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Biomedical subjects

J Werner

Publications and source records attributed to J Werner.

At least 19 recordsLinked to original sources

[Fulminant pancreatitis--surgical point of view].

Today, treatment of acute pancreatitis is mainly conservative and surgery is on the retreat. Infection of pancreatic necrosis is still the main risk factor of morbidity and mortality in the course of necrotizing disease. A prophylactic treatment with antibiotics can reduce both infectious complications and mortality. Thus, antibiotics should be administered in severe pancreatitis. If pancreatic infection is suspected, fine needle aspiration should be performed. Today, infected pancreatic necrosis is a well accepted indication for surgery. Aim of the surgical procedure is to remove the septic focus by debridement of the infected pancreatic and peripancreatic necrosis. The optimal timepoint for the surgical intervention is the 3rd to 4th week after onset of the disease. At that time, necrotic tissue is well demarcated. Therefore bleeding complications and removal of vital tissue can be avoided. Today, surgical procedures should combine the necrosectomy with a postoperative method to continuously remove necrosis and debris. This is the case with the following two techniques, the postoperative continuous lavage and the closed packing. In contrast, sterile necrosis is usually treated conservatively. Fulminant acute pancreatitis is a rare subgroup of acute pancreatitis, characterized by a rapidly progressive multiple organ failure in the first days following the onset of the disease with a high probability of death despite ICU therapy. There is poor outcome with both, surgical and conservative therapies. Thus, surgery should only be peformed as an ultima ratio.

Anti-Bacterial Agents↗

Effect of a pneumoperitoneum on systemic cytokine levels, bacterial translocation, and organ complications in a rat model of severe acute pancreatitis with infected necrosis.

BACKGROUND: Infection of pancreatic necrosis (IPN) is strongly associated with sepsis and multiple organ dysfunction and is an absolute indication for surgery. Patients with IPN are critically ill at the time of surgery and may benefit from a minimally invasive approach with reduced surgical trauma. Recently, several minimally invasive necrosectomy techniques have been reported. However, the effects and potential dangers of a pneumoperitoneum in IPN cases are unknown. This study aimed to determine the effects of a pneumoperitoneum on systemic cytokine levels, bacterial translocation, and systemic organ complications in a rat model of IPN. METHODS: For this study, IPN was induced in Wistar rats using retrograde intraductal infusion of 3% taurocholate. After 8 h, the animals were subjected to either laparoscopy (pneumoperitoneum at 8 mmHg) or laparotomy for 1 h and killed after 1 or 3 h. Severe acute pancreatitis with IPN was proved by serum amylase and lipase, histology, tissue activity of myeloperoxidase (MPO), and bacteriology. Systemic levels for interleukin-10 (IL-10), IL-6, tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccarides were determined by enzyme-linked immunoassay (ELISA). Systemic organ damage and dysfunction were evaluated using MPO activity (lung), serum creatinine (kidney), and serum aminotransferases (liver). RESULTS: Necrotizing pancreatitis developed in all the animals. Most of the animals (85%) had proven infected necrosis. Elevated cytokine levels and deteriorated organ parameters demonstrated systemic inflammation and organ failure. Although there was a tendency toward a higher level of proinflammatory cytokines after laparotomy, there were no significant differences between laparotomy and laparoscopy. Furthermore, these alterations were not accompanied by any differences in bacterial translocation (lipopolysaccharides), systemic organ damage, or mortality between laparoscopy and laparotomy. CONCLUSION: In the current model of infected pancreatic necrosis, a pneumoperitoneum did not result in increased cytokine release or bacterial translocation. However, the putative advantage of less surgical trauma with the laparoscopic approach did not play a significant role in the setting of severe acute pancreatitis with IPN.

Animals↗

[Acute pancreatitis: surgical therapy].

Today, treatment of acute pancreatitis is mainly conservative and surgery is on the retreat. Infection of pancreatic necrosis is still the main risk factor of morbidity and mortality in the course of necrotizing disease. A prophylactic treatment with antibiotics can reduce both infectious complications and mortality. Thus, antibiotics should be administered in severe pancreatitis. If pancreatic infection is suspected, fine needle aspiration should be performed. Today, infected pancreatic necrosis is a well accepted indication for surgery. Aim of the surgical procedure is to remove the septic focus by debridement of the infected pancreatic and peripancreatic necrosis. The optimal timepoint for the surgical intervention is after the third week after onset of the disease. At that time, necrotic tissue is well demarcated. Therefore bleeding complications and removal of vital tissue can be avoided. Today, surgical procedures should combine the necrosectomy with a postoperative method to continuously remove necrosis and debris. This is the case with the following two techniques, the postoperative continuous lavage and the closed packing.

