Automated Aortic Anatomy Analysis: from Image to Clinical Indicators.

Most cerebrovascular diseases (including strokes and aneurysms) are treated endovascularly with catheters that are navigated from the groin through the vessels to the brain. Many patients have complex anatomy of the aortic arch and supra-aortic vessels, which can make it difficult to select the best catheters for navigation, resulting in longer procedures and more complications or failures. To this end, we propose a framework dedicated to the analysis of the aortic arch and supra-aortic trunks. This framework can automatically compute anatomical and geometrical features from meshes segmented beforehand via CNN-based pipeline. These features such as arch type, tortuosity and angulations describe the navigational difficulties encountered during catheterization. Quantitative and qualitative validation was performed by experienced neuroradiologists, leading to reliable vessel characterization.Clinical relevance- This method allows clinicians to determine the type and the anatomy of the aortic arch and its supra-aortic trunks before endovascular procedures. This is essential in interventional neuroradiology, such as navigation with catheters in this complex area.

Characterization of Surgical Tools for Specific Endovascular Navigation.

PURPOSE: The aim of this work was to mechanically characterize a specific active guidewire and catheters that are commercially available, for further implementation into numerical simulation of endovascular navigation towards complex targets. METHODS: For the guidewire, 3-point bending tests and bending with added masses were used to obtain the Young moduli of its various components. To study its behavior, the guidewire was activated under "ideal" conditions and its performance was investigated. As for the various catheters, they were measured and 3-point bending tests were conducted to determine their mechanical properties. RESULTS & CONCLUSION: The Young moduli of the shaft and the distal tip of the guidewire were determined. We defined a suitable current intensity to activate the guidewire related to an optimal curvature. Then, the time of activation/deactivation was measured at 1.7 s. On the flip side, parts of the catheters were considered either elastic or viscoelastic. In all cases, the rigidity gradients along the various catheters were highlighted. The characterization of the aforementioned surgical tools provides the opportunity to simulate the endovascular nagivation process.

The Journey of Lipoproteins Through the Cell: One Birthplace, Multiple Destinations.

Bacterial lipoproteins are a very diverse group of proteins characterized by the presence of an N-terminal lipid moiety that serves as a membrane anchor. Lipoproteins have a wide variety of crucial functions, ranging from envelope biogenesis to stress response. In Gram-negative bacteria, lipoproteins can be targeted to various destinations in the cell, including the periplasmic side of the cytoplasmic or outer membrane, the cell surface or the external milieu. The sorting mechanisms have been studied in detail in Escherichia coli, but exceptions to the rules established in this model bacterium exist in other bacteria. In this chapter, we will present the current knowledge on lipoprotein sorting in the cell. Our particular focus will be on the surface-exposed lipoproteins that appear to be much more common than previously assumed. We will discuss the different targeting strategies, provide numerous examples of surface-exposed lipoproteins and discuss the techniques used to assess their surface exposure.

Requirements analysis and preliminary design of a robotic assistant for reconstructive microsurgery.

Microanastomosis is a microsurgical gesture that involves suturing two very small blood vessels together. This gesture is used in many operations such as avulsed member auto-grafting, pediatric surgery, reconstructive surgery - including breast reconstruction by free flap. When vessels have diameters smaller than one millimeter, hand tremors make movements difficult to control. This paper introduces our preliminary steps towards robotic assistance for helping surgeons to perform microanastomosis in optimal conditions, in order to increase gesture quality and reliability even on smaller diameters. A general needs assessment and an experimental motion analysis were performed to define the requirements of the robot. Geometric parameters of the kinematic structure were then optimized to fulfill specific objectives. A prototype of the robot is currently being designed and built in order to providing a sufficient increase in accuracy without prolonging the duration of the procedure.

Electrophysiological correlates of attentional processes in patients with liver cirrhosis without minimal or clinically-overt hepatic encephalopathy.

