[Hormonal influence on hearing]. / Hormonelle Beeinflussung des Hörvermögens.

BACKGROUND: Hearing loss leads to impairments in communication, social interactions, and cognitive functions. This renders early treatment particularly important. A causal therapy is not yet available. Human and animal studies have shown that certain hormones can have a positive effect on hearing. OBJECTIVE: This review provides an overview of the effects of various hormones on hearing and describes the potential benefit for future therapeutic approaches. MATERIALS AND METHODS: A systematic literature review of reviews dealing with the effects of various hormones on hearing in humans and animals published in PubMed between 2015 and 2020 was conducted. RESULTS: Hormones may mediate antiapoptotic effects on structure-relevant cells of the cochlea and auditory pathway, and may influence hair cell functionality or the electrolyte balance of the endo- and perilymph. Current research focuses on glucocorticoids; the mineral corticoid aldosterone; the sex hormones estrogen, progesterone, and testosterone; the growth hormones GH (growth hormone) and IGF­1 (insulin-like growth factor 1); thyroid hormones; and insulin. Study results are still inconsistent at this time, but various hormones appear to represent a possible future treatment option for acute hearing loss. Long-term hormone treatment, which would be necessary particularly in the case of age-related hearing loss, does not currently represent a sensible course of action due to the side effect profile of the systemic treatment/lack of practicable topical application options. CONCLUSION: The mode of action of hormones is complex. Whether they can be used in the future for individualized treatment of patients with acute hearing impairment requires further investigation.

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma.

INTRODUCTION: The number of aging cancer patients has increased continuously and will do so further in the future. The immune system of elderly people experiences critical changes over the time. Therefore, tumor-induced changes in the immune system are believed to differ in young and elderly cancer patients as well. METHODS: The effect of aging on the immune system was measured in peripheral blood lymphocytes (PBL) of healthy volunteers (n = 48, 21-84 yrs.) divided into three different age groups. Seventy years was set as a cut-off for defining subjects as elderly. Results were compared to two groups of adult cancer patients, which donated PBL and tumor infiltrating lymphocytes (TIL): young cancer patients (40-69 yrs.; blood: n = 13; TIL: n = 17) and elderly cancer patients (70-90 yrs.; blood: n = 20; TIL: n = 15) with head and neck squamous cell carcinoma (HNSCC). Frequencies and phenotypes of CD4+ and CD8+ T cells as well as regulatory T cells (Treg) were assessed by flow cytometry. RESULTS: We observed lower frequencies of CD8+ cytotoxic T cells during aging in both groups. Frequencies of tumor infiltrating regulatory T cells were significantly higher than in the peripheral blood but showed a significant decline in older tumor patients. With increasing age, expression of immunosuppressive CD73 and CCR7 was lower and expression of PD1 elevated on peripheral T cells in healthy volunteers and tumor patients. CONCLUSION: Immunosenescence takes place in healthy donors and cancer patients. Our results suggest that in elderly tumor patients, the immune system is impaired and the tumor-induced immune escape is less pronounced. The increased expression of PD1 implies the potential for effective immunotherapies in elderly, as treatment with checkpoint inhibitors could be more beneficial for elderly HNSCC patients.

[Oncoimmunology in old age]. / Onkoimmunologie im Alter.

Physiological aging processes of the immune system are associated with an increased susceptibility to infectious, autoimmune and tumor diseases. In accordance with the general demographic development the number of tumor patients in advanced age also increases. An end to this development is not yet foreseeable. In tumor treatment, immunotherapy with checkpoint inhibitors is becoming increasingly more important; however, only a few studies on the efficacy and side-effect profiles in older patients exist so far. In this review article the changes in the immune system in old age and the influence on carcinogenesis are discussed. In addition, the current state of research on the immunotherapy of patients in advanced age who suffer from head and neck cancer is presented.

[Hebephrenia - a viable psychopathological construct?] / Hebephrenie ­ ein brauchbares psychopathologisches Konstrukt?

