Transpupillary thermotherapy with indocyanine green dye enhancement for the treatment of occult subfoveal choroidal neovascularization in age-related macular degeneration.

BACKGROUND AND OBJECTIVES: Transpupillary thermotherapy (TTT) with indocyanine green (ICG) dye enhancement (TTT+) and TTT alone were compared for safety and effectiveness as a treatment of occult subfoveal choroidal neovascularization in age-related macular degeneration. PATIENTS AND METHODS: Twenty-one patients were randomized to receive TTT (12 eyes) or TTT+ (9 eyes) and observed for at least 6 months. ETDRS visual acuity and fluorescein and ICG angiography were obtained every 3 months. RESULTS: The median initial visual acuity was 20/80 in the TTT group and 20/100 in the TTT+ group. At 6 months, loss of less than 3 lines of visual acuity was present in 7 of 12 eyes (58%) in the TTT group and 5 of 9 eyes (56%) in the TTT+ group. At the final examination, there was no active choroidal neovascularization exudation in 6 of 12 eyes (50%) in the TTT group and 5 of 9 eyes (56%) in the TTT+ group. The median final visual acuity was 20/125 in the TTT group and 20/160 in the TTT+ group. Ocular or systemic complications were not encountered in either group. CONCLUSION: TTT with ICG dye enhancement was as safe and effective as TTT alone in this study. However, modifications of treatment protocol would be needed to see whether there is any advantage to using ICG dye enhancement.     

Inhibition of PDC-E2 Human Combinatorial Autoantibodies by Peptide Mimotopes

Immunohistochemical studies have shown that a unique immunoreactive molecule is present near the apical region of human biliary epithelial (BE) cells in patients with primary biliary cirrhosis (PBC). This can be visualized by confocal microscopy in PBC livers using a number of unique monoclonal antibodies to the E2 component of pyruvate dehydrogenase complex (PDC-E2), the autoantigen most commonly recognized by antimitochondrial antibodies (AMA). One such antibody, the murine mAb C355.1 was used to identify peptide mimotopes of PDC-E2 by screening a random dodecapeptide phage library ON 159.2 to identify the possible biochemical nature of this apical staining molecule. Out of 36 independent clones, 29 showed a common sequence and seven other sequences were singly represented. Three common amino acid motifs (SYP, TYVS and VRH) were found among these eight sequences. Similar to C355.1, the human combinatorial antibodies derived from a patient with PBC, SP1 and SP4, recognize the inner lipoyl domain of PDC-E2. However, when these antibodies are used to stain PBC BE cells, SP4 stains the apical region of PBC BE cells with high intensity whereas SP1 produces only cytoplasmic staining. Competitive inhibition of immunohistochemical staining using PDC-E2 specific human combinatorial antibodies SP1 and SP4 was performed using five of the above dodecapeptides. Interestingly, the peptides selected with C355.1 differentially inhibited the binding of SP1 and SP4 to PBC BE cells. Finally, rabbit sera raised against one such peptide (WMSYPDRTLRTS) stained BE cells from patients with PBC with a higher intensity than controls. Comparable data was obtained with immunoelectronmicroscopy. These data suggest that a molecular mimic of PDC-E2 is present at the external aspect of PBC BE cells.     

Context-specific memory and apolipoprotein E (ApoE) epsilon 4: cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease.

The aim of the study was to determine whether the epsilon 4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the epsilon 4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale-Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of epsilon 4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an epsilon 4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative epsilon 4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies.     

Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder.

BACKGROUND: Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding eszopiclone to fluoxetine. METHODS: Patients who met DSM-IV criteria for both MDD and insomnia (n = 545) received morning fluoxetine and were randomized to nightly eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S). RESULTS: Patients in the ESZ+FLX group had significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p < .05). Eszopiclone co-therapy also resulted in: significantly greater changes in HAM-D-17 scores at Week 4 (p = .01) with progressive improvement at Week 8 (p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 (p < .05); and significantly more responders (59% vs. 48%; p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates. CONCLUSIONS: In this study, eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect.