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Quantification of the relative ellipsoid zone reflectivity (rEZR) might be a structural surrogate parameter for an early disease progression in the context of age-related macular degeneration (AMD). Within the European multicenter, cross-sectional MACUSTAR study, we have devised an automatic approach to determine the mean rEZR [arbitrary units, AU] at two independent visits in SD-OCT volume scans in study participants. Linear mixed-effects models were applied to analyze the association of AMD stage and AMD associated high-risk features including presence of pigmentary abnormalities, reticular pseudodrusen (RPD), volume of the retinal-pigment-epithelial-drusenoid-complex (RPEDC) with the rEZR. Intra-class correlation coefficients (ICC) were determined for rEZR reliability analysis. Within the overall study cohort (301 participants), we could observe decreased rEZR values (coefficient estimate ± standard error) of - 8.05 ± 2.44 AU (p = 0.0011) in the intermediate and of - 22.35 ± 3.28 AU (p

Quantifying intraocular inflammation is crucial in managing uveitis patients. We assessed the minimum B-scan density for reliable automated vitreous intensity (VI) assessment, using a novel approach based on optical coherence tomography (OCT). OCT volume scans centered on the macula were retrospectively collected in patients with uveitis. Nine B-scans per volume scan at fixed locations were automatically analyzed. The following B-scan selections were compared against the average score of 9 B-scans per volume scan as a reference standard: 1/3/5/7 central scans (1c/3c/5c/7c), 3 widely distributed scans (3w). Image data of 49 patients (31 females) were included. The median VI was 0.029 (IQR: 0.032). The intra-class-correlation coefficient of the VI across the 9 B-scans was 0.923. The median difference from the reference standard ranged between 0.001 (7c) and 0.006 (1c). It was significantly lower for scan selection 3w than 5c, p(adjusted) = 0.022, and lower for selection 7c than 3w, p(adjusted) = 0.003. The scan selections 7c and 3w showed the two highest areas under the receiver operating curve (0.985 and 0.965, respectively). Three widely distributed B-scans are sufficient to quantify VI reliably. Highest reliability was achieved using 7 central B-scans. Automated quantification of VI in uveitis is reliable and requires only few OCT B-scans.

Detection and evaluation of inflammatory activity in uveitis is essential to the management of the condition, and yet continues to be largely dependent on subjective clinical measures. Optical coherence tomography (OCT) measurement of vitreous activity is an alternative to clinical vitreous haze scoring and has passed a number of early validation studies. In this study we aimed to evaluate the impact of ‘operator factors’ on the variability of the technique as part of the validation process, and to help evaluate its suitability for ‘real world’ use. Vitreous haze index was calculated as a ratio between the reflectivity of the vitreous and of the outer retina in each scan. Different scanning conditions were tested and their effect on the measurement is reported. Our results show that the ‘quantitative imaging’ technique of OCT-measured vitreous activity had good reliability in normal subjects under a range of ‘real world’ conditions, such as when the operator changes the averaging value. The technique was however vulnerable to highly inaccurate focussing or abnormal downward displacement of the image. OCT-based quantification of vitreous activity is a promising alternative to current subjective clinical estimates, with sufficient ‘tolerance’ to be used in routine clinical practice as well as clinical trials.

Aims: to characterize and analyze the responses of rat dorsal Lateral Geniculate Nucleus (dLGN) to different kinds of retinal inputs and outline its role in retino-cortical transmission. Methods: various light stimulation approaches were used together with pharmacological manipulations. A selective blocker of the bipolar ON cells (LAP4) and a potassium channel blocker (4-AP) were employed produce highly clean (LAP4, pure OFF output) and noisy (4-AP) responses to visual stimuli. The effect on geniculo-cortical transmission was studied via Visual Evoked Potential recordings, while the effect on the activation pattern of the dLGN was evaluated via immunostainings for the protein c-fos. Results: the rat dLGN showed a differential activation of excitatory and inhibitory neurons in the two experimental conditions, thus playing a great role in regulating retino-cortical transmission of different visual inputs. Indeed, it appeared to act as an effective filter for the noisy stimuli (4-AP) activating a strong inhibitory circuitry and effectively suppressing the information flow to the visual cortex. We also analyzed the spatial distribution of cells expressing c-fos in dLGN obtaining clear evidence for a non homogeneous arrangement of active cells. Conclusions: these data confirm the important role of dLGN in visual processing, with either suppression or enhancement of sensory transmission depending on the characteristics of the input signals, presumably according to the amount of information conveyed. The inhomogeneous distribution of active cells could be related either to a peculiar distribution of synapses and synaptic weights or to a strong shaping of active regions due to inhibitory circuits

