Human Papillomavirus (HPV) – Structure,epidemiology and pathogenesis

The number of cancers is constantly increasing. An important role in the etiology of many of them is played by the viral factor, by oncogenic viruses, such as the Human Papillomavirus. The article shows current epidemiological situation and describes the structure of the virus and modes of transmission. It also explains the role of HPV infection in cancer with particular emphasis on oropharynx and head and neck cancer.     

Influence of Human Leukocyte Antigen in the Pathogenesis of Me´nie`re's Disease in the South Korean Population

In order to study the associations of Ménière's disease (MD) with human leukocyte antigen (HLA) alleles in the South Korean population, we examined the distribution of HLA class I and II alleles in 39 MD patients and 199 healthy controls. The frequencies of HLA-Cw*0303 (relative risk (RR) = 2.5; p < 0.02) and -Cw*0602 (RR = 3.7; p < 0.03) were significantly increased in patients with MD compared to controls. However, HLA-B44 (RR = 0.2, p < 0.004) and -Cw*0102 (RR = 0.3; p < 0.03) were significantly decreased in patients compared to controls. When the association between hearing level and the presence of HLA alleles was evaluated, the frequencies of HLA-B13 (RR = 7.4; p < 0.004), -B39 (RR = 45.7; p < 0.003), -Cw*0303 (RR = 4.5; p < 0.02) and -Cw*0602 (RR = 6.5; p < 0.02) were significantly increased and those of -B44 (RR = 0.1; p < 0.02) and -Cw*0102 (RR = 0.1; p < 0.03) were significantly decreased in MD patients with hearing losses (stages II-IV) compared to controls. The frequency of HLA-B13 was significantly higher in MD patients with hearing loss (stages II-IV) than in those with normal hearing (stage I). In terms of HLA-DRB1, -DQA1 and -DQB1 allele frequencies, a significantly higher frequency of DRB1*15 was seen in the patients (RR = 2.4; p < 0.03). These results suggest that some HLA alleles may be a useful genetic marker for predicting prognosis in South Korean patients with MD.     

Human leukocyte antigen-A, -B, -C and -DR alleles and soluble human leukocyte antigen class I serum level in Ménière's disease

Previous studies have suggested that many human leukocyte antigen (HLA)-A, -B, -C and -DR alleles are associated with Ménière's disease (MD), an inner ear disorder with a proposed autoimmune etiopathogenesis. Despite some discrepancies many reports are in agreement with a hypothesis suggesting an influence of serologically detected HLA-C products in the susceptibility to the disease. To confirm these data we investigated the distribution of HLA-A, -B, -C and -DR antigens that well define the HLA polymorphism using DNA typing. Furthermore, as autoimmune factors have been claimed to play a role in MD, we investigated the serum level of soluble HLA class I (sHLA-I). Molecular typing of HLA class I and II was performed using polymerase chain reaction sequence-specific primers in 41 patients affected by MD, 34 patients affected by other inner ear diseases (OIDs) and 101 healthy subjects. An ELISA technique was employed to investigate the serum level of sHLA-I in 17 MD patients, 10 OID patients and 83 healthy subjects. The results showed a significantly increased frequency of the Cw*07 specificities in MD patients when compared to OID patients (63.4% vs 32.3%; p = 6.9 x 10(-3); relative risk [RR] = 3.6) and healthy subjects (63.4% vs 35.6%; p = 2.28 x 10(-3); RR = 3.1). The sHLA-I concentrations detected in sera did not differ significantly between MD patients (616 +/- 271 ng/ml), OID patients (570 +/- 307 ng/ml) and healthy subjects (518 +/- 340 ng/ml).     

Expression of Human ß-defensin 1 mRNA in Human Nasal Mucosa

The vestibulo-ocular reflex (VOR) allows clear vision during head movements by generating compensatory eye movements. Its response is reduced following damage to the vestibular endorgan, but recovers over time. The VOR is mediated by both direct and indirect anatomical pathways; most direct pathways include only two central synapses, both located in the brainstem. To investigate the possibility that a direct pathway is modified during the recovery of VOR gain, we measured the oculomotor response to single current pulses delivered to the vestibular labyrinth of two alert cats after plugging the contralateral horizontal canal. The response was also measured after motor learning induced by continuously worn lenses (optically induced motor learning) in two cats. The gain of the VOR was monitored concurrently. The eye movement evoked by a current pulse increased more than 100% during recovery from a plug. The electrically evoked eye movement did not change during optically induced motor learning either before the plug or after recovery. The gain of the VOR was modified in both situations. We conclude that direct VOR pathways are modified significantly during recovery after a plug, but not during optically induced learning. Our results suggest that significant modification of direct pathways may require a change in vestibular sensory input.     

