10 research outputs found
Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study
Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis
Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase II multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase II study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 \u3bcg/ml, 20 \u3bcg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 \u3bcg/ml (+35.3%; 97.06% confidence interval [CI], 15.88\u201354.71; P < 0.001) and 58.0% receiving rhNGF 20 \u3bcg/ml (+38.4%; 97.06% CI, 18.96\u201357.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 \u3bcg/ml (+31.4%; 97.06% CI, 11.25\u201351.49; P = 0.001) and 74.0% receiving rhNGF 20 \u3bcg/ml (+30.9%; 97.06% CI, 10.60\u201351.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK
Evaluation of in vitro effects of selected physical and chemical agents on detected in Poland Acanthamoeba strains - factors of increasing threats for public health
Comparison of chlorhexidine disinfectant in vitro effect on environmental and ocular Acanthamoeba strains, the amoebic agents of human keratitis - an emerging sight-threatening corneal disease in Poland
Assessment of in vitro dynamics of pathogenic Acanthamoeba strains originating from contact lens wearers with infectious keratitis
Recently, incidents of Acanthamoeba keratitis, the vision-threatening eye disease, are reported with
increasing frequency worldwide, particularly in contact lens wearers. In our study, the retrospective assessment of in
vitro dynamics of subsequent pathogenic Acanthamoeba isolates cultured at 24°C, detected in Polish contact lens
wearers with keratitis is presented and results compared with those of environmental A. castellanii Neff strain. There
were delayed the proper diagnosis that influenced prolonged and severe course of this eye disease and treatment
difficulties. The corneal material was examined directly to visualize developmental amoeba stages for diagnose
verification, microbiologically tested for the specific identification of bacteriae and fungi, and in vitro grown in culture
medium in temperature 24°C. Among twenty-six keratitis incidents analyzed, eleven were cases of Acanthamoeba
keratitis; in the six of them, Acanthamoeba strains and concomitant bacterial and/or fungal infectious agents were
detected. In vitro assays showed variability in population density of several clinical strains in the exponential growth
phase expressed in various range of overall amoeba number and different proportion between trophozoites and cysts.
The clear influence of temperature on the in vitro cultivation of the amoebae was observed: statistically significant lower
population dynamics was revealed by most of pathogenic clinical isolates in comparison with those showed by
environmental strain. The in vitro monitoring of dynamics of Acanthamoeba strains isolated from infected eyes may be
helpful for diagnostics verification, especially in mixed infectious keratitis
The first investigation on differences in the effectiveness of mycophenolate mofetil and azathioprine antimetabolites determined in Polish patients treated for non-infectious uveitis
Comparative examination on selected amphizoic amoebae in terms of their in vitro temperature tolerance - a possible indirect marker of potential pathogenicity of Acanthamoeba strains
Resolving the dark matter of ABCA4 for 1054 Stargardt disease probands through integrated genomics and transcriptomics
Contains fulltext :
225504.pdf (Publisher’s version ) (Closed access)PURPOSE: Missing heritability in human diseases represents a major challenge, and this is particularly true for ABCA4-associated Stargardt disease (STGD1). We aimed to elucidate the genomic and transcriptomic variation in 1054 unsolved STGD and STGD-like probands. METHODS: Sequencing of the complete 128-kb ABCA4 gene was performed using single-molecule molecular inversion probes (smMIPs), based on a semiautomated and cost-effective method. Structural variants (SVs) were identified using relative read coverage analyses and putative splice defects were studied using in vitro assays. RESULTS: In 448 biallelic probands 14 known and 13 novel deep-intronic variants were found, resulting in pseudoexon (PE) insertions or exon elongations in 105 alleles. Intriguingly, intron 13 variants c.1938-621G>A and c.1938-514G>A resulted in dual PE insertions consisting of the same upstream, but different downstream PEs. The intron 44 variant c.6148-84A>T resulted in two PE insertions and flanking exon deletions. Eleven distinct large deletions were found, two of which contained small inverted segments. Uniparental isodisomy of chromosome 1 was identified in one proband. CONCLUSION: Deep sequencing of ABCA4 and midigene-based splice assays allowed the identification of SVs and causal deep-intronic variants in 25% of biallelic STGD1 cases, which represents a model study that can be applied to other inherited diseases