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Biomedical subjects

M Dahan

Publications and source records attributed to M Dahan.

At least 19 recordsLinked to original sources

Water-soluble pegylated quantum dots: from a composite hexagonal phase to isolated micelles.

We present a simple method based on the dispersion of fluorescent quantum dots (QD) into a liquid crystal phase that provides either nanostructured material or isolated QD micelles depending on water concentration. The liquid-crystal phase was obtained by using a gallate amphiphile with a poly(ethylene glycol) chain as the polar headgroup, named I. The hydration of QD/I mixtures resulted in the formation of a composite hexagonal phase identified by small-angle X-ray scattering and by polarized light and fluorescence optical microscopy, showing a homogeneous distribution of fluorescence within hexagonal phase. This composite mesophase can be converted into isolated QD-I micelles by dilution in water. The fluorescent QD-I micelles, purified by size exclusion chromatography, are well monodisperse with a hydrodynamic diameter of 20-30 nm. Moreover, these QD do not show any nonspecific adsorption on lipid or cell membranes. By simply adjusting the water content, the PEG gallate amphiphile I provides a simple method to prepare a self-organized composite phase or pegylated water soluble QD micelles for biological applications.

Electrons↗

Size, charge, and interactions with giant lipid vesicles of quantum dots coated with an amphiphilic macromolecule.

Semiconductor colloidal quantum dots (QDs) are promising fluorescent probes for biology. Initially synthesized in organic solvents, they can be dispersed in aqueous solution by noncovalent coating with amphiphilic macromolecules, which renders the particles hydrophilic and modifies their interactions with other biological compounds. Here, after coating QDs with an alkyl-modified polyacrilic acid, we investigated their colloidal properties in aqueous buffers by electrophoresis, electron microscopy, light scattering, and rate zonal centrifugation. Despite polymer dispersity and variation of the size of the inorganic nanoparticles, the polymer-dot complexes appeared relatively well-defined in terms of hydrodynamic radius and surface charge. Our data show that these complexes contain isolated QD surrounded by a polymer layer with thickness 8-10 nm. We then analyzed their interaction with giant unilamellar vesicles, either neutral or cationic, by optical microscopy. At neutral pH, we found the absence of binding of the coated particles to lipid membrane, irrespective of their lipid composition. An abrupt surface aggregation of the nanoparticles on the lipid membrane was observed in a narrow pH range (6.0-6.2), indicative of critical binding triggered by polymer properties. The overall features of QDs coated with amphiphilic polymers open the route to using these nanoparticles in vivo as optically stable probes with switchable properties.

Coated Materials, Biocompatible↗

Detection of oncogenic virus genomes and gene products in lung carcinoma.

We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic in humans. Thus, viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40) were investigated on tissue sections (prepared in tissue microarrays) with different techniques of immunohistochemistry and in situ hybridisation. None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied. Of note, in five cases of tumours with lymphoid infiltrates, we detected scattered EBV (EBER)-positive bystander lymphocytes. In three cases, a faint nuclear staining was found with the anti-latent nuclear antigen/LANA1 (HHV-8) antibody. These cases were checked by PCR with two sets of primers (orf 26 and orf 75) and remained negative for this latter virus. Taken together, our data strongly suggest that the conventional human oncogenic viruses (HPV, EBV, HCMV, HHV-8 and SV40) are unlikely to play some role in the development of lung carcinomas..

Adenocarcinoma↗

Diagnostic value of bronchoscopy, CT and transbronchial biopsies in diffuse pulmonary lymphangiomatosis: case report and review of the literature.

The authors present the case of a 48-year-old man with diffuse pulmonary lymphangiomatosis. This rare lymphatic disorder is characterized by proliferation of anastomosing lymphatic vessels varying in size. Clinical presentation and imaging findings are highly suggestive. Bronchoscopic examination of this patient showed, for the first time to our knowledge, vesicles disseminated throughout the bronchial tree. Histopathological examinations are necessary to differentiate lymphangiomatosis from lymphangiectasis. The diagnosis can be made by transbronchial biopsy without performing open lung biopsy which was, until now, considered necessary for diagnosis.

Biopsy, Needle↗

Measurement of the radiative and nonradiative decay rates of single CdSe nanocrystals through a controlled modification of their spontaneous emission.

We present a simple method to measure the radiative and nonradiative recombination rates of individual fluorescent emitters at room temperature. By placing a single molecule successively close and far from a dielectric interface and simultaneously measuring its photoluminescence decay and its orientation, both the radiative and nonradiative recombination rates can be determined. For CdSe nanocrystals, our results demonstrate that the fluorescence quantum efficiency, determined at the single-molecule level, is 98% in average, far above the value expected from conventional ensemble experiments. The bidimensional nature of the transition dipole is also directly evidenced from a single-particle measurement.

