Does Glucose Variability Influence the Relationship Between Mean Plasma Glucose and HbA1cHbA_{1c} Levels in Type 1 and Type 2 Diabetic Patients?

Objective: The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between $HbA_{1c}$ and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-$HbA_{1c}$ relationship. Research Design and Methods: Analyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-$HbA_{1c}$ relationship. Results: GV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-$HbA_{1c}$ relationship in type 1 diabetic patients so that high GV led to a higher $HbA_{1c}$ level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the $HbA_{1c}$ level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency. Conclusions: In only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with $HbA_{1c}$. This effect is more pronounced at higher $HbA_{1c}$ levels. However, the impact of GV on the $HbA_{1c}$ level in type 1 diabetes is modest, particularly when $HbA_{1c}$ is close to the treatment target of 7%

Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

<p>Abstract</p> <p>Background</p> <p>The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only.</p> <p>Methods/Design</p> <p>This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis.</p> <p>Discussion</p> <p>This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous parents of affected children compared to the consanguineous parents of healthy children. If our hypothesis proves to be correct, further studies are needed to obtain different risk figure estimates for the different proportions of DNA identical-by-descent. With more precise information about their risk status, empowerment of couples can be improved when making reproductive decisions.</p

Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to harvest these SVF cells and give them back to the patient within a single surgical procedure, thereby avoiding lengthy and costly in vitro culturing steps. However, this requires SVF-isolates to contain sufficient ASCs capable of differentiating into the desired cell lineage. We have investigated whether the yield and function of ASCs are affected by the anatomical sites most frequently used for harvesting adipose tissue: the abdomen and hip/thigh region. The frequency of ASCs in the SVF of adipose tissue from the abdomen and hip/thigh region was determined in limiting dilution and colony-forming unit (CFU) assays. The capacity of these ASCs to differentiate into the chondrogenic and osteogenic pathways was investigated by quantitative real-time polymerase chain reaction and (immuno)histochemistry. A significant difference (P = 0.0009) was seen in ASC frequency but not in the absolute number of nucleated cells between adipose tissue harvested from the abdomen (5.1 ± 1.1%, mean ± SEM) and hip/thigh region (1.2 ± 0.7%). However, within the CFUs derived from both tissues, the frequency of CFUs having osteogenic differentiation potential was the same. When cultured, homogeneous cell populations were obtained with similar growth kinetics and phenotype. No differences were detected in differentiation capacity between ASCs from both tissue-harvesting sites. We conclude that the yield of ASCs, but not the total amount of nucleated cells per volume or the ASC proliferation and differentiation capacities, are dependent on the tissue-harvesting site. The abdomen seems to be preferable to the hip/thigh region for harvesting adipose tissue, in particular when considering SVF cells for stem-cell-based therapies in one-step surgical procedures for skeletal tissue engineering

Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib

Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of CECs in parallel with hematopoietic progenitor cells (HPCs) in the blood of renal cell cancer patients during sunitinib treatment. We analyzed the kinetics of a specific population of small VEGFR2-expressing CECs (CD45(neg)/CD34(bright)), HPCs (CD45(dim)/CD34(bright)), and monocytes in the blood of 24 renal cell cancer (RCC) patients receiving 50 mg/day of the multitargeted VEGF inhibitor sunitinib, on a 4-week-on/2-week-off schedule. Blood was taken before treatment (C1D1), on C1D14, C1D28, and on C2D1 before the start of cycle 2. Also plasma VEGF and erythropoietin (EPO) were determined. Remarkably, while CD34(bright) HPCs and monocytes decreased during treatment, CD34(bright) CECs increased from 69 cells/ml (C1D1) to 180 cells/ml (C1D14; P = 0.001) and remained high on C1D28. All cell populations recovered to near pre-treatment levels on C2D1. Plasma VEGF and EPO levels were increased on C1D14 and partly normalized to pre-treatment levels on C2D1. In conclusion, opposite kinetics of two circulating CD34(bright) cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused by sunitinib targeting of immature tumor vessel

Assessing aspects of auditory handicap by means of pupil dilatation

The demand on extra effort and concentration during listening are notorious handicapping effects of hearing impairment as is shown by self-assessment studies. In an attempt to explore new ways of assessing hearing handicap, the present study focuses on an objective measure of mental effort during listening. Pupil dilatation is used as the index of mental effort. Results for 14 hearing-impaired and 14 normal hearing listeners show a relation between pupil dilatation and difficulty in speech reception in noise, as manipulated by the speech-to-noise ratio. In addition the study shows that, with regard to effort and concentration, hearing-impaired subjects benefit less than normals from easier listening situations (e.g. at 5 dB above the individual speech-reception threshold). The results show a significant correlation between self-rated handicap and pupil dilatation

Evaluation of donor site function and morbidity of the fasciocutaneous radial forearm flap

To assess the results of the use of the free radial forearm flap in terms of objective morbidity and subjective patient response. The donor sites were examined from 37 patients who underwent reconstruction with a free fasciocutaneous radial forearm flap in the head and neck after ablative tumor surgery. Patients were asked to fill in a written questionnaire. The following additional tests were performed: resting skin temperature of digits I and V, temperature after submersion in iced water, grip and pinch tests, and goniometry. Resting skin temperature was slightly decreased for donor hands 0.69 degrees C (P <.001) and 0.31 degrees C (P = .048) for digits I and V, respectively, but recovery after submersion in iced water showed no differences. The strength tests and goniometry revealed no statistically significant findings between donor and control sides. On the questionnaire, 9 patients (24%) reported slightly impaired function, 14 (38%) could not wear their watch or bracelet, 17 (46%) reported numbness, 5 (14%) reported soreness, 5 (14%) reported itching, 6 (16%) reported cold intolerance, 5 (14%) reported bad cosmetic appearance, and 9 (24%) expressed the opinion that they were insufficiently counseled. There is a negligible objective morbidity of a free radial forearm flap harvest procedure, but a number of patients have subjective complaints when asked. Elaborate presurgical counseling can probably reduce these complaint