[Fever and weight loss in a 57-year-old patient]. / Fièvre et perte de poids chez une patiente de 57 ans.

Presentation of a 57-year-old female patient with fever of unknown origin, asthenia, and weight loss for I month. History and examination were unremarkable. Blood analysis showed an important inflammatory syndrome. Other paraclinic tests were all normal. Finally, sophisticated exams (CT-scan, and FDG PET-scan) allowed the diagnosis of giant cell arteritis, confirmed by biopsy of the temporal arteries. Differential diagnosis and treatment are discussed.

Radiopaque polymeric materials for medical applications. Current aspects of biomaterial research.

The aim of this review is to give an overview and some insight into different radiopaque polymeric materials that are currently used as medical implants or inserts. The advantages and limitations of each radiopaque polymeric material are summarized. The main method used to make medical implants radiologically visible is based on blending polymers with conventional radiopaque agents, blends which usually are a physical mixture of acrylic derivatives and inorganic salts. Other methods reported involve either the formation of single-phase radiopaque polymer salt complexes somehow preventing the release of the radiopacifying element by entrapment of the complex in a crosslinked network, or radiopaque polymerized monomers characterized by a radiopacifying element associated with the monomer unit prior to polymerization. In the near future, research will certainly concentrate on biocompatible radiopaque polymers with covalently bound opaque elements leading to stable polymers with properties equivalent to the nonopaque, parent polymer.

Iodine-containing cellulose mixed esters as radiopaque polymers for direct embolization of cerebral aneurysms and arteriovenous malformations.

The present study deals with the synthesis and characterization of radiopaque polymers which could, when solubilized in an appropriate water-miscible solvent, be useful embolic materials for the treatment of cerebral aneurysms and arteriovenous malformations. For this purpose cellulose (both microcrystalline and powdered) and partially substituted cellulose acetate (two different viscosity grades) were selected as starting materials to prepare iodine-containing polymers through various synthetic routes. The materials obtained were characterized by IR and NMR spectroscopy, molecular weight, iodine content, radiopacity and solubility in selected injectable organic solvents. The embolic liquids were evaluated for their precipitation behavior in a phosphate buffer solution (pH 7.4) mimicking physiological conditions using an in vitro aneurysm model. A sheep model was also used to assess in vivo the radiopacity and precipitation properties of a highly concentrated solution of a cellulose acetate 2,3,4-triiodobenzoate mixed ester. All materials with 4-iodo- and 2,3,5-triiodobenzoyl groups gave sufficient radiopacity to be regarded as possible embolization materials, whereas iododeoxycellulose and iododeoxycellulose acetate were not radiopaque because of their low iodine content. Esters synthesized using cellulose as starting material were not soluble in the selected organic solvents due to the presence of many residual hydroxyl groups, but could be used for other biomedical applications where insoluble radiopaque materials are used. In contrast, solubility of the materials as well as satisfactory precipitation properties were ensured using cellulose acetate as the starting material. In conclusion, cellulose acetate iodobenzoate mixed esters dissolved in diglyme or dimethyl isosorbide (dimethyl sulfoxide is probably less appropriate because of its toxicity and hemolytic properties) could be useful embolic liquids for the treatment of cerebral aneurysms or arteriovenous malformations.

In vitro assessment of new embolic liquids prepared from preformed polymers and water-miscible solvents for aneurysm treatment.

Treatment of cerebral aneurysms by embolic liquids has been proposed as an alternative strategy to coil or balloon techniques. In order to assess the feasibility of this approach, a general screening of preformed polymers dissolved in biocompatible, water-miscible solvents has been carried out. The solubilizing capacity of the solvents has been evaluated by the solubility parameters approach. The viscosity of the solutions has been determined and the precipitation characteristics of the embolic liquids have been investigated in phosphate buffer solution pH 7.4 at 37 degrees C to mimic physiological conditions. The radiopaque agent bismuth (III) oxide was added to solutions having appropriate precipitation characteristics and the angiographic assessment, in an in vitro aneurysm model, were consistent with the precipitation properties and confirmed that only hard and coherent masses allowed satisfactory embolization. However, the solubilizing prediction using the calculation of the solubility parameters was only partially successful owing to the highly hydrophilic functional groups of the chosen solvents. This failing justifies the experimental screening that was carried out. This study pointed out that the frequently used solvent dimethyl sulfoxide could be replaced by more biocompatible solvents offering the possibility of using other preformed polymers. In conclusion, nine solutions of the selected polymer-solvent combinations could be used as embolic liquids for the treatment of cerebral aneurysms with respect to their satisfactory precipitation properties and viscosity.

