Clipless management of the renal vein during hand-assist laparoscopic donor nephrectomy

BACKGROUND: Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can occur, and is often due to interference from previously placed clips. We report our experience with a clipless technique in which no vascular clips are placed on tributaries of the renal vein at or near the renal hilum in order to avoid laparoscopic stapling device misfires. METHODS: From December 20, 2002 to April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor nephrectomy (LDN) at our institution. Clipless management of the renal vein tributaries was used in all patients, and these vessels were divided using either a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO). The medical and operative records of the donors and recipients were reviewed to evaluate patient outcomes. RESULTS: The mean follow-up time was 14 months. Of the 50 LDN procedures, there were no laparoscopic stapling device malfunctions and no vascular complications. All renal allografts were functioning at the time of follow-up. CONCLUSION: Laparoscopic stapling device failure due to deployment across previously placed surgical clips during laparoscopic live donor nephrectomy can be prevented by not placing clips on the tributaries of the renal vein. In our series, there were no vascular complications and no device misfires. We believe this clipless technique improves the safety of laparoscopic donor nephrectomy

An off-board quantum point contact as a sensitive detector of cantilever motion

Recent advances in the fabrication of microelectromechanical systems (MEMS) and their evolution into nanoelectromechanical systems (NEMS) have allowed researchers to measure extremely small forces, masses, and displacements. In particular, researchers have developed position transducers with resolution approaching the uncertainty limit set by quantum mechanics. The achievement of such resolution has implications not only for the detection of quantum behavior in mechanical systems, but also for a variety of other precision experiments including the bounding of deviations from Newtonian gravity at short distances and the measurement of single spins. Here we demonstrate the use of a quantum point contact (QPC) as a sensitive displacement detector capable of sensing the low-temperature thermal motion of a nearby micromechanical cantilever. Advantages of this approach include versatility due to its off-board design, compatibility with nanoscale oscillators, and, with further development, the potential to achieve quantum limited displacement detection.Comment: 5 pages, 5 figure

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.

Assessing Susceptibility from Early-Life Exposure to Carcinogens

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action

Acute graft versus host disease

Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD

Executive Functioning in Daily Life in Parkinson's Disease: Initiative, Planning and Multi-Task Performance

Impairments in executive functioning are frequently observed in Parkinson's disease (PD). However, executive functioning needed in daily life is difficult to measure. Considering this difficulty the Cognitive Effort Test (CET) was recently developed. In this multi-task test the goals are specified but participants are free in their approach. This study applies the CET in PD patients and investigates whether initiative, planning and multi-tasking are associated with aspects of executive functions and psychomotor speed. Thirty-six PD patients with a mild to moderate disease severity and thirty-four healthy participants were included in this study. PD patients planned and demonstrated more sequential task execution, which was associated with a decreased psychomotor speed. Furthermore, patients with a moderate PD planned to execute fewer tasks at the same time than patients with a mild PD. No differences were found between these groups for multi-tasking. In conclusion, PD patients planned and executed the tasks of the CET sequentially rather than in parallel presumably reflecting a compensation strategy for a decreased psychomotor speed. Furthermore, patients with moderate PD appeared to take their impairments into consideration when planning how to engage the tasks of the test. This compensation could not be detected in patients with mild PD

Differential Selection on Carotenoid Biosynthesis Genes as a Function of Gene Position in the Metabolic Pathway: A Study on the Carrot and Dicots

Background: Selection of genes involved in metabolic pathways could target them differently depending on the position of genes in the pathway and on their role in controlling metabolic fluxes. This hypothesis was tested in the carotenoid biosynthesis pathway using population genetics and phylogenetics. Methodology/Principal Findings: Evolutionary rates of seven genes distributed along the carotenoid biosynthesis pathway

Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo

Dorsal/ventral patterning of the sea urchin embryo depends upon the establishment of a Nodal-expressing ventral organizer. Recently, we showed that spatial positioning of this organizer relies on the dorsal-specific transcription of the Hbox12 repressor. Building on these findings, we determined the influence of the epigenetic milieu on the expression of hbox12 and nodal genes. We find that Trichostatin-A, a potent and selective histone-deacetylases inhibitor, induces histone hyperacetylation in hbox12 chromatin, evoking broad ectopic expression of the gene. Transcription of nodal concomitantly drops, prejudicing dorsal/ventral polarity of the resulting larvae. Remarkably, impairing hbox12 function, either in a spatially-restricted sector or in the whole embryo, specifically rescues nodal transcription in Trichostatin-A-treated larvae. Beyond strengthen the notion that nodal expression is not allowed in the presence of functional Hbox12 in the same cells, these results highlight a critical role of histone deacetylases in regulating the spatial expression of hbox12

Targeting of Pseudorabies Virus Structural Proteins to Axons Requires Association of the Viral Us9 Protein with Lipid Rafts

The pseudorabies virus (PRV) Us9 protein plays a central role in targeting viral capsids and glycoproteins to axons of dissociated sympathetic neurons. As a result, Us9 null mutants are defective in anterograde transmission of infection in vivo. However, it is unclear how Us9 promotes axonal sorting of so many viral proteins. It is known that the glycoproteins gB, gC, gD and gE are associated with lipid raft microdomains on the surface of infected swine kidney cells and monocytes, and are directed into the axon in a Us9-dependent manner. In this report, we determined that Us9 is associated with lipid rafts, and that this association is critical to Us9-mediated sorting of viral structural proteins. We used infected non-polarized and polarized PC12 cells, a rat pheochromocytoma cell line that acquires many of the characteristics of sympathetic neurons in the presence of nerve growth factor (NGF). In these cells, Us9 is highly enriched in detergent-resistant membranes (DRMs). Moreover, reducing the affinity of Us9 for lipid rafts inhibited anterograde transmission of infection from sympathetic neurons to epithelial cells in vitro. We conclude that association of Us9 with lipid rafts is key for efficient targeting of structural proteins to axons and, as a consequence, for directional spread of PRV from pre-synaptic to post-synaptic neurons and cells of the mammalian nervous system