Antibiotic Prophylaxis↗

Observation of Feshbach resonances in an ultracold gas of 52Cr.

We have observed Feshbach resonances in collisions between ultracold 52Cr atoms. This is the first observation of collisional Feshbach resonances in an atomic species with more than one valence electron. The zero nuclear spin of 52Cr and thus the absence of a Fermi-contact interaction leads to regularly spaced resonance sequences. By comparing resonance positions with multichannel scattering calculations we determine the s-wave scattering length of the lowest (2S+1)Sigma(+)(g) potentials to be 112(14) a(0), 58(6) a(0), and -7(20) a(0) for S=6, 4, and 2, respectively, where a(0)=0.0529 nm.

Journal Article↗

An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.

The occurrence of an APP T174I mutation is described in a large American family of African descent with Alzheimer disease. The clinical characteristics were an unusually early onset of disease (early 30s), similar to a previously reported age at onset of this mutation in an Austrian family. Distinct from that family, seizures and myoclonus were prominent features of the disease in this kindred.

Adult↗

Platelet function in acute experimental pancreatitis induced by ischaemia-reperfusion.

BACKGROUND: Ischaemia-reperfusion (IR)-associated microcirculatory changes play a major role in acute post-transplantation pancreatitis. The pathophysiological role of platelets in these events is unknown. The aim of this study was to examine platelet adhesion and function during early reperfusion after pancreatic ischaemia. METHODS: Rats were subjected to warm pancreatic ischaemia by cross-clamping of the pancreatic vessels for 1 h. After 1 h of reperfusion, platelet-endothelium interaction was evaluated after platelet separation and staining by fluorescence microscopy. Amylase levels and pancreatic histology were evaluated 24 h after reperfusion. Animals treated according to an identical protocol, but without ischaemia, served as controls. RESULTS: Mild pancreatitis had developed by 24 h after IR; serum amylase levels were significantly higher than those in control animals. The numbers of adherent platelets in capillaries and venules were significantly increased, and platelet velocity in capillaries was significantly decreased, in the IR group compared with controls. There was significantly more oedema and inflammation in pancreatic tissue after IR. CONCLUSION: Warm ischaemia for 1 h followed by reperfusion for 24 h caused mild pancreatitis in this experimental model. The pancreatic microcirculation was characterized by pronounced platelet-endothelium interaction in capillaries and venules. These results suggest that platelet activation may play an important role in acute post-transplantation pancreatitis.

Acute Disease↗

Robust and self-tuning blood flow control during extracorporeal circulation in the presence of system parameter uncertainties.

Three different discrete controllers were designed and tuned to be used in conjunction with a rotary blood pump during cardiopulmonary heart-lung support. The controllers were designed to operate in both steady and pulsatile modes. The system and methods were tested in a circulatory haemodynamic simulator. To guarantee stable control of the non-linear circulatory system in the presence of patient parameter uncertainties, a proportional plus integral (PI) and an H infinity controller were robustly tuned, using a non-linear time-varying model. (H infinity refers to the Hardy space, the set of bounded functions, analytic in the right half plane. The H infinity controller is the solution to the H infinity norm optimisation problem.) A self-tuning general predictive controller (GPC), together with an adaptive Kalman filter (KF) estimator, was compared with the two robustly tuned controllers. The closed-loop blood flow control circuit was set up in simulation routines first. The blood flow controllers were validated in a circulatory hydrodynamic simulator (MOCK) combined with a rotary blood pump. Parameters of the system simulator were changed continuously, and the controllers were tested over a wide range of different operating points. Disturbances in the form of discontinuous additive parameter uncertainties were applied. The closed-loop systems remained robustly stable. The robustly tuned H infinity controller showed the best control performance, in contrast to the GPC controller, which was near instability in regions of strongly varying non-linear system gain. Compared with the H infinity controller, the PI controller showed slightly worse behaviour, but the closed-loop response was acceptable, even in regions of strongly varying non-linear system gain and during pulsatile perfusion. The rotary blood pump could provide stationary and pulsatile perfusion under control conditions. Controlled variables were hereby mean blood flow, pulsatility index and heart rate. All three controllers were developed for an arterial mean flow of 0-6 l min(-1) and a heart rate of up to 70 beats per minute. Pulsatile closed-loop perfusion could provide up to 30 mmHg pressure variation in the simulated ascending aorta at a mean flow of 3 l min(-1).

Aorta↗

Prefabrication of large fasciocutaneous flaps using an isolated arterialised vein as implanted vascular pedicle.

