Therapeutic anti-VEGF in ophthalmology: physiopathology and treatment of age-related macular degeneration

Bei der altersabh?ngigen Makuladegeneration (AMD) handelt es sich um eine komplexe Erkrankung des Netzhaut-/Pigmentepithel-/ Aderhaut-Komplexes, die typischerweise zu einem Verlust der Sehsch?rfe und des zentralen Gesichtsfeldes führt. Bei der h?ufigen neovaskul?ren Sp?tform kann ein Sehverlust mittels VEGF-Inhibitoren verhindert und bei einem Teil der Patienten sogar erstmals eine Sehverbesserung erreicht werden.     

Amplification and overexpression of vinculin are associated with increased tumour cell proliferation and progression in advanced prostate cancer

Androgen withdrawal is the standard treatment for advanced prostate cancer. Although this therapy is initially effective, nearly all prostate cancers become refractory to it. Approximately 15% of these castration-resistant prostate cancers harbour a genomic amplification at 10q22. The aim of this study was to explore the structure of the 10q22 amplicon and to determine the major driving genes. Application of high-resolution array-CGH using the 244k Agilent microarrays to cell lines with 10q22 amplification allowed us to narrow down the common amplified region to a region of 5.8 megabases. We silenced each of the genes of this region by an RNAi screen in the prostate cancer cell lines PC-3 and 22Rv1. We selected genes with a significant growth reduction in the 10q22 amplified cell line PC-3, but not in the non-amplified 22Rv1 cells, as putative target genes of this amplicon. Immunohistochemical analysis of the protein expression of these candidate genes on a tissue microarray enriched for 10q22 amplified prostate cancers revealed vinculin as the most promising target of this amplicon. We found a strong association between vinculin gene amplification and overexpression (p < 0.001). Further analysis of 443 specimens from across all stages of prostate cancer progression showed that vinculin expression was highest in castration-resistant prostate cancers, but negative or very low in benign prostatic hyperplasia (p < 0.0001). Additionally, high tumour cell proliferation measured by Ki67 expression was significantly associated with high vinculin expression in prostate cancer (p < 0.0001). Our data suggest that vinculin is a major driving gene of the 10q22 amplification in prostate cancer and that vinculin overexpression might contribute to prostate cancer progression by enhancing tumour cell proliferation.     

An unusual reason for Kock pouch urinary incontinence

We report the case of Kock pouch incontinence resulting from perforation of the efferent nipple valve by an unsuccessful catheterization attempt in a patient with a spinal cord injury. Continence was reestablished by surgical revision.     

Comparison of the performance of different HPV genotyping methods for detecting genital HPV types

Classification of high-risk HPV types for cervical cancer screening depends on epidemiological studies defining HPV type-specific risk. The genotyping tests that are used, are however, not uniform with regard to type-specific detection rates making comparisons between different studies difficult. To overcome the lack of a "gold standard" four tests were evaluated crosswise using 824 cervical smears pretested by HC2. The tests evaluated were the L1-PCR-based assays PGMY09/11 LBA, HPV DNA Chip and SPF LiPA and an E1 consensus PCR followed by cycle sequencing (E1-PCR). A subset of 265 samples was tested in addition with the GP5+/6+ reverse line blot assay. Differences were noted in the sensitivity and range for specific HPV types, e.g. with detection rates for HPV53 ranging from 2.3% to 11.6%. HPV16 was the most prevalent type detected by all tests except for the SPF-10 LiPa, which detected HPV31 more often. Kappa values calculated ranged from poor (k=0.20) to intermediate (k=0.54) for HPV positivity, but were higher for high-risk type positivity (k=0.31-0.61) and best for recognition of HPV16 (k=0.53-0.72). The analytical sensitivity of the tests ranged between 15% and 97% for individual types and specificity was highly dependent on which test system was used as "gold standard" for the analysis. The results of histology were used for calculation of clinical sensitivity and specificity. E1-PCR, PGMY09/11 LBA and SPF-10 LiPA had a high clinical sensitivity (>95%) for the detection of cervical intraepithelial neoplasia 2 or higher, whereas the HPV DNA Chip reached only 84.1%.     

A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women

Objectives

To evaluate the effects of an estrogen-reduced, continuous-combined hormone therapy preparation (HT) containing 1 mg estradiol valerate (1EV) and 2 mg dienogest (2DNG) on the number of moderate and severe hot flushes.

Methods

This study compared the effects of an oral continuous-combined HT containing 1 mg EV and 2 mg DNG (1EV/2DNG) with those of placebo. The planned treatment duration was 12 weeks. Data were obtained from 324 postmenopausal women. The primary efficacy variable was the individual relative change of the mean number of moderate and severe hot flushes per week. Weeks 5–12 of treatment were compared with the 2 weeks preceding the treatment phase.

Results

Moderate and severe hot flushes were reduced by 80.8 ± 30.9% in the 1EV/2DNG group and by 41.5 ± 39.4% in the placebo group. This difference was statistically significant (p < 0.0001; Wilcoxon's rank sum test). The incidence of all types of hot flushes (mild + moderate + severe) was reduced by 75.2 ± 30.2% under 1EV/2DNG and by 35.3 ± 37.0% under placebo.In the subset of non-hysterectomized women, exposure to 1EV/2DNG led to 2.4 ± 6.2 days with bleeding in the reference period of 84 days of treatment, versus 0.3 ± 1.3 days in the placebo group.The safety profile of 1EV/2DNG was very similar to that of placebo.