Ewald Hecker was the first psychiatrist to describe the disease entity of hebephrenia in some detail, focusing mainly on disturbances of affect. Later Emil Kraepelin and Eugen Bleuler saw hebephrenia as a subtype of dementia praecox or schizophrenia. Willy Mayer-Gross and Karl Leonhard characterized hebephrenia with highly differentiated psychopathological descriptions, whereas this construct only played a minor role in the works of Klaus Conrad and Kurt Schneider. The International Classification of Diseases (ICD-10) lists hebephrenia as a subtype of schizophrenia but in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no subtypes of schizophrenia are mentioned and the concept of hebephrenia is thus lost. Hebephrenia can be seen as an ideal type describing a psychopathological course pattern. This construct can be useful to conceptualize a group of disorders of affect which otherwise escape description, especially since these psychopathological alterations of affect are difficult to operationalize. To have a viable concept of these disorders is relevant for the prognosis and therapy planning. If the concept of hebephrenia is abolished, important psychopathological knowledge might be lost for future generations of psychiatrists.

[The role of innate immunity in otitis media]. / Rolle des angeborenen Immunsystems bei Otitis media.

Otitis media (OM) belongs to the most common pediatric diseases and causes more medical contacts, surgical interventions, and drug prescriptions than any other infectious disease. Recent findings have identified a critical role of innate immunity in recovery from OM. The middle ear mucosa identifies invading pathogens by sensing pathogen-associated molecule patterns (PAMPs) via pattern recognition receptors such as the Toll-like receptors (TLRs). They generate immediate antimicrobial responses and cytokine release, leading to an inflammatory reaction as seen in acute or chronic OM. Cross-talk between TLRs can enhance or suppress the healing process in the middle ear. In order to prevent over-activation on the one hand and insufficient immune response on the other, the signaling network between different TLRs must be integrated and controlled by positive and negative feedback loops. This guarantees a proper immune response in the middle ear after infection. In this review, we focus on the involvement of the innate immune system and TLRs in OM, as well on their relevance for new vaccination strategies and immunotherapies.

[Otitis media: definition, pathogenesis, clinical presentation, diagnosis and therapy]. / Otitis media ­ Definition, Pathogenese, Klinik, Diagnose und Therapie.

A number of diseases of the middle ear are summed up under the term otitis media: acute otitis media, recurrent acute otitis media, otitis media with effusion, chronic suppurative otitis media and chronic otitis media epitympanalis (= cholesteatoma). Acute otitis media belongs to the most common pediatric diseases and is often caused by bacterial infection. Since the advent of pneumococcal vaccines the quantity of AOM caused by pneumococci has declined; vaccination against NTHi and Moraxella catarrhalis are being developed. Main pillar of conservative treatment of AOM is symptomatic therapy of otalgia and fever as well as restoring the Eustachian tubal function. When indicated, amoxicillin represents antibiotic medication of choice. Acute mastoiditis, facial nerve paresis, labyrinthitis, Gradenigo syndrome, sinus vein thrombosis, meningitis and brain abscess belong to the complications of AOM among others. Both innate and adaptive immune system are involved in recovery of OM with innate immunity playing a critical role. Dysfunction of the Eustachian tube often underlies OM. Manometric measurement of Eustachian tube function may be useful for indication of balloon Eustachian tuboplasty. Several theories explain pathogenesis of cholesteatoma and multiple pro-inflammatory processes promote its progress in the course of the disease.

[Psychiatry as a practical science : Considerations following Wolfgang Wieland (1933-2015)]. / Psychiatrie als praktische Wissenschaft : Überlegungen nach Wolfgang Wieland (1933­2015).

In the light of historical and modern criticism of the discipline of psychiatry and psychotherapy as a medical subspecialty, this paper deals with aspects of the theory of medicine as postulated by the physician and philosopher Wolfgang Wieland. According to his contributions medicine is a practical science aiming at establishing rational action. Central to this model is a diagnosis, which helps to subsume individual cases under general principles from which essential therapeutic options can be derived. Hence, psychiatry and psychotherapy become a medical subspecialty by adopting the basic model of medical reasoning and action as described by Wieland. Nevertheless, the limits of such an approach must be taken into consideration. Especially in a psychiatric and psychotherapeutic context it is of particular importance that even when being guided by general principles the responsibility for the personality of each individual patient should be adequately met. Furthermore, attention should be paid to the limits of the subspecialty of psychiatry and psychotherapy as a medical discipline, which also requires a critical analysis of the concept of psychiatric illness.

