Biomedical subjects

C Merle

Publications and source records attributed to C Merle.

At least 19 recordsLinked to original sources

PubMed2005

[Intolerance to and/or drug interactions of anti-HIV and anti-HVC therapy].

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.

Antiviral Agents↗

PubMed2005

Vancomycin biodegradable poly(lactide-co-glycolide) microparticles for bone implantation. Influence of the formulation parameters on the size, morphology, drug loading and in vitro release.

The present study investigates vancomycin microencapsulation in biodegradable PLAGA microparticles. To optimize encapsulation efficiency by the double emulsion (w/o/w) solvent evaporation/extraction process, two parameters were studied: surfactant (Span 80) rate and external aqueous phase saturation. In vitro dissolution studies, laser granulometry and scanning electron microscopy were performed to characterize the microparticles. The best results were obtained by stabilizing the first emulsion with 0.5% Span 80 and saturating the external phase with sodium chloride. Such parameters allowed a 95% drug encapsulation efficiency. This process yielded round microparticles with a mean diameter of approximately 170 microm and presenting a smooth surface without any pores. Moreover, this formulation induces a sustained drug release at a constant rate over a period of 10 days. Such materials could be associated with biphasic calcium phosphate granules to form an antibiotic-loaded injectable bone substitute offering a long-term activity in situ.

Anti-Bacterial Agents↗

PubMed2005

Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement.

TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.

5-alpha-Dihydroprogesterone↗

PubMed2004

[Postoperative quality of life for patients with a vestibular schwannoma].

OBJECTIVES: To determine the prognoses criteria of quality of life's impairment after vestibular schwannoma surgery. STUDY DESIGN: Our study includes retrospectively 104 consecutive patients operated between 1991 & 2000 of a vestibular schwannoma. Patients with bilateral tumors were not included, neither patients lost of follow-up. The french version of the Short Form-36 self assessment questionnaire was sent to all patients. RESULTS: The response rate was 68% (71 patients). The patients' postoperative quality of life was lower of the norm, especially for psychical dimensions. This impairing of health whatever age, tumor size, operative approach or follow-up time. Sex and 2nd surgery were the only factors associated with a lower score. Women had worse rating of physical functioning. CONCLUSION: To operate small tumors should not assume that the impact on patients'life would be necessary less than following the removal of larger tumors. Women should have particularly clear explications before surgery and while follow-up.

Adult↗

PubMed2004

[Clinical assessment of the risk of Human Immunodeficiency virus (HIV) infection in the population consulting an anonymous and free screening center].

INTRODUCTION: The anonymous and free AIDS screening centers were developed in France in 1987 to incite the general population to undergo screening for HIV infection. The aim of this paper was to conduct a prospective study describing the principle characteristics and level of risk of those consulting a center in the Year 1999. POPULATION AND METHODS: A face to face physician-consultant questionnaire was proposed to all the consultants that Year. It included 20 questions regrouped in general characteristics of the subject, number of previous screenings, reason for screening, type of risk taken, date of last risk taken, and number of sexual partners during the past 12 Months and throughout their life without the use of a condom. RESULTS: Two thousand six hundred seventy-eight persons consulted (sex ratio=1) aged a mean of 25.8 Years. The men were older than the women (respectively 27 versus 24.6; p<0.05). The reason for screening was a decision made by the couple in 44.6 p. 100, an unprotected sexual relationship in 47.6 p. 100 another reason in 7.6 p. 100 and drug abuse in 0.2 p. 100 of cases. The sex mode declared was heterosexual in 94.5 p. 100 and homo or bisexual in 5.4 p. 100. The majority of those consulting (66.2 p. 100) had had between 0 and 2 partners during the past 12 Months; 66 p. 100 had had more than 10 during their life without using a condom. The assessment of the global risk by the physician was: very high in 1 p. 100, high in 2.5 p. 100, moderate in 13.3 p. 100, low in 70.7 p. 100 and nil in 12.5 p. cent. Five HIV infections were diagnosed, all in persons at high or very high risk. DISCUSSION: These results should stimulate the radical differentiation of the management of persons consulting according to the level of risk identified by the medical questionnaire.

Adolescent↗

PubMed2003

Compactibility study of calcium phosphate biomaterials.

