Pathways to self-organization: Crystallization via nucleation and growth.

Crystallization, a prototypical self-organization process during which a disordered state spontaneously transforms into a crystal characterized by a regular arrangement of its building blocks, usually proceeds by nucleation and growth. In the initial stages of the transformation, a localized nucleus of the new phase forms in the old one due to a random fluctuation. Most of these nuclei disappear after a short time, but rarely a crystalline embryo may reach a critical size after which further growth becomes thermodynamically favorable and the entire system is converted into the new phase. In this article, we will discuss several theoretical concepts and computational methods to study crystallization. More specifically, we will address the rare event problem arising in the simulation of nucleation processes and explain how to calculate nucleation rates accurately. Particular attention is directed towards discussing statistical tools to analyze crystallization trajectories and identify the transition mechanism.

Dynamical phases of attractive particles sliding on a structured surface.

Inspired by experiments on quartz crystal microbalance setups, we study the mobility of a monolayer of Lennard-Jones particles driven over a hexagonal external potential. We pay special attention to the changes in the dynamical phases that arise when the lattice constant of the external substrate potential and the Lennard-Jones interaction are mismatched. We find that if the average particle separation is such that the particles repel each other, or interact harmonically, the qualitative behavior of the system is akin to that of a monolayer of purely repulsive Yukawa particles. On the other hand, if the particles typically attract each other, the ensuing dynamical states are determined entirely by the relative strength of the Lennard-Jones interaction with respect to that of the external potential.

Spectrum of viral infections in patients with cystic fibrosis.

This review explores the extensive influence of viral infections leading to chronic deterioration of lung function in patients with cystic fibrosis (CF). The mechanisms how viral agents affect the pathogenesis as well as the inflammatory and immune response of CF are discussed. Viral infections of the upper and lower respiratory tract due to viruses in CF patients and methods for diagnosis of respiratory viruses are described in detail. The importance of respiratory and non-respiratory viral agents for the pathogenesis, especially for the exacerbation of bacterial lower respiratory tract infections and course of CF, is stressed, especially emphasizing respiratory syncytial virus, influenza virus, rhinovirus, and human herpes viruses. Possible harmful effects of further viruses like adenovirus, bocavirus, coronavirus, metapneumovirus, parainfluenzavirus on the lung function of CF patients are discussed. The potential use of adenovirus-based vectors for somatic gene therapy is mentioned.

The influence of virus infections on the course of COPD.

Chronic obstructive pulmonary disease (COPD) is extensively influenced by viral infections. The mechanisms of how viral agents affect the pathogenesis and prognosis of COPD are numerous. In general, patients with infectious exacerbations are characterized by longer hospitalization periods and greater impairment of several lung function parameters than those with non-infectious exacerbations. Prodromal, clinical, and outcome parameters fail to distinguish virally from non-virally induced illnesses in cases of exacerbations. The importance of infections with respiratory and non-respiratory viral agents for pathogenesis and course of COPD is detailed. Human adenovirus, non-respiratory viruses including human immunodeficiency virus, human metapneumovirus, influenza virus, human rhinovirus, and respiratory syncytial virus are especially stressed.

Osmotic compression of droplets of hard rods: a computer simulation study.

By means of computer simulations, we study how droplets of hard, rodlike particles optimize their shape and internal structure under the influence of the osmotic compression caused by the presence of spherical particles that act as depletion agents. At sufficiently high osmotic pressures, the rods that make up the drops spontaneously align to turn them into uniaxial nematic liquid-crystalline droplets. The nematic droplets or "tactoids" that are formed this way are not spherical but elongated, resulting from the competition between the anisotropic surface tension and the elastic deformation of the director field. In agreement with recent theoretical predictions, we find that sufficiently small tactoids have a uniform director field, while large ones are characterized by a bipolar director field. From the shape and director-field transformation of the droplets, we are able to estimate the surface anchoring strength and an average of the elastic constants of the hard-rod nematic.

