scholarly journals Evaluation of Immunosuppressive Therapy Use for Tracheal Transplantation with Trachea-Mimetic Bellows Scaffolds in a Rabbit Model

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jae Yeon Lee ◽  
Jeong Hun Park ◽  
Soo Jin Son ◽  
Mina Han ◽  
Gonhyung Kim ◽  
...  
Keyword(s):  
Weight Loss ◽  
Immunosuppressive Therapy ◽  
Rabbit Model ◽  
High Dose ◽  
Tracheal Reconstruction ◽  
Tracheal Transplantation ◽  
Group 3 ◽  
Group 2 ◽  
Oral Doses ◽  
Group 1

The objective of this study was to evaluate the use of immunosuppressive therapy with high-dose cyclosporine, high-dose azathioprine, and a combination of low-dose cyclosporine and azathioprine after tracheal reconstruction by using a trachea-mimetic graft of polycaprolactone (PCL) bellows-type scaffold in a rabbit model. Twenty-four healthy New Zealand white rabbits were used in the study. All underwent circumferential tracheal replacement using tissue-engineered tracheal graft, prepared from PCL bellows scaffold reinforced with silicone ring, collagen hydrogel, and human turbinate mesenchymal stromal cell (hTMSC) sheets. The control group (Group 1) received no medication. The three experimental groups were given daily cyclosporine intramuscular doses of 10 mg/kg (Group 2), azathioprine oral doses of 5 mg/kg (Group 3), and azathioprine oral doses of 2.5 mg/kg plus cyclosporine intramuscular doses of 5 mg/kg (Group 4) for 4 weeks or until death. Group 1 had longer survival times compared to Group 2 or Group 3. Each group except for Group 1 experienced decreases in amount of nutrition and weight loss. In addition, compared with the other groups, Group 2 had significantly increased serum interleukin-2 and interferon-γ levels 7 days after transplantation. The results of this study showed that the administration of cyclosporine and/or azathioprine after tracheal transplantation had no beneficial effects. Furthermore, the administration of cyclosporine had side effects, including extreme weight loss, respiratory distress, and diarrhea. Therefore, cyclosporine and azathioprine avoidance may be recommended for tracheal reconstruction using a native trachea-mimetic graft of PCL bellows-type scaffold in a rabbit model.

Epidural Clonidine or Bupivacaine as the Sole Analgesic Agent during and after Abdominal Surgery 

1999 ◽  
Vol 90 (5) ◽  
pp. 1354-1362 ◽  
Author(s):  
Marc De Kock ◽  
Philippe Gautier ◽  
Athanassia Pavlopoulou ◽  
Marc Jonniaux ◽  
Patricia Lavand'homme
Keyword(s):  
High Dose ◽  
General Anesthetics ◽  
Visual Analogue Pain ◽  
Pain Scores ◽  
Arterial Blood ◽  
Sedation Scores ◽  
Group 3 ◽  
Group 2 ◽  
High Doses ◽  
Group 1

Background The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Methods Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. Results During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Conclusion Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.

scholarly journals Impact of Intensive Lifestyle Modification on Levels of Adipokines and Inflammatory Biomarkers in Metabolically Healthy Obese Women

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ricardo Gomez-Huelgas ◽  
Josefina Ruiz-Nava ◽  
Sonia Santamaria-Fernandez ◽  
Antonio Vargas-Candela ◽  
Ana Victoria Alarcon-Martin ◽  
...  
Keyword(s):  
Weight Loss ◽  
Lifestyle Modification ◽  
Inflammatory Biomarkers ◽  
Inflammatory Biomarker ◽  
Metabolically Healthy Obese ◽  
Group 3 ◽  
Healthy Obese ◽  
Metabolically Healthy ◽  
Group 2 ◽  
Group 1

Background. For the metabolically healthy obese (MHO) subjects, it is unclear whether weight loss provides cardiometabolic benefits. Our objective was to evaluate whether changes in adipokine and inflammatory biomarker levels were related to lifestyle modification (with Mediterranean diet and physical exercise program). Methods. 115 women (35-55 years) with BMI of 30-40 kg/m2 and ≤1 metabolic syndrome criteria were included. After a 2-year intervention, participants were classified by percent weight loss: Group 1, <5%; Group 2, ≥5%-<10%; and Group 3, ≥10%. Anthropometric data, inflammatory biomarker (IL-6, TNFa, and hsCRP) and adipokine levels (adiponectin and resistin), and lifestyle program adherence at baseline and 2 years were analyzed. Results. The final sample comprised 67 women. 23 (38.3%) lost <5%, 22 (36.7%) lost ≥5%-<10%, and 22 (36.7%) lost ≥10% of baseline weight. After 2 years, in Group 1, adiponectin, hsCRP, IL-6, and TNFa decreased (-1.2 ng/ml, p=0.003; -2.1 mg/l, p=0.003; -2.4 pg/ml, p<0.001; and -2.4 pg/ml, p=0.001, respectively) and resistin increased (+2.4 ng/ml, p<0.001). In Group 2, hsCRP and IL-6 decreased (-2.0 mg/l, p=0.009 and -2.6 pg/ml, p=0.001) but TNFa increased (+0.2 pg/ml, p=0.02). In Group 3, resistin increased (+3.5 ng/ml, p<0.001) but hsCRP, IL-6, and TNFa decreased (-2.0 mg/l, p=0.009; -2.5 pg/ml, p<0.001; and -4.1 pg/ml, p<0.001). Adiponectin, hsCRP, and physical exercise correlated significantly to subjects’ dietary adherence. Conclusion. Weight loss reduces inflammatory biomarkers in the MHO but induces a deterioration in the adipokine profile, which does not improve with diet and exercise intervention. These findings allow us to clarify mechanisms behind inflammation and metabolic disorder genesis so as to prevent development of obesity-associated comorbidities.

High-dose lidocaine does not affect defibrillation efficacy: implications for defibrillation mechanisms

1998 ◽  
Vol 274 (4) ◽  
pp. H1113-H1120 ◽  
Author(s):  
Michael R. Ujhelyi ◽  
J. Jason Sims ◽  
Allison Winecoff Miller
Keyword(s):  
Ventricular Fibrillation ◽  
Cycle Length ◽  
Low Dose ◽  
High Dose ◽  
Channel Blockade ◽  
Group 3 ◽  
Baseline Values ◽  
Group 2 ◽  
Very High ◽  
Group 1

This study assessed the effect of low (10 mg ⋅ kg−1 ⋅ h−1) and very high (18 mg ⋅ kg−1 ⋅ h−1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 ( n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 ( n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% ( P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values ( P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 ± 2.7 to 12.9 ± 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation ( P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values. However, there is a possibility that an unidentified action of lidocaine is responsible for these effects.

Evaluation of the Impact of Three Different Pre-Transplant Strategies On the Outcome of Myeloma Patients Candidates to High-Dose Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1223-1223
Author(s):  
Alessandro Corso ◽  
Silvia Mangiacavalli ◽  
Luciana Barbarano ◽  
Annalisa Citro ◽  
Paola Brasca ◽  
...  
Keyword(s):  
Patient Flow ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Oral Dexamethasone ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p<0.00001). The number of responsive pts progressively increased from 87% after Vel-Dex (CR 31%), to 96% after transplant (CR 38%). Response rates of group 1 and 2 patients were not significantly different either after induction (p=0.6), after DCEP (p=0.5), and after Tx (p=0.65). On intention to treat basis, vel-dex induction produced a better, although not significant, PFS (34.6 months vs 29 in group 1 and 26.8 in group 2, p=0.56). OS were not statistically different among the three groups, event though the different follow-up could affect the analysis (median OS 110 in group 1, 66 months in group 2, and not reached in group 3, p=0.37). In multivariate analysis PFS was improved only by the achievement of CR (p=0.001). No significant difference was observed between VGPR or PR (p=0.43). Conclusion In this study, only CR not VGPR impacts on the outcome. Vel-Dex producing a significant high CR rate after TX (38%), seems to improve survival of MM patients candidate to high-dose therapy with respect to conventional pre-transplant strategies. Disclosures Morra: Roche:.

