[Hyperandrogenism after menopause: Ovarian or adrenal origin?] / Une hyperandrogénie chez la femme ménopausée : origine ovarienne ou origine surrénalienne ?

Postmenopausal hyperandrogenism is an androgen excess originating from either the adrenals and/or the ovaries. Clinically, symptoms can be moderate (increase in terminal hair growth, acnea) or severe with signs of virilization (alopecia, clitoridomegaly). In either setting, physicians need to exclude relatively rare but potentially life-threatening underlying tumorous causes, such as adrenal androgen-secreting tumors. The objectives of this review are to evaluate which hormonal measurements (T, delta 4 androstenedione, 17 OH progesterone, SDHEA, FSH, LH) and/or imaging (pelvic ultrasound, MRI or adrenal CT-scan) could be useful identifying the origin of the androgen excess. Our review illustrates that the rate of progression of hirsutism and/or alopecia, and serum testosterone levels are in favor of tumors. Pelvic MRI and adrenal CT-scan are useful tools for identifying the different causes of androgen excess.

From adverse drug event detection to prevention. A novel clinical decision support framework for medication safety.

BACKGROUND: Errors related to medication seriously affect patient safety and the quality of healthcare. It has been widely argued that various types of such errors may be prevented by introducing Clinical Decision Support Systems (CDSSs) at the point of care. OBJECTIVES: Although significant research has been conducted in the field, still medication safety is a crucial issue, while few research outcomes are mature enough to be considered for use in actual clinical settings. In this paper, we present a clinical decision support framework targeting medication safety with major focus on adverse drug event (ADE) prevention. METHODS: The novelty of the framework lies in its design that approaches the problem holistically, i.e., starting from knowledge discovery to provide reliable numbers about ADEs per hospital or medical unit to describe their consequences and probable causes, and next employing the acquired knowledge for decision support services development and deployment. Major design features of the framework's services are: a) their adaptation to the context of care (i.e. patient characteristics, place of care, and significance of ADEs), and b) their straightforward integration in the healthcare information technologies (IT) infrastructure thanks to the adoption of a service-oriented architecture (SOA) and relevant standards. RESULTS: Our results illustrate the successful interoperability of the framework with two commercially available IT products, i.e., a Computerized Physician Order Entry (CPOE) and an Electronic Health Record (EHR) system, respectively, along with a Web prototype that is independent of existing healthcare IT products. The conducted clinical validation with domain experts and test cases illustrates that the impact of the framework is expected to be major, with respect to patient safety, and towards introducing the CDSS functionality in practical use. CONCLUSIONS: This study illustrates an important potential for the applicability of the presented framework in delivering contextualized decision support services at the point of care and for making a substantial contribution towards ADE prevention. Nonetheless, further research is required in order to quantitatively and thoroughly assess its impact in medication safety.

REMOVAL: Pelvic MRI in a 17-year-old XY girl with 5-alpha reductase deficiency and a homozygous Gly115Asp mutation in SRD5A2.

This article has been removed: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been removed at the request of the Editor-in-chief and the corresponding author for legal reasons regarding the patient consent.

[Callas or the trajectory of the meteor]. / Callas ou la trajectoire du météore.

The lyric career of Maria Callas, though exceptional, is also noteworthy for its brevity. The first signs of downturn appeared at the age of 36 and her voice fell silent at only 40. Though the literature has massively commented on this premature worsening, few analyses of its characteristics have been made public so far The purpose of our study was to realise a perceptual and acoustical analysis of recorded arias by the artist at the climax to the fall. The audible impairments were first verbally described, and then compared to acoustical observations based on spectrographic analyses and fundamental-frequency measurements.

[Evaluation of a dysphonic population. Interest of a therapeutic team composed by the phoniatrician and the speech therapist]. / Evaluation d'une population de dysphoniques suivis en équipe phoniatrie/orthophonie.