Liver cirrhosis is often accompanied by a spectrum of cognitive deficits, labelled hepatic encephalopathy (HE). The precise specification of cognitive impairment associated with HE has not been yet elucidated. The aim of this study was an attempt to examine cortical function in cirrhotic patients using EEG event-related potentials during a demanding task involving selective attention. We compared group of 30 patients with liver cirrhosis without minimal or overt HE with education-, age- and sex-matched 29 non-cirrhotic controls. Both groups performed an attentional blink (AB) task, which requires detecting and identifying two target characters in a longer series of rapidly and sequentially presented characters. EEG signals from 32 electrodes were measured and then analyzed in the paradigm of event-related potentials (ERP). Though the groups did not differ in the detection rate of the target stimuli, ERP waveforms revealed two group differences of component amplitudes. The first difference was related to the waveform amplitude within the 200-400 ms after first target in the right frontal region (frontocentral N2 component). Moreover, in patient group this amplitude positively correlated with the blood plasma level of alkaline phosphatase and gamma-glutamyl transpeptidase. The second amplitude difference was observed in the midline parieto-occipital regions within the 400-600 ms after the first target (P3b component). The AB task and ERP analysis allowed to find differences in cortical functioning in cirrhotic patients even without overt cognitive deficits. Our finding demonstrates that liver dysfunction can influence cortical processing associated with detecting and categorizing stimulus change.

Cognitive evoked response potentials in patients with liver cirrhosis without diagnosis of minimal or overt hepatic encephalopathy. A pilot study.

Liver cirrhosis is often accompanied by cognitive deficits called minimal hepatic encephalopathy (MHE) when it is observed to a moderate extent. In the present study, brain activity and cognitive functioning were examined in patients with liver cirrhosis without MHE or overt clinical hepatic encephalopathy. A battery of neuropsychological tests and event related potentials (ERPs) were used. Moreover, an additional n-back task was administered with two difficulty levels (1- and 2-back). This task was designed to engage cognitive processes of storage and manipulation of information in working memory. The participants have to decide whether the letter shown was the same as a target (congruence condition). No significant differences were found in the performance of either the neuropsychological tests or the n-back task. However, the expected effects of decreased performance as well as a decrease in P3 amplitude with difficulty level were identified. The interaction of group x congruence condition was also observed in the P2 component time window. These results may indicate group differences manifesting in early stages of information processing in working memory. It confirms that the patients whose neuropsychological performance is within the normal range can still reveal subtle changes in CNS functioning visible in ERP research. The study confirms the usability of the ERP method in diagnosis of neurocognitive functions in patients with liver cirrhosis, which seems to be more sensitive than neuropsychological tests.

Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients.

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3(-/-) mice. Interestingly, in our hands, neither of the independently derived Cxcr3(-/-) lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-gamma production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3(-/-) recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.

Event-related cerebral potentials for the diagnosis of subclinical hepatic encephalopathy in patients with liver cirrhosis.

PURPOSE: Subclinical hepatic encephalopathy (SHE) seems to be a common problem in liver cirrhosis, however, studies assessing the pathogenesis of this disease remain unclear. Currently no gold standard exists for the diagnosis of this complex neuropsychiatric syndrome. The present study was undertaken firstly to examine the diagnostic usefulness of auditory event-related cerebral potentials (ERPs) in the detection of SHE, and secondly to compare it with that of the most validated psychometric test. MATERIAL AND METHODS: 22 patients with liver cirrhosis without overt hepatic encephalopathy and 28 healthy controls were studied, using auditory ERPs. In addition they underwent a battery of neuropsychological and laboratory tests. RESULTS: P300 latency analysis turned out that cirrhotics patients had significantly longer P300 latency than controls. The only neuropsychological test showing significant difference between clinical and control group was the similarities subtest of WAIS-R. CONCLUSIONS: The results of the present study suggest that ERPs are more sensitive method than psychometric tests in detecting early changes in the brain function of patients with cirrhosis and for this reason this neurophysiological method should be applied in clinical practice.

Identification of novel metabolites of pioglitazone in rat and dog.

1. Four new metabolites of pioglitazone were identified by liquid chromatography-mass spectrometry (LC-MS/MS) as being formed by hydroxylation (M-VII and M-VIII), opening of the thiazolidinedione ring (M-X) and by desaturation of the terminal ethyl side chain or tether ethoxy moiety (M-IX), respectively. The structure of one of the hydroxylated metabolites (M-VII) was confirmed by chemical modification using the Jones reaction. 2. Oxidative cleavage of the thiazolidinedione ring is a novel pathway not previously reported for pioglitazone. 3. The hydroxylated M-VII was detected in incubations with rat, dog and human liver and kidney microsomes, and in plasma from rats and dogs dosed orally with [(3)H]pioglitazone. 4. The carboxylic acid derivative of M-VII (M-V) and its taurine conjugate were the major radioactive components in dog bile.

