Birger Jettkant

Determination of Microcirculatory Changes and Angiogenesis in a Model of Frostbite Injury In Vivo

BACKGROUND The breakdown of skin microcirculation and the leukocyte-endothelium interaction are assumed to play a key role in the pathophysiology of frostbite injuries. However, little is known as yet. The aim was to develop an in vivo frostbite model to monitor microcirculatory changes and angiogenesis after frostbite injury. MATERIALS AND METHODS Deep partial thickness frostbite injuries were inflicted with a no-touch-technique to the ears of hairless mice (n=9). To this end, a gas jet of nitrogen vapor (T=-195,8±2.7°C) was delivered onto an area of 1.9 mm(2) for 1,5 s. Intravital fluorescent microscopy in combination with FITC-dextran and Rhodamin 6G as fluorescent dyes was used to assess microcirculatory changes, leukocyte behavior, and angiogenesis during the 14 d of wound healing. RESULTS The area of no perfusion decreased significantly over the observed period, and perfusion was almost completely restored due to angiogenesis by d 14 (day 1: 1.89 [mm(2)]±0.44SEM, d 14: 0.02±0.01). No post-traumatic extension of the trauma could be observed. Edema formation increased significantly up to d 7. The number of adherent leukocytes showed a significant increase during the first 7 d. Functional vessel density showed a significant post-frostbite decrease to 60% of the baseline value. CONCLUSIONS This novel frostbite model provides a simple and nonetheless highly effective technique of creating locally limited reproducible frostbite injuries using a no touch technique. Tissue damage can be fully attributed to the thermal trauma, and the model allows repetitive intravital fluorescent microscopy of the microcirculation, leukocyte-endothelium interaction, and angiogenesis.

Considerations for the design and technical setup of a human whole-body exposure chamber.

Exposures to air contaminants, such as chemical vapors and particulate matter, pose important health hazards at workplaces. Short-term experimental exposures to chemical vapors and particles in humans are a promising attempt to investigate acute effects of such hazards. However, a significant challenge in this field is the determination of effects of co-exposures to more than one chemical or mixtures of chemical vapors and/or particles. To overcome such a challenge, studies have to be conducted under standardized exposure characterization and real time measurements, if possible. A new exposure laboratory (ExpoLab) was installed at IPA, combining sophisticated engineering designs with new analytical techniques, to fulfill these requirements. Low-dose as well as high-dose exposure scenarios are achieved by means of a calibration-gas-generator. Exposure monitoring can be carried out with a high performance real time mass spectrometer and other suitable analyzers (e.g. gas chromatograph). Numerous automated security facilities guarantee the physical integrity of the volunteers, and the waste atmosphere is removed using either charcoal filtration or catalytic post-combustion. Measurements of sulfur hexafluoride, carbon dioxide, aniline and carbon black are presented to demonstrate the performance of the exposure unit with respect to the temporal and spatial stability of generated atmospheres. The variations of generated contents in the atmospheres at steady state are slightly higher than the measurement precision of the analyzers (the typical standard deviation of generated atmospheres is < 2%). The technical components of ExpoLab and its monitoring systems ensure high quality standards in validity and reliability of generating and measuring exposure atmospheres.

The influence of a weight-bearing platform on the mechanical behavior of two Ilizarov ring fixators: tensioned wires vs. half-pins

BackgroundA weight-bearing platform applied at the distal end of an Ilizarov external frame allows patients with hindfoot transfixations, foot deformities or plantar skin lesions to bear weight. This leads to an indirect loading of the fracture or osteotomy site. However, the effect on the fracture/osteotomy sites motion or compressive loads is unknown. The aim of this study was to analyze the mechanical effects of a weight-bearing platform on the traditional all-wire, four-ring frame in comparison to a two-ring frame consisting of half-pins.MethodsTwo frame configurations, with either anatomically positioned wires or half-pins, were analyzed with and without a weight-bearing platform applied underneath the distal ring. Composite tibiae with a mid-diaphyseal osteotomy of 3.5 mm were used in all the experiments. An axial load was applied with the use of a universal test machine (UTS®). Interfragmentary movements, the relative movements of bone fragments and movements between rings were recorded using displacement transducers. Compressive loads at the osteotomy site were recorded with loading cells.ResultsIndirect loading with a weight-bearing platform altered the force transmission through the osteotomy. Indirect loading of the tibiae decreased the extent of the axial micro-motion by 50% under the applied weight load when compared to direct weight loading (p < 0.05). The half pin frame was 25% stiffer than the wire frame under both direct and indirect loading of the tibiae (p < 0.05). Compressive loads under indirect loading were reduced by 67% in the wire frame and by 57% in the half-pin frames compared to direct loading of the bones (p < 0.05). While axial loading in the wire frames resulted in plain axial movements at the site of the osteotomy, it was coupled with translational movements and angular displacements in the half pin mountings. This effect was more apparent in the case of indirect loading.ConclusionsA weight-bearing platform has substantial influence on the biomechanical performance of an Ilizarov external fixator. Half-pins induce greater stiffness to the Ilizarov external fixator and allow the usage of only one ring per bone segment, but shear stresses at the osteotomy under axial loading should be considered. The results allow an estimation of the size and direction of interfragmentary movements based on the extent of weight bearing.

