Antibiotic Bactericidal Activity Is Countered by Maintaining pH Homeostasis in Mycobacterium smegmatis.

Antibiotics target specific biosynthetic processes essential for bacterial growth. It is intriguing that several commonalities connect the bactericidal activity of seemingly disparate antibiotics, such as the numerous conditions that confer broad-spectrum antibiotic tolerance. Whether antibiotics kill in a manner unique to their specific targets or by a universal mechanism is a critical and contested subject. Herein, we demonstrate that the bactericidal activity of diverse antibiotics against Mycobacterium smegmatis and four evolutionarily divergent bacterial pathogens was blocked by conditions that worked to maintain intracellular pH homeostasis. Single-cell pH analysis demonstrated that antibiotics increased the cytosolic pH of M. smegmatis, while conditions that promoted proton entry into the cytosol prevented intracellular alkalization and antibiotic killing. These findings led to a hypothesis that posits antibiotic lethality occurs when antibiotics obstruct ATP-consuming biosynthetic processes while metabolically driven proton efflux is sustained despite the loss of proton influx via ATP synthase. Consequently, without a concomitant reduction in respiratory proton efflux, cell death occurs due to intracellular alkalization. Our findings indicate the effects of antibiotics on pH homeostasis should be considered a potential mechanism contributing to antibiotic lethality. IMPORTANCE Since the discovery of antibiotics, mortality due to bacterial infection has decreased dramatically. However, infections from difficult to treat bacteria such as Mycobacterium tuberculosis and multidrug-resistant pathogens have been on the rise. An understanding of the cascade of events that leads to cell death downstream of specific drug-target interactions is not well understood. We have discovered that killing by several classes of antibiotics was stopped by maintaining pH balance within the bacterial cell, consistent with a shared mechanism of antibiotic killing. Our findings suggest a mechanism of antibiotic killing that stems from the antibiotic's ability to increase the pH within bacterial cells by disrupting proton entry without affecting proton pumping out of cells. Knowledge of the core mechanism necessary for antibiotic killing could have a significant impact on the development of new lethal antibiotics and for the treatment of recalcitrant and drug-resistant pathogens.

Frontiers of robotic endoscopic capsules: a review.

Digestive diseases are a major burden for society and healthcare systems, and with an aging population, the importance of their effective management will become critical. Healthcare systems worldwide already struggle to insure quality and affordability of healthcare delivery and this will be a significant challenge in the midterm future. Wireless capsule endoscopy (WCE), introduced in 2000 by Given Imaging Ltd., is an example of disruptive technology and represents an attractive alternative to traditional diagnostic techniques. WCE overcomes conventional endoscopy enabling inspection of the digestive system without discomfort or the need for sedation. Thus, it has the advantage of encouraging patients to undergo gastrointestinal (GI) tract examinations and of facilitating mass screening programmes. With the integration of further capabilities based on microrobotics, e.g. active locomotion and embedded therapeutic modules, WCE could become the key-technology for GI diagnosis and treatment. This review presents a research update on WCE and describes the state-of-the-art of current endoscopic devices with a focus on research-oriented robotic capsule endoscopes enabled by microsystem technologies. The article also presents a visionary perspective on WCE potential for screening, diagnostic and therapeutic endoscopic procedures.

DC current pulses for OTSC clip fragmentation: technology and experimental study.

BACKGROUND: The OTSC clip is used in endoscopic management of gastrointestinal lesions. In rare cases, the removal of the OTSC clip might be desirable. The objective of the study is to investigate feasibility, efficacy, and safety of a novel endoscopic instrument system for removal of the OTSC clip. METHODS: The study series has been conducted in a porcine model. Clip removal is performed with a prototype instrumentation that is designed to locally melt the clip by applying an electrical current pulse onto the clip structure. This system has been evaluated in an animal study (n = 10) in a pig model. A cap prototype with an elongated sleeve has been used for extraction of the OTSC clip fragments. RESULTS: 23 of 24 implanted OTSC clips were successfully opened by applying in a total of 74 current pulses. Superficial mucosal coagulation marks were observed in 14 of the 24 application sites. No other findings such as hemorrhage, deep thermal wall lesions, or perforation were observed. CONCLUSIONS: The study confirms the effectiveness and safety of the proposed endoscopic removal technique. Safe extraction of the clip fragments was feasible with an elongated sleeve at the distal cap. Limitations of the methods are the animal model and the experimental nature of the prototype instrumentation.

