Molecular Status Evaluation in a Standardized Laboratory in a Cohort of Patients with Chronic Myeloid Leukemia At the Instituto Mexicano Del Seguro Social (IMSS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4452-4452
Author(s):  
Luis A Meillón ◽  
Carolina Sandoval-Sanchez ◽  
Nancy Delgado-Lopez ◽  
Manuel Ayala ◽  
Yolanda Lugo ◽  
...  

Abstract Abstract 4452 Background: Molecular Monitoring of BCR-ABL through standardized qPCR according to the international scale (IS) has been recently included in the follow-up of CML patients treated with tyrosine kinase inhibitors (TKIs) at the IMSS. The Molecular Biology Laboratory of the “Hospital of Specialties” at the “National Medical Center Siglo XXI”, have recently achieved full standardization of the qPCR technique to the international scale (using a conversion factor provided by Adelaide lab). The use of the IS in the molecular monitoring expressed as Bcr-Abl/Abl ratio in percentage is very important, since this is the best way to adopt appropriate strategies with TKI therapy. Objective: To report the evaluation of molecular status of 485 patients with CML attended at the Instituto Mexicano del Seguro Social using the IS in a reference standardized Mexican laboratory. Material and Methods: From August 2011 to May 2012, peripheral blood samples of 485 patients with CML, were sent to our laboratory. We extracted RNA as previously described. A minimum of 5 ml of whole blood was required in order to maximize optimal results. Then we put these results in our database and classified patient samples in five groups according the percentage of Bcr-Abl/Abl in the international scale: The first group were patients with >10% of Bcr-Abl; the second group were patients with >1–10% of Bcr-Abl; the third group were patients with >0.1–1%; the fourth group were patients with ≤0.1% and the fifth group were patients with undetectable Bcr-Abl transcripts. Results: We found the following distribution: Group I (> 10% Bcr-Abl): 91 patients (18.76%); Group II (>1–10% Bcr-Abl): 65 patients (13.4%); Group III (>0.1–1% Bcr-Abl) 83 patients (17.11%); Group IV (≤0.1% Bcr-Abl) 122 patients (25.15%); and Group V: undetectable Bcr-Abl: 124 patients (25.56%). Conclusion: Fifty percent of CML patients treated with nilotinib, imatinib or dasatinib, have reached a deep molecular response, that is, Major Molecular response (MMR) or better. Another 17% has reached a molecular response (>0.1–1%) that is equivalent to Complete Cytogenetic response (CCyR). This information is very useful for clinicians and should be interpreted individually according the lenght of treatment with TKIs, following current CML guidelines and recommendations. Until now, molecular monitoring using the IS was only possible through sending samples to US laboratories. It is important that Mexican clinicians at our institution have now the opportunity to rely on a Mexican validated and standardized laboratory. The results of the molecular response in this cohort of CML patients can be compared to the data of another countries using the IS. Classifying patients according to their molecular status could help to optimized therapies at our institution. Disclosures: Nacho-Vargas: Novartis Oncology: Employment.

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 257-263 ◽  
Author(s):  
Michael W. Deininger

Abstract Monitoring treatment responses in chronic myeloid leukemia (CML) is based on complete blood counts (CBCs) to determine hematologic response, karyotyping of bone marrow metaphase cells to delineate cytogenetic response and quantitative reverse transcription polymerase chain reaction (qPCR) to quantify expression of BCR-ABL1 mRNA (molecular response; MR) in peripheral blood. Fluorescence in situ hybridization (FISH) to identify BCR-ABL1 in interphase nuclei and mutational analysis of the BCR-ABL1 kinase domain (KD) are used in certain clinical circumstances. As most patients treated with tyrosine kinase inhibitors (TKIs) achieve complete cytogenetic responses (CCyRs), qPCR with its increased sensitivity and dynamic range has become the main tool used to monitor CML patients. Landmark analyses of large TKI trials have established MR milestones that identify patients with high risk of failure, are the basis of consensus management guidelines, and have led to a strong push toward qPCR test standardization. Today many laboratories report BCR-ABL1 qPCR results on the international scale (IS), a system based on the conversion of laboratory-specific numerical values to conform to a universal scale. The fact that qPCR is technically demanding and liable to assay variations poses considerable challenges for its routine clinical use. This is important as the prevalence of patients on chronic TKI therapy increases and critical clinical decisions are made based on qPCR results, for example if discontinuation of TKI therapy should be considered. Here we will review the current state of molecular monitoring in CML, focusing on qPCR, the definition of TKI failure and the results of TKI discontinuation studies.