This study investigated the micromechanism responsible for the densification and consolidation of powders during dynamic compaction, an experimental process in which ceramic is formed without heating. Three calcium-deficient apatites (CDA: two powders and a fibrous compound) and a biphasic calcium phosphate (BCP) were studied to determine their aptitude (rheological and physical properties) for compactibility under various dynamic compaction pressures. Powders were investigated for their physicochemistry, particle size, and flow time, and compacts for their compaction rate, density, specific area, mechanical characteristics, and disintegration time. Powder particles showed different morphological features depending on the synthesis protocol used, specific area and rheological behaviour. Compacts were not obtained with BCP, regardless of the gas pressure used, whereas CDA produced compacts with good mechanical properties (high hardness and compression stress), particularly for the fibrous compound. The poor compressibility and compactibility of BCP powders were confirmed, whereas fibrous CDA powders showed good compactibility conducive to high-quality filling of biomaterials.

Biocompatible Materials↗

PubMed2003

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility.

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles (200 microm mean diameter) was most efficient with a simple emulsion technique that dispersed 122.5 mg/g of polymer. Scanning electron micrographs showed smooth or pitted particles. Dissolution studies were correlated with microparticle morphology, indicating higher release with pitted particles when vancomycin was encapsulated in a dissolved state. The cytocompatibility of these poly(epsilon-caprolactone) microparticles was demonstrated by a direct contact cytotoxic assay. This material can be considered as an efficient drug delivery system for bone implantation.

Absorbable Implants↗

PubMed2003

Purification and characterization of a membrane glycoprotein from the fish pathogen Flavobacterium psychrophilum.

AIMS: The cell envelope of the fish pathogen Flavobacterium psychrophilum contains more than 50 polypeptides resolved by sodium dodecyl sulphate-polyacrylaminde gel electrophoresis analysis including a major component named P60. Here, we have developed a simple and efficient procedure for the purification of P60 and therefore permitting its biochemical characterization. METHODS AND RESULTS: Membrane proteins were selectively extracted from isolated cell envelopes with the mild non-ionic detergent Triton X-100. About 10 polypeptides were identified from the detergent fraction, including P60. The P60-enriched fraction was thereafter subjected to an anion exchange chromatographic step in the presence of Triton X-100. The molecule was purified at the milligram level (yield, about 75%; purification factor, 6.2). Analyses performed by charge shift electrophoresis, Triton X-114 phase separation and by detection of sugar-modified components showed that P60 is a true amphiphilic membrane-associated glycoprotein. CONCLUSIONS: The method described in this paper provides pure and non-denaturated P60 and should prove to be easily scaled-up. As sugar-modified protein, P60 should be included in the growing list of glycosylated prokaryotic proteins. SIGNIFICANCE AND IMPACT OF THE STUDY: It offers the possibility of obtaining P60 in amounts allowing the testing of the potential of P60 as a candidate for anti-flavobacteria subunit vaccines, as P60 is one of the major antigens.

Animals↗

PubMed2002

Hydroxylated human homotrimeric collagen I in Agrobacterium tumefaciens-mediated transient expression and in transgenic tobacco plant.

Potential contamination of animal-derived collagen with pathogens has led to the demand for safe recombinant sources of this complex molecule. In continuation of our previous work [Ruggiero et al. (2000) FEBS Lett. 469, 132-136], here we show that it is possible to produce recombinant hydroxylated homotrimeric collagen in tobacco plants that are co-transformed with a human type I collagen and a chimeric proline-4-hydroxylase (P4H). This is to our knowledge the first time that transient expression in tobacco was used to improve the quality of a recombinant protein produced in plants through co-expression with an animal cell-derived modifying enzyme. We demonstrated the functionality of the new chimeric P4H and thus improved the thermal stability of recombinant collagen I from plants to 37 degrees C.

Agrobacterium tumefaciens↗

PubMed2001

Unhydroxylated triple helical collagen I produced in transgenic plants provides new clues on the role of hydroxyproline in collagen folding and fibril formation.

Human unhydroxylated homotrimeric triple-helical collagen I produced in transgenic plants was used as an experimental model to provide insights into the role of hydroxyproline in molecular folding and fibril formation. By using chemically cross-linked molecules, we show here that the absence of hydroxyproline residues does not prevent correct folding of the recombinant collagen although it markedly slows down the propagation rate compared with bovine fully hydroxylated homotrimeric collagen I. Relatively slow cis-trans-isomerization in the absence of hydroxyproline likely represents the rate-limiting factor in the propagation of the unhydroxylated collagen helix. Because of the lack of hydroxylation, recombinant collagen molecules showed increased flexibility as well as a reduced melting temperature compared with native homotrimers and heterotrimers, whereas the distribution of charged amino acids was unchanged. However, unlike with bovine collagen I, the recombinant collagen did not self-assemble into banded fibrils in physiological ionic strength buffer at 20 degrees C. Striated fibrils were only obtained with low ionic strength buffer. We propose that, under physiological ionic strength conditions, the hydroxyl groups in the native molecule retain water more efficiently thus favoring correct fibril formation. The importance of hydroxyproline in collagen self-assembly suggested by others from the crystal structures of collagen model peptides is thus confirmed experimentally on the entire collagen molecule.

Animals↗

PubMed2001

[Thrombotic microangiopathy during HIV infection. A retrospective study performed in infectious diseases units in southern France].

OBJECTIVES: To describe and analyze the clinical and biological manifestations of thrombotic microangiopathy (TMA) and evaluate the therapeutic strategies. METHODS: A retrospective study was performed in 14 infectious diseases units of southern France. All HIV patients presenting TMA during the last decade were selected (n = 14). RESULTS: The principle signs observed, aside from defining TMA (association of microangiopathic hemolytic anemia, thrombocytopenia and renal failure), were diarrhea (n = 9) and a high level of lacticodehydrogenase (LDH). Patients were at an advanced stage of HIV infection (median of CD4+ cells counts = 70/mm3). Specific etiology was identified in 7 cases: bacterial infection (n = 5), CMV retinitis associated with Kaposi's sarcoma (n = 1) and intravenous drug use (n = 1). Various treatments were used: plasmatic exchange (5 cases), fresh frozen plasma (6 cases), steroid therapy (4 cases), acetyl salicylic acid (3 cases), adaptation of antiretroviral treatment (3 cases). The global prognostic was poor with 50% mortality within 2 months. A high level of LDH (> 2500 UI/L) was associated with premature death in 5 of the 6 cases observed. CONCLUSION: Our data confirm the severity of TMA in case of HIV infection. The common treatment remains the use of plasmatic exchange and fresh frozen plasma; an optimal antiretroviral therapy must be associated.

AIDS-Related Opportunistic Infections↗

PubMed2001

Nursing considerations of the neonate with congenital heart disease.

Nursing care of the neonate with CHD incorporates a knowledge base of the anatomy and physiology of congenital heart defects, surgical repair, complications associated with CHD, diagnostic testing, medical therapy, and psychosocial support. The neonatal nurse is a vital member of the cardiac team in providing accurate assessments, implementing medical therapies, and supporting the family.

Algorithms↗

PubMed2001

Association of vancomycin and calcium phosphate by dynamic compaction: in vitro characterization and microbiological activity.

Dynamic compaction has rarely been used to produce drug-delivery devices in granule form. This report considered four processes associating vancomycin and compared dynamic compaction with wet granulation, a classical method. In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation. In the dynamic compaction study, BCP powder was compacted at 1.1, 1.5 and 1.9 MPa. The compacts obtained were crushed and sieved (200-500 microm), and the vancomycin solution was adsorbed on the resulting granules. After crushing and sieving, the compaction of BCP and vancomycin powders produced vancomycin-loaded granules. In each study, 4.76% of vancomycin was associated with BCP. Granules were characterized in terms of porosity, vancomycin release and vancomycin biological activity. Physicochemical studies of BCP and vancomycin showed their structural integrity after dynamic compaction, which prolonged vancomycin release time from 1 to 6 days. However, a microbiological assay indicated that vancomycin had been altered since only 27.7% was found to be active.

Anti-Bacterial Agents↗

PubMed2001

A new injectable bone substitute combining poly(epsilon-caprolactone) microparticles with biphasic calcium phosphate granules.

Previous studies have shown the effectiveness of an injectable bone substitute (IBS) composed of biphasic calcium phosphate in 2% hydroxypropyl methylcellulose gel (50/50 w/w). A therapeutic agent in the form of a drug can be added to the biomaterial by encapsulation into microparticles to protect the active agent, control its release and preserve the material rheological properties. Poly(epsilon-caprolactone) was used in this study because of its biocompatibility and resorbability, as tested in orthopaedic implants and surgical sutures. Particles (80-200 microm) were manufactured by a solvent evaporation-extraction process (1 g of polymer, 11-15 ml methylene chloride, with a stirring speed of 400-600 rpm) and introduced into the IBS in a 5-50% (V/V) range. Injectability was evaluated by texture analysis. With less than 45% of particles, the material had rheological properties similar to those of the reference IBS, whereas injectability decreased markedly with more than 45% of particles. A preliminary in vitro release study showed that this type of triphasic IBS could be efficient for drug delivery systems with osteoconduction properties.

Anti-Bacterial Agents↗

PubMed2001

Bleeding reflux esophagitis: a prospective 1-year study in a university hospital.

