Héctor Gatica

Earlier immunomodulatory treatment is associated with better visual outcomes in a subset of patients with Vogt-Koyanagi-Harada disease

To evaluate clinical outcomes of first‐line immunomodulatory therapy (IMT) and prednisone alone or late IMT in Vogt‐Koyanagi‐Harada disease.

Motion correction and myocardial perfusion SPECT using manufacturer provided software. Does it affect image interpretation

PurposeMyocardial perfusion SPECT is an excellent tool for the assessment of coronary artery disease (CAD); however, it is affected by several artifacts, such as patient motion during acquisition, which increases false-positive rates. Therefore, the purpose of this work is to analyze changes in perfusion scores after motion-correction software application.MethodsThe population included 160 99mTc-sestamibi CAD studies, divided into two groups: with and without perfusion defects, equally divided into subgroups according to movement during standard acquisition. A Siemens ECAM 180 was used for processing without correction and with automatic and manual e.soft 2.5 modalities. Visual interpretation as well as QPS software was compared using Pearson correlation and kappa agreement statistics.ResultsModerate agreement was observed between SPECT interpretations after motion correction versus the original report, according to the presence of perfusion defects. Manual correction using the software obtained the lowest agreements. Perfusion summed stress scores (SSS) correlation from different processing modalities versus non-corrected studies differed significantly independent of the degree of motion. Mean SSS in 40 patients with no motion was 3.9 ± 3.9 when no correction was applied; with automatic correction was 8.8 ± 10 (p = 0.03) and with manual correction was 3.1 ± 3.5 (p = ns versus non-corrected). Automatic correction was better when applied to patients with mild to moderate motion. In those with mild or no motion, software overestimated or created new perfusion defects.ConclusionMotion-correction software must be used with caution when trying to optimize myocardial perfusion SPECT based on individual analysis. Acquisition should be always repeated in cases with severe motion and in no or mild motion it seems preferable to avoid correction.

L-type calcium channels in growth plate chondrocytes participate in endochondral ossification

Longitudinal bone growth occurs by a process called endochondral ossification that includes chondrocyte proliferation, differentiation, and apoptosis. Recent studies have suggested a regulatory role for intracellular Ca2+ (Ca  i2+ ) in this process. Indirect studies, using Ca2+ channel blockers and measurement of Ca  i2+ , have provided evidence for the existence of Ca2+ channels in growth plate chondrocytes. Furthermore, voltage‐gated Ca2+ channels (VGCC), and specifically L‐ and T‐type VGCCs, have been recently described in murine embryonic growth plates. Our aim was to assess the effect of L‐type Ca2+ channel blockers on endochondral ossification in an organ culture. We used cultures of fetal rat metatarsal rudiments at 20 days post gestational age, with the addition of the L‐type Ca2+ channel blockers verapamil (10–100 µM) or diltiazem (10–200 µM) to the culture medium. Longitudinal bone growth, chondrocyte differentiation (number of hypertrophic chondrocytes), and cell proliferation (incorporation of tritiated thymidine) were measured. Verapamil dose‐dependently decreased growth, the number of hypertrophic chondrocytes, and cell proliferation, at concentrations of 10–100 µM. Growth and the number of hypertrophic chondrocytes decreased significantly with diltiazem at 50–100 µM, and proliferation decreased significantly at concentrations of 10–200 µM. Additionally, there was no increase in apoptosis over physiological levels with either drug. We confirmed the presence of L‐type VGCCs in rat rudiments using immunohistochemistry, and showed that the antagonists did not alter the pattern of VGCC expression. In conclusion, our data suggest that L‐type Ca2+ channel activity in growth plate chondrocytes is necessary for normal longitudinal growth, participating in chondrocyte proliferation and differentiation. J. Cell. Biochem. 101: 389–398, 2007.

Evaluation of the Glucocorticoid Receptor as a Biomarker of Treatment Response in Vogt-Koyanagi-Harada Disease

Purpose This study is aimed to investigate the role of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMC) as biomarkers of glucocorticoid (GC) resistance and to validate a set of clinical predictive factors in patients with Vogt-Koyanagi-Harada (VKH) disease. Methods This was a prospective cohort study that included a total of 21 patients with VKH. A complete ophthalmologic evaluation was carried out at baseline that recorded the presence of any clinical predictive factors (visual acuity ≤ 20/200, tinnitus, chronic disease, and fundus depigmentation). Real-time quantitative PCR was performed to measure the mRNA levels of GR alpha (GRα) and beta (GRβ) isoforms at baseline and at 2 weeks after prednisone therapy initiation. Results There were no differences between GRα and GRβ levels in GC-sensitive and GC-resistant patients at baseline before treatment initiation. After 2 weeks of prednisone treatment, GC-sensitive patients had a median 5.5-fold increase in levels of GRα, whereas GC-resistant patients had a median 0.7-fold decrease in levels of this isoform (P = 0.003). Similarly, GRβ increased in GC-sensitive patients, in comparison with GR-resistant patients (6.49-fold versus 1.01 fold, respectively, I = 0.04). The mRNA levels of GR isoforms were independent of disease activity. Fundus depigmentation and chronic disease at diagnosis were associated with GC resistance (P = 0.03, odds ratio = 21.0; and P = 0.008, odds ratio = 37.8, respectively). However, associations with visual acuity or tinnitus were not confirmed in this study. Conclusions The evaluation of clinical predictive factors and determination of the change in expression of GR isoforms as potential biomarkers can contribute to the early identification of GC-resistant patients with VKH.