[Ameloblastoma of the jaws. A retrospective analysis from 1994 to 2007]. / Améloblastomes des mâchoires. Analyse rétrospective de 1994 à 2007.

INTRODUCTION: Ameloblastomas and keratocysts are the most frequent epithelial odontogenic tumors of the jaws. They have a high recurrence rate. This retrospective study reviews the features of ameloblastomas operated on in our unit from 1994 to 2007. PATIENTS AND METHODS: The studied parameters were sex, ethnic origin, age at diagnosis, clinical signs, radiographic presentation, site distribution, histological type, treatment, and follow-up records. RESULTS: One hundred and sixteen patients were included (with 239 surgical samples). The mean age was 36 years, with a majority of Europeans, 60% of multilocular radiolucent lesions with root resorption, mandibular location (93%). Twenty-one percent of the patients presented with an impacted tooth, the third molar in 79% of cases. Fifty percent of the lesions were from 5 to 13cm in length, 10% longer than 13cm. The most common histological type was follicular ameloblastoma. Patients were treated by enucleation in 82% of cases and radical mandibular resection with reconstruction in 11% of cases. The follow-up was documented for 96% of the patients with a 44% recurrence rate. Seventy-four percent of patients with a double recurrence presented with a "follicular" ameloblastoma. DISCUSSION: We prefer a well-performed enucleation which preserves surrounding bone. The high rate of follicular type recurrence should more systematically lead to a combined treatment: periostectomy and tooth extraction. Our data was compared with previously published large series.

Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis.

The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.

Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant.

Osteopetrosis is an inherited disorder characterized by bone sclerosis due to reduced bone resorption. Here we report that human osteopetrotic osteoblast-like (Ob) cells express a defective phenotype in primary cultures in vitro, and that bone marrow transplant (BMT) corrects osteoblast function. DNA analysis at polymorphic short-tandem repeat loci from donor, recipient, and primary Ob-like cells pre-BMT and 2 yr post-BMT revealed that Ob were still of recipient origin post-BMT. Osteopetrotic Ob-like cells obtained pre-BMT showed normal and abnormal 1,25(OH)2D3-induced alkaline phosphatase (ALPase) and osteocalcin production, respectively, and failed to produce macrophage colony-stimulating factor (M-CSF) in response to IL-1a and TNF-alpha. These parameters were all normalized in primary Ob-like cells prepared 2 yr post-BMT. X-linked clonality analysis at the human androgen receptor (HUMARA) locus revealed that osteoblasts showed a polyclonal and an oligoclonal derivation pre- and post-BMT respectively, indicating that a limited number of progenitor reconstituted this population. Because osteoblasts were still of recipient origin post-BMT, this suggests that functional osteoclasts, due to the replacement of hematopoeitic cells, provided a local microenvironment in vivo triggering the differentiation and/or recruitment of a limited number of functional osteoblasts.

Protein carboxyl methylation in kidney brush-border membranes.

Protein carboxyl methylation activity was detected in the cytosol and in purified brush-border membranes (BBM) from the kidney cortex. The protein carboxyl methyltransferase (PCMT) activity associated with the BBM was specific for endogenous membrane-bound protein substrates, while the cytosolic PCMT methylated exogenous substrates (ovalbumin and gelatin) as well as endogenous proteins. The apparent Km for S-adenosyl-L-methionine with endogenous proteins as substrates were 30 microM and 4 microM for the cytosolic and BBM enzymes, respectively. These activities were sensitive to S-adenosyl-L-homocysteine, a well known competitor of methyltransferase-catalyzed reactions, but were not affected by the presence of chymostatin and E-64, two protein methylesterase inhibitors. The activity of both cytosolic and BBM PCMT was maximal at pH 7.5, while BBM-phospholipid methylation was predominant at pH 10.0. Separation of the = methylated proteins by acidic gel electrophoresis in the presence of the cationic detergent benzyldimethyl-n-hexadecylammonium chloride revealed distinct methyl accepting proteins in the cytosol (14, 17, 21, 27, 31, 48, 61 and 168 kDa) and in the BBM (14, 60, 66, 82, and 105 kDa). Most of the labelling was lost following electrophoresis under moderately alkaline conditions, except for a 21 kDa protein in the cytosol and a 23 kDa protein in the BBM fraction. These results suggest the existence of two distinct PCMT in the kidney cortex: a cytosolic enzyme with low selectivity and affinity, methylating endogenous and exogenous protein substrates, and a high-affinity BBM-associated methylating activity.