Mechanical stress on tensioned wires at direct and indirect loading: a biomechanical study on the Ilizarov external fixator.

BACKGROUND The biomechanical effect of indirect weight loading with the Ilizarov ring fixator using a weight-bearing platform has not yet been investigated. The problem of wire loosening and breakage occurs more frequently when patients are mobilised with a weight-bearing platform. Therefore, the aim of this research was to compare the influence of direct and indirect weight loading on the tensioned wires. METHOD A universal testing machine (UTS, Germany) was used in this study. A composite tibia model with a standard four-ring Ilizarov fixator and 1.8-mm wires in anatomical position was used to simulate a clinical situation. Wire strain was measured with two strain gauges positioned at the ring-wire interface of each wire. After a standardised 2-mm mid-diaphyseal osteotomy, an axial load of up to 1000 N was applied to the bone; the different methods of weight loading were evaluated in two experimental set-ups. RESULTS A higher axial load was necessary to achieve an osteotomy gap closure at indirect loading. Mechanical stress on the tensioned wires was 400% higher on the proximal wires and 250% higher on the distal wires at a maximum axial loading of 1000 N. Mechanical stress remained on the wires in indirect loading, even after bone end contact, and led to excessive stress under higher weight-bearing amounts. CONCLUSION There is a substantial change in the biomechanical characteristics of the Ilizarov ring fixator when mobilising a patient with a weight-bearing platform. The considerable higher mechanical stress on the wires needs to be considered when patients are mobilised with a weight-bearing platform.

Different Patterns in Changes of Exhaled Breath Condensate pH and Exhaled Nitric Oxide After Ozone Exposure

Study objective was the evaluation of pH in exhaled breath condensate (EBC-pH) and nitric oxide in exhaled breath (FeNO) as biomarkers of ozone induced inflammation. We recently demonstrated that an ozone exposure of 240 ppb is sufficient to reduce lung function indices. We enrolled ten healthy subjects exposed in an intermittent exercise protocol to ozone concentrations of 240 ppb and 40 ppb (sham exposure). EBC-pH and FeNO were assessed before (pre), immediately post (post), and 16 h after exposure (16 h). Findings are that compared to baseline, EBC-pH was significantly higher immediately after sham and ozone exposures, but not 16 h later. There was a negative net change in EBC-pH after adjusting for effects after sham exposure (net-ΔpHpost -0.38%, net-ΔpH16h -0.23%). Concerning FeNO, we observed no changes of values after sham exposure compared to baseline, but measured a significant lower net response at the end of exposure (net-ΔFeNOpost -17.5%) which was transient within 16 h (net-ΔFeNO16h -9.4%). We conclude that exercise known to enhance EBC-pH may compensate for EBC acidification associated with inflammation resulting in diminished change of this biomarker. Ozone imposes an oxidative burden and reactions between reactive oxygen species and NO might be an explanation for reduced FeNO levels.

Direct and indirect loading of the Ilizarov external fixator: the effect on the interfragmentary movements and compressive loads

The amount of weight bearing and the force transmission to the frame have an important influence on the results of treatment with an Ilizarov external fixator. The frame provides beneficial interfragmentary movements and compressive loads at the fracture site through elastic wires. Mobilisation can be achieved by applying a weight-bearing platform at the distal end of the fixator. The effect on the interfragmentary movements and the compressive loads in indirect and direct loading were analysed in this study using a composite tibia bone model. Displacement transducers were attached to measure the interfragmentary movements and to detect relative movements of the bone fragments and movements between the rings. The compressive loads in the osteotomy were measured with loading cells in the defect zone. The weight-bearing platform had a substantial effect on the biomechanical behaviour of the frame. It led to an indirect force transmission through the fixator with respect to the osteotomy, resulting in lower compressive loads, lower interfragmentary movements and higher mechanical stress on the frame.

An extension of olfactometry methods: An expandable, fully automated, mobile, MRI-compatible olfactometer

BACKGROUND fMRI experiments on olfaction offer new insights into the complex, but in contrast to other sensory systems, less studied cognition of odors. To perform these experiments is still a challenge. NEW METHOD To address the challenge posed by MR settings, an olfactometer design is presented including specific improvements to the limited number of already existing olfactometers. Innovative features such as pneumatically controlled pinch valves, useable in the scanner and providing exact stimulus timing as well as a 3D-printed nasal mask inlet for common sleep laboratory masks that can be used for lateral divided stimulus presentation are introduced. To ensure a fully automated and mobile system, the use of a flexible and easily-adapted Matlab-Code and a portable adaptable container system are presented. RESULTS The functional efficiency of these features are proven by results of an fMRI study as well as testing temporal resolution and concentration stability with a mass spectrometer. COMPARISON WITH EXISTING METHODS The 24-channel olfactometer design presented here provides an inexpensive alternative to the currently available olfactometers including the achievement of fast onset times, lateral divided stimulus presentation and high flexibility and adaptability to different scientific questions. CONCLUSION The olfactometer design presented in this paper can be seen as a realistic and feasible solution to overcome the challenges of presenting olfactory stimuli within the MR setting.