Clinical Significance of β-Tricalcium Phosphate and Polyphosphate for Mastoid Cavity Obliteration during Middle Ear Surgery: Human and Animal Study

Objectives

Mastoid obliteration is used to obliterate the mastoid cavity following a mastoidectomy or to prevent the formation of a retraction pocket. This study evaluated the effectiveness of β-tricalcium phosphate and polyphosphate (β-TPP) for mastoid obliteration in middle ear surgeries in prospective human and animal studies.

Methods

Twenty patients with chronic otitis media underwent mastoid obliteration using β-TPP after a intact canal wall mastoidectomy or simple mastoidectomy. The clinical data were prospectively evaluated including: the diagnosis, temporal bone computed tomography (TBCT), otoscopic findings, pure tone audiogram, and complications. In the animal experiment, β-TPP was applied into the right bulla in five rats, and the opposite bulla was used as the control in the non-obliterated state. The skulls of five other rats were drilled out and the holes were obliterated with β-TPP. TBCT were obtained at 3, 6, and 9 months after the obliteration and histologic analysis was done at 3 and 9 months after surgery.

Results

In the human study, fourteen TBCTs were obtained at 12 months after the surgery. All demonstrated no bone resorption in the obliterated mastoids. Among the 15 cases displaying retracted tympanic membranes preoperatively, 11 showed no retraction, 2 showed retraction postoperatively, 1 was lost to follow-up and 1 was a case of postoperative wound infection. Among 20 cases, one case developed a postoperative infection that necessitated a second operation. Sixteen underwent ossiculoplasty; hearing improvements were obtained in 15 cases and 1 case showed decreased hearing. In the animal study, new bone formation without significant bone resorption in the radiologic and histologic findings were noted in both the skull and bulla groups.

Conclusion

Although β-TPP is a foreign material having the possibility of infection, mastoid obliteration with it can be a treatment option in middle ear surgeries to prevent retraction pockets or the recurrence of diseases.     

Meniere’s,migraine, and motion sickness

Conclusion: Elevated Motion Sickness Susceptibility (MSS) in Meniere?s disease (MD) is likely to be a consequence of the onset of MD and not migraine per se.

Objectives: Pathologies of the vestibular system influence MSS. Bilateral vestibular deficits lower MSS, vestibular neuritis or benign paroxysmal positional vertigo have little overall effect, whereas vestibular migraine elevates MSS. However, less is known about MSS in MD, a condition in which many patients experience vestibular loss and migraine symptoms.

Methods: The authors conducted an online survey that posed diagnostic and disease questions before addressing frequency of headaches, migraines, visual display dizziness (VDD), syncope, social life, and work impact of dizziness (SWID4) and motion sickness susceptibility (MSSQ). The two groups were: diagnosed MD individuals with hearing loss (n?=?751) and non-MD individuals in the control group (n?=?400).

Results: The MD group showed significantly elevated MSS, more headache and migraine, increased VDD, higher SWID4 scores, and increased syncope. MSS was higher in MD than controls only after the development of MD, but not before, nor in childhood. Although elevated in MD compared with controls, MSS was lower than migraine patients from past data. Multivariate analysis revealed VDD, SWID4, and MSS in adulthood as the strongest predictors of MD, but not headache nor migraine.     

Interleukin 5, IL6, IL12, IFN-γ, RANTES and Fractalkine in human nasal polyps, turbinate mucosa and serum

Polyps are considered to develop as an end result of an inflammatory process. Cytokines and chemokines in the respiratory mucosa may be a key to polyp pathophysiology. The main objective was to identify IL-5, IL-6, IL-12, RANTES, IFN- and Fractalkine in humans on the protein level in nasal polyps and mucosa from the inferior turbinate (IT). Furthermore, the cytokines and chemokines RANTES and Fractalkine were analyzed in plasma. Tissue homogenates and plasma from 13 patients were analyzed by the ELISA technique. All the patients had longstanding nasal/paranasal polyposis. Fractalkine was detected in polyps and IT in two different patients. IL-5 was expressed in polyps and IT. IL-6 was expressed in all patients with a higher level in polyps than IT. IL-12 was present in plasma, polyps and IT, though at an increased level in polyps. RANTES was present at a higher level in plasma than in polyps and IT. IFN- was detectable in polyps and IT. Fractalkine is detected in nasal polyps, which is a new observation. The overall results indicate a mixed T_H1/T_H2 cytokine profile in nasal polyps. RANTES and IL-12 are strongly present in plasma, suggesting an ongoing inflammatory drive. IL-6 and IL-12 are up-regulated in polyps versus the IT. Up-regulation of IL-6 may be explained by increased fibroblast activity dependant on an ongoing local inflammation possibly initiated by an infection. IL-5, RANTES and IFN- are equally represented in polyps and IT, indicating equilibrium between the nasal polyps and surrounding tissue, and that an up-regulation of cytokines in the polyp indicates a potential for polyp growth.     

