Michael Gaihede

Cholesteatoma of the external ear canal: etiological factors, symptoms and clinical findings in a series of 48 cases

BackgroundTo evaluate symptoms, clinical findings, and etiological factors in external ear canal cholesteatoma (EECC).MethodRetrospective evaluation of clinical records of all consecutive patients with EECC in the period 1979 to 2005 in a tertiary referral centre. Main outcome measures were incidence rates, classification according to causes, symptoms, extensions in the ear canal including adjacent structures, and possible etiological factors.ResultsForty-five patients were identified with 48 EECC. Overall incidence rate was 0.30 cases per year per 100,000 inhabitants. Twenty-five cases were primary, while 23 cases were secondary: postoperative (n = 9), postinflammatory (n = 5), postirradiatory (n = 7), and posttraumatic (n = 2). Primary EECC showed a right/left ratio of 12/13 and presented with otalgia (n = 15), itching (n = 5), occlusion (n = 4), hearing loss (n = 3), fullness (n = 2), and otorrhea (n = 1). Similar symptoms were found in secondary EECC, but less pronounced. In total the temporomandibular joint was exposed in 11 cases, while the mastoid and middle ear was invaded in six and three cases, respectively. In one primary case the facial nerve was exposed and in a posttraumatic case the atticus and antrum were invaded. In primary EECC 48% of cases reported mechanical trauma.ConclusionEECC is a rare condition with inconsistent and silent symptoms, whereas the extent of destruction may be pronounced. Otalgia was the predominant symptom and often related to extension into nearby structures. Whereas the aetiology of secondary EECC can be explained, the origin of primary EECC remains uncertain; smoking and minor trauma of the ear canal may predispose.

Diffuse Large B-Cell Lymphoma Classification System That Associates Normal B-Cell Subset Phenotypes With Prognosis

PURPOSE Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell-associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. PATIENTS AND METHODS We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. RESULTS Similar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP-treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell-like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1-signature and major histocompatibility complex class II-signature genes, which are known to have a positive impact on prognosis. CONCLUSION Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.

Middle ear pressure regulation--complementary active actions of the mastoid and the Eustachian tube.

Hypothesis: Middle ear pressure (MEP) is actively regulated by both the Eustachian tube and the mastoid air cell system. Background: MEP is a highly significant factor involved in many clinical conditions related to otitis media. Basic knowledge on its overall regulation remains insufficient, but the Eustachian tube and mastoid gas exchange are important factors. The main focus has been aimed at the tube; however, evidence points to the mastoid as equally important. More detailed methods are demanded to study their complementary functions. Methods: A catheter was inserted into the mastoid of 12 human volunteers (patients for parotidectomy). This enabled monitoring MEP directly, and experiments were performed with volume displacements of ±50, 100, and 200 &mgr;l resulting in a range of overpressure and underpressure. The following counter-regulation was recorded over 10 minutes. Results: In some cases, MEP counter-regulation presented as Eustachian tube openings with steep and fast pressure changes toward 0 Pa, whereas in others, gradual and slow pressure changes presented related to the mastoid; these changes sometimes crossed 0 Pa into opposite pressures. In many cases, combinations of these distinct mechanisms were found. Conclusion: The human mastoid as well as the Eustachian tube was capable of active counter-regulation of the MEP in short-term experimental pressure changes in healthy ears. Thus, these 2 systems seemed to function in a complementary way, where the mastoid was related to continuous regulation of smaller pressures, whereas the tube was related to intermittent regulation of higher pressures.

Tympanometric preconditioning of the tympanic membrane.

