Port site herniation of the small bowel following laparoscopy-assisted distal gastrectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Port-site herniation is a rare but potentially dangerous complication after laparoscopic surgery. Closure of port sites, especially those measuring 10 mm or more, has been recommended to avoid such an event.</p> <p>Case presentation</p> <p>We herein report the only case of a port site hernia among a series 52 consecutive cases of laparoscopy-assisted distal gastrectomy (LADG) carried out by our unit between July 2002 and March 2007. In this case the small bowel herniated and incarcerated through the port site on day 4 after LADG despite closure of the fascia. Initial manifestations experienced by the patient, possibly due to obstruction, and including mild abdominal pain and nausea, occurred on the third day postoperatively. The definitive diagnosis was made on day 4 based on symptoms related to leakage from the duodenal stump, which was considered to have developed after severe obstruction of the bowel. Re-operation for reduction of the incarcerated bowel and tube duodenostomy with peritoneal drainage were required to manage this complication.</p> <p>Conclusion</p> <p>We present this case report and review of literature to discuss further regarding methods of fascial closure after laparoscopic surgery.</p

The R403Q Myosin Mutation Implicated in Familial Hypertrophic Cardiomyopathy Causes Disorder at the Actomyosin Interface

Mutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC). Mutations in the beta-myosin heavy chain (MHC) remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype.Here we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1), whose kinetic features have much in common with slow beta-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP) and absence (apo) of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface.These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state

Interest groups in multiple streams:specifying their involvement in the framework

Although interests inhabit a central place in the multiple streams framework (MSF), interest groups have played only a minor role in theoretical and empirical studies until now. In Kingdon’s original conception, organized interests are a key variable in the politics stream. Revisiting Kingdon’s concept with a particular focus on interest groups and their activities—in different streams and at various levels—in the policy process, we take this argument further. In particular, we argue that specifying groups’ roles in other streams adds value to the explanatory power of the framework. To do this, we look at how interest groups affect problems, policies, and politics. The influence of interest groups within the streams is explained by linking the MSF with literature on interest intermediation. We show that depending on the number of conditions and their activity level, interest groups can be involved in all three streams. We illustrate this in case studies reviewing labor market policies in Germany and chemicals regulation at the European level

Identification of functional differences between recombinant human α and β cardiac myosin motors

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is >ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding

Secondary solid cancer screening following hematopoietic cell transplantation

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients

A myosin II nanomachine mimicking the striated muscle

The contraction of striated muscle (skeletal and cardiac muscle) is generated by ATP-dependent interactions between the molecular motor myosin II and the actin filament. The myosin motors are mechanically coupled along the thick filament in a geometry not achievable by single-molecule experiments. Here we show that a synthetic one-dimensional nanomachine, comprising fewer than ten myosin II dimers purified from rabbit psoas, performs isometric and isotonic contractions at 2 mM ATP, delivering a maximum power of 5 aW. The results are explained with a kinetic model fitted to the performance of mammalian skeletal muscle, showing that the condition for the motor coordination that maximises the efficiency in striated muscle is a minimum of 32 myosin heads sharing a common mechanical ground. The nanomachine offers a powerful tool for investigating muscle contractile-protein physiology, pathology and pharmacology without the potentially disturbing effects of the cytoskeletal-and regulatory-protein environment

DNA methylation as a biomarker in breast cancer

In cancer, epigenetic changes such as covalent addition of methyl groups to the genomic DNA itself are more prominent than genetic changes. Cytosine-phosphate-guanosine (Cl methylation negatively affects gene transcription of an adjacent gene. It is thought that DNA methylation significantly contributes to all hallmarks of cancer. Next to being a potential therapy target, DNA methylation is an emerging field of biomarkers. Technically, DNA provides a stable and robust analyte that is particularly suitable for clinical applications, Moreover, there are numerous potential human DNA sources that could facilitate integration of methylation tests in clinical practice. In breast cancer, DNA methylation has shown promise as a potential biomarker for early detection, therapy monitoring, assessment of prognosis or prediction of therapy response. In particular, paired-like homeodomain transcription factor 2 (PITX2) DNA methylation has been validated using a robust assay for paraffin-embedded tissue for clinically relevant outcome prediction in early breast cancer patients treated by adjuvant tamoxifen therapy