The improvement of middle ear ventilation by laser ablation of the epipharyngeal eustachian tube: a prospective study

A long-lasting dysfunction of the eustachian tube seems to be the etiologic origin for development of chronic otitis media (COM) with mesotympanic perforation, otitis media with effusion (OME), and chronic atelectasis of the middle ear. Surgical interventions in the middle ear generally treat the sequelae of the tube dysfunction but not the dysfunction itself. This prospective clinical study investigated how far fiber-guided laser ablation of the posterior half of the epipharyngeal tubal ostium led to better middle ear ventilation in the otologic disease patterns mentioned below. There were 38 adult patients included in the analysis. The patients in one group had a perforated tympanic membrane [COM before primary tympanoplasty (n = 14) or revision tympanoplasty (n = 5)]; the patients in a second group had an intact eardrum [OME resistant to therapy (n = 3), with an atelectasis of the middle ear (n = 2) or problems of pressure equalization with fast changes in ambient pressure (diving, flying) (n = 14)]. Laser ablation of the posterior half of the epipharyngeal tubal ostium was performed, generally with local anesthesia, if tubal function testing was pathologic (Valsalva maneuver, passive tube opening, tympanogram). In patients with COM the procedure was performed 8 weeks before the middle ear surgery. All patients were checked 8 weeks postoperatively and in the course of the following year. The intervention seemed to have had a positive effect on tube function in 68.4% of patients operated on (P = 0.001). In 26 of the 38 patients that had undergone operation, an improvement the results of tubal function tests could be seen in the postoperative follow-up. In the COM group the Valsalva maneuver improved in 14 of 19 patients (73.6%) (P = 0.001), and the passive tube opening improved in nine of 18 patients (50%). In the group with an intact eardrum the Valsalva maneuver improved in 13 of 18 patients (72.2%) (P = 0.001). The resulting condition remained stable after 1 year. None of the patients showed any complications as a result of the therapy. Minimally invasive shaping of the distal eustachian tube under topical anesthesia can be recommended for patients with the above-mentioned diagnoses who have pathologic middle ear ventilation. Especially prior to tympanoplasties, and especially in otologic revision procedures, where middle ear ventilation is a prerequisite for successful otologic surgery, the function of the eustachian tube can be optimized in 70% of the patients, particularly if there are pathological findings (tubal tonsil, narrow orifice of the tubal ostium, adenoids). The placement of permanent ear tubes in adults with recurrent OME can also be avoided by the procedure described. The resultant conditions remained stable for the next year. Patients with tympanic ventilation problems due to rapid pressure changes (flying, diving) can also benefit from this procedure.     

Cystatin C and carotid intima-media thickness in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND: Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis. PREDICTORS: Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels. OUTCOMES & MEASUREMENTS: Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT. RESULTS: In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C-based estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), had no independent association with internal and common carotid IMT. LIMITATIONS: There were few participants with severe kidney disease. CONCLUSIONS: Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.     

National Institute of Neurological Disorders and Stroke (NINDS): advances in understanding and treating neuropathy, 24-25 October 2006; Bethesda, Maryland

Abstract   National Institute of Neurological Disorders and Stroke sponsored a meeting to explore the current status of basic and clinical research in peripheral neurobiology and clinical neuropathy. The goal of the workshop was to identify areas where additional research could lead to the development of new therapeutics in the next 5 years. Participants discussed the current understanding of disease mechanisms of axonal and demyelinating neuropathies, existing techniques in research, disease biomarkers, and assessment of neuropathy. Painful neuropathies were discussed at the basic scientific and clinical levels in relation to new insights into etiology and treatment. The meeting concluded with a discussion on therapeutic development in neuropathy and the need for a unified approach to multicenter trials. Short-term goals of the workshop were to form a working group for neuropathy, the Peripheral Neuropathy Study Group, and to translate new scientific findings into therapies and complete clinical trials.     