Preconditioning is a general biomechanical phenomenon, where tissue characteristics change due to repetitive loading-unloading experiments, resulting in an increased compliance. Increasing compliance by repetitive tympanometric measurements has previously been described and may be related to rate of pressure change during recordings. Presently, 9 tympanometries were performed in a group of normal adults (n = 103 ears) at 4 different rates: 50, 100, 200, and 400 daPa/s. Compliance showed an initial larger increase from trial to trial, tending to reach a steady state during later trials, and the pattern was found identical in all 4 groups. However, stratifying data according to compliance at 1st trial of each ear, the preconditioning effect was found significantly correlated to compliance (P < 0.001), so that low compliance was associated with low preconditioning and vice versa. Stratification also illustrated that, while most ears reached a steady state, some ears with high compliance (> or = 1.04 cm3) did not. In this way identification is possible of tympanic membranes, which are less resistant to pressure loads and therefore may be susceptible to development of retraction pockets. Repeatable measures of compliance with insignificant effect of preconditioning could be obtained after 5 tympanometries, and measures of precision of compliance are reported.

Sequelae of secretory otitis media : Changes in middle ear biomechanics

A new method previously introduced investigating the pressure volume relationship of the middle ear system describes dynamic mechanical properties of the system: the variables measured are hysteresis, compliance, and P(ec0) expressing the zero position of the tympanic membrane. The present study investigates the mechanical properties in 69 adolescents treated with ventilation tubes during childhood due to secretory otitis media. The tympanic membranes displayed various degrees of atrophy, sclerosis, and retraction of the pars flaccida. Atrophy was quantitatively related to decreasing hysteresis and increasing compliance, while myringosclerosis showed opposite effects. P(ec0) was significantly lower for the group of former secretory otitis media than for normals (p < 0.001). This reflects a retraction pattern of the tympanic membrane, which may be explained by a low opening pressure of the eustachian tube or previous pressure load of the drum. Signs of retraction were not found by tympanometry. Treatment with ventilation tubes was associated with a dramatic increase of tympanic membrane pathology (66%) compared to untreated ears (12%), as assessed by otomicroscopy (p < 0.001). However, these changes specific to treatment were not found in the corresponding mechanical variables of the middle ear system, as the effects of combined atrophy and myringosclerosis tend to counterbalance.

Mechanics of the Middle Ear System: Age-Related Changes in Viscoelastic Properties

Morphological studies of age-related changes in the tympanic membrane have suggested a decreased elasticity for increasing age, whereas age-related changes in admittance measured by tympanometry have revealed inconsistent results. In this study we report on the viscoelastic properties of the middle ear system by means of a new method in two different age groups. This method measures hysteresis (μJ), which describes the viscous properties of the system, and compliance (mm3/kPa) reflecting its elasticity. Moreover, Pec0 (kPa) was recorded, which corresponds to middle ear pressure measured by tympanometry. Recordings were made in a group of 30 older normal subjects (mean age 77 years) and results were compared to previous findings in a group of 39 younger normal subjects (mean age 29). Hysteresis was markedly decreased in the older normal group compared to the younger one (p = 0.057). This may reflect morphological changes previously reported in the tympanic membrane and can be related to theoretical considerations on tympanic membrane rupture pressures. Compliance and Pec0 were not influenced by variation in age (p = 0.645 and 0.966).

In vivo areal modulus of elasticity estimation of the human tympanic membrane system: modelling of middle ear mechanical function in normal young and aged ears

The quasi-static elastic properties of the tympanic membrane system can be described by the areal modulus of elasticity determined by a middle ear model. The response of the tympanic membrane to quasi-static pressure changes is determined by its elastic properties. Several clinical problems are related to these, but studies are few and mostly not comparable. The elastic properties of membranes can be described by the areal modulus, and these may also be susceptible to age-related changes reflected by changes in the areal modulus. The areal modulus is determined by the relationship between membrane tension and change of the surface area relative to the undeformed surface area. A middle ear model determined the tension-strain relationship in vivo based on data from experimental pressure-volume deformations of the human tympanic membrane system. The areal modulus was determined in both a younger (n = 10) and an older (n = 10) group of normal subjects. The areal modulus for lateral and medial displacement of the tympanic membrane system was smaller in the older group (mean = 0.686 and 0.828 kN m(-1), respectively) compared to the younger group (mean = 1.066 and 1.206 kN m(-1), respectively), though not significantly (2p = 0.10 and 0.11, respectively). Based on the model the areal modulus was established describing the summated elastic properties of the tympanic membrane system. Future model improvements include exact determination of the tympanic membrane area accounting for its shape via 3D finite element analyses. In vivo estimates of Youngs modulus in this study were a factor 2-3 smaller than previously found in vitro. No significant age-related differences were found in the elastic properties as expressed by the areal modulus.

