HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the ...brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.
The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.
The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.
The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.
High-quality communication is a key determinant and facilitator of patient-centered care. Nurses engage in most of the communication with patients and patients' families in the intensive care unit.
...To perform a qualitative analysis of nurses' communications.
Ethnographic observations of 315 hours of interactions and 53 semistructured interviews with 33 nurses were conducted in a 26-bed cardiac-medical intensive care unit in an academic hospital and a 26-bed general intensive care unit in a Veterans Affairs hospital in Portland, Oregon. Communication interactions were categorized into 5 domains of patient-centered care. Interviews were analyzed to identify major themes in nurses' roles and preferences for communicating with patients and patients' families within the domains.
Most communication occurred in the domains of biopsychosocial information exchange, patient as person, and clinician as person. Nurses endorsed the importance of the domains of shared power and responsibility and therapeutic alliance but had relatively few communication interactions in these areas. Communication behaviors were strongly influenced by the nurses' roles as translators of information between physicians and patients and the patients' families and what the nurses were and were not willing to communicate to patients and patients' families.
Critical care, including communication, is a collaborative effort. Understanding how nurses engage in patient-centered communication in the intensive care unit can guide future interventions to improve patient-centered care.
We describe two cases of airway foreign bodies (FB) consisting of a dental crown. The shape and composition of dental crowns complicate their extraction from the tracheobronchial tree, sometimes ...necessitating thoracotomy. We describe the use of a multidisciplinary approach involving rigid and flexible bronchoscopy in concert with the use of wire snares under fluoroscopic guidance for extraction of these challenging FB. These cases illustrate that this multidisciplinary approach can allow successful extraction of the difficult FB from much of the tracheobronchial tree and the avoidance of thoracotomy.
Renal parenchymal cells produce cytokines, colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), which recruit ...autoreactive T cells and, in turn, elicit renal injury in MRL-Fas(lpr) mice.
To determine whether select T-cell populations regulate intrarenal nephritogenic cytokines (CSF-1, GM-CSF, and TNF-alpha) and renal disease, we compared MRL-Fas(lpr) mice that are genetically deficient in T-cell receptor (TCR) alpha beta T cells, CD4 T cells, and major histocompatibility complex class I (MHC class I), lacking CD8 and double negative (DN) T cells, with wild-type mice. To identify the T cells instrumental in downstream (effector) events, we delivered CSF-1 or GM-CSF into the kidney via gene transfer in these select T-cell-deficient and wild-type strains.
Intrarenal CSF-1, GM-CSF, and TNF-alpha were absent or dramatically reduced in TCR alpha beta, CD4, and class I-deficient MRL-Fas(lpr) strains as compared with wild-type mice. In addition, the decrease in CSF-1, GM-CSF, and TNF-alpha was associated with a reduced kidney leukocytic infiltrates and spontaneous autoimmune nephritis. Intrarenal ex vivo retroviral gene transfer of CSF-1 and GM-CSF failed to elicit nephritis in these T-cell-deficient MRL strains (TCR alpha beta, CD4, CD8/DN) as compared with wild-type mice.
Multiple T-cell populations initiate renal disease by increasing intrarenal nephritogenic cytokines, CSF-1, GM-CSF, and TNF-alpha. CSF-1 and GM-CSF recruit additional CD4 and CD8 and DN T cells, which augment downstream events, resulting in progressive autoimmune renal disease. We suggest that MRL-Fas(lpr) kidney disease is driven by a T-cell amplification feedback loop dependent on multiple T-cell populations.
To measure the in vivorate of alveolar epithelial fluid clearance of the human lung inpatients with pulmonary alveolar phospholipoproteinosis (PAP).
Prospective clinical study.
The medical-surgical ...ICUs of a university teachinghospital.
Four patients with idiopathic PAPrequiring therapeutic lung lavage.
Large-volume lung lavage with isotonic saline solution using fiberopticbronchoscopy followed by serial sampling of alveolar fluid using awedged bronchial catheter.
The rate of alveolar epithelial fluid clearance was calculated bymeasuring the concentration of protein in sequential samples. Alveolarepithelial fluid clearance over the first hour after lung lavage was53 ± 14% (mean ± SD). Sequential samples in two patientsindicated a sustained high rate of clearance over several hours. Plasmaand alveolar fluid epinephrine levels were in the normal range in twopatients.
Alveolar fluidclearance is rapid after lung lavage in patients with PAP and appearsto be driven by catecholamine-independent mechanisms. The rapid rate ofalveolar epithelial fluid transport explains why patients with PAPtolerate large-volume lung lavage.