Olfactory Neuroblastoma: Past,Present, and Future?

OBJECTIVE: To consider the long-term survival and outcomes in patients with olfactory neuroblastoma undergoing craniofacial resection. STUDY DESIGN: A single-center prospective cohort study. METHODS: All patients with olfactory neuroblastoma treated in a 23-year period with craniofacial resection (with or without radiotherapy) were analyzed; a multivariate analysis was included. RESULTS: Forty-two patients aged 12 to 70 years were assessed, 83% of whom had received no preceding treatment. Craniofacial resection was used in all cases, combined with radiotherapy in 24 patients (57%). Duration of follow-up ranged from 2 to 206 months (mean follow-up period, 57 mo). The disease-free actuarial survival and overall survival were 77% and 61% at 5 years and 53% and 42% at 10 years, respectively. A Cox regression analysis identified intracranial extension and orbital involvement as independent factors affecting outcome. CONCLUSION: Craniofacial resection combined with radiotherapy offers the gold standard of care against which other approaches such as endoscopic resection must be judged.     

Are Interaural Time and Level Differences Represented by Independent or Integrated Codes in the Human Auditory Cortex?

Sound localization is important for orienting and focusing attention and for segregating sounds from different sources in the environment. In humans, horizontal sound localization mainly relies on interaural differences in sound arrival time and sound level. Despite their perceptual importance, the neural processing of interaural time and level differences (ITDs and ILDs) remains poorly understood. Animal studies suggest that, in the brainstem, ITDs and ILDs are processed independently by different specialized circuits. The aim of the current study was to investigate whether, at higher processing levels, they remain independent or are integrated into a common code of sound laterality. For that, we measured late auditory cortical potentials in response to changes in sound lateralization elicited by perceptually matched changes in ITD and/or ILD. The responses to the ITD and ILD changes exhibited significant morphological differences. At the same time, however, they originated from overlapping areas of the cortex and showed clear evidence for functional coupling. These results suggest that the auditory cortex contains an integrated code of sound laterality, but also retains independent information about ITD and ILD cues. This cue-related information might be used to assess how consistent the cues are, and thus, how likely they would have arisen from the same source.     

Associations between dietary quality,noise, and hearing: Data from the National Health and Nutrition Examination Survey, 1999–2002

Abstract

Objective: A statistically significant relationship between dietary nutrient intake and threshold sensitivity at higher frequencies has been reported, but evidence conflicts across studies. Here, the potential interaction between noise and diet in their association to hearing was examined. Design: This cross-sectional analysis was based on Healthy Eating Index data and audiological threshold pure-tone averages for low (0.5 to 2 kHz) and high (3 to 8 kHz) frequencies. Study sample: Data were drawn from the National Health and Nutrition Examination Survey, 1999–2002. Results: Controlling for age, sex, race/ethnicity, education, diabetes, hypertension, and smoking we found statistically significant relationships between dietary quality and high-frequency threshold sensitivity as well as noise exposure and high-frequency thresholds. In addition, there was a statistically significant interaction between dietary quality and reported noise exposure with respect to high-frequency threshold sensitivity in participants, where greater reported noise exposure and poorer diet were associated with poorer hearing (p's < 0.05). Conclusions: The current findings support an association between healthier eating and better hearing at higher frequencies; the strength of this relationship varied as a function of participant noise history, with the most robust relationship in those that reported military service or firearm use.     

Psychological, neural, endocrine, and immune study of stress in tinnitus patients: any correlation between psychometric and biochemical measures?

OBJECTIVES: The present study was carried out in tinnitus patients in order to study the psychological distress and the biochemical measures of this stressful condition. Psychological features were compared to immune and neuroendocrine parameters in order to verify in these subjects the possible presence of psychological and somatic responses to stress. METHODS: We studied 85 tinnitus patients who underwent hematochemical immune tests: lymphocyte subpopulations (CD3; CD4; CD3+CD4; CD8; CD19; CD16NK; CD3+CD16+CD56; and CD4/CD8), cortisol, adrenocorticotropic hormone, beta-endorphin, prolactin, and urinary catecholamine. RESULTS: Clinically, significant scores were obtained for hysteria, depression, paranoia, hypochondrias, and social introversion; and high scores were obtained for anxiety, depression, care for health, difficulty of treatment, low self-esteem, family and work difficulties, and social discomfort. There was a low to medium level of self-perception of stress. The less a subject felt stressed, the higher was his or her satisfaction level in the areas of psychological and physical functioning. The scores on the tests and the biochemical measures did not show a significant correlation, but there was a tendency to correlation for the lymphocytes CD19 and CD16NK and for adrenocorticotropic hormone. CONCLUSIONS: The comparison between the psychometric and biochemical variables did not reveal any significant correlation among stress perception, daily satisfaction, and the biochemical parameters of stress.     

Patient,disease, and outcome characteristics of benign paroxysmal positional vertigo with and without Meniere’s disease

Abstract

Background: Meniere’s disease (MD)-associated benign paroxysmal positional vertigo (BPPV) is complex and difficult to diagnose, and reports of its prevalence, pathologic features and outcomes are sparse and conflicting.

Objective: Report disease characteristics and outcomes associated with the presence of MD in patients with BPPV.

Materials/methods: A retrospective study of patients with BPPV between 2007 and 2017 at a single, high-volume institution.

Results: Of 1581 patients with BPPV identified, 7.1% had MD and 71.9% of those patients had BPPV in the same ear(s) as MD. Patients with MD were more likely to have lateral semicircular canalithiasis (11.6% vs. 5.5%, p?=?.009) and multiple canalithiasis (7.1% vs. 2.5%, p?=?.005). MD was associated with an increased rate of resolution of BPPV (p?=?.008) but also increased time to resolution (p?=?.007). There was no association between MD and recurrence of BPPV.

Conclusions: MD is associated with lateral canalithiasis. Contrary to prior reports, BPPV in MD can affect either ear and was not associated with poorer outcomes than idiopathic BPPV.

Significance: The largest series to date investigating disease and outcome characteristics for BPPV in MD is presented. These data inform diagnosis and expectations in the management of these complex patients.     

Cochlear implantation in Pendred syndrome and non-syndromic enlarged vestibular aqueduct – clinical challenges,surgical results,and complications

Objective: To explore specific clinical issues, surgical results, and complications of 80 cochlear implantations (CI) in 55 patients with Pendred syndrome (PS) or non-syndromic enlarged vestibular aqueduct (NSEVA).

Background: Previous studies have focused either on unselected case series or on populations with mixed cochlear malformations. PS/NSEVA accounts for up to 10% of congenital SNHL, rendering this a large group of cochlear implant candidates. The abnormal inner ear anatomy of these patients may be associated with a lower surgical success rate and a higher rate of complications.

Study design: Retrospective review of patients’ medical records and CT/MRI.

Setting: Tertiary referral center.

Materials and methods: The medical records and CT/MRI images of 55?PS/NSEVA patients receiving 80 cochlear implantations from 1982–2014 were reviewed. Demographic data, surgical results, intra-operative incidents, and post-operative complications were retrieved.

Results: Complications occurred in 36% of implantations; 5% hereof major complications. Gushing/oozing from the cochleostoma occurred in 10% of implantations and was related to transient, but not prolonged post-operative vertigo.

Conclusion: Intra-operative risks of gushing/oozing and post-operative vertigo are the primary clinical issues in PS/NSEVA patients regarding CI. Nonetheless, the surgical success rate is high and the major complication rate is low; similar to studies of unselected series of CI recipients.     

Hearing impairment,cochlear morphology,and peroxynitrite (ONOO−) formation in adult and aging NOS II knockout mice

Conclusion: Nitric oxide synthase (NOS) II induction is a protective mechanism against age-related degeneration of the cochlea.

Objectives: An induction of NOS II has been described in different inner ear pathologies. The objective was to examine the role of NOS II in age-related degeneration of the cochlea.

Methods: The hearing ability in adult and aging NOS II knockout mice (KO) and their wildtype (WT) littermates was explored via auditory brainstem response (ABR) measurements. Inner ear morphological differences were studied with scanning electron microscopy (SEM). Immunohistochemistry was used to examine the induction of NOS II in the inner ear of aging WT mice. Expression of nitrotyrosin, a marker protein for the reactive oxygen species peroxynitrite, was compared between KO and WT mice using immunohistochemistry.

Results: Adult KO mice exhibited a mild hearing impairment. WT mice showed an induction of NOS II after 6 months of age. Age-related hearing deterioration was accelerated in KO mice, which was accompanied by increased nitrotyrosin formation and outer hair cell loss.