Surgical technique and preliminary results of endoscopic subfascial division of perforating veins

Purpose: Direct surgical ligation of incompetent perforating veins has been reported to effectively treat severe chronic venous insufficiency. It is associated, however, with significant wound complications. We evaluate our early experience with endoscopic subfascial division of the perforating veins.Methods: From August 5, 1993, to December 31, 1994, 11 legs in nine patients (five male and four female) were treated with endoscopic subfascial division of perforating veins. Nine of the 11 legs had active or recently healed venous ulcers. Mean duration of the ulcerations was 5.6 years. Standard laparoscopic equipment with two 10-mm ports was used to perform clipping and division of medial perforating veins through two small incisions made just below the knee, avoiding the area of ulcer and lipodermatosclerosis. Carbon dioxide was insufflated at a pressure of 30 mm Hg into the subfascial space to facilitate dissection, and a pneumatic thigh tourniquet was used to obtain a bloodless operating field. Concomitant removal of superficial veins was performed in eight limbs. Mean follow-up was 9.7 months (range, 2 to 13 months).Results: A mean of 4.4 perforating veins (range, 2 to 7) were divided; tourniquet time averaged 58 minutes (range, 30 to 72). Wound infection of a groin incision and superficial thrombophlebitis were early complications; each occurred in one patient. In seven legs the ulcer healed or did not recur and symptoms resolved. In three legs the ulceration improved, and in one it was unchanged.Conclusions: Endoscopic subfascial division of perforating veins seems to be a safe technique, with favorable early results obtained in a small number of patients. This preliminary experience supports further clinical trials to evaluate this technique

Viral population estimation using pyrosequencing

The diversity of virus populations within single infected hosts presents a major difficulty for the natural immune response as well as for vaccine design and antiviral drug therapy. Recently developed pyrophosphate based sequencing technologies (pyrosequencing) can be used for quantifying this diversity by ultra-deep sequencing of virus samples. We present computational methods for the analysis of such sequence data and apply these techniques to pyrosequencing data obtained from HIV populations within patients harboring drug resistant virus strains. Our main result is the estimation of the population structure of the sample from the pyrosequencing reads. This inference is based on a statistical approach to error correction, followed by a combinatorial algorithm for constructing a minimal set of haplotypes that explain the data. Using this set of explaining haplotypes, we apply a statistical model to infer the frequencies of the haplotypes in the population via an EM algorithm. We demonstrate that pyrosequencing reads allow for effective population reconstruction by extensive simulations and by comparison to 165 sequences obtained directly from clonal sequencing of four independent, diverse HIV populations. Thus, pyrosequencing can be used for cost-effective estimation of the structure of virus populations, promising new insights into viral evolutionary dynamics and disease control strategies.Comment: 23 pages, 13 figure

Does hostile neck anatomy preclude successful endovascular aortic aneurysm repair?

AbstractObjectivesPoor outcomes have been reported with endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy. Unsupported endografts with active fixation may offer certain advantages in this situation. We compared EVAR results using the Ancure (Guidant) endograft in patients with and without hostile neck anatomy.MethodsRecords of EVAR patients from October 1999 to July 2002 at a tertiary care hospital were retrospectively reviewed from a division database. Patients with elective open abdominal aortic aneurysm (AAA) repair during the same period were reviewed to determine those unsuitable for EVAR. Hostile neck anatomy, assessed by computer tomography (CT) scans and angiograms, was defined as one or more of the following: (1) neck length ≤10 mm, (2) focal bulge in the neck >3 mm, (3) >2-mm reverse taper within 1 cm below the renal arteries, (4) neck thrombus ≥50% of circumference, and (5) angulation ≥60 degrees within 3 cm below renals.ResultsThree hundred and twenty-two patients underwent EVAR with an average follow-up of 18 months. Patients in Phase II trials (n = 41), repaired with other graft types (n = 48), or without complete anatomic records (n = 27) were excluded. Demographics and co-morbidities were similar in the 115 good-neck (GN) and 91 bad-neck (BN) patients except for age (mean, 72.9 years GN vs 75.7 BN; P = 0.13), gender (11% female GN vs 22% BN; P =.04); neck length (mean, 21.8 mm GN vs 14.4 mm BN: P < .001), and angulation (mean, 22 degrees GN vs 40 degrees BN; (P < .001). Perioperative mortality (0 GN vs 1.1% BN), late mortality (5.2% GN vs 4.4% BN), all endoleaks (19.1% GN vs 17.6% BN), proximal endoleaks (0.8% GN vs 2.1% BN), and graft migration (0 for both groups) did not reach statistical significance. Neck anatomy precluded EVAR in 106 of 165 (64%) patients with open AAA.ConclusionsUnsupported endografts with active fixation can yield excellent results in treating many medically compromised patients with hostile neck anatomy. Nonetheless, an unsuitable neck remains the most frequent cause for open abdominal AAA

Phospholipase C-eta enzymes as putative protein kinase C and Ca2+ signalling components in neuronal and neuroendocrine tissues

