Home About us Contact
|
Home About us Contact | ||
|
|
||
Significant Obstacle (significant + obstacle)
Selected AbstractsSplit-Liver Transplantation: A ReviewAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2003John F. Renz Split-liver transplantation (SLT), a procedure where one cadaver liver is divided to provide for two recipients, offers immediate expansion of the existing cadaver donor pool. To date, the principal beneficiaries of SLT have been adult/pediatric recipient pairs with excellent outcomes reported; however, the current scarcity of cadaver organs has renewed interest in expanding these techniques to include two adult recipients from one adult cadaver donor. Significant obstacles to the widespread application of SLT exist and must be resolved by the transplant community before greater utilization can be realized. This manuscript reviews the historic background, surgical techniques, current results, and obstacles impeding further application of SLT. [source] IBDfinder and SNPsetter: Tools for pedigree-independent identification of autozygous regions in individuals with recessive inherited disease,HUMAN MUTATION, Issue 6 2009Ian M. Carr Abstract Autozygosity mapping of recessive genes can be performed on a small number of affected individuals from consanguineous pedigrees. With the advent of microarray SNP analysis, acquiring genotype data has become extremely simple and quick, in comparison to gene mapping with microsatellite markers. However, the subsequent data analysis required to identify autozygous regions can still be a significant obstacle. For rapid gene identification, it may be desirable to integrate information from heterogeneous groups of affected individuals, both familial and isolated, under various assumptions of ancestry and locus heterogeneity, that are not amenable to formal linkage analysis. Unfortunately, there are few computer programs aimed specifically at facilitating this type of data sifting. Here, we demonstrate two new programs that facilitate the identification of autozygous regions within a heterogeneous SNP dataset derived from familial and sporadic affected individuals. Hum Mutat 30:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] Tissue Engineering Using Laminar Cellular AssembliesADVANCED MATERIALS, Issue 32-33 2009Joseph Yang Abstract As proposed in the late 1980s by Langer and Vacanti, the ultimate goal of tissue engineering is the development of structures that can be used to treat or replace damaged or diseased organs and tissues. For the regeneration of various organs such as the heart, liver, and kidney, the development of adequate vascular networks within the engineered tissues remains a significant obstacle in the formation of cell-dense structures that resemble the native parenchyma. While tissue engineering using biodegradable scaffolds has been successful in the re-creation of tissues where extracellular matrix is abundant, we have developed cell-sheet-based tissue engineering for the construction of tissues using laminar assemblies of cells harvested from temperature-responsive culture dishes. Using cell sheet engineering, we present new strategies for the development of organ-like tissue structures containing well-organized vascular networks. [source] Effects of PEGylation on the preservation of cationic lipid/DNA complexes during freeze-thawing and lyophilizationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2002Taylor K.C. Armstrong Abstract The incorporation of components with covalently attached polyethylene glycol (PEG) into nonviral vectors has been shown to prevent aggregation in serum and extend the circulating half-life of lipid/DNA complexes (lipoplexes) in vivo. The tendency of synthetic vectors to aggregate during processing and storage also represents a significant obstacle in the development of lipoplexes as marketable pharmaceutical products. The extreme instability of lipoplexes formulated as aqueous suspensions has generated interest in preserving nonviral vectors as frozen or lyophilized formulations. Previous work has demonstrated that stabilizing excipients are capable of protecting lipoplexes during freezing and lyophilization, but there is little known about the ability of PEGylation to protect vectors during these stresses. This study incorporates up to 10% by weight dioleoyl phosphatidylethanolamine conjugated to PEG-2000 and PEG-5000 into lipoplexes and assesses the maintenance of particle size and transfection after agitation, freeze-thawing, and lyophilization. Our results indicate that the incorporation of PEGylated components alone (up to 10% by weight) is insufficient to preserve particle size during these stresses. However, when sucrose was employed in combination with PEGylated components, a small protective effect of PEGylation was observed. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2549,2558, 2002 [source] Assessment and prevention of gastrointestinal toxicity of non-steroidal anti-inflammatory drugsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2006Majella E. Lane Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesic, anti-inflammatory and, in the case of aspirin, for anti-thrombotic actions. The serious gastrointestinal side-effects associated with these drugs are of concern and pose a significant obstacle to their use. This review discusses the pathogenic mechanisms by which the conventional acidic NSAIDs induce gastrointestinal toxicity, with particular emphasis on non-prostaglandin effects. Methods of assessment of NSAID-induced enteropathy are reviewed, with particular emphasis on the use of functional measurement of NSAID-induced changes in the gastrointestinal tract. The advances in our knowledge of the pathogenesis of these effects have resulted in the development of a range of novel NSAIDs. Where functional assessment of the effects of NSAIDs has been employed, it appears to be more useful as an indicator of early-stage changes rather than a predictor of the effects of long-term NSAID exposure. Successful pharmaceutical strategies now offer considerable promise for reducing the severity of NSAID damage to the gastrointestinal tract. The utility of intestinal permeability measurements for selection and assessment of these strategies is discussed. [source] Lessons for Aboriginal tobacco control in remote communities: an evaluation of the Northern Territory ,Tobacco Project'AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 1 2010David Thomas Abstract Objective: To evaluate a Northern Territory (NT) government-led pilot ,Tobacco Project' in six remote communities. Methods: Monthly surveys of staff, semi-structured interviews with staff and community members, observation of the delivery of tobacco control interventions, review of Project documents, and monitoring of tobacco consumption using sales (or wholesale orders) of tobacco. Results: There was a substantive amount of tobacco control activity delivered in three of the Project communities. In two of these locations, the majority of work was primarily driven and undertaken by resident staff. Overall, most of the Project's efforts related to community education and awareness-raising. There was variable impact of the Project on tobacco consumption across the six communities. More tobacco control activity was consistently associated with a greater reduction in tobacco consumption. An important predictor of local activity was the presence of strong community drivers. A significant obstacle to the Project was the lack of new resources. Conclusions: Despite the minimal impact of this Project on tobacco consumption overall, there was a consistent association between on-the-ground tobacco control activity and reductions in tobacco consumption. Implications: New initiatives will not only need to provide new funding, but identify and then support local staff, who are central to improving local tobacco control activity and so reducing smoking and smoking-related illnesses and deaths. [source] "Click Peptides",Chemical Biology-Oriented Synthesis of Alzheimer's Disease-Related Amyloid , Peptide (A,) Analogues Based on the "O- Acyl Isopeptide Method"CHEMBIOCHEM, Issue 10 2006Youhei Sohma Abstract A clear understanding of the pathological mechanism of amyloid , peptide (A,) 1,42, a currently unexplained process, would be of great significance for the discovery of novel drug targets for Alzheimer's disease (AD) therapy. To date, though, the elucidation of these A,1,42 dynamic events has been a difficult issue because of uncontrolled polymerization, which also poses a significant obstacle in establishing experimental systems with which to clarify the pathological function of A,1,42. We have recently developed chemical biology-oriented pH- or phototriggered "click peptide" isoform precursors of A,1,42, based on the "O -acyl isopeptide method", in which a native amide bond at a hydroxyamino acid residue, such as Ser, is isomerized to an ester bond, the target peptide subsequently being generated by an O,N intramolecular acyl migration reaction. These click peptide precursors did not exhibit any self-assembling character under physiological conditions, thanks to the presence of the one single ester bond, and were able to undergo migration to give the target A,1,42 in a quick and easy, one-way (so-called "click")conversion reaction. The use of click peptides could be a useful strategy to investigate the biological functions of A,1,42 in AD through inducible activation of A,1,42 self-assembly. [source] Special considerations for haematology patients in relation to end-of-life care: Australian findingsEUROPEAN JOURNAL OF CANCER CARE, Issue 2 2007P. MCGRATH bsocwk, senior research fellow Recent haematology clinical guidelines recommend that palliative care specialists should have central roles in haemato-oncology teams. However, the available research evidence indicates there are presently significant obstacles to the integration of palliative care in haematology. The following discussion presents findings from an Australian study designed to address the problems associated with lack of referral of haematology patients to the palliative system through the development of a best-practice model for end-of-life care for these diagnostic groups. The preliminary step in the development of such a model is to document the factors that denote the special characteristics of the end-of-life stage of haematological conditions and their treatments. This article presents the list of special considerations from a nursing perspective, including issues associated with the high-tech nature of treatments, the speed of change to a terminal event, the need for blood products and possibility of catastrophic bleeds, the therapeutic optimism based on a myriad of treatment options and the clinical indices of the terminal trajectory. The nursing insights provide an important foundation for building a practical, patient-centred model for terminal care in haematology. [source] Thyroid tumor marker genomics and proteomics: Diagnostic and clinical implicationsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Angelo Carpi Two systems biology concepts, genomics and proteomics, are highlighted in this review. These techniques are implemented to optimize the use of thyroid tumor markers (TTM). Tissue microarray studies can produce genetic maps and proteomics, patterns of protein expression of TTM derived from preoperative biopsies and specimens. For instance, papillary and medullary thyroid cancers harbor RAS, RET, and BRAF genetic mutations. Follicular thyroid cancers harbor translocations and fusions of certain genes (PAX 8 and PPAR-gamma). Proteomic analysis from various tissue sources can provide useful information regarding the overall state of a thyroid cancer cell. Understanding the molecular events related to these genetic and protein alterations can potentially clarify thyroid cancer pathogenesis and guide appropriate molecular targeted therapies. However, despite the realization that these emerging technologies hold great promise, there are still significant obstacles to the routine use of TTM. These include equivocal thyroid nodule tissue morphologic interpretations, inadequate standardization of methods, and monetary costs. Interpretative shortcomings are frequently due to the relative scarcity of cellular material from fine-needle aspiration biopsy (FNAB) specimens. This can be rectified with large needle aspiration biopsy (LNAB) techniques and is exemplified by the favorable performance of galectin-3 determinations on LNAB specimens. J. Cell. Physiol. 