Search

This paper documents the design, implementation and evaluation of the Unfolding Space Glove—an open source sensory substitution device. It transmits the relative position and distance of nearby objects as vibratory stimuli to the back of the hand and thus enables blind people to haptically explore the depth of their surrounding space, assisting with navigation tasks such as object recognition and wayfinding. The prototype requires no external hardware, is highly portable, operates in all lighting conditions, and provides continuous and immediate feedback—all while being visually unobtrusive. Both blind (n = 8) and blindfolded sighted participants (n = 6) completed structured training and obstacle courses with both the prototype and a white long cane to allow performance comparisons to be drawn between them. The subjects quickly learned how to use the glove and successfully completed all of the trials, though still being slower with it than with the cane. Qualitative interviews revealed a high level of usability and user experience. Overall, the results indicate the general processability of spatial information through sensory substitution using haptic, vibrotactile interfaces. Further research would be required to evaluate the prototype’s capabilities after extensive training and to derive a fully functional navigation aid from its features.

Purpose Endometriosis is a benign, but potentially serious gynaecological condition in terms of abdominal pain and impaired fertility. Laparoscopic excision techniques are considered the therapeutic standard. HybridAPC is presented as a novel technique for the non-contact thermal ablation of peritoneal endometriosis with simultaneous protection of the underlying thermosensitive structures by creating a needle-free elevated fluid cushion which enables a safer exposure and distance, as well as potentially improved peritoneal conditioning prior to APC. Methods In this prospective randomized clinical trial, 39 patients with 132 superficial endometriotic lesions in total were treated with HybridAPC or sharp excision in an initial laparoscopic procedure according to randomization. In a second-look laparoscopy, adhesion formation was rated macroscopically. Histologic samples were taken from previously treated areas for evaluation of eradication rate. Results The eradication rate was not significantly different between HybridAPC treatment and sharp excision (65 vs. 81%, p = .55). Adhesions formed in 5% of HybridAPC-treated lesions and in 10% after sharp excision (p = .49). HybridAPC treatment was significantly faster than sharp excision (69 vs. 106 s, p Conclusion This clinical trial demonstrates the feasibility of this novel surgical technique with a promising impact on adhesion prevention. Compared to sharp excision, HybridAPC is likely to be a safe, tissue-preserving, and fast method for the treatment of peritoneal endometriosis.

We apply virtual reality headsets with eye tracking capabilities to evaluate new training methods for patients living with loss of peripheral vision (“tunnel vision”). It can be shown that systematic gaze patterns, taught in a virtual reality environment, are able to significantly increase the effectively perceived visual area of the participants as well as reduce the number of obstacle collisions in navigation tasks.

Background Thermal damage to the muscle layer during mucosal application of argon plasma coagulation (APC) may be avoided by creating a fluid cushion within the submucosal layer, but the minimum injection volume needed or the ideal injection fluid are yet to be established. We conducted a systematic ex vivo study with this aim. Methods All experiments were performed in an ex vivo porcine gastrointestinal tract model. Five different fluids (saline, Glyceol, Gelafundin, Voluven, and Eleview) of different volumes were injected into the submucosa of different parts of the gastrointestinal tract. APC was applied to the mucosa at different power settings. Immediately after APC treatment, the temperature was measured through a thermocouple placed inside the fluid cushion, just on top of the muscle layer. The minimum volume of fluid needed to protect the muscle layer from thermal damage was determined. Results There was no difference in the temperature measured among the different injection fluids at the surface of the muscle, in all the locations, at equal injection volumes and power settings. The minimum amounts of fluid needed to protect the muscle layer were 2 and 3 mL for power settings of 30-90 W and 90-120 W, respectively. Conclusions Normal saline and 4 commercially available submucosal injection fluids possess similar thermal protective effects. To reduce the likelihood of thermal damage to deeper layers when APC is applied, a minimum injection volume of 3 mL is recommended if less than 90 W power will be utilized over 3 sec.