Statistical limitations of percent ideal body weight as measure for nutritional failure in patients with cystic fibrosis.

BACKGROUND: For the past decade, percentage of ideal body weight (%IBW) was recommended by European and US nutrition consensus reports as preferred clinical measure of nutritional status in children with cystic fibrosis (CF). We and others have demonstrated that the %IBW method underestimates the prevalence of nutritional failure in CF, but the underlying mechanism for this methodological flaw remains incompletely defined. DESIGN: We performed model calculations from cross sectional growth data of healthy and CF-children to assess the methodological limitations of %IBW calculation. RESULTS: Here we demonstrate that an intrinsic limitation of %IBW method is that it largely ignores the statistical principle of regression to the mean. The key assumption of %IBW is that ideal weight-for-age is on exactly the same percentile ranking as height-for-age. We show that this assumption is only valid if the individual's height is close to the reference median. When the stature deviates from the median of the reference population, however, the increments of height-for-age and weight-for-age percentiles are not the same. In consequence, %IBW method systematically underestimates the ideal weight for smaller-than-average individuals, like CF-patients, which results in significant underestimation of the prevalence of malnutrition in this group of patients. CONCLUSION: There is increasing scientific evidence that calculation of %IBW as a measure of nutritional status in children with CF is flawed and should be discontinued. It is expected that future guidelines will recommend the use of alternative measures of weight-for-height proportion, e.g. BMI percentiles, to assess underweight and malnutrition in patients with CF.

[The effects of physical training on the body composition of patients with COPD]. / Die Auswirkungen von Sport auf die Körperzusammensetzung von COPD-Patienten.

AIM: The following controlled trial was conducted to determine the positive effects of exercise on the body composition of patients suffering from COPD. METHODS: A group consisting of 23 COPD patients who regularly participated in a guided exercise programme was compared with a control group consisting of 19 COPD patients who did not exercise. The relative changes of body mass index (BMI), body cell mass in % [BCM-(%)], extra cellular mass/body cell mass index (ECM/BCM index) and phase angle (angle between sinus current and sinus voltage) after 6 months and after one year were analysed for statistical differences. The values of BMI, BCM-(%), ECM/BCM index and phase angle at the beginning of the study were compared with the results during the course of the 18 months training merely within the exercising group. The body composition of the patients was determined with the help of the bioelectric impedance analysis (BIA) using the system "Nutriguard M" produced by "Data Input". RESULTS: Significantly raised phase angle values as well as significantly increased BCM-(%) values and a decreased ECM/BCM index were found in the group of patients who exercised compared with the COPD patients who did not exercise. While there were no differences concerning the BMI value, significant increases in BCM-(%) and phase angle and a significant decrease of the ECM/BCM index could be detected within the group that had been exercising. The best values were recorded after 6 months of exercising. The differences of the group responses resulted from a worsening of the body composition in the control group rather than from improvements in the exercise group. CONCLUSION: Physical exercise can improve or at least stabilise the body composition of COPD patients and should be recommended.

Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions.