scholarly journals High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 610-616 ◽  
Author(s):  
MR Bishop ◽  
JR Anderson ◽  
JD Jackson ◽  
PJ Bierman ◽  
EC Reed ◽  
...  
Keyword(s):  
High Dose Chemotherapy ◽  
High Dose ◽  
Continuous Intravenous Infusion ◽  
Colony Stimulating Factor ◽  
Group 3 ◽  
Macrophage Colony Stimulating Factor ◽  
Group 2 ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Group 1

Between June 1989 and June 1992, 144 patients participated in sequential clinical trials using peripheral blood progenitor cells (PBC) as their sole source of hematopoietic rescue following high-dose chemotherapy. All patients had received prior extensive combination chemotherapy and had marrow defects that precluded autologous bone marrow transplantation (ABMT). PBC were collected according to a single apheresis protocol. The initial 86 patients (group 1) had PBC collected without mobilization. Beginning in April 1991, PBC were mobilized solely with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Thirty-four patients (group 2) received rHuGM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion, and 24 patients (group 3) received rHuGM-CSF at a dose of 250 micrograms/m2/d by continuous intravenous infusion. Patients underwent at least six aphereses and had a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg collected. Cytokines were not routinely administered immediately after transplantation. A median of nine aphereses were required to collect PBC in group 1 and seven aphereses for groups 2 and 3 (P = .03). The time required to recover 0.5 x 10(9)/L granulocytes after transplant was significantly shorter (P = .0004) for the mobilized groups; the median time to recovery was 26 days for group 1, 23 days for group 2, and 18 days for group 3. Transplantation of PBC mobilized with rHuGM-CSF resulted in a shorter time to platelet (P = .04) and red blood cell (P = .01) transfusion independence. Mobilization with rHuGM-CSF alone resulted in efficient collection of PBC, that provided rapid and sustained restoration of hematopoietic function following high-dose chemotherapy. Mobilization of PBC with rHuGM-CSF alone is an effective method for patients who have received prior chemotherapy and have bone marrow abnormalities.

scholarly journals Effects of Aqueous Colocasia esculenta Extracts on Selected Biochemical Parameters in Phenyl Hydrazine Induced Male Anemic Albino Rats

2020 ◽  
pp. 13-23
Author(s):  
Adekunle Abiodun Ayoade ◽  
Adedayo Emmanuel Ogunware ◽  
Ifeoluwa Israel Odekunle ◽  
Pelumi Abimbola Adedigba
Keyword(s):  
Plant Extract ◽  
Total Protein ◽  
Low Dose ◽  
Colocasia Esculenta ◽  
High Dose ◽  
Phenyl Hydrazine ◽  
Group 3 ◽  
Group 2 ◽  
Protein Serum ◽  
Group 1

Aims: In this study, the effect of Colocasia esculenta a hematinic plant on biochemical parameters levels (Direct, Total and unconjugated bilirubin, creatinine, total protein, serum albumin and urea) was assessed to determine if the plant extract can reverse the abnormality in the values of these parameter. Methodology: The experimental animals were divided into four groups as follows; group 1(non-anemic control), group 2 (anemic untreated), group 3 (anemic treated with low dose of plant extract 100 mg/ml), group 4 (anemic treated with high dose of plant extract 500 mg/ml). Anemia was induced in group 1, group 2 and group 3 with 60 mg/kg of phenyl hydrazine for 2 days. After induction of anemia group 2 and group 3 was treated with 100 mg/kg and 500 mg/kg of plant extract for 7 days. After 7-day blood sample was collected through heart puncture and centrifuged for serum. Then, Bilirubin, creatinine, total protein, serum albumin and urea test were carried out. Results: The anemic untreated group had the highest bilirubin, creatinine and urea value of 1.3 mg/dl, 3.97 mg/dl and 71.78 g/l respectively compared to the non-anemic control (bilirubin-0.4 mg/dl, creatinine-3.13 mg/dl and urea 60.35 mg/dl), anemic treated with low dose (bilirubin-0.37 mg/dl,creatinine-1.40 mg/dl and urea-41.82), and anemic treated with high dose (bilirubin-0.25 mg/dl, creatinine-0.86 mg/dl, and urea-48.66 mg/dl) with significant increase in phenyl hydrazine value at p<0.05 .The anemic nontreated group experienced a reduced value of total protein and albumin of 49.78 g/l and 24.46 g/l respectively compared to the non-anemic control (total protein-66.2 g/l and albumin-37.67 g/l) ,anemic treated with low dose (total protein-67.5 g/l and albumin-19.2 g/l), and anemic treated with high dose (total protein-21.9 g/l and albumin-81.6 g/l). Conclusion: The obtained results from this study revealed the anti-anemia potentials of aqueous extracts of Colocasia esculenta.

