M. Jakob

Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge.

Human MSCs may respond to TLR ligation, and recent research has suggested that many tissues contain tissue‐specific MSCs, possibly located in periendothelial and perivascular regions. At present, the functional consequences of these findings are unclear. We hypothesized that tissue‐specific MSCs could play an instructional role during early phases of bacterial challenge. To investigate this hypothesis further, we set up a coculture system of glandular MSCs and peripheral blood neutrophils so that we could analyze the cellular interactions of these cells in response to LPS challenge. We found that stimulation with bacterial endotoxin induced chemokine receptor expression and mobility of MSCs. Activated MSCs secreted large amounts of inflammatory cytokines and recruited neutrophils in an IL‐8‐ and MIF‐dependent manner. Recruited and activated neutrophils showed a prolonged lifespan, an increased expression of inflammatory chemokines, and an enhanced responsiveness toward subsequent challenge with LPS. Our findings demonstrate a complex, functional interaction between tissue‐resident MSCs and peripheral blood neutrophils upon bacterial challenge and suggest a role for MSCs in the early phases of pathogen challenge, when classical immune cells have not been recruited yet.

Mesenchymal stem cells augment the anti-bacterial activity of neutrophil granulocytes.

Background Mesenchymal stem cells (MSCs) participate in the regulation of inflammation and innate immunity, for example by responding to pathogen-derived signals and by regulating the function of innate immune cells. MSCs from the bone-marrow and peripheral tissues share common basic cell-biological functions. However, it is unknown whether these MSCs exhibit different responses to microbial challenge and whether this response subsequently modulates the regulation of inflammatory cells by MSCs. Methodology/Principal Findings We isolated MSCs from human bone-marrow (bmMSCs) and human salivary gland (pgMSCs). Expression levels of TLR4 and LPS-responsive molecules were determined by flow cytometry and quantitative PCR. Cytokine release was determined by ELISA. The effect of supernatants from unstimulated and LPS-stimulated MSCs on recruitment, cytokine secretion, bacterial clearance and oxidative burst of polymorphonuclear neutrophil granulocytes (PMN) was tested in vitro. Despite minor quantitative differences, bmMSCs and pgMSCs showed a similar cell biological response to bacterial endotoxin. Both types of MSCs augmented anti-microbial functions of PMNs LPS stimulation, particularly of bmMSCs, further augmented MSC-mediated activation of PMN. Conclusions/Significance This study suggests that MSCs may contribute to the resolution of infection and inflammation by promoting the anti-microbial activity of PMNs. This property is exerted by MSCs derived from both the bone-marrow and peripheral glandular tissue.

[Salivary gland stem cells : Can they restore radiation-induced salivary gland dysfunction?].

ZusammenfassungStammzellen wird eine gewichtige Rolle im Rahmen von regenerativer Medizin und Tissue-Engineering beigemessen, da sie spezifische Eigenschaften besitzen, die ihre Verwendung bei diesen Verfahren aussichtsreich erscheinen lässt. Je nach Herkunft zählen hierzu die Differenzierungsfähigkeit in unterschiedliche Zelltypen und die Fähigkeit zur langfristigen Proliferation. Stammzellen wurden bislang aus vielen unterschiedlichen Geweben isoliert. Weil sie in vielen Geweben nur selten vorkommen und die Gewebegewinnung Komorbiditäten verursachen kann, besteht ein großes Interesse an der Identifikation und Charakterisierung weiterer Zellquellen für die Gewinnung von Stammzellen.Daher wurde in den letzten Jahren auch Speicheldrüsengewebe, zunächst bei Tieren, später auch beim Menschen auf die Anwesenheit von Stammzellen untersucht. Der klinische Hintergrund ist die Xerostomie, die sehr häufig nach einer Strahlentherapie, aber auch nach Radiojodtherapie auftritt.In der vorliegenden Arbeit wird ein Überblick über die Isolierung und Charakterisierung von Stammzellen aus Speicheldrüsen gegeben und diskutiert, welche Rolle Stammzellen im Rahmen der Erforschung neuer Therapieoptionen für Erkrankungen wie die postradiogene Xerostomie haben werden.AbstractAdult stem cells are actively investigated in the fields of regenerative medicine and tissue engineering, as they exhibit specific characteristics that make them promising candidates for cellular therapies. Depending on their tissue of origin these characteristics include long-term proliferation and the capacity to differentiate into various cell types. To date adult stem cells have been isolated from a multitude of tissues. Non-embryogenic adult tissues contain only small numbers of such stem cells and the derivation of such tissues can cause comorbidities. Therefore, there is ongoing interest in the identification and characterisation of novel cell sources for stem cell isolation and characterisation.Recently, salivary gland tissue has also been explored as a possible source of stem cells, first in animals and later in humans. Such salivary gland-derived stem cells might be useful in the treatment of radiation-induced salivary gland hypofunction, and possibly also in other diseases with loss of acinar cells, such as sequelae of radio iodine treatment or Sjögren’s disease.In this paper we review the current status of salivary gland stem cell biology and application and discuss the possible role of stem cells in the development of novel therapies for salivary gland dysfunctions such as postradiogenic xerostomia.Adult stem cells are actively investigated in the fields of regenerative medicine and tissue engineering, as they exhibit specific characteristics that make them promising candidates for cellular therapies. Depending on their tissue of origin these characteristics include long-term proliferation and the capacity to differentiate into various cell types. To date adult stem cells have been isolated from a multitude of tissues. Non-embryogenic adult tissues contain only small numbers of such stem cells and the derivation of such tissues can cause comorbidities. Therefore, there is ongoing interest in the identification and characterisation of novel cell sources for stem cell isolation and characterisation.Recently, salivary gland tissue has also been explored as a possible source of stem cells, first in animals and later in humans. Such salivary gland-derived stem cells might be useful in the treatment of radiation-induced salivary gland hypofunction, and possibly also in other diseases with loss of acinar cells, such as sequelae of radio iodine treatment or Sjögrens disease.In this paper we review the current status of salivary gland stem cell biology and application and discuss the possible role of stem cells in the development of novel therapies for salivary gland dysfunctions such as postradiogenic xerostomia.