"Even if anesthetics are widely used in the medical practice to ensure the induction and maintenance of general anesthesia, there is still an unresolved issue which relates to their mechanism of action therefore to the nature of their molecular target site(s). Since a large number of very different chemical molecules are used in general anesthesia, this suggests that a large variety of molecular targets must exist. Some of these might affect axonal conduction and membrane excitability. In some cases, this action could either occur at the presynaptic level, modifying the neurotransmitter release and reuptake, or at the postsynaptic level, modifying the receptor sensitivity. These functional alterations might also affect one or more neuronal phenotypes for example by dampening the activity of the Glutamatergic circuits, or by enhancing the activity of GABAergic networks (or other inhibitory systems). Despite the underlying complexity of molecular targets, all general anesthetics induce a general and profound inhibition of cortical EEG activity while sparing evoked cortical responses. Based on these considerations, I decided to begin the investigation of the electrophysiological basis of the action of general anesthetics on the visual thalamus and on cortical circuits for vision in the rat. In this project I will compare the effects of different anesthetic molecules including sevofluorane, propofol and ketamine. Fot these experiments rats are curarized (one bolus of atracurium, 5 mg\/kg, each 20 minutes) and mechanically ventilated by the insertion of a cannula in trachea (the oxygen and CO2 level are continuously monitored). In these experiments I record: i) visual evoked potentials (VEPs) by superficial electrodes implanted in the skull; ii)intracellular visual cortex activity by sharp electrodes; iii) the pattern of activation of neurons in the LGN and cortex by the expression of the c-fos gene protein product known to report neuronal firing; iv) by applying the synaptic biosensor, GreenZip, which has been recently developed in my laboratory, I will record synaptic network activity with single synapse resolution. In these experiments, rats will be visually stimulated with light pulses (20 msec) or with alternating black and white horizontal stripes at constant overall luminance (2Hz reversal, 0.5 cycle\/degree). In a set of preliminary experiments that I will present at the meeting, I have characterized the effect of sevoflurane, a volatile anesthetic . I found that sevofluorane increases in a dose-dependent manner both the amplitude and the latency of VEPs, while the general cortical electrical activity is reduced. Among the working hypotheses I’m exploring : i)an unbalance between inhibition and excitation in thalamic or cortical circuits by the anesthetic ; ii) an increase in the pool of available vesicles for visually evoked activity because of reduced background activity . At the meeting I will present an account on this work describing the methodological approach and my preliminary results."

Delivery of nutrients and oxygen within three-dimensional (3D) tissue constructs is important to maintain cell viability. We built 3D cell-laden hydrogels to validate a new tissue perfusion model that takes into account nutrition consumption. The model system was analyzed by simulating theoretical nutrient diffusion into cell-laden hydrogels. We carried out a parametric study considering different microchannel sizes and inter-channel separation in the hydrogel. We hypothesized that nutrient consumption needs to be taken into account when optimizing the perfusion channel size and separation. We validated the hypothesis by experiments. We fabricated circular microchannels (r?=?400 µm) in 3D cell-laden hydrogel constructs (R?=?7.5 mm, volume?=?5 ml). These channels were positioned either individually or in parallel within hydrogels to increase nutrient and oxygen transport as a way to improve cell viability. We quantified the spatial distribution of viable cells within 3D hydrogel scaffolds without channels and with single- and dual-perfusion microfluidic channels. We investigated quantitatively the cell viability as a function of radial distance from the channels using experimental data and mathematical modeling of diffusion profiles. Our simulations show that a large-channel radius as well as a large channel to channel distance diffuse nutrients farther through a 3D hydrogel. This is important since our results reveal that there is a close correlation between nutrient profiles and cell viability across the hydrogel. © 2009 Springer-Verlag.