Argon plasma coagulation is a promising new approach to combat obesity. During the procedure, a large area of the gastric lamina mucosae and the parietal cells that are located in this layer are ablated. This reduces the secretion of the hormone ghreline, which is known to play a major role in inducing appetite. One hypothesis is that this procedure partly suppresses the feeling of hunger which lowers the food-intake and body weight effectively. To rule out side effects, the treatment of other structures of the gastric wall that are much more sensitive to thermal injury, such as the tela submucosa and the lamina muscularis propria, needs to be avoided. The possibility of layer specific tissue differentiation is explored in this work using optical emission spectroscopy on ex vivo human stomach tissue. The optical emission generated during the plasma treatment of each layer is measured with two different spectrometers. The three main layers of the gastric wall can be differentiated by specific emissions lines of electrolytic ions and trace elements. In order to evaluate the diagnostic quality of this method a linear support vector classifier is used to differentiate the three layers against each other on the basis of these emission lines of these elements. This differentiation between ‘mucosa’ and ‘submucosa’ results in a sensitivity of up to 82% and specificity of up to 92%. However, a lower sensitivity and specificity is found for a classification between ‘submucosa’ and ‘muscularis’ which implies that a classification between ‘mucosa’ and ‘not mucosa’ would be a much more suitable classification for a later clinical application.

People living with a degenerative retinal disease such as retinitis pigmentosa are oftentimes faced with difficulties navigating in crowded places and avoiding obstacles due to their severely limited field of view. The study aimed to assess the potential of different patterns of eye movement (scanning patterns) to (i) increase the effective area of perception of participants with simulated retinitis pigmentosa scotoma and (ii) maintain or improve performance in visual tasks. Using a virtual reality headset with eye tracking, we simulated tunnel vision of 20° in diameter in visually healthy participants (n = 9). Employing this setup, we investigated how different scanning patterns influence the dynamic field of view—the average area over time covered by the field of view—of the participants in an obstacle avoidance task and in a search task. One of the two tested scanning patterns showed a significant improvement in both dynamic field of view (navigation 11%, search 7%) and collision avoidance (33%) when compared to trials without the suggested scanning pattern. However, participants took significantly longer (31%) to finish the navigation task when applying this scanning pattern. No significant improvements in search task performance were found when applying scanning patterns.

An electrosurgical argon plasma with a 5% admixture of molecular hydrogen is studied in order to investigate time averaged plasma parameters by optical emission spectroscopy (OES). Electron densities in the range of 1015–1016 cm−3 are determined from the Stark broadening of the time averaged line profiles of the Balmer-α and -β emission lines of hydrogen. A two-profile fit corresponding to regions of different electron densities is found to provide a better representation of the line broadening than a single profile fit. This is consistent with time resolved ICCD imaging, acquired with 150 ns time resolution, that shows strong radial gradients in the plasma emission and the asymmetry produced by the discharge arrangement. Gas temperatures are determined using two different methods. Firstly, simulated spectra for different rotational temperatures are fitted to the measured N2(C-B, 0-1) emission band originating from ambient air diffusion into the argon/hydrogen gas flow. From the best fit, rotational temperatures between 1500 K and 1800 K are inferred. These measurements are in good agreement with those inferred by the second method, which is based on the collisional broadening of the emission lines of neutral argon at 750 nm and 751 nm. This latter method may be useful for the measurement of gas temperatures when the device is used inside hollow organs during endoscopic or laparoscopic interventions, where air mixing will be limited. Therefore, the results of this study are highly relevant to applications of these devices, e.g. for controlling tissue effects and the avoidance of excessive heating.

This prospective, randomized, controlled, single-blinded study investigates the peritoneal adhesion formation of HybridAPC (waterjet elevation of the peritoneum with subsequent argon plasma coagulation) versus only waterjet (elevation with the same instrument, but without subsequent argon plasma coagulation) in a rat model (24 female Wistar rats). Bilateral lesions were created on the abdominal wall with HybridAPC on one sidewall and waterjet elevation on the other sidewall of the peritoneum in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Incidence of adhesion formation was 2.3% for HybridAPC; no adhesions occurred for peritoneal elevation with saline (p = 1.00). Histologic evaluation revealed no acute inflammation in both groups. An overall moderate degree of granulation tissue formation and myonecrosis was observed in the HybridAPC group, whereas no chronic inflammation and myonecrosis occurred after elevation without thermal ablation (p

Objective To investigate peritoneal adhesion formation of monopolar contact coagulation (MCC) versus noncontact argon plasma coagulation (APC) in a rat model. Design Randomized, controlled, single-blinded animal study. Setting University laboratory. Animal(s) Sixteen female Wistar rats. Intervention(s) Bilateral lesions were created on the abdominal wall with MCC and APC in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. Main Outcome Measure(s) Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Result(s) Average energy intake was 99.5 ± 7.39 J for APC and 95.7 ± 9.62 J for monopolar contact coagulation. Incidence of adhesion formation was 50.0% for noncontact APC and 85.4% for MCC. MCC induced significantly more vascular adhesions. Histological evaluation revealed no significant differences regarding average depth of lesions induced by APC and MCC. Both groups showed almost identical morphology of necrosis and granulation tissue formation. Conclusion(s) This study compares for the first time adhesion formation of MCC versus noncontact APC in a rat model. With a similar energy intake, contact coagulation induced a significantly higher rate of adhesion formation. APC-induced adhesions were significantly less vascularized compared with MCC adhesions. Besides the thermal effects of both coagulation methods, the direct mechanical contact of the MCC electrode with the highly sensitive peritoneum is thus determined to be a pivotal additional stimulus for adhesion formation.

