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At least 577 records · Page 32Linked to original sources

The etiology of medical gridlock: causes of emergency department overcrowding in New York City.

Overcrowding of emergency departments in New York City is the most apparent symptom of a crumbling health care system. There is a growing need for the care of a largely impoverished population suffering from an increasing prevalence of AIDS, substance abuse, and psychiatric disease. Institutions crippled by critical shortages of inpatient beds and nurses lack the resources to meet this rising demand. Although the epidemic of medical gridlock began in New York City, it is spreading rapidly to involve other areas of the country. Short-term efforts to resolve this crisis have thus far been unsuccessful. Long-range solutions are likely to be costly and may require a reconfiguration of societal health care priorities.

Acquired Immunodeficiency Syndrome↗

Missed slipped capital femoral epiphysis: illustrative cases and a review.

Slipped capital femoral epiphysis (SCFE) is a fairly common condition affecting older children and adolescents, and has the potential for long-term, crippling sequelae. Early recognition is the single most important controllable factor, but the diagnosis is often missed or delayed, resulting in progression of the slip. A SCFE should be suspected and promptly evaluated in any older child or adolescent presenting with a limp or complaints of hip, groin, thigh, or knee pain, especially if the patient is overweight. The diagnosis is usually made by anteroposterior and frog-leg lateral radiographs of the hips. Common errors at initial presentation include: not obtaining hip radiographs (due to either no hip pain or the lack of an impressive history and physical findings); misreading hip radiographs (the findings can be subtle); and lack of timely referral. Early involvement of and treatment by an orthopedic surgeon can greatly reduce the potential complications. We present three cases of SCFE that highlight common errors made at initial presentation, and a discussion that includes the differential diagnosis of an older child or adolescent with a painful limp.

Adolescent↗

Indirect mechanisms of HIV pathogenesis: how does HIV kill T cells?

Although twelve years have passed since the identification of HIV as the cause of AIDS, we do not yet know how HIV kills its target, the CD4+ T cell, nor how this killing cripples the immune system. Prominent theories include direct killing of infected CD4+ T cells by the action or accumulation of cytopathic viral DNA, transcripts or proteins, or by virus-specific cytotoxic T lymphocytes, and indirect killing of uninfected CD4+ T cells (and other immune cells) by autoimmune mechanisms, cytokines, superantigens, or apoptosis. In the past year, studies have provided tantalizing clues as to why infected cells may not die and how these infected cells kill innocent bystander cells.

Acquired Immunodeficiency Syndrome↗

Do clustered beta-propeller domains within the N-terminus of LRP1 play a functional role?

The six beta-propellers located within the N-terminus of low density lipoprotein receptor-related protein 1 (LRP1) are arranged in two clusters that contain two and four beta-propellers, respectively. Working with LRP1 deletion mutants, we found that randomly removing large segments of amino acid sequences did not affect the intracellular trafficking of LRP1 as long as the clustered beta-propeller domains were retained. However, deletion mutants with crippled beta-propeller clusters invariably exhibited retarded exit from the endoplasmic reticulum (ER). To determine potential functions of the clustered beta-propellers, we generated a series of deletion mutants in which the beta-propellers were systematically removed from the C-terminal end of the second cluster. The resulting minireceptors, designated LRPbeta1-6, beta1-5, beta1-4, beta1-3, and beta1-2 containing decreasing numbers of the beta-propellers, were stably expressed in LRP1-null CHO cells. Binding/degradation assays with receptor-associated protein or alpha2-macroglobulin showed that removing one or more beta-propellers had little effect on binding or degradation of these ligands. However, minireceptors containing odd number of beta-propellers (i.e., LRPbeta1-3 and beta1-5) showed prolonged retention within the ER and remained endoglycosidase H-sensitive, whereas minireceptors containing even number of beta-propellers (i.e., LRPbeta1-2, beta1-4 and beta1-6) exited ER at variable rates. Cell surface biotinylation experiments showed that LRPbeta1-3 was absent from the cell surface. Prolonged retention of LRPbeta1-3 within the ER was accompanied by increased association with molecular chaperone Grp78/Bip. These results suggest that the clustered beta-propellers may play a role in folding and intracellular trafficking of LRP1.

Animals↗

The zinc finger transcription factor Growth factor independence 1 (Gfi1).