Journal Article↗

Cardiac abnormalities 15 years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Institut Gustave Roussy.

The purpose of this paper was to determine the cardiac status in children 15 years or more after adriamycin therapy for a solid tumour. Of the 447 pts, 229 pts were fully studied and 218 were not. The following cardiac evaluations were proposed to all the 447 consecutive patients (pts): (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-hour holter ECG; (3) (131)l-mlBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO(2) max measurement. The radiation doses delivered to 6 points in the heart were estimated for all patients who had received radiotherapy. Congestive heart failure was diagnosed in 24 of 229 (10%) evaluated pts, with a median interval of 15 years (0.3-24 years) from the first symptom after adriamycin treatment. Among the 205 remaining pts, 13 asymptomatic pts (6%) had severe (n=4) (FS<20%) or marked (n=9) (20< or =FS<25%) systolic dysfunction. In the 192 others, the median meridional end-systolic wall stress was 91 (53-135) and it exceeded 100 g cm(-2) in 52 pts. Using a Cox model, only the cumulative dose of adriamycin and the average radiation dose to the heart, were identified as risk factors for a pathological cardiac status. In conclusion, the risk of cardiac failure or severe abnormalities increases with adriamycin treatment, radiotherapy and time since treatment, even after a follow-up of 15 years or more. In our series, after an average follow-up of 18 years, 39% of the children had a severe cardiac dysfunction or major ventricular overload conditions. The risk increases with the dose of adriamycin and radiation received to the heart, without evidence for threshold.

Adolescent↗

[Surgical management of emphysema].

Surgery is an important therapeutic option for emphysema patients with invalidating dyspnea and poor quality-of-life. Preoperative tests must determine the degree of functional impairment (dyspnea score, walking test, quality-of-life) and evaluate lesion reversibility (imaging, function tests, TLCO, blood gases, scintigraphy, right microcatheterism) and assess the patient's general health status. Besides lung transplantation, the only surgical alternative is resection which, depending on the type of parenchymal damage, can involve excision of bullae or volume reduction. Several modalities can be proposed: atypical resection of the apexes via sternotomy, multiple unilateral atypical resection, simple lobectomy. The choice depends on the distribution of the parenchymal destruction and also on the severity of the emphysema and the patient's age. Operative mortality is now well below 10%. Volume reduction provides significant functional improvement in 80% of patients but with a temporary effect (4-5 years). Bullae excision is particularly important since functional recovery is achieved early and persists.

Dyspnea↗

Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade.

AIMS: To assess cytokeratin (CK) and thyroid transcription factor (TTF)-1 expression in primary epithelial lung tumours by comparison with non-pulmonary carcinomas and to correlate it with their histological type and grade. METHODS AND RESULTS: Immunohistochemistry using antibodies against CKs 5/6, 7, 19, 20 and TTF-1 was applied to 165 primary and 37 secondary epithelial lung tumours. CK5/6 is a sensitive and specific marker of lung squamous carcinomas being positive in 100% of cases. CK7 is a common marker of primary lung adenocarcinomas (100% of cases) but with a lower specificity since it is also observed in other primary lung carcinomas (70% of large-cell neuroendocrine carcinomas, 40% of large-cell carcinomas, 23% of squamous carcinomas) but also in 27% of non-pulmonary adenocarcinomas. Addition of an anti-CK20 may be useful to prove or disprove the pulmonary origin of an adenocarcinoma when there is a history of colon cancer. CK19 is ubiquitous but a predominant or exclusive 'dot-like' pattern is very suggestive of high-grade neuroendocrine carcinoma. TTF-1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma if a thyroid origin is excluded. Its expression in neuroendocrine lung tumours depends on the tumour grade. CONCLUSIONS: Immunohistochemical expression of CKs and TTF-1 may be correlated with histological type and grade of lung primary epithelial tumours and may allow them to be distinguished from non-pulmonary carcinomas.

Adenocarcinoma↗

The effect of periodontal treatment on the salivary bacterial load and early plaque formation.

AIM: The purpose of the present study was to investigate in periodontitis patients the relationship between the number of bacteria in the saliva and the amount of de novo plaque formation before and after treatment. METHODS: At baseline, before any treatment was provided, patients rinsed with 10 ml sterile saline. After professional tooth cleaning the patients were instructed to abolish all tooth cleaning procedures for the subsequent 24 h. After this period, the rinsing procedure was repeated and the amount of de novo plaque was assessed. Three months after the initial periodontal therapy was completed the experiment was repeated. The microbiological evaluation of the rinsing samples was carried out by means of phase contrast microscopy and anaerobic culturing. RESULTS: After treatment the amount of de novo plaque was less compared to before treatment, 0.40 and 0.65 respectively. Both before and after treatment more de novo plaque was present at sites with inflammation than at healthy sites. In order to evaluate the contribution of the numbers of salivary bacteria to the amount of de novo plaque formation an analysis was carried out for healthy sites. This analysis included only healthy sites as determined before treatment and the same sites after treatment. The results showed a significant reduction in the de novo plaque formation after treatment (0.49 before and 0.22 after treatment). Phase contrast microscopic evaluation showed that the number of bacteria in the rinsing samples after treatment was less than before treatment. After treatment also a reduction was found in the prevalence of Prevotella intermedia, Tannerella forsythensis and Peptostreptococcus micros in the rinsing samples. CONCLUSION: The present study confirms the observation in the literature that the periodontal condition is of major importance in the rate of de novo plaque formation. In addition, the results suggest that the number of bacteria in the saliva may play a role.