Phosphoinositol-specific phospholipase C enzymes (PLCs) are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C activation. A sixth class of phosphoinositol-specific PLC with a novel domain structure, PLC-eta (PLCeta) has recently been discovered in mammals. Recent research, reviewed here, shows that this class consists of two enzymes, PLCeta1 and PLCeta2. Both enzymes hydrolyze phosphatidylinositol 4,5-bisphosphate and are more sensitive to Ca2+ than other PLC isozymes and are likely to mediate G-protein-coupled receptor (GPCR) signalling pathways. Both enzymes are expressed in neuron-enriched regions, being abundant in the brain. We demonstrate that they are also expressed in neuroendocrine cell lines. PLCeta enzymes therefore represent novel proteins influencing intracellular Ca2+ dynamics and protein kinase C activation in the brain and neuroendocrine systems as putative mediation of GPCR regulation

Organosilicate Spin-on Glasses II. Effect of Physical Modification on Mechanical Properties

Porous copolymer films were synthesized from a methylsilsequioxane:1,2-bis(trimethoxysilyl)ethane (MSSQ:BTMSE) matrix and either an aromatic-core or aliphatic-core porogen at 10, 20, or 30 wt % porogen loading. Films were characterized using scanning electron microscopy (SEM), IR spectroscopy, and ellipsometry. Depth-sensing indentation experiments were performed to measure apparent film modulus, E, and hardness, H. Indentation load-displacement traces and SEM images were used to determine the threshold load for cracking, Pc. The aliphatic-core porogen produced a greater porosity film than the aromatic-core porogen for 10 wt % loading and smaller porosity films for 20 and 30 wt % loadings. IR spectra, normalized for film thickness and density, indicated decreased O-Si-O networking in porous MSSQ:BTMSE films. The combination of increased porosity and decreased O-Si-O networking led to a decreased apparent E and H relative to the unmodified MSSQ:BTMSE film. However, low-porosity (approximately 7%), aliphatic-porogen MSSQ:BTMSE films are optimized relative to unmodified MSSQ with smaller dielectric constant and greater E and H.This work is supported by the Korean Collaborative Project for Excellence in Basic System IC Technology (System IC 2010: 98- B4-C0-00-01-00-02). Financial support from the Ministry of Science and Technology (MOST) and the Korean Ministry of Education through the National Research Laboratory Fund and the Brain Korea 21 Program, respectively, is also greatly acknowledged

Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

<p>Abstract</p> <p>Background</p> <p>Peroxiredoxin 6 (<it>PRDX6</it>) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the <it>PRDX6 </it>gene to uncover common variants, and tested association with ALI following major trauma.</p> <p>Methods</p> <p>To examine the extent of variation in the <it>PRDX6 </it>gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. <it>In silico </it>modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma.</p> <p>Results</p> <p>Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using <it>in silico </it>modeling. Chi²analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses.</p> <p>Conclusions</p> <p>This study revealed novel SNPs within the <it>PRDX6 </it>gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of <it>PRDX6 </it>genetic variation in other diseases, where oxidative stress is suspected.</p

Taking the First Steps towards a Standard for Reporting on Phylogenies: Minimum Information about a Phylogenetic Analysis (MIAPA)

In the eight years since phylogenomics was introduced as the intersection of genomics and phylogenetics, the field has provided fundamental insights into gene function, genome history and organismal relationships. The utility of phylogenomics is growing with the increase in the number and diversity of taxa for which whole genome and large transcriptome sequence sets are being generated. We assert that the synergy between genomic and phylogenetic perspectives in comparative biology would be enhanced by the development and refinement of minimal reporting standards for phylogenetic analyses. Encouraged by the development of the Minimum Information About a Microarray Experiment (MIAME) standard, we propose a similar roadmap for the development of a Minimal Information About a Phylogenetic Analysis (MIAPA) standard. Key in the successful development and implementation of such a standard will be broad participation by developers of phylogenetic analysis software, phylogenetic database developers, practitioners of phylogenomics, and journal editors. This paper is part of the special issue of OMICS on data standards.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63208/1/omi.2006.10.231.pd

Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs

Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold

Expression of methylation-related genes is associated with overall survival in patients with non-small cell lung cancer

The abnormality of DNA methylation is involved in tumour progression, and thus has a modulating effect on clinical outcome of cancer patients. In this study, we measured the mRNA expression levels of three methylation-regulating genes (DNMT1, DNMT3b, and MBD2) in 148 tumour samples from patients with non-small cell lung cancer (NSCLC) using quantitative real-time polymerase chain reaction and then determined their prognostic values. Our data showed that the high level of DNMT1 expression was significantly associated with an increased risk of death in all NSCLC patients (hazard ratio (HR), 1.74; 95% confidence interval (95% CI), 1.04–2.90). However, the high level of DNMT3b expression was significantly associated with poor prognosis only in young patients (<65 years). The high level of MBD2 expression had a significantly reduced risk for death only in male patients and in squamous cell lung carcinoma (SQLC) patients. All three combination groups with DNMT1 and DNMT3b, DNMT1 and MBD2 or DNMT3b and MBD2 revealed significant combined effects in male patients and SQLC patients. Our results suggest that DNMT1, DNMT3b, and MBD2 may play important roles in modulating NSCLC patient survival and thus be useful for identifying NSCLC patients who would benefit most from aggressive therapy

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with kno