The Status of SEMS Versus Plastic Stents for Benign Biliary Strictures.

PURPOSE OF REVIEW: Benign biliary strictures can be treated with plastic stents and self-expandable metal stents (SEMS). This review article delineates the latest scientific evidence for their usage. RECENT FINDINGS: Despite evolving literature on both type of stents as treatment modalities of benign biliary strictures, which encompass mainly anastomotic strictures and strictures related to chronic pancreatitis, no final conclusions can be drawn regarding the superiority of a particular stent. SEMS tend to have higher stricture resolution rates and fewer procedural requirements which are partly offset by higher stent migration and stricture recurrence rates compared with plastic stents. Additional studies focusing on new SEMS types with anti-migration features as well as cost-effectiveness calculations are necessary for clinical decision-making when treating patients with benign biliary strictures.

A new class of supramolecular ligands stabilizes 14-3-3 protein-protein interactions by up to two orders of magnitude.

We report the first supramolecular stabilizers of the interaction between 14-3-3ζ and two of its effectors, Tau and C-Raf, which are involved in neurodegenerative diseases and proliferative signal transduction, respectively. These supramolecular ligands open up an opportunity to modulate functions of 14-3-3 with these effectors.

Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center experience.

COMPLEX BENIGN ESOPHAGEAL STRICTURES ARE DEFINED BY LENGTH (≥2 CM), SMALL DIAMETER, AND STRICTURE ANGULATION OR TORTUOSITY. THE LONG-TERM COURSE OF COMPLEX ESOPHAGEAL STRICTURES BASED ON LENGTH IS CURRENTLY UNCLEAR. WE SUSPECT THAT THE ESOPHAGEAL STRICTURE LENGTH MIGHT IMPACT THE EFFECTIVENESS OF ENDOSCOPIC DILATION THERAPY. WE PERFORMED A RETROSPECTIVE STUDY OF ALL BENIGN ESOPHAGEAL STRICTURES OF 2 CM OR LONGER TREATED AT A SINGLE CENTER BETWEEN JULY 1, 2010, AND MAY 31, 2014. PRIMARY OUTCOMES WERE CHANGED IN DYSPHAGIA SCORE AT THE END OF FOLLOW-UP COMPARED TO FIRST DILATION AT OUR FACILITY AND THE NEED FOR GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY DURING FOLLOW-UP. DATA WERE STRATIFIED INTO FOUR SUBGROUPS ACCORDING TO STRICTURE LENGTH 20­29, 30­49, 50­99, AND 100 MM OR LONGER. EIGHTY-SEVEN PATIENTS (MEAN AGE 66 YEARS, 54% WOMEN) WERE FOLLOWED OVER A MEDIAN OF 40 MONTHS. PATIENTS UNDERWENT A MEDIAN OF 6 DILATIONS, AVERAGING 0.3 DILATIONS PER MONTH. MEDIAN DYSPHAGIA SCORE REMAINED UNCHANGED AT 2; 37 (43%) PATIENTS REPORTED RESOLUTION OR IMPROVED DYSPHAGIA AND 50 (57%) PATIENTS REPORTED NO IMPROVEMENT OR WORSENED DYSPHAGIA. GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY WAS NEEDED FOR 23 (26%) AND 3 (3%) PATIENTS, RESPECTIVELY. MEDIAN DEGREE OF DYSPHAGIA AT THE END OF FOLLOW-UP DID NOT DIFFER BETWEEN THE FOUR STRICTURE LENGTH SUBGROUPS, YET NO PATIENT HAD IMPROVEMENT IN THE 100 MM OR LONGER SUBGROUP. MORE THAN HALF OF PATIENTS WITH LONG BENIGN ESOPHAGEAL STRICTURES HAD UNCHANGED DYSPHAGIA OR DEVELOPED WORSE DYSPHAGIA DURING FOLLOW-UP. LONG-TERM OUTCOMES DID NOT DIFFER BETWEEN DIFFERENT STRICTURE LENGTHS: .

[Cushing's syndrome in a manic patient with a long-standing bipolar disorder: cause or coincidence?]. / Het syndroom van Cushing bij een manische patiënte met een lang bestaande bipolaire stoornis: oorzaak of bijvangst?