scholarly journals The combination of microfracture with induction of Wnt / β- Catenin pathway, leads to enhanced cartilage regeneration

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Nikitas P. Schizas ◽  
Olga Savvidou ◽  
Kalliopi Diamantopoulou ◽  
Stamatios Papadakis ◽  
Panayiotis J. Papagelopoulos ◽  
...  
Keyword(s):  
Drinking Water ◽  
Glycogen Synthase ◽  
Rabbit Model ◽  
Lithium Carbonate ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Post Surgery ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Introduction Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/β-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-β (Gsk3-β) and therefore induces Wnt/β-catenin signaling. Materials and methods Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted. Results Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six. Conclusion The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model.

WT1 Levels At Diagnosis and POST-Induction Provide Prognostic Information in Adult De Novo AML. Results From the Spanish Cetlam Group.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2524-2524
Author(s):  
Josep F Nomdedeu ◽  
Montserrat Hoyos ◽  
Maite Carricondo ◽  
Elena Bussaglia ◽  
Camino Estivill ◽  
...  
Keyword(s):  
Bone Marrow ◽  
De Novo ◽  
High Dose ◽  
Prognostic Impact ◽  
Post Induction ◽  
Group 3 ◽  
Group 2 ◽  
De Novo Aml ◽  
Intermediate Dose ◽  
Group 1