A novel robotic system for single-port laparoscopic surgery: preliminary experience.

BACKGROUND: The concept of single-access procedures has gained greater attention from general surgeons during the past 5 years. Despite this wide momentum, these procedures pose several changes for the surgeon, such as impaired eye-hand coordination and restricted manipulation. In this context, robotic-assisted surgery represents a promising technology to enhance the dexterity of laparoscopic surgeons. METHODS: A novel teleoperated robotic system for minimally invasive surgery (MIS) called SPRINT (Single-Port lapaRoscopy bImaNual roboT) has been developed. SPRINT is a master-slave robotic platform designed for bimanual interventions through a single-access port. The system is basically composed by two main arms having a maximum diameter of 18 mm and a stereoscopic-camera (Karl-Storz, Tuttlingen, Germany). The arms may be inserted into a cylindrical introducer that has a maximum diameter of 30 mm. The surgeon console is composed of two master manipulators, a foot-switch, and a 3D full-HD display. RESULTS: In an animal study, a small-bowel enteroenterostomy and the ligation of a mesenteric vessel bundle have been performed. As preliminary experience, the system has been placed within the peritoneal cavity through an incision of approximately 10 cm: the robot has been suspended in an open fashion, due to some mechanical constraints of the current prototype. The procedures have been performed in an authorized laboratory on a female pig of approximately 50 Kg. CONCLUSIONS: Two typical surgical maneuvers have been performed successfully with the SPRINT surgical platform: an intestinal anastomosis and a vessel ligation. Moreover, the speed, precision, and force with which the SPRINT robot executed the commands by the surgeon controlling the master console have been subjectively described as adequate to the tasks. Based on this preliminary demonstration, bimanual robot solutions, such as the SPRINT robot, may offer more dexterity and precision to single-port techniques in the next future.

The anal fistula claw: the OTSC clip for anal fistula closure.

AIM: Surgical closure of high or complex anal fistulae is often a difficult challenge. A special Nitinol clip, the OTSC clip (Ovesco AG), was evaluated for fistula closure in a porcine model. METHOD: A total of 20 fistulae were created in 10 animals by seton insertion. Four weeks after fistula induction the setons were removed: one internal fistula opening per animal was left untreated as control whereas the other opening was closed by the OTSC clip using a specially developed transanal clip applicator. The safety and technical feasibility of the clip application were tested. Another 4 weeks later, fistulae were macroscopically assessed for closure. For histological examination, the anorectum including the fistula tract was excised en bloc. RESULTS: Four weeks after clip placement, all external and internal fistula openings were macroscopically closed. The clip application site presented with an increased scarring. Microscopically, 40% of residual tracts and a more intense chronic inflammation were seen in the untreated control fistulae. After clip placement, 10% of the fistulae persisted associated with a higher density of collagen fibres indicating a better fistula scarring and healing. No unexpected side-effects or complications caused by the clip were observed. CONCLUSION: Fistula closure using the OTSC clip represents a promising sphincter-preserving minimally invasive procedure. This study demonstrated the safety and feasibility of the 'anal fistula claw' for fistula closure. In spite of limitations of the porcine model the results justify clinical applications and further investigations.

