The Detection of Bacteria in the Maxillary Sinus Secretion of Patients With Acute Rhinosinusitis Using an Electronic Nose: A Pilot Study.

OBJECTIVE: Detecting bacteria as a causative pathogen of acute rhinosinusitis (ARS) is a challenging task. Electronic nose technology is a novel method for detecting volatile organic compounds (VOCs) that has also been studied in association with the detection of several diseases. The aim of this pilot study was to analyze maxillary sinus secretion with differential mobility spectrometry (DMS) and to determine whether the secretion demonstrates a different VOC profile when bacteria are present. METHODS: Adult patients with ARS symptoms were examined. Maxillary sinus contents were aspirated for bacterial culture and DMS analysis. k-Nearest neighbor and linear discriminant analysis were used to classify samples as positive or negative, using bacterial cultures as a reference. RESULTS: A total of 26 samples from 15 patients were obtained. After leave-one-out cross-validation, k-nearest neighbor produced accuracy of 85%, sensitivity of 67%, specificity of 94%, positive predictive value of 86%, and negative predictive value of 84%. CONCLUSIONS: The results of this pilot study suggest that bacterial positive and bacterial negative sinus secretion release different VOCs and that DMS has the potential to detect them. However, as the results are based on limited data, further conclusions cannot be made. DMS is a novel method in disease diagnostics and future studies should examine whether the method can detect bacterial ARS by analyzing exhaled air.

Identifying chronic rhinosinusitis without nasal polyps by analyzing aspirated nasal air with an electronic nose based on differential mobility spectrometry.

BACKGROUND: The diagnosis of chronic rhinosinusitis (CRS) is a complicated procedure. An electronic nose (eNose) is a novel method that detects disease from gas-phase mixtures, such as human breath. AIMS/OBJECTIVES: To determine whether an eNose based on differential mobility spectrometry (DMS) can detect chronic rhinosinusitis without nasal polyps (CRSsNP) by analyzing aspirated nasal air. MATERIALS AND METHODS: Adult patients with CRSsNP were examined. The control group consisted of patients with septal deviation. Nasal air was aspirated into a collection bag and analyzed with DMS. The DMS data were classified using regularized linear discriminant analysis (LDA) models with 10-fold cross-validation. RESULTS: The accuracy of the DMS to distinguish CRSsNP from patients with septal deviation was 69%. Sensitivity and specificity were 67 and 70%, respectively. Bonferroni-corrected statistical differences were clearly noted. When a subgroup with more severe inflammatory disease was compared to controls, the classification accuracy increased to 82%. CONCLUSIONS: The results of this feasibility study demonstrate that CRSsNP can potentially be differentiated distinguished from patients with similar nasal symptoms by analyzing the aspirated nasal air using DMS. Further research is warranted to evaluate the ability of this novel method in the differential diagnostics of CRS.

Differentiation of aspirated nasal air from room air using analysis with a differential mobility spectrometry-based electronic nose: a proof-of-concept study.

Over the last few decades, breath analysis using electronic nose (eNose) technology has become a topic of intense research, as it is both non-invasive and painless, and is suitable for point-of-care use. To date, however, only a few studies have examined nasal air. As the air in the oral cavity and the lungs differs from the air in the nasal cavity, it is unknown whether aspirated nasal air could be exploited with eNose technology. Compared to traditional eNoses, differential mobility spectrometry uses an alternating electrical field to discriminate the different molecules of gas mixtures, providing analogous information. This study reports the collection of nasal air by aspiration and the subsequent analysis of the collected air using a differential mobility spectrometer. We collected nasal air from ten volunteers into breath collecting bags and compared them to bags of room air and the air aspirated through the device. Distance and dissimilarity metrics between the sample types were calculated and statistical significance evaluated with Kolmogorov-Smirnov test. After leave-one-day-out cross-validation, a shrinkage linear discriminant classifier was able to correctly classify 100% of the samples. The nasal air differed (p< 0.05) from the other sample types. The results show the feasibility of collecting nasal air by aspiration and subsequent analysis using differential mobility spectrometry, and thus increases the potential of the method to be used in disease detection studies.

In vitro detection of common rhinosinusitis bacteria by the eNose utilising differential mobility spectrometry.

Acute rhinosinusitis (ARS) is a sudden, symptomatic inflammation of the nasal and paranasal mucosa. It is usually caused by respiratory virus infection, but bacteria complicate for a small number of ARS patients. The differential diagnostics between viral and bacterial pathogens is difficult and currently no rapid methodology exists, so antibiotics are overprescribed. The electronic nose (eNose) has shown the ability to detect diseases from gas mixtures. Differential mobility spectrometry (DMS) is a next-generation device that can separate ions based on their different mobility in high and low electric fields. Five common rhinosinusitis bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa) were analysed in vitro with DMS. Classification was done using linear discriminant analysis (LDA) and k-nearest neighbour (KNN). The results were validated using leave-one-out cross-validation and separate train and test sets. With the latter, 77% of the bacteria were classified correctly with LDA. The comparative figure with KNN was 79%. In one train-test set, P. aeruginosa was excluded and the four most common ARS bacteria were analysed with LDA and KNN; the correct classification rate was 83 and 85%, respectively. DMS has shown its potential in detecting rhinosinusitis bacteria in vitro. The applicability of DMS needs to be studied with rhinosinusitis patients.

Retrospective analysis of a combined endoscopic and transcutaneous technique for the management of parotid salivary gland stones.

