Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Association between Vitamin D and Dental Caries in a Sample of Canadian and American Preschool-Aged Children

Background: Inadequate vitamin D levels may increase the risk of caries during childhood. The purpose of this study was to investigate the association between 25-hydroxyvitamin D (25(OH)D) status and severe early childhood caries (S-ECC) in preschool children. Methods: Data were obtained from children <72 months of age in two case–control studies in Winnipeg, Manitoba and Richmond, Virginia. Serum analysis assessed 25(OH)D, calcium and parathyroid concentrations. Data on demographics, dental history and oral hygiene were obtained via questionnaires. Bivariate and multiple logistic regression analyses were performed to assess the relationships between demographic and biological variables and S-ECC. A p-value of ≤0.05 was significant. Results: Data were available for 200 children with S-ECC and 144 caries-free controls. Children with S-ECC had significantly lower 25(OH)D levels than those who were caries-free (p < 0.001), and children with deficient 25(OH)D levels were 10 times more likely to have S-ECC (p < 0.001). Multiple logistic regression revealed that having higher 25(OH)D and calcium concentrations (p = 0.019 and p < 0.0001, respectively), as well as being breastfed in infancy (p < 0.001), were significantly and independently associated with lower odds of S-ECC, while dental insurance (p = 0.006) was associated with higher odds of S-ECC. Conclusions: This study provides additional evidence of an association between nutritional status, specifically vitamin D and calcium levels, and S-ECC

Association between Downstream Taste Signaling Genes, Oral Microbiome, and Severe Early Childhood Caries

Polymorphisms in taste receptor genes have been shown to play a role in early childhood caries (ECC), a multifactorial, biofilm-mediated disease. This study aimed to evaluate associations between severe-ECC (S-ECC), the oral microbiome, and variants in genes that encode components of the G protein-coupled receptor (GPCR) signaling cascade involved in taste sensation. A total of 176 children (88 caries-free; 88 with S-ECC) were recruited. Analyses of 16S and ITS1 rRNA microbial genes and seven (GNAQ, GNAS, GNAT3, GNAI2, RAC1, RALB, and PLCB2) human genes were pursued using next-generation sequencing. Regression analyses were performed to evaluate associations between genetic variants, S-ECC, and the supragingival plaque microbiome. Results suggest that PLCB2 rs2305645 (T), rs1869901 (G), and rs2305649 (G) alleles had a protective effect on S-ECC (rs2305645, odds ratio (OR) = 0.27 (95% confidence interval (CI): 0.14–0.51); rs1869901, OR = 0.34 (95% CI: 0.20–0.58); and rs2305649, OR = 0.43 (95% CI: 0.26–0.71)). Variants in GNAQ, GNAS, GNAT3, PLCB2, RALB, and RAC1 were associated with oral fungal and bacterial community composition. This study revealed that three loci at PLCB2 are significantly associated with S-ECC. Variants in multiple genes were associated with the composition of dental biofilm. These findings contribute to the current knowledge about the role of genetics in S-ECC

A systematic correlation of morphology and function using spectral domain optical coherence tomography and microperimetry in patients with geographic atrophy

This study has been designed to describe the functional impact of distinct pathologies within the retinal layers in patients with geographic atrophy (GA) by means of a point-to-point correlation between optical coherence tomography (OCT) and microperimetry. METHODS: Retinal morphology and function of 23 patients suffering from GA of the retinal pigment epithelium (RPE) have been investigated using the Spectralis OCT (Heidelberg Engineering) and the MP1 microperimeter (Nidek Technologies). The point-to-point overlay of morphology and function has been done using proprietary software, allowing OCT image grading to define distinct alterations of the neurosensory retina, the RPE and the choroid. By overlaying the retinal sensitivity map on the OCT data set, retinal layer alterations could be evaluated regarding their impact on visual function. RESULTS: A total of 1005 stimulation points in the lesion area in 2107 spectral domain OCT B-scans were graded in 43 eyes of 23 patients (mean best corrected visual acuity=20/70). Retinal sensitivity decreases with an increasing number of morphological alterations graded (p<10(-13)). Alterations of the RPE and the external limiting membrane (p<0.02) were associated with absolute scotomas. Furthermore, the loss of the external limiting membrane as the largest area of morphological alteration among our patients with GA (mean area=5.65 mm(2)), had a significant impact (p<10(-4)) on sensitivity (-1.3 dB). CONCLUSIONS: Mapping retinal sensitivity to distinct retinal pathologies revealed outer retinal layers, in addition to the RPE, as significant for sensitivity loss. Therefore in GA the RPE loss and the alteration of outer retinal layers should be analysed, which could also provide insight into lesion progression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions