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Hannover, Germany

Novoa E.,Klinik fur Hals Nasen Ohrenkrankheiten | Podvinec M.,Klinik fur Hals Nasen Ohrenkrankheiten | Podvinec M.,University of Basel | Angst R.,Kinderklinik | And 2 more authors.
International Journal of Pediatric Otorhinolaryngology | Year: 2013

Objective: Otogenic lateral sinus thrombosis (LST) in children represents a serious condition with potential long-lasting morbidity. The role of adjunct anticoagulation therapy and the benefit of an analysis of prothrombotic factors are unclear. The aim of the study was to report therapeutic management and outcome, analyze prothrombotic factors in children with otogenic LST treated with mastoidectomy/antibiotics/anticoagulation and to evaluate the results with a review of the literature. Methods: Retrospective chart review of 9 children with otogenic LST (2000-2009) and literature search in PubMed. Results: The most frequent sign was fever in 88%, while neurologic findings were seen in 55%. Streptococci was the most common bacteria (55%). Prothrombotic factors were normal in all children. All patients received therapeutic anticoagulation, without experiencing bleeding complications. Eight children made a full recovery, neurologic sequelae persisted in one. The literature review of 115 children identified fever as the most prominent sign, reported the absence of neurologic findings in almost 50% of cases and confirmed the major role of streptococci. Anticoagulation, as adjunct therapy, was given to 38% of patients in the therapeutic range with a trend towards better neurologic outcome. A prothrombotic analysis was reported in 5 studies with positive results in 2. Conclusions: Surgery and antibiotics represent the mainstay of the therapy. Anticoagulation can be safely added in view of the high potential for morbidity and might reduce neurologic sequelae. Bacteria with thrombotic activity seem to be an important aetiology. In contrast, a prothrombotic disposition seems to play a minor role in the development of otogenic LST. © 2013 Elsevier Ireland Ltd. Source

Hofmann S.R.,TU Dresden | Morbach H.,University of Wurzburg | Schwarz T.,University of Wurzburg | Rosen-Wolff A.,TU Dresden | And 3 more authors.
Clinical Immunology | Year: 2012

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown origin. We previously demonstrated that monocytes from CRMO patients fail to express the immune-modulatory cytokine interleukin10 (IL10) in a chromatin dependent manner. Here, we demonstrate that attenuated extracellular-signal regulated kinase (ERK)1 and 2 signaling in response to TLR4 activation results in failure to induce IL-10 expression in monocytes from CRMO patients. Attenuated ERK1/2 activation results in 1) reduced levels of Sp-1, a transcription factor that induces IL-10 expression in monocytes, and 2) impaired H3S10 phosphorylation of the IL10 promoter, an activating epigenetic mark. The pro-inflammatory cytokines tumor necrosis factor (TNF)α and IL-6 are not negatively affected, resulting in an imbalance towards pro-inflammatory cytokines. Thus, impaired ERK1/2 signaling with subsequently reduced Sp-1 expression and H3S10 phosphorylation of the IL10 promoter may centrally contribute to the pathophysiology of CRMO. © 2012 Elsevier Inc. Source

Scholle S.,Robert Koch Krankenhaus Apolda GmbH | Wiater A.,Kinderklinik | Scholle H.C.,Universitatsklinikum Jena
Sleep Medicine | Year: 2011

Objective: To provide normative values for pediatric sleep cardiorespiratory parameters following AASM rules, assessing effects of gender, age, and Tanner stage. Methods: One-night polysomnograhy was performed at subjects' habitual bedtimes in 16 laboratories on 209 healthy German children, 1-18. years old. Results: Normative values of cardiorespiratory parameters in pediatric sleep are presented. No obstructive and mixed apneas occurred. Hypopneas were seldom. Respiratory frequency and apnea-hypopnea-index decreased with age (p<. 0.001). In all groups central apneas ≥20. s were present but uncommon. Oxygen desaturations or respiratory arousals following central apnea were rare. Heart rate showed an inverse correlation to age (p<. 0.001). Heart rate was lower in sleep, lowest in stage N. The mean heart rate of females was higher than males (p<. 0.05). Neither Tanner stage nor corresponding age (p<. 0.05) influenced: mean apnea duration, central apnea index ≥20. s, hypopnea index, index of periodic breathing, or oxygen saturation nadir. All other parameters except maximal apnea duration and central apnea index after movements with oxygen desaturation show dependency on both Tanner stage and corresponding age (p<. 0.05). Conclusions: Using AASM rules, the development of cardiorespiratory parameters in healthy children, ages 1-18 is shown. Age-related norms may improve sleep pathology identification. © 2011 Elsevier B.V.. Source

Scholle S.,Robert Koch Krankenhaus Apolda GmbH | Wiater A.,Kinderklinik | Scholle H.C.,Universitatsklinikum Jena
Sleep Medicine | Year: 2012

Objective: This study focused on differences in arousals during sleep, using the arousal rules of the American Academy of Sleep Medicine, by gender, age, and maturity in healthy children. Methods: One-night polysomnography was performed on 209 healthy German children (age 1-18. years) at their habitual bedtimes in 16 laboratories. Subjects were grouped by gender (112 females, 97 males), age, and Tanner stage. Results: Normative values of arousal events in sleep are presented, including indexes of spontaneous and respiratory arousals, total electroencephalogram (EEG) arousals, phasic increase in submental electromyogram (EMG) in stage R, and leg movements. With increasing age, a decrease was seen in: EEG arousal index ≥1-2.9. s, EEG arousal index ≥3. s, index of total EEG arousals, index of respiratory arousals, chin EMG enhancement in stage R ≥1-2.9 and ≥3. s, index of total leg movements, and leg movements with EEG arousals (p< 0.05). Only spontaneous arousals showed no association with age. There was a significant negative correlation between Tanner stage and arousals ≥1-2.9. s, respiratory arousals, leg movements, and leg movements with arousals (p< 0.05). Only arousals ≥3. s and total leg movements showed gender differences (p< 0.05). Conclusions: For the diagnosis of pediatric sleep disturbances, the given arousal data enable estimation of the degree of deviation from normal findings for age and maturity. There is need for further research on, and further discussion of, the arousal rules of the American Academy of Sleep Medicine. © 2011 Elsevier B.V. Source

Hofmann S.R.,TU Dresden | Schwarz T.,University of Wurzburg | Moller J.C.,TU Dresden | Morbach H.,University of Wurzburg | And 4 more authors.
Clinical Immunology | Year: 2011

Chronic non-bacterial osteomyelitis (CNO) is an auto-inflammatory disorder that affects the skeletal system. Interleukin (IL-)10 is an immune-modulatory cytokine that controls inflammation, and limits inflammatory cytokine responses. Dysregulation of IL-10 expression has been shown to result in autoimmune and infectious diseases.We investigated IL-10 expression by monocytic cells from CNO patients and controls. In response to stimulation with LPS, IL-10 expression from CNO monocytes was reduced (p< 0.001). This was independent of IL10 promoter polymorphisms. Thus, we investigated Sp1 recruitment to the IL10 promoter and saw markedly reduced binding in CNO monocytes. This was accompanied with reduced phosphorylation of histone H3 serine 10 (H3S10), an activating epigenetic mark.Impaired recruitment of Sp1 to the IL10 promoter, and reduced H3S10 phosphorylation, may be a reflection of deficient MAPK signaling in CNO monocytes in response to LPS stimulation. Thus, we have discovered a mechanism that may be central in the pathophysiology of CNO. © 2011 Elsevier Inc. Source

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