Robot-assisted endoscope guidance versus manual endoscope guidance in functional endonasal sinus surgery (FESS)

Abstract Background: Having one hand occupied with the endoscope is the major disadvantage for the surgeon when it comes to functional endoscopic sinus surgery (FESS). Only the other hand is free to use the surgical instruments. Tiredness or frequent instrument changes can thus lead to shaky endoscopic images. Methods: We collected the pose data (position and orientation) of the rigid 0° endoscope and all the instruments used in 16 FESS procedures with manual endoscope guidance as well as robot-assisted endoscope guidance. In combination with the DICOM CT data, we tracked the endoscope poses and workspaces using self-developed tracking markers. Results: All surgeries were performed once with the robot and once with the surgeon holding the endoscope. Looking at the durations required, we observed a decrease in the operating time because one surgeon doing all the procedures and so a learning curve occurred what we expected. The visual inspection of the specimens showed no damages to any of the structures outside the paranasal sinuses. Conclusion: Robot-assisted endoscope guidance in sinus surgery is possible. Further CT data, however, are desirable for the surgical analysis of a tracker-based navigation within the anatomic borders. Our marker-based tracking of the endoscope as well as the instruments makes an automated endoscope guidance feasible. On the subjective side, we see that RASS brings a relief for the surgeon.

Klinische Symptome der metamizolinduzierten Agranulozytose in der HNO

BACKGROUND Despite the controversial international debate on the use of metamizole as a standard analgesic, the prescription figures for Germany have increased constantly during recent years. However, metamizole can lead to the rare and severe medical condition called agranulocytosis. MATERIALS AND METHODS Between January 2009 and January 2014, 5 patients with metamizole-induced agranulocytosis presented themselves at the Interdisciplinary Emergency Center of the University Clinic Bonn. According to their leading ENT symptoms, they were transferred to the otorhinolaryngological department. We retrospectively evaluated metamizole medication, all general patient data and previous diseases, as well as disease course and the respective therapies. RESULTS Within the scope of the different treatments--surgery after trauma (n=2), elective orthopedic surgery (n=2), tonsillitis treatment (n=1)--the patients (n=5; mean age 30 years) had made regular ambulant use of metamizole for several days or weeks (4-28 days, mean 16.8 days). Daily oral dose ranged from 625 to 2000 mg/d (mean 1500 mg/d). Subsequently, patients required treatment for clinical symptoms of agranulocytosis (e.g. tonsillitis with severe odynophagia and significantly reduced general condition). All patients were monitored in an intermediate or intensive care unit (3-14 days, mean 10 days). No patients died. DISCUSSION As our cases show, when using metamizole as a standard analgesic, the treating otolaryngologist should look for clinical symptoms of agranulocytosis and inform patients about possible adverse effects. We recommend strict indication setting, regular blood analyses during long-term medication and consideration of alternative analgesics (e.g. NSAR).