Flap prefabrication represents a new trend in microsurgical tissue transfer. Based on the concept of neovascularisation, in Chinchilla Bastard rabbits (n=40), an isolated venous pedicle dissected from the femoral and saphena magna vein was arterialised by end-to-end anastomosis to the femoral artery at the inguinal ligament. This arterialised venous loop was implanted beneath a random-pattern vascularised abdominal fasciocutaneous flap as large as 8 x 15 cm(2) to investigate the development of neovascularisation at various evaluating times of 4, 8, 12, 16 and 20 days. To prevent neoangiogenesis from occurring between the underlying vascular bed and abdominal flap, a silicone sheet with the corresponding dimension of 8 cm x 15 cm x 0.25 mm was placed and fixed on the abdominal wall. The flap viability and the neovascularisation process in the prefabricated abdominal skin flaps were evaluated by macroscopic observation, blood analysis, selective microangiography and histology. The experimental results showed that newly formed vessels originating from the implanted isolated venous pedicle were evident on the angiograms 4 days after pedicle implantation. In the 8- and 12-day groups, newly formed vessels became larger and some were connected to the originally available vasculature in the abdominal fasciocutaneous flaps. In the 20-day group, entire flaps were perfused by the blood flow supplied from the newly implanted venous pedicles through newly formed vessels and their vascular connections. This study indicated that large flap prefabrication can be created by implantation of an isolated arterialised venous pedicle into a random-pattern vascularised fasciocutaneous flap. Twenty days appears to be the minimal length of time required after arterialised venous pedicle implantation for the maturation of neovascularisation in the prefabricated flap.

Animals↗

Surgery in the treatment of acute pancreatitis--open pancreatic necrosectomy.

Management of acute necrotizing pancreatitis has changed significantly over the past years. Early management is non-surgically and solely supportive. Today, more patients survive the early phase of severe pancreatitis due to improvements of intensive-care-medicine. Pancreatic infection is the major risk factor with regard to morbidity and mortality in the late phase of severe acute pancreatitis. Whereas early surgery and surgery for sterile necrosis can only be recommended in selected cases, pancreatic infection is a well accepted indication for surgical treatment. Surgery should ideally be postponed until four weeks after the onset of symptoms as necrosis is well demarcated at that time. Four surgical techniques can be performed with comparable results regarding mortality: necrosectomy combined with (1) open packing, (2) planned staged relaparotomies with repeated lavage, (3) closed continuous lavage of the retroperitoneum, and (4) closed packing. However, closed continuous lavage of the retroperitoneum, and closed packing seem to be associated with a lower morbidity compared to the other two approaches. Advances in radiologic imaging, new developments of interventional radiology and other minimal access interventions have revolutionized the management of many surgical conditions over the past decades. However, minimal invasive surgery and interventional therapy for infected necrosis should be limited to specific indications in patients who are critically ill and otherwise unfit for conventional surgery. Open surgical debridement is the "gold standard" for treatment of infected pancreatic and peripancreatic necrosis.

Debridement↗

Placebo-controlled phase I/II studies of minocycline in amyotrophic lateral sclerosis.

Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. In Trial 1, 19 subjects received 200 mg/day or placebo for 6 months; there were no significant differences in adverse events (AE). In Trial 2, 23 subjects received up to 400 mg/day in an 8-month crossover trial. The mean tolerated dose was 387 mg/day, there was a trend toward more gastrointestinal AE (p = 0.057), and blood urea nitrogen and liver enzymes became elevated (p < 0.05). Using these data, the authors have designed and launched a phase III trial.

Adult↗

Rate-responsive pacing using the atrio-ventricular conduction time: design and test of a new algorithm.

The cardio-circulatory system of chronotropic incompetent patients is unable to adapt heart rate adequately to the level of strain. A common therapy is the implantation of a pacemaker that stimulates the heart at a rate derived from a strain related sensor signal. The paper describes a new pacemaker concept that uses a well-defined time interval in the electrogram as a sensor parameter, the atrioventricular conduction time (AVCT). Identification experiments with patients delivered the stationary and dynamic behaviour of AVCT subject to variations in the exercise rate and the pacing frequency. Furthermore, it was demonstrated that AVCT is perturbed by respiratory activity. The new rate-responsive algorithm, which uses the internal model control principle, explicitly takes into account the closed-loop nature of the underlying system. The major design objectives were: extended range of the individual heart rate; effective attenuation of the respiratory-related disturbance; and stability. Seven patients undergoing incremental exercise were paced with this AVCT-based algorithm. The experiments confirmed the suitability of this concept with respect to the design goals. The patients' peak intrinsic heart rate at exercise was 100 +/- 20min(-1). When paced with the AVCT algorithm, the paced heart rate was 126 +/- 12min(-1). The increase was significant (26 +/- 13min(-1); 15 to 53 min(-1)), which clearly demonstrated the potential of this concept to restore chronotropic competence.

