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.

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.

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.

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.

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.

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.

Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity (II): Optimization of the C3 amino substituent.

Analogs of the previously reported 1,5-benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonist 1 were prepared which explore substitution and/or replacement of the C-3 phenyl urea moiety. Agonist efficacy on the isolated guinea pig gallbladder (GPGB) was retained with a variety of substituted ureas and amide analogs. Three compounds were identified which were orally active in the mouse gallbladder emptying assay (MGBE). The 2-indolamide (52) and N-(carboxymethyl)-2-indolamide (54) derivatives had improved affinity for the human CCK-A receptor but reduced agonist efficacy on the GPGB. Neither indolamide was orally active in a rat feeding assay. In contrast, the (3-carboxyphenyl)urea derivative (29, GW7854) had moderately increased affinity for the human CCK-B receptor but was a potent full agonist on the GPGB and was orally active in both the MGBE and rat feeding assays. GW7854 was a full agonist (EC50 = 60 nM) for calcium mobilization on CHO K1 cells expressing hCCK-A receptors and a potent antagonist of CCK-8 (pA2 = 9.1) on CHO K1 cells expressing hCCK-B receptors. GW7854 is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in two in vivo models of CCK-A-mediated agonist activity.

Optimization of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists.

We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the C3 and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at C3. Structure-activity relationships at the N1-anilidoacetamide "trigger" moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the N1-anilidoacetamide moiety. Evaluation of several analogs in an vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.

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.

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.

Transscleral suture fixation and anterior chamber intraocular lenses implanted after removal of posteriorly dislocated crystalline lenses.

The surgical technique is described for simultaneous removal of posteriorly dislocated crystalline lenses and implantation of anterior chamber (AC) or scleral fixation posterior chamber (PC) intraocular lenses (IOL) using pars plana vitrectomy. Twenty-two patients underwent this complex operation. Observation time ranged from 2 to 10 months (mean 5 months). Best-corrected post-operative visual acuity was 1.0 in half the patients in the AC group (n = 12), and in 80% of the PC group (n = 10). It was less than 0.5 in 25% of cases in the AC group whereas all PC patients had visual acuity 0.5 or better. In nine cases with pre-operative ocular hypertension, post-operative intraocular pressure became normal, although topical glaucoma therapy was necessary in three patients in the AC group and in one from the PC group. No severe complications were found. Removal of posteriorly dislocated crystalline lens using pars plana vitrectomy and limbal incision is a safe procedure. Simultaneous AC or transscleral PC lens implantation is a good alternative to contact lenses. Visual rehabilitation was good in both groups of patients, although post-operative visual acuity was better after PC transscleral fixation than after AC surgery.

Pars plana vitrectomy, lensectomy, or extraction in transscleral intraocular lens fixation for the management of dislocated lenses in a family with Marfan's syndrome.

BACKGROUND AND OBJECTIVES: Congenital lens subluxation may be a difficult therapeutic problem. Surgical treatment options include iris manipulation or lens decision, aspiration, intracapsular or extracapsular extraction, and lensectomy through the pars plana. It is not established which kind of aphakic correction is the most appropriate in these cases. PATIENTS AND METHODS: A father and his two sons with Marfan's syndrome were operatively treated for lens dislocation in both eyes. Pars plana vitrectomy was done in all eyes. Dislocated lenses were removed by lensectomy in three eyes and with an intracapsular method in three eyes. The outside-in scleral fixation technique was used for primary posterior chamber intraocular lens (PC IOL) implantation in all cases. RESULTS: All eyes achieved good visual acuity (20/20-20/25). Time of observation ranged between 8 and 20 months. There were no intraoperative or post-operative complications. CONCLUSION: Pars plana vitrectomy and primary scleral-fixated IOL implantation is a safe procedure and gives good visual rehabilitation in adult patients with Marfan's syndrome.

[Meralgia paraesthetica in a body-builder]. / Meralgia paraesthetica beim Bodybuilder.

The article describes the case of meralgia paraesthetica, a disease not uncommon, of a bodybuilder. Extensive literature of meralgia paraesthetica shows us several reasons for the injury of the lateral cutaneous nerve of the thigh, but the genesis of the nerve-injury by strain in training is unusual. Diagnostics and therapy of that disease do not present any difficulty.

[Clinical value of ultrasonographic assessment of fetal hypotrophy and the effects of its treatment]. / Wartosc kliniczna ultrasonograficznej oceny hipotrofii plodu i efektów jej leczenia.

The clinical usefulness was assessed of ultrasonography in the study of fetal hypotrophism determining the parameters BIP, THQ and placental parameters. Fetal growth was assessed and in case of hypotrophism adequate therapeutic management was undertaken. The study was carried out on 56 pregnant women referred for diagnosis and treatment of fetal hypotrophism in the period 1983-1985. The control group comprised 56 women with physiological pregnancy. The study was carried out with examinations at weekly intervals from the 24th week of pregnancy till labour using a Hellige-Panavista unit with a 2.5 MHz probe. The BIP and THQ dimensions were calculated a together with placental parameters. The oestriol level was determined in 24-hour urine. The underlying disease and fetal hypotrophism were treated. The most valuable indicator for the determination of asymmetrical and symmetrical type of hypotrophism and for its monitoring was the BIP/THQ index. Ultrasonography makes possible a rapid and accurate diagnosis of fetal condition and control of its treatment. Ultrasonographic observation of the placenta is a source of valuable information for the obstetrician. Oestriol determination is without any greater significance for monitoring of fetal hypotrophism.

[Retinal detachment after cataract extraction in myopic eyes]. / Odwarstwienie siatkówki po operacji zacmy w oczach krótkowzrocznych.

In the years 1981-1992, 67 myopic eyes had been surgically treated because of the cataract. Intracapsular extraction had been performed in 64.2%, extracapsular in 35.8% of the cases. Visual acuity higher than 1/50 was achieved in 14.9%, 1/50-4/50 in 16.4%, 5/50-5/12 in 26.9%, 5/10-5/5 in 41.8% of the cases. In 4.5% of the cases, retinal detachment was ascertained and all of them concerned the patients with extracapsular extraction.

[A case of bird-shot type chorioretinopathy]. / Przypadek chorioretinopatii typu birdshot.

A case of a 39-years-old man with progressive deterioration of visual acuity, which occurred during the birdshot chorioretinopathy, is presented. The major findings in this rare disorder concern the ocular fundus. The most marked are the patterned distribution of depigmented spots without hyperpigmentation, radiation from the optic disc in association with vitritis, retinal vasculopathy with frequent cystoid macular oedema, and involvement of the optic nerve head. HLA testing showed very strong disease association with HLA-A 29 (95.8%).

[3 cases of tumors of the optic disk]. / Trzy przypadki guzów tarczy nerwu wzrokowego.

Presented are 3 cases of tumors affecting the papilla of the optic nerve. On the basis of the ophthalmoscopic picture, of fluorescein angiography and of clinical symptoms the authors identified a capillary haemangioma, a pigmentary naevus and a meningeal hernia. In all the cases observation did not detect any increase in the changes.

[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.

[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.