The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential

Autologous stem cell transplantation (ASCT) is widely used to consolidate first remission in AML. We determined the significance of circulating CD34+ cells at the day of blood stem cell collection in 78 AML patients. Patients mobilizing more than 60,000 CD34+ cells/ml had shorter overall survival (OS; P=0.0274), shorter time to progression (TTP; P=0.0014), and a higher relapse rate (P=0.0177). High levels of CD34+ cells were an independent marker for shorter OS and TTP in a multivariate analysis. These data suggest that ASCT is associated with unfavorable outcome in AML patients with high levels of mobilized peripheral CD34+ cells.     

The prevalence of obesity and its related risk factor in the north of iran in 2006

Background: The main objective of this study was to evaluate the prevalence of the obesity and the related risk factors in the north of Iran. Methods: This was a population-based cross-sectional study that enrolled 2495 subjects (1247 males and 1248 females) using stratified cluster sampling. Interviewers recorded the data using a multidimensional questionnaire including anthropometric indexes. Body mass index equal to or greater than 25 was considered as overweight and that of 30 and 40 as obese and pathologic obese respectively. SPSS 16.0 software was used for statistical data analysis. Results: Mean age of the subjects was 39.2 [95% CI: 38.6, 39.8] yr. Mean body mass index was 25.3 [95% CI: 25.0, 25.6] kg/m(2) for men and 27.5 [95% CI: 27.2, 27.9] kg/m2 for women. The prevalence rates of overweight, obesity and pathologic obesity were 29.9% (745/2495), 22.5% (561/2495) and 1.8% (44/2495) respectively. The prevalence of obesity was higher in urban residents than rural ones, 27.3% versus 18.9% respectively (P<0.001). The prevalence rates of obesity and pathologic obesity were much higher in women than men were, 30.3% versus 15.4% and 3.0% versus 0.6% respectively (P=0.001). The odds ratio estimate was 1.68 [95% CI: 1.40, 2.02] for urban area compared to rural area; 2.60 [95% CI: 2.14, 3.15] for females compared to males; 5.95 [95% CI: 3.54, 9.99] for married people compared to single people; 1.89 [95% CI: 1.44, 2.84] for age group of 55-65 years compared to age group of 15-24 years; 1.76 [95% CI: 1.17, 2.64] for illiterate people compared to those who had academic education; 1.98 [95% CI: 1.13, 2.49] for poor people compared to people with high economic level. Conclusion: The prevalence of obesity and overweight is very high in the north of Iran, hence is a signal of serious health problem, and should be the focus of special attention.     

Simplified MSI marker panel for diagnosis of colorectal cancer

Background: Colorectal cancers (CRCs) tumors are diagnosed by microsatellite instability (MSI) due to accumulation of insertion/deletion mutations in tandem repeats of short DNA motifs (1–6 bp) called microsatellites. Microsatellite instability (MSI) is not only a hallmark marker for screening of hereditary nonpolyposis colorectal cancer (HNPCC), but also a prognostic and predictive marker for sporadic colorectal cancer. Our objective was to determine and study of five mononucleotide microsatellite markers status among Iranian patients with HNPCC and sporadic colorectal cancer. Material and Methods: In the current investigation 80 sporadic CRC and 80 HNPCC patients were evaluated for MSI. The pentaplex panel including 5 quasimonomorphic mononucleotide repeats (NR-21, BAT-26, BAT-25, NR-27 and NR-24) was used. Results: Our findings showed that the NR-21 was the most frequent instable marker among the other markers. 53% and 25.6% specimens had instability in sporadic CRC and HNPCC, respectively. Furthermore, the frequencies of instability BAT-25 was determined in 20% sporadic CRC and 23% HNPCC samples. Interestingly our results demonstrated that the frequency of instability NR-24 was similar 20% sporadic CRC and 20.5% HNPCC. Moreover, percentage of NR-27 in HNPCC was 19.2 and 0% in sporadic CRC. Finally, BAT-26 was instable in 21.8% HNPCC patients while we could find 6.6% instability for BAT-26 in sporadic cases. Conclusion: It seems that among 5 mononucleotides markers NR-21 was the most useful marker for diagnosis HNPCC and sporadic cancer. Following NR-21, BAT-25 and NR-24 are the most reliable markers. Therefore using a triplex panel including 3 aforementioned MSI markers should be more promising markers for identifying MSI status in both patients with HNPCC and/or sporadic colorectal cancer.     

