scholarly journals Penicillin and cephalosporin cross-reactivity: role of side chain and synthetic cefadroxil epitopes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gador Bogas ◽  
Cristobalina Mayorga ◽  
Ángela Martín-Serrano ◽  
Rubén Fernández-Santamaría ◽  
Isabel M. Jiménez-Sánchez ◽  
...  

Abstract Background Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX. Methods Fifty-four patients with confirmed IHRs to AX based on skin test (ST) and/or drug provocation test (DPT) were included. Serum sIgE to AX and benzylpenicillin was determined by Radioallergosorbent test (RAST). Two potential determinants of CX, involving intact or modified R1 structure, with open betalactam ring, were synthesised and sIgE evaluated by RAST inhibition assay. Results Tolerance to CX (Group A) was observed in 64.8% cases and cross-reactivity in 35.2% cases (Group B). Cross-reactivity with CO was only found in 1.8% cases from Group B. ST to CX showed a negative predictive value of 94.6%. RAST inhibition assays showed higher recognition to CX as well as to both synthetic determinants (66% of positive cases) in Group B. Conclusions Cross-reactivity with CX in AX allergic patients is 35%, being ST not enough for prediction. R1, although critical for recognition, is not the unique factor. The synthetic determinants of CX, 1-(HOPhG-Ser-Bu) and 2-(pyrazinone) are promising tools for determining in vitro cross-reactivity to CX in AX allergic patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 814-814 ◽  
Author(s):  
Marco Tucci ◽  
Lucia Lombardi ◽  
Steve Reshkin ◽  
Rosa A. Cardone ◽  
Silvestris Franco

Abstract Accelerated osteoclastogenesis is the major event promoting the skeletal impairment in multiple myeloma (MM). Osteoclasts (OC) are directly activated by myeloma cells (MC), although these cells themselves may apparently undergo to OC-like morphologic transformation and produce bone erosion in vitro. Since OCs exert their function and promote osteoclastogenesis through activation of several adhesion molecules, including avb3, we investigated the role of this integrin expressed by MCs in their OC-like activity in vitro. Bone marrow MCs were purified from eight patients with severe skeletal disease (group A) and from two patients without bone lesions (group B). U266 and RPMI-8226 MC lines were the controls. Semi-nested PCR assessed the CDR3 immunoglobulin (Ig) gene rearrangement, whereas OC markers including TRAcP, cathepsin-k, calcitonin-receptor, carbonic anhydrase and vATPase were evaluated by RT-PCR. The cytoskeletal rearrangement of F-actin was analyzed by immunofluorescence. av and b3 expression on MCs was evaluated by flow-cytometry, whereas bone erosion on calcium phosphate discs and number of pits was measured by dedicated software. The effect of avb3 stimulation on the activation of osteoclastogenic function was investigated by exploring the phosphorilation of transcriptional kinases and downstream molecules, as ERK1/2 and cFos, respectively. The primary role of avb3 in OC-like functional transdifferentiation was explored in MCs by siRNA silencing for both chains. Ontogenetic derivation from the B-cell lineage was confirmed by the monoclonal CDR3 rearrangement, CD138/CD38 and Pax-5 expression. Cells from patients of group A expressed OC markers, in contrast with those of group B or U266 and RPMI-8226. Formation of the F-actin ring confirmed the differentiation of MCs toward the OC-like phenotype. Cells from group A expressed av and b3 (80±7% and 75±9%) similarly to U266 and RPMI-8226 (>90% in both instances), whereas a minimal expression was demonstrated in group B (av:6±2%; b3:8±3%). avb3+ cells produced a high number of erosive pits, at variance from avb3− cells (35±8 vs. 4±1 pits/cm2 ). The highest phosphorilation of ERK1/2 and expression of cFos was revealed in patients of group A as compared to B (840±110 OD and 905±210 OD vs. 270±35 OD and 315±80 OD, p<0.0001 in both instances). Finally, the silencing of av and/or b3 chain inhibited the erosion by avb3+ cells, resulting in a reduced number of pits (7±2 pits/cm2) similar to the pattern obtained with avb3− cells. Similarly, an inhibition of both ERK1/2 and cFos was demonstrated in silenced cells from group A with values similar to those of group B. Since avb3 drives both adhesion of Ocs to extracellular matrix and activation of osteoclastogenesis, it is conceivable that avb3+ MCs may functionally transdifferentiate to OCs in response to integrin activation induced by the contact with stromal cells within the marrow environment, thus resulting in a typical OC-like behaviour. In addition, our data suggest that MCs induce this effect by avb3, since its silencing reduces the OC-like activity in vitro.