Growth Factor Independence 1 (Gfi1) is a transcriptional repressor with a molecular weight between 47 and 55 kDa The protein has six C-terminal C2H2-type zinc-finger domains and a characteristic stretch of 20 amino acids, called the SNAG-domain, at its N-terminus. Expression of Gfi1 ranges from the hematopoietic and lymphoid system, to sensory epithelia, lung and parts of the CNS. Gene knock-out studies revealed that Gfi1 is essential for the development of granulocytes and plays a role in T-cell differentiation and macrophage-dependent cytokine production, indicating that this protein shares responsibility for different lines of defense against pathogens. Also, Gfi1 is required for the proper development of inner ear hair cells illustrated by ataxia and deafness in knock-out mice. While hereditary hearing loss has so far not been associated with Gfi1 malfunction, crippling mutations in the Gfi1 gene have been reported in patients suffering from neutropenia suggesting an important role of Gfi1 in this human disease.

Amino Acid Sequence↗

Trapezius musculocutaneous flap in severe shoulder and neck burn.

Scarring of the neck produces problems with function and appearance. The highly mobile anterior neck with its thin skin cover is particularly prone to flexion contractures that can range from minimally restrictive to crippling mentosternal synechiae. The trapezius muscle is the basis for muscle and musculocutaneous flaps that are of great usefulness in reconstructing defects of the head and neck and the upper back specially when there are no other regional flaps available. Use of trapezius musculocutaneous flap in the treatment of cicatricial contracture deformity of neck results in satisfactory function and external appearance and is a good method for the repair of soft tissue defects of the neck with the advantage of invariable blood supply. There is no deformation in the donor region which is hidden posteriorly. Its blood supply is rich enough to avoid any local necrosis after transplantation. Up to the present time this flap has been used to cover defects following excision of tumors in the head and upper parts of neck. Use of the trapezius musculocutaneous flap in seven patients who suffered from severe scarring in anterior neck and shoulder due to burn during an 8-year period (1995-2003) is described with good results achieved.

Adult↗

A Bir1-Sli15 complex connects centromeres to microtubules and is required to sense kinetochore tension.

Proper connections between centromeres and spindle microtubules are of critical importance in ensuring accurate segregation of the genome during cell division. Using an in vitro approach based on the sequence-specific budding yeast centromere, we identified a complex of the chromosomal passenger proteins Bir1 and Sli15 (Survivin and INCENP) that links centromeres to microtubules. This linkage does not require Ipl1/Aurora B kinase, whose targeting and activation are controlled by Bir1 and Sli15. Ipl1 is the tension-dependent regulator of centromere-microtubule interactions that ensures chromosome biorientation on the spindle. Elimination of the linkage between centromeres and microtubules mediated by Bir1-Sli15 phenocopies mutations that selectively cripple Ipl1 kinase activation. These findings lead us to propose that the Bir1-Sli15-mediated linkage, which bridges centromeres and microtubules and includes the Aurora kinase-activating domain of INCENP family proteins, is the tension sensor that relays the mechanical state of centromere-microtubule attachments into local control of Ipl1 kinase activity.

Aurora Kinases↗

Magnetic source imaging supports clinical decision making in glioma patients.

OBJECTIVE: This study addresses the potential utility of preoperative functional imaging with magnetoencephalography (MEG) for the selection of glioma patients who are likely to benefit from resective surgical treatment regarding postoperative morbidity. METHODS: One hundred and nineteen patients with gliomas adjacent to sensorimotor, visual and speech related brain areas were investigated preoperatively with a MAGNES II biomagnetometer. In each patient the pre-surgical evaluation was focussed on the visual, sensorimotor cortex and/or of the speech related brain areas. A grading system was then used according to the distance of the MEG activation sources to the nearest tumour border to determine the further treatment. The therapeutic options consisted in conservative treatment, stereotactic biopsy and/or a radiation and chemotherapy, substantial cytoreduction and the gross total removal of the lesion. RESULTS: From 119 investigated patients, 55 patients (46.2%) were not considered for surgery due to tumour invasion to functional cortex. Sixty four patients (53.8%) were chosen for resective surgery. In the surgical group only four patients (6.2%) suffered from neurological deterioration. CONCLUSIONS: Magnetic source imaging (MSI) proved to be a valuable help in the clinical decision making process of lesions adjacent to functional important brain areas. The relative high number of patients in whom MSI warns of the postoperative crippling sequelae may lead to a better selection of patients who benefit from resective surgery. This method may help to find the patients for whom conservative treatment seems to be more favourable concerning quality of life in the surviving time.

Adolescent↗

Utilizing data grid architecture for the backup and recovery of clinical image data.