The aim of this study is to systematically investigate under standardized experimental conditions the effects of instrument contamination and wear on the quality of bipolar vessel sealing (BVS) achieved using a reusable instrument.The study was designed as a prospective, randomized, and controlled in vitro study and conducted in an academic research environment. Reusable bipolar coagulation forceps (BiClamp® 200 C, ERBE Elektromedizin) were used to apply sealing pressures of 300-1,100 mN/mm(2) to 239 renal arteries from commercially slaughtered female pigs (Swabian-Hall Swine). Forceps jaws were coated with porcine blood, blood and collagen, or blood, collagen, and fat to simulate instrument contamination with biological material during surgery. Clinical wear was mimicked by sandpaper abrasion. The main outcome measures were seal success (resistance to 250 mmHg intraluminal pressure for 2 min) and seal stability (burst pressure).Sealing pressure had a significant impact, with 800 mN/mm(2) producing the best sealing results. Seal success increased with total energy applied to the tissue, a higher maximum temperature, and longer coagulation as indicated by desiccation time. Experimental contamination had no significant impact on seal success and only a limited effect on seal stability. Similarly, abrasive wear also had no significant effect on either seal quality or seal strength.The impact of bipolar forceps contamination and wear on seal success and quality was negligible in our in vitro model. To achieve high-quality seals, it is essential to use adequate sealing pressures. Our findings could have direct implications for the design and clinical handling of BVS instruments.

Background New therapies are needed for pancreatic cancer. Objective To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. Design A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. Setting San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. Patients A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. Intervention Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. Main Outcome Measurements Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. Results The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). Limitations Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. Conclusion EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

Electrosurgical vessel sealing produces seals that can withstand intraluminal pressures well above the physiological range. In many cases it is more efficient than other methods, such as sutures, hemoclips, and ultrasonic coagulation devices, but bears lateral thermal damage as a side effect. The overall aim of this study was to compare the thermal lateral damage (TL) in vivo versus ex vivo using two different bipolar vessel sealing instruments in an epigastric vein animal model.A total of 96 thermofusions of bilateral epigastric veins were carried out in a prospective, randomized and controlled study design. The laparoscopic BiClamp (type Maryland) and the bipolar clamp Kelly model Clermont-Ferrand were used for ex vivo versus in vivo investigation. After exposure of the two bilateral epigastric veins the proximal sections were bilaterally coagulated in vivo with the two different instruments. For ex vivo coagulation, the uncoagulated section of the vein was removed and coagulated ex vivo. The TL was investigated by infrared measurement, light microscope and histological analysis.The comparison of the extent of coagulation damage between ex vivo and in vivo coagulation did not differ significantly: no differences between in vivo and ex vivo measurements were found for the Kelly clamp. In the case of the Maryland clamp only a significant greater TL in vivo was shown for stereomicroscopic measurements.Ex vivo TL results are comparable with in vivo results. This might prospectively spare in vivo studies with respect to TL and might facilitate the design of future experiments for the development of bipolar electrocoagulation devices.

Objective To investigate the peritoneal adhesion formation of two pulsed noncontact argon plasma coagulation (APC) modes in a rat model. Design Prospective, randomized, controlled, and blinded study. Setting Laboratory facilities of a university department of obstetrics and gynecology. Animal(s) Ten female Wistar rats. Intervention(s) Bilateral lesions were created on the abdominal wall with low and high APC energy in a standard fashion. After 10 days the rats were killed to evaluate the peritoneal trauma sites. Main Outcome Measure(s) Adhesion incidence, quantity, and quality were scored 10 days after surgery and studied by histopathologic analysis. Result(s) The area of coagulation was 30 ± 8.4 mm 2 in the case of high APC energy and 12 ± 5.6 mm 2 (low APC energy). Macroscopic thermal damage of the peritoneum is significantly higher when applying high APC energy. Adhesions due to APC with high energy occurred in 64% and with low energy in 6% of cases. High energy results mainly in dense adhesions. The lesions in the high-energy group showed intense granulation tissue formation with centrally located myocyte necrosis with intense neutrophilic inflammation. Conclusion(s) This study describes for the first time that different noncontact APC energy settings induce peritoneal adhesions in a reproducible rat model. Higher energy produced significantly deeper tissue defects and adhesions of higher grade. A plasma coagulation system that develops fewer adhesions can be achieved by lower temperature and a more homogeneous application and if the application area desiccates more slowly.