Conclusions

Continuous-combined HT preparation with 1 mg EV and 2 mg DNG induced a significant reduction of moderate and severe hot flushes compared to placebo (p < 0.0001).Thus, this low-estrogen preparation is an effective and safe option for HT.     

Elbow dislocation with fracture of the coronoid process and comminuted fracture of the radius head

In fractures of the elbow with an associated fracture of the coronoid process, the size of the coronoid fragment determines the stability of the joint. A diminution of the arch of the incisura semilunaris by about 30 degrees causes instability of the elbow. We present an alternative way of treating the special case of a fracture of the coronoid process combined with comminuted fracture of the proximal end of the radius. A suitable fragment of the head of the radius is used to reconstruct the coronoid process. The stability achieved allows early functional postoperative treatment with a good range of movement at the elbow joint.     

Familial exudative vitreoretinopathy mimicking persistent hyperplastic primary vitreous

PURPOSE: To report an unusual case of familial exudative vitreoretinopathy in an infant. METHODS: Case report. A 6-day-old girl had unilateral microphthalmia in the right eye, with a retrolental plaque initially diagnosed as persistent hyperplastic primary vitreous. Three months later, peripheral retinal vascular changes and a fibrovascular ridge were noted in the left eye, suggesting familial exudative vitreoretinopathy as the cause in both eyes. RESULTS: The microphthalmic right eye was unsalvageable. The left eye developed an exudative retinal detachment despite photocoagulation of the peripheral avascular retina. Additional cryotherapy resulted in resolution of the detachment and regression of the vascular changes. CONCLUSIONS: With highly asymmetric involvement, neonatal familial exudative vitreoretinopathy can mimic persistent hyperplastic primary vitreous. Fellow eye involvement can progress rapidly.     

Long-term retinal toxicity of intravitreal commercially available preserved triamcinolone acetonide (Kenalog) in rabbit eyes

PURPOSE: To investigate whether intravitreal Kenalog (IVTK; Bristol Meyers Squibb Company, Princeton, NJ) produces histologic or electroretinographic changes in the rabbit retina up to 3 months after injection. METHODS: Ten Dutch-belted rabbits were injected with 4 mg/0.1 mL Kenalog in one eye and 0.1 mL physiologic salt solution (PSS) in the fellow eye. Simultaneous bilateral dark-adapted electroretinography was performed 2 weeks and 12 weeks after injection in 10 and 6 rabbits, respectively. Saturated a-wave amplitude, maximal scotopic b-wave amplitude, and individual a-wave and b-wave amplitudes of IVTK-injected and control eyes were compared at 2 and 12 weeks after injection. Light microscopy was performed on both eyes of three animals 3 months after injection. Immunohistochemistry was performed with antibodies recognizing vimentin and human alveolar macrophage (HAM)-56, markers of glial cells and macrophages, respectively. RESULTS: No significant difference was observed in the saturated a-wave or maximal scotopic b-wave amplitudes between the PSS-injected eyes and the IVTK-injected eyes at 2 weeks (P = 0.95 and P = 0.56, respectively) and 12 weeks (P = 0.82 and P = 0.17) after injection. Light microscopy and immunohistochemistry disclosed only rare macrophages in the vitreous of IVTK-injected eyes. Retinal layers, retinal pigment epithelium, and choriocapillaris in treatment and control eyes were unremarkable. CONCLUSIONS: No demonstrable electroretinographic or histologic changes occurred to suggest immediate or delayed widespread retinal toxicity of IVTK.     

Prospective randomized trial of wavefront-guided laser in situ keratomileusis with the CustomCornea and CustomVue laser systems

PURPOSE: To compare visual function, safety, and higher-order aberrations (HOAs) after wavefront-guided laser in situ keratomileusis (LASIK) with the LadarVision CustomCornea (Alcon Laboratories, Inc.) and Star S4 CustomVue (Visx) laser systems. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: Seventy-eight eyes of 39 patients with myopia with or without astigmatism were randomized for LASIK treatment in 1 eye with the CustomCornea laser; the other eye was treated with the CustomVue laser. Patients were followed for 6 months after surgery. The primary outcome measures were uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, and changes in HOAs. RESULTS: At 6 months, the mean logarithm of the minimum angle of resolution (logMAR) UCVA was -0.0135 +/- 0.07 (SD) in the CustomVue group and 0.0417 +/- 0.12 in the CustomCornea group (P = .023). Eighty-eight percent of eyes in the CustomVue group had 20/20 or better UCVA compared with 67% in the CustomCornea group (P<.02). At 6 months, 91% of eyes in the CustomVue group and 79% in the CustomCornea group were within +/-0.50 diopter (D) of emmetropia (P<.1); 88% and 50%, respectively, were within +/-0.25 D (P<.001). Both platforms led to a small increase in total HOAs. The CustomVue system reduced trefoil and induced less of an increase in total HOAs, whereas the CustomCornea platform increased trefoil but induced less of an increase in spherical aberrations and coma. CONCLUSIONS: Both laser systems were effective, safe, and predictable. Wavefront-guided LASIK with the CustomVue system resulted in better visual acuity, with more eyes having 20/20 acuity than in the CustomCornea group.