Sialendoscopy is used in the diagnosis and treatment of various symptoms relating to the salivary gland, e.g. chronic swelling or obstruction and inflammation of the salivary duct. Small intraductal stones can be removed with various instruments during sialendoscopy, whereas larger ones can be fragmented with extracorporeal shockwave lithotripsy or laser. However, 5-10% of the patients with parotid stones cannot be treated with these methods. In patients with large impacted stones or stones in a hilus area, a combined endoscopic and transcutaneous technique can be employed. The stone is approached endoscopically, a skin flap is raised over or a small incision is made through the illuminated area, and the stone is removed by an external route with minimal morbidity. This retrospective study analysed the cases of 8 patients treated using the combined technique, 6 of whom became symptom free. Superficial parotidectomy was performed in 1 patient. No complications were observed, and ductal stents were not used. The average diameter of the stones was 7.6 mm (range 7.0-10.2). The combined technique is recommended for the removal of large and impacted intraductal stones in the parotid gland. No major complications have been reported.

HHV-6-positivity in diseases with demyelination.

BACKGROUND: The triggering agent of multiple sclerosis is still unknown and many viruses, including human herpesvirus-6 (HHV-6), are under suspicion. In earlier study we found patients who had HHV-6 reactive OCBs in their CSF. We wanted to investigate whether HHV-6 has an active role in diseases with demyelination. OBJECTIVE: To analyze the HHV-6-reactive cases in detail and investigate the possible independent role of HHV-6 in the development of central nervous system involvements with demyelination. STUDY DESIGN: We studied serum and CSF samples that were collected over a period of one year, from all patients who had oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and were examined in the Department of Neurology, University Central Hospital of Helsinki, Finland. Clinical evaluation was accomplished blinded of HHV-6 analysis and follow-up time was two years. All patients underwent MRI of the head and clinically indicated CSF analysis. RESULTS: The 17 patients with HHV-6-reactive OCBs were significantly younger and had significantly more IgG-OCBs in comparison to patients without HHV-6-reactive OCBs. Initial diagnoses in patients with HHV-6-reactive OCBs remained the same during the follow-up time. CONCLUSION: Patients with HHV-6-positive OCBs appear to form a separable group. In progressive neurological diseases HHV-6 may have a role in long-term infection with demyelination.

[Combined technique in the removal of parotid gland stones]. / Yhdistelmätekniikka korvasylkirauhasen kivien poistossa.

Sialendoscopy is used in the diagnostics and treatment of salivary gland swelling. Small intraductal stones can be removed with various instruments during sialendoscopy. In cases with larger fixed stones a combined technique can be applied. The stone is approached endoscopically, skin flap is raised or a small incision is made through the illuminated area and the stone is removed via the external route with minimal morbidity. In this series five out of seven patients treated by the combined technique became symptomless. Superficial parotidectomy was performed on one patient. The combined technique is recommended in the removal of stones that are large, fixed in the duct or located in the gland's hilus.

Viruses and multiple sclerosis.

Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents.

Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid.

Demyelinating diseases of the central nervous system (CNS) often include elevated IgG production in intrathecal space presenting as oligoclonal bands (OCBs) in cerebrospinal fluid (CSF). In most demyelinating diseases, e.g. in multiple sclerosis (MS), the underlying cause is not known. We used isoelectric focusing and affinity immunoblot to study the specificity of CSF OCBs to human herpesvirus-6 (HHV-6) in patients with demyelinating diseases of the CNS including MS. Eighty patients with positive OCB finding were included in the study. The OCBs reacted with the HHV-6 antigen in 18 cases (23%). Twelve of 46 MS patients (26%), 5 of 24 other demyelinating diseases (21%) and 1 of 10 other neurological disorders (10%) had HHV-6 specific OCBs in CSF. A specific intrathecal HHV-6 A and B antibody production was shown in a proportion of patients with demyelinating diseases and might suggest a role in the pathogenesis of these diseases.

Tula hantavirus NSs protein accumulates in the perinuclear area in infected and transfected cells.

The small RNA segment of some hantaviruses (family Bunyaviridae) encodes two proteins: the nucleocapsid protein and, in an overlapping reading frame, a non-structural (NSs) protein. The hantavirus NSs protein, like those of orthobunya- and phleboviruses, counteracts host innate immunity. Here, for the first time, the NSs protein of a hantavirus (Tula virus) has been observed in infected cells and shown to localize in the perinuclear area. Transiently expressed NSs protein showed similar localization, although the kinetics was slightly different, suggesting that to reach its proper location in the infected cell, the NSs protein does not have to cooperate with other viral proteins.

Co-localization of human herpes virus 6 and tissue plasminogen activator in multiple sclerosis brain tissue.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of unknown etiology. Several viruses have been suggested as playing a role in the pathogenesis of MS. The aim of this study was to investigate the interrelationship of human herpesvirus 6 (HHV-6) and plasminogen activation at the cellular level in MS plaques. MATERIAL/METHODS: Brain tissue specimens obtained from autopsies of 15 patients with MS and 10 controls were studied immunohistochemically for HHV-6 and cytomegalovirus (CMV) antigen and tissue plasminogen activator (tPA) protein. The presence of Ebstein-Barr virus (EBV) EBER RNA was studied using RNA in situ hybridization. RESULTS: HHV-6 antigen was identified in the cells of 67% (10/15) of MS brain sections and 30% (3/10) of the control sections. All samples were negative for CMV antigen and all samples with intact RNA were negative for EBV EBER RNA as demonstrated by in situ hybridization. tPA expression was found to be increased in MS plaques compared with the control samples. Interestingly, in 5 MS samples both HHV-6 antigen and tPA stained clearly, compared with none in the controls, but HHV-6 and tPA only occasionally co-localized in the same cells. CONCLUSIONS: At the cellular level, HHV-6 and plasminogen activation seem to co-localize in MS.