BACKGROUND AND STUDY AIM: Endoscopic-ultrasound-guided elastography (EUS-elastography) is a recently introduced imaging procedure that distinguishes tissues on the basis of their specific consistency. The aim of this prospective study was to investigate the role of this new technique in the characterization and differentiation of focal pancreatic lesions. PATIENTS AND METHODS: This prospective study enrolled 70 patients with unclassified solid lesions of the pancreas and 10 controls with a healthy pancreas. In all patients elastography recordings were compared with cytology/histology findings as the gold standard. RESULTS: Adequate EUS-elastography of the pancreas was performed in all healthy controls but in only 56 % of patients with solid pancreatic lesions. The main limitation of elastographic image acquisition was incomplete delineation of the border of lesions greater than 35 mm in diameter (39 %) or of lesions at some distance from the transducer (10 %). Elastographic recordings were also hampered by the fact that the surrounding tissue, which is used as an internal reference standard for strain calculation, was insufficiently displayed in the case of larger lesions. The reduced ratio of target to surrounding tissue resulted in the formation of color artifacts and in impaired reproducibility. In contrast, the majority of lesions smaller than 35 mm in diameter were adequately and reproducibly evaluated by EUS-elastography (91 %). The clinical use for differential diagnosis, however, seems limited, since strain images from all kinds of pancreatic masses were found to be harder than the surrounding tissues, irrespective of the underlying nature of the lesion (i. e., malignant vs. benign). EUS-elastography predicted the nature of pancreatic lesions with poor diagnostic sensitivity (41 %), specificity (53 %), and accuracy (45 %). CONCLUSION: EUS-elastography of the pancreas has the potential to obtain some complementary information that would improve tissue characterization. Its clinical utility, however, remains questionable, and it seems unlikely that the information provided will obviate the necessity of obtaining tissue samples for confirmation of a final pathologic diagnosis.

Oxygen generation by combined electrolysis and fuel-cell technology: clinical use in COPD patients requiring long time oxygen therapy.

BACKGROUND: Oxy-Gen lite, a recently developed combined electrolysis and fuel cell technology, de-novo generates oxygen with high purity for medical use from distilled water and room air. However, its use in patients with chronic respiratory failure has never been evaluated. OBJECTIVES: To test the clinical applicability and safety of Oxy-Gen lite technology, we enrolled 32 COPD patients with chronic hypoxemia and long-term oxygen therapy (LTOT) in a controlled, randomized, multicenter clinical trial. MATERIALS AND METHODS: Standard continuous oxygen therapy with a maximal flow rate of 2 L/min was tested against pulsatile oxygen delivery by Oxy-Gen lite. Oxygen saturation at seated-rest was recorded over 30 min and used as a primary read-out parameter. Oxygen saturation was also recorded during mild physical strain (speaking out loud) or overnight's sleep. RESULTS: Both methods of oxygen supply established oxygen saturations within the normal range (i.e., upper plateau of the sigmoid oxyhaemoglobin dissociation curve) compared to breathing room air (p<0.0001). Mean oxygen saturation under standard continuous oxygen flow or Oxy-Gen lite technology during rest, physical strain or sleep proved statistically equivalent (95%CI<2.5% of reference saturation). CONCLUSION: The use of Oxy-Gen lite in COPD patients with hypoxemia and LTOT

[Damage to the respiratory tract due to aspirated alendronate]. / Schädigung des Respirationstrakts durch aspiriertes Alendronat.

We describe the rare case of a high-grade chemical irritating-toxic damage to the larynx, the trachea and the bronchial system due to the aspiration of the bisphosphonate alendronate. The aspiration of alendronate was caused by oropharyngeal dysphagia. The 68-year-old female patient was sent to hospital with increasing hoarseness and a tormenting continuous cough of high intensity. X-Ray pictures of the thorax showed dystelectasis of the right middle lobe. Severe damage to the bronchial system caused by the aspirated alendronate was demonstrated by flexible bronchoscopy. Anti-obstructive, antiphlogistic and antibiotic treatment led to a gradual improvement of the symptoms. The administration of alendronate should be avoided in cases of dysphagia. Besides the danger of oesophageal injury, there is also the risk of aspiration that can be associated with severe damage to the bronchial system as this case study demonstrates.

Depletion-induced percolation in networks of nanorods.

Above a certain density threshold, suspensions of rodlike colloidal particles form system-spanning networks. Using Monte Carlo simulations, we investigate how the depletion forces caused by spherical particles affect these networks in isotropic suspensions of rods. Although the depletion forces are strongly anisotropic and favor alignment of the rods, the percolation threshold of the rods decreases significantly. The relative size of the effect increases with the aspect ratio of the rods. The structural changes induced in the suspension by the depletant are characterized in detail and the system is compared to an ideal fluid of freely interpenetrable rods.

Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts.

PU.1, a transcription factor of the ETS family, plays a pivotal role in normal hematopoiesis, and particularly in myeloid differentiation. Altered PU.1 function is possibly implicated in leukemogenesis, as PU.1 gene mutations were identified in some patients with acute myeloid leukemia (AML) and as several oncogenic products (AML1-ETO, promyelocytic leukemia-retinoic acid receptor alpha, FMS-like receptor tyrosine kinase 3 internal tandem duplication) are associated with PU.1 downregulation. To demonstrate directly a role of PU.1 in the blocked differentiation of leukemic blasts, we transduced cells from myeloid cell lines and primary blasts from AML patients with a lentivector encoding PU.1. In NB4 cells we obtained increases in PU.1 mRNA and protein, comparable to increases obtained with all-trans retinoic acid-stimulation. Transduced cells showed increased myelomonocytic surface antigen expression, decreased proliferation rates and increased apoptosis. Similar results were obtained in primary AML blasts from 12 patients. These phenotypic changes are characteristic of restored blast differentiation. PU.1 should therefore constitute an interesting target for therapeutic intervention in AML.

[Improvement in expiratory peak flow (PEF) of COPD patients due to "lung" sport for 12 months]. / Verbesserung des exspiratorischen Spitzenflusses (PEF) von COPD-Patienten durch Lungensport über 12 Monate.

This prospective, randomised, controlled study deals with the question whether it is possible to induce an improvement of peak expiratory flow (PEF) in patients suffering from COPD by a structured "lung" sport programme over a longer period of time (12 months). Furthermore, a comparison with the spontaneous course of the disease was performed. A group of 7 COPD patients (1 man, 6 women, mean age 70 years, COPD grade II - III according to GOLD) who regularly took part in a structured lung sport programme was compared with a control group of 10 COPD patients (5 men, 5 women, mean age 67.5 years, COPD grade II - III according to GOLD) who denied doing sport. The PEF values of the patients were measured after 0 and 12 months during exacerbation-free intervals. The relative changes of PEF in percent after one year were statistically compared. There was an improvement of PEF of about + 10.4 % (standard deviation SD +/- 8.9 %) after 12 months of lung sport. The spontaneous course of the disease of the patients who denied doing sport led to a decrease of PEF of about - 8.8 % (standard deviation SD +/- 11.5 %). The difference in PEF changes with respect to "lung" sport and to the spontaneous course of COPD was highly significant (p < 0.01) in spite of a high standard deviation. The long lasting improvement of PEF due to sport among COPD patients speaks in favour of a positive effect of "lung" sport.

[Post-operative sclerosing mesenteritis]. / Postoperative sklerosierende Mesenteritis.

For the first time we describe a sclerosing mesenteritis that appeared acutely after abdominal operations. The patient suffered from diffuse abdominal symptoms. There was a hard tumour in the left middle and lower abdomen. Histological analysis revealed fibrosis and bone tissue. Symptoms improved after application of prednisone and high-calorie infusions.

[Ureteral rupture when changing a suprapubic vesical catheter]. / Ureterruptur beim suprapubischen Katheterwechsel.

We describe, for the first time, a rupture of the ureter caused by changing a suprapubic vesical catheter. The guide wire passed into the ostium of the left ureter during the procedure, and the catheter was pushed over the wire into the left ureter blocking it. The lesion was diagnosed by intravenous pyelography. A pigtail stent was placed in the left ureter.

Depletion induced isotropic-isotropic phase separation in suspensions of rod-like colloids.