[The Concept of Typology in Psychiatry in the Context of Historical Contributions of Max Weber and Karl Jaspers]. / Das Typuskonzept in der Psychiatrie - Überlegungen nach Max Weber und Karl Jaspers.

Against the background of Max Weber's and Karl Jaspers' outstanding historical contributions to the conceptual development of different typologies, the importance of a psychiatric typology is examined. The term "ideal type" was introduced into social science by Weber as an analytical construct to describe and classify cultural phenomena. This concept was adopted for the psychiatric context by Jaspers who proposed to establish a typological system in the field of psychotic disturbances without an organic correlate. He emphasized the importance of the course of psychopathological symptoms for such a typological system. The concept of typology can be regarded as a promising heuristic approach in psychiatry, providing a classification system for complex psychopathological symptoms. Even though several historic typologies exist in psychopathology, their usefulness in the fields of therapy and prognosis needs to be critically assessed. Also, new typologies will have to be developed, taking into account neurobiological knowledge now available.

Infrasound a new weapon in cancer therapy?

BACKGROUND: Researchers take different positions when describing the effects of infrasound on the human body. Although several studies investigated the likely harmful effects of infrasound exposure from wind turbines a significant connection has not been found yet. There is evidence that infrasound interacts with cell metabolism and may disrupt cell membrane integrity. OBJECTIVES: The suggested impairment of the cells' ultrastructure by infrasound leads to the question of whether infrasound can be therapeutically used, for instance in cancer therapy. This review provides the current state of the literature. METHOD: Current literature on infrasound in cancer therapy including all studies with the search terms 'cancer' and 'infrasound' were identified and reviewed until the year 2020. RESULTS: The present state of research reveals promising effects of targeted infrasound in cancer therapy. Infrasound directly affects the tumor cells' ultrastructure and seems to sensitize several types of cancer to chemotherapy, presumably due to membrane permeabilization. The application of infrasound on tumor cells without other therapeutic agents demonstrates different effects that probably depend on the type of cells, the applied frequency and sound pressure level as well as the time of exposure. CONCLUSIONS: The mechanism of infrasound on cancer cells is not completely understood yet, hence, further studies have to be conducted to clarify the ultrastructural and metabolic changes inside the tumor cells. The development of suitable infrasound generators for the application in a clinical setting would be an important course of action.

Results of endoscopic sinus surgery for the treatment of inverted papillomas.

Fifty-one patients suffering from inverted papillomas of the nose and paranasal sinuses were reexamined in a retrospective study. Thirty-five had undergone surgery by an intranasal endoscopic approach and 16 had undergone surgery by an extranasal approach. The recurrence rate following endoscopic interventions was 17% (6/35), as compared to 19% (3/16) after extranasal operations. Endoscopic surgery proved to be successful even in the treatment of large lesions affecting the posterior ethmoidal sinus, the nasofrontal duct, or the sphenoidal sinus. Its indication thus no longer needs to be restricted to limited lesions of the anterior nasal cavity. Patients with inverted papillomas will benefit from this surgical technique which remains minimally invasive and thus retains the paranasal bony framework, preserves unaffected mucosa capable of recovery, and prevents damage to the patients' cosmetic features.

Enlarged middle fossa vestibular schwannoma surgery: experience with 735 cases.

OBJECTIVE: To show the clinical outcome in patients with sporadic vestibular schwannoma (VS) operated on by the enlarged middle cranial fossa approach (EMFA). STUDY DESIGN: Retrospective case review. SETTING: A tertiary referral center with four neurotologists experienced in EMFA surgery. PATIENTS: There were 376 women and 359 men, with a mean age of 51.1 years (range, 12-77). INTERVENTION: Enlarged middle cranial fossa approach surgery. MAIN OUTCOME MEASURES: Magnetic resonance imaging and computed tomography scans were used for follow-up and re-evaluation of the operative sites. Facial nerve function and hearing were tested. RESULTS: Overall complete VS removal was achieved in 97.1% of patients. There were two recurrences (0.3%) after microscopically complete tumor removal. Depending on the tumor size, postoperative normal and near-normal facial outcome ranged from 83% to 99% (average, 92%), and hearing at or near the preoperative level (+/-15 dB pure-tone average or +/-15% speech discrimination) was preserved in 60.2%, 48.2%, 23.9%, and 17.6%, respectively. CONCLUSIONS: The EMFA is an excellent low-morbidity approach for VS removal with limited cerebellopontine angle extension (2 cm). Specific advantages of the EMFA are the superior internal auditory canal exposure, resulting in an extremely low tumor recurrence rate; best capability for hearing preservation; and minimal incidence of cerebrospinal fluid leaks. Postoperative facial function outcome compares with that of other surgical approaches. The best results are achieved in subjects with small tumors and good hearing, advocating early diagnosis and treatment.