Hypercortisolism is associated with mood disorders such as depression and bipolar disorder. A 75-year-old female patient who had been diagnosed with bipolar disorder forty years ago was admitted to our hospital with a severe, therapy-resistant mania. Careful diagnostic considerations, resulted in the patient being diagnosed with Cushing's syndrome. Treatment with metyrapone led to a swift improvement of the patient's symptoms. Could Cushing's syndrome underlie this patient's psychiatric history? Or are two co-existing, intertwining causes responsible for the psychiatric symptoms? The case illustrates that even if a patient has a long history of psychiatric problems that have been plausibly diagnosed over time, clinicians and psychiatrists should always consider the possibility that there may be an underlying somatic cause for the patient's psychiatric symptoms.

Note: High resolution alternating current/direct current Harman technique.

This note describes the construction and engineering of a high precision Harman set-up for metrology of the thermoelectric figure of merit (ZT) of modules and materials based on steady state AC and DC measurements. The Harman technique presented in this article has a resolution of milli-ZT and it does not employ lock-in amplifiers or AC bridges; rather, the technique is developed to avoid typical complications experienced in AC Harman systems. By one-time reference measurements the best operation point for the system is chosen, minimizing the effects of capacitive loads due to AC signals.

Directed evolution of novel adeno-associated viruses for therapeutic gene delivery.

Gene therapy vectors based on adeno-associated virus (AAV) are currently in clinical trials for numerous disease targets, such as muscular dystrophy, hemophilia, Parkinson's disease, Leber's congenital amaurosis and macular degeneration. Despite its considerable promise and emerging clinical success, several challenges impede the broader implementation of AAV gene therapy, including the prevalence of neutralizing antibodies in the human population, low transduction of a number of therapeutically relevant cell and tissue types, an inability to overcome physical and cellular barriers in vivo and a relatively limited carrying capacity. These challenges arise as the demands we place on AAV vectors are often different from or even at odds with the properties nature bestowed on their parent viruses. Viral-directed evolution-the iterative generation of large, diverse libraries of viral mutants and selection for variants with specific properties of interest-offers an approach to address these problems. Here we outline progress in creating novel classes of AAV variant libraries and highlight the successful isolation of variants with novel and advantageous in vitro and in vivo gene delivery properties.

Fe2o3 shell growth on Pt nanoparticles.

Fe2O3 shells have been synthesized around Pt cores to create Pt@Fe2O3 core-shell nanoparticles. The synthesis conditions allow control of the shell shape and allow the preparation of both hexagonal shells and spherical shells. 2D cross-sectional TEM images show that the cores are not positioned at the centers of the shells. By rotating the nanoparticles and monitoring the apparent motions of the cores in the 2D cross-sectional images, it is possible to determine quantitatively the radial position of the Pt core with respect to the center of the Fe2O3 shell. The distribution of core positions within the core-shell structures is bimodal. These observations suggest that the Fe2O3 shells grow on the Pt cores by a nucleation process, rather than layer-by-layer growth.

Tailoring the shapes of Fe(x)Pt(100-x) nanoparticles.

Fe(x)Pt(100-x) nanoparticles of varying composition have been synthesized with various shapes and sizes using a high pressure synthesis method which allows control of synthesis conditions, in particular the reaction temperature. Tailoring the shapes and sizes of Fe(x)Pt(1-x) nanoparticles allows one to control a variety of properties that are relevant to the many potential applications of metallic nanoparticles. Shape and composition can be used to control catalytic activity and to achieve high packing density in self-assembled films. Variation of both nanoparticle size and shape has been achieved by using various different solvents. The solvents used in the nanoparticle synthesis can influence the product because they can play a role as surfactants. Using solvents of various types it has been possible to synthesize Fe(x)Pt(100-x) nanoparticles with a variety of shapes including spherical, rod-like, cubic, hexagonal and high aspect ratio wires. Control of nanoparticle shape opens the door to their being used in various technological applications for which spherical nanoparticles are ineffective.

Abnormal crosstalk between pancreatic acini and macrophages during the clearance of apoptotic cells in chronic pancreatitis.

