The effect of hydroxyethyl starch 6% 130/0.4 compared with gelatin on microvascular reactivity.

We compared the effects on microvascular reactivity of hydroxyethylstarch (Volulyte(®) ) and gelatin (Geloplasma(®) ) during acute haemodilution. The hypothesis was that Volulyte would provide better microvascular reactivity than Geloplasma. Forty patients undergoing elective cardiac surgery were randomly assigned to receive either Volulyte or Geloplasma as the exclusive priming solution of the cardiopulmonary bypass. To evaluate microvascular reactivity, postocclusive reactive hyperaemia was examined before and after cardiopulmonary bypass. Microvascular reactivity assessments included the rate of the occlusion and reperfusion slopes and reperfusion times. After cardiopulmonary bypass, increases in reperfusion time were significantly smaller in the Volulyte group (3 (-27 to 9 [-35 to 33]%) vs 29 (-17 to 76 [-34 to 137]%) in the Geloplasma group, p = 0.02 between groups). Rate of reperfusion increased in the Volulyte group (26 (-17 to 43 [-59 to 357])%), whereas it decreased in the Geloplasma group (-22 (-47 to 16 [-84 to 113])%), p = 0.02 between groups. The shorter reperfusion times and increased reperfusion rate suggest that Volulyte maintains better microvascular reactivity than Geloplasma.

Involvement of T-cell receptor-beta alterations in the development of otosclerosis linked to OTSC2.

Otosclerosis is a common form of hearing loss, characterized by disordered bone remodeling in the otic capsule. Within the otosclerotic foci, several immunocompetent cells and immune-modulating factors can be found. Different etiological theories involving the immune system have been suggested. However, a genetic component is clearly present. In large otosclerosis families, seven autosomal-dominant loci have been found, but none of the disease-causing genes has been identified. This study focused on the exploration of the second otosclerosis locus on chromosome 7q34-36 (OTSC2), holding the T-cell receptor beta locus (TRB locus). A significantly lower T-cell receptor-beta (TCR-beta) mRNA expression and percentage of blood circulating TCR-alphabeta(+) T cells was detected in OTSC2 patients compared with controls and patients with the complex form of the disease. Further analysis illustrated more significant disturbances in specific T-cell subsets, including an increased CD28(null) cell population, suggesting a disturbed T-cell development and ageing in OTSC2 patients. These disturbances could be associated with otosclerotic bone remodeling, given the known effects of immunocompetent cells on bone physiology. These data implicate the TRB locus as the causative gene in the OTSC2 region and represent an important finding in the elucidation of the disease pathology.

Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patients.

Otosclerosis is one of the most common forms of hearing loss in the European population. We have identified a SNP in the TGFB1 (transforming growth factor beta 1) gene that is associated with susceptibility to otosclerosis. The protective allele of this variant, with isoleucine at position 263 of the protein, is more biologically active than the risk allele, which has a threonine in this position. Because recent studies have shown that not only common, but also rare variants can be involved in complex diseases, we performed DNA sequence analysis of the exons and intron-exon boundaries of TGFB1 in 755 otosclerosis patients and 877 control samples. We found 3 different nonsynonymous variants (E29, A29 and I241) in four otosclerosis patients, but no such changes were found in controls. In silico analysis shows that these variations could influence TGF-beta1 function and activity. Taking into account that most rare missense alleles are thought to have a biological effect, the data suggest that multiple rare amino acid changing variants in TGF-beta1 may contribute to susceptibility to otosclerosis.