In vitro models of intracranial arteriovenous fistulas for the evaluation of new endovascular treatment materials.

BACKGROUND AND PURPOSE: The purpose of this study was to create and test an in vitro model of intracranial arteriovenous fistulas (AVFs) that simulates the geometry of human vasculature and allows realistic testing of devices used in endovascular therapy. METHODS: The models were derived from corrosion casts of the main cervicocranial arteries and veins obtained from two nonfixed human specimens. Wax copies of the casts were produced and combined to create complex models simulating various types of intracranial AVFs. Wax assemblies were embedded with liquid silicone solidified into transparent blocks containing, after wax evacuation, hollow reproductions of the original vascular trees. The models were connected to a pulsatile pump and their compatibility with various imaging techniques and endovascular treatment materials was evaluated. RESULTS: The models were compatible with digital subtraction angiography, CT, MR imaging, and transcranial Doppler sonography. They provided a realistic endovascular environment for the simulation of interventional neuroradiologic procedures. CONCLUSION: Anatomically accurate and reproducible in vitro models of intracranial AVFs provide a valuable method for evaluating new endovascular treatment materials and for teaching purposes.

N-Substituted lysines as sources of lysine in nutrition.

Twenty seven alpha-N- and epsilon-N-substituted derivatives of lysine belonging to eight different classes: (1) natural dipeptides, (2) alpha-N-acyl-, (3)epsilon-N-acyl-, (4)epsilon-N-(alpha-amino acyl)-, (5)epsilon-N-(omega-amino acyl)-, (6)alpha-N-epsilon-N-di-amino acyl-, (7)epsilon-N-acylglycyl- and (8)Schiff's bases were synthesized. The "in vitro" utilization of some of them was tested by a rat growth assay. Only the derivatives which provided biologically available lysine were hydrolysed by one or more of the intestinal mucosa, liver or kidney homogenates. It is argued that derivatives which can be split by any of the above homogenates are potential sources of lysine. The derivatives of classes (1), (4), (6) and (8) are nearly as efficient as free lysine while lysine in classes (2) and (7) is not utilized at all. From the classes (3) and (5) only some are utilized: epsilon- formyl- and epsilon-acetyl- partially and epsilon-(gamma-glutamyl)-totally. The biologically available derivatives were 4 to 7 times less reactive than free lysine in the Maillard reaction and could therefore be used to fortify foods which have to be submitted to severe heat-treatments. A cheap method of synthesis of epsilon-(gamma-glutamyl)-lysine is proposed and its metabolic transit described.

Comparative hemolytic activity of undiluted organic water-miscible solvents for intravenous and intra-arterial injection.

In humans, nonaqueous solvents are administered intravascularly in two kinds of situations. They have been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. The need for these vehicles had increased in recent years, since the drug development process has yielded many poorly water-soluble drugs. The use of water-miscible nonaqueous solvents in therefore one of the approaches for administering these products as reference solutions useful in formulation bioequivalence studies. The intravascular use of organic solvents has also gained importance owing to a new approach for the treatment of cerebral malformations using precipitating polymers dissolved in water-miscible organic solvents. At present, the solvent most commonly used for the liquid embolics to solubilize the polymers is dimethyl sulfoxide, which exhibits some local and hemodynamic toxicities. In order to find new, less toxic vehicles for pharmaceutical formulations for the intravenous and intra-arterial routes and for embolic materials, 13 water-miscible organic solvents currently used (diluted with water) for pharmaceutical applications, were evaluated in this study. Their hemolytic activity and the morphological changes induced when mixed with blood (1:99, 5:95, 10:90 solvent:blood) were estimated in vitro. From these data, the selected organic solvents could be subdivided into four groups depending on their hemolytic activity: very highly hemolytic solvents (ethyl lactate, dimethyl sulfoxide), highly hemolytic solvents (polyethylene glycol 200, acetone), moderately hemolytic solvents (tetrahydrofurfuryl alcohol, N-methyl-2-pyrrolidone, glycerol formal, ethanol, Solketal, glycofurol) and solvents with low hemolytic activity (propylene glycol, dimethyl isosorbide, diglyme).

