Evaluation of prosthetic mesh closure in semiopen-abdomen patients

Abstract Background. To avoid the adverse consequences of abdominal compartment syndrome and to reduce the high mortality the celiotomy wound in patients with abdominal sepsis was closed without tension using prosthetic mesh. This produces a semiopen situation that permits staged reinterventions together with the functional reconstitution of the continuity of the abdominal wall. Material and Methods. Twenty-five patients with intra-abdominal sepsis of various causes were evaluated retrospectively to assess the results of semiopen management of the septic abdomen and reoperations on demand in severe peritonitis. All of the patients were in a state of neglected peritonitis, and had at least one failing organ system. The Mannheim Peritonitis Index (MPI) scoring system was used for stratification of abdominal sepsis. Results. The mean MPI score of 25 patients was 24, ranging 10 to 33. Eight (32%) patients were reexplored (MPI=21). There were overall 9 (36%) complications in patients with mean MPI score of 23. Six (24%) mesh-related complications (infection and enterocutaneous fistulas) developed (MPI=19). The mean MPI score of patients without complications was 24. Four (16%) patients died with index MPI score of 26 due to fulminant hepatitis, myocardial infarction, and multiple organ failure. The admission period averaged 63 days. Conclusions. In 25 critically ill patients with abdominal sepsis the mortality was lower than expected, relative to heterogeneous data from the literature; also, major complications occurred less frequently although the mean MPI score was high. The authors conclude that this approach is a reliable contribution to the complex treatment of these patients. Electronic Publication     

Detection and genotyping of oocysts of Cryptosporidium parvum by real-time PCR and melting curve analysis

Several real-time PCR procedures for the detection and genotyping of oocysts of Cryptosporidium parvum were evaluated. A 40-cycle amplification of a 157-bp fragment from the C. parvum beta-tubulin gene detected individual oocysts which were introduced into the reaction mixture by micromanipulation. SYBR Green I melting curve analysis was used to confirm the specificity of the method when DNA extracted from fecal samples spiked with oocysts was analyzed. Because C. parvum isolates infecting humans comprise two distinct genotypes, designated type 1 and type 2, real-time PCR methods for discriminating C. parvum genotypes were developed. The first method used the same beta-tubulin amplification primers and two fluorescently labeled antisense oligonucleotide probes spanning a 49-bp polymorphic sequence diagnostic for C. parvum type 1 and type 2. The second genotyping method used SYBR Green I fluorescence and targeted a polymorphic coding region within the GP900/poly(T) gene. Both methods discriminated between type 1 and type 2 C. parvum on the basis of melting curve analysis. To our knowledge, this is the first report describing the application of melting curve analysis for genotyping of C. parvum oocysts.     

Ectodermal dysplasias: Classification and organization by phenotype,genotype and molecular pathway

An international advisory group met at the National Institutes of Health in Bethesda, Maryland in 2017, to discuss a new classification system for the ectodermal dysplasias (EDs) that would integrate both clinical and molecular information. We propose the following, a working definition of the EDs building on previous classification systems and incorporating current approaches to diagnosis: EDs are genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. Genetic variations in genes known to be associated with EDs that affect only one derivative of the ectoderm (attenuated phenotype) will be grouped as non‐syndromic traits of the causative gene (e.g., non‐syndromic hypodontia or missing teeth associated with pathogenic variants of EDA “ectodysplasin”). Information for categorization and cataloging includes the phenotypic features, Online Mendelian Inheritance in Man number, mode of inheritance, genetic alteration, major developmental pathways involved (e.g., EDA, WNT “wingless‐type,” TP63 “tumor protein p63”) or the components of complex molecular structures (e.g., connexins, keratins, cadherins).     

The effect of glucose dynamics on plasma copeptin levels upon glucagon,arginine, and macimorelin stimulation in healthy adults

Pituitary - Non-osmotic stimulation tests using glucagon, arginine, or macimorelin were recently evaluated for their ability to assess posterior pituitary function. Glucagon and arginine, but not...     

Effects of paracetamol and etodolac on plasma adrenaline levels of rats

Adrenaline, which is released from the adrenal medulla, is an important compound in the reaction of sympathetic nerve system. This hormone can increase the body’s normal metabolic rate up to 100 %, and thus improves the effectiveness of the whole body. It has been considered to be involved in the control of inflammation. Therefore, we investigated whether there are effects of paracetamol and etodolac on adrenaline levels of rats after oral administration. The rats were divided into three subgroups while analysing the effects of adrenaline on paracetamol and etodolac. The first group was the control, second group was composed of rats given paracetamol, and third group was composed of rats given etodolac. In order to measure adrenaline plasma concentration, we have used the high-performance liquid chromatography coupled with fluorescence detection. According to the result of the analysis, there are statistically important differences at adrenaline levels between control group and rats-applied drugs. Obtained results showed that although adrenaline level in the paracetamol-applied group decreased, adrenaline level in the etodolac-applied group increased. It is concluded that different effects of etodolac and paracetamol on circulating adrenaline levels can be related to their different effects on inflammation, COX enzymes, prostaglandins, etc. Also we can suggest usage of paracetamol instead of etodolac in patients with cardiovascular system diseases.     

Early and multiple origins of metastatic lineages within primary tumors

Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases.It has long been understood that tumorigenesis is an evolutionary process (1) associated with the accumulation of somatic mutations (2). However, many aspects of that process that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages (3, 4). Somatic mutations have revealed tumor type-specific drivers by comparison of primary tumor and normal tissues (5, 6), and studies examining the evolutionary process of cancer across multiple sites have used a handful of subjects to identify ubiquitous, shared, and private mutations (1) and to reconstruct a number of tumor phylogenies using parsimony or unweighted pair group methods with arithmetic mean (1, 7) but have lacked the power to generalize about the tumorigenic or metastatic process across cancer types (1).Tumor phylogenetics, using a larger sample with explicit evolutionary models, can be applied using molecular evolutionary models to reconstruct ancestral states of somatic mutations and infer cancer chronograms, revealing novel information about the timing of gene mutations and their contributions to tumorigenesis and metastasis and addressing three fundamental aspects of cancer biology. First, the topology of divergence of primary and metastatic lineages can differentiate between a linear model of cancer progression, in which all metastatic tumors are descended from a single original primary cell such that all metastases are more closely related to each other than they are to any tissue in the primary tumor, and a branched model, in which metastases can originate from divergent lineages within primary tumors. Second, molecular evolutionary trees and chronograms can quantify how early metastatic lineages arise in tumor development, clarifying the role of mutations in facilitating metastasis. Last, integration of temporal inferences across patients can convey the order of occurrence of driver mutations, guiding development of targeted therapeutics effective against primary tumors and metastases.Here, we perform tumor phylogenetics to address these questions. Although ascertaining variable degrees of tumor heterogeneity (1) by computational analyses of subclonality within primary tumors has proven challenging (8), another approach to revealing heterogeneity is analysis of the sequence divergence of major clones extracted from distant sites. We replayed the “tape of cancer” and mapped genetic mutations on the tree of cancer evolution extending from normal tissue to primary tumor and metastases. Analyzing new exome sequence data from primary and metastatic sites, we applied maximum likelihood and Bayesian approaches to reveal phylogenetic relationships and tumor evolution chronology. We identified genetic mutations associated with tumorigenesis that commonly precede the first genetic divergence of all cancer lineages, also examining those that precede all metastases. Furthermore, we quantified the temporal distributions of the first genetic divergence of metastases from the primary tumor and evaluated the temporal order of gene mutations in cancer.