Endonasal endoscopic closure of cerebrospinal fluid fistulas at the anterior cranial base.

This study reports our indications and limits for endonasal endoscopic closure of dural defects with a cerebrospinal fluid (CSF) leak at the anterior cranial base, and demonstrates our surgical technique. Fifty-three patients with CSF rhinorrhea were reassessed for the success rate of closure of the CSF leak. Surgery was successful in 98%, and 68% of fistulas were closed endoscopically. A free graft of autogenous mucoperiosteum of the inferior turbinate was the most frequently used tissue for defect closure. The endonasal endoscopic route proved relatively safe for the closure of dural tears, irrespective of the cause, up to about 10 x 10 mm. It is characterized by minimal morbidity because of the preservation of sinus ventilation and bony structures, supraorbital nerves, and olfactory fibers. Defects larger in size, predominantly of traumatic origin, were closed via the transfacial approach. The decision on the surgical approach was additionally based on the extent of the facial soft tissue injuries and the localization of the leak.

Cranial nerve and hearing function after combined-approach surgery for glomus jugulare tumors.

In this retrospective study, oncologic and functional results of 46 patients treated for glomus jugulare tumor are reported. The standard surgical approach was the combined transmastoid-transcervical approach, modified according to the individual tumor growth, and eventually combined with a transtemporal or a suboccipital approach. Complete tumor removal resulted in a cure rate of 90%. New-onset cranial nerve palsies developed in less than 22% of patients. In 54% of cases it was possible to retain middle ear function. From a total of 12 patients with incomplete tumor removal and postoperative irradiation, progressive tumor growth was noted in 4 patients, and was controlled by salvage irradiation or surgery. Radical tumor removal by ablative surgery can be modified by efforts to reduce multilating resections. In their place, individually tailored and combined multidirectional surgical approaches may allow total tumor removal with lower morbidity.

Nasal airway changes after Le Fort I--impaction and advancement: anatomical and functional findings.

Twenty patients were studied prospectively to assess intranasal anatomical changes and functional changes resulting from a one-piece Le Fort I-osteotomy with anterior and superior positioning of the maxilla. Presurgical and 3 months postsurgical rhinological inspection, anterior rhinomanometry and acoustic rhinometry were performed. Interalar width was measured and cephalograms were used to assess maxillary movement. Rhinoscopically, three septal perforations (15%) were noticed. Turbinate enlargement was less common postoperatively. Interalar width increased significantly. These findings correlate with a significant increase in cross-sectional diameter at the Isthmus nasi revealed by acoustic rhinometry 3 months postoperatively. The mean total nasal airflow measured by anterior rhinomanometry was unchanged indicating no increase in resistance despite decreased intranasal dimensions in cases where the impaction is not higher than 5 mm.

Advantages of the enlarged middle cranial fossa approach in acoustic neurinoma surgery. A review.

Utilizing an enlarged middle cranial fossa approach to the cerebello-pontine angle without destruction of the labyrinth or cochlea the authors have since 1981 operated on 263 unilateral acoustic neurinomas. Tumour sizes ranged between 3 mm intrameatal and 35 mm within the cerebello-pontine angle. Complete tumour removal was accomplished in 96%. There was one postoperative mortality, and only rarely neurological complications. Excellent function of the facial nerve was obtained in 78% (in small and medium sized neurinomas 90% House I and II) and severe paralysis persisted in only 6%. Preservation of hearing was possible in 70% of the small tumours, and in 50% of the total group. Against this background comparable data of the literature are reviewed, and the indications for the enlarged midfossa approach analyzed.