PURPOSE: To evaluate a population of dysphonic treated in rehabilitation by comparing the VHI score and GRB scale. MATERIALS AND METHODS: 300 questionnaires were completed, only 42 cases were matched before and after 15 rehabilitation sessions; that is 84 questionnaires. Patients were divided into two groups: group 1 (impaired mobility of the vocal cords), group 2 (benign mucosal lesions). All patients completed a VHI questionnaire, a questionnaire evaluating subjective voice abuse (SSVS), a GRB score. The two tests were correlated to the diagnosis of voice pathology but also used for follow up after voice therapy. The tests used for statistical studies were: comparison by pathology by unpaired series tests (theoretical deviation=0); mean tests, Wilcoxon type. RESULTS: Patients were more handicapped by impaired mobility of the vocal cord than by a nodule or a cyst. The patients' vocal handicap (VHI) was significantly lower after 15 therapy sessions, in all of its components. The perceptual evaluation GRB is also significantly better for these patients after 15 therapy sessions. We could not demonstrate a favorable evolution, that is a diminution of the SSVS before and after 15 sessions. CONCLUSION: The efficacy of speech therapy for certain vocal cord pathologies has been demonstrated both in respect of the Vocal Handicap felt by the patient as well as the Hirano scale.

Congenital hypogonadotropic hypogonadism in females: clinical spectrum, evaluation and genetics.

Congenital hypogonadotropic hypogonadisms (CHH) are a well-known cause of pubertal development failure in women. In a majority of patients, the clinical spectrum results from an insufficient and concomitant secretion of both pituitary gonadotropins LH and FSH that impedes a normal endocrine and exocrine cyclical ovary functioning after the age of pubertal activation of gonadotropic axis. In exceptional but interesting cases, they can result from an elective deficit of one of the gonadotropins follicle-stimulating hormone (FSH) or luteinizing hormone (LH) by genetic anomaly of their specific ss sub-unit. CHH prevalence, estimated from teaching hospital series, is considered to be two to five fold less important in women compared to men bearing the disease. This frequency is probably under-estimated in reason of under-diagnosis of forms with partial pubertal development. Isolated or apparently isolated forms (i.e., Kallmann syndrome with anosmia or hyposmia not spontaneously expressed by the patients) of these diseases are most of the time discovered during adolescence or in adulthood in reason of lacking, incomplete or even apparently complete pubertal development, but with almost constant primary amenorrhea. In a minority of cases and mainly in familial forms, genetic autosomal causes have been found. These cases are related to mutations of genes impinging the functioning of the pituitary-hypothalamic pathways involved in the normal secretion of LH and FSH (mutations of GnRHR, GnRH1, KISS1R/GPR54, TAC3, TACR3), which are always associated to isolated non syndromic CHH without anosmia. Some cases of mutations of FGFR1, and more rarely of its ligand FGF8, or of PROKR2 or its ligand PROK2 have been shown in women suffering from Kallmann syndrome or its hyposmic or normosmic variant. In complex syndromic causes (mutations of CHD7, leptin and leptin receptor anomalies, Prader-Willi syndrome, etc.), diagnosis of the CHH cause is most often suspected or set down before the age of puberty in reason of the associated clinical signs, but some rare cases of paucisymptomatic syndromic causes can initially be revealed during adolescence, like isolated non syndromic CHH or Kallmann syndrome.

[The adult ovary is not in sleepiness: major role of forkhead proteins]. / La somnolence feinte de l'ovaire adulte : importance des protéines forkhead au sein de l'ovaire adulte.

The aim of this review is to underscore the major role of forkhead proteins in the adult ovary. Indeed, they revolutionize the idea of terminal differentiation of adult tissues with for example the in vivo reprogrammation of an adult organism on the one hand, and, on the other hand, the therapeutic possibilities of fertility preservation in women. In mammals, SRY, a transcription factor encoded by the Y chromosome, is responsible for the development of the undifferentiated gonads into testes. However, testis differentiation can occur in its absence. The studies of M. Treier demonstrate that FOXL2 is required to maintain the ovarian phenotype. Indeed, the absence of Foxl2 in an adult mouse ovary leads to an up regulation of testis-specific genes and a transformation of granulosa and theca cells into Sertoli-like and Leydig-like cells. The maintenance of the ovarian phenotype is an active process throughout life. Although multiple follicles are present in mammalian ovaries, most of them remain dormant. During reproductive life, some follicles are activated for development. There is an inefficient activation of dormant follicles within cryopreserved ovaries. An inhibition of the FOXO3a pathway in the mouse ovary leads to an enhancement of the activation of the dormant follicles. After transplantation, there are more preovulatory stage follicles and, after fertilization and embryo transfer, they lead to a healthy progeny. In human ovarian cortical fragments, the same inhibition and a xenotransplantation permit a development of more primordial follicles to the preovulatory stage. Thus, this treatment may be a hope to treat infertile women with cryopreserved ovaries or with a diminishing ovarian reserve.

