Outcome of Older AML Patients with Adverse Cytogenetics, Including Single or Multiple Monosomies, Treated with the DNA Hypomethylating Agent Decitabine

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2609-2609
Author(s):  
Michael Lübbert ◽  
Claudia Schmoor ◽  
Anne Hagemeijer ◽  
Björn Hackanson ◽  
Rainer Claus ◽  
...  
Keyword(s):  
Chromosomal Abnormalities ◽  
Performance Status ◽  
Normal Karyotype ◽  
Risk Groups ◽  
Best Supportive Care ◽  
Control Group ◽  
Monosomy 7 ◽  
Cell Counts ◽  
Treatment Naïve ◽  
White Blood Cell Counts

Abstract Abstract 2609 Background: The monosomal karyotype (MK+) has recently been identified as the single most adverse cytogenetic prognosticator of AML outcome (1, 2). We made the recurrent - and seemingly paradoxical - observation that MDS/AML patients (pts) with complex karyotypes (CK+) including monosomy 7 showed encouraging responses to decitabine (DAC, ref.s 3, 4). We now evaluated a large cohort of AML pts >60 years ineligible for induction chemotherapy treated on a single phase II multicenter DAC study (trial 00331) for the effect of the MK+ genotype upon outcome. Methods: Comparisons of response rate (RR), i.e. attainment of complete and partial remissions (CR/PR) and overall survival (OS) were performed in 179 treatment-naive AML pts with available cytogenetics (median age 72 years) treated with DAC as described (ref. 3, given over 72 hours, every 6 weeks), for up to 4 courses, followed by “maintenance” with 3 daily 1-hour infusions of DAC 20 mg/m2 every 4–6-weeks. Median white blood cell counts prior to treatment was 7.500/μl (range 0.5–241,000), 79% had a performance status ECOG >1. Cytogenetic risk groups are shown in Table 1. All karyotypes were centrally reviewed and scored for MK (A.H.). Analyses were adjusted for the parameters which had a strong effect on outcome in multivariate analyses of RR and OS, i.e., performance status (on RR and OS) and platelet counts (on OS). Results: By the established definition of MK+, i.e either 1 autosomal monosomy and at least one structural change (MK1) or 2 or more autosomal monosomies (MK2), 39/179 patients were scored as MK+, with chromosomes 7 (n=17), 17 (n=17), and 5 (n=8) being most frequently lost. 17 pts had a single monosomy, as part of a median of 5 abnormalities (range, 2–21), 22 pts had multiple monosomies (median 3, range 2–11), as part of a median of 9.5 abnormalities (range, 4–17). As shown in Table 1, abnormal cytogenetics (AA) were associated with a lower RR and OS compared to pts with normal karyotype. When analyzing pts with AA (n=123) according to the presence (n=39) or absence of MK+ (n=84), MK+ patients had a higher RR than MK-, irrespective of a CK+ genotype. Since it has been shown by several groups that multiple monosomies may herald an even worse prognosis of AML than single monosomy, it was notable that pts with multiple monosomies (MK2, n=22) had a 45% RR and 25% 1-year OS (Fig. 1) compared with 24% and 12% in those with a single monosomy (MK1, n=17), both comparisons p=0.11. Conclusions: Patients with normal-karyotype AML had a better outcome with DAC treatment than those with chromosomal abnormalities. Patients with single or even multiple monosomies still appeared to respond to this treatment, supporting our previous, surprising observation that pts with highly complex karyotype including monosomies may benefit from DAC. Because of a lack of control group in our trial, it is difficult to hypothesize if this encouraging result may be related to modes of action of DAC which differ from low-dose chemotherapy, e.g., with cytarabine. The role of MK will be further studied prospectively in a randomized clinical trial in the same patient population (NCT00867672), and retrospectively in a randomized trial of higher-risk MDS patients treated with either DAC or Best Supportive Care (EORTC 06011). Disclosures: Off Label Use: Decitabine is approved for treatment of different types of MDS, in the present study its activity in AML of older patients was studied. Germing:Celgene: Consultancy, Research Funding.

