Julia Vent

Depth of olfactory sulcus and olfactory function.

The aim of this study was to identify whether the depth of the olfactory sulcus relates to olfactory function in healthy subjects. Forty-four healthy, male volunteers (age range 22-45 years, mean age 28.3 years) were included in this study. Olfactory function was measured for phenyl ethyl alcohol odor thresholds, odor discrimination, and odor identification. Magnetic resonance imaging of the olfactory sulcus was performed immediately following olfactometry. Based on previous investigations the depth of the olfactory sulcus was measured in the plane of the posterior tangent through the eyeballs. Olfactory function correlated significantly with left-sided depth of the olfactory sulcus (r(44)=0.33, P=0.03); no such correlation was seen for the right side. In addition, olfactory sulcus depth was found to be significantly deeper on the right compared to the left side (t=5.61, P<0.001). The present results suggest that there is small, but significant relation between morphological brain structures and measures of olfactory function. Further, lateralization of olfactory sulcus depth may correlate to functional lateralization in the olfactory system. Thus, it may be carefully speculated that sensory input in the olfactory system results in cortical growth in the area of the olfactory sulcus, at least at some developmental stage.

p16 Expression in carcinoma of unknown primary: Diagnostic indicator and prognostic marker

Carcinoma of unknown primary (CUP) of the neck are heterogeneous tumors in their clinical and biological characteristics, and a preoperative prognostic marker is desirable to optimize staging and therapy and to improve outcome and survival. For CUP syndrome, no optimized diagnostic and treatment strategy or biomarker have yet been determined.

Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis.

Juvenile-onset recurrent respiratory papillomatosis (RRP) is associated with low risk human papillomavirus (HPV) types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2–4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR) or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH) revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR) showed integration in the aldo-keto reductase 1C3 gene (AKR1C3) on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related) malignancies.

Prevalence and risk factors for oral human papillomavirus infection in 129 women screened for cervical HPV infection

BACKGROUND Oncogenic human papillomaviruses (HPV) are known to be associated with carcinomas of the uterine cervix. Furthermore, current studies have shown that HPV-infection is also associated with a subtype of oropharyngeal cancers. In general, a sexual transmission of the viruses has been shown by numerous studies in the genital lesions. However, there are unknown factors regarding the prevalence and transmission of HPV in the oropharynx. The aim of this study was to evaluate HPV prevalence in the oropharynx in female participants with and without genital HPV infection. In addition, we analyzed risk factors for an oropharyngeal colonization with HPV in their sexual partners, too. METHODS 129 Female participants were tested for presence of HPV-DNA by oral lavage, brush cytology of the tonsils and of the cervix. In addition, 15 male partners of these patients were included in the study. HPV-DNA was detected by PCR (polymerase chain reaction) amplification. For HPV-genotyping, PCR products were hybridized with type-specific digoxigenin-labeled oligonucleotide probes and discriminated into 14 high risk (HR) and 6 low risk (LR)-HPV types. The 129 female and 15 male participants were interviewed by a standardized questionnaire for socioeconomic details, drinking, smoking and sexual behaviours. RESULTS 59 (45.7%) Female participants were negative for a genital HPV-infection. Of these women, 3 (5.1%) showed a positive HPV-PCR result (HR and LR) in the oropharynx. 70 (54.3%) Female participants were positive for a genital HPV infection. In this group, 4 (5.7%) had a positive HPV-detection (HR and LR) in the oral cavity and oropharynx. Female participants with cervical HPV-infection had no higher risk for HPV-detection in the oropharynx (not significant). The analysis of sexual risk factors revealed no specific risk factor for an oral HPV-infection. CONCLUSION A correlation between cervical and oral colonization by HPV could not be demonstrated in our small cohort. Our limited data suggest that sexual transmission of HPV from the cervix uteri to the oropharynx is a rare and unlikely event.

Methylene blue for easy and safe detection of salivary duct papilla in sialendoscopy.

Sialendoscopy is one of the new challenges in treating salivary gland diseases, mainly sialolithiasis. It is an unpleasant situation if the sialendoscopy operator experiences problems in finding the papilla or during introduction of the endoscopic devices, especially because the intervention is usually performed under local anesthesia. One key step in performing sialendoscopy is the safe, atraumatic entering of the papilla with the endoscope, which is much more difficult for the submandibular gland than for the parotid. The ostium represents the narrowest part of the Wharton duct with mean diameters between 0.5 and 1.5 mm. The small, single-device sialendoscope measures 1.3 mm (Karl Storz Company, Tuttlingen, Germany). Thus, before a sialendoscopy can be performed, the ostium needs to be dilated with a cone-shaped dilatator and probes. Damage to the orifice can result in failure of the whole procedure. Therefore, a smooth probe implementation into the duct is the key, which makes secure detection of the ostium necessary. The surgeon should also be familiar with the exact anatomy of the individual, especially when the duct must be incised. At intraductal sialolithiasis with stones close to the orifice, incision of the duct should start preferably from the position of the caruncula, which therefore needs to be localized first. Especially if the gland and duct are inflamed or if the sialolith is of a significant size, the entire floor of the mouth can be edematous, making the duct entrance invisible. Because we are dealing with a salivary duct, it would be advantageous to identify the ostium by observing its secretion. A helpful method is massaging the gland, but even then some glands express only a little saliva; hence, the secretion may not be visualized on the smooth reflecting mucosa (Fig 1). To overcome this problem, we suggest tipping methylene blue (1% methylthioninium chloride; Neopharma GmbH & Co.KG, Aschau, Germany) onto the area of the caruncula. Then massaging the gland followed by a slow sweeping of the duct in a distal direction should express at least minor amounts of saliva. In contrast to no use of dye, after meth-

