Abstract The aim of this study was to compare the efficacy of femoral nerve block with indwelling catheter-based multiple infiltrations of bupivacaine for postoperative pain management after iliac ...bone harvesting. Sixty paediatric patients undergoing iliac harvesting were randomized into three groups: group A, preoperative femoral nerve block; group B, multiple bolus infiltration of 0.5% bupivacaine via indwelling catheter at the donor site; group C, controls – single dose of 0.5% bupivacaine infiltration given subcutaneously. The primary outcome measure was postoperative pain intensity at rest and at function. The time to maximum pain score, time to ambulation, duration of analgesia, and length of hospital stay were also assessed. Group B patients had the best pain relief and return to function, however the duration of pain relief was longer in group A. Subjects in group A had concomitant motor blockade causing delayed ambulation. Group C showed the worst outcomes. Indwelling catheter-based infiltration of bupivacaine was the most efficient method for providing enhanced pain relief after iliac bone graft harvesting. There was no increase in operating time or hospital stay. Femoral nerve block provided the next best results, but had the significant disadvantage of motor nerve blockade.
Purpose
The aim of this paper is to review the pathophysiology of thermoregulation mechanism, various causes of fever after maxillofacial surgery and the different treatment protocols advised in the ...literature.
Discussion
Fever is one of the most common complaints after major surgery and is also considered to be an important clinical sign which indicates developing pathology that may go unnoticed by the clinician during post operative period. Several factors are responsible for fever after the maxillofacial surgery, inflammation and infection being the commonest. However, other rare causes such as drug allergy, dehydration, malignancy and endocrinological disorders, etc. should be ruled out prior to any definite diagnosis and initiate the treatment. Proper history and clinical examination is an essential tool to predict the causative factors for fever. Common cooling methods like tepid sponging are usually effective alone or in conjunction with analgesics to reduce the temperature.
Conclusion
Fever is a common postoperative complaint and should not be underestimated as it may indicate a more serious underlying pathology. A specific guideline towards the management of such patients is necessary in every hospital setting to ensure optimal care towards the patients during post operative period.
Hemophilia is the most common inherited bleeding disorder. Hemophilic patients should be cosidered as special patients. There is no contraindication to general dental treatment for hemophiliacs, as ...they generally do not involve bleeding. But caution must be used with any surgical procedures that involve the local and general anesthesia. Such patients should always be managed in the setting of specialized units with appropriate clinical expertise and laboratory support. Recent advances in the management of hemophilia have enabled many hemophiliac patients to receive surgical dental procedures in an outpatient dental care on a routine basis. The purpose of this case report is to provide a few management strategies when providing full mouth rehabilitation under anesthesia and replacement therapies that are available. In addition, overviews of possible complication that may be encountered when providing such treatment are discussed here.
Abstract Corneal dystrophies are a group of inherited disorders localized to various layers of the cornea that affect corneal transparency and visual acuity. The deposition of insoluble protein ...materials in the form of extracellular deposits or intracellular cysts is pathognomic. Mutations in TGFBI are responsible for superficial and stromal corneal dystrophies. The gene product, transforming growth factor β induced protein (TGFBIp) accumulates as insoluble deposits in various forms. The severity, clinicopathogenic variations, age of the onset, and location of the deposits depend on the type of amino acid alterations in the protein. Until 2006, 38 different pathogenic mutants were reported for the TGFBI -associated corneal dystrophies. This number has increased to 63 mutants, reported in more than 30 countries. There is no effective treatment to prevent, halt, or reverse the deposition of TGFBIp. This review presents a complete mutation update, classification of phenotypes, comprehensive reported incidents of various mutations, and current treatment options and their shortcomings. Future research directions and possible approaches to inhibiting disease progression are discussed.
To establish a method for assessing graft viability, in-vivo, following corneal transplantation.
Optimization of calcein AM fluorescence and toxicity assessment was performed in cultured human ...corneal endothelial cells and ex-vivo corneal tissue. Descemet membrane endothelial keratoplasty grafts were incubated with calcein AM and imaged pre and post preparation, and in-situ after insertion and unfolding in a pig eye model. Global, macroscopic images of the entire graft and individual cell resolution could be attained by altering the magnification of a clinical confocal scanning laser microscope. Patterns of cell loss observed in situ were compared to those seen using standard ex-vivo techniques.
Calcein AM showed a positive dose-fluorescence relationship. A dose of 2.67μmol was sufficient to allow clear discrimination between viable and non-viable areas (sensitivity of 96.6% with a specificity of 96.1%) and was not toxic to cultured endothelial cells or ex-vivo corneal tissue. Patterns of cell loss seen in-situ closely matched those seen on ex-vivo assessment with fluorescence viability imaging, trypan blue/alizarin red staining or scanning electron microscopy. Iatrogenic graft damage from preparation and insertion varied between 7-35% and incarceration of the graft tissue within surgical wounds was identified as a significant cause of endothelial damage.