In chronic pancreatitis (CP), both the progressive loss of acinar parenchyma and aggressive fibro-inflammatory reactions ultimately lead to irreversible organ destruction. Dying cells are normally removed by macrophages and elimination is associated with anti-inflammatory cytokine switch. We investigated whether defective clearance of damaged acini by macrophages such as compromised phagocytosis or altered cytokine reaction occurs in CP and thus represents a causative link between acinar loss and fibro-inflammation. In a checkerboard-like co-culture system, we assessed normal and CP macrophages for their phagocytic and cytokine responses to dying pancreatic acinar cells of normal or CP origin by FACS, confocal microscopy, QRT-PCR, and ELISA. In CP, phagocytosis of apoptotic acini by macrophages was not impaired; however, the associated cytokine responses were gradually perturbed. Most interestingly, only normal acini suppressed TGFbeta1 expression and accumulation specifically in normal macrophage cultures, while CP acini lost this ability. Both types of apoptotic acini induced pro-inflammatory cytokine bursts of varying strength in both types of macrophages; however, the most significant difference (more than 50-fold higher expression of IL-1beta, IL-6, and IL-8) was evident between CP/CP and normal/normal combinations, indicating that acinar and macrophage alterations synergistically lead to the ultimate CP-specific bias. In combination with in situ data comparing circulating inflammatory cells to pancreatic resident ones, our results indicate that cytokine expression in inflammatory cells undergoes spatiotemporal modulation, most likely through a successive interplay of acinar, stromal, and circulating factors. Thus, clearance of injured pancreatic acini by macrophages is associated with a unique cytokine reaction which may constitute a basis for progression of SAPE (sentinel acute pancreatitis event) to the irreversible fibro-inflammation in CP.

The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis.

BACKGROUND: Recurrent inflammation in chronic pancreatitis (CP) is not well understood. AIMS: To investigate whether decorin, an extracellular matrix (ECM) proteoglycan with macrophage modulating activity, is a pathogenic factor allowing diseased pancreatic stroma to sustain inflammation by affecting the cytokine profile of accumulating inflammatory cells. METHODS: Decorin was examined in 18 donors and 32 patients with CP by quantitative reverse transcription polymerase chain reaction (QRT-PCR), western blotting, and immunohistochemistry of pancreatic specimens. QRT-PCR was used to assess cytokine expression in donor peripheral blood mononuclear cells (PBMC), exposed or not to decorin in vitro, and to compare it with the cytokine profile of circulating and resident mononuclear cells (MNC) of patients with CP. RESULTS: In CP, desmoplasia is associated with overexpression of decorin in the growing ECM and enlarged pancreatic nerves. In culture, exposure of MNC to decorin stimulated expression of the MNC recruiting chemokine MCP-1. In biopsies, MNC infiltrates in decorin rich CP tissue showed a 300-fold upregulation of MCP-1 compared with decorin free peripheral blood, whereas no difference was found in basal MCP-1 expression in PBMC of patients versus donors. This effect was specific for MCP1-other inflammatory cytokines, such as interleukin 1beta and tumour necrosis factor alpha, were not affected. CONCLUSION: Decorin is a molecular marker of desmoplasia in CP, and excessive decorin may allow fibrotic masses to nourish and protract inflammation by deregulating the process of MNC accumulation and activation. These data provide a molecular basis for surgical resection of diseased tissue as a treatment option in CP.

[Undertreatment of depression; causes and recommendations]. / Onderbehandeling bij depressie; oorzaken en aanbevelingen.

Efficacious forms of treatment for depression are available, but too many people suffering from depression are either treated inadequately or not at all. This undertreatment may play a role in the failure to reduce in the prevalence of depression. Possible causes of undertreatment include delayed help-seeking, delayed treatment, non-compliance, mediocre self-care and inappropriate treatment. Furthermore, the treatment culture is insufficiently population-based and proactive, and the chronic-recurrent nature of many depressions is too often neglected. Both the content and organisation of mental health care, in primary care and speciality services alike, should explicitly target reduction of the prevalence of depression in the population, in particular by trying to narrow the gap between the 'efficacy' and 'effectiveness' of treatment modalities. Important elements in this approach include 'individualized stepped care' models, implementation of optimal care by means of care programs, redefinition of the roles of care-provider and patient (greater emphasis on partnership) and abolition of the distinction between somatic health care and mental health care.

[Lysis therapy of thrombosis of the superior mesenteric artery]. / Lysetherapie bei arterieller Thrombose der Arteria mesenterica superior.