New 4-point pharmacophore method for molecular similarity and diversity applications: overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures.

A new 4-point pharmacophore method for molecular similarity and diversity that rapidly calculates all potential pharmacophores/pharmacophoric shapes for a molecule or a protein site is described. The method, an extension to the ChemDiverse/Chem-X software (Oxford Molecular, Oxford, England), has also been customized to enable a new internally referenced measure of pharmacophore diversity. The "privileged" substructure concept for the design of high-affinity ligands is presented, and an example of this new method is described for the design of combinatorial libraries for 7-transmembrane G-protein-coupled receptor targets, where "privileged" substructures are used as special features to internally reference the pharmacophoric shapes. Up to 7 features and 15 distance ranges are considered, giving up to 350 million potential 4-point 3D pharmacophores/molecule. The resultant pharmacophore "key" ("fingerprint") serves as a powerful measure for diversity or similarity, calculable for both a ligand and a protein site, and provides a consistent frame of reference for comparing molecules, sets of molecules, and protein sites. Explicit "on-the-fly" conformational sampling is performed for a molecule to enable the calculation of all geometries accessible for all combinations of four features (i.e., 4-point pharmacophores) at any desired sampling resolution. For a protein site, complementary site points to groups displayed in the site are generated and all combinations of four site points are considered. In this paper we report (i) the details of our customized implementation of the method and its modification to systematically measure 4-point pharmacophores relative to a "special" substructure of interest present in the molecules under study; (ii) comparisons of 3- and 4-point pharmacophore methods, highlighting the much increased resolution of the 4-point method; (iii) applications of the 4-point potential pharmacophore descriptors as a new measure of molecular similarity and diversity and for the design of focused/biased combinatorial libraries.

Angiotensin converting enzyme inhibitors. (Mercaptoaroyl)amino acids.

A series of (mercaptoaroyl)amino acids and related compounds was synthesized and tested for ability to inhibit angiotensin converting enzyme (ACE). The most active compound was N-(3-chloro-2-mercaptobenzoyl)-N-cyclopentylglycine, having an in vitro I50 = 0.28 microM. Substitution of the aromatic 3-position by small polar groups enhanced ACE inhibitory activity, whereas bulky groups diminished it. Alteration of the beta relationship between the mercaptan and amide carbonyl or masking of the thiol by acylation reduced activity. Replacement of the thiol by nitro, hydroxy, or carboxy gave compounds lacking ACE inhibitory activity.

Angiotensin-converting enzyme inhibitors: new orally active 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.

The preparation of a series of 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) in vitro and in vivo were examined. These compounds are assumed to act as prodrugs since they undergo rapid ring-opening reactions to give the corresponding biologically active free SH compounds when incubated with rat plasma or when treated with aqueous 0.1 N HCl or phosphate buffer (pH 7.4). The thiazepines 23-25 and 30 are potent inhibitors of ACE when administered po to rats and are comparable in potency to captopril (1). The most active thiazines in rats, po, were 42 and 45. Of the benzothiazepines studied, 22a was the most active in inhibiting ACE in the conscious normotensive rat, ID50 = 0.15 mg/kg, po. The acute antihypertensive effects of oral administration of a number of these compounds on mean arterial pressure and heart rate were studied in spontaneously hypertensive rats (SHR) maintained on a sodium-deficient diet.

Angiotensin-converting enzyme inhibitors. 9. Novel [[N-(1-carboxy-3-phenylpropyl)amino]acyl]glycine derivatives with diuretic activity.

