Erkrankungen der Adnexe in den Tropen: Amniontransplantation bei nichtinfektiösen Trachom-assoziierten Hornhautulzera

BACKGROUND: Corneal ulcers with fornix shortening associated with late stages of cicatrizing trachoma contribute significantly to blindness in many developing countries. We report on the outcome of ocular surface and fornix reconstruction using amnion membrane transplantation. PATIENTS AND METHODS: From 2001 to 2005, cryopreserved human amnion membrane without mitomycin C was grafted to 25 eyes of 17 patients with trophic corneal ulcers and symblepharon (cicatrizing trachoma: 19 eyes of 14 patients, Stevens-Johnson syndrome: 4 eyes of 2 patients, alkali burns: 2 eyes of 1 patient) in a controlled case series. Follow-up was done up to 6 months. STATISTICS: Fischer's exact probability test. RESULTS: Of 25 eyes, 9 of 19 eyes with trachoma, 3 of 4 eyes with Stevens-Johnson syndrome, and 2 of 2 eyes with chemical burns showed complete reepithelialization and stromal recovery after 28-35 days (mean: 31+/-2.3 days). The primary success rate of trachoma eyes was not significantly different from the other indications (p=0.256). At 6 months post-op, 15 of 19 trachoma eyes (79%) compared to 2 of 6 non-trachoma eyes (33.3%) had developed a recurrence of symblephara (p=0.0592), and 13 of 15 eyes (86.6%) with a cicatricial trachoma compared to 1 of 6 with non-trachoma diagnosis experienced a recurrence of corneal vascularization (difference nonsignificant: p=0.1752). Persistent long-term reepithelialization was observed only in 1 of 19 trachoma eyes (5.3%) versus 4 of 6 non-trachoma eyes (66.7%, p=0.005); 3 of 19 trachoma eyes with a recurrence of ulcers had perforated after 6 months. CONCLUSIONS: Human amnion membrane without mitomycin C can be used for ocular surface reconstruction in selected patients with cicatrizing trachoma. Its efficacy in the long-term rehabilitation of cicatrizing trachoma seems to be limited due to the progressive scarring.     

Mikrobielle Keratitis

PURPOSE: To determine the risk factors and the influence of complementary/alternative medicines (CAM) for infectious keratitis in a monsoon-free region of the Sultanate of Oman. STUDY DESIGN: Retrospective single center cohort study. OUTCOME MEASURES: Demographic data, risk factors, and pathogens. METHODS: Patients with purulent stromal keratitis admitted from 2001-2004 were evaluated for clinical and microbiological data, CAM use, duration of hospitalization, and outcome of treatment. STATISTICS: chi(2)-test, Z-test. RESULTS: A total of 320 patients (326 eyes) out of 7,524 admissions had severe infectious stromal keratitis requiring inpatient treatment. The average age was 35.1+/-2.5 years (range 1.5-63 years), the male:female ratio was 2:3 in the age group >or=13 years and 2:1 in the age group 相似文献   

Safety and radiosensitizing efficacy of sanazole (AK 2123) in oropharyngeal cancers: randomized controlled double blind clinical trial

Oropharynx is an important site of cancer in India. Global comparison indicates higher incidences in India. Radiotherapy remains an important treatment modality. Efforts to improve loco-regional treatment and prolong survival are areas of focus. Radiosensitizers in hypoxic tumors have shown promise. AIM: To study the safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell carcinoma (stage T2-4, N0-3, M0) as phase-II double blind controlled trial in patients treated with conventional radiotherapy. SETTINGS AND DESIGN: Single institutional, randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: Group 1 (control; n = 23) received normal saline infusion, group 2 (test; n = 23) received sanazole biweekly 1.25 g intravenous infusion 15 minutes before radiotherapy. Surrogate end points of efficacy were tumor and nodal size; safety parameters were mucositis, salivary and skin reactions, dysphagia, vomiting, dysgeusia and neurological deficit. Investigators blinded to the trial evaluated patients, weekly during treatment for six weeks and thereafter monthly for three months. STATISTICAL METHODS: Non-parametric, Friedman's, Chi square, Mann-Whitney U tests. RESULTS: In the test, 15 (65%) patients had complete response, five (22%) partial/no response, two (9%) died, one (4%) lost to follow up. In the control, five (22%) patients had complete response, 16 (70%) partial/no response, one (4%) died, one (4%) lost to follow up. Short-term loco-regional response was better in the test (DF = 3, 95% Confidence Interval 0.418, 0.452, P = 0.0048). In the test group significant vomiting and one case of grade 3 neurological deficit was observed. CONCLUSION: The study validates the usefulness of sanazole for initial loco-regional control in oropharyngeal cancers.     

Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer

This study was carried out to evaluate and compare the biodistribution profile of tamoxifen when administered intravenously (i.v.) as a simple solution or when encapsulated in polymeric nanoparticulate formulations, with or without surface-stabilizing agents. Tamoxifen-loaded, poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were prepared by solvent displacement process that allowed in situ surface modification via physical adsorption of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock polymeric stabilizer (Pluronic). The nanoparticles were characterized for particle size and surface charge. Presence of PEO chains on nanoparticle surface was ascertained by electron spectroscopy for chemical analysis (ESCA). In vivo biodistribution studies were carried out in Nu/Nu athymic mice bearing a human breast carcinoma xenograft, MDA-MB-231 using tritiated [(3)H]-tamoxifen as radio-marker for quantification. PEO-PCL nanoparticles with an average diameter of 150-250 nm, having a smooth spherical shape, and a positive surface charge were obtained with the formulation procedure. About 90% drug encapsulation efficiency was achieved when tamoxifen was loaded at 10% by weight of the polymer. Aqueous wettability, suspendability, and ESCA results showed surface hydrophilization of the PCL nanoparticles by the Pluronics. The primary site of accumulation for the drug-loaded nanoparticles after i.v. administration was the liver, though up to 26% of the total activity could be recovered in tumor at 6h post-injection for PEO-modified nanoparticles. PEO-PCL nanoparticles exhibited significantly increased level of accumulation of the drug within tumor with time as well as extended their presence in the systemic circulation than the controls (unmodified nanoparticles or the solution form). Pluronic surfactants (F-68 and F-108) presented simple means for efficient surface modification and stabilization of PCL nanoparticles to achieve preferential tumor-targeting and a circulating drug reservoir for tamoxifen.     

Poly(Ethylene Oxide)-Modified Poly(β-Amino Ester) Nanoparticles as a pH-Sensitive System for Tumor-Targeted Delivery of Hydrophobic Drugs: Part 2. <Emphasis Type="BoldItalic">In Vivo</Emphasis> Distribution and Tumor Localization Studies

Purpose This study was carried out to determine the biodistribution profiles and tumor localization potential of poly(ethylene oxide) (PEO)-modified poly(β-amino ester) (PbAE) as a novel, pH-sensitive biodegradable polymeric nanoparticulate system for tumor-targeted drug delivery. Methods The biodistribution studies of PEO-modified PbAE and PEO-modified poly(ɛ-caprolactone) (PCL), a non-pH-sensitive polymer, nanoparticle systems were carried out in normal mice using ¹¹¹indium-oxine [¹¹¹In] as a lipophilic radiolabel encapsulated within the polymeric matrix, and the distribution of the nanoparticles was studied in plasma and all the vital organs following intravenous administration. Solid tumors were developed on nude mice using human ovarian carcinoma xenograft (SKOV-3) and the change in concentrations of tritium [³H]-labeled paclitaxel encapsulated in polymeric nanoparticles was examined in blood, tumor mass, and liver. Results Study in normal mice with a gamma-emitting isotope [¹¹¹In] provided a thorough biodistribution analysis of the PEO-modified nanoparticulate carrier systems, whereas ³H-paclitaxel was useful to understand the change in concentration and tumor localization of anticancer compound directly in major sites of distribution. Both PEO-PbAE and PEO-PCL nanoparticles showed long systemic circulating properties by virtue of surface modification with PEO-containing triblock block copolymer (Pluronic?) stabilizer. Although the PCL nanoparticles showed higher uptake by the reticuloendothelial system, the PbAE nanoparticles effectively delivered the encapsulated payload into the tumor mass. Conclusions PEO-modified PbAE nanoparticles showed considerable passive tumor targeting potential in early stages of biodistribution via the enhanced permeation and retention (EPR) mechanism. This prompts a detailed biodistribution profiling of the nanocarrier for prolonged periods to provide conclusive evidence for superiority of the delivery system.