Laparoscopic-assisted transgastric cholecystectomy and secure endoscopic closure of the transgastric defect in a survival porcine model.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery holds promise for surgical interventions. Before the feasibility of this technique can be established, however, secure sealing of the transluminal access needs to be thoroughly investigated. PATIENTS AND METHODS: Following antibiotic prophylaxis and gastric disinfection, nine pigs underwent transgastric cholecystectomy by means of a flexible endoscope with the aid of a transabdominal 5-mm trocar. The gastric wall was punctured and dilated. The gallbladder was retracted with a laparoscopic grasper. The cystic duct and artery were dissected with a flexible monopolar ball electrode. The cystic duct was interrupted with flexible scissors between endoclips. Cholecystectomy was completed and the gallbladder was retrieved through the stomach. The gastric defect was closed using a single modified over-the-scope clip (OTSC) (Ovesco, Tübingen, Germany) and grasping the serosal and muscle layer of the gastric wall. The animals were sacrificed 4 weeks later. RESULTS: Laparoscopic-assisted transgastric cholecystectomy was successful in all cases without significant perioperative complications. All animals survived without postoperative complications. The mean operating time was 128 minutes (range, 85 - 205 minutes). The gastric defect closure resulted in inversion of the gastric wall layers within an average time of 6.8 +/- 5 minutes. At 4 weeks postoperative, only minimal thin adhesions were observed in the right hypochondrium. CONCLUSIONS: We found gastric closure using the OTSC to be a reliable tool for closing the transgastric access. Laparoscopic-assisted transgastric cholecystectomy by means of a flexible endoscope was technically feasible, but remains a demanding procedure.

Virtual reality: feasibility of implementation in a regional burn center.

OBJECTIVE: Burn care providers continue to search for non-pharmacologic adjuncts for pain control. Virtual reality (VR) has been shown to be a useful adjunct by reducing pain during burn care and therapy. The feasibility of implementation for clinical use (non-research related) has not been studied in a burn center. The purpose of this study was to determine staff resources needed to implement VR in a regional burn center. METHODS: Ten patients with burns participated in VR during occupational or physical therapy sessions. A portable computer and VR head mounted device (Proview VO35, Kaiser Electro-Optics, Inc.) and the "SnowWorld" software (Patterson and Hoffman, University of Washington) were used. Two staff members trained in the use of VR participated in each session in order to adhere to infection control policies. VR set-up time, patient instruction time, VR therapy time, and equipment cleaning time were recorded and rounded to the nearest minute. RESULTS: A mean of 59 staff time minutes (S.D. 18; range 29-85) were required for set-up, instruction, VR therapy, and cleaning. Set-up required the most time, averaging 23min. Instruction, participation, and clean-up means were 6, 13, and 16min respectively. Time for set-up decreased over time, however technical difficulties with the VR equipment accounted for most of the variability in the time required. CONCLUSIONS: These results suggest VR requires a significant time commitment from staff for implementation. One clear disadvantage was the lack of on-site technical support for equipment troubleshooting. In the current healthcare environment where therapists and nurses are accounting for each minute, it would be difficult for smaller burn centers to allocate staff and resources to implement a VR program. Further research is needed to determine if VR benefits are worth the implementation costs.

A prospective, randomized, comparative trial of a COX-2 selective nonsteroidal anti-inflammatory drug versus placebo in inguinal herniorrhaphy patients.