Adult↗

A possible genetic factor in the pathogenesis of ovarian dermoid cysts.

This study was undertaken in order to evaluate a possible genetic influence on the pathogenesis of ovarian dermoid cysts. We have performed a case-control study comparing the prevalence of a history of dermoid cysts in first-degree relatives of women with dermoid cysts and among first-degree relatives of women without dermoid cysts. The study group included 285 women with an established diagnosis of ovarian dermoid cysts. The control group included 378 women with sonographically normal ovaries. To assess the relationship between a first-degree family history of dermoid cysts and the diagnosis of ovarian dermoid cysts, a multivariate stepwise logistic regression model was applied. In 28 families of the study group (9.8%), a dermoid cyst was found in at least 1 first-degree relative as compared with only eight families (2%) among the controls (adjusted odds ratio -5.60; 95% CI 2.24-14.2). The data suggest a genetic predisposition towards dermoid cysts which merits further exploration.

Adult↗

Transverse fluctuations of single DNA molecules attached at both extremities to a surface.

We present a simple method to stretch DNA molecules close to a surface without any chemical modification of either the molecules or the surface. By adjusting the pH of the solution, only the extremities of DNA molecules are tethered to a glass coverslip made hydrophobic, while stretching is achieved using a hydrodynamic flow. These extended molecules provide a very favorable template for DNA-protein interaction studies by purely optical means. Pursuing these experiments requires first a full characterization of the thermally driven fluctuations of the tethered DNA molecules. For this purpose, these fluctuations were recorded by fluorescence microscopy and were analyzed in terms of normal modes. Our experimental results are well described by a model accounting for the nonlinear elastic behavior of the chain. Remarkably, the proximity of the molecules to a rigid surface does not alter the main features of their dynamics, and our results are in agreement with previous studies on extended DNA in viscous solutions.

Biophysical Phenomena↗

Statistical aging and nonergodicity in the fluorescence of single nanocrystals.

The relation between single particle and ensemble measurements is addressed for semiconductor CdSe nanocrystals. We record their fluorescence at the single molecule level and analyze their emission intermittency, which is governed by unusual random processes known as Lévy statistics. We report the observation of statistical aging and ergodicity breaking, both related to the occurrence of Lévy statistics. Our results show that the behavior of ensemble quantities, such as the total fluorescence of an ensemble of nanocrystals, can differ from the time-averaged individual quantities, and must be interpreted with care.

Cadmium Compounds↗

[Funnel chest: filling technique with deep custom made implant].

Through 97 patients over 9 years, the authors present a surgical treatment for "funnel chest" using custom-made silicone elastomer prothesis which are deeply placed, behind muscle and aponevroses. They justify the choice of this simple and non invasive technique, by the fact that this deformation is only morphological in most cases or even only inaesthetic with exceptional cardiac or pulmonary consequences. Patient's motivation being mainly due to psychological disconfort, the non invasive aspect of the technique leads them to choose surgery, particularly as results are good and complications seldom.

Adolescent↗

[Surgery of chest wall tumors].

The treatment of the chest wall tumors are based on the following principles. The surgery is the only curative treatment of the disease and the pain. The pre-operative assessment may find its beneficial only to eliminate the non surgical affections, to foresee the peroperative dangers and to prepare the reconstruction. The use of more adapted and better supported prosthesis has pushed back today the limits of the resections to the possibilities of covering. Finally the quality of the result depends more than one multidisciplinary work that technical prowess's of only one operator.

Humans↗

[Nodular bronchioloalveolar carcinoma at early stage].