scholarly journals Prevalence of Chromosomal Abnormalities in Infertile Couples in Romania

2015 ◽  
Vol 18 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Dana Mierla ◽  
M. Malageanu ◽  
R. Tulin ◽  
D. Albu
Keyword(s):  
Retrospective Study ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Control Group ◽  
Chromosomal Anomalies ◽  
Exact Test ◽  
Infertile Women ◽  
Infertile Men ◽  
Significant Statistical Association

AbstractThe purpose of this study was to establish a correlation between the presence of chromosomal abnormalities in one of the partners and infertility. This retrospective study was performed at the Department of Reproductive Medicine, Life Memorial Hospital, Bucharest, Romania, between August 2007 to December 2011. Two thousand, one hundred and ninety-five patients with reproductive problems were investigated, and the frequency of chromosomal abnormalities was calculated. The control group consisting of 87 fertile persons who had two or more children, was investigated in this retrospective study. All the patients of this study were investigated by cytogenetic techniques and the results of the two groups were compared by a two-tailed Fisher’s exact test. In this study, 94.99% patients had a normal karyotype and 5.01% had chromosomal abnormalities (numerical and structural chromosomal abnormalities). In the study group, numerical chromosomal abnormalities were detected in 1.14% of infertile men and 0.62% of infertile women, and structural chromosomal abnormalities were detected in 1.38% of infertile men and 1.87% of infertile women, respectively. The correlation between the incidence of chromosomal anomalies in the two sexes in couple with reproductive problems was not statistically significant. Recently, a possible association between infertility and chromosomal abnormalities with a significant statistical association has been reported. Our study shows that there is no association between chromosomal abnormalities and infertility, but this study needs to be confirmed with further investigations and a larger control group to establish the role of chromosomal abnormalities in the etiology of infertility.

scholarly journals Nonclonal chromosomal alterations and poor survival in cytopenic patients without hematological malignancies

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Osamu Imataki ◽  
Hiroyuki Kubo ◽  
Akihiro Takeuchi ◽  
Makiko Uemura ◽  
Norimitsu Kadowaki
Keyword(s):  
Single Cell ◽  
Chromosomal Aberration ◽  
Hematological Malignancies ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Aspiration ◽  
Normal Karyotype ◽  
Rank Test ◽  
Control Group ◽  
Chromosomal Alterations

Abstract Background Clonal chromosomal alterations (CCAs) reflect recurrent genetic changes derived from a single evolving clone, whereas nonclonal chromosomal alterations (NCCAs) comprise a single or nonrecurrent chromosomal abnormality. CCAs and NCCAs in hematopoietic cells have been partially investigated in cytopenic patients without hematological malignancies. Methods This single-center retrospective study included 253 consecutive patients who underwent bone marrow aspiration to determine the cause of cytopenia between 2012 and 2015. Patients with hematological malignancies were excluded. CCA was defined as a chromosomal aberration detected in more than two cells, and NCCA was defined as a chromosomal aberration detected in a single cell. Results The median age of the patients was 66 years. There were 135 patients without hematological malignancies (median age, 64 years; 69 females); of these, 27 patients (median age, 69 years; 8 females) harbored chromosomal abnormalities. CCAs were detected in 14 patients; the most common CCA was −Y in eight patients, followed by inv.(9) in three patients and mar1+, inv. (12), and t (19;21) in one patient each. NCCAs were detected in 13 patients; the most frequent NCCA was +Y in four patients, followed by del (20), + 8, inv. (2), − 8, and add (6) in one patient each. Moreover, nonclonal translocation abnormalities, including t (9;14), t (14;16), and t (13;21), were observed in three patients. One patient had a complex karyotype in a single cell. The remaining 106 patients with normal karyotypes comprised the control group (median age, 65 years; range, 1–92 years; 56 females). Further, follow-up analysis revealed that the overall survival of the NCCA group was worse than that of the CCA and the normal karyotype groups (P < 0.0001; log-rank test). The survival of the NCCA-harboring cytopenic patients was worse than that of the CCA-harboring cytopenic patients without hematological malignancies, suggesting that follow-up should be considered for both CCA- and NCCA-harboring cytopenic patients.