OBJECTIVE: The standard opioid treatment for postoperative pain can be associated with nausea, vomiting, and constipation. In addition, opioids often provide insufficient pain relief. The purpose of this study was to compare postoperative pain and functional outcomes in patients undergoing inguinal herniorrhaphy who receive a COX-2 selective nonsteroidal anti-inflammatory drug (COX-2) or placebo preoperatively and for 4 days postoperatively. METHODS: A prospective, randomized, blinded, placebo-controlled trial was conducted in adults undergoing elective, outpatient, unilateral inguinal herniorrhaphy. Patients received rofecoxib (50 mg, 1 h prior to incision) or placebo. Doses were re-administered once daily on postoperative days 1-4. Patients were also given hydrocodone bitartrate for use as needed in the postoperative period. Pain outcomes were assessed, including pain intensity (1-10 visual-analogue scale) and the use of hydrocodone bitartrate. In addition, functional outcomes such as activity and return of bowel function were examined for 5 postoperative days. Incidence and severity of side effects were examined. Statistics are mean +/- standard deviation. RESULTS: Fifty-five subjects completed the study. Twenty-six patients received rofecoxib and 29 patients received placebo. Patients who received COX-2 demonstrated improved bowel function as reflected by more bowel movements on postoperative day 2 and postoperative day 3. COX-2-treated patients also reported better oral intake on these same days. In addition, COX-2-treated patients had less difficulty coughing on postoperative day 1. Overall satisfaction with pain management was better in COX-2-treated patients (very satisfied vs. satisfied). There were no statistically significant differences between groups in the amount of hydrocodone bitartrate consumption. There were no complications during the study period. CONCLUSIONS: Administration of a COX-2 selective nonsteroidal anti-inflammatory drug prior to and following outpatient inguinal herniorrhaphy improves functional outcomes when compared with placebo and increases patient satisfaction. These results suggest that multimodal pain therapy with COX-2 inhibitors may have a role in outpatient inguinal hernia repair.

Wireless therapeutic endoscopic capsule: in vivo experiment.

BACKGROUND AND STUDY AIM: Capsule endoscopy is becoming well established as a diagnostic technique for the gastrointestinal tract. Nevertheless swallowable capsule devices that can effectively perform surgical and therapeutic interventions have not yet been developed. Such devices would also be a valuable support for natural orifice transluminal endoscopic surgery (NOTES). The objective of this study was to assess the feasibility of using a swallowable wireless capsule to deploy a surgical clip under remote control. MATERIALS AND METHODS: A wireless endoscopic capsule, diameter 12.8 mm and length 33.5 mm, was developed. The device is equipped with four permanent magnets, thus enabling active external magnetic steering. A nitinol clip is loaded on the topside of the capsule, ready to be released when a control command is issued by an external operator. Repeated ex vivo trials were done to test the full functionality of the therapeutic capsule in terms of efficiency in releasing the clip and reliability of the remote control. An in vivo test was then carried out in a pig: the capsule was inserted transanally and steered by means of an external magnetic arm towards an iatrogenic bleeding lesion. The clip, mounted on the tip of the capsule, was released in response to a remote signal. The procedure was observed by means of a flexible endoscope. RESULTS: A wireless capsule clip-releasing mechanism was developed and tested. During ex vivo trials, the capsule was inserted into the sigmoid section of a phantom model and steered by means of the external magnet to a specific target, identified by a surgical suture at a distance of 3 cm before the left flexure. The capsule took 3 to 4 minutes to reach the desired location moving under external magnetic guidance, while positioning of the capsule directly on the target took 2 to 3 minutes. Successful in vivo clipping of an iatrogenic bleed by means of a wireless capsule was demonstrated. CONCLUSIONS: This study reports the first successful in vivo surgical experiment using a wireless endoscopic capsule, paving the way to a new generation of capsule devices able to perform both diagnostic and therapeutic tasks.

An over-the-scope clip (OTSC) system for closure of iatrogenic colon perforations: results of an experimental survival study in pigs.

BACKGROUND AND STUDY AIM: Perforation of the colon is a relatively rare complication of flexible endoscopy of the lower gastrointestinal tract. It has a reported incidence from between 0.2 % in diagnostic procedures to 0.5 % - 3 % in therapeutic procedures. Given the growing number of colonoscopies, the absolute number of iatrogenic perforations is not unimportant. The treatment of choice is most often surgical repair, since reliable and simple endoscopic techniques for perforation closure are currently unavailable. We aimed to evaluate our novel over-the-scope clip (OTSC) system for closure of iatrogenic perforations. MATERIAL AND METHODS: We have developed a nitinol clip that will capture perforations of 10 - 15 mm, compressing the lesions until healing. The OTSC was studied in a prospective experimental trial in pigs (50 - 60 kg, n=10) for the closure of an iatrogenic perforation of approximately 5 --10 mm on the serosal side, that was created by repeated endoscopic biopsy. The follow-up period was 12 weeks. Follow-up colonoscopy was performed at 4 and 12 weeks. Successful, tight closure of the lesion with absence of peritonitis in the postoperative course was the primary endpoint of the study. RESULTS: Nine animals had an uneventful clinical course. At termination of the study, macroscopic and microscopic examination of the clipping sites in the bowel wall showed normal tissue healing. One animal died 1 day postoperatively for reasons unrelated to the procedure. CONCLUSIONS: In this experimental study the OTSC clip system was found to be a simple and secure closure method for iatrogenic colon perforations, and thus might be an alternative to surgical repair.

Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the space flight environment has never been accomplished because of significant technological and logistical hurdles. Moreover, the effects of space flight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared with identical ground control cultures. Global microarray and proteomic analyses revealed that 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground-based microgravity culture model. Space flight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during space flight missions and provide novel therapeutic options on Earth.

Precision in stitches: Radius Surgical System.

BACKGROUND: The Radius Surgical System is a manual manipulator with two additional degrees of freedom compared with conventional laparoscopic instruments (CLIs). This study aimed to compare the performance of laparoscopic suturing tasks with the use of the Radius Surgical System and CLIs, respectively. METHODS: Five experienced laparoscopic surgeons performed laparoscopic surgical tasks in a training box. The tasks consisted of knot-tying, suturing, and needle control tasks. The needle control task was performed to evaluate the precision of the needle drive by analysis of the needle exit point on a suture pad. In the knot-tying and suturing tasks, required time and accuracy value were measured. Needle control tasks were performed on three different angulations of plane. The angles between the instrument plane and the target plane (AIT) were 30 degrees, 60 degrees, and 90 degrees. The distance of the exit point to the center of the target field, the number of actions needed to fulfill a single task, and the required time were recorded and analyzed. RESULTS: In the knot-tying and frontal suturing tasks, there were no significant differences between the two groups. In the sagittal suturing task, the required time in the Radius group was significantly shorter than in the CLI group. In the needle control tasks on 30 degree and 60 degree AIT, the distance was significantly shorter in the Radius group than in the CLI group. There were no significant differences in the number of actions or the required time. In the frontal and sagittal needle control task on 90 degree AIT, the distance was significantly shorter in the Radius group than in the CLI group. The number of actions and the required time were significantly less in the Radius group than in the CLI group. CONCLUSIONS: The two additional degrees of freedom contributed to accurate and controlled needle guidance, especially in difficult spatial situations.

Experimental results of mesh fixation by a manual manipulator in a laparoscopic inguinal hernia repair model.

BACKGROUND: Laparoscopic mesh fixation using a stapler can lead to complications such as nerve injury and bowel injury. However, mesh fixation by suturing with conventional laparoscopic instruments (CLI) is difficult because of limited degrees of freedom. A manual manipulator--Radius Surgical System (Radius)--whose tip can deflect and rotate, gives the surgeon two additional degrees of freedom. The aim of this study is to evaluate the introduction of Radius to mesh fixation in laparoscopic inguinal hernia repair. METHODS: A model for inguinal hernia repair was prepared using animal organs in a trainer. Mesh fixation was performed using Radius, stapler, and CLI. Tensile strength during extraction of mesh toward the vertical direction, and execution time, were measured. RESULTS: The mean number of fixation points of Radius, stapler, and CLI was 9.3 +/- 1.5, 8.5 +/- 1.4, and 9.0 +/- 1.0, respectively. The mean tensile strength of fixation of mesh of Radius, stapler, and CLI was 140.7 +/- 48.9, 73.1 +/- 23.4, and 53.6 +/- 31.5 (N), respectively. The mean tensile strength per one fixation point by Radius, stapler, and CLI was 16.5 +/- 5.3, 8.7 +/- 2.8, and 6.3 +/- 3.6 (N), respectively. The mean execution time of Radius, stapler, and CLI was 479 +/- 108, 54 +/- 31, and 431 +/- 77 (sec), respectively. CONCLUSIONS: The mesh fixation by Radius was stronger than that by staples and CLI. Two additional degrees of freedom were useful in difficult angles. The introduction of Radius is feasible and facilitates the fixation of mesh with sutures in laparoscopic inguinal hernia repair.