Background and study aims Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection of large gastrointestinal tumors. However, this technique has disadvantages such as a long intervention time, complexity of the procedure, and a higher rate of complications. The primary aims of the study were to show the feasibility of ESD in the pig colon and to evaluate a new ESD technique comprising the use of a newly developed hybrid knife for colon procedures combining RF (radiofrequency) application and a distance-dependent water-jet application. Materials and methods ESD was conducted at three different locations in the colon according to the computer-generated randomization list, using either the standard technique (injection needle, flex knife, and hook knife as therapeutic instruments and DRY CUT and SWIFT COAG as RF currents), or the new ESD technique (hybrid knife as the therapeutic instrument combined with the new cutting mode ENDO CUT D) in 12 healthy pigs. The perforation and bleeding rates were documented and statistically analyzed. Intervention time, resected specimen size, thermal and mechanical damage of the resection bed, and number of instrument changes required were also recorded. Results A total of 16 and 18 ESD procedures were performed by the standard and new techniques, respectively. Complete en bloc resection was achieved in all cases. The standard ESD technique showed a perforation rate of 25 % (4/16) whereas the new ESD technique resulted in a 5.5 % perforation rate (1/18) ( P = 0.035); bleeding rates were similar. The new ESD technique was significantly safer compared with the standard ESD technique. Conclusions A new ESD technique for the successful en bloc resection in thin-walled regions such as pig colon has been described. This procedure is as effective as the standard procedure but is easier to handle and significantly safer.

BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16 - 18 W) and simultaneous cooling with CO 2 (standardized pressure: 675psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R liver = 0.71; R spleen = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 ( P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.

Starting point of the present paper was the result of a virtual screening using the open conformation of the large extracellular loop (LEL) of the CD81-receptor (crystal structure: PDB-ID: 1G8Q). After benzyl salicylate had been experimentally validated to be a moderate inhibitor of the CD81-LEL-HCV-E2 interaction, further optimization was performed and heterocyclic-substituted benzyl salicylate derivatives were synthesized. The compounds were tested for their ability to inhibit the interaction of a fluorescence-labeled antibody to CD81-LEL using HUH7.5 cells. No compound showed an increase concerning the inhibition of the protein-protein interaction compared to benzyl salicylate.

We describe a collection of structurally diverse inhibitors of protein-protein-interactions (PPIs). This collection is compared against the FDA drug database and a subset of the ZINC database by machine learning methods which rely on classical QSAR descriptors. We obtain a decision tree that contains three descriptors. Of particular importance is a constitutional descriptor related to molecular shape and size. Validation of the decision tree by various procedures indicates that it does not result from chance correlations and has predictive value. We conclude that constitutional descriptors may be valuable tools in the preselection of potential PPI inhibitors from compound databases.

Bipolar electrothermal vessel sealing is a widely used method for the sealing of blood vessels and tissue of up to several millimeters diameter. Despite their wide-spread usage, instruments and generator modes are often traditionally developed and enhanced. A systematic investigation of the thermofusion process and the subsequent derivation of new model-based control strategies have the potential to improve the vessel sealing process and reduce unwanted side-effects. Based on a previously developed mathematical model of bipolar vessel sealing, optimization based control strategies are developed that could possibly reduce the thermal damage to the lateral tissue. Assuming that it is sufficient to ensure a certain tissue temperature for successful thermofusion, it is shown that the lateral damage could be significantly reduced by optimizing the generator voltage. Furthermore it is shown, that an optimized voltage trajectory may still reduce the lateral damage to some extent if it is assumed that tissue desiccation is required. Additionally, optimally pulsed voltage strategies are presented and compared to currently employed typical generator modes. The results illustrate that optimized control strategies can potentially reduce the thermal damage to the lateral tissue and thus make bipolar vessel sealing more suitable for surgical procedures in the vicinity of sensitive structures, particularly nerves.

Radiofrequency-induced thermofusion is a frequently used electrosurgical procedure for the sealing of blood vessels. A disadvantage of vessel sealing instruments is that the generated thermal energy spreads to the surrounding tissue and may irreversibly damage it. This is particularly problematic when operating close to sensitive structures such as nerves. Given their advantages, there is nonetheless a lot of interest in using bipolar vessel sealing for surgical procedures. To select instruments that may be safely used in such cases, it is important to reliably quantify the thermal spread to the surrounding tissue. Mathematical models can help to evaluate the transient behavior, that is the evolution of the thermal spread over time, more precisely. A finite element model allows for a detailed analysis of inhomogeneities in the spatial temperature distribution. As a first step towards a finite model of the bipolar vessel sealing process, a model of the coagulation of chicken egg white is presented here. Egg white has thermal and electrical properties that are very similar to tissue, making it suitable as a substitute for the analysis of the coagulation process. It has the additional advantage, that the spatial and temporal evolution of the thermal spread can be visually gauged. The presented model describes the experimentally observed spatial temperature distribution, the shape of the coagulated egg white, and the formation of hotspots. Furthermore, it is shown that the model can correctly predict the shape of the coagulated egg white in further experiments.

Background For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. Objective We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barrett9s oesophagus (BO). Design BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) ≤3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). Results There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1±6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). Conclusions In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. Trial registration number NCT1871636

An approach to estimate equilibrium re bond lengths of organic molecules which contain standard bonding situations for CC, CH, CO and CN distances from only one equation is presented. For this, optimizations of molecular geometries using correlated post-Hartree–Fock and density functional methods have been performed. A selection scheme was developed to determine the most reliable methodology for prediction of equilibrium re distances of covalent bonds from a set of investigated theoretical methods. Consequently, distances computed in the CCSD(T) procedure via exponential extrapolation from a consecutive set of Dunning cc-pVXZ basis sets by use of Eqn (2) are accurate up to ± 0.0005 A in comparison to experimentally available re distances. Applications for predictions of the experimentally unknown re distances of methanol, methylamine and methylenimine are presented. Additionally the estimation of re distances of larger, chemically more interesting molecules is possible by lower order calculations (e.g. DFT B3LYP/cc-pVDZ) via linear correlation statistics using the results from our re reference model system via Eqn (3). Copyright © 2006 John Wiley & Sons, Ltd.

A method is suggested for combining the quantum chemical principle of isolated molecules and the systematics of homologous families for different functional groups in traditional organic chemistry. The classification of organic compounds is performed by statistical treatments of fundamental quantum mechanical quantities such as total and partial energies. We used the total energies (computed by DFT BLYP and B3LYP, HF and MP2 methods, which are size-extensive, applying the 6–31 G** and some other basis sets) of isolated molecules obtained by gradient optimizations to classify homologous series of organic compounds by linear least-squares regressions versus the total number of electrons. Two numerical parameters, slope (h) and intercept (s), are obtained characterizing each family of homologous compounds. Families of for example 17 different functional groups of the same CH2-homologous unit are grouped on parallel lines with the same slope h, differing only in their s parameters. Isomeric compounds differ in their s values if they belong to the same homologous unit. Compounds of other homologous units (conjugated alkenes, cumulenes and benzenoides) are found with different slopes h on regression lines. Energy partitioning leads also to linear regressions of different statistical accuracy for the components which add fully to the observed h and s parameters. The h and s parameters allow the prediction of unknown total energies of homologous compounds from total energies of a subset of smaller compounds which belong to the same homologous family. Likewise, atomization energies can be predicted using the derived h and s parameters. Copyright © 2002 John Wiley & Sons, Ltd.

Optimized bond lengths for molecules containing CO bonds have been calculated by HF, post HF (MP2, LMP2, MP4(SDQ), CCSD(T) and DFT (BLYP, B3LYP, B3PW91, BHandH) methods using different basis sets. Linear regressions of calculated and experimentally available re CO bond lengths of organic molecules have been performed. The best basis set out of the set of up to 10 standard basis sets within a theoretical method was derived from a ranking procedure based on statistical parameters. This ranking scheme allows also the determination of the best method/basis set combination for all selected methods and basis sets. We studied the application of our recently developed prediction schemes for estimations of higher order basis set CO distances from lower order calculations and estimations of CO re bond lengths from linear regression equations. These procedures allow predictions of near re CO distances of high accuracy even form modest level of theory. Therefore this leads to a chance for treatment of large or difficult to handle molecules for which experimental determinations of re structures are inaccessible.