[Analysis of combined glaucoma and cataract operations with intraocular lens implantation: a study based on own material]. / Ocena operacji trójproceduralnych jaskry i zacmy z wszczepieniem sztucznej soczewki wewnatrzgalkowej--doswiadczenia wlasne.

PURPOSE: To analyse results and complications of glaucoma and cataract surgery with IOL implantation. MATERIAL AND METHODS: 28 patients (32 eyes) underwent glaucoma and cataract surgery with IOL implantation during the period of January 1998-December 1999. The follow up time ranged from 6 to 30 months. RESULTS: Postoperative visual acuity was 5/12-5/5 in 78.13% of cases. Intraoperatively there were 4 patients of posterior capsule tears with vitreous loss. The most common postoperative complications were Descemet's membrane folds (28.13%), corneal oedema (21.87%) and increased intraocular pressure (18.75%), but they were only transitory. Finally postoperative intraocular pressure was good in 93.76%. In 2 cases glaucoma medication was longer required. Delayed follow-up showed that visual field deteriorated before surgery had not worsened. CONCLUSIONS: Combined, simultaneous operation of glaucoma and cataract does not seem to give rise to more complications than both procedures performed separately. The procedure is safe and gives good visual rehabilitation.

Inhibition of major groove DNA binding bZIP proteins by positive patch polyamides.

Cell permeable synthetic ligands that bind to predetermined DNA sequences offer a chemical approach to gene regulation, provided inhibition of a broad range of DNA transcription factors can be achieved. DNA minor groove binding polyamides containing aminoalkyl substituents at the N-1 of a single pyrrole residue display inhibitory effects for a bZIP protein which binds exclusively in the DNA major groove. For major groove protein inhibition, specific protein-DNA contacts along the phosphate backbone were targeted with the positively charged dimethylamino substituent on the backbone of a minor groove binding polyamide hairpin. Remarkably, these polyamides bind DNA with enhanced affinity and uncompromised specificity when compared to polyamides with the aminoalkyl moiety at the C-terminus. By adding bZIP transcription factors to the class of protein-DNA complexes that can be disrupted by minor groove binding ligands, these results may increase the functional utility of polyamides as regulators of gene expression.

Alternative heterocycles for DNA recognition: an N-methylpyrazole/N-methylpyrrole pair specifies for A.T/T.A base pairs.

Side-by-side pairs of three five-membered rings, N-methylpyrrole (Py), N-methylimidazole (Im), and N-methylhydroxy-pyrrole (Hp), have been demonstrated to distinguish each of the four Watson Crick base pairs in the minor groove of DNA. However, not all DNA sequences targeted by these pairing rules achieve affinities and specificities comparable to DNA binding proteins. We have initiated a search for new heterocycles which can expand the sequence repetoire currently available. Two heterocyclic aromatic amino acids. N-methylpyrazole (Pz) and 4-methylthiazole (Th), were incorporated into a single position of an eight-ring polyamide of sequence ImImXPy-gamma-lmPyPyPy-beta-Dp to examine the modulation of affinity and specificity for DNA binding by a Pz/Py pair and or a Th/Py pair. The X/Py pairings Pz/Py and Th/Py were evaluated by quantitative DNase I footprint titrations on a DNA fragment with the four sites 5'-TGGNCA-3' (N=T, A, G, C). The Pz/Py pair binds T.A and A.T with similar affinity to a Py/Py pair but with improved specificity. disfavoring both G.C and C.G by about 100-fold. The Th/Py pair binds poorly to all four Watson Crick base pairs. These results demonstrate that in some instances new heterocyclic aromatic amino acid pairs can be incorporated into imidazole-pyrrole polyamides to mimic the DNA specificity of Py/Py pairs which may be relevant as biological criteria in animal studies become important.

[Analyses of results of deep sclerectomy ab externo in open angle glaucoma based on own material]. / Analiza wyników glebokiej sklerektomii ab externo w jaskrze otwartego kata w oparciu o material wlasny.