Author(s):  
Anton Bózner ◽  
Mikuláš Gažo ◽  
Jozef Dostál

It is anticipated that Japanese quail /Coturnix coturnix japonica/ will provide animal proteins in long term space flights. Consequently this species of birds is of research interest of international space program INTERCOSMOS. In the year 1987 we reported on an experiment /2/ in which the effect of chronic acceleration of 2 G hypergravitation, the hypodynamy and the simultaneous effect of chronic acceleration and the location in the centre of the turntable of the centrifuge on the protein fractions in skeletal muscles was studied. The ultrastructure of the heart muscle was now in this experiments examined as well.Japanese quail cockerels, aged 48 days were exposed to 2 G hypergravitation /group IV/ in a 6,4 m diameter centrifuge, to hypodynamy /group III/ and their combination /group V/, respectively for 6 days / Fig.1/. The hypodynamy in group III was achieved by suspending the birds in jackets without contact the floor. The group II was located in the centre ofthe turntable of the centrifuge. The control group I. was kept under normal conditions. The quantitative ultrastructure of myocard was evaluated by the methods of Weibel/3/ - this enables to determine the number, relative size and volume of mitochondria volume of single mitochondria, defficiency of mitochondrial cristae and volume of myofibrils.


2006 ◽  
Vol 17 (4) ◽  
pp. 300-305 ◽  
Author(s):  
Sérgio Lima Santiago ◽  
José Carlos Pereira ◽  
Ana Christina Bonato Figueiredo Martineli

This study evaluated the influence of time after application of oxalate solutions in reducing dentin hydraulic conductance. Fifty dentin discs were obtained from extracted human third molars and assigned to 5 groups (n=10), according to the desensitizing agent used: Group I: OxaGel; Group II: experimental agent DD-1: Group III: experimental agent DD-2. In Groups IV and V, a placebo gel and deionized water were used as control, respectively. The agents were applied for 3 min, washed out and the hydraulic conductance was measured immediately and at 5-, 15- and 30-min intervals, and after acid etching. Data were analyzed statistically by two-way ANOVA and Duncan's test at 5% significance level. Groups I, II and III did not differ significantly from each other in any of the time intervals (p>0.05). Likewise, Groups IV and V were statistically similar to each other (p>0.05). The active agents reduced significantly dentin permeability in comparison to control groups (p<0.05). Dentin permeability measured in vitro decreased significantly with time regardless of the agent applied (either active or control agents). The results of Group V, in which no dentin desensitizing agent was employed, indicates that the assessment of dentin permeability by this method must be interpreted with caution.


2021 ◽  
pp. 39-45
Author(s):  
Nura I. Al-Zail ◽  
Salah F. Kamies

Pyrethroid cyhalothrin (PC) is an insecticide that is used worldwide for pest control in agriculture and household use. Samoa extract (SE) is a potent antioxidant protecting cells from oxidative stress. The present study investigates the protective and therapeutic effect of SE on PC-induced changes in sperm quality in male rats. Fifty adult male albino rats were divided into five groups: group I: served as control; group II: received PC i.p. only (6.2 mg/kg b.wt.); group III: received SE only (100 mg/kg b.wt., p.o.) for eight weeks; group IV: received SE as a protective agent daily for eight weeks, then followed by the administration of PC (i.p.) three times a week for two weeks; group V: exposed to PC (i.p.) three times a week for two weeks, then treated with the SE daily for 8 weeks. Results showed that PC caused markedly impaired sperm quality (a count, viability, motility, and abnormality). Compared to PC-treated animals, SE in the protective group markedly restored the alteration of sperm indices. However, SE in the curative group was found to be less effective in restoring PC-induced alterations. In conclusion, the data of this study revealed that the SE as a protective agent is more effective than as a therapeutic agent. Keywords: Samoa; Pyrethroid; Sperm quality; Rat


1994 ◽  
Vol 267 (5) ◽  
pp. F703-F708 ◽  
Author(s):  
M. Giordano ◽  
P. Castellino ◽  
E. L. McConnell ◽  
R. A. DeFronzo