[Obesity and female reproduction]. / Obésité et fertilité de la femme.

Weight, fat mass and obesity have been shown to play a major role in female reproduction. Obese women have a greater risk than nonobese women of infertility and they fail to become pregnant in both natural and assisted conception cycles. This cannot be explained only by their lack of ovulation. There are several potential mechanisms. On one hand, the endometrium seems to be partially responsible for this low fecundity in obese women. On the other hand, the oocyte seems to be implied. In a model of obese mouse, maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and an increased generation of reactive oxygen species (ROS). Furthermore, compared with controls, obese mice have significantly more decreased embryonic IGF-IR staining, smaller fetuses and smaller pups. In this model, all weaned pups have been fed with a regular diet. At 13 weeks, pups delivered from obese mice were significantly larger, and these pups demonstrated early development of a metabolic-type syndrome. These findings suggest that maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stages and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception.

Effects of conidia of various Aspergillus species on apoptosis of human pneumocytes and bronchial epithelial cells.

Aspergillus species can cause mycoses in human and animals. Previously, we demonstrated that A. fumigatus conidia from a human isolate inhibited apoptosis in human pneumocytes and bronchial epithelial cells. In the current study, we studied the effects of A. fumigatus conidia non-human origin and A. flavus, A. nidulans, A. niger and A. oryzae conidia on human cells apoptosis. Human pneumocytes or bronchial epithelial cells were simultaneously exposed to apoptotic inductors and aspergilli conidia. The cell cultures were analyzed by flow cytometry, immunoblotting, and examination of nuclear morphology. Similar to A. fumigatus conidia, A. flavus conidia inhibited cellular apoptosis while A. nidulans, A. niger and A. oryzae conidia did not affect apoptosis. We further studied the species specificity of conidia: there were no differences in the inhibition of apoptosis by A. fumigatus conidia from either human or bird isolates. In order to determine whether the inhibition of apoptosis by conidia is limited to certain strains, the effect on human cell apoptosis of different A. fumigatus human clinical isolates and A. fumigatus of environmental origin was evaluated. All A. fumigatus isolates inhibited apoptosis; an anti-apoptotic factor was released by conidia. For TNF-induced apoptosis, the anti-apoptotic effect of conidia of all isolates was found to be associated with a reduction of caspase-3 in human cells. The results suggest that suppression of apoptosis may play a role in reducing the efficacy of host defense mechanisms during infection with Aspergillus species.

[Communication disorders marked with hypophonia. Indication and speech therapy through the LSVT method]. / Les troubles de communication marqués par l'hypophonie: indication et rééducation par la méthode L.S.V.T.

This work relates a clinical experiment about use of the Lee Silverman Voice Treatment (LSVT). This method is mainly designed for communication/voice disorders caused by Parkinson's disease. Their authors widely diffused worldwide this treatment that is now supported and illustrated, among other things, by some neuro-radiological studies. Our work will deal with the indications provided by the speech therapist (Parkinson and non-parkinson hypophonia), the implications for the patient and the practice of speech therapy according to some therapeutic programs led in our center. Beyond the initial reluctance that one may feel when discovering this practice, we noticed a systematic and dramatic improvement of communication (clearly illustrated by the video) that will be expressed by some Vocal Handicap Index scales. Attention will be paid to stability of the treatments involved as well as their peripheral effects. In conclusion, we shall state the pertinence of the LSVT proposal as well as the precautions to taken when it is administered.