Abstract Abstract 2524 WT1 monitoring is an almost universal target to follow de novo AML. Its exppression in myeloid malignancies is upregulated in parallel to the blast percentage. Recently, WT1 determination has been standardized as result of an European Leukemia Net initiative. Early reports have demonstrated that the best results are obtained when peripheral blood is used to establish clinical predictions. Pediatric studies in AML have shown that raised WT1 levels after induction associate with unfavourable outcome. Despite all the mentioned, WT1 quantitation has not yet gained widespread use, in part because some AML show normal WT1 levels at diagnosis. To investigate the prognostic impact of the normalized bone marrow WT1 levels at diagnosis and post-induction in a consecutive series of de novo AML patients enrolled in the CETLAM group trials. Available bone marrow samples at diagnosis (586 cases) and post induction (367 cases) were obtained in each participating center and sent to the CETLAM repository center at the Hospital de la Santa Creu i Sant Pau for complete immunophenotype and molecular analyses. One μg of RNA was reverse transcribed to cDNA in a total reaction volume of 20μl containing Cl2Mg 5mM, 10× Buffer, DTT 10mM, dNTP's 10mM each, random hexamers 15μM, RNAsin 20 units (Promega) and 200 units of MMLV enzyme. WT1 expression levels were determined by real-time quantitative polymerase chain reaction (RQ-PCR) in an ABI PRISM 7700® Genetic Analyzer (Applied Biosystems, Foster City, CA) using the primers and conditions described by the ELN group (Cilloni et al J. Clin. Oncol 2009;27:5195-201). For WT1 copy number titration, the IPSOGEN® (Marseille, France) plasmid was employed. Results were expressed as copies and four normal bone marrow samples were used as test controls. Patients were treated between 2004 and 2011 according to the CETLAM03 protocol. Adults up to 70 years of age received induction chemotherapy with idarubicin, intermediate-dose cytarabine and etoposide, followed by consolidation with mitoxantrone and intermediate-dose ara-C. Subsequently, patients with favourable cytogenetics at diagnosis received one cycle of high-dose cytarabine.G-CSF priming during induction and consolidation was used. Patients with favorable cytogenetics and high leukocyte counts at diagnosis were treated with autologous transplantation instead of high-dose cytarabine. Furthermore, patients with a normal karyotype but an adverse molecular profile (FLT3 mutations or MLL rearrangements) were allocated to the treatment for unfavorable cases; this included allogeneic transplantation from an HLA-identical donor. Overall survival (OS) was measured from the date of enrolment until the date of death. Leukemia-free survival (LFS) for patients who achieved a CR was calculated from the date of CR to relapse or death. OS and LFS were plotted by the Kaplan-Meier method; differences between curves were analyzed by the log-rank test. The probability of relapse was calculated using cumulative incidence estimates and taking into account the competing risk of death in remission. A WT1 cut-off value of 5065.2 copies at diagnosis was obtained. Two hundred and four samples had WT1 levels greater than this value, whereas 382 samples showed levels below this cut-off. These groups had statistically different OS 55±3 vs 33±5 p<0.001, LFS 52±3 vs 30±6 p:0.004 and CIR 34±3 vs 56±6 p<0.001. As regards the post-induction results, four groups were established: Group 0 (135 patients) with WT1 levels between 0 and 17.5 copies, Group 1 (107 patients) with WT1 values ranging from 17.6 to 76 copies, Group 2 (54 patients) with WT1 between 76.1 and 170.5 copies and Group 3 (71 patients) with WT1 levels after induction greater than>170.6 copies. These groups showed statistically significant differences(p<0.001) in terms of OS: Group 0 59±4 months, Group 1 50±5 months, Group 2 45±7 months and Group 3 23±6 months. LFS was also statiscally different: Group 0: 58±4, Group 1: 46±5, Group 2: 39±8 and Group 3:19±8 (all p<0.001). Lastlly, CIR was markedly different between the four groups: Group 0:25±4, Group 1: 44±5, Group 2: 46±8 and Group 3: 68±8(p<0.001) . WT1 quantitation at diagnosis and post-induction provide a simple and well standardized measurement of the prognostic risk of adult AML patiens. Larger series need to be analyzed to ascertain whether this determination could be incorporated to initial AML risk stratification. Disclosures: No relevant conflicts of interest to declare.

Effect of intracisternal antithrombin III on subarachnoid hemorrhage-induced arterial narrowing

1989 ◽  
Vol 70 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Dennis G. Vollmer ◽  
Kazuhiro Hongo ◽  
Neal F. Kassell ◽  
Hisayuki Ogawa ◽  
Tetsuya Tsukahara ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Antithrombin Iii ◽  
White Male ◽  
Rabbit Model ◽  
Content Type ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

✓ The ability of antithrombin III, an endogenous plasma glycoprotein, to reverse the arterial narrowing in a rabbit model of cerebral vasospasm was evaluated. The vasodilator activity of antithrombin III on rabbit arteries was first assessed in vitro using a myograph-arterial ring preparation. Antithrombin III (10 IU/ml) induced a 55.4% ± 2.66% (mean ± standard error of the mean) relaxation in basilar artery precontracted with serotonin (5-HT) in five specimens as compared with a 9.8% ± 1.6% relaxation of common carotid artery in six specimens. For in vivo analysis, 21 New Zealand White male rabbits were separated into three groups: Group 1 served as normal controls; Group 2 received a subarachnoid blood injection (SAH) and were sacrificed on Day 3 thereafter; and Group 3 animals were subjected to SAH, then received a 2-hour intracisternal infusion of antithrombin III (100 IU) in saline prior to sacrifice on Day 3. Basilar artery caliber was determined using a morphometric method to analyze perfusion-fixed arterial segments. Control basilar artery diameter in Group 1 was 0.64 ± 0.02 mm. In Group 2 a 27% reduction in arterial caliber to 0.47 ± 0.03 mm was observed by Day 3 post SAH (p < 0.0001). Group 3 animals had a mean basilar artery diameter of 0.68 ± 0.02 mm. This was significantly larger than the untreated SAH rabbits in Group 2 (p < 0.0001), but not different from control artery diameters in Group 1. The findings demonstrate that antithrombin III in saline has a significant ability to reverse delayed narrowing of the rabbit basilar artery after SAH.