INTRODUCTION: For surgeons the acute intestinal ischaemia is still a diagnostic and therapeutic challenge. If clinically suspected, the diagnostic procedures such as duplex sonography and arterial angiography should be carried out immediately. Although the diagnosis is often quickly clear, perioperative mortality rate remains high. We report the acute local thrombolytic therapy as an alternative treatment. CASE REPORT: A 80-year-old male patient was referred to our hospital with a complete occlusion of the superior mesenteric artery. Duplex sonography and the arterial angiogram confirmed the clinical diagnosis. Because the patient was assessed to be at high risk we decided to avoid an operation and local thrombolytic therapy using rt-PA and urokinase was carried out. RESULT: The local thrombolytic therapy was successful and led to a complete restoration of the arterial flow within the superior mesenteric artery. The clinical symptoms subsided and no complications were observed. CONCLUSION: Local thrombolytic therapy appears to be a suitable therapeutic option in patients suffering of mesenteric arterial occlusion. Although the duplex sonography often confirms the diagnosis with high accuracy the angiography remains the diagnostic gold standard.

[The importance of vascular injuries in sport accidents--a rare but serious complication]. / Die Besonderheit von Gefässverletzungen nach Sportunfällen - eine seltene, aber ernst zu nehmende Komplikation.

There are about 1.5 million sports injuries in Germany every year, but concomitant vascular injuries are rarely encountered. Only single cases have been reported in the literature. The records of 216 patients with vascular injuries who were admitted to the university hospital in Jena between 1987 and 1996 were retrospectively reviewed. Six patients sustained a vascular injury during the accident in different kinds of sport. Vascular repair was successfully performed in three cases. Organ resection was necessary in two cases and one patient was treated conservatively. Most vascular lesions are related to blunt trauma which might create delayed symptoms of ischemia. Therefore measurement of limb pressures, Doppler scan, duplex ultrasonography and angiography are adjuncts in patients evaluation. In case of bleeding or complete ischemia the prompt arterial reconstruction is indicated and subsequently minimizes the risk of reperfusion injury.

Differentiation of positive autofluorescence bronchoscopy findings by comparative genomic hybridization.

Up to 50% of the results of autofluorescence bronchoscopy (AF) of histologically benign lesions are false-positive. For better differentiation of such lesions we have used comparative genomic hybridization (CGH). We studied biopsy material from 47 patients by CGH. For a comparison of findings, the patients were grouped as follows: Group 1, patients with manifest malignant lesions (n=10); group 2, patients with positive autofluorescence and negative (benign) histology (n=16); group 3, patients with negative autofluorescence and negative histology, who belong to a typical high-risk group for lung cancer (n=21). The biopsy specimens of 21/47 patients (45%) showed chromosome aberrations. In 8/10 cases (80%) in group 1, one or several chromosome lesions were detected. Chromosome aberrations were found in 13/16 specimens (81%) taken in group 2. None of the 21 biopsy specimens from the patients of group 3 showed any chromosome lesions. The chromosome aberrations detected in groups 1 and 2 show nearly identical distribution patterns. Lesions of chromosome 3 are the most frequent ones in both groups. The results of the CGH investigation show that regions of the bronchial mucosa with positive AF finding and benign histology frequently are seriously damaged and may develop into potentially malignant lesions.

May pentoxifylline improve lung function after one-lung flooding?

One-lung flooding makes the intraoperative sonography of round pulmonary lesions possible. During the flooded phase, the flooded lung suffers a significant reduction in perfusion. After ischemia and reperfusion, neutrophil granulocytes lead to further tissue injuries. A study was made on four animals to determine whether administration of pentoxifylline--a potent inhibitor of granulocyte adhesion to the endothelium--improves lung function after one-lung flooding. Two animals were subjected to thoracotomy with extended hemodynamic monitoring. Thoracoscopy was performed on two other animals, which were extubated after the flooding liquid was drained and survived for 24 degrees h. A bolus of 1 mg/kg of pentoxifylline was administered at the time of thoracotomy/thoracoscopy. followed by continuous infusion of pentoxifylline at a rate of 1.5 mg/kg per hour until 30 degrees min after reventilation (thoracotomy), or until extubation, respectively. The control group consisted of animals employed in previous experiments. Except for pentoxifylline administration, they were subjected to identical experimental conditions. The control group for the thoracotomy experiment comprised 14 animals, that for the thoracoscopy experiment three animals. The experiments proved that 30 degrees min after the draining of the flooding liquid and reventilation, all four pentoxifylline-treated animals had a higher partial arterial oxygen pressure and a lower pulmonary shunt volume compared with the control animals. In the two animals that survived, a positive effect on lung function was no longer detectable 24 degrees h after extubation. The administration did not lead to a drop in the pulmonary arterial pressure and did not cause any hemodynamic changes other than a moderate tachycardia.

