Rapid desensitization for non-immediate reactions in patients with cystic fibrosis

AbstractNon-immediate hypersensitivity reactions to antibiotics in patients with CF represent a real-life challenge for clinicians. Desensitization is often performed in patients who have exhausted all therapeutic options. Whilst desensitization is an established procedure for immediate reactions we assessed the outcomes and safety of desensitization for non-immediate reactions.We retrospectively reviewed 275 desensitization procedures in 42 patients with a range of non-immediate reactions to six commonly used antibiotics. Desensitization was performed using a 7-step rapid intravenous protocol on a normal medical ward.250 (91%) of overall desensitization procedures were successful; however, this figure incorporates certain individuals having multiple successful procedures. Individual patient success ranged from 55% with tazocin through to 88% with tobramycin. In the 25 patients who failed desensitization the reactions were mild and the majority occurred within 48h of starting treatment. Prophylactic anti-histamines and steroids did not reduce the risk of reaction.Whilst the mechanisms remain uncertain we can confirm that rapid desensitization is a safe and effective way of re-introducing an antibiotic to a patient with a non-immediate reaction

Detection of somatic changes in human cancer DNA by DNA fingerprint analysis.

Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 cases. The changes included alterations in the relative intensities of hybridising DNA fragments, and, in three cases of cancers of gastrointestinal origin, the appearance of novel minisatellite fragments not seen in the corresponding constitutional DNA. The results of this preliminary study suggests that DNA fingerprint analysis provides a useful technique for identifying somatic changes in cancers

Lewis X antigen mediates adhesion of human breast carcinoma cells to activated endothelium. Possible involvement of the endothelial scavenger receptor C-Type lectin

Lewis x (Lex, CD15), also known as SSEA-1 (stage specific embryonic antigen-1), is a trisaccharide with the structure Galβ(1–4)Fucα(1–3)GlcNAc, which is expressed on glycoconjugates in human polymorphonuclear granulocytes and various tumors such as colon and breast carcinoma. We have investigated the role of Lex in the adhesion of MCF-7 human breast cancer cells and PMN to human umbilical endothelial cells (HUVEC) and the effects of two different anti-Lex mAbs (FC-2.15 and MCS-1) on this adhesion. We also analyzed the cytolysis of Lex+-cells induced by anti-Lex mAbs and complement when cells were adhered to the endothelium, and the effect of these antibodies on HUVEC. The results indicate that MCF-7 cells can bind to HUVEC, and that MCS-1 but not FC-2.15 mAb inhibit this interaction. Both mAbs can efficiently lyse MCF-7 cells bound to HUVEC in the presence of complement without damaging endothelial cells. We also found a Lex-dependent PMN interaction with HUVEC. Although both anti-Lex mAbs lysed PMN in suspension and adhered to HUVEC, PMN aggregation was only induced by mAb FC-2.15. Blotting studies revealed that the endothelial scavenger receptor C-type lectin (SRCL), which binds Lex-trisaccharide, interacts with specific glycoproteins of Mr␣∼␣28 kD and 10 kD from MCF-7 cells. The interaction between Lex+-cancer cells and vascular endothelium is a potential target for cancer treatment.Fil: Elola, Maria Teresa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capurro, Mariana Isabel. University of Toronto; CanadáFil: Barrio, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; ArgentinaFil: Coombs, Peter J.. Imperial College London; Reino UnidoFil: Taylor, Maureen E.. Imperial College London; Reino UnidoFil: Drickamer, Kurt. Imperial College London; Reino UnidoFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentin

Variation in Prices Charged to Patients for Specialty Intraocular Lenses Inserted during Universally Covered Cataract Surgery

