearly the same pattern. Most impressive findings are the very weak expression of Gal-1 and the total absence of the TF antigen. Laryngeal cancer reveals high amounts of sLeA, Gal-1 and the TF antigen. CONCLUSION: On the basis of our findings in normal tissue of the aeradigestive tract, these three markers qualified as potential tumour markers for carcinoma of the aerodigestive tract. In particular, the high expression of TF in cancer tissue and its absence from the normal tissue is promising for its establishment as a new tumour marker in this field.

Individuals infected with JC polyomavirus do not present detectable JC virus DNA in oropharyngeal fluids.

JC virus (JCV) is ubiquitous in the human population. Primary infection normally occurs during childhood and is followed by a lifelong persistent infection. The main mode of transmission remains unknown. Several authors have hypothesized that JCV transmission occurs through the respiratory route, and that respiratory secretions could represent a possible source of viral particles. The present study intended to evaluate oropharyngeal fluids from patients infected with JCV, in order to ascertain if respiratory secretions could indeed constitute a source of exposure to this polyomavirus. Oropharyngeal washing samples from 25 patients co-infected with JCV and human immunodeficiency virus type 1 were evaluated for the presence of JCV DNA. Regardless of the titre of antibodies or the presence of viral urinary excretion, JCV genome was not detected in oropharyngeal samples collected from any of the patients infected with JCV included in this study, which may suggest that oropharyngeal fluids are an unlikely source for JCV infection.

Numerical simulation of in-vitro dispersion and deposition of nanoparticles in dry-powder-inhaler aerosols.

Aerosol dispersion and deposition inside an idealized mouth-throat has been numerically simulated using a stochastic Lagrangian model accounting for Brownian motion and particle-wall interaction. Delivery of nanoparticles to the lungs is extremely difficult, mainly due to their low inertia, and for this reason they are often loaded into larger carrier particles. Bearing in mind the potentialities of nanoparticles in advanced drug delivery, a set of monodisperse particles with diameters in the nanqsize range, as well as in the respirable and carrier ranges, were considered in the present simulations. Deposition patterns were obtained by tracking a total of 16,000 particles for each diameter. The results have shown that similar patterns were obtained in the mouth-throat for 400 nm particles and larger. A clear correspondence between secondary flow structures in the fluid and these deposition patterns was observed, demonstrating the role of the convective transport processes for this size range. In contrast, a much more uniform distribution of the particles adhering to the walls was noted for a size of 200 nm. It was also found that a very large amount of these particles (nearly 80%) is lost by deposition on the mouth-throat, thus recommending the use of larger carrier particles.