224: 612,619, 2010. © 2010 Wiley-Liss, Inc. [source] Obstacles to desegregating public housing: Lessons learned from implementing eight consent decreesJOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 2 2003Susan J. Popkin Between 1992 and 1996 the U.S. Department of Housing and Urban Development (HUD) settled a number of legal cases involving housing authorities and agreed to take remedial action as part of court-enforced consent decrees entered into with plaintiffs. These housing authorities faced significant obstacles that impaired their ability to comply swiftly and fully with all of the elements in the desegregation consent decrees. The obstacles fell into two broad categories: contextual obstacles (racial composition of waiting lists and resident populations, lack of affordable rental housing, and inadequate public transportation), and capacity and coordination obstacles (conflict among implementing agencies and ineffective monitoring by HUD). Findings presented here highlight the sizable potential delay between the time a legal remedy is imposed and when plaintiffs in public housing segregation disputes realize any benefits. They also reinforce the argument that implementation problems will be legion when policies impose a significant scope of required changes on a large number of actors who must collaborate, yet are not uniformly capable or sympathetic to the goals being promoted. © 2003 by the Association for Public Policy Analysis and Management. [source] The molecular genetics of holoprosencephaly,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Erich Roessler§ Abstract Holoprosencephaly (HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic, and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. Published 2010 Wiley-Liss, Inc. [source] Dental Services for Migrant and Seasonal Farmworkers in US Community/Migrant Health CentersTHE JOURNAL OF RURAL HEALTH, Issue 3 2006Sherri M. Lukes RDH ABSTRACT:,Context: Migrant and seasonal farmworkers are recognized as a medically underserved population, yet little information on need, access, and services is available,particularly with regard to oral health care. Purpose: This study describes the facilities, services, staffing, and patient characteristics of US dental clinics serving migrant and seasonal farmworkers, and identifies trends and issues that may impede or improve dental care access and service. Methods: National databases were used to identify community and migrant health centers providing oral health care to migrant and seasonal farmworkers. Mailed surveys collected information on clinic history, operational details, services provided, patient demographics, employment and resource needs, and perceived barriers to care. Findings: Among the 81 respondents (response rate 41%), hours of operation varied from 1 evening a week to more than 40 hours a week; 52% had no evening hours. Almost all the clinics offered preventive, diagnostic, and basic restorative dental services, and roughly two thirds also offered complex restorative services. Patients most frequently sought emergency dental care (44%) followed by basic restorative services (32%) and preventive services (26%). The dentist position was the most difficult to fill, and new funding sources were cited as the most important resource need. Respondents perceived cost of services, lack of transportation, and limited clinic hours as primary barriers to care. Conclusions: While some barriers to care have been almost universally addressed (eg, language), there is evidence that some impediments remain and may present significant obstacles to a broad improvement in oral health care for migrant and seasonal farmworkers. [source] Single-port laparoscopic surgery, the new evolution of endoscopic surgeryASIAN JOURNAL OF ENDOSCOPIC SURGERY, Issue 3 2009H. Rivas Abstract Introduction: Laparoscopic surgery through a single port is gaining great interest throughout the world. Our group has pioneered and been a leader on these novel techniques. Here we describe our experience based on a model of single-port laparoscopic cholecystectomy. Materials and Methods: From January 2008 until August 2009, over 200 patients have undergone single-port laparoscopic surgery at our institution. Here, we analyze a cohort of the initial 100 cholecystectomies in order to evaluate a proposed technique, common challenges, the learning curve and potential solutions. Results: Single-port laparoscopic surgery was feasible in all patients from this cohort. Patients were strictly selected. Operating times similar to those of conventional laparoscopy were only achieved after completing 50 cases. Common technical challenges included clashing instruments, deflection of laparoscope due to conflict with light source, and organ retraction. Acceptance by surgeons and lack of patience and time may become significant obstacles that prevent the procedure's widespread adoption. The excellent aesthetic results are superior to laparoscopy. Other benefits of laparoscopy are preserved and may prove to be superior on clinical trials. Discussion: Single-port laparoscopic surgery is becoming popular worldwide. Safe and successful adoption requires learning the basic concepts of this method, identifying challenges, and implementing solutions. Once these essentials are mastered, the learning curve may be shortened, especially for experienced laparoscopic surgeons, and this technique may then be used to replicate many abdominal operations. Transparency with patients and team building are essential requirements for a successful adoption. Clinical trials are ideal before universal adoption. [source] | ||||||||||||||||