Corneal tomographic features of postrefractive surgery ectasia.

The purpose of this study was to evaluate the tomographic features of postrefractive surgery eyes. This was a retrospective evaluation of clinical data. Three patients with post-LASIK (laser-assisted in situ keratomileusis) and two patients with post-SMILE (small incision lenticule extraction) ectasia were imaged with Scheimpflug imaging (SI, Pentacam) and optical coherence tomography (OCT, RTVue). Curvature and wavefront aberrations of the air-epithelium interface (A-E) and epithelium-Bowman's layer interface (E-B) were derived. OCT of normal and keratoconic eyes from an earlier study were compared with the data of the ectasia eyes. Curvature and aberrometry of the A-E interfaces were statistically similar between SI and OCT. However, OCT revealed a steeper and more aberrated E-B interface than A-E though correlation between them was inferior to the correlation for keratoconic eyes. Furthermore, the magnitude of differences between the A-E and E-B interfaces was greater in the ectasia eyes than the keratoconic eyes. OCT could possibly assist better in selecting appropriate treatment plan for postrefractive surgery ectasia eyes than conventional tomographers.

Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats.

BACKGROUND: The isolation and testing of monkey islets after transplantation in small animal models provides basic information about their functional capacity. We describe the effect of cyclosporine A (CsA), tacrolimus (FK506) or prednisolone monotherapy on preventing monkey islet graft rejection after xenoTx in a rat model. Histopathological aspects are reported. METHODS: Indian bonnet monkey (Macaca radiata radiata) islets were isolated by a simple stationary digestion technique using collagenase. The islets were purified with dextran density gradients and were transplanted under the renal capsule of normal or diabetic rats. The rats received a daily dose of CsA, or FK506, or prednisolone, and the grafts were removed at different intervals to determine islet survival. The effect of discontinuation of CsA on islet graft survival was also monitored. Histological examination of islets transplanted into normal or streptozotocin-induced diabetic rats was carried out. In diabetic rats, islet survival was determined by the graft's ability to achieve euglycemia. RESULTS: Reversal of diabetes was achieved in all transplanted diabetic rats, demonstrating the efficacy of the isolated monkey islets. Histological examination indicated that monkey islets survived in the presence of continuous high-dose immunosuppressive monotherapy in rats. Various types of infiltrating cells were observed in the grafted area at varying times after transplantation, depending on the immunosuppressive treatment. After discontinuation of CsA, the grafts were protected for a short period. CONCLUSIONS: This study provided evidence for monkey islet survival after transplantation into rats receiving immunosuppressive monotherapy. Basic information on infiltrating cell types may be important in the study of xenograft rejection.

Molecular diversity of Glanzmann thrombasthenia in southern India: new insights into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin (ITGA2B, ITGB3).

The molecular basis of Glanzmann thrombasthenia (GT) was studied in 40 families from southern India. Of 23 identified mutations (13 in the alphaIIb (ITGA2B) gene and 10 in the beta3 (ITGB3) gene), 20 were novel and three were described previously. Three mutations in the beta3 gene-p.Leu143Trp (Leu117Trp), p.Tyr307Stop (Tyr281Stop), and p.Arg119Gln (Arg93Gln)-were detected in 12, three, and two families, respectively, with definite founder effects observed for the first two mutations. Alternative splicing was predicted in silico for the normal variant and a missense variant of the beta3 gene, and for 10/11 frameshift or nonsense mutations in alphaIIb or beta3. The prediction was confirmed experimentally for a c.2898_2902dupCCCCT mutation in exon 28 of the alphaIIb gene that induced exon skipping. Seven out of nine missense mutations substituted highly conserved amino acids buried in the proteins' cores, predicting structural abnormalities. Among these, a beta3 substitution, p.Cys39Gly (Cys13Gly) was found to cause intracellular degradation of the beta3 subunit, in contrast to previous findings that mutations at Cys435, the partner of Cys13 in a disulfide bond, cause constitutive activation of alphaIIbbeta3. The two patients with a beta3 Arg93Gln mutation had normal clot retraction, consistent with a recent finding that this substitution is associated with normal surface expression of alphaIIbbeta3. In conclusion, this study demonstrates that a variety of mutations account for GT in southern Indian patients, provides new insights into mRNA splicing, and highlights the role of specific amino acids in structure-function correlations of alphaIIbbeta3.

Prenatal diagnosis of Glanzmann thrombasthenia.

BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet function, which results in major morbidity due to persistent, spontaneous, mucocutaneous bleeding and menorrhagia in women. Platelet transfusions are often needed to control the bleeding. Glanzmann thrombasthenia results from mutations in the genes located on chromosome 17q21-23, encoding the platelet glycoprotein (GP) IIb/IIIa receptor. METHODS: This report describes, for the first time in India, the prenatal diagnosis performed in a family who had a child with GT. As the molecular defect had not been identified at the time of chorionic villus sampling (CVS), prenatal diagnosis was done by linkage assessment. Haplotype analysis was performed using polymorphic markers on chromosome 17q 12-21, which included the dinucleotide repeat polymorphisms (CA)n in BRCA1 gene and locus D17S579 and (CT)n within GP IIIa intron 6, and the known restriction fragment length polymorphism (RFLP) markers Fok I (GP IIb exon 26), Taq I (GP IIIa exon 8) and Sma I (GP IIIa exon 9). The specific mutation in this family was subsequently confirmed. RESULTS: Both parents and the foetus were heterozygous for all the dinucleotide repeat polymorphisms and the affected child was homozygous. Both parents and the affected child were homozygous for Fok I RFLP. The father was heterozygous, and the mother, affected child and foetus were homozygous for Taq I and Sma I. The Fok I RFLP was identical for all the family members and hence did not provide any information for haplotype analysis (foetus not tested). CONCLUSION: The findings from dinucleotide repeat polymorphisms in BRCA1, D17S579, and GP IIIa intron 6 and the Sma I and Taq I RFLPs in GP IIIa strongly suggested that the foetus had inherited the father's mutant and the mother's normal alleles. Hence, the foetus was diagnosed to be a heterozygous carrier of GT by haplotype analysis. A private sequence alteration was later identified in the affected child in GP IIIa IVS1 (-14C --> A). The parents and foetus were heterozygous for this mutation. This confirmed the findings of the haploytpe analysis.