INTRODUCTION: The aim of our study was to describe the main characteristics of bronchioloalveolar carcinoma (BAC) in the light of the latest WHO classification. The clinical, pathological and radiological features of 16 consecutive resected cases of early BAC (stage IA) were reviewed. METHODS: Retrospective pathology of 249 adenocarcinomas over a 32 months period. RESULTS: Computerised tomography (CT) features which supported a diagnosis of BAC included a peripheral location, irregular margins forming a star pattern, pleural tagging, ground-glass attenuation and an air bronchogram. Immunochemistry was positive in all cases for cytokeratins 7 and 19, EMA and TTF-1, but was only variably positive for ACE, P53 and MIB-1. For 14 out of 16 patients clinical outcome was favourable with no evidence to date of recurrence since surgery. Of the others, one developed extra-thoracic metastases and the other a local recurrence requiring further surgery. CONCLUSION: Recognising these characteristics of BAC is important as early diagnosis and treatment of this condition can be associated with an excellent prognosis.

Adenocarcinoma, Bronchiolo-Alveolar↗

A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure.

OBJECTIVES: This study was designed to assess the prognostic value of a new variable derived from a cardiopulmonary exercise test, the circulatory power, a surrogate of cardiac power, at peak exercise, in patients with chronic heart failure. BACKGROUND: Peak exercise cardiac power and stroke work are invasive parameters with recently proven prognostic value. It is unclear whether these variables have better prognostic value than peak oxygen uptake (VO(2)). METHODS: The study population comprised 175 patients with chronic heart failure (ejection fraction <45%) who underwent a cardiopulmonary exercise test. Circulatory power and circulatory stroke work were defined as the product of systolic arterial pressure and VO(2) and oxygen pulse, respectively. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS: With a mean follow-up of 25+/-10 months, ejection fraction, heart rate, systolic arterial pressure, peak VO(2), VCO(2), the anaerobic threshold, minute ventilation, the ventilatory equivalents of oxygen and carbon dioxide, the half times of VO(2) and VCO(2) recoveries, and the circulatory stroke work and power predicted outcome. Multivariate analysis demonstrated that the peak circulatory power (chi-square=19.9, P<0.001) (but not peak circulatory stroke work) was the only variable predictive of prognosis. CONCLUSION: The prognostic value of cardiopulmonary exercise tests in heart failure patients can be improved by assessing a new variable, the circulatory power - a surrogate of cardiac power - at peak exercise.

Adult↗

Pancreatitis secondary to hyperparathyroidism during pregnancy.

BACKGROUND: It has been suggested that magnesium can be used to reduce serum calcium levels seen with hyperparathyroidism during pregnancy, thus reducing maternal and fetal risk. CASE: A young woman presented at 32 weeks' gestation with abdominal pain from pancreatitis caused by hyperparathyroidism from a parathyroid adenoma. She was started on magnesium sulfate tocolysis for preterm labor. During treatment, serum parathyroid hormone was undetectable, but serum calcium and vitamin D-1,25 were elevated. When magnesium was discontinued, her vitamin D-1,25 was suppressed and the parathyroid hormone was elevated. CONCLUSION: For some patients, because of persistent hypercalcemia, magnesium sulfate might not be a viable treatment option for hyperparathyroidism during pregnancy.

Adenoma↗

Expression of matrix metalloproteinases in healthy and diseased human gingiva.

BACKGROUND, AIMS: The aim of our study was to investigate the patterns of several metalloproteinases (MMP-1, MMP-2 and MT1-MMP) mRNAs expression using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and to correlate them with clinical parameters and bacteriological diagnosis in healthy versus diseased human gingiva. METHODS: To identify the cell origin of MMP production, in situ hybridization (ISH) was also performed for the MMPs on the same samples. 17 gingival biopsies were collected (13 affected by advanced periodontitis and 4 healthy used as controls) and plaque index, gingival index, pocket depth and bleeding on probing were measured. Subgingival microbial samples were also collected to be analysed by a DNA probe technique. The biopsies were processed both for RT-PCR and ISH. We also investigated a model for bacterial induced MMP expression in human gingival fibroblasts (HGF) infected by Eikenella corrodens. RESULTS: We found an expression of the mRNA encoding MMP-1 only in diseased gingiva but at low levels relative to beta-actin (mean+/-SD: diseased versus healthy: 0.013+/-0.024 versus 0). Although the frequencies and levels of mRNA encoding for MMP-2 or MT1-MMP are not significantly different between each group (mean+/-SD: 0.329+/-0.344 versus 0.137+/-0.219 for MMP-2; 0.485+/-0.374 versus 0.466+/-0.296 for MT1-MMP), using ISH, we observed an expression of both mRNAs in fibroblasts of pathological specimens at sites that histologically showed signs of chronic inflammation and connective tissue remodelling. In vitro infection of HGF by Eikenella corrodens stimulated 3-fold the production of the mRNA encoding MMP-2 while other mRNAs remained unchanged. CONCLUSION: Our results did not reveal significant differences in the expression of mRNAs encoding for the MMPs between healthy and periodontitis-affected patients, reflecting the great heterogeneity in the periodontal status of individuals. However, they indicate that gingival fibroblasts are an active source of MMP-2 production in response to a periopathogen.

Adolescent↗