Genipin, a natural and non-toxic cross-linking reagent, was evaluated for its effects on the drug/protein release and swelling of chitosan microspheres. Chitosan microspheres, using albumin as a ...model protein, were prepared and cross-linked with 0.5
mM genipin for 4 to 16
h or for 4
h using 0.5 to 2.0
mM genipin. The degree of cross-linking, swelling and the release of albumin from the microspheres was determined by the ninhydrin assay, measuring change in mass between dry and wet spheres, and in 31-day elution tests, respectively. The degree of cross-linking increased up to maximum of 33% to 34% with up to 8 hour cross-linking time or with up to 1.0
mM genipin concentration. Additional cross-linking time or concentration did not significantly increase degree of cross-linking. Swelling ratios decreased significantly from 119.2% in the uncross-linked condition to 108.8% at 16
h cross-linking time. However, increasing the genipin concentration resulted in much smaller decreases in swelling. The release of albumin was reduced with as little as 4
h cross-linking time to 30.9% of uncross-linked microspheres for up to 24 days and by as much as 52.3–60.0% for up to 31 days with 8–16
h cross-linking time. Using genipin concentrations of 1.0 to 2.0
mM for 4
h, greatly reduced albumin release to only 12.4% to 27.1% on day 24. These data demonstrate that protein and drug delivery rates from chitosan microspheres may be controlled and extended by controlling the degree of cross-linking with genipin.
Degree of deacetylation (DDA) and molecular weight (MW) of chitosans are important to their physical and biological properties. In this study, two chitosans, HS (DDA = 73.3%) and AT (DDA = 76.8%), ...were deacetylated with 45% sodium hydroxide under nitrogen atmosphere at 80 °C or 90 °C for up to 120 min, to obtain two series of chitosans. The polymers produced were characterized for MW by gel permeation chromatography, DDA by titration and UV-vis methods, and crystallinity, hydrophilicity and thermal stability by X-ray diffraction, water contact angle and differential scanning calorimetry respectively. Films, made by solution casting in dilute acetic acid at ambient conditions, were evaluated for biological activity by albumin adsorption and the attachment and growth of a pre-osteoblast cell line. Chitosans with between 80-93% DDA's (based on titration) were reproducibly obtained. Even though deacetylation under nitrogen was supposed to limit chain degradation during decetylation, MW decreased (by maximum of 37.4% of HS and 63.0% for AT) with increasing deacetylation reaction time and temperature. Crystallinity and decomposition temperature increased and water contact angles decreased with processing to increase DDA. Significantly less albumin was absorbed on films made with 93% DDA chitosans as compared with the original materials and the AT chitosans absorbed less than the HS chitosans. The cells on higher DDA chitosan films grew faster than those on lower DDA films. In conclusion, processing conditions increased DDA and influenced physicochemical and biological properties. However, additional studies are needed to unambiguously determine the influence of DDA or MW on in vitro and in vivo performance of chitosan materials for bone/implant applications.
Traumatic brain injury (TBI) has been called "the most complicated disease of the most complex organ of the body" and is an increasingly high-profile public health issue. Many patients report ...long-term impairments following even "mild" injuries, but reliable criteria for diagnosis and prognosis are lacking. Every clinical trial for TBI treatment to date has failed to demonstrate reliable and safe improvement in outcomes, and the existing body of literature is insufficient to support the creation of a new classification system. Concussion, or mild TBI, is a highly heterogeneous phenomenon, and numerous factors interact dynamically to influence an individual's recovery trajectory. Many of the obstacles faced in research and clinical practice related to TBI and concussion, including observed heterogeneity, arguably stem from the complexity of the condition itself. To improve understanding of this complexity, we review the current state of research through the lens provided by the interdisciplinary field of systems science, which has been increasingly applied to biomedical issues. The review was conducted iteratively, through multiple phases of literature review, expert interviews, and systems diagramming and represents the first phase in an effort to develop systems models of concussion. The primary focus of this work was to examine concepts and ways of thinking about concussion that currently impede research design and block advancements in care of TBI. Results are presented in the form of a multi-scale conceptual framework intended to synthesize knowledge across disciplines, improve research design, and provide a broader, multi-scale model for understanding concussion pathophysiology, classification, and treatment.
There is a significant clinical need to develop alternatives to autografts and allografts for bone grafting procedures. Porous, biodegradable scaffolds based on the biopolymer chitosan have been ...investigated as bone graft substitutes, and the addition of calcium phosphate to these scaffolds has been shown to improve the mechanical properties of the scaffold and may increase osteoconductivity. In this study, in vitro mineralization was examined for osteoblasts seeded in a porous scaffold composed of fused chitosan/nano-hydroxyapatite microspheres. Human fetal osteoblasts were cultured on composite and chitosan scaffolds for 21 days. On days 1, 4, 7, 14, and 21, total dsDNA, alkaline phosphatase, type I collagen, and osteocalcin production were measured. Total cellularity (measured by dsDNA), alkaline phosphatase, and type I collagen production were similar between the two scaffold groups. However, osteocalcin production occurred significantly earlier (day 7 vs. day 21) and was more than three times greater (0.0022 vs. 0.0068 ng/mL/ng DNA) on day 21 when osteoblasts were cultured on composite scaffolds. Osteocalcin is a marker of late osteoblastic differentiation and mineralized bone matrix formation. Therefore, the increase in osteocalcin production seen when cells were cultured on composite scaffolds may indicate that these scaffolds were superior to chitosan-only scaffolds in facilitating osteoblast mineralization. Composite scaffolds were also shown to be biocompatible and osteoconductive in a preliminary critical size rat calvarial defect study. These results demonstrate the potential of composite chitosan/nano-hydroxyapatite scaffolds to be used in bone tissue engineering.
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