Adults with severe growth hormone (GH) deficiency (GHD) may develop a cluster of cardiovascular risk factors that may contribute to a reduced life expectancy with increased mortality due to cardiovascular disease. In adolescents with severe GHD there is also increasing evidence which suggests that the discontinuation of GH replacement therapy at the completion of linear growth may result in adverse effects on body composition, lipid profile, cardiac morphology and performance. In contrast, relatively few studies have investigated whether or not children with GHD have metabolic and cardiac abnormalities that may place them at higher risk of cardiovascular disease at an early age. This review focuses on the effect of both GHD and GH replacement on cardiovascular risk factors in children and adolescents with GHD

A 85-year-old male developed a false, non septic, non anastomotic aneurysm, 20 years after right aorto-femoral Dacron grafting for claudication. On account of the proximity to the femoral anastomosis, and the association with a profunda femoris stenosis, a conventional surgical repair was preferred to an endovascular treatment. The patient underwent a successful aneurysm resection followed by PTFE interposition between the primary graft and the profunda femoris artery, with uneventful recovery.

Hypothesis The operation for isolated, stenotic, and symptomatic kinking of the internal carotid artery is safe and effective in preventing stroke and relieving the symptoms of cerebral ischemia. Design A consecutive sample clinical study with a mean follow-up of 44 months. Setting The surgical department of an academic tertiary care center and an affiliated secondary care center. Patients Fifty-four patients with a mean age of 67 years underwent 55 revascularizations of the internal carotid artery. The surgical procedures consisted of the following: shortening and reimplantation in the common carotid artery in 36 cases, bypass grafting in 15 cases, and transposition into the external carotid artery in 4 cases. Main Outcome Measures Cumulative survival, primary patency, and stroke-free and neurologic symptom-free rates expressed by standard life-table analysis. Results No patients died in the postoperative period. The postoperative stroke rate was 1.8%. The cumulative rates (SEs) at 5 years were as follows: survival, 70% (10.2%); primary patency, 89% (7.8%); overall stroke free, 92% (6.8%); ipsilateral stroke free, 96% (5.3%); neurologic symptom free, 90% (7.5%); and ipsilateral symptom free, 93% (6.5%). Conclusion Revascularization of the internal carotid artery for the treatment of isolated, stenotic, and symptomatic kinking is safe and effective in preventing stroke and relieving symptoms of cerebrovascular insufficiency.

The authors report a case of lower gastrointestinal hemorrhage in a 69-year-old male, in which the sequence colonoscopy-angiography identified the source of bleeding as a rare Angiodysplasia (AD) of the rectum. Such vascular abnormalities are one of the most common causes of major lower gastrointestinal tract bleeding in the elderly and usually occurs predominantly in the right side of the colon. The clinical presentation of Angiodysplasia is varied and accurate diagnosis usually requires a combination of diagnostic techniques such as colonoscopy and angiography. The optimal management is uncertain and should be individualized for each patient depending on severity and rate of rebleeding. A conservative medical approach is indicated for many patients, while endoscopic treatment does not seem modify the risk of recurrent bleeding. In case of massive hemorrhage or recurrent bleeding surgery still represents the definitive treatment for Angiodysplasia. However the risk of rebleeding following surgery is a considerable problem and varies in literature from 5% to 30%.

A case of 31-year-old male with a retroperitoneal tumor is described. Abdominal ultrasound revealed a left para-aortic calcific mass, adjacent to the left lobe of the liver and to the upper pole of the left kidney. A CT-scan of the abdomen showed the mass to originate from the left adrenal gland. At operation, a large, retroperitoneal mass, adherent to the left kidney and the spleen, but not infiltrating, was excised. Histologically the tumor was diagnosed as a calcified osteo-producing fibroma. Benign retroperitoneal tumors represent about 25% of all retroperitoneal neoplasm. This reported case represents a retroperitoneal tumor of slow growth and benign clinical course whose characteristic consists of the heavy calcifications which are normally absent in a fibroma type mass.