Clinical experience with Alloderm: a one-staged composite dermal/epidermal replacement utilizing processed cadaver dermis and thin autografts.

UNLABELLED: Alloderm has been advocated for the management of acute burns. However, few studies have demonstrated the feasibility of this technique. METHODS: We reviewed the medical records of all patients treated in our burn center who received Alloderm since 1999. RESULTS: Alloderm was used in 21 burn patients and 6 patients with traumatic skin loss. The average size of Alloderm used in the burn patients was 517+/-144 cm(2) (range 24-3000 cm(2)). The average Alloderm thickness used was 0.008 in. and autografts were harvested at an average of 0.007 in. Overall, Alloderm was used in a variety of locations including the face in 3 patients (2 burns, 1 traumatic skin loss) and hands in 7 patients (6 burns, 1 traumatic skin loss). Successful take was observed in 26/27 patients. CONCLUSIONS: Alloderm can be used successfully in patients with acute burns requiring grafting.

Experimental assessment of a new mechanical endoscopic solosurgery system: Endofreeze.

BACKGROUND: The assistance received by the surgeon from support personnel during operative laparoscopy is extremely important. This includes retraction of instruments and endoscope positioning. However, human assistance is costly and often does not provide satisfaction for the surgeon. The aim of this study was to develop a mechanical arm capable of allowing easy handling and holding of laparoscopic instruments under the surgeon's control. METHODS: We designed a system, named Endofreeze, based on a particular kinematical construction that maintains an invariant point of constraint motion just above the trocar puncture site through the abdominal wall. The goal was to develop this way a highly intuitive mechanical holding system for laparoscopic instruments, with sufficient precision of action, activated by a single hand movement. We tested a couple of prototypes with different holding arms while performing cholecystectomy in phantom models with swine inserts and compared the results obtained in similar conditions using different holding and positioning systems. RESULTS: The system allows transparent and intuitive operation, and its setup is easy and quick. It may be adapted either as an instrument retractor or as an optic positioning device. Compared to different systems available or prototypes previously tested, such as AESOP 2000, ENDOASSIST, FIPS Endoarm, TISKA Endoarm, and the Martin Arm, in similar conditions, it was more intuitive, allowing shorter time for completion of surgery. CONCLUSION: Endofreeze is a new intuitive mechanical positioning system for endoscopic solo surgery. In phantom models, it demonstrated a shorter time requirement for completion of surgery when compared to other systems available. In our opinion, it represents a valid compromise between human and robotic control for conventional laparoscopic instruments.

A549 lung epithelial cells grown as three-dimensional aggregates: alternative tissue culture model for Pseudomonas aeruginosa pathogenesis.

A three-dimensional (3-D) lung aggregate model was developed from A549 human lung epithelial cells by using a rotating-wall vessel bioreactor to study the interactions between Pseudomonas aeruginosa and lung epithelial cells. The suitability of the 3-D aggregates as an infection model was examined by immunohistochemistry, adherence and invasion assays, scanning electron microscopy, and cytokine and mucoglycoprotein production. Immunohistochemical characterization of the 3-D A549 aggregates showed increased expression of epithelial cell-specific markers and decreased expression of cancer-specific markers compared to their monolayer counterparts. Immunohistochemistry of junctional markers on A549 3-D cells revealed that these cells formed tight junctions and polarity, in contrast to the cells grown as monolayers. Additionally, the 3-D aggregates stained positively for the production of mucoglycoprotein while the monolayers showed no indication of staining. Moreover, mucin-specific antibodies to MUC1 and MUC5A bound with greater affinity to 3-D aggregates than to the monolayers. P. aeruginosa attached to and penetrated A549 monolayers significantly more than the same cells grown as 3-D aggregates. Scanning electron microscopy of A549 cells grown as monolayers and 3-D aggregates infected with P. aeruginosa showed that monolayers detached from the surface of the culture plate postinfection, in contrast to the 3-D aggregates, which remained attached to the microcarrier beads. In response to infection, proinflammatory cytokine levels were elevated for the 3-D A549 aggregates compared to monolayer controls. These findings suggest that A549 lung cells grown as 3-D aggregates may represent a more physiologically relevant model to examine the interactions between P. aeruginosa and the lung epithelium during infection.

