Selected ENT symptoms in functional disorders of the upper cervical spine and temporomandibular joints.

This paper discusses otorhinolaryngological symptoms associated with functional disorders of the upper cervical spine. Hints aimed to avoid misdiagnoses of cross-organ otorhinolaryngological symptoms as phobic or psychogenic disorders are presented. Clinically relevant neuroanatomical convergence of the upper cervical spine (occiput to C3) is fundamental for the interpretation of functional otorhinolaryngological symptoms. Based thereon, evidence for the most common cervical differential diagnoses of dizziness, tinnitus, dysphagia, and craniomandibular dysfunction is presented separately. The corresponding therapeutic options and their contraindications are discussed in the concluding chapter. The importance of interdisciplinary cooperation in related fields is emphasized.

[Impact of TGF-beta1 antisense on collagen-binding integrins in keloid]. / TGF-beta1-Antisense beeinflusst kollagenbindende Integrine im Keloid.

BACKGROUND: The treatment of keloids remains challenging due to sparse knowledge about the pathogenesis of this disease. Transforming growth factor (TGF)-beta1 plays a central role in keloid formation. Cell-matrix communication is controlled by integrins, the expression of which can be regulated by TGF-beta1. METHODS: Using immunohistochemistry we compared expression patterns of alpha1beta1, alpha2beta1 und alpha3beta1 in normal skin and keloid tissue. Secondly, the effect of TGF-beta1-antisense after 48 h and 72 h incubation in a keloid-derived fibroblast monolayer was analyzed by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: alpha1beta1 and alpha2beta1 were highly expressed in keloid fibroblasts. Incubation with TGF-beta1-antisense lead to a reduction on protein level. RT-PCR demonstrated an increase of all alpha subunits, while on an mRNA level a decrease of the subunit beta1 could be observed. CONCLUSION: Integrin expression is directly modulated by TGF-beta1. An abnormal response in the keloid as a result of an altered TGF-beta1 pathway could be a key element to understanding the development of keloids.

[Fever, redness, swelling, and pain in the submental region]. / Fieber, Rötung, Schwellung und Schmerzen submental.

A 76-year-old woman presented with fever, redness, swelling, and pain under the chin. Some submental lymph nodes were detected by ultrasound and computed tomography. The diagnosis was a submental phlegmon, for which surgery was performed. The lymph nodes were removed, and antibiotic therapy with daily lavage was done. The histology of the lymph nodes suggested giant cell arteritis.

Abrogation of TGF-beta by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin.

The transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer good prospects for the modulation of wound healing, specifically those targeting TGF-beta. The aim of this study was to analyze the effect of TGF-beta targeting on the expression of angiogenic vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and in vitro angiogenic activity in fibroblasts isolated from radiation-induced chronic dermal wounds. The expression of angiogenic VEGF in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of VEGF in isolated fibroblasts was analyzed by ELISA and multiplex RT-PCR. Human endothelial cells (ECs) were grown in conditioned medium produced from the treated fibroblasts. EC migration was measured using a modified Boyden chamber; EC tube formation was analyzed under a light microscope. Immunohistochemical investigation and microarray analysis demonstrated a decreased expression of VEGF protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment significantly up-regulated VEGF secretion in vitro. Addition of conditioned medium from TGF-beta antisense-treated fibroblasts resulted in an increase in EC cell migration and tube formation. In conclusion, our results demonstrate that TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in radiation-induced dermal wounds.

TGF-beta1 antisense therapy modulates expression of matrix metalloproteinases in keloid-derived fibroblasts.

Transforming growth factor-beta1 (TGF-beta1) has been identified as an important regulator of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta1. The purpose of this study was to analyze the effect of TGF-beta1 targeting on the expression of matrix metalloproteinases (MMPs) in fibroblasts cultured from earlobe keloids. The expression of MMP-2 and -9 in tissue samples from keloids was investigated by immunohistochemistry. The effect of TGF-beta1 targeting using antisense oligonucleotides on the expression of MMPs in keloid-derived fibroblasts was analysed by ELISA and multiplex RT-PCR. Immunohistochemical studies demonstrated an increased expression of MMP protein in tissue samples from keloids compared to normal human skin. Antisense TGF-beta1 oligonucleotide treatment significantly downregulated MMP-9 secretion in vitro. In conclusion, TGF-beta1 antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in keloids.

TGF-beta antisense oligonucleotides modulate expression of matrix metalloproteinases in isolated fibroblasts from radiated skin.

BACKGROUND: Transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. The purpose of this study was to analyze the effect of TGF-beta targeting on the expression of matrix metalloproteinases (MMPs) in fibroblasts isolated from radiation-induced chronic dermal wounds. MATERIALS AND METHODS: The expression of MMPs in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of MMPs in isolated fibroblasts was analysed by ELISA and multiplex RT-PCR. RESULTS: Immunohistochemical investigation and microarray analysis demonstrated an increased expression of MMP protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment significantly down-regulated MMP secretion in vitro. CONCLUSION: TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in radiation-induced chronic wounds.

[Regenerative medicine in head and neck reconstructive surgery]. / Regenerative Medizin. Chancen für die rekonstruktive Kopf-Hals-Chirurgie.