Optimized bond lengths have been calculated by DFT methods using six functionals and 10 basis sets. None of the predicted values agreed completely with the experimental r e distances and they are in general too large. Available accurate experimental r e distances for CH and CC bonds of simple organic molecules have been linearly correlated with corresponding DFT optimized molecular structures. These regression equations can be used for prediction of accurate experimental r e equilibrium distances of CH and CC bonds of medium-sized to large molecules. The derived regression equations also enable the introduction of distance dependent scaling factors which allow very accurate predictions of higher order basis set geometries from lower order calculations. Analytical equations for the determination of these scaling factors have been derived. Thus, large savings of CPU time (dependent on the size of the system) are possible. Applications to both small hydrocarbons with up to six carbon atoms and larger molecules such as alanin dipeptide and vitamin A are presented. Likewise, more critical test cases such as singlet and triplet methylencarbene and strained cyclic hydrocarbons are considered.

Complete surgical removal of cancer tissue with effective preservation of healthy tissue is one of the most important challenges in modern oncology. We present a method for real-time, in situ differentiation of tissue based on optical emission spectroscopy (OES) performed during electrosurgery not requiring any biomarkers, additional light sources or other excitation processes. The analysis of the optical emission spectra, enables the differentiation of healthy and tumorous tissue. By using multi-class support vector machine (SVM) algorithms, distinguishing between tumor types also seems to be possible. Due to its fast reaction time (0.05s) the method can be used for real-time navigation helping the surgeon achieve complete resection. The system’s easy realization has been proven by successful integration in a commercial electro surgical unit (ESU). In a first step the method was verified by using ex vivo tissue samples. The histological analysis confirmed, 95% of correctly classified tissue types.

Bipolar radiofrequency-induced thermofusion has become a widely accepted method successfully used in open and particularly in minimally-invasive surgery for the sealing of blood vessels and tissue of up to several millimeters diameter. Despite its wide-spread application, the thermofusion process itself is not well understood on a quantitative and dynamic level, and manufacturers largely rely on trial-and-error methods to improve existing instruments. To predict the effect of alternative generator control strategies and to allow for a more systematic approach to improve thermofusion instruments, a mathematical model of the thermofusion process is developed. The system equations describe the spatial and temporal evolution of the tissue temperature due to Joule heating and heat transfer, and the loss of tissue water due to vaporization. The resulting effects on the tissue properties, most importantly the electrical resistivity, heat capacity and thermal conductivity, are considered as well. Experimental results indicate that the extent of the lateral thermal damage is directly affected by Joule heating of the lateral tissue. The experimental findings are supported by simulation results using the proposed mathematical model of thermofusion.

Thermal ablation for Barrett's oesophagus has widely been established in gastrointestinal endoscopy during the last decade. The mainly used methods of radiofrequency ablation (RFA) and argon-plasma coagulation (APC) carry a relevant risk of stricture formation of up to 5-15%. Newer ablation techniques that are able to overcome this disadvantage would therefore be desirable. The aim of the present study was to compare the depth of tissue injury of the new method of Hybrid-APC versus standard APC within a randomized study in a porcine oesophagus model.Using a total of eight explanted pig oesophagi, 48 oesophageal areas were ablated either by standard or Hybrid-APC (APC with prior submucosal fluid injection) using power settings of 50 and 70 W. The depth of tissue injury to the oesophageal wall was analysed macroscopically and histopathologically.Using 50 W, mean coagulation depth was 937 ± 469 µm during standard APC, and 477 ± 271 µm during Hybrid-APC (p = 0.064). Using 70 W, coagulation depth was 1096 ± 320 µm (standard APC) and 468 ± 136 µm (Hybrid-APC; p = 0.003). During all settings, damage to the muscularis mucosae was observed. Using standard APC, damage to the submucosal layer was observed in 4/6 (50 W) and 6/6 cases (70 W). During Hybrid-APC, coagulation of the submucosal layer occurred in 2/6 (50 W) and 1/6 cases (70 W). The proper muscle layer was only damaged during conventional APC (50 W: 1/6; 70 W: 3/6).Ex-vivo animal study with limited number of cases.Hybrid-APC reduces coagulation depth by half in comparison with standard APC, with no thermal injury to the proper muscle layer. It may therefore lead to a lower rate of stricture formation during clinical application.