1982 ◽  
Vol 47 (03) ◽  
pp. 218-220 ◽  
Author(s):  
P Sié ◽  
E Letrenne ◽  
C Caranobe ◽  
M Genestal ◽  
B Cathala ◽  
...  

SummaryIn order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and serum demonstrated that the levels of II rAg and of AT III, assessed by the Laurell technique with Behring antisera, were not reduced by the coagulation process. The patients were, a posteriori, classified into two groups according to the absence (group A) or the presence (group B) of factors predisposing to liver failure such as metastasis, cirrhosis, and prolonged shock. II rAg and AT III levels are significantly correlated; they are in the normal range in group A but reduced in group B. Thus II rAg or AT III level determinations are useful markers in the detection of liver failure associated to the consumption phenomenon. These results also suggest that part of the decreased AT III levels reported in severe cases of disseminated intravascular coagulation may be the consequence of an associated liver failure.


2021 ◽  
pp. 112972982110154
Author(s):  
Raffaella Mauro ◽  
Cristina Rocchi ◽  
Francesco Vasuri ◽  
Alessia Pini ◽  
Anna Laura Croci Chiocchini ◽  
...  

Background: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. Materials and methods: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. Results: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0–65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 ( p = 0.001) and with NA ( p = 0.001). Conclusions: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2876
Author(s):  
Giovanni Manfredi Assanto ◽  
Giulia Ciotti ◽  
Mattia Brescini ◽  
Maria Lucia De Luca ◽  
Giorgia Annechini ◽  
...  

Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. Patients and Methods: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. Results: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. Conclusion: A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Xiao-yu Liu ◽  
Hai-feng Shi ◽  
Jie Zheng ◽  
Ku-lin Li ◽  
Xiao-xi Zhao ◽  
...  

Objective. The objective of this study was to investigate the impact of left atrial (LA) size for the ablation of atrial fibrillation (AF) using remote magnetic navigation (RMN). Methods. A total of 165 patients with AF who underwent catheter ablation using RMN were included. The patients were divided into two groups based on LA diameter. Eighty-three patients had small LA (diameter <40 mm; Group A), and 82 patients had a large LA (diameter ≥40 mm; Group B). Results. During mapping and ablation, X-ray time (37.0 (99.0) s vs. 12 (30.1) s, P<0.001) and X-ray dose (1.4 (2.7) gy·cm2 vs. 0.7 (2.1) gy·cm2, P=0.013) were significantly higher in Group A. No serious complications occurred in any of the patients. There was no statistical difference in the rate of first anatomical attempt of pulmonary vein isolation between the two groups (71.1% vs. 57.3%, P=0.065). However, compared with Group B, the rate of sinus rhythm was higher (77.1% vs. 58.5%, P<0.001) during the follow-up period. More patients in Group A required a sheath adjustment (47/83 vs. 21/82, P<0.001), presumably due to less magnets positioned outside of the sheath. In vitro experiments with the RMN catheter demonstrated that only one magnet exposed created the sheath affects which influenced the flexibility of the catheter. Conclusions. AF ablation using RMN is safe and effective in both small and large LA patients. Patients with small LA may pose a greater difficulty when using RMN which may be attributed to the fewer magnets beyond the sheath. As a result, the exposure of radiation was increased. This study found that having at least two magnets of the catheter positioned outside of the sheath can ensure an appropriate flexibility of the catheter.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Iwahashi ◽  
J Kirigaya ◽  
M Horii ◽  
T Abe ◽  
E Akiyama ◽  
...  

Abstract Background The early transmitral flow velocity (E) divided by the early diastolic velocity of the mitral valve annulus (e') is referred to as the “E/e' ratio,” is useful even for ST elevation acute myocardial infarction (STEMI). However, the role of late diastolic velocity (a') which reveals the atrial function for STEMI is still unclear. Objectives We evaluated the clinical usefulness of tissue Doppler including atrial function for a first-time STEMI by long time follow up. Furthermore, we evaluated the meaning of each parameters by performing immediately after PCI or 2 weeks later. Methods We treated consecutive 571 first-time STEMI patients by immediate PCI within 12 hours after onset, and we examined 270 patients at immediately after PCI (GroupA, 65 years, 250 male) and 301 patients at 2 weeks after onset (GroupB, 64 years, 243 male). We examined trans mitral flow and TDI, then defined E/e' as LV filling pressure and A/a' as left atrial function. We followed them for a long time (&gt;5 years). The primary end point (PE) was cardiac death or re-admission for heart failure (HF). Results We followed the patients in Group A for 10 years, Group B for 5 years. PE occurred in 64 patients in GroupA during 10 years, and 45 patients in GroupB during 5 years. We analyzed the univariate and multivariate Cox hazard analyses and we compared e' and a', E/e' and A/a' (Table). In GroupA, a' and A/a' were the independent predictors, on the other hand neither a' nor A/a' were the predictors in GroupB. E/e' was an independent predictor both in GroupA and B. Conclusion TDI parameters have different meanings by the timing of echocardiography after onset of a first-time STEMI. These results demonstrated that atrial dysfunction immediately after onset of STEMI suggests the poor prognosis after STEMI. Cox Hazard Proportional Analysis Funding Acknowledgement Type of funding source: None


