Fiber reinforced hydrated networks recapitulate the poroelastic mechanics of articular cartilage.

The role of poroelasticity on the functional performance of articular cartilage has been established in the scientific literature since the 1960s. Despite the extensive knowledge on this topic there remain few attempts to design for poroelasticity and to our knowledge no demonstration of an engineered poroelastic material that approaches the physiological performance. In this paper, we report on the development of an engineered material that begins to approach physiological poroelasticity. We quantify poroelasticity using the fluid load fraction, apply mixture theory to model the material system, and determine cytocompatibility using primary human mesenchymal stem cells. The design approach is based on a fiber reinforced hydrated network and uses routine fabrication methods (electrohydrodynamic deposition) and materials (poly[ɛ-caprolactone] and gelatin) to develop the engineered poroelastic material. This composite material achieved a mean peak fluid load fraction of 68%, displayed consistency with mixture theory, and demonstrated cytocompatibility. This work creates a foundation for designing poroelastic cartilage implants and developing scaffold systems to study chondrocyte mechanobiology and tissue engineering. STATEMENT OF SIGNIFICANCE: Poroelasticity drives the functional mechanics of articular cartilage (load bearing and lubrication). In this work we develop the design rationale and approach to produce a poroelastic material, known as a fiber reinforced hydrated network (FiHy™), that begins to approach the native performance of articular cartilage. This is the first engineered material system capable of exceeding isotropic linear poroelastic theory. The framework developed here enables fundamental studies of poroelasticity and the development of translational materials for cartilage repair.

Thin-film models for an active gel.

In this study, we present a free-boundary problem for an active liquid crystal starting with the Beris-Edwards theory that uses a tensorial order parameter and includes active contributions to the stress tensor and then derive from it the Eriksen model for an active polar gel and scalar order parameter to analyse the rich defect structure observed in applications such as the adenosinetriphosphate-driven motion of a thin film of an actin filament network. The small aspect ratio of the film geometry allows for an asymptotic approximation of the free-boundary problem in the limit of weak elasticity of the network and strong active terms. The new thin-film model captures the defect dynamics in the bulk as well as wall defects and thus presents a significant extension of previous models based on the Leslie-Erickson-Parodi theory. As an example we derive the explicit solution for an active gel confined to a channel, which has discontinuous director profile leading to a bidirectional flow structure generated by the active terms.

Azathioprine and mercaptopurine in the management of patients with chronic, active microscopic colitis.

BACKGROUND: Microscopic colitis (MC) is a common chronic diarrhoeal disease, and remission can be induced with budesonide. However, diarrhoea relapses frequently when budesonide is tapered and a few patients become budesonide intolerant. AIM: To examine retrospectively the effect of azathioprine (AZA) and mercaptopurine (MP) in patients with chronic, active MC. METHODS/PATIENTS: Data on all MC patients who received AZA or MP in the years 1997-2011 at three centres representing three countries were pooled for analysis. The indications for thiopurine therapy were frequent relapses after short-term treatment (N = 26), budesonide dependency on 6 mg (N = 15) and budesonide intolerance (N = 5). The response to thiopurine treatment was defined as clinical remission, intolerance or nonresponse. RESULTS: Forty-six MC patients (32 CC and 14 LC), 32 female; median age 59 years (range: 36-83) with a median disease duration of 3 years (range: 0.5-18) were included. Thirteen patients (28%) achieved long-term clinical remission on AZA therapy. AZA failed in 31 patients (67%) due to intolerance and in 2 patients (4%) because of nonresponse. Thirteen of 31 AZA-intolerant patients were switched to MP and 6 patients (46%) obtained clinical remission. Thus, the overall response rate to thiopurines was 19/46 (41%). The main side effects were nausea/vomiting and abnormally elevated liver enzymes. CONCLUSIONS: In this retrospective case series, the majority of chronic, active MC patients were intolerant to AZA leading to cessation of treatment. However, further studies are needed to explore the efficacy, acceptance, tolerance and safety of MP in patients with chronic, active MC refractory to budesonide.

Microscopic colitis: Current status, present and future challenges: statements of the European Microscopic Colitis Group.

Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.