Background. This is a prospective, randomized, controlled, single-blinded study to investigate peritoneal adhesion formation of standard argon plasma coagulation (APC) versus aerosol plasma coagulation in a rat model. Methods. Bilateral lesions were created on the abdominal wall of 16 female Wistar rats with standard and aerosol plasma coagulation APC energy in a standard fashion. After 10 days, the rats were killed humanely to evaluate the peritoneal trauma sites. Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Results. Average energy intake was 97.7 ± 3.1 J for APC and 93.8 ± 4.2 J for aerosol plasma coagulation. Incidence of adhesion formation was 74.2% for standard APC and 16.1% for aerosol plasma coagulation ( P < .0001). Standard APC mainly results in dense adhesions. Histological evaluation revealed no significant difference with regard to the average depth of lesions created by APC and aerosol plasma coagulation ( P = 0.21) at day 10; both groups showed an identical morphology of necrosis and granulation tissue formation. Conclusions. This study compares adhesion formation of standard APC versus aerosol plasma coagulation in a rat model. Standard APC produced significantly more adhesions. Aerosol plasma coagulation creates fewer adhesions, which are of lower grade, which seems to be achieved mainly by improved peritoneal conditioning in this animal model.

Electric scalpels are used for cutting of biological tissue, for example, for resection of tumour tissue in surgery. During the electrosurgical procedure a plasma is ignited in a gap between the electric scalpel and the tissue. In this study, the plasma operated on porcine kidney and a tissue substitute (cellulose impregnated with isotonic saline) is characterised by means of voltage-current measurements, microphotography, optical emission spectroscopy and numerical simulation. The molecular emission of nitrogen is used for the determination of the gas temperature and the reduced electric field. The electron density is determined using the measured electric current density.

Electrosurgery is the use of radio-frequency electric current for the cutting of biological tissue e.g. for resection of tumour tissue. In this work, the optical emission of plasma being generated during the electrosurgical procedure is investigated with a high resolution echelle spectrometer to find differences between tumour tissue and normal renal tissue in a pre-clinical ex vivo study. Trace elements like zinc, iron, copper and cadmium are present in the tissue spectra as well as the electrolytes magnesium, calcium, sodium and potassium and some diatomic molecules such as hydroxyl radical, cyano radical, dicarbon, nitrogen monohydride and molecular nitrogen which are mainly dissociated from polyatomic molecules. With the atomic emission line of cadmium at 228.8 nm the treated tissue can be differentiated in tumorous and healthy tissue with correct assignment of 95% for tumour tissue and 92% for normal renal tissue.

Purpose To test the efficacy of internally CO 2 -cooled radiofrequency (RF) ablation in vivo and to compare its effectiveness to a standard water-cooled RF probe and to a gas-cooled microwave (MW) device. Method and materials 49 ablations were performed on 15 pigs under general anesthesia using 15G monopolar CO 2 -cooled RF applicators, 17G monopolar water-cooled RF applicators and 15G internally CO 2 -cooled microwave devices. The power of the MW device was 45 W, the current of the gas-cooled RF device was 1200–1600 mA. At the water-cooled RF probe, maximum power of 200 W was set. Ablation time was 15 min. The short and long axes of the ablation zone were measured. Histological analyses and NADH-staining were performed. The diameters and the ablation volumes were compared using an analysis of variance. Results No spots of untreated tissue were observed close to the cooled needle track in any of the ablation zones. The largest short axis diameter was 3.4 ± 0.5 cm achieved with the gas-cooled monopolar applicator. With the water-cooled applicators, short axis diameter was significantly smaller, reaching 2.5 ± 0.4 cm. Gas-cooled MW probes achieved 2.9 ± 1.0 cm. The largest ablation volume was 31.5 ± 12 ml (gas-cooled RF), and the smallest was 12.7 ± 4 ml (water-cooled RF). Short/long axis ratio was largest for gas-cooled RF probes with 0.73 ± 0.08 versus 0.64 ± 0.04 for the water-cooled probes and 0.49 ± 0.25 for the microwave applicator. Conclusion Gas-cooled RF applicators may have a higher potential for effective destruction of liver lesions than comparable water-cooled RF systems, and may be an alternative to standard RF and MW ablation devices.