In-situ graft viability assessment using clinical imaging devices provides comparable information to ex-vivo methods. This method shows high sensitivity and specificity, is non-toxic and can be used to evaluate immediate cell viability in new grafting techniques in-vivo.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Effective treatment of chronic pain, in particular neuropathic pain, without the side effects that often accompany currently available treatment options is an area of significant unmet medical need. ...A phenotypic screen of mouse gene knockouts led to the discovery that adaptor protein 2-associated kinase 1 (AAK1) is a potential therapeutic target for neuropathic pain. The synthesis and optimization of structure–activity relationships of a series of aryl amide-based AAK1 inhibitors led to the identification of 59, a brain penetrant, AAK1-selective inhibitor that proved to be a valuable tool compound. Compound 59 was evaluated in mice for the inhibition of μ2 phosphorylation. Studies conducted with 59 in pain models demonstrated that this compound was efficacious in the phase II formalin model for persistent pain and the chronic-constriction-injury-induced model for neuropathic pain in rats. These results suggest that AAK1 inhibition is a promising approach for the treatment of neuropathic pain.
FcγRs are critical mediators of mAb cancer therapies, because they drive cytotoxic processes upon binding of effector cells to opsonized targets. Along with NK cells, monocytes are also known to ...destroy Ab-coated targets via Ab-dependent cellular cytotoxicity (ADCC). However, the precise mechanisms by which monocytes carry out this function have remained elusive. In this article, we show that human monocytes produce the protease granzyme B upon both FcγR and TLR8 activation. Treatment with TLR8 agonists elicited granzyme B and also enhanced FcγR-mediated granzyme B production in an additive fashion. Furthermore, monocyte-mediated ADCC against cetuximab-coated tumor targets was enhanced by TLR8 agonist treatment, and this enhancement of ADCC required granzyme B. Hence we have identified granzyme B as an important mediator of FcγR function in human monocytes and have uncovered another mechanism by which TLR8 agonists may enhance FcγR-based therapies.
Abstract
Monocytes and macrophages are critical for the effectiveness of monoclonal antibody therapy. Cellular responses to antibody-coated targets are largely mediated by Fcγ receptors (FcγR), which ...cluster and become activated upon binding immune complexes. FcγRIIb is an inhibitory FcγR that negatively regulates these responses, so deletion or down-regulation of this receptor may substantially enhance the outcome of antibody therapy.
Toll-like receptor (TLR) agonists are being used and tested as immune-stimulatory agents for cancer. We screened a panel of TLR agonists to test their effect on FcγRIIb expression and found significant receptor downregulation with TLR4 and TLR8 agonists. We selected the TLR4 agonist lipopolysaccharide (LPS) for further examination and found that it led to the ubiquitination of FcγRIIb protein. In a search of our microarray database of monocytes treated with a TLR7/8 agonist (in which FcγRIIb was down-regulated), we found that membrane-associated ring finger (C3HC4) 3 (MARCH3), an E3 ubiquitin ligase, was significantly upregulated. We next tested whether this same E3 ligase was also upregulated with LPS treatment and whether it was required for LPS-mediated FcγRIIb downregulation. Results showed that LPS significantly increased MARCH3 expression and that siRNA against MARCH3 prevented the LPS-mediated decrease in FcγRIIb. These data suggest that LPS effects the downregulation of FcγRIIb through ubiquitination and that this is mediated by the E3 ligase MARCH3.
Abstract TGFBI -associated corneal dystrophies are characterized by accumulation of insoluble deposits of the mutant protein transforming growth factor β−induced protein (TGFBIp) in the cornea. ...Depending on the nature of mutation, the lesions appear as granular (non-amyloid) or lattice lines (amyloid) in the Bowman's layer or in the stroma. This review article emphasizes the structural biology aspects of TGFBIp. We discuss the tinctorial properties and ultrastructure of deposits observed in granular and lattice corneal dystrophic mutants with amyloid and non-amyloid forms of other human protein deposition diseases and review the biochemical and putative functional role of the protein. Using bioinformatics tools, we identify intrinsic aggregation propensity and discuss the possible protective role of gatekeepers close to the “aggregation-prone” regions of native TGFBIp. We describe the relative aggregation rates of lattice corneal dystrophy (LCD) and granular corneal dystrophy (GCD2) mutants using the three-parameter model, which is based on intrinsic properties of polypeptide chains. The predictive power of this model is compared with two other algorithms. We conclude that the model is able to predict the aggregation rate of mutants which do not alter overall net charge of the protein. The need to understand the mechanism of corneal dystrophies from the structural biology viewpoint is emphasized.
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