[Contribution of the study of singing in tune in musically non-expert subjects: importance of short term memory of the pitch (19 to 28 year-old subjects)]. / Contribution à l'étude de la justesse chantée chez des sujets sans pratique musicale experte: rôle de la mémoire à court terme des hauteurs tonales (sujets de 19 à 28 ans).

INTRODUCTION: In the singing, which requires precise knowledge of the relevant musical code in use, accuracy of intonation plays a central role. Singing in tune requires to perceive pitch precisely and to memorize it before planning and executing the accurate vocal motion, which allows the exact emission of the correct pitch. OBJECTIVES: Our work investigated the role of short term memory of pitch on singing accuracy. MATERIAL AND METHOD: For that purpose, the experimental protocol of Deutsch (1970) was adapted for a perception and a production task. Participants were selected for their singing accuracy and separated into two groups of ten singing in tune and ten out-of-tune. All participants perceived pitch height exactly and were musically non-experts. For the perception and the production tasks, participants had to either compare or reproduce single pitches or two-pitch-sets. For the perception task, participants had to compare either single pitches or two-pitch patterns, all separated by a five seconds delay. For the production task, participants had to reproduce either single pitches or two-pitch patterns after a five seconds delay. The five seconds delay was either filled with intervening numbers, or with intervening tones, or without any disturbing sound. RESULTS: In perception and production task, the presence of intervening tones disturbs deeply the success of the subjects for every trial. Performance of the in-tune singing group is better for all the exercises while the other group had difficulties on single pitches and two-pitch patterns and was more disturbed by the effect of the intervening material. CONCLUSION: The outcome suggests that short term memory of pitch and accuracy of intonation would be closely linked. Further research needs to specify if that would mean that troubles in singing in tune are a consequence of a low-efficient short term memory of pitch, or if that troubles would hold up the right construction of the short term memory of pitch.

Cell wall biogenesis in a double chitin synthase mutant (chsG-/chsE-) of Aspergillus fumigatus.

Previous studies (Aufauvre-Brown et al., 1997; Mellado et al., 1996a,b ) have shown that only two genes of the Aspergillus fumigatus chitin synthase family, chsG and chsE, play a role in the morphogenesis of this fungal species. An A. fumigatus strain lacking both chsG (class III CHS) and chsE (class V CHS) genes was constructed by gene replacement of the chsE gene with a copy that has its conserved coding region interrupted by the hph resistance cassette in an A. fumigatus chsG- genetic background. Unexpectedly the double disruption was not lethal. The double mutant AfchsG-/chsE- strain (i) has reduced chitin synthase activity with or without trypsin stimulation, (ii) has a reduced colony radial growth rate, (iii) produces highly branched hyphae, (iv) exhibits aberrant features, such as periodic swellings along the length of the hyphae and a block in conidiation that can be partially restored by an osmotic stabilizer (v) shows alterations in the shape and germination capacity of the conidia, and (vi) has a cell wall that contains half the chitin of the parental strain and is, unexpectedly, highly enriched in alpha-(1-3) glucan.

[Evaluation of vocal abuse by the patient and correlation with vocal cords lesions]. / Evaluation du surmenage vocal par le patient et corrélation avec la présence de lésions cordales.

OBJECTIVE: The aim of this study was to evaluate the recognition by the patient of quantitative vocal abuse and its assessment. MATERIALS AND METHODS: 336 files of patients presenting with dysphonia were evaluated with a questionnaire composed of 4 items. We compared the patients, evaluation of their vocal abuse with the presence or absence of benign lesions on the vocal cords. RESULTS AND CONCLUSION: Abuse and misuse are often confused and the word abuse does not seem to be the most appropriate to describe the quantitative excess of voice use which is distinct from misuse.

Molecular characterization of a cell wall-associated beta(1-3)endoglucanase of Aspergillus fumigatus.