Topical Therapy in Anosmia: Relevance of Steroid-Responsiveness†

Objectives/Hypothesis: The use of steroids either systemically or topically is known as a common therapy in patients with anosmia. Nevertheless, investigations giving proof for the benefit of a topical therapy are very rare, and no prognostic factors are known. In our study, we for the first time evaluated the additional effect of a topical therapy not only with steroids but also with antibiotics after conventional pretreatment with oral steroids and propose the steroid‐responsiveness of an anosmia as a prognostic factor.

Effects of short inter-stimulus intervals on olfactory and trigeminal event-related potentials

Conclusion: Chemosensory event-related potentials (CSERPs) were identified in all measurements using the 20 s and the 10 s inter-stimulus interval (ISI) protocol, reducing the recording time to 75% or 57% compared with the standard protocol. A possible explanation for the rising CSERP amplitudes by shortening the ISI in CO2 stimulation is due to a phenomenon known as trigeminal sensitization during repeated stimulation. Objectives: CSERPs are influenced by the ISI. The aim of this study was to evaluate the changes in CSERPs by decreasing the ISI from 30 s to 20 s or 10 s, respectively. Subjects and methods: Ten normosmic healthy subjects participated this study. Phenyl ethyl alcohol (PEA), hydrogen sulphide (H2S) and carbon dioxide (CO2) were used in CSERP measurements with different ISI protocols (30 s (standard), 20 s and 10 s). Amplitudes and latencies of ISI protocols were submitted to ANOVA for repeated measurements and t tests for paired samples. Results: The amplitudes of CSERPs with PEA and H2S stimuli were decreasing with shortening the ISI significantly. In contrast, the highest amplitudes of trigeminal CSERPs were recorded with the 10 s ISI protocol with CO2. The ANOVA revealed a significantly different effect of shortening the ISI on CSERPs on the right and the left side.

On the Sustainability of Guideline Implementation

BackgroundAllergic rhinitis (AR) is a disorder associated with a high financial burden and is considered an important risk factor for the development of asthma. The ARIA guideline (Allergic Rhinitis and its Impact on Asthma) addresses this problem and provides recommendations for treating allergic rhinitis. The objective of the present analysis was to estimate the compliance with guidelines among ear, nose and throat (ENT) specialists and general practitioners.MethodsThe data of 121,593 patients collected during 9 prospective observational studies carried out from 1998 to 2005 were examined using individual patient data meta-analysis method.ResultsOnly 14.8% of patients with allergic rhinitis were treated according to the recommendations. Of the others, 73.8% received insufficient treatment. In addition, 36.1% of the patients who were treated by ENT specialists received therapy according to guidelines, whereas only 16% of the general practitioners heeded the recommendations. Patients suffering from rhinitis and asthma were treated by ENT specialists according to the ARIA guideline in 50% of cases. It could be observed that the rate of guideline compliance was highest in the year of publication.ConclusionThe results are evidence of the successful implementation process of the ARIA guidelines. However, they have not yet found their way into the daily routine of general practitioners.

Prevention and Treatment of Complications after Polymethylmethacrylate-Microspheres Injections

The present article focuses on the peculiarities of polymethylmethacrylate as facial filler highlighting the injection technique, known adverse effects, and all options for complication management. Supplemented by a historical overview and case series, the authors share their experience with this widespread and in the last decade heavily criticized injectable filler substance.

The problem of placebo-controlled trials allowing rescue medication: how to assess efficacy in rhinosinusitis and allergic rhinoconjunctivitis when both groups receive active rescue treatment.

Purpose of reviewThe assessment of pharmacological efficacy of rhinosinusitis and rhinoconjunctivitis has been performed in various studies involving standardized measures such as symptom scores, various health-related quality of life scales, the sino-nasal outcome test, or the rhinoconjunctivitis quality of life questionnaire. However, the methods and study designs are heterogeneous, and a methodological standard is still lacking. The aim of this review was – from a clinical and a methodological point of view – to evaluate placebo-controlled trials permitting the use of rescue medication and to provide insight into the specific challenges of such clinical trials. Using studies published within the past 24 months as examples, we here demonstrate the problems in evaluating and interpreting these studies and describe possibilities for refining the methodology in order to improve future study designs. Recent findingsThe World Allergy Organization has recently published recommendations for the standardization of clinical trials on respiratory allergy in which methodological aspects regarding the use of rescue medication are discussed. SummaryThis study summarizes the recommendations for study design, outcome measures, and statistical analysis to be used in planning, performing, and analyzing clinical studies on rhinoconjunctivitis and rhinosinusitis that allow the use of rescue medication.