Role of esophageal brushing cytology in monitoring patients treated with sclerotherapy for esophageal varices.

Recent reports claim that there might be a relationship between sclerotherapy for esophageal varices and cancer of the esophagus. The discovery of a squamous cell cancer of the lower esophagus in a patient treated three years previously with sclerotherapy led us to set up a follow-up protocol. In order to assess this relationship and to monitor the evolution of such lesions, 68 patients treated with sclerotherapy with polidocanol because of esophageal varices were examined endoscopically at six-month intervals, and brushing samples were taken. The ages of the patients ranged between 35 and 81 years, and all had portal hypertension due to cirrhosis; 10 patients with the same disease but without bleeding varices were also examined. The interval between sclerotherapy and the first cytologic follow-up examination averaged 34 months, while the interval to the last follow-up examination averaged 40 months. One patient was examined four times (1.4%), 10 three times (14.7%), 39 twice (57.4%) and 18 only once (26.5%). Two cases were interpreted as nuclear hyperplasia associated with inflammation and were found to have regressed at a subsequent examination; all the other cases were reported as negative although sometimes associated with inflammation. None of the controls showed any abnormalities. While the occurrence of esophageal cancer after sclerotherapy might be associated with other risk factors, such as alcohol intake and smoking, esophageal brushing cytology can successfully monitor these patients and detect early stages of neoplasia.     

Comparison of NMR and molecular modeling results for a rigid and a flexible oligosaccharide

Three-bond heteronuclear coupling constants (³J_CH) are extremelyuseful in describing flexible models for oligosaccharides. Weshow that antiphase methods for measuring ³J_CH in oligosaccharideshave limited reliability but that the coupling constants canbe reliably measured in natural abundance by quantitative J-correlationmethods. Interpretation of ³J_CH data for a pentasaccharide (lacto-N-fuco-pentaose2) from human milk are consistent with a rigid model for theLewis^a trisaccharide epitope but for an antigenic tetrasaccharidefragment from the cell wall polysaccharide of viridans streptococci,³J_CH data imply a considerably more flexible model. NuclearOverhauser effect (NOE) data are reported for a heptasacchariderepeating unit isolated from the cell wall polysaccharide ofStreptococcus gordonii 38. The results for a tetrasaccharidefragment are similar to data reported for the same fragmentin the cell wall polysaccharide from S.mitis 322. This resultimplies a similar conformation for the tetrasaccharide fragmentin the polysaccharide and in the heptasaccharide and also impliesthat anisotropy of motion is not significant in the interpretationof the nuclear Overhauser effects in the polysaccharide. Interpretationof the NOE results for the tetrasaccharide fragment, like the³J_CH data, implies a flexible model with three conformationsin fast exchange. The results of the two experimental techniquesare combined with molecular modeling results including moleculardynamics simulation to provide a clear delineation between flexibleand rigid oligosaccharide epitopes. The blood group Lewis^a trisaccharideantigenic determinant is highly restricted in its motions bysteric interactions while the antigenic tetrasaccharide fragmentof the S.gordonii 38 heptasaccharide is considerably more mobile.We propose that some branched oligosaccharides are relativelyrigid and some are flexible depending on subtle details of thelinkages. oligosaccharide conformation molecular dynamics     

兔食管静脉曲张模型的建立

目的建立新西兰兔的食管静脉曲张模型,为下一步的临床研究提供可靠的小型动物模型。方法采用门静脉左支完全夹闭法造模,并通过外观、超声、胃镜等检查检验手段对造模结果加以评估。结果术后8周存活动物100%可见食管静脉曲张。结论通过门静脉左支夹闭法,基本可以建立兔食管静脉曲张模型。     

Surgical treatment of bleeding esophageal varices

Massive bleeding from varices in the esophagus and stomach secondary to liver disease is a serious surgical emergency, as the patient may bleed to death. The problem is further complicated by the difficulties in making a diagnosis and the poor general condition of the patient due to the long standing liver disease. For the past two years at the San Francisco Hospital this problem has been handled by exploring the stomach and esophagus and ligating the bleeding point. No effort has been made to lower the pressure in the veins to the liver. The results have been sufficiently encouraging to warrant further trial.     

Mechanics and hemodynamics of esophageal varices during peristaltic contraction

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.     

Selection of operation in patients with bleeding esophageal varices.

The results of surgical treatment of bleeding esophageal varices over an 8-year period in 155 patients are reviewed. Primary treatment of bleeding was conservative, with intravenous administration of vasopressin and balloon tamponade. Emergency operations were carried out after 48 hours in persons with persistent bleeding who were surgical candidates. Operative mortality was higher in this group (40%) than in those undergoing elective or urgent operations (each 10%). Postoperative encephalopathy occurred in 35% of patients and was correlated closely to late death after establishment of a shunt. The mesocaval shunt is no better than the portacaval but appears to be a good alternative in an emergency. In a controlled trial the distal splenorenal shunt was found to be associated with a lower rate of postoperative encephalopathy than the portacaval shunt, but thus far the long-term survival rates have not differed.     

Comparison of Hi-C results using in-solution versus in-nucleus ligation

BackgroundChromosome conformation capture and various derivative methods such as 4C, 5C and Hi-C have emerged as standard tools to analyze the three-dimensional organization of the genome in the nucleus. These methods employ ligation of diluted cross-linked chromatin complexes, intended to favor proximity-dependent, intra-complex ligation. During development of single-cell Hi-C, we devised an alternative Hi-C protocol with ligation in preserved nuclei rather than in solution. Here we directly compare Hi-C methods employing in-nucleus ligation with the standard in-solution ligation.ResultsWe show in-nucleus ligation results in consistently lower levels of inter-chromosomal contacts. Through chromatin mixing experiments we show that a significantly large fraction of inter-chromosomal contacts are the result of spurious ligation events formed during in-solution ligation. In-nucleus ligation significantly reduces this source of experimental noise, and results in improved reproducibility between replicates. We also find that in-nucleus ligation eliminates restriction fragment length bias found with in-solution ligation. These improvements result in greater reproducibility of long-range intra-chromosomal and inter-chromosomal contacts, as well as enhanced detection of structural features such as topologically associated domain boundaries.ConclusionsWe conclude that in-nucleus ligation captures chromatin interactions more consistently over a wider range of distances, and significantly reduces both experimental noise and bias. In-nucleus ligation creates higher quality Hi-C libraries while simplifying the experimental procedure. We suggest that the entire range of 3C applications are likely to show similar benefits from in-nucleus ligation.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0753-7) contains supplementary material, which is available to authorized users.     

Simulation of quadrupedal locomotion using a rigid body model

Locomotion of the horse is simulated using a mathematical model based on rigid body dynamics. A general method to generate the equations of motion for a two-dimensional rigid body model with an arbitrary number of hinge joints is presented and a numerical solution method, restricted to tree-structured models, is described. Joint movements originating from muscular forces or moments are simulated, but the method also allows that parts of the model follow strictly the pattern of kinematic data. Moment-generators with first-order linear feedback were used as a rotational muscle-equivalent. Ground-hoof interaction forces are approximated by a viscoelastic model and pseudo-Coulomb friction in vertical and horizontal directions respectively. Results of model simulations are compared to experimentally recorded data. Subsequently, adjustments are made to improve the agreement between simulation and experimental results.