OBJECTIVES: The prevalence of bleeding from reflux esophagitis has not been studied. The aim of the study was to evaluate the 1-yr prevalence of bleeding from reflux esophagitis, as well as the independent factors associated with bleeding. METHODS: All patients with reflux esophagitis diagnosed with upper digestive tract endoscopy in Reims Hospital in 1996 were included. Studied parameters were prospectively recorded and compared between patients with bleeding and nonbleeding reflux esophagitis. RESULTS: Endoscopy was performed in 1983 patients of whom 219 (11.0%) had overt upper digestive tract hemorrhage. Reflux esophagitis was the cause of bleeding in 32 patients (14.6%). Reflux esophagitis was diagnosed in 391 patients during the same period of time. Bleeding reflux esophagitis accounted for 8.2% of them. Independent factors associated with bleeding were grade 3 or 4 (Savary-Miller) esophagitis (odds ratio [OR]: 25.5, 95% confidence interval [CI]: 9.6-67.9), cirrhosis (OR: 5.7, 95% CI: 1.7-18.9), Eastern Cooperative Oncology Group performance status > or = 3 (OR: 4.6, 95% CI: 1.5-14.2), and anticoagulant therapy (OR: 3.9, 95% CI: 1.2-12.5). A history of reflux esophagitis or heartburn was noted in only 28.1% or 37.5% of the patients with bleeding reflux esophagitis, respectively. CONCLUSIONS: In this population of patients with reflux esophagitis, the prevalence of bleeding esophagitis was high (8.2%). Bleeding esophagitis occurred primarily in patients with severe esophagitis and was the revealing clinical form of gastroesophageal reflux disease in the majority of cases, suggesting that bleeding prevention would hardly be effective.

Adult↗

PubMed2000

Influence of isostatic compression on the stability of vancomycin loaded with a calcium phosphate-implantable drug delivery device.

It is essential to prevent microbial infections after osteoarticular trauma or prosthesis implantation. As an alternative to antibiotic parenteral administration, antibiotic-loaded biomaterials allow high concentrations to be obtained in situ without systemic toxicity. Although the formulation of biphasic calcium-phosphate (BCP)-vancomycin granules by isostatic compression has recently been used to produce drug-delivery devices, the stability of vancomycin needs to be proven. In this study, vancomycin was associated with BCP powders by isostatic compression at 100, 140, or 200 MPa and then extracted or released by a rotating paddle system for 24 h. Vancomycin assays were performed by spectrophotometric and microbiological methods. The results show that all vancomycin associated with the material was recovered after extraction without degradation. Thus, vancomycin was not denaturated after application of 100, 140, or 200 MPa of isostatic compression. The results for vancomycin released from granules compressed at the three pressures were not significantly different (p =.01) whether assays were performed microbiologically or spectrophotometrically, indicating a good correlation between the two methods. This process involving high pressure appears to be a good means of developing drug delivery devices loaded with therapeutic agents without denaturating the components.

Anti-Bacterial Agents↗

PubMed2000

Isostatic compression, a new process for incorporating vancomycin into biphasic calcium phosphate: comparison with a classical method.

Isostatic compression has rarely been used to load calcium-phosphate biomaterials with therapeutic agents. This report, concerning four processes associating vancomycin, compares isostatic compression with wet granulation, a classical method. In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation. In the isostatic compression study, BCP powder was compressed at 100, 140 and 200 MPa. The blocks obtained were crushed and 200-500 microm, sieved; thus, the vancomycin solution was absorbed on these granules. Compaction of BCP and vancomycin powders gave, after crushing and sieving, granules loaded with vancomycin. In each study, 5% vancomycin was associated with BCP. Vancomycin release profiles were assessed by an in vitro culture chamber dissolution test. Physicochemical studies of BCP and vancomycin showed their structural integrity after isostatic compression. Isostatic compression prolonged vancomycin release time from 3 to 7 days and the release time became greater as isostatic pressure increased, probably because of the porosity decrease of the granules during compression.

Calcium Phosphates↗

PubMed2000

[First confirmed case of laryngeal diphtheria in Djibouti].

The first bacteriologically confirmed case of laryngeal diphtheria in Djibouti was reported in 1998. It involved a three-year-old native-born infant who had been vaccinated during the first year of life with three doses of a combined vaccine against diphtheria, tetanus, poliomyelitis, and pertussis. A rapid clinical improvement was observed under erythromycin treatment. Other cases of laryngeal diphtheria have been observed. It is important to reverse decreasing vaccinal coverage in Djibouti and to warn incoming travelers of the need to be adequate immunized against diphtheria. Enhanced epidemiologic surveillance of this disease is also needed.

Child, Preschool↗