PURPOSE: The evaluation of postoperative results of the non-penetrating deep sclerectomy in primary open angle glaucoma. MATERIAL AND METHODS: From September 1999 to October 2000 the procedure was performed in 10 patients (15 eyes). There were 7 men and 3 women aged from 45 to 87 years. Preoperative IOPs ranged from 16 to 38 mm Hg. The follow up time ranged from 3 to 12 months. RESULTS: Success was considered an IOP of less than 20 mm Hg without medication in 87%. There were a few early postoperative complications included hypotony (9 patients), hyphema (1 patient), chorioidal detachment (3 patients). Late complication was bleb fibrosis in only 1 patient. Visual acuity and visual field were not worse than before surgery. CONCLUSIONS: Our experience confirms that the non penetrating deep sclerectomy appears to be a safe and effective procedure in open angle glaucoma.

Recognition of the DNA minor groove by pyrrole-imidazole polyamides: comparison of desmethyl- and N-methylpyrrole.

Polyamides consisting of N-methylpyrrole (Py), N-methylimidazole (Im), and N-methyl-3-hydroxypyrrole (Hp) are synthetic ligands that recognize predetermined DNA sequences with affinities and specificities comparable to many DNA-binding proteins. As derivatives of the natural products distamycin and netropsin, Py/Im/Hp polyamides have retained the N-methyl substituent, although structural studies of polyamide:DNA complexes have not revealed an obvious function for the N-methyl. In order to assess the role of the N-methyl moiety in polyamide:DNA recognition, a new monomer, desmethylpyrrole (Ds), where the N-methyl moiety has been replaced with hydrogen, was incorporated into an eight-ring hairpin polyamide by solid-phase synthesis. MPE footprinting, affinity cleavage, and quantitative DNase I footprinting revealed that replacement of each Py residue with Ds resulted in identical binding site size and orientation and similar binding affinity for the six-base-pair (bp) target DNA sequence. Remarkably, the Ds-containing polyamide exhibited an 8-fold loss in specificity for the match site versus a mismatched DNA site, relative to the all-Py parent. Polyamides with Ds exhibit increased water solubility, which may alter the cell membrane permeability properties of the polyamide. The addition of Ds to the repertoire of available monomers may prove useful as polyamides are applied to gene regulation in vivo. However, the benefits of Ds incorporation must be balanced with a potential loss in specificity.

[Devic disease: a rare cause of retrobulbar optic neuritis: a case report]. / Choroba Devica--rzadka przyczyna pozagalkowego zapalenia nerwu wzrokowego--opis przypadku.

A case of 58-year-old woman with recurrent retrobulbar optic neuritis (ron) and transverse myelitis is presented. The patient was admitted to the opthalmology unit because of acute right retrobulbar optic neuritis. In 1997 she complained of left retrobulbar optic neuritis. One year later transverse myelitis of thoracic spine with spastic paraparesis occurred. MRI examination showed T2 hyperintensive focus in the thoracic spine (Th8-Th9, probably demyelinisation). Nowadays MRI examination of the optic nerves and brain showed demyelinisation focus in the right optic nerve. There was no pathological changes in the brain. The diagnosis of Devic disease was established. Treatment with intravenous methyloprednisolon was administered with slight improvement. The pathology and clinical course of Devic disease are discussed.

delta-Amino beta-keto esters, a designed polyfunctionalized chiral building block for alkaloid synthesis. Asymmetric synthesis of (R)-(+)-2-phenylpiperidine and (-)-SS20846A.

[formula: see text] delta-Amino beta-keto esters 3 and 11 are designed polyfunctionalized chiral building blocks for alkaloid synthesis and are prepared in one step from the corresponding sulfinimine (N-sulfinyl imine). Concise highly enantioselective four-step syntheses of 2-phenylpiperidine (7) and SS20846A (14) from 3 and 11, respectively, are described.

Structural effects of DNA sequence on T.A recognition by hydroxypyrrole/pyrrole pairs in the minor groove.