1990 ◽  
Vol 2 (4) ◽  
pp. 351 ◽  
Author(s):  
YF Wong ◽  
EP Loong ◽  
KR Mao ◽  
PP Tam ◽  
NS Panesar ◽  
...  

Salivary oestradiol (E2) and progesterone (P) levels have been shown to reflect the biologically active fractions in the serum. The luteal-phase status of stimulated cycles was investigated after in vitro fertilization and embryo transfer (IVF-ET). Thirty patients were randomly allocated to one of three luteal therapy groups: group A had no support, group B had intramuscular P and group C had intramuscular P and human chorionic gonadotrophin (hCG). One pregnancy was achieved in group A, two in group B and three in group C. Significant correlations between salivary and serum levels of E2 and of P in matched samples during luteal phase were found. Salivary E2 levels from luteal day 8 through day 14 and P levels from day 3 through day 14 were significantly higher in the pregnant than in the nonpregnant cycles. Among the nonpregnant cycles, salivary E2 and P levels were significantly higher in group C than in group A or B. These findings suggest that, in stimulated cycles for IVF-ET, determination of salivary E2 and P levels may be used as reliable alternatives to serum concentrations for assessing the luteal phase. Also, the additional hCG has an enhanced luteotrophic effect, as reflected by the higher salivary E2 and P levels, which may lead to a better pregnancy rate.


2014 ◽  
Vol 490-491 ◽  
pp. 867-871
Author(s):  
Guo Hui Wang ◽  
Wei Yi Chen

To understand the effect of mechanical stimulation on posterior sclera reinforcement (PSR), the rabbit scleral fibroblasts after PSR were subjected to stretch in vitro and MMP-2 and TIMP-2 expression of scleral fibroblasts were evaluated. Three-week-old rabbits were monocularly performed by eyelid suturation randomly to prepare experimental myopia eye. After 60 days, the experimental myopia eyes were treated by PSR. After 6 months, the posterior pole scleral fibroblasts (normal sclera - group A, sclera after operation - group B and fusion region of sclera and reinforcing band group C) were isolated and cultured in vitro. The cells were subjected to cyclic stretch regimens (sine wave, 3% and 6% elongation amplitude, 0.1Hz, 48h duration) by FX-4000 Tension System. The MMP-2 and TIMP-2 expression of scleral fibroblasts were evaluated by ELISA method. The results show that after cyclic stretch to the scleral fibroblasts of the normal sclera and the sclera after operation, the MMP-2 expression was significantly reduced and the TIMP-2 expression was significantly increased, the MMP-2 and TIMP-2 expression of the scleral fibroblasts of the fusion region after operation was no changed. It was indicated that the mechanical stimulation could regulate the MMP-2 and TIMP-2 expression of scleral fibroblasts and play an important role in the process of treating high myopia with PSR surgery.


PEDIATRICS ◽  
1978 ◽  
Vol 62 (4) ◽  
pp. 620-621
Author(s):  
Gerald W. Fischer ◽  
James W. Bass ◽  
George H. Lowell ◽  
Martin H. Crumrine

The article by Bortolussi et al. on pneumococcal septicemia and meningitis in the neonat (Pediatrics 60:352, September 1977) was of great interest to us, since we have been analyzing the effect of antibody directed against Streptococcus pneumoniae on group B Streptococcus type III. We have recently shown (unpublished data) that antibody directed against S. pneumoniae type 14 precipitates the hot hydrochloric acid-extracted polysaccharide antigen of group B Streptococcus type III. Further studies have shown that this antibody is opsonic for group B Streptococcus type III in an in vitro bactericidal assay and protective in a suckling rat model of group B Streptococcus type III sepsis.1


2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.


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