Mechanics of the middle ear system: computerized measurements of its pressure–volume relationship

A new method is described measuring the pressure-volume relationship of the middle ear system (MES). These measurements express the dynamic mechanical properties of the MES. Ear canal pressure changes are measured in response to tympanic membrane (TM) volume displacements in a material of 39 younger normal adults. During one recording procedure several displacements curves are obtained from which one curve is isolated representing the neutral position of the TM. From this curve the following variables are determined: hysteresis (microJ) describing the viscoelastic properties of the MES, compliance (mm3/kPa) describing its elasticity, Prange (kPa) describing the pressure range of the curve, and Pec0 (kPa) describing the ear canal pressure for the neutral position of the TM. Normative data are presented and compared with tympanometric measurements. Compliance correlates significantly to static admittance (P<0.001), while Pec0 correlates significantly to middle ear pressure (P<0.001). Further, data on repeatability and sources of measurement errors are reported, which support a high reliability of the method. Compared with tympanometry the method is more detailed and has several advantages, which are discussed, and it has been found valuable for future mechanical studies of the MES. These studies include possibilities for diagnostics of middle ear disorders and derivation of pressure-volume equations useful in modeling of the MES.

Stable Phenotype Of B‐Cell Subsets Following Cryopreservation and Thawing of Normal Human Lymphocytes Stored in a Tissue Biobank

Cryopreservation is an acknowledged procedure to store vital cells for future biomarker analyses. Few studies, however, have analyzed the impact of the cryopreservation on phenotyping.

Accuracy of tympanometric middle ear pressure determination in secretory otitis media: dose-dependent overestimation related to the viscosity and amount of middle ear fluid.

Hypothesis: Tympanometric measurements of middle ear pressure in children with secretory otitis media are overestimated in a dose-response manner because of increased hysteresis explained by the viscosity and amount of middle ear fluid. Background: Tympanometric middle ear pressure is important in evaluating children with secretory otitis media. These measurements are influenced by hysteresis appearing as a peak pressure difference in bidirectional tympanometry. This represents an inaccuracy of 0.5 × peak pressure difference, which is only 5 to 25 daPa in normal ears. However, previous experiments found increased hysteresis, suggesting an inaccuracy of 225 daPa in secretory otitis media ears. Materials and Methods: In 56 patients with secretory otitis media, bidirectional tympanometry was performed; Type B curves were excluded. The middle ear fluid was semiquantified subsequently at surgery according to viscosity (serous, seromucoid, or mucoid) and amount (small, medium, or large). A control group included 28 normal children. Peak pressure difference was calculated by the difference between middle ear pressure determined by a positive and negative pressure sweep. Results: Mean peak pressure difference was 10 and 69 daPa in the normal and secretory otitis media groups, respectively (p < 0.001). However, peak pressure difference ranged to 205 daPa in the secretory otitis media group and showed a significant positive correlation to viscosity and amount of the fluid (both p < 0.0001). Conclusion: Peak pressure difference is significantly increased in secretory otitis media because of additional damping explained by the viscosity and amount of the fluid. The mean error was 5 daPa in normal ears and 35 daPa in secretory otitis media ears, but ranged to greater than 100 daPa. These results were only a low estimate of the inaccuracy, because patients with Type B tympanograms could not be included, and errors of more than 100 daPa can be anticipated.