P823Clinical benefits of high dose statins according to the atherothrombotic risk stratification after acute myocardial infarction. The FAST-MI registries

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Puymirat ◽  
V Tea ◽  
F Schiele ◽  
C Baixas ◽  
X Lamit ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Risk Stratification ◽  
High Dose ◽  
Intermediate Risk ◽  
Group 3 ◽  
Baseline Characteristics ◽  
Group 2 ◽  
Group 1

Abstract Background High dose statins prescription are strongly recommended in patients after acute myocardial infarction (AMI) in current guidelines. Aim We aimed to assess the clinical impact on major cardiovascular events (MACE) of high dose statins prescription at discharge according to the atherothrombotic risk stratification in a routine-practice population of AMI patients, and to determine the relative efficacy of currently recommended high dose statins according to risk level. Methods We used data from the 2005, and 2010 FAST-MI nationwide registries, including 7,839 patients with AMI (54% STEMI) admitted to cardiac intensive care units in France. Atherothrombotic risk stratification was performed using the TIMI Risk Score for Secondary Prevention (TRS-2P). Patients were defined in 3 categories: Group 1 (Low-risk; TRS-2P=0/1); Group 2 (Intermediate-risk; TRS-2P=2); and, Group 3 (High-risk; TRS-2P≥3). Baseline characteristics and the rate of MACE (defined as death, stroke or re-MI) at 5-years were analyzed according to TRS-2P categories, and the impact of high dose statins (i.e. atorvastatin 80mg/day or rosuvastatin 20mg/day) at discharge was compared using Cox multivariate analysis among the different risk groups. Results A total of 7,348 patients discharge alive and in whom TRS-2P was available. Prevalence of Groups 1, 2, and Group 3 was 41.5%, 25% and 33.5% respectively. Over the 5-year period, the overall risk of patients admitted for AMI decreased in Group 3 from 41% to 27% (P<0.001). Optimal medical therapy at discharge (defined by the use of dual antiplatelets therapy, statins for all; and, beta-blocker, ACE-I or ARB when appropriate) was 53% in Group 3, 67% in Group 2, and 80% in Group 1 (P<0.001). High dose statins prescription at discharge was 18.5% (Group 3), 31.3% (Group 2), and 41.3%% (Group 1). High dose statins prescription was associated with lower MACE at five-year in the overall population compared to patients with intermediate/low dose statins or without statin prescription (14.3% vs. 29.6%; Δ absolute risk= 15.3%; HR adjusted on baseline characteristics and management: 0.86, 0.76–0.97, P=0.018). The decrease in MACE at five-year was observed in all TRS-2P categories (Group 1: 8.1% vs. 10.7%, Δ= 2.6%; Group 2: 14.8% vs. 21.6%, Δ= 6.8%; Group 3: 30.8% vs. 51.6%, Δ= 20.8%). Finally, the benefits of high dose statins in low- and intermediate-risk was lower (HR=0.97; 95% CI, 0.74–1.26; P=0.81 and HR=1.06; 95% CI, 0.81–1.38; P=0.81) compared to high-risk patients (HR=0.78; 95% CI, 0.65–0.94; P=0.008). Five-year events-free survival Conclusions High dose statins prescription at discharge after AMI was associated with lower MACE at five-year regardless of the atherothrombotic risk stratification, although the highest absolute reduction was found in the high risk TRS2P class. Acknowledgement/Funding The FAST-MI 2010 registry is a registry of the French Society of Cardiology, supported by unrestricted grants from: Merck, the Eli-Lilly-Daiichi-Sanky

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