Microsystems in medicine - results of an international survey.

The utilization of microsystems technology (MST) in medical applications is instrumental in opening up new market segments, in the creation of novel, more effective diagnosis and therapy options in medicine, as well as in the further development of MST. However, the players in the healthcare industry are faced with technical and non-technical difficulties. The present study analyzes this emerging field from the viewpoint of medicine, market, and MST. It identifies applications of medical devices with microsystems components and analyzes their potentials in great detail. Thus, especially the creation of new market segments is expected from a broad use of MST in medicine. Furthermore, problems and conditions during the entry of microsystems into medical products are illuminated, in particular considering the specific market features of the healthcare industry. The high expenditure necessary for establishing this technology in healthcare industry is the most significant obstacle, since this market is dominated by small and medium-sized enterprises (SMEs). But there are non-technical difficulties as well. This article presents selected results of the study, which was carried out in the scope of the EU project netMED (virtual institute on micromechatronics for biomedical industry).

Complex regional pain syndrome as a complication of a chemical burn to the foot.

Complex regional pain syndrome (CRPS) is an unusual complication after burns; however, it is important to recognize so that appropriate treatment can be administered. A 60-year-old man suffered an alkali burn to the right foot. Subsequently, the patient developed CRPS with severe pain and vasomotor changes. Multimodal treatment included the early use of ropivacaine and fentanyl via epidural catheter. Oral extended-release morphine, gabapentin, and amitriptyline also were administered. Once pain was controlled, early aggressive physical therapy was instituted, and attention was turned toward wound coverage. One year after discharge, the patient was ambulating well and has returned to work. His pain was managed with a single morning dose of gabapentin and a nonsteroidal anti-inflammatory agent. Current examination of the foot revealed mild forefoot swelling without residual erythema. Ambiguities exist in the mainstay of treatment for CRPS, but this multimodal method of controlling CRPS after burn injury allowed for control of the patient's pain, early mobilization, and eventual return to work.

Indirect coronary angiography: a feasibility study.

The diagnostic method of choice to proof coronary artery disease and to localize stenoses and to judge the stage of the disease is coronary angiography. A new angiographic technique invented by. Wolffgram and Krieter that works without cannulation of the coronary arteries could simplify the interventional procedure. In addition, a technique like this could be used for angiography after CABG surgery directly on the table for quality assurance reasons. This angiography could be performed by the cardiac surgeon without necessarily involving a cardiologist. A feasibility study was successfully done in a cooperation of the Departments. for Cardiology and Cardiac Surgery, Munich University, Steinbeis Transfer Centre for rHealthcare Technologies, Tuebingen and Fraunhofer Technology Development Group (TEG), Stuttgart.

Mechanisms of bacterial pathogenicity.

Pathogenic bacteria utilise a number of mechanisms to cause disease in human hosts. Bacterial pathogens express a wide range of molecules that bind host cell targets to facilitate a variety of different host responses. The molecular strategies used by bacteria to interact with the host can be unique to specific pathogens or conserved across several different species. A key to fighting bacterial disease is the identification and characterisation of all these different strategies. The availability of complete genome sequences for several bacterial pathogens coupled with bioinformatics will lead to significant advances toward this goal.