Grid Computing represents the latest and most exciting technology to evolve from the familiar realm of parallel, peer-to-peer and client-server models. However, there has been limited investigation into the impact of this emerging technology in medical imaging and informatics. In particular, PACS technology, an established clinical image repository system, while having matured significantly during the past ten years, still remains weak in the area of clinical image data backup. Current solutions are expensive or time consuming and the technology is far from foolproof. Many large-scale PACS archive systems still encounter downtime for hours or days, which has the critical effect of crippling daily clinical operations. In this paper, a review of current backup solutions will be presented along with a brief introduction to grid technology. Finally, research and development utilizing the grid architecture for the recovery of clinical image data, in particular, PACS image data, will be presented. The focus of this paper is centered on applying a grid computing architecture to a DICOM environment since DICOM has become the standard for clinical image data and PACS utilizes this standard. A federation of PACS can be created allowing a failed PACS archive to recover its image data from others in the federation in a seamless fashion. The design reflects the five-layer architecture of grid computing: Fabric, Resource, Connectivity, Collective, and Application Layers. The testbed Data Grid is composed of one research laboratory and two clinical sites. The Globus 3.0 Toolkit (Co-developed by the Argonne National Laboratory and Information Sciences Institute, USC) for developing the core and user level middleware is utilized to achieve grid connectivity. The successful implementation and evaluation of utilizing data grid architecture for clinical PACS data backup and recovery will provide an understanding of the methodology for using Data Grid in clinical image data backup for PACS, as well as establishment of benchmarks for performance from future grid technology improvements. In addition, the testbed can serve as a road map for expanded research into large enterprise and federation level data grids to guarantee CA (Continuous Availability, 99.999% up time) in a variety of medical data archiving, retrieval, and distribution scenarios.

Diagnostic Imaging↗

Fractures of the forefoot.

Fractures of the forefoot are common injuries of various causes. Although not crippling, forefoot fractures can be debilitating if they go undiagnosed or are mistreated. Whenever patients complain of foot pain with ambulation or difficulty ambulating, radiographs should be taken as part of a standard routine to assess for bony pathology. This article discusses the classification and treatment of metatarsal fractures, digital and sesamoid fractures, and open fractures about the forefoot.

Compartment Syndromes↗

Mouse Ubc9 knockout: many path(way)s to ruin.

In this issue of Developmental Cell, Nacerddine et al. (2005) describe a targeted germ line mutation of the mouse SUMO-specific E2 Ubc9, which abrogates the SUMO conjugation pathway, broadly crippling nuclear function in proliferating cells of the early embryo. This study reveals the wide-ranging roles for this protein modifier in nuclear organization, chromosome segregation, and Ran-driven nucleo-cytoplasmic transport.

Animals↗

Design of beta-carboline derivatives as DNA-targeting antitumor agents.

This research studied the structure-activity relationship of beta-carboline derivatives as antitumor agents, in which 41 synthesized compounds and their cytotoxicity to tumor and normal cell lines were assayed. It was proved that substituent in position-9 of the beta-carboline ring could reinforce the DNA intercalating ability and consequently cytotoxicity to tumor cell lines, and the amidation of amino group at the end of the DNA targeting side chain in position-3 could cripple the DNA intercalating activity of these compounds, which resultingly initiated the cytotoxic selectivity to tumor cell lines rather than to normal ones. Furthermore, the S and G2-M arrest induced by these compounds confirmed that they could target DNA and lead to DNA destructions in Hela cells. In short, this study may provide a framework to design a novel antitumor drug that could surpass Adriamycin.

Antineoplastic Agents↗

Genetic control of an epigenetic cell degeneration syndrome in Podospora anserina.

Filamentous fungi frequently present degenerative processes, whose molecular basis is very often unknown. Here, we present three mutant screens that result in the identification of 29 genes that directly or indirectly control Crippled Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete Podospora anserina. Two of these genes were previously shown to encode a MAP kinase kinase kinase and an NADPH oxidase involved in a signal transduction cascade that participates in stationary phase differentiations, fruiting body development and defence against fungal competitors. The numerous genes identified can be incorporated in a model in which CG results from the sustained activation of the MAP kinase cascade. Our data also emphasize the complex regulatory network underlying three interconnected processes in P. anserina: sexual reproduction, defence against competitors, and cell degeneration.

Adaptation, Physiological↗

Health care value-based purchasing.

Two Institute of Medicine studies have focused attention on the glaring deficiencies in health care safety and quality. These studies and others serve as wake-up calls within both the private and government-sponsored United States health care industry. As a result of the "quality chasm" and crippling rise in health care cost, the concept of value-based purchasing (VBP) has gained increasing momentum. The stakeholders affected by the health care value equation include consumers, employers, insurers, and providers. VBP creates quality standards and stakeholder incentives to improve quality of care and become more cost efficient. The greatest challenge is the development of methods and information sources that will allow reliable, accurate, and credible measures of health care quality. VBP presents the ambitious hope of creating transparent measures of quality and cost efficiency that would allow the consumer to make health care purchasing decisions. If this can be achieved, then the competitive forces that increase value in other industries will function in health care.