A Retrospective Comparison of Matched Elderly Patients Treated with Laromustine (Cloretazine®) or Best Supportive Care or Low Dose Ara-C in the LRF AML14 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2960-2960 ◽  
Author(s):  
Robert Hills ◽  
Susan O’Brien ◽  
Verena Karsten ◽  
Alan K. Burnett ◽  
Francis Giles
Keyword(s):  
High Risk ◽  
Supportive Care ◽  
Low Dose ◽  
De Novo ◽  
Performance Status ◽  
Single Agent ◽  
Best Supportive Care ◽  
Cell Counts ◽  
Retrospective Comparison ◽  
De Novo Aml

Abstract Background : A substantial proportion of older patients with AML are considered unlikely to benefit from an intensive treatment approach. They often receive either best supportive care (BSC), low dose treatment such as Low Dose Ara-C (LDAC), or clinical trials of novel agents. In one of the few randomised studies where patients were prospectively considered likely to be unfit for intensive therapy, LDAC was superior to BSC with 18% v 1% patients achieving CR. No patients with high risk cytogenetics (Grimwade 1998), achieved CR (Burnett 2007). Laromustine (Cloretazine®) is a novel sulfonylhydrazine alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links. Laromustine has previously shown clinical activity in patients with de novo AML and high risk MDS (Giles et al. JCO 2007). A confirmatory phase II study of single agent laromustine was conducted in previously untreated patients ≥ 60 years old with de novo AML, prospectively considered likely to be unfit for intensive chemotherapy. Patients had at least one poor risk factor, defined by age ≥70, performance status 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Eighty-five patients received induction therapy with 600 mg/m2 laromustine. Second induction cycles were administered in 14 patients after partial response or hematologic improvement. Eighteen patients received at least one consolidation cycle of cytarabine 400 mg/m2/day CIV for 5 days. Methods: A retrospective non-randomised comparison was performed between the 85 patients treated with laromustine, and 121 patients satisfying the same entry criteria, treated in the AML 14 trial with either BSC or LDAC. Outcomes were compared using Mantel-Haenszel and logrank methods for unadjusted comparisons, and regression methods for adjusted analyses. Results : Patients in AML14 were slightly older than those treated with laromustine (median age 75 v 73), and tended to have higher white blood cell counts; by contrast, there were significantly fewer cardiac or respiratory comorbidities reported in the AML14 population. Other important risk factors such as performance status and cytogenetics were similar between the groups. Responses overall (CR/CRp) were seen in 33% (28/85) of patients treated with laromustine, compared with 2% (1/60) and 23% (14/61) in patients treated with BSC and LDAC (p&lt;0.0001, p=0.2, respectively). In particular, 1 patient with −5/del(5q), and 3 patients with −7/del(7q) cytogenetics experienced a CR with laromustine; patients in AML 14 with adverse cytogenetics saw no remissions. Survival was significantly improved in the laromustine group compared to BSC (1 year survival 20% v 8%, unadjusted HR 0.58 [0.40–0.84] p=0.004), and roughly comparable to that of LDAC (1 year survival 20% v 25%, HR 1.04 [0.73–1.49] p=0.8). Analyses adjusted for differences in baseline demographics, and using propensity scores gave consistent figures. Conclusions: Retrospective comparison of unrandomised data has significant limitations even though care has been taken to match for factors known to be predictive for survival. Laromustine was able to achieve a higher CR rate than LDAC or BSC, and produced remissions in groups where no remissions have previously been seen with LDAC or BSC. Laromustine gave significantly better survival than BSC, and demonstrated similar survival to LDAC.