A series of molecules 1 having sulfonamide diuretic moieties covalently linked to non-sulfhydryl angiotensin-converting enzyme inhibitors (ACEI) were prepared and tested for both activities. IC50 values for ACEI as low as 7 nM were observed. Discernable diuretic activity was seen for several hydrochlorothiazide-based molecules. Effects of the ACEI and diuretic structures on the respective potencies are discussed.

Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives.

Compounds 1a-g consisting of enalaprilat covalently bonded to aryl sulfonamides, including several known thiazide diuretics, were synthesized and tested for ACE inhibitory and diuretic and overall antihypertensive effects. All compounds were potent ACE inhibitors in vitro, with IC50 = 6.5-85 nM. At 10 mg/kg iv or ip in the rat, 1a-g inhibited the AI pressor response by 76-100%; inhibition declined significantly upon oral dosing. Compounds 1a and 1f at 100 mg/kg ip in the sodium-depleted, spontaneously hypertensive rats reduced blood pressure 28-35% and 41-42%, respectively. Compounds 1a and 1f elicited natriuresis and kaliuresis without accompanying volume increases in the rat; 1c at 25 mg/kg iv induced delayed diuresis. Compound 1f has been chosen for further development.

Infrahyoid myocutaneous flap in reconstructive maxillofacial cancer and trauma surgery.

We report the use of an island infrahyoid myocutaneous flap, pedicled on the superior thyroid vessels, in a group of 21 patients. This flap allows reconstruction of intraoral defects or defects of the lower portion of the face, as large as 10 x 4 cm. We used it in 15 cases to repair parts of the oral cavity, after tumour resection, in 2 patients with mandibular osteoradionecrosis and in 4 patients with gunshot injuries. Among the 21 flaps, no muscular necrosis was observed; however, 4 total necrosis and 4 partial necrosis (< or = 25% of the skin area) of the skin paddle were recorded. Loss of the skin paddle was primarily attributable to the anatomical variations of the veins draining this flap.

Mesenchymal chondrosarcoma of the jaws. Report of four cases.

Mesenchymal chondrosarcoma (MCS), described in 1959 by Lichtenstein & Bernstein, is a very rare malignant tumour. Only 46 cases have been previously reported in the jaws. Over a period of 30 years, four chondrosarcomas of mesenchymal type (of which one has already been published in 1987 with a three-month follow up) were treated in our department. Two patients have been followed for more than 17 years, of whom one has died of an intracranial extension and the other is still alive after surgical treatment of numerous recurrences and metastases. The two others are tumour-free with a follow up of 18 months and 11 years respectively. Histological, epidemiological and clinical features and treatment of MCS are discussed relevant to the data published in the literature.

Ventilator associated pneumonia and endotracheal tube repositioning: an underrated risk factor.

Aspiration of secretions toward lower airways potentially occurs during endotracheal tube (ETT) repositioning in mechanically ventilated patients in the intensive care unit and may be a risk factor for developing ventilator-associated pneumonia (VAP). This case-control study confirms that repositioning of the ETT is an independent risk factor for VAP.

Decision-making needs of patients with depression: a descriptive study.

The study's purpose was to explore the decision-making needs of patients considering treatment options for their depression. Semi-structured interviews were guided by the Ottawa Decision Support Framework. Of 94 participants, 67 were uncertain about their decision. Common decisions identified were whether or not to take medications, attend support groups, undergo electroconvulsive therapy, and location of care. Those feeling certain were more likely to have made a decision (RR 1.37; 95% CI: 1.05, 1.78). However, 40 patients who had 'made a decision' in the recent past were uncertain about their decision. Compared with those who were certain, the uncertain group felt less informed (2.65 vs. 1.64; P < 0.001), less supported (2.63 vs. 1.88; P < 0.001) and less clear about how they valued the benefits and risks of options (2.57 vs. 1.69; P < 0.001). Other influential factors included concerns about confidentiality, distress from depression, embarrassment, panic attacks and lack of energy. Few patients wanted to defer decision making to their physician (n = 8) or family (n = 1). To support decision making, participants identified the need for: discussions with their psychiatrist, nurse or family doctor; access to printed information; and information provided by health professionals and health societies.