We evaluated the dose-response relationship between the plasma amino acid (AA) concentration and renal hemodynamics in eight normal subjects. After an overnight fast, a balanced 10% AA solution was infused for 180 min at five separate infusion rates: 0.5 (group I), 1.0 (group II), 2.0 (group III), 4.0 (group IV), and 6.0 (group V) ml.kg-1.min-1 on separate days. Basal plasma AA concentration was 1.87 +/- 0.1 mmol/l and increased to 2.26 +/- 0.1 (group I), 2.66 +/- 0.2 (group II), 3.79 +/- 0.5 (group III), 5.81 +/- 0.4 (group IV), and 7.41 +/- 0.4 mmol/l (group V). Basal glomerular filtration rate (GFR) and renal plasma flow (RPF) averaged 95 +/- 4 and 476 +/- 29 ml.1.73 m-2.min-1, respectively, and rose to 98 +/- 5 and 506 +/- 40 (group I) [P = not significant (NS)], 102 +/- 3 and 533 +/- 30 (group II) (P < 0.05 vs. basal), 110 +/- 4 and 567 +/- 29 (group III), 115 +/- 7 and 610 +/- 55 (group IV), and 117 +/- 7 and 614 +/- 66 ml.1.73 m-2.min-1 (group V) (P = NS vs. group IV). Basal plasma glucagon concentration averaged 68 +/- 10 pg/ml and increased to 74 +/- 10 (group I), 83 +/- 11 (group II) (P < 0.05 vs. basal), 100 +/- 14 (group III), 121 +/- 14 (group IV), and 229 +/- 35 pg/ml (group V) (P < 0.01 vs. basal). Increases in plasma growth hormone (GH) and insulin levels were observed only during groups IV and V.(ABSTRACT TRUNCATED AT 250 WORDS)


2017 ◽  
Vol 5 (4(SE)) ◽  
pp. 63-68
Author(s):  
N.T. Lethi ◽  
A.M. Moorthy

The purpose of the study was to investigate the effect of selected yogic practices physical exercises and physiotherapy treatment on sitting of low back pain patients. One hundred low back pain patients are taken from the Thavanur town, Kerala. The age, height and weight of the subjects ranged from 30 to 40 years, 158 to 169 centimetres and 55 to 70 kilograms respectively. The selected subjects were randomly assigned into five equal groups of 20 subjects each. Group I underwent Yogic practices, group II underwent physical exercises, group III underwent physiotherapy treatments, group IV yoga and physiotherapy treatments and group V acted as control.  Prior to and after the training the subjects were tested on sitting of low back pain patients through the Oswestry low back pain disability questionnaire. Analysis of covariance was used to determine the significantly difference existing between pretest and posttest on sitting of low back pain patients. The result of the study proved that due to twelve weeks of the experimental training was reduced back pain while sitting for the low back pain patients.


2020 ◽  
pp. 58-60
Author(s):  
R. Mangala Devi ◽  
R. Sarojini ◽  
S. Vasanth

Background: Depression is a common psychiatric disorder. Drug therapy is the cornerstone in the management of depression. Anti-depressants are associated with many unwanted side-effects. Thus, various herbal products have been tried. The advantages of herbal treatments include safety, cheap and acceptability due to their traditional values. The objective of the present study was to evaluate the anti-depressant activity of Cymbopogon citratus (lemon grass) in albino mice and to compare with Imipramine. Methods: 30 Swiss albino male mice weighing around 25-30 g were divided into 5 groups (n=6). Group I (Control) mice were given normal feed and water, Group II (Standard) received 20 mg/kg T. Imipramine orally, Group III (Test-1) received 5 mg/kg aqueous extract of C. citratus (lemon grass) orally and Group IV (Test-2) received 10 mg/kg C. citratus (lemon grass) orally, and Group V (Test-3) received both T. Imipramine (10 mg/kg) and C. citratus (10 mg/kg) orally. Duration of immobility was observed for last 4 mins of total 6 mins period in groups 1-5 by tail suspension test on 1st, 8th and 15th day.Results: Duration of immobility recorded in seconds was analyzed by one-way analysis of variance, followed by Tukey’s post-hoc test Conclusion: Lemon grass has a significant antidepressant effect. Combined effect of lemon grass at 10 mg/kg and imipramine 10 mg/kg is not synergistic.


2013 ◽  
Vol 59 (2) ◽  
pp. 71-74
Author(s):  
Aliz-Beáta Tunyogi ◽  
I Benedek ◽  
Judit Beáta Köpeczi ◽  
Erzsébet Benedek ◽  
Enikő Kakucs ◽  
...  