High-Resolution Genomic Arrays Facilitate Detection of Novel Cryptic Chromosomal Lesions in MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 370-370
Author(s):  
Christine L. O’Keefe ◽  
Ramon Tiu ◽  
Lukasz Gondek ◽  
Aaron Viny ◽  
Karl Theil ◽  
...  
Keyword(s):  
High Resolution ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Genomic Analysis ◽  
Normal Karyotype ◽  
Chromosome 7 ◽  
Comparative Genomic ◽  
Stem Loop ◽  
Monosomy 7 ◽  
Normal Cytogenetics

Abstract The evolution of abnormal hematopoietic clones characterized by acquired chromosomal abnormalities is the central event in the pathogenesis of MDS. Defective chromosomes have significant clinical implications in the management of MDS and suggest the presence of an inherent chromosomal instability. As karyotypic lesions are not found in all MDS patients, it is possible that in some the dysplastic clone may evolve without a chromosomal defect or, more likely, the resolution of routine metaphase cytogenetics is not sufficient to detect smaller lesions; in many instances lack of growth precludes the analysis. Array-based comparative genomic hybridization (A-CGH) allows for a high-resolution genomic scan that circumvents some of the limitations associated with the use of conventional cytogenetics. We hypothesized that high-resolution genomic analysis of genetic gains and losses by A-CGH may detect cryptic lesions, particularly in patients with negative/non-informative cytogenetics that may be of clinical/scientific significance. We examined bone marrow cells from 39 MDS patients (18 RA/RARS, 11 RAEB-t, 6 CMML and 4 secondary AML) and 11 controls using a 2632 BAC microarray and CGH. Dye swapping on duplicate arrays assured reproducibility of the CGH results, confirmed globally by a high resolution 50K SNP microarray in 4 patients and by microsatellite analysis in others. By traditional cytogenetics 19 patients had chromosomal lesions, 18 were normal and 2 tests non-informative. When A-CGH was applied, a normal karyotype was found in only 15% of patients in comparison to 46% by metaphase cytogenetics. Of note is that both cases with uninformative cytogenetics showed an abnormal CGH result and in several patients (N=11) with an abnormal karyotype additional lesions were found. Karyotypic results were confirmed in 7 cases; discordant analysis may be due to a lower proportion of dysplastic cells in marrow. Irrespective of the genomic area affected, when we studied the raw number of lesions more advanced forms of MDS (RAEB-t/AML) were evenly distributed between patients subdivided on sheer number of lesions (0, 1–17, &gt;17). Many hotspots of genomic instability shared between patients were identified. For example, 1p26.3, 10q26 and 4p16 lesions were found in 2 or more patients. Interestingly, these regions contain genes of potential pathologic significance, including tubulin gamma complex associated protein 2 (TUBGCR2) and histone stem-loop binding protein (SLBP). Cryptic lesions on chromosome 7 (e.g. 7p21, 7q31) were identified in 5 patients with normal cytogenetics. These patients suffered from severe cytopenias, consistent with the prognosis of monosomy 7 and highlighting a consensus defect on chromosome 7. Certain chromosomes were rarely or never affected, implying that a more targeted array might be designed for clinical use. A-CGH Cytogenetics Unsuccessful Normal Abnormal Unsuccessful (N=2) 0 0 2 Normal (N=18) 0 3 15 Abnormal (n=19) 0 3 16 In summary, our study highlights the superior level of resolution of A-CGH as compared to metaphase analysis in the diagnosis of MDS. A prospective analysis is underway to determine the prognostic value of CGH-detected lesions and their pathophysiologic significance.

Acute Erythroid Leukemia (AEL): A Clinical, Morphological, Cytogenetic and Follow-Up Study of 69 Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3271-3271
Author(s):  
Elisa Luño ◽  
Carmen Sanzo ◽  
Francesc Sole ◽  
Mirian Gonzalez ◽  
Isabel Granada ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Abnormalities ◽  
Remission Rate ◽  
Normal Karyotype ◽  
Intensive Chemotherapy ◽  
Old Patients ◽  
Monosomy 7 ◽  
Risk Of Death ◽  
Multilineage Dysplasia ◽  
Risk Of Relapse

Abstract AEL is a uncommon type of acute leukemia. The subjects in this retrospective study were 69 patients diagnosed as having AEL to assess the incidence of different subtypes, detect prognostic factors, and compare there profile with others AML. 63 patients (82,5%) were diagnosed of erythroleukemia (EL) and 7 (17,5%) were pure erythroid leukemia according to WHO classification. 63,6% of EL presented erythroid maturation (immature/mature erythroid ratio &lt;25%), and 36,4% &gt;25%. Three of seven pure erythroid leukemia showed immature erythroid precursors identified by ultrastructural methods, and four had erythroid cells at all maturation stage. 49 (71%) were de novo AEL, only 3 pure erythroid leukemia, 9 (13%) were therapy related, in nine (13%) was preceded by a MDS, and 2 suffer a BC-CML, all of this later, pure erythroid leukemia. The three cases of pure erythroid proliferations with only immature precursors were two Down’s syndrome, both 2 years old, and one BC-CML. The chromosomal abnormalities were classified by SWOG and MRC. BC-CML were excluded from survival analyses. A p value &lt;0.01 was considered significant. There were 38 males and 31 females. The median age was 62 years. The medians hemoglobin 80 g/l; white cell 3,8x109/L; absolute neutrophil 1,0x109/L and platelet 36,0x109/L. Multilineage dysplasia were present in 74,5% (41/55). The overall incidence of chromosomal abnormalities was 79,7%(55/69). 35(50,7%) patients had complex karyotype, 26/49(53,1%) in de novo acute erythroid leukemia. Single abnormalities include 4 monosomy 7, 2 del(5q), two +8, two + 21. 39/64 patients (60,9%) received intensive chemotherapy (9 were consolidated with SCT) and 19/39 (48,7%) achieved CR. Remission rate was 83,3% for normal karyotype and 85,7% and 62,5% for intermediate cytogenetic groups according SWOG (p=0,003) and MCR(p=0,037). The median OS was 4 months with a projected actuarial DFS at 12 months 32,5%. Patients under 40 years (p=0,0001) with normal karyotype (p=0.0003) or intermediate SWOG (p=0.0002) or MRC (p=0.0019) citogenetic groups, who received intensive chemotherapy (p&lt;0.0001) had a longer OS, and younger patients (p=0.0056) with normal karyotype (p=0.0038), or intermediate SWOG (p=0.0006) or MRC (p=0.039) citogenetic groups, consolidated with SCT (p=0.0023) showed the longest DFS. Multivariate analysis showed that only karyotype, is a powerful prognostic indicator both for OS and DFS, besides treatment for OS and age for DFS. The higher risk of relapse is for ≥65 years old patients (OR=2,84) with unknown (OR=7,86) or unfavourable (OR=4,29) SWOG groups and the higher risk of death is for unfavourable (OR=4,33) SWOG groups and those treat with supportive care (OR =3,31). When AEL were compared with a consecutive series of 339 de novo AML, 109 of them ≥ 65 years, and 68 therapy related AML, EL excluded, these series are similar for age and sex but AEL present more frequent multilineage dysplasia (p&lt;0,001), and SWOG or MRC unfavourable citogenetic groups (p&lt;0,001), beside the low remission rate, high risk of relapse and death, was similar at elderly patients AML and therapy related AML.