Opportunistic cytomegalovirus infection causing colonic perforation in a patient with systemic lupus erythematosus.

We present the case of a 58-year-old woman with a long-standing history of systemic lupus erythematosus (SLE) who developed a cytomegalovirus (CMV) infection with colonic perforation and subsequent purulent peritonitis whilst using combined immunosuppressive therapy. The pathogenesis and the clinical presentation of this unique case is discussed in detail. Opportunistic infection should always be kept in mind in SLE patients presenting with fever. Viral serology should be routinely performed in these patients, especially when immunosuppressive therapy is given, to avoid delay in instituting adequate management and therapy.

Low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission.

BACKGROUND: Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments. AIM: To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. METHODS: The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 µmol/L CDCA or DCA. RESULTS: When adding 100 µmol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P=0.004 and P=0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min. CONCLUSIONS: Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.

Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.

Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls.

BACKGROUND: Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. METHODS: Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re-assessed. KEY RESULTS: All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. CONCLUSIONS & INFERENCES: Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.

Quantifying hydrodynamic slip: a comprehensive analysis of dewetting profiles.

To characterize nontrivial boundary conditions of a liquid flowing past a solid, the slip length is commonly used as a measure. From the profile of a retracting liquid front (e.g., measured with atomic force microscopy), the slip length can be extracted with the help of a Stokes model for a thin liquid film dewetting from a solid substrate. Specifically, we use a lubrication model derived from the Stokes model for strong slippage and linearize the film profile around the flat, unperturbed film. For small slip lengths, we expand the linearized full Stokes model for small slopes up to third order. Using the respective model, we obtain, in addition to the slip length, the capillary number, from which we can estimate the viscosity of the fluid film. We compare numerical and experimental results, test the consistency and the validity of the models/approximations, and give an easy-to-follow guide of how they can be used to analyze experiments.

[Coronary stents, dual antiplatelet therapy and peri-operative problems]. / Koronare Stents, duale Antiplättchentherapie und die perioperative Problematik.

Up to 90% of all percutaneous coronary interventions include coronary artery stenting. Dual antiplatelet therapy, usually involving acetylsalicyl acid combined with clopidogrel, is mandatory for patients with coronary artery stents. The duration of antiplatelet therapy for bare metal stents is 3-4 weeks, for drug eluting stents 6-12 months. Preoperative discontinuation of both drugs increases the risk of stent thrombosis, continuation the risk of relevant bleeding. According to the recommendations of anaesthesiological and cardiological societies, perioperative management has to balance the risk of bleeding vs stent thrombosis. Surgery involving a high risk of bleeding can require the discontinuance of both substances. In cases of high thrombosis risk, at least the acetylsalicyl acid should be continued until the day of surgery. For patients under antiplatelet therapy scheduled for local anaesthesia, national recommendations exist. A close collaboration between the anaesthesiologist, cardiologist and surgeon is essential for appropriate pre-, intra- and postoperative management.

A thin-film model for corotational Jeffreys fluids under strong slip.

We derive a thin-film model for viscoelastic liquids under strong slip which obey the stress tensor dynamics of corotational Jeffreys fluids.

Slip vs. viscoelasticity in dewetting thin films.

Ultrathin polymer films on non-wettable substrates display dynamic features which have been attributed to either viscoelastic or slip effects. Here we show that in the weak- and strong-slip regime, effects of viscoelastic relaxation are either absent or essentially indistinguishable from slip effects. Strong slip modifies the fastest unstable mode in a rupturing thin film, which questions the standard approach to reconstruct the effective interface potential from dewetting experiments.

New slip regimes and the shape of dewetting thin liquid films.

We compare the flow behavior of liquid polymer films on silicon wafers coated with either octadecyl-(OTS) or dodecyltrichlorosilane (DTS). Our experiments show that dewetting on DTS is significantly faster than on OTS. We argue that this is tied to the difference in the solid/liquid friction. As the film dewets, the profile of the rim advancing into the undisturbed film is monotonically decaying on DTS but has an oscillatory structure on OTS. For the first time we can describe this transition in terms of a lubrication model with a Navier-slip condition for the flow of a viscous Newtonian liquid.

A thin-film equation for viscoelastic liquids of Jeffreys type.