Relationship of pulmonary function response to ozone exposure and capsaicin cough sensitivity.

Abstract Context: Challenge studies in humans have shown considerable interindividual variability in pulmonary impairment across ozone exposure. Objective: Since previous results suggested effect modulation by neural mechanism, we investigated sensory C-fiber reactivity in relationship to ozone-triggered response pattern. Methods: Cough reflex thresholds reflecting C-fiber sensitivity were evaluated by capsaicin single breath dose–response method. Capsaicin concentrations triggering, respectively, two and five or more coughs (C2, C5) were recorded. Sixteen healthy subjects were randomly exposed in an intermittent exercise protocol to ozone concentrations of 240 and 40 ppb (sham exposure). Ozone responsiveness was defined by a decrease in forced expiratory volume in 1 s (FEV1) of more than 5%. Results: Based on a dichotomous classification, subjects with enhanced reactivity to ozone had lower cough thresholds than non-responders (C2, p = 0.035; C5, p = 0.086). Over all, we could demonstrate relationships between capsaicin sensitivity and ozone-triggered changes in FEV1, peak expiratory flow and maximal expiratory flow at 50% vital capacity but not in specific airway resistance. Conclusion: Our results suggest that capsaicin challenge tests might be useful to characterize subjects with enhanced pulmonary function response towards inhalant irritants.

The Influence of Humidity on Assessing Irritation Threshold of Ammonia

A large number of occupational exposure limit values (OELs) are based on avoiding of sensory irritation of the eyes and the upper respiratory tract. In order to investigate the chemosensory effect range of a chemical, odor and sensory irritation thresholds (lateralization thresholds, LTs) can be assessed. Humidity affects olfactory function and thus influences odor thresholds; however, a similar effect has not been shown for sensory irritation thresholds. The purpose of the present study was to explore whether LTs for ammonia vapor vary depending on the water vapor content of the inspired stimulus. Eight healthy nonsmoking volunteers were simultaneously exposed to ammonia vapor through one nostril and clean air through the other and were asked to determine which nostril received the chemical. Within experimental runs, ascending ammonia concentrations (60–350 ppm) that were either dry or humidified were administered at fixed time intervals. Geometric mean LTs obtained at wet (181 ppm) or dry (172 ppm) conditions did not differ significantly (P = 0.19) and were within the range of those reported by previous studies. These results suggest that humidity is not a critical factor in determining sensory irritation thresholds for ammonia, and future studies will examine if these findings are transferable to sensory irritation thresholds for other chemicals.

Mikro- und Nanosystemtechnik – medizintechnologische Aspekte am Beispiel eines Blasendrucksensors

In der minimal invasiven Diagnostik, Therapie und Therapiekontrolle, bei Implantaten oder Medikamentdosiersystemen sind heute mikro- und nanotechnologische Komponenten wesentliche Bausteine von Gesamtsystemen. Aktuelle Entwicklungen zeigen ein weites Feld von Einsatzmöglichkeiten der Mikro- und Nanotechnik für medizinische Anwendungen. Allein der Weltmarkt physikalischer Sensoren für Druck, Temperatur und Beschleunigung erreichte im Jahr 2003 ein Handelsvolumen von mehreren 100 Milliarden EUR. Aufgrund extremer Miniaturisierung durch mikro- und nanotechnologische Methoden bieten sich kleinste Sensoren für medizinische Anwendungen immer mehr an. Werden physikalische Sensoren mit einer Telemetrieeinheit zur drahtlosen Datenübertragung verbunden, biokompatibel verpackt und minimal invasiv implantiert, können Parameter von Körperfunktionen - wie Drücke in Organen oder Blutdruck, Beschleunigung von Gefäßwänden, Temperatur oder Nervenströme - permanent und kabellos gemessen werden. Für den Bereich der Drucksensorik eröffnen sich in der chirurgischen Diagnostik eine Reihe von Möglichkeiten, die von Druckmessungen im Gehirn nach Trauma, Kompartmentdruckmessungen im Abdomen, Organen oder Extremitäten bis hin zu Blasendruckmessungen bei Patienten mit Querschnittssyndrom reichen. In der vorliegenden Arbeit wird am Beispiel eines Blasendrucksensors dieser Hochtechnologiebereich aus chirurgischer Sicht dargestellt und diskutiert.