SNP-a Karyotyping Provides a Clonal Molecular Marker and Is Associated with a High Incidence of Segmental Uniparental Disomy in Patients with CMML

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3657-3657
Author(s):  
Michael McDevitt ◽  
Andrew Jeffrey Dunbar ◽  
Christine O’Keefe ◽  
Hideki Makishima ◽  
Ramon V. Tiu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Chromosomal Abnormalities ◽  
Uniparental Disomy ◽  
Normal Karyotype ◽  
Myeloproliferative Disorders ◽  
Size Exclusion ◽  
Response Monitoring ◽  
Monosomy 7 ◽  
Entire Cohort ◽  
Diagnosis And Prognosis

Abstract Chronic myelomonocytic leukemia (CMML) patients display poor prognosis with median survival of 20 months (range 10–60). The WHO classification recognizes CMML as an overlap syndrome with mixed clinical and histomorphological features of both myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD). The underlying molecular basis for the poor prognosis and clinical and pathological features including the dysplasia and monocytosis are currently unknown. A lack of clonal markers in the majority of patients impedes diagnosis and prognosis assignment, as well as treatment response monitoring. Individual cases are associated with rare (5;12) translocations, RAS mutations, and unbalanced chromosomal changes. Since chromosomal defects have a major impact on the diagnosis and prognosis of myeloid malignancies, it is likely that cytogenetic methods with higher resolution and an ability to detect uniparental disomy (UPD) could explain clinical heterogeneity and point to potential therapeutic targets in CMML. Our study included 101 cases including 70 cases of both CMML1 and 2 and CMML-derived AML. We also studied 31 M4/M5/monocytic subtype AML cases (8 FLT3+) to allow interpretation of the 17 CMML cases that were analyzed at the time of AML transformation. Both 250K and a more sensitive 6.0 SNP-A array were utilized. Copy number variants (CNV) were identified and excluded from analysis by comparison with simultaneous arrays with CD3+ normal T cells from the test individual, or when not available, by comparison of results with published and our extensive internal CNV databases, and experimentally determined size exclusion parameters from over 500 MDS and AML cases run on the same platform. In total, 67/70 patients had samples sent for metaphase cytogenetics (MC) and 45% of these cases had an abnormal karyotype. Expected lesions commonly associated with MDS/CMML, such as +8 (N=4) and −7/del(7q) (N=5) were observed. When SNP-A was applied to the entire cohort, defects found by MC were confirmed. Also, new chromosomal abnormalities were identified for a total detection rate of 55/70 (79%). When patients with CMML-1, CMML-2 vs CMML-derived AML were analyzed for gains, losses and UPD, several results are apparent. First, subcytogenetic loci on the chromosomes affected by large gains (e.g., 8 and 21) and losses (e.g., del7 or del5) were identified in additional patients. Second, cytogenetic amplification (amp) and deletion (del) regions seen by MC were confirmed by SNP-A. Examples of recurrent amplifications and deletions included amp21q21 (N=8), amp8p23.2–q24.3 (N=5), amp13q31.1(N=4), amp20p(N=3), del7q21.1(N=4), del12p12.2(N=4), del7q34(N=3), and del5q(N=3). We found a high prevalence of segmental UPD, not otherwise detectable by MC, occurring in 54 % of primary CMML/CMML-derived AML. Recurrent lesions were identified on chrs. 1(N=3), 2(N=3), 4(N=5), 6(N=3), 7(N=5), 11(N=7), 13(N=3), 14(N=3), and 21(N=4). Fifteen of seventy (21%) had UPD as a sole or isolated abnormality. In 6/7 of the UPD11 cases, this was present as a sole abnormality. In a separate abstract we present 12 UPD11q cases with MDS/MPD-U and sAML; in 7 of these cases inactivating c-Cbl mutations were found. All were associated with CMML cases associated with AML transformation. Overall survival was compared for patients with CMML (WHO 1 and 2), CMML into AML, and M4/M5 with either normal karyotype and normal SNP-A results (no amplifications, deletions, UPD), relative to those with detectable genomic lesions. Outcome was poor for all CMML groups however. In summary, SNP-A-based karyotyping complements MC and allows for precise definition of chromosomal aberrations in patients with CMML, including copy-neutral LOH/UPD. UPD is common in CMML and overlapping regions may point to potential causative genes. The identification of c-Cbl demonstrates the utility of this approach, identifying pathways to explore for therapeutic intervention. Overall, SNP-A reveals evidence for significant cytogenetic and subcytogenetic genomic instability in CMML, perhaps not surprisingly with the known adverse prognosis of this disorder. UPD 7 and UPD 21 abnormalities are particularly interesting based on the frequency of these lesions, and the known association of monosomy 7 with CMML. They may provide markers for diagnosis and response monitoring, as more novel therapeutics are being developed for this poor prognosis disorder.