Synthesis of enantiomerically pure, sn-1 modified sn-2-deoxy-2-amido-glycero-3-phospholipids.

The synthesis of two types of enantiomerically pure sn-2-deoxy-2-amido-glycero-phospholipids differing in the connection of the alkyl chain at the sn-1-position is described. Both types of lipids were prepared from L-serine-methylester as the chiral starting material.

[Stage-adapted therapy of pleural empyema. Results during 1992-1998]. / Stadiengerechte Therapie des Pleuraempyems. Ergebnisse im Zeitraum 1992-1998.

Despite the decreasing number of patients suffering tuberculosis and the use of modern broad spectrum antibiotics the pleural empyema did not lose its relevance. The main reasons are increasing numbers of patients with drug and alcohol abuse or immunodeficiency of different causes. We retrospectively analysed the data of 73 patients treated of pleural empyema between 1992 and 1998. Considering the known stages of pleural empyema we present the corresponding therapeutic results. All patients classified as stage I were treated with a chest drain and cure was achieved in all of them (100%). The treatment for patients classified as stage II was different: 5 out of 32 were treated with a continuous irrigation and suction chest drain system. 18 patients first underwent thoracoscopy and were afterwards treated with a continuous irrigation and suction system. Another 9 patients primarily underwent an early open decortication. In 40% the treatment with the suction and irrigation system was successful. Using video-assisted thoracoscopy (VATS) cure was achieved in 94.4%, with open decortication in 100%. The preferred treatment of patients classified as stage III is the open decortication. After the first operation 80% (30 patients) were cured. 6 patients needed thoracoplastic procedures after the first intervention. No patient was discharged neither with a permanent chest drain nor a permanent thoracic window. With the results a cause dependent analysis of morbidity and mortality was done. The overall morbidity rate was 27.9% and the overall mortality 5.4%. The treatment of pleural empyema still remains to be problematic. Corresponding to our results pleural empyema classified as stage I is best treated with a simple chest tube. The video-assisted thoracoscopy (VATS) lacks of complications and is a very efficient method in treating stage II. The method of choice in stage III is the open decortication which in the case of a chronic and recurrent or persistent infection should be followed by a thoracoplastic procedure.

One-lung flooding for video-assisted thoracoscopic surgery in animal experiments on pigs--oxygenation and intrapulmonary shunt.

Unilateral flooding of the lung after intubation with a double-lumen tube makes intraoperative sonography of the lung during video-assisted thoracoscopic surgery possible. After flooding with 15 ml/kg, the arterial partial oxygen pressure (with FiO2=1.0) is higher than that in total atelectasis by about 100 mmHg, while it is only slightly less than that during bilateral lung ventilation. Compared to total atelectasis, lung flooding reduces the pulmonary right-to-left shunt volume. The pulmonary function normalizes within 8 h after the operation.

Arthropod and helminth parasites from the Plains Pocket Gopher, Geomys bursarius bursarius from the hosts' northern boundary range in Minnesota.

As part of a continuing and more general study of the diversity of parasites from subterranean mammals in central North America, individuals of the Plains Pocket Gopher, Geomys bursarius bursarius, were collected from 7 localities in northwestern Minnesota from September 1991 through October 1996. Arthropods collected included the fleas, Opisocrostis bruneri (4 of 124, 3.2%), Foxella ignota ignota (85 of 124, 68.5%); the chewing louse, Geomydoecus geomydis geomydis from 98 of 124 (79%), and larvae of the tick, Dermacentor variabilis (1 of 124, 0.8%). Nematodes found included Physaloptera limbata (2 of 118 gophers, 1.7%), Capillaria americana (4 of 118, 3.4%), and Ransomus rodentorum (31 of 118, 26.3%). Cestodes recovered included Anoplocephaloides infrequens (12 of 136 gophers, 8.8%), Anoplocephaloides variabilis (19 of 136, 14%), Andrya macrocephala (20 of 136, 14.7%), and Hymenolepis weldensis from 12 of 136, 8.8%. The acanthocephalan, Moniliformis clarki was found in 1 of 118 gophers (0.8%). No parasites were found in the cheek pouches, thoracic, or peritoneal cavities.