Autologous transplantation is regarded as the gold standard in the treatment of congenital or acquired deformities. However, the availability of autologous tissue for transplantation is often limited. Regenerative medicine aims to activate individuals' own intrinsic regenerative mechanisms and embraces tissue engineering, cell/system biology, gene therapy and stem-cell biology. Most approaches in tissue engineering are based on the expansion of small autologous cell aggregates. Tissue engineering supplemented by isolated and amplified stem cells is another very promising option for producing autologous transplants and getting over the limited availability. The association of stem cell-based tissue engineering and gene therapy allows the creation of regenerative tissue in the optimal ambience of regulatory proteins. This leads to great opportunities in the transplantation of skin, bones or cartilage. This paper presents the current status and the possible benefits, but also the limitations, of regenerative medicine in reconstructive surgery of the head and neck.

[Clinical experience with the hygienic reprocessing of rigid endoscopes lacking a working channel with reference to practicability in clinical routine]. / Erfahrungen in der hygienischen Aufbereitung starrer optischer Instrumente mit Reinigungs-Desinfektions-Geräten in Bezug auf Praktikabilität im klinischen Alltag.

BACKGROUND: Contaminated medical products may be vectors for infections. A safe disinfection method for the optical instruments used by ENT specialists is undoubtedly needed. So far, a standard method that sufficiently covers the risk of infection for patients and medical staff alike, while serving the need of practicability in daily routine, has not been established. PATIENTS AND METHODS: In the ENT departments of the Mannheim and Kaiserslautern hospitals, a study on the practicability of disinfection rigid optical instruments lacking working channels was conducted using cleaning and disinfection automats. A total of 735 patients were examined (Hopkins 30 degrees and 70 degrees) and the endoscopes subsequently sterilized using a cleaning and disinfection automat. RESULTS: Each cleaning cycle took about 40 min. Examining 70-100 patients a day, a minimum of eight 70 degrees Hopkins endoscopes would be needed. CONCLUSION: The sterilization of medical products such as endoscopes is the best practice, but certain hindrances, such as loss of time and costs involved, complicate its general application.

[Vacuum-assisted closure of nonhealing wounds in head and neck reconstructive surgery]. / Vakuumassistierte Therapie zur Wundbehandlung im Kopf-Hals-Bereich.

Chronic wounds are characterized by slow or nonexistent wound healing. Usually their treatment is expensive. Therefore new concepts in management are of interest in order to reduce treatment time and costs. One option is vacuum sealing. The concept of topical negative pressure is not new, and many chronic nonhealing wounds could be closed successfully with the help of vacuum sealing. Until now, there has been no documented case of vacuum sealing in head and neck reconstructive surgery. Our case shows the effectiveness of a vacuum-assisted device in successful closure of a chronic nonhealing wound in this region.

[A comparison of the gene expression patterns of human chondrocytes and chondrogen differentiated mesenchymal stem cells for tissue engineering]. / Vergleich der Genexpressionsmuster humaner Chondrozyten und chondrogen differenzierter mesenchymaler Stammzellen für das Tissue-Engineering.

BACKGROUND: Tissue engineering is a promising method for the generation of chondrogenic grafts for reconstructive surgery. In cultured chondrocytes, the dedifferentiation of cells seems unavoidable for multiplication. METHODS: In this study, we investigated the expression of distinct markers during the dedifferentiation of human chondrocytes (HC) harvested during septoplasty and human mesenchymal stem cells (hMSC) from cartilage biopsies in cell culture using the microarray technique. RESULTS: The genes for collagen 1alpha1, 2alpha1, 3alpha1, 4alpha1, 11alpha1, biglycan, fibromodulin and lumican were activated during the dedifferentiation of the HCs, collagen 9alpha2, 9alpha3, 10alpha1 and chondroadherin were inactivated. During chondrogenic differentiation of hMSCs, the genes for collagen 3alpha1, 9alpha2, 9alpha3, 10alpha1, 11alpha1 were activated, collagen 4alpha1 and fibromodulin inactivated and the genes for Col 1alpha1, biglycan und chondroadherin constantly expressed. CONCLUSION: The genetic profile for the investigated markers in human chondrocytes generated from hMSCs resembles the profile in differentiated chondrocytes. Collagen 2alpha1, 9alpha2, 9alpha3, 10alpha1 could represent markers for the differentiation of chondrocytes, Col 1alpha1, 3alpha1 und 4alpha1, biglycan, fibromodulin and lumican markers for the dedifferentiation into a more fibroblastoid cell type.

[Physiology, role and neuropharmacology of yawning]. / Physiologie, Rolle und Neuropharmakologie des Gähnens.

Yawning is a physiological event that can be divided into three distinct phases: a long inspiratory phase, a brief acme and a rapid exspiration. The reason for yawning is not yet well defined. However this semi-voluntary event increases vigilance and aims to alert when drowsiness occurs. Yawning may have an important role for social communication. The neuropharmacology of yawning is complex and knowledge of its mechanisms is incomplete. While under the control of several neurotransmitters, yawning is largely affected by dopamine. Dopamine may activate oxytocin production in the paraventricular nucleus of the hypothalamus, oxytocin may then activate cholinergic neurotransmission in the hippocampus, and finally acetylcholine might induce yawning via the muscarinic receptors of the effectors. In fact, this scheme is simplified. Many other molecules can modulate yawning, such as nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opium derivate peptides.