C677T MTHFR polymorphism of the mother as a possible risk factor for the formation of chromosomal aneuploidy in the fetus

2016 ◽  
pp. 156-158
Author(s):  
N.P. Veropotvelyan ◽  
◽  
Y.S. Pogulyay ◽  
D.A. Nesterchuk ◽  
M.N. Sviridov ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Chromosomal Abnormalities ◽  
Normal Karyotype ◽  
Mthfr C677t ◽  
Control Group ◽  
Mthfr Polymorphism ◽  
C677t Mthfr ◽  
Homozygous Genotype ◽  
Comparison Groups ◽  
Definition Of

The article presents the data of its own investigation to determine the existence of relationship formation chromosomal aberrations in the fetus with the mother’s genotype polymorphism C677T MTHFR. Materials and methods. Two groups were formed: 1 group – of women with chromosomal abnormalities in the fetus (n=131); 2 group the fruits that have been identified with the use of СA prenatal karyotyping (n=110). By way of comparison groups used women with karyotyped fruits without chromosomal abnormalities (n=139). Control group consisted of 114 healthy women who have one or more of a healthy child. In all groups performed the definition of polymorphism C677T MTHFR. Results. The genotype of C/T was significantly (p<0.01) 1.33 times more common in the group of women who had a fetus with normal karyotype and a control group of women, against women who had a fetus with CA. Genotype T/T was significantly 6.3 times (p<0.01) is more common in women selected for the prenatal diagnosis compared with women in the control group. When calculating the odds ratio shows that the risk of having a fetus with signs of chromosomal aberrations increased 7-fold (OR=7.000) in women with genotype T/T 677 MTHFR. Conclusion. Homozygous genotype for the mutant allele of MTHFR C677T T polymorphism in women with a high probability it determines the group at risk of chromosomal abnormalities in the fetus. Key words: folate metabolism, chromosomal abnormalities.

scholarly journals Procalcitonin as a Biomarker in Rhinosinusitis: A Systematic Review

2018 ◽  
Vol 33 (2) ◽  
pp. 103-112 ◽  
Author(s):  
Amanda E. Dilger ◽  
Anju T. Peters ◽  
Richard G. Wunderink ◽  
Bruce K. Tan ◽  
Robert C. Kern ◽  
...  
Keyword(s):  
Antibiotic Prescription ◽  
Data Extraction ◽  
Protein Body ◽  
Group Versus ◽  
Antibiotic Use ◽  
Control Group ◽  
Reactive Protein ◽  
Persistent Symptoms ◽  
Cell Counts ◽  
White Blood Cell Counts

Objectives (1) To describe the existing literature on procalcitonin (PCT) as a biomarker in patients with acute rhinosinusitis (ARS), (2) to analyze outcomes in ARS patients who were treated with PCT-guided therapy versus traditional management, and (3) to compare PCT to other biomarkers used in diagnosis of bacterial ARS. Data Sources: PubMed and Embase. Review Methods: A systematic search in the PubMed and Embase databases was performed to identify studies related to PCT as a biomarker in ARS. After critical appraisal of validity by 2 authors, 6 studies with a total of 313 patients were selected for data extraction and analysis. We identified 2 randomized control trials (RCTs) of PCT-based guidelines for antibiotic management of ARS in outpatient settings and 4 observational studies that compared PCT to other biomarkers in patients with ARS. Results The 2 RCTs demonstrated a reduction (41.6% in 1 study and 71% in the other) in antibiotic prescription rate in the PCT-guided group versus the control group with no change in the number of days with impaired activity due to illness (9.0 vs 9.0 days [ P = .96]; 8.1 vs 8.2 days [95% confidence interval −0.7 to 0.7]), number of days of work missed, and percentage of patients with persistent symptoms at 28 days. In the observational cohort studies, PCT did not consistently correlate with C-reactive protein, body temperature, and/or white blood cell counts. Conclusions The limited existing literature on the role of PCT in diagnosis, management, and prediction of clinical outcomes in ARS suggests that PCT-based guidelines for antibiotic prescription are a safe and effective method of minimizing unnecessary antibiotic use.

Diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess

2018 ◽  
Vol 132 (7) ◽  
pp. 615-618
Author(s):  
Y Nakao ◽  
T Tanigawa ◽  
F Kano ◽  
H Tanaka ◽  
N Katahira ◽  
...  
Keyword(s):  
Mean Platelet Volume ◽  
Laboratory Data ◽  
Peritonsillar Abscess ◽  
Control Group ◽  
Platelet Volume ◽  
Protein Levels ◽  
Cell Counts ◽  
Diagnostic Role ◽  
White Blood Cell Counts

AbstractObjectiveTo assess the diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess.MethodsMean platelet volume and other laboratory data were retrospectively investigated.ResultsMean platelet volume was significantly lower in the tonsillitis group (7.8 per cent ± 0.7 per cent) than in the control group (8.7 per cent ± 0.6 per cent; p < 0.0001), and it was significantly lower in the abscess group (7.5 per cent ± 0.6 per cent) than in the no abscess group (8.0 per cent ± 0.7 per cent; p = 0.0277). White blood cell counts and C-reactive protein levels were not significantly different between patients with an abscess and those without. The mean platelet volume cut-off values for the diagnosis of tonsillitis and peritonsillar abscess were 7.95 fl and 7.75 fl, respectively.ConclusionOur results suggest that a decreased mean platelet volume is associated with the development and severity of tonsillitis. This finding provides useful diagnostic information for physicians treating patients with tonsillitis.

scholarly journals Mean platelet volume in the differential diagnosis of tuberculous and bacterial meningitis

2017 ◽  
Vol 11 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Carlos Rodrigo Camara-Lemarroy ◽  
Guillermo Delgado-Garcia ◽  
Juan Gilberto De la Cruz-Gonzalez ◽  
Hector Jorge Villareal-Velazquez ◽  
Fernando Gongora-Rivera
Keyword(s):  
Differential Diagnosis ◽  
Bacterial Meningitis ◽  
Mean Platelet Volume ◽  
Control Group ◽  
Platelet Volume ◽  
Platelet Counts ◽  
Cell Counts ◽  
Glucose Ratio ◽  
White Blood Cell Counts ◽  
Inflammatory Burden

Introduction: Mean platelet volume (MPV) has been shown to reflect the inflammatory burden in different inflammatory and autoimmune diseases. Our objective was to analyze the MPV in patients with tuberculous (TBM) and bacterial meningitis (BM). Methodology: The demographic and clinical data of 73 consecutive patients that presented with either BM (n = 35) or TBM (n = 38) were retrospectively analyzed, as well as that of 28 age- and sex-matched controls. Results: MPV was 8.78 ± 1.58 fL in patients with BM and 6.42 ± 1.39 fL in the TBM group (p < 0.05). In the control group, MPV was 7.4 ± 0.66 fL, significantly higher and lower when compared with TBM and BM, respectively. MPV was significantly associated with diagnosis (adjusted OR: 5.15, 95% CI: 1.090–23.7; p = 0.03). With the optimal cut-off value of 7.62 fL, MPV had 82% sensibility and 78% specificity for the differential diagnosis of TBM versus BM. Lower platelet counts, higher serum creatinine, higher white blood cell counts, and higher blood-cerebrospinal fluid glucose ratio were also predictive of BM. Conclusions: Platelet counts were lower and MPV was higher in patients with BM compared to patients with TBM.  Platelet indices, available in routine bloodwork, could be useful in the early differential diagnosis of these entities.

Sign in / Sign up

Export Citation Format

Share Document