Cx29 and Cx32, two connexins expressed by myelinating glia, do not interact and are functionally distinct

In rodents, oligodendrocytes and myelinating Schwann cells express connexin32 (Cx32) and Cx29, which have different localizations in the two cell types. We show here that, in contrast to Cx32, Cx29 does not form gap junction plaques or functional gap junctions in transfected cells. Furthermore, when expressed together, Cx29 and Cx32 are not colocalized and do not coimmunoprecipitate. To determine the structural basis of their divergent behavior, we generated a series of chimeric Cx32-Cx29 proteins by exchanging their intracellular loops and/or their C-terminal cytoplasmic tails. Although some chimerae reach the cell membrane, others appear to be largely localized intracellularly; none form gap junction plaques or functional gap junctions. Substituting the C-terminus or the intracellular loop and the C-terminus of Cx32 with those of Cx29 does not disrupt their colocalization or coimmunoprecipitation with Cx32. Substituting the C-terminus of Cx29 with that of Cx32 does not disrupt the coimmunoprecipitation or the colocalization with Cx29, whereas substituting both the intracellular loop and the C-terminus of Cx32 with those of Cx29 diminishes the coimmunoprecipitation with Cx29. Conversely, the Cx32 chimera that contains the intracellular loop of Cx29 coimmunoprecipitates with Cx29, indicating that the intracellular loop participates in Cx29-Cx29 interactions. These data indicate that homomeric interactions of Cx29 and especially Cx32 largely require other domains: the N-terminus, transmembrane domains, and extracellular loops. Substituting the intracellular loop and/or tail of Cx32 with those of Cx29 appears to prevent Cx32 from forming functional gap junctions.     

PANIC-ATTAC: a mouse model for inducible and reversible beta-cell ablation

OBJECTIVE—Islet transplantations have been performed clinically, but their practical applications are limited. An extensive effort has been made toward the identification of pancreatic β-cell stem cells that has yielded many insights to date, yet targeted reconstitution of β-cell mass remains elusive. Here, we present a mouse model for inducible and reversible ablation of pancreatic β-cells named the PANIC-ATTAC (pancreatic islet β-cell apoptosis through targeted activation of caspase 8) mouse.RESEARCH DESIGN AND METHODS—We efficiently induce β-cell death through apoptosis and concomitant hyperglycemia by administration of a chemical dimerizer to the transgenic mice. In contrast to animals administered streptozotocin, the diabetes phenotype and β-cell loss are fully reversible in the PANIC-ATTAC mice, and we find significant β-cell recovery with normalization of glucose levels after 2 months.RESULTS—The rate of recovery can be enhanced by various pharmacological interventions with agents acting on the glucagon-like peptide 1 axis and agonists of peroxisome proliferator–activated receptor-γ. During recovery, we find an increased population of GLUT2⁺/insulin⁻ cells in the islets of PANIC-ATTAC mice, which may represent a novel pool of potential β-cell precursors.CONCLUSIONS—The PANIC-ATTAC mouse may be used as an animal model of inducible and reversible β-cell ablation and therefore has applications in many areas of diabetes research that include identification of β-cell precursors, evaluation of glucotoxicity effects in diabetes, and examination of pharmacological interventions.Diabetes is an epidemic affecting 180 million people worldwide with rising prevalence (1). Successful islet transplantation with the Edmonton protocol was considered a significant step toward a cure (2). However, because of the scarcity of available islets and limited viability of transplanted islets, this procedure has not yet found widespread application. Extensive efforts have been directed toward identifying pancreatic β-cell stem cells for transplantation and approaches to stimulate β-cell regeneration.In the past, the potential β-cell precursors have been identified among embryonic stem cells, ductal cells, acinar cells, and nonendocrine epithelial cells (3–7). More recently, the proliferation of pre-existing β-cells has been shown to be the major source of β-cell regeneration in lineage tracing studies (8). The mechanisms of β-cell regeneration therefore remain controversial, and different methodologies and animal models may be at the source of these inconsistent observations.Both in vitro islet culture and diabetic animal models have been used extensively in characterization of pancreatic β-cell death and regeneration and identification of β-cell precursors. However, the findings gained from islet cultures in vitro cannot always be extrapolated to the in vivo situation because of the complexity of β-cell physiology. Current in vivo pancreas injury models include toxin administration, pancreatectomy, and ductal ligation. Studies using these models have provided valuable insights for physiological and pathophysiological regulation of β-cells. However, these animal models use acute, extreme, and nonphysiological insults, and none of them show significant β-cell recovery after injury.In the present study, we describe a pancreas injury model with inducible and reversible β-cell ablation. In the current transgenic mouse model, the PANIC-ATTAC (pancreatic islet β-cell apoptosis through targeted activation of caspase 8) mouse, β-cell death is induced in a specific and well-defined manner through treatment of a chemical dimerizer. Importantly, the PANIC-ATTAC mice show extensive β-cell regeneration and normalization of glucose levels after treatment. We found an increased population of GLUT2⁺/insulin⁻ cells, which may serve as β-cell precursors. The PANIC-ATTAC mouse model has the potential to be highly informative in many areas of diabetes research and provides an opportunity to characterize β-cell pathophysiology during diabetes progression.     