Patients often pay for specialty intraocular lenses (IOLs) for cataract surgery covered by universal insurance. This practice creates the potential for inequitable pricing where the medical service provider is also the retailer. We measured the variation in prices between cataract surgeons for the same IOL and associated testing.We telephoned every cataract surgeon in Ontario, Canada, and asked their price for the most common type of specialty IOL as a prospective patient. We measured the total prices quoted and variation between providers.We contacted 404 ophthalmologists. There were 256 that performed cataract surgery but 127 offered the most commonly employed specialty IOL and would provide a price to patients over the telephone. We obtained prices from all 127 ophthalmologists. Prices for the same lens and associated testing varied substantially between ophthalmologists from $358 to$2790 (median $615, interquartile range$528-$915). There was variation in all components of the total out-of-pocket price, including the price for the IOL itself, charges for uninsured eye measurements, and non-specific supplemental fees.Although cataract surgery is covered by public health insurance, some ophthalmologists charge much more than others for the same specialty IOL and associated testing. Greater access to price information and better regulatory control could help ensure patients receive fair value for out-of-pocket health expenses

Wind-thermal power system dispatch using MLSAD model and GSOICLW algorithm

The decision support model of mean-lower semi-absolute deviation (MLSAD) and the optimization algorithm of group search optimizer with intraspecific competition and lévy walk (GSOICLW) are presented to solve wind-thermal power system dispatch. MLSAD model takes the profit and downside risk into account simultaneously brought by uncertain wind power. Using a risk tolerance parameter, the model can be converted to a single-optimization problem, which is solved by an improved optimization algorithm, GSOICLW. Afterwards, both the model and the algorithm are tested on a modified IEEE 30-bus power system. Simulation results demonstrate that the MLSAD model can well solve wind-thermal power system dispatch. The study also verifies GSOICLW obtains better convergent dispatching solutions, in comparison with other evolutionary algorithms, such as group search optimizer and particle swarm optimizer.NRF (Natl Research Foundation, S’pore)EDB (Economic Devt. Board, S’pore)Accepted versio

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

<p>Abstract</p> <p>Background</p> <p>Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in <it>Calca </it>-/- mice.</p> <p>Methods</p> <p>We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty <it>Calca </it>-/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), <it>Calca </it>-/- mice without UHMWPE particles (Group 3), <it>Calca </it>-/- mice with UHMWPE particles (Group 4), <it>Calca </it>-/- mice without UHMWPE particles and calcitonin substitution (Group 5), and <it>Calca </it>-/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.</p> <p>Results</p> <p>Bone resorption was significantly increased in <it>Calca </it>-/- mice compared with their corresponding WT. The eroded surface in <it>Calca </it>-/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in <it>Calca </it>-/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.</p> <p>Conclusions</p> <p>As anticipated, <it>Calca </it>-/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.</p

The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P = .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally

The N-glycome of human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Complex carbohydrate structures, glycans, are essential components of glycoproteins, glycolipids, and proteoglycans. While individual glycan structures including the SSEA and Tra antigens are already used to define undifferentiated human embryonic stem cells (hESC), the whole spectrum of stem cell glycans has remained unknown. We undertook a global study of the asparagine-linked glycoprotein glycans (N-glycans) of hESC and their differentiated progeny using MALDI-TOF mass spectrometric and NMR spectroscopic profiling. Structural analyses were performed by specific glycosidase enzymes and mass spectrometric fragmentation analyses.</p> <p>Results</p> <p>The data demonstrated that hESC have a characteristic N-glycome which consists of both a constant part and a variable part that changes during hESC differentiation. hESC-associated N-glycans were downregulated and new structures emerged in the differentiated cells. Previously mouse embryonic stem cells have been associated with complex fucosylation by use of SSEA-1 antibody. In the present study we found that complex fucosylation was the most characteristic glycosylation feature also in undifferentiated hESC. The most abundant complex fucosylated structures were Le^xand H type 2 antennae in sialylated complex-type N-glycans.</p> <p>Conclusion</p> <p>The N-glycan phenotype of hESC was shown to reflect their differentiation stage. During differentiation, hESC-associated N-glycan features were replaced by differentiated cell-associated structures. The results indicated that hESC differentiation stage can be determined by direct analysis of the N-glycan profile. These results provide the first overview of the N-glycan profile of hESC and form the basis for future strategies to target stem cell glycans.</p