Aged↗

Mechanical and optical characteristics of a new fiber optical system used for cardiac contraction measurement.

In order to obtain a better physiological performance and a closer restoration of the regular rhythm of failing hearts, a new fiber optical sensor system for the measurement of cardiac contraction has been developed. It consists of an opto-electrical unit and a sensing fiber which has to be positioned in the heart. The objective of this new fiber optic sensor system is to use the inotropic information to adjust a stimulation algorithm in single or multichamber pacing or to detect arrhythmia in insufficient heart function. In this study, the mechanical and optical characteristics of different fibers are investigated. The relationship between the attenuation (with an achieved numerical maximum of 0.3 dB), the bending diameter and the angle of bending is determined in a range of 20-160 mm. The most suitable fiber for the application in cardiological problems is determined (WT8 fiber), for which the sensitivity is analyzed. Additionally, power spectra are calculated from WT8 fiber signals obtained from pig hearts, working under physiological conditions. The maximal frequency response was 23 Hz. It is concluded that the fiber optical measurement of cardiac contraction is not only feasible and reproducible, but the WT8 fiber also shows optimal behavior in the range of parameters occurring in the heart chambers. Nevertheless, in order to restrict the measured signal reliably to bending processes within the chambers only, it is concluded that a special combined fiber has to be constructed with a high sensitivity only at its terminal section within the heart.

Algorithms↗

[Imaging methods in the diagnosis and therapy of cystic echinococcosis].

Imaging studies, ultrasonography, play a central role for the diagnosis and follow-up of cystic echinococcosis (hydatid disease) due to the non-specific clinical symptoms and still inadequate sensitivity and specificity of currently available serological tests. Due to the increasing number of people immigrating to central Europe from countries with a high incidence of cystic echinococcosis, cystic echinococcosis has become an important differential diagnosis of cystic lesions. The imaging modality to localize and stage the disease depends on the organs affected. Ultrasonography is the most important imaging technique to screen for abdominal lesions (more than 75 % of the cases). Therefore, an expert committee of the WHO Working Group on echinococcosis has recently suggested a standardized ultrasonographic classification of hepatic cystic echinococcosis. This classification proofs to be very useful for staging echinococcal cysts with respect to parasite activity. Ultrasonography is not only an excellent tool for the primary diagnosis and therapeutic decision but also for follow-up of patients treated for cystic echinococcosis. Indications for computed tomography or magnetic resonance tomography are restricted to extra abdominal disease, patients not suited for ultrasonography because of obesity or meteorism, complicated cysts and planning of surgery or interventional therapy. Apart from surgery three other treatment options are well established: (1) chemotherapy with albendazole or mebendazole, (2) percutaneous drainage and sterilization (PAIR) and (3) observation of inactive echinococcal stages ("watch and wait" approach).

Albendazole↗

The dromotropic pacemaker: system analysis and design considerations.

Patients suffering from chronotropic incompetence are generally treated with a rate-responsive pacemaker that stimulates the heart at a rate derived from a strain related sensor signal. The pacemaker concept described here uses a well-defined time interval in the electrogram as sensor parameter (AVCT: atrio-ventricular conduction time). AVCT is directly controlled by the autonomic nervous system. The design of the new algorithm was based on a thorough experimental analysis of AVCT subject to variations of the exercise rate and the pacing frequency. There it was demonstrated that AVCT is disturbed by the respiratory activity. The new rate-responsive algorithm which uses the internal model control principle explicitly takes into account the closed-loop nature of the underlying system. The major design objectives were: a) extended range of the individual heart rate, b) effective attenuation of the respiratory related disturbance and c) dynamic stability. Seven patients undergoing an incremental exercise test were paced with the new AVCT-based algorithm. When paced with this algorithm the paced heart rate was 126 +/- 12 min(-1) whereas the peak intrinsic heart rate was only 100 +/- 20 min(-1). The increase which was significant (26 +/- 13 min(-1); 15.53 min(-1)) clearly demonstrated the potential of this concept to restore chronotropic competence. A reanalysis of the experiments was undertaken in order to facilitate the individual parameterization in clinical practice. It could be demonstrated that a rather simple screening test is sufficient to gain the knowledge necessary for the individual parameterisation.

Algorithms↗