Synthetic polyamides composed of three types of aromatic amino acids, N-methylimidazole (Im), N-methylpyrrole (Py) and N-methyl-3-hydroxypyrrole (Hp) bind specific DNA sequences as antiparallel dimers in the minor groove. The side-by-side pairings of aromatic rings in the dimer afford a general recognition code that allows all four base-pairs to be distinguished. To examine the structural consequences of changing the DNA sequence context on T.A recognition by Hp/Py pairs in the minor groove, crystal structures of polyamide dimers (ImPyHpPy)(2) and the pyrrole counterpart (ImPyPyPy)(2) bound to the six base-pair target site 5'-AGATCT-3' in a ten base-pair oligonucleotide have been determined to a resolution of 2.27 and 2.15 A, respectively. The structures demonstrate that the principles of Hp/Py recognition of T.A are consistent between different sequence contexts. However, a general structural explanation for the non-additive reduction in binding affinity due to introduction of the hydroxyl group is less clear. Comparison with other polyamide-DNA cocrystal structures reveals structural themes and differences that may relate to sequence preference.

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.

We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified as a structurally novel PPARgamma agonist. Structure-activity relationships identified the 2-aminobenzophenone moiety as a suitable isostere for the chemically labile enaminone moiety in compound 2, affording 2-((2-benzoylphenyl)amino)-3-(4-(benzyloxy)phenyl)propionic acid (9). Replacement of the benzyl group in 9 with substituents known to confer in vivo potency in the thiazolidinedione (TZD) class of antidiabetic agents provided a dramatic increase in the in vitro functional potency and affinity at PPARgamma, affording a series of potent and selective PPARgamma agonists exemplified by (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(methylpyridin-2-ylamino+ ++)ethoxy ]phenyl¿propionic acid (18), 3-¿4-[2-(benzoxazol-2-ylmethylamino)ethoxy]phenyl¿-(2S)-((2- benzoylph enyl)amino)propanoic acid (19), and (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propanoic acid (20). Compounds 18 and 20 show potent antihyperglycemic and antihyperlipidemic activity when given orally in two rodent models of type 2 diabetes. In addition, these analogues are readily prepared in chiral nonracemic fashion from L-tyrosine and do not show a propensity to undergo racemization in vitro. The increased potency of these PPARgamma agonists relative to troglitazone may translate into superior clinical efficacy for the treatment of type 2 diabetes.

[The use of perfluorocarbon liquid in the surgical removal of lenses luxated to the vitreous cavity]. / Zastosowanie plynu perfluorokarbonowego do usuwania soczewek zwichnietych do komory szklistej.

BACKGROUND: Removal of lenses dislocated to the vitreous cavity can be hazardous. The use of perfluorocarbon liquids during pars plana vitrectomy may reduce the risk of intraoperative and postoperative complications. We report our experience in using this surgical technique. MATERIAL AND METHODS: The authors describe a series of 14 patients in whom a posteriorly dislocated crystalline (11 eyes) or intraocular (3 eyes) lens was successfully removed with the use of perfluorodecalin through the limbal incision. Simultaneously, posterior chamber, scleral fixation IOLs were implanted in 10 cases and anterior chamber IOL in one case. In one patient AC IOL was implanted secondarily. RESULTS: With a minimum follow-up of one month (average, 8 months), the visual acuity improved in 4 eyes, remained the same in 10, and worsened in one eye. Very good visual acuity (5/5-5/10) was achieved in 86% of patients. Complications were not frequent and not severe despite one case of retinal detachment. CONCLUSIONS: Application of pars plana vitrectomy and the use of liquid perfluorocarbon allow for the safe management of eyes with luxated lenses.

A structural basis for recognition of A.T and T.A base pairs in the minor groove of B-DNA.

Polyamide dimers containing three types of aromatic rings-pyrrole, imidazole, and hydroxypyrrole-afford a small-molecule recognition code that discriminates among all four Watson-Crick base pairs in the minor groove. The crystal structure of a specific polyamide dimer-DNA complex establishes the structural basis for distinguishing T.A from A.T base pairs. Specificity for the T.A base pair is achieved by means of distinct hydrogen bonds between pairs of substituted pyrroles on the ligand and the O2 of thymine and N3 of adenine. In addition, shape-selective recognition of an asymmetric cleft between the thymine-O2 and the adenine-C2 was observed. Although hitherto similarities among the base pairs in the minor groove have been emphasized, the structure illustrates differences that allow specific minor groove recognition.