[Giant-cell tumors: three recurrent cases in young patients]. / Tumeurs à cellules géantes: à propos de trois cas récidivants chez des sujets jeunes.

INTRODUCTION: True giant-cell tumor is a rare jaw osteolytic benign tumor belonging to the larger family of giant-cell tumors. It is particular because of the risk of recurrence and potential metastatic spread. OBSERVATION: Since 1973, we have managed four cases of true giant-cell tumors in our unit. The three cases reported here concerned young patients who developed recurrence after tumorectomy-curettage. DISCUSSION: Based on a literature review we defined this entity among the other giant-cell tumors. We emphasize the importance of early definitive diagnosis based on rigorous clinical and radiological confrontations. Because of its benign nature, the most conservative surgical treatment (tumorectomy-curettage) is generally proposed for the young patient. We noted however that in the three cases presented here, more radical surgical treatment with an enlarged tumorectomy removing the adjacent bone was advisable because of the high risk of recurrence and metastasis.

[Double-barrel fibular free flap for mandibular reconstruction: beneficial alternative for dental implanted rehabilitation (5 cases)]. / Lambeau libre de péroné en double barre: intérêt du montage dans les reconstructions mandibulaires pour une réhabilitation prothétique sur implants (5 cas).

INTRODUCTION: As major loss of mandibular bone stock requires a vascularized transfer, fibula free flap reconstruction is considered to be the best free flap for its length and reliability. Its main advantage is to accept dental implants. Single or double-barrel reconstruction can be performed. Double-barrel reconstruction is generally preferred because the bone superposition offers enough height to allow dental implants. MATERIAL AND METHODS: We reviewed five selected cases of double-barrel fibula free flap adaptive mandibular reconstruction performed among a series of 11 oral rehabilitations with planned dental implants, focusing on the technical aspects. RESULTS: Today, dental rehabilitation has been achieved in three double-barrel fibula flaps. Details are reported concerning the implant step. DISCUSSION: In this perspective, we discuss the choice of the reconstructive technique in order to obtain adequate bone height. Early in our experience and for different reasons discussed in the text, we used a single barrel fibula flap. This technique provided sufficient height in some cases, but had to be completed by bone grafts in few patients. Our experience illustrates the usefulness of the double barrel technique which provide definitive bone height sufficient for dental implants. The double-barreled technique should be considered as the best solution.

[Leiomyosarcoma of the gingiva. Apropos of a case. Review of the literature]. / Léiomyosarcome de la gencive. A propos d'un cas. Revue de la littérature.

Leiomyosarcoma (LMS) accounts for 7% of all smooth tissue sarcomas. The rarity of smooth muscle cells in the oral cavity makes LMS a rare tumor in this localization. We report a case of gingival LMS in a 43-year-old woman. We reviewed 23 cases of LMS or the oral cavity report in the literature since 1980. Age of occurrence varied from 2.5 to 63 years with a predominance in the 20 to 30 years age range. In two-thirds of the cases, the first symptom was the development of a painful mass. In half the mass developed in the maxilla and in one-quarter it occurred in the gingival mucosa alone. In nearly all cases treatment was wide excision resection. Surgery with chemotherapy and radiotherapy is reserved for high-grade or recurrent leiomyosarcoma.

[Sphenoid fissure syndrome in orbital fractures. Case presentation and literature review]. / Syndrome de la fente sphénoïdale au cours des fractures de l'orbite. Présentation d'un cas et revue de la littérature.

The superior orbital syndrome has been reported as a very rare complication of orbital fracture. In emergency clinical examination and computed tomography of the cranio-orbital region have provided diagnosis of the compression of the superior orbital fissure content by oedema and/or hematoma. These examinations have determined the type of cranio-orbital fractures and the absence of extra-dural haemorrhage, optical nerve damage or compression, which required emergency treatment. After surgical treatment of the cranio-orbital fracture by temporal and transconjunctival approach, the orbital fissure syndrome has required supervision. The recovery of ophthalmoplegia has taken several months. Minor after effects have been observed for the patient reported.