Abstract Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder; the molecular hallmark of the disease is the BCR-ABL gene rearrangement, which usually occurs as the result of a reciprocal translocation between chromosomes 9 and 22. Tyrosine kinase inhibitors (TKI) were the first drugs that targeted the constitutively active BCR-ABL kinase and it have become the standard frontline therapy for CML. Monitoring the treatment of CML patients with detection of bcr-abl transcript levels with real time qualitative polymerase chain reaction (RQ-PCR) is essential in evaluating the therapeutic response. Material and method: At the Clinical Hematology and BMT Unit Tîrgu Mureș, between 2008-2011, we performed the molecular monitoring of bcr-abl transcript levels with RQ-PCR in 16 patients diagnosed with CML. Results: We have 11 patients on imatinib treatment who achieved major molecular response. One patient lost the complete molecular response after 5 years of treatment. Two patients in blast crisis underwent allogeneic hematopoietic stem cell transplantation from identical sibling donors. The first patient is in complete molecular remission after 4 years of the transplant with mild chronic GVHD. The other patient had an early relapse with treatment refractory disease and died from evolution of the disease. Three patients with advanced phases of the disease present increasing transcript levels. We performed the dose escalation, and for two of them the switch to the second generation of TKI. Conclusions: Regular molecular monitoring of individual patients with CML is clearly desirable. It allows for a reassessment of the therapeutic strategy in cases of rising levels of BCR-ABL as an early indication of loss of response.


2013 ◽  
Vol 14 (1) ◽  
pp. 56-60 ◽  
Author(s):  
S Nagalaxmi Reddy ◽  
DN Jayashankar ◽  
Mohanthomas Nainan

ABSTRACT Aim Aim of this study was to compare class II composite restoration using flowable composites as lining with various thickness and curing techniques by evaluating cervical marginal microleakage. Materials and methods Fifty intact molars, each prepared with two box-only class II cavities, were randomly divided into five groups: Group I, P60 filling alone; group II, ultrathin flowable composite lining (0.5-1mm) cocured with overlying composite; group III, thin lining (1-1.5) cocured with overlying composite; group IV, ultrathin lining (0.5-1 mm) precured and group V, thin lining (1-1.5) precured. The teeth were then thermocycled for 1500 cycles (between 5 and 60 °C) and immersed in dye for 24 hours. Cervical microleakage was measured as the extent of dye penetration. Results Cocured specimens (groups II and III) showed least microleakage and control specimens (group I) showed maximum microleakage. On comparison of curing techniques, cocured specimens (groups II and III) showed less microleakage than precured (groups IV and V). On comparison of lining thickness and type of curing, group IV showed less microleakage than group V. Groups II and III were statistically not significant. Conclusion It was concluded from the results that ultrathin cocured flowable composite lining specimens improved the marginal sealing with decreased microleakage. Clinical significance In this study, the application of additional flowable composite lining with various thicknesses presented different influences in marginal quality of class II box only composite restorations. A new technique applying an ultrathin flowable composite lining with cocuring technique improved the marginal sealing with decreased microleakage. Restorations with thin lining presented reduced marginal integrity after thermocycling. How to cite this article Reddy SN, Jayashankar DN, Nainan M, Shivanna V. The Effect of Flowable Composite Lining Thickness with Various Curing Techniques on Microleakage in Class II Composite Restorations: An in vitro Study. J Contemp Dent Pract 2013;14(1):56-60.


2013 ◽  
Vol 57 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Dariusz Bednarek ◽  
Katarzyna Dudek ◽  
Krzysztof Kwiatek ◽  
Małgorzata Świątkiewicz ◽  
Sylwester Świątkiewicz ◽  
...  

Abstract The aim of the study was to evaluate the immune effects of genetically modified (GM), insect resistant corn (MON810) expressing toxin protein of Bacillus thuringiensis, and glyphosate-tolerant soybean meal (Roundup Ready MON-40-30-2), which are used as the feed mixture components in domestic animals. The study was conducted on 60 pigs (36 fatteners and 24 sows), 20 calves, 40 broilers, and 40 laying hens. Each species was divided into four basic nutritional groups: group I (control) - conventional feed, group II - feed consisted of GM soybean meal and non-modified corn, group III - non-modified soybean meal and GM corn, group IV - GM soybean meal and GM corn. Moreover, in the experiment on fatteners two additional groups were formed: group V - animals fed both conventional soybean meal and bruised grain, and group VI - GM soybean meal and conventional bruised grain. The results of study did not reveal any significant effect of feed mixtures containing GM components on the immune response in all animals regardless of their species and technological producing groups.


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