Consumer Behavior↗

Type I interferons in host defense.

Type I interferons (IFNs) are a family of cytokines specialized to coordinate immunity to viruses and other intracellular infections. In the past several years, many of the receptors and signaling pathways that link pathogen detection to induction of type I IFNs have been identified and characterized. An integrated picture has emerged in which type I IFNs have essential functions in several seemingly disparate processes: they restrict viral spread by engaging machinery that ultimately cripples and kills infected cells, yet they are also positively linked to the activation and expansion of lymphocytes that are important for control of intracellular infections. These advances highlight the context-specific actions of type I IFNs and clarify the multiple points at which they are integrated into both innate and adaptive immunity.

Animals↗

Diagnosis and management of iliac vein compression syndrome.

Iliac vein compression syndrome (IVCS) is the most probable cause of iliofemoral deep venous thrombosis (DVT). One half to two thirds of patients with left-sided iliofemoral DVT have intraluminal webs or spurs from chronic extrinsic compression of the left iliac vein at the crossing point of the right common iliac artery. Approximately 2% to 5% of those with chronic deep venous insufficiency of the left leg may have IVCS. IVCS occurs when compression of the common iliac vein is severe enough to inhibit the rate of venous outflow. In its more severe manifestation, IVCS is known to cause acute iliofemoral DVT. IVCS is caused by the combination of compression and the vibratory pressure of the right iliac artery on the iliac vein that is pinched between the artery and the pelvic bone. With the advent of catheter-directed thrombolytic therapy for patients presenting with iliofemoral DVT, the underlying cause has been unveiled and IVCS is gaining recognition. Patients presenting with symptoms of chronic venous insufficiency often fail conservative treatment, and because of their crippling symptoms, they may have a high rate of work absence or are on permanent disability. If IVCS can be identified as the cause and corrected, the patients' quality of life would improve. With the advent of endovascular stenting, the underlying cause can be easily corrected, and long-term patency is acceptable. Diagnosis can be made by being highly suspicious when patients present in either the acute or chronic state and selecting the best diagnostic tool to confirm the diagnosis. This article discusses the prevalence of IVCS, its significance for the affected population, and the relevance of recognition, and reviews the best methods of its diagnosis and treatment. Special emphasis is placed on diagnostic tools and their efficacy, and our results to date are reported.

Adult↗

Murine macrophage transcriptional and functional responses to Bacillus anthracis edema toxin.

Edema toxin (EdTx), which is a combination of edema factor and a binding moiety (protective antigen), is produced by Bacillus anthracis, the etiological agent of anthrax. EdTx is an adenylyl cyclase enzyme that converts adenosine triphosphate to adenosine-3',5'-monophosphate, resulting in interstitial edema seen in anthrax patients. We used GeneChip analysis to examine global transcriptional profiles of EdTx-treated RAW 264.7 murine macrophage-like cells and identified 71 and 259 genes whose expression was significantly altered by the toxin at 3 and 6h, respectively. Alteration in the expression levels of selected genes was confirmed by real time-reverse transcriptase polymerase chain reaction. The genes with up-regulated expression in macrophages in response to EdTx-treatment were known to be involved in inflammatory responses, regulation of apoptosis, adhesion, immune cell activation, and transcription regulation. Additionally, GeneChip analysis results implied that EdTx-induced activation of activator protein-1 (AP-1) and CAAAT/enhancer-binding protein-beta (C/EBP-beta). Gel shift assays were therefore performed, and an increase in the activities of both of these transcription factors was observed within 30 min. EdTx also inhibited tumor necrosis factor alpha production and crippled the phagocytic ability of the macrophages. This is the first report detailing the host cell global transcriptional responses to EdTx.

Animals↗

[Be careful in using flecainide by hemodialyzed patients].

Cardiac arrhythmias are frequent by hemodialyzed patients and may lead to the prescription of antiarrhythmic drugs among which flecainide. However there is for this latter a wide interindividual variability in the dose-plasma concentration relationship because of a genetically controlled polymorphic metabolism. That explains why it is not possible to adjust dose only to renal clearance. It becomes even more difficult at hemodialysis stage, especially if hepatic insufficiency and/or certain medications join to it. So this antiarrhythmic drug has to be cautiously initiated and plasma concentrations have to be carefully monitored to avoid side effects, sometimes crippling as in our observation, sometimes as cardiac complications.

Aged↗