Organic solvents for pharmaceutical parenterals and embolic liquids: a review of toxicity data.

Non-aqueous solvents have long been used in subcutaneous or intramuscular pharmaceutical formulations to dissolve water-insoluble drugs. In recent years, the need for these vehicles was increased since the drug discovery process has yielded many poorly water-soluble drugs. Besides, preparations containing embolic materials dissolved in undiluted non-aqueous water-miscible solvents have been proposed for the intravascular treatment of aneurysms, arteriovenous malformations, or tumors. These organic solvents, regarded as chemically and biologically inert, may show pharmacological and toxicological effects. Therefore, knowledge of tolerance and activity of non-aqueous solvents is essential before they can be administered, especially when given undiluted. This paper focuses on thirteen organic solvents reported as possible vehicles for injectable products and details toxicological data when they have been administered intravascularly. These solvents can be subdivided into three groups according to their description in the literature either for intravenous pharmaceutical parenterals or for intravascular embolic liquids: well-documented organic solvents (propylene glycol, polyethylene glycols, ethanol), solvents described in specific applications (dimethyl sulfoxide, N-methyl-2-pyrrolidone, glycofurol, Solketal, glycerol formal, acetone), and solvents not reported in intravascular applications but potentially useful (tetrahydrofurfuryl alcohol, diglyme, dimethyl isosorbide, ethyl lactate). This review of the literature shows that toxicity data on intravascular organic solvents are insufficient because they concern solvents diluted with water and because of the lack of comparative evaluation using the same methodologies.

Blastomatous tumors of the respiratory tract.

Two cases of blastomatous tumors of the respiratory tract are presented. The first is a pulmonary blastoma of an 81-year-old man, diagnosed as adenocarcinoma by cytologic examination, the cells being exfoliated from the large carcinomatous component. The patient died 1 year after manifestation of the symptoms. The second case is a tumor that developed in the nasopharynx of a 62-year-old man. This is the first reported case of a nasopharyngeal blastoma that presented a histology comparable to that seen in the pulmonary tumor. The presence of a hamartomatous benign mesenchymal component raises histogenetic considerations as to whether this was an independent part of an otherwise malignant tumor or whether it was induced by the malignant growth. Following incomplete surgical treatment and postoperative radiation, no recurrence was observed during the next 8 months.

[Biologic availability and metabolic transit of amino acids modified by technological processing]. / Disponibilité biologique et transit métabolique des acides aminés modifiés par les traitements technologiques.

The biological availability of amino acids modified by industrial processes has been measured in trials on rats, and their metabolic transit (urinary and faecal excretions, transformation into CO2 and retention in organs) has been studied using molecules labelled with 14C. Maillard reaction products. epsilon-fructose-lysine is not utilized as lysine source. However, less than 10 p. 100 of this substance, bound to proteins, is excreted unmodified in the urine. Intestinal flora destroys most of the fraction which is not absorbed. Premelanoidins are partially absorbed and "burnt" in the organism, whereas high molecularightwe melanoïdins are totally excreted in the faeces. epsilon-(gamma-glutamyl)-lysine and epsilon-(beta-aspartyl)-lysine isopeptides. 80 to 100 p. 100 of free epsilon-(gamma-glutamyl)-lysine are utilized by the Rat. It seems to be absorbed by the intestine, and subsequently hydrolyzed by the kidney, thus releasing lysine. Utilization of this isopeptide bound to proteins has not been shown till now. Free epsilon-(beta-aspartyl)-lysine is not utilized as lysine source. Methionine sulfoxyde and methionine sulfone. Methionine sulfone is not utilized as methionine source whereas most of the free and bound methionine sulfoxide is, in part, it is "reduced" by the liver (perfused liver). Lysino-alanine. Formation of lysino-alanine reduces the availability of lysine and cystine. It is partially excreted in urines, mainly as free lysino-alanine, but also as acetylated derivatives and unknown catabolites.