Cognitive screening in multiple sclerosis

Cognitive screening tests in multiple sclerosis (MS) are time- and cost-saving test instruments. In the case of a positive test result (alert function) a comprehensive cognitive test procedure should be administered. This paper explains what cognitive screening in MS means and presents several screening instruments used in MS with their statistical test characteristics, e. g. sensitivity and specificity.     

Neurobehavioral performance of adult and adolescent agricultural workers

There are many occupational hazards associated with working in agriculture including risk of injury and exposure to pesticides. Research examining neurobehavioral effects of pesticide exposure have focused primarily on the acute effects in adults working in agriculture. Organophosphate poisoned populations have shown a consistent pattern of deficits when compared to a non-exposed or non-poisoned population on measures of motor speed and coordination, sustained attention, and information processing speed. Fewer studies have examined the effect of long-term low-level exposure on nervous system functioning in agricultural workers. Pesticides are thought to pose a considerably higher risk to children than to adults, yet little is known about the extent or magnitude of health problems related to occupational exposure to pesticides in children and adolescents. The present study compared the neurobehavioral performance of adolescents and adults working in agriculture and examined the impact of years working in agriculture on neurobehavioral performance. One hundred seventy-five Hispanic adolescent and adults completed a neurobehavioral test battery consisting of 10 computer-based tests measuring attention, response speed, coordination and memory. Age, gender, school experience, and years working in agriculture all impacted performance on the neurobehavioral tests. Comparison of adult and adolescents did not reveal decreased neurobehavioral performance in adolescents. On several tests the adolescents performed better than adult counterparts. The adolescents and adults were engaged in comparable agricultural working environments at the time of the neurobehavioral testing. These findings suggest that, at the time of exposure to pesticides, adolescents are not more vulnerable to the effects of working in agriculture. Evidence from this study suggests that cumulative exposure to low levels of pesticides over many years of agricultural work is associated with neurological impairment as measured by the Selective Attention, Symbol-Digit, Reaction Time tests. Experience handling pesticides was also associated with deficits in neurobehavioral performance.     

Spatial frequencies or emotional effects? A systematic measure of spatial frequencies for IAPS pictures by a discrete wavelet analysis

The influence of the emotional attributes of a visual scene on early perception processes remains a key question in contemporary affective neurosciences. The International Affective Picture System (IAPS; Lang et al., 2005) was developed to provide a set of standardized stimuli for experimental investigations of emotional processes. These stimuli have been widely used in brain activity investigations to study the influence of valence and/or arousal on visual processing. However, visual perception is strongly influenced by the physical properties of the images shown, especially their spatial frequency content, an aspect that has been unexpectedly neglected at large. In this study, we examine the complete set of IAPS with a discrete wavelet transform to highlight relations between the energy in different spatial frequencies and the emotional features of the pictures. Our results showed that these associations are weak when the complete dataset is considered, but for selected subsets of pictures, clear differences are present in both affective and spatial frequency content. The IAPS remains a powerful tool to explore emotional processing, but we strongly suggest that researchers use subsets of images that are controlled for the energy of their spatial frequencies when investigating emotional influence on visual processing.