Background: Ablative therapies such as radiofrequency and cryotechnology are widely used in oncological intervention but not in the pancreatic field because of their high operative risks. A new flexible bipolar ablation device (Cryotherm probe [CTP]) was developed combining radiofrequency and cryotechnology. Objective: To evaluate the efficacy of the CTP in destroying neoplastic tissue of explanted pancreatic tumors of patients with pancreatic adenocarcinoma. Design: Ex vivo clinical study. Setting: Inpatient hospital setting. Patients: This study involved 16 explanted pancreatic tumors from 16 patients. Interventions: CTP application was performed on explanted pancreatic tumors. Anatomic specimens were divided into 4 groups; each group received a predefined application time of 120 to 600 seconds. Main Outcome Measurements: The coagulation diameter (short axis) perpendicular to the device's longitudinal axis was used as the primary outcome measure. Results: All pancreatic specimens showed histological signs of coagulative necrosis. There was a positive correlation between the short axis of the obtained necrosis and duration of application (r = 0.74). Limitations: This study was an ex vivo study with all limitations typical of this kind of study. Conclusions: The CTP is effective in destroying neoplastic pancreatic tissue, creating an ablation zone, the extent of which is related to the duration of application. ZR 0 ZS 0 Z8 1 ZB 2 BACKGROUND: Ablative therapies such as radiofrequency and cryotechnology are widely used in oncological intervention but not in the pancreatic field because of their high operative risks. A new flexible bipolar ablation device (Cryotherm probe [CTP]) was developed combining radiofrequency and cryotechnology.OBJECTIVE: To evaluate the efficacy of the CTP in destroying neoplastic tissue of explanted pancreatic tumors of patients with pancreatic adenocarcinoma.DESIGN: Ex vivo clinical study.SETTING: Inpatient hospital setting.PATIENTS: This study involved 16 explanted pancreatic tumors from 16 patients.INTERVENTIONS: CTP application was performed on explanted pancreatic tumors. Anatomic specimens were divided into 4 groups; each group received a predefined application time of 120 to 600 seconds.MAIN OUTCOME MEASUREMENTS: The coagulation diameter (short axis) perpendicular to the device's longitudinal axis was used as the primary outcome measure.RESULTS: All pancreatic specimens showed histological signs of coagulative necrosis. There was a positive correlation between the short axis of the obtained necrosis and duration of application (r = 0.74).LIMITATIONS: This study was an ex vivo study with all limitations typical of this kind of study.CONCLUSIONS: The CTP is effective in destroying neoplastic pancreatic tissue, creating an ablation zone, the extent of which is related to the duration of application.

OBJECTIVES To evaluate a newly developed computer-controlled cutting system for the generation of standardized resections and to systematically compare the hemostatic properties and tissue effect of 2 cutting modes, namely, AUTO CUT and DRY CUT used in urologic procedures. METHODS An isolated perfused kidney model was used to assess blood loss and coagulation depth after resection of tissue specimens of standardized geometry, size, and cutting velocity with a resection loop. Three different effect settings (E1, E3, and E6; 200 W) of the electrosurgical modes AUTO CUT and DRY CUT were compared. Blood loss was determined semiquantitatively by weighing a swab before and after placing it onto the resection area. The coagulation depth was estimated microscopically on cross sections. RESULTS The computer-controlled cutting system creates resections of standardized geometry and size with a high reproducibility. An effect level-dependent increase in hemostasis and coagulation depth could be demonstrated with the cutting modes DRY CUT and AUTO CUT using this computer-controlled cutting system. The hemostatic effect with DRY CUT is significantly more pronounced than with AUTO CUT (E1, E3: P < .0001, E6: P = .004), and the coagulation is significantly deeper (E1, E3, E6: P < .0001). CONCLUSIONS The computer-controlled cutting system creating reproducible resections in combination with the isolated perfused kidney model offers the possibility to systematically investigate bleeding rate and coagulation depth. The stronger hemostatic properties of the DRY CUT mode are more favorable for urologic interventions requiring a higher hemostatic effect than the AUTO CUT mode.

17beta-Estradiol (E2) is implicated in the genesis and the development of estrogen-dependent diseases. Its concentration is mainly regulated by 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction of the weak estrogen estrone (E1) to the highly potent E2. This enzyme is thus an important target for the treatment of hormone-dependent diseases. Thirty-seven novel substituted 6-phenyl-2-naphthols were synthesized and evaluated for 17beta-HSD1 inhibition, selectivity toward 17beta-HSD2 and the estrogen receptors (ERs) alpha and beta, and pharmacokinetic properties. SAR studies revealed that the compounds most likely bind according to binding mode B to the active site, i.e., the 6-phenyl moiety mimicking the steroidal A-ring. While substitution at the phenyl ring decreased activity, introduction of substituents at the naphthol moiety led to highly active compounds, especially in position 1. The 1-phenyl compound 32 showed a very high inhibitory activity for 17beta-HSD1 (IC50 = 20 nM) and good selectivity (17beta-HSD2 and ERs) and pharmacokinetic properties after peroral application.