Transfusion efficacy of ABO major-mismatched platelets (PLTs) in children is inferior to that of ABO-identical PLTs

BACKGROUND: ABO major compatibility is essential in transfusions of red blood cells but is not requisite in PLT transfusions. In adults there is some evidence that transfusion efficacy of ABO blood group–identical platelets (PLTs) is superior to major‐mismatched PLTs. However, in children this question has not been investigated for more than 30 years. STUDY DESIGN AND METHODS: In a prospective study, the efficacy (based on the 1‐hour percentage of PLT recovery [PPR_1hr]) of 400 eligible ABO blood group–identical or out‐of‐group apheresis PLT concentrates (APCs), transfused mainly prophylactically to 50 children with hematologic malignancies, solid tumors, or aplastic anemia was investigated. The primary objective was to compare PPR_1hr between ABO‐identical and major‐mismatched transfusions. RESULTS: After ABO major‐mismatched transfusions, PPR_1hr was significantly lower than after ABO blood group–identical transfusions (median 21% vs. 32%; p = 0.034). Multivariate analysis showed major‐mismatched transfusions to be significantly more often unsuccessful than identical transfusions (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.52‐10.39; p = 0.005). Using flow cytometry and fluorescent microscopy, it could be demonstrated that PLTs of subgroup A₁, significantly expressing A antigen on their surface, were rapidly cleared from the circulation of group O or B recipients. In contrast, major‐mismatched transfusions of A₂ PLTs, expressing no detectable A antigen, were as successful as identical transfusions (OR, 1.13; 95% CI, 0.16‐7.88; p = 0.90). CONCLUSION: These data clearly indicate that in children ABO major‐mismatched PLT transfusions result in inferior transfusion efficacy, with the only exception of group A₂ PLTs. ABO minor‐mismatched PLTs showed comparable efficacy to identical transfusions.     

Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin

The objective was to evaluate whether removal of neutralisingantibodies potentially resensitises a secondary non-responder tobotulinum neurotoxin A (BoNT/A). Neutralising antibodies directed against BoNT/A are produced during long term treatment withBoNT/A-hemagglutinin complex in up to 10% of patients with cervicaldystonia. These patients become secondary non-responders. Otherserotypes of BoNT are not yet generally available and may also bear therisk of inducing antibody formation. Plasma exchange (PE) (onetreatment cycle) and immunoadsorption on a protein A column (IA-PA;three treatment cycles) was employed over 15 months to removeneutralising antibodies from a severely disabled secondarynon-responder with cervical dystonia. After plasmaexchange or IA-PA, BoNT/A was reinjected. Antibodies were measured witha sensitive functional toxin neutralising test.
Repeated use of plasma exchange and IA-PA depletedneutralising antibodies to below the detection limit and subsequently allowed successful BoNT/A injection into dystonic muscles. No seriousside effects were found related to the depletion of IgG.
In conclusion PE or IA-PA performed before BoNT/Areadministration may provide an alternative strategy in treatingselected secondary non-responders who are severely disabled.

     

The Factors Affecting Bone Density in Cirrhosis

Background:

Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients.

Objectives:

We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it.

Patients and Methods:

In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant.

Results:

A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m² were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower vitamin D, higher Child score, and less GFRc.

Conclusions:

Abnormal DEXA was highly prevalent among patients with cirrhosis. The risk of this finding was increased by lower vitamin D levels, advanced disease, and impaired renal function.     

A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen

BACKGROUND: The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents. STUDY DESIGN AND METHODS: Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression. RESULTS: RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes. CONCLUSION: Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.