Evaluation of radial distribution of cartilage degeneration and necessity of pre-contrast measurements using radial dGEMRIC in adults with acetabular dysplasia

Background The purpose of the present study was to investigate the radial distribution patterns of cartilage degeneration in dysplastic hips at different stages of secondary osteoarthritis (OA) by using radial delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and to assess whether pre-contrast measurements are necessary. Methods Thirty-five hips in 21 subjects (mean age ± SD, 27.6 ± 10.8 years) with acetabular dysplasia (lateral CE angle < 25°) were studied. Severity of OA was assessed on radiographs using Tönnis grading. Pre- (T1pre) and post-contrast T1 (T1Gd) values were measured at 7 sub-regions on radial reformatted slices acquired from a 3-dimensional (3D) T1 mapping sequence using a 1.5 T MR scanner. Values of radial T1pre, T1Gd and ΔR1 (1/T1Gd - 1/T1pre) of subgroups with different severity of OA were compared to those of the subgroup without OA using nonparametric tests, and bivariate linear Pearson correlations between radial T1Gd and ΔR1 were analyzed for each subgroup. Results Compared to the subgroup without OA, the subgroup with mild OA was observed with a significant decrease in T1Gd in the anterosuperior to superior sub-regions (mean, 476 ~ 507 ms, p = 0.026 ~ 0.042) and a significant increase in ΔR1 in the anterosuperior to superoposterior and posterior sub-regions (mean, 0.93 ~ 1.37 s-1, p = 0.012 ~ 0.042). The subgroup with moderate to severe OA was observed with a significant overall decrease in T1Gd (mean, 404 ~ 452 ms, p = 0.001 ~ 0.020) and an increase in ΔR1 (mean, 1.17 ~1.69 s-1, p = 0.001 ~ 0.020). High correlations were observed between radial T1Gd and ΔR1 for all subgroups (r = −0.869 ~ −0.944, p < 0.001). Conclusions Radial dGEMRIC without pre-contrast measurements is useful for evaluating different patterns of cartilage degeneration in the entire hip joint of patients with hip dysplasia, particularly for those in early stages of secondary OA.

Detection of Chlamydia and complement factors in neovascular membranes of patients with age-related macular degeneration

PURPOSE To investigate whether Chlamydia pneumoniae and complement factors were present in surgically removed choroidal neovascular membranes (CNV) of patients with age-related macular degeneration (AMD). METHODS Paraffin sections of 26 CNV were stained for C. pneumoniae or the complement factors H (CFH) and C5, whereas macrophages were identified by positive CD68 staining. Clinical characteristics have been correlated to the immunohistochemical findings. RESULTS C. pneumoniae was found in 68% of the investigated membranes, and 88% of these membranes were also positive for CD68. Staining for CFH and C5 gave a positive reaction in 68 and 41% of the membranes, respectively. Patients with C5-positive membranes had significantly larger CNV mean area and were younger than patients with CFH-positive membranes at the operation time point. CONCLUSIONS Correlations between clinical symptoms and complement factor C5 could be shown. The results strengthen the hypothesis of an involvement of the complement system in AMD.

Long-term intraocular pressure changes in patients with neovascular age-related macular degeneration treated with ranibizumab

BACKGROUND/AIMS To investigate the long-term effects of multiple intravitreal injections (IVTs) of ranibizumab (Lucentis) on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration. METHODS In 320 eyes, IOP measurements were performed at baseline prior to injection and compared with IOP measurements of the last visit. Correlations between mean IOP change and total number of IVTs, visual acuity or patient age were tested. RESULTS The mean IOP increase was 0.8 ± 3.1 mm Hg (p < 0.0001). Seven eyes showed final IOP values between 22 and 25 mm Hg. The mean follow-up was 22.7 ± 14.1 months. No further correlations between IOP change and number of IVTs, visual acuity or patient age have been found. CONCLUSIONS This study demonstrated a statistically significant IOP increase in patients treated with repeated injections of ranibizumab. However, IOP increase required no glaucoma treatment during the study. Therefore, repeated injections with ranibizumab can be considered safe with regard to long-term IOP changes in patients without ocular hypertension or glaucoma.

Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration

To investigate the consequences of inborn excessive erythrocytosis, we made use of our transgenic mouse line (tg6) that constitutively overexpresses erythropoietin (Epo) in a hypoxia-independent manner, thereby reaching hematocrit levels of up to 0.89. We detected expression of human Epo in the brain and, to a lesser extent, in the lung but not in the heart, kidney, or liver of tg6 mice. Although no acute cardiovascular complications are observed, tg6 animals have a reduced lifespan. Decreased swim performance was observed in 5-mo-old tg6 mice. At about 7 mo, several tg6 animals developed spastic contractions of the hindlimbs followed by paralysis. Morphological analysis by light and electron microscopy showed degenerative processes in liver and kidney characterized by increased vascular permeability, chronic progressive inflammation, hemosiderin deposition, and general vasodilatation. Moreover, most of the animals showed severe nerve fiber degeneration of the sciatic nerve, decreased number of neuromuscular junctions, and degeneration of skeletal muscle fibers. Most probably, the developing demyelinating neuropathy resulted in muscular degeneration demonstrated in the extensor digitorum longus muscle. Taken together, chronically increased Epo levels inducing excessive erythrocytosis leads to multiple organ degeneration and reduced life expectancy. This model allows investigation of the impact of excessive erythrocytosis in individuals suffering from polycythemia vera, chronic mountain sickness, or in subjects tempted to abuse Epo by means of gene doping.

Behavioral and anatomical abnormalities in a sodium iodate-induced model of retinal pigment epithelium degeneration

We characterized changes in the visual behavior of mice in which a loss of the retinal pigment epithelium (RPE) was experimentally induced with intravenous (i.v.) administration of sodium iodate (NaIO3). We compared and correlated these changes with alterations in neural retinal structure and function. RPE loss was induced in 4-6 week old male C57BL/6 mice with an i.v. injection of 1% NaIO3 at three concentrations: 35, 50, or 70 mg/kg. At 1, 3, 7, 14, 21, and 28 days (d) as well as 6 months post injection (PI) a behavioral test was performed in previously trained mice to evaluate visual function. Eye morphology was then assessed for changes in both the RPE and neural retina. NaIO3-induced RPE degeneration was both dose and PI time dependent. Our low dose showed no effects, while our high dose caused the most damage, as did longer PI times at our intermediate dose. Using the intermediate dose, no changes were detectable in either visual behavior or retinal morphology at 1 d PI. However, at 3 d PI visual behavior became abnormal and patchy RPE cell loss was observed. From 7 d PI onward, changes in retinal morphology and visual behavior became more severe. At 6 months PI, no recovery was seen in any of these measures in mice administered the intermediate dose. These results show that NaIO3 dosage and/or time PI can be varied to produce different, yet permanent deficits in retinal morphology and visual function. Thus, this approach should provide a unique system in which the onset and severity of RPE damage, and its consequences can be manipulated. As such, it should be useful in the assessment of rescue or mitigating effects of retinal or stem cell transplantation on visual function.

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration. METHODS: During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594 [ClinicalTrials.gov].).

Effects of anatomic conformation on three-dimensional motion of the caudal lumbar and lumbosacral portions of the vertebral column of dogs

OBJECTIVE: To determine the association between the 3-dimensional (3-D) motion pattern of the caudal lumbar and lumbosacral portions of the canine vertebral column and the morphology of vertebrae, facet joints, and intervertebral disks. SAMPLE POPULATION: Vertebral columns of 9 German Shepherd Dogs and 16 dogs of other breeds with similar body weights and body conditions. PROCEDURE: Different morphometric parameters of the vertebral column were assessed by computed tomography (CT) and magnetic resonance imaging. Anatomic conformation and the 3-D motion pattern were compared, and correlation coefficients were calculated. RESULTS: Total range of motion for flexion and extension was mainly associated with the facet joint angle, the facet joint angle difference between levels of the vertebral column in the transverse plane on CT images, disk height, and lever arm length. CONCLUSIONS AND CLINICAL RELEVANCE: Motion is a complex process that is influenced by the entire 3-D conformation of the lumbar portion of the vertebral column. In vivo dynamic measurements of the 3-D motion pattern of the lumbar and lumbosacral portions of the vertebral column will be necessary to further assess biomechanics that could lead to disk degeneration in dogs.

Cerebellar cortical degeneration with selective granule cell loss in Bavarian mountain dogs

Three Bavarian mountain dogs aged between 18 and 20 months, not related to each other, were presented with chronic signs of cerebellar dysfunction. On sagittal T2-weighted magnetic resonance imaging brain images, the tentative diagnosis of cerebellar hypoplasia was established based on an enlarged cerebrospinal fluid space around the cerebellum and an increased cerebrospinal fluid signal between the folia. Post-mortem examination was performed in one dog and did show an overall reduction of cerebellar size. On histopathologic examination, a selective loss of cerebellar granule cells with sparing of Purkinje cells was evident. Therefore, the Bavarian mountain dog is a breed where cerebellar cortical degeneration caused by the rather exceptional selective granule cell loss can be seen as cause of chronic, slowly progressive cerebellar dysfunction starting at an age of several months.