Selective resection of the semicircular canals of rabbits with preservation of hearing.

The goal of this investigation was to develop a method of surgical removal of the semicircular canals of the rabbit without induction of auditory impairment. Four different surgical techniques were utilized: i) fenestration of the lateral semicircular canal; ii) fibrin glue perfusion of the canal following fenestration; iii) removal of the lateral semicircular canal by drilling after fenestration and fibrin glue perfusion, and iv) removal of all three canals after fenestration and fibrin gluing. Brainstem auditory potentials were recorded repeatedly for up to 3 months after operation and demonstrated preservation of hearing in all rabbits in the first group and in 78% of the second group. In the third group the potentials could be recorded in 67% of the animals and showed a 20 dB deterioration of hearing. After removal of all three semicircular canals residual hearing could be recorded in 50% of the rabbits. These animals regularly showed a 30-40 dB deterioration of hearing. A precise microsurgical technique using fibrin glue and bone chips for interruption of the peri- and endolymph flow proved crucial for hearing preservation.

Arachidonic acid metabolism in nasal tissue and peripheral blood cells in aspirin intolerant asthmatics.

Aspirin intolerance (AI) is characterized by polypous rhinosinusitis, bronchial asthma and adverse reactions to aspirin. The common intolerance to all cyclo-oxygenase inhibitors allows us to focus study of the pathogenesis of AI on the metabolism of arachidonic acid (AA). We studied the metabolism of AA in nine aspirin intolerant asthmatics (AIA) and eight healthy volunteers (controls) by measuring prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT = LTC4/D4/E4) in nasal tissue and peripheral blood cells (PBCs) using a specific immunoassay. In all patients with AI the tests were performed before and after bronchial provocation with lysine-ASA. In the control group the tests were done before and after 500 mg ASA p.o. The release of pLT in nasal polyps of AIA was found to be significantly higher than in normal mucosa of AIAs and controls. In every tissue a significant increase of pLT after aspirin challenge was observed. Nasal polyps of AIA show a significantly lower release of PGE2 than normal mucosa of AIAs and controls. Peripheral blood cells of AIA show a significantly higher release of pLT and a significantly lower release of PGE2 than PBCs of controls. Therefore clinical manifestations of AI may be based on an alteration of AA metabolism in AIA.

Preservation of hearing in bilateral acoustic neurinomas by deliberate partial resection.

With the aim of preserving hearing, 20 acoustic neurinomas in 17 patients with neurofibromatosis 2 were intentionally submitted to an incomplete (80%) tumour removal. In 12 cases this was an operation on the last hearing ear with total deafness of the contralateral ear. If an auditus existed in both ears the better hearing ear was selected for the primary intervention. Early audiological controls evidenced residual hearing in 19 of the 20 cases operated on by the enlarged middle fossa approach, which was utilized inspite of the tumour diameters being between 1 and 6 cm in the cerebello-pontine angle. The oncologic and functional follow-up over 1 to 7 years showed different patterns of slow progression of hearing loss and of persistent auditory function over 2 to 7 years. Facial nerve function was excellent in 16 of the 18 controlled cases. Continued CT or MRT imaging revealed no signaling in 2 cases, constant tumour sizes in 10 cases and slow progression in 3 cases. With regard to the importance of an auditory communication in the younger adult, the described treatment modality appears to be the first choice method.

Experimental sensorineural hearing loss following drill-induced ossicular chain injury.

In a guinea pig model, a standardized drill-induced injury to the body of the incus was applied, and the effects on hearing were characterized by electrocochleography. Drilling resulted in a threshold shift within seconds, and after 15 min it averaged 35.7 dB for clicks, 35 dB nHL for 4 kHz bursts, 36.7 dB nHL for 6 kHz bursts and 39 dB nHL for 8 kHz bursts. The deterioration of the threshold shift remained stable throughout the 5-week post-operative observation period. In five animals a disarticulation of the incudostapedial joint was performed prior to drilling, but this did not reduce the threshold shift. Caution is mandatory during drilling around an intact ossicular chain to avoid a permanent sensorineural hearing loss, and disarticulation of the incudostapedial joint prior to drilling has no protective value.