Sliding free transverse rectus abdominis myocutaneous flap for closure of a massive abdominal wall defect: A case report

Despite considerable advances in reconstructive surgery, massive abdominal wall defects continue to pose a significant surgical challenge. We report the case of a 72‐year‐old morbidly obese female patient with Clostridium septicum‐related gas gangrene of the abdominal wall. After multidisciplinary treatment and multiple extensive debridements, a massive full‐thickness defect (40 cm × 35 cm) of the right abdominal wall was present. The abdominal contents were covered with a resorbable mesh to prevent evisceration. Finally, the composite defect was successfully reconstructed through a contralateral extended free transverse rectus abdominis myocutaneus (TRAM) flap (50 cm × 38 cm). An arterio‐venous loop to the superficial femoral vessels using the great saphenous vein was necessary to allow the flap to reach the defect. Postoperatively, a minor wound healing disorder of the flap was successfully treated with split skin grafting. Six month after surgery, the patient presented with a completely healed flap coverage area and a small abdominal hernia without the need of further surgical revision. This case illustrates the use of a sliding free TRAM flap for closure of a massive abdominal wall defect.     

Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior

Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case–control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10⁻⁷) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.     

Frequency of fall-related injuries of female patients referred to the trauma center in the city of Kashan from years 2005 to 2008

Objective:Falls are one of the life events leading to injury and in serious cases cause high morbidity and mortality.This research was conducted to determine the fall incidence among female population ...     

One-stage double free flap arteriovenous loop reconstruction of a massive abdominothoracic defect following necrotizing fasciitis: A case report

We report the case of a 67-year old male with necrotizing fasciitis after injection of the glenohumeral joint. After extensive debridement a massive defect from the left hip joint to the left upper arm, exposing ribs, scapula, axillary vessels and brachial plexus (45 × 40 cm) was present. Reconstruction was performed with a conjoined right myocutaneous tensor fasciae lata/vastus lateralis flap and a left myocutaneous vastus lateralis flap in combination with an arteriovenous loop originating from the axillary vessels using the greater saphenous vein. Revisional surgeries were necessary including ribs resection and flap re-advancements. Due to multiorganic failure invasive ventilation, renal replacement- and extensive transfusion therapy was required. After 241 days the patient was discharged for rehabilitation. At the 12 months follow-up wounds were sufficiently closed without the need for further intervention. This case illustrates that immediate diagnosis followed by an aggressive multidisciplinary treatment approach is crucial for the patient survival.     

Möglichkeiten der Weichteilrekonstruktion bei Pseudarthrosen

Die Unfallchirurgie - Pseudarthrosen können als Komplikation einer vorhergegangenen operativen oder konservativen Frakturbehandlung oder nach elektiven Knocheneingriffen entstehen. Ihre...     

Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca²⁺-activated K⁺ channels (K_Ca2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca²⁺-dependent. Further, the Ca²⁺ dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.Small-conductance Ca²⁺-activated K⁺ (SK or K_Ca2) channels are highly unique in that they are gated solely by changes in intracellular Ca²⁺ (Ca²⁺_i) concentration. Hence, the channels function to integrate changes in Ca²⁺ concentration with changes in membrane potentials. SK channels have been shown to be expressed in a wide variety of cells (1–3) and mediate afterhyperpolarizations following action potentials in neurons (1, 4, 5). We have previously documented the expression of several isoforms of SK channels in human and mouse atrial myocytes that mediate the repolarization phase of the atrial action potentials (6, 7). We further demonstrated that SK2 (K_Ca2.2) channel knockout mice are prone to the development of atrial arrhythmias and atrial fibrillation (AF) (8). Conversely, a recent study by Diness et al. suggests that inhibition of SK channels may prevent AF (9). Together, these studies underpin the importance of the precise control for the expression of these ion channels in atria and their potential to serve as a future therapeutic target for AF.Current antiarrhythmic agents target the permeation and gating properties of ion channel proteins; however, increasing evidence suggests that membrane localization of ion channels may also be pharmacologically altered (10). Furthermore, a number of disorders have been associated with mistrafficking of ion channel proteins (11, 12). We have previously demonstrated the critical role of α-actinin2, a cytoskeletal protein, in the surface membrane localization of cardiac SK2 channels (13, 14). Specifically, we demonstrated that cardiac SK2 channel interacts with α-actinin2 cytoskeletal protein via the EF hand motifs in α-actinin2 protein and the helical core region of the calmodulin (CaM) binding domain (CaMBD) in the C terminus of SK2 channel. Moreover, direct interactions between SK2 channel and α-actinin2 are required for the increase in cell surface localization of SK2 channel.Here, to further define the functional interactome of SK2 channel in the heart, we demonstrate the role of filamin A (FLNA), another cytoskeletal protein, in SK2 channel surface membrane localization. In contrast to α-actinin2 protein, FLNA interacts not with the C terminus, but with the N terminus of the cardiac SK2 channel. FLNA is a scaffolding cytoskeletal protein with two calponin homology domains that has been shown to be critical for the trafficking of a number of membrane proteins (15–19). Our data demonstrate that FLNA functions to enhance membrane localization of SK2 channels. Moreover, using live-cell imaging, we demonstrate the critical roles of Ca²⁺_i on the membrane localization of SK2 channel when the channels are coexpressed with α-actinin2, but not FLNA. A decrease in Ca²⁺_i results in a significant decrease in SK2 channel membrane localization. Our findings may have important clinical implications. A rise in Ca²⁺_i—for example, during rapid pacing or atrial tachyarrhythmias—is predicted to increase the membrane localization of SK2 channel and result in the abbreviation of the atrial action potentials and maintenance of the arrhythmias.     

SV40: a possible co-carcinogen of asbestos in the pathogenesis of mesothelioma?

BACKGROUND: The etiopathogenic role of asbestos in causing malignant mesothelioma of the pleura is clearly supported by an impressive amount of data. Despite the frequent association with previous exposure to asbestos, only a relatively small fraction of those exposed develop malignant mesothelioma. The long latency period between initial exposure and onset of the tumor suggests that human mesothelioma, like many other tumors, has a multi-stage evolution with the occurrence of many mutating events involving various tumorigenic agents, probably in part initiating and in part promoting development. Recently this has raised great interest in the scientific world, in an attempt to identify possible factors which together with asbestos may have a role in developing this rare malignant tumor. Ionizing radiations and genetic susceptibility have occasionally been identified as the culprits. A virus called SV40 has been gaining increasing scientific credibility since the mid 1990's as a potential co-carcinogen of asbestos. OBJECTIVES: The aim of this article was to examine the supposed interaction between asbestos and SV40 in the pathogenesis of mesothelioma and the way this simian virus has become a human virus. METHODS: All biomolecular and epidemiological data available from medical literature along with the results of the experiments performed during the last 7 years in our department laboratories were reviewed and compared. RESULTS: The first two pieces of experimental evidence of the presence of SV40-like DNA sequences in mesothelioma samples were obtained in 1994 in the United States, and one year later in our laboratories. After these two studies many research groups started carrying out similar experiments, obtaining comparable results in most cases. Moreover, beyond the mere detection of viral DNA sequences large amount of biomolecular data has recently been added in favour of its role in the pathogenesis of mesothelioma. Epidemiological studies published to date were unable to provide similar unanimous results. Data regarding the source of human infection are still debatable, even if the inadvertent administration of contaminated poliovaccines to millions of people in Europe and the United States between 1955 and 1963 remains one of the most reasonable hypotheses. CONCLUSIONS: On the basis of all the biomolecular data reviewed and partially on the basis of epidemiological studies, SV40 seems to be the best candidate as a cofactor with asbestos in the development of human mesothelioma.