When non-adsorbing polymers are added to an isotropic suspension of rod-like colloids, the colloids effectively attract each other via depletion forces. We performed Monte Carlo simulations to study the phase diagram of such rod-polymer mixture. The colloidal rods were modeled as hard spherocylinders; the polymers were described as spheres of the same diameter as the rods. The polymers may overlap with no energy cost, while the overlap of polymers and rods is forbidden. Large amounts of depletant cause phase separation of the mixture. We estimated the phase boundaries of isotropic-isotropic coexistence both in the bulk and in confinement. To determine the phase boundaries we applied the grand canonical ensemble using successive umbrella sampling [J. Chem. Phys. 120, 10925 (2004)], and we performed a finite size scaling analysis to estimate the location of the critical point. The results are compared with predictions of the free volume theory developed by Lekkerkerker and Stroobants [Nuovo Cimento D 16, 949 (1994)]. We also give estimates for the interfacial tension between the coexisting isotropic phases and analyze its power-law behavior on the approach of the critical point.

[Gastrointestinal tuberculosis as the main manifestation of systemic tuberculosis]. / Darmtuberkulose als Hauptmanifestation einer systemischen Tuberkulose.

We describe a rare case of tuberculosis with mainly gastrointestinal problems. The 52-year-aged female patient came to hospital with unclear pain in the lower abdomen and ascites that was refractory to therapy. The computed tomography of the thorax showed right-sided confluating lymphoid nodes, the CT of the abdomen showed ascites and nodular structures near the coecum. Tissue samples were taken from the mucosa of the colon, the inflammatory altered peritoneum, the left bronchus of the upper lobe and the confluating lymphoid nodes in the mediastinum during colonoscopy, diagnostic laparoscopy and bronchoscopy. The samples from the peritoneum showed granulomas with caseating necroses in histological slices. Mycobacterium tuberculosis was detected by PCR in the tissue samples from the lymphoid tissue of the mediastinum. Furthermore, Mycobacterium tuberculosis grew in cultures from samples of the abdominal ascites. The symptoms and pathological findings improved under a therapy comprising isoniazid, rifampicin, ethambutol and pyrazinamid.

[Retroperitoneal bronchogenic cyst]. / Retroperitoneale bronchogene Zyste.

We describe a 35-year-old female patient who underwent surgery because of a coincidentally occurring cryptic tumour near the left adrenal gland and a right renal carcinoma (pT1, N0, G2, R0). The left-sided tumour was intraoperatively identified as a cystic structure filled with secretion. Histopathological analysis provided the diagnosis of a bronchogenic cyst.

[Villous adenoma of the renal pelvis and ureter]. / Villöses Adenom des Nierenbeckens und Ureters.

Villous adenomas of the urinary tract are extremely rare tumours belonging to the adenoepithelial metaplasias. They can be associated with other neoplasias, especially with carcinomas. We describe the case of an 85-year-old female patient suffering from a villous adenoma of the renal pelvis and ureter.

Assessment of body composition of patients with COPD.

The intention of the study was to determine nutritional state and body cell mass in patients with COPD in comparison with healthy volunteers between 50 and 75 years of age. Therefore, body cell mass (BCM), phase angle and the relation between extra cellular mass and body cell mass ECM/BCM was measured with the help of bioelectrical impedance analysis (BIA). While 10.4 % of COPD patients (male 5.0 %, female 18.8 %) had a BMI of < 18.5, no subject was underweight in the healthy volunteers. Overweight was found in 31.7 % patients (male 36.0 %, female 25.0 %) and in 54.2 % healthy subjects (male: 62.5 %, female 46.9 %), 17.1 % of our patients (male 16.0 %, female 18.8 %) versus 21.7 % of healthy subjects (male 14.3 %, female 28.1 %) were obese. While there was no statistic significance for a lower BMI in COPD patients, there were significantly decreased values concerning muscle mass -- represented by BCM-values -- and state of nutrition -- represented by BCM, phase angle and ECM/BCM values -- in COPD patients compared with healthy volunteers. These results suggest that BMI alone doesn't allow conclusions regarding to nutritional state and physical training. A malnutrition requiring intervention might exist in spite of a normal or even high BMI in COPD patients.