Posttherapeutische Lebensqualität beim Nasopharynxkarzinom

BACKGROUND This retrospective study analysed patient characteristics and quality of live (QoL) for patients with nasopharyngeal carcinoma (NPC) after treatment. MATERIAL AND METHODS A cross-sectional investigation was conducted to assess the QoL of 20 NPC patients with cancer-free survival of more than one year, which were treated with radiotherapy (RT) or chemoradiotherapy (RCT) during the period 2001-2009 at the University Hospital Bonn, Germany. The QoL was assessed by the FACT-NP (functional assessment of cancer therapy-nasopharyngeal) questionnaire. RESULTS The median age of the patients was 57 ± 13 years and the male/female ratio was 2.33/1.3 (15%) patients were treated with RT and 17 (85%) with RCT. The global QoL was good in our patients. Xerostomia, chewing, decrease of gustatory sense, discontent with sexual life and ear problems were of major concern with the majority of patients and affected the QoL negatively. Pain, lost of working ability, emotional distress, or family problems were no significant factors. CONCLUSION The expected reduction of QoL after treatment must be explained in detail to the NPC patient. The integration of the family and partner, an antidepressant therapy or psycho-oncological support can be useful and necessary.

Comparative functional cell biological analysis of mesenchymal stem cells of the head and neck region: potential impact on wound healing, trauma, and infection.

Mesenchymal stem cells (MSCs) are multipotent mesenchymal progenitor cells, originally identified in bone‐marrow. Little is known about MSCs of the head and neck region. We investigated cell biological properties with a potential impact on wound healing of 2 different tissue‐resident MSC populations.

Histologie nach Tonsillektomie

BACKGROUND The necessity to rule out clinically occult malignancies by routine histological examination of all tonsillectomy specimens is a controversial topic. METHODS Clinical and histological findings of all patients who underwent tonsillectomy at the University of Bonn, Germany from January 2002 to March 2007 were retrospectively reviewed. A meta-analysis of PubMed literature regarding the histological results of tonsil specimens was performed. The incidence of clinically occult tonsil malignancy was recorded and potential risk factors for malignancy were analyzed. A cost-effectiveness ratio of microscopic analysis of all specimens was also performed. RESULTS Clinically occult tonsil malignancies were detected in 2 out of the 1,523 patients (0.13%) in this study. In the meta-analysis of 24 studies (61,550 patients) 6 cases of clinically occult tonsil malignancies (0.01%) were identified. Statistically 7,694 tonsils have to be histologically examined to detect 1 case of occult malignancy which corresponds to an average cost per case of 385,000 EUR. DISCUSSION Considering economical aspects we recommend that histological examination should be performed when the following risk factors are present: a history of cancer, tonsil firmness or lesions, tonsillar asymmetry, swelling of neck lymph nodes, constitutional symptoms, anamnestic unilateral symptoms and prior peritonsillar abscess.

Histology after tonsillectomy

BACKGROUND The necessity to rule out clinically occult malignancies by routine histological examination of all tonsillectomy specimens is a controversial topic. METHODS Clinical and histological findings of all patients who underwent tonsillectomy at the University of Bonn, Germany from January 2002 to March 2007 were retrospectively reviewed. A meta-analysis of PubMed literature regarding the histological results of tonsil specimens was performed. The incidence of clinically occult tonsil malignancy was recorded and potential risk factors for malignancy were analyzed. A cost-effectiveness ratio of microscopic analysis of all specimens was also performed. RESULTS Clinically occult tonsil malignancies were detected in 2 out of the 1,523 patients (0.13%) in this study. In the meta-analysis of 24 studies (61,550 patients) 6 cases of clinically occult tonsil malignancies (0.01%) were identified. Statistically 7,694 tonsils have to be histologically examined to detect 1 case of occult malignancy which corresponds to an average cost per case of 385,000 EUR. DISCUSSION Considering economical aspects we recommend that histological examination should be performed when the following risk factors are present: a history of cancer, tonsil firmness or lesions, tonsillar asymmetry, swelling of neck lymph nodes, constitutional symptoms, anamnestic unilateral symptoms and prior peritonsillar abscess.

Workspace and pivot point for robot-assisted endoscope guidance in functional endonasal sinus surgery (FESS).

For the further development of robot‐assisted endoscope guidance in functional endoscopic sinus surgery (FESS), ground data about the workspaces and endoscope movements in conventional FESS are needed.