We derive a novel thin-film equation for linear viscoelastic media describable by generalized Maxwell or Jeffreys models. As a first application of this equation we discuss the shape of a liquid rim near a dewetting front. Although the dynamics of the liquid is equivalent to that of a phenomenological model recently proposed by Herminghaus et al. (S. Herminghaus, R. Seemann, K. Jacobs, Phys. Rev. Lett. 89, 056101 (2002)), the liquid rim profile in our model always shows oscillatory behaviour, contrary to that obtained in the former. This difference in behaviour is attributed to a different treatment of slip in both models.

Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy.

Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.

Physical and genetic mapping of novel microsatellite polymorphisms on human chromosome 19.

We describe here the identification of 11 novel microsatellite polymorphisms on human chromosome 19. These dinucleotide repeat polymorphisms were detected in chromosome 19-specific cosmids that were physically mapped by fluorescence in situ hybridization. For each repeat, flanking oligonucleotide primers were synthesized and the polymerase chain reaction assay was performed on a panel of 100 unrelated individuals to determine the heterozygosity and allele frequencies. To characterize these markers further, genetic and radiation hybrid maps were constructed. These microsatellite polymorphisms will be valuable in further linkage analysis of inherited diseases on chromosome 19p.

Cognitive control of eating behaviour and the disinhibition effect.

Restrained eaters have been reported to overeat following a high caloric preload, a phenomenon referred to as the disinhibition effect. However this effect has not been found when subjects were classified by the restraint subscales of the Three-Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985) or the Dutch Eating Behaviour Questionnaire (van Strien et al., 1986). The present study investigates the disinhibition effect in 133 normal-weight young women, using a two-factorial classification including the TFEQ-restraint and the TFEQ-disinhibition scale. The subjects were requested to consume ice-cream ad libitum during a taste test following a 200-ml milkshake preload or without preload. The results show that the behavioural disinhibition effect occurs only in subjects with simultaneous high scores on both subscales. In addition, subjects with high disinhibition scores consumed more ice-cream than low disinhibition subjects irrespective of their degree of restraint. While subjects with a more rigid control of eating behaviour did not show a difference in the amount of ice-cream consumed with or without preload, subjects with a more flexible control of eating behaviour reduced their intake following the preload condition. With regard to the Revised Restraint Scale (RRS Herman & Polivy, 1980) multiple regression results show that high RRS scores may be due to either higher TFEQ-restraint or higher TFEQ-disinhibition scores. The interpretation of the results favours the renaming of the TFEQ-disinhibition scale to "susceptibility to eating problems" because high scores on this scale indicate overeating in a variety of situations without requiring prior inhibition i.e. dietary restraint. It is supposed that high susceptibility to eating problems may be caused by rigid control of eating behaviour, whereas flexible control of eating behaviour may be a less problematic strategy of long-term weight control.

[Sore throat patients as the topic of a general practice quality circle. Determination and development of a practice guideline. Quality Assurance Study group for General Medicine]. / Halsschmerzpatienten als Thema eines hausärztlichen Qualitätszirkels.Bestandsaufnahme und Erarbeitung einer Handlungsleitlinie.

UNLABELLED: The present paper describes the institutionalization of a general practitioners' quality circle and the development of management guidelines for the treatment of patients with sore throat. Doctors participating: An invitation to attend an "information meeting" on the subject quality control and a quality circle sent to 200 general practitioners and internists, evoked a response by 18 physicians, ten of whom participated in the first meeting of the quality circle. Practical procedure: Stocktaking of the procedure in the doctor's office on the basis of a documentation questionnaire, the discussion of a video of the counselling of a patient with a sore throat, interviews with patients and the personal experience of the participating physicians was compared with a current analysis of the literature. The results of the comparison were taken as a basis for the development of management guidelines following the Dutch NHG Standard (Nederlands-Huisartsen-Genootschap-Standarden). RESULTS AND CONCLUSIONS: A wide variation was found in the treatment offered to patients with sore throats in the doctor's office. Deviation from text book information does not indicate a priori any quality deficit in the GP's practice. With respect to the management guideline worked out, it was agreed that in the individual case, a wellfounded deviation can be justified.