A 74 kDa beta(1-3)endoglucanase of Aspergillus fumigatus was recently isolated from a cell wall autolysate and biochemically characterized. In this study, we report the cloning and the disruption of the ENGL1 gene encoding this beta(1-3)endoglucanase. ENGL1 contains an open reading frame of 2181 bp encoding a polypeptide of 727 amino acids. Sequence analysis showed that ENGL1 is the first characterized member of a new family of beta(1-3)glucanases. Disruption of ENGL1, however, did not lead to a phenotype distinct from the parental strain, indicating that this cell wall-associated beta(1-3)endoglucanase does not play an essential role in constitutive cell growth.

A new experimental murine aspergillosis model to identify strains of Aspergillus fumigatus with reduced virulence.

Experimental animals are an obligate screen to investigate microorganism pathogenicity. Numerous animal models have been used to analyse the virulence of the opportunistic human pathogen Aspergillus fumigatus but none of the experimental models used previously have been satisfactory. This report discuss these models and presents a murine model of pulmonary aspergillosis that is very easy and the most adapted to compare the pathogenicity of A. fumigatus strains. Strains to be tested are inoculated intranasally and synchronously to mice and strains isolated from the lung of mice killed by the infection are typed. The number of colonies recovered is directly correlated to the virulence of the strain.

Comparison of restriction fragment length polymorphism, microsatellite length polymorphism, and random amplification of polymorphic DNA analyses for fingerprinting Aspergillus fumigatus isolates.

Aspergillus fumigatus fingerprints generated by random amplification of polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP) upon hybridization with repeated DNA sequences, and PCR detection of microsatellite length polymorphism (MLP) were compared among 67 isolates. In contrast to RAPD, RFLP and MLP gave discriminating and significantly concordant genotyping results.

[Value of the relative phonetogram (RP) for the evaluation of organic dysphonias]. / Valeur du phonétogramme relatif (PR) dans l'évaluation des dysphonies organiques.

UNLABELLED: The phonetogram in a recognized element of voice evaluation, but its relation to perceptual voice quality is unclarified. The phonetograms area is easy to measure since the existence of efficient computer software. So information about frequency and intensity range can be united in one single parameter. The individual phonetogram area in relation to a gender- and training-specific normal value constitutes the "relative phonetogram (RP)". A prospective evaluation of the relative phonetogram was performed by means of a statistical analysis of its correlation to perceptual voice assessment (grade/rough/breathy) and to maximal phonation time. The acoustic parameters jitter, shimmer, SNR were examined in the same way, to allow for comparison of the RP's importance with the importance of common "objective" features in the identical group of patients. 114 patients with two subsets are included: 61 patients after partial laryngectomy (laser or conventional surgery), 53 patients with different glottic pathologies. The perceptive evaluation was done by a trained jury of an ENT-specialist and a speech therapist. The phonetogram and the maximal phonation time were measured by a trained medical student with regard of the examination references publicated by the Union of European Phoniatrics. The computer software for area measurement was MSImageProPlus, the one for sound analysis was Dr. Speech (Tiger Electronics). Statistical program: SPSS 8.0. RESULTS: The comparison between the two subsets of patients shows lower RPs for partial laryngectomy than for other patients in all degrees of hoarseness. In both subsets there is a correlation between RP and hoarseness values: the average values of RP differ significantly in dependence of grande. This is even more marked for the patients after laryngeal surgery. Furthermore high RPs are only present in patients with (relatively) high maximal phonation time, and mean RP correlates with maximal phonation time. A correlation between the parameters of sound analysis and the score of "grade" exists, but is not as marked as for the RP. CONCLUSION: The significance of the RP's mean value for subsets of 15-20 patients has been demonstrated. It is justified to interpret a certain variance of this parameter as difference in the degree of hoarseness. In this context, the importance of the mean RP is higher than the importance of jitter, shimmer, SNR (when measured with the above mentioned computer program, which allows no evaluation of parameter combinations). Therefore this parameter could be interesting for comparison of dysphonic patients, for instance after glottic cancer treatment.

Detection of Aspergillus galactomannan: comparison of an enzyme-linked immunoassay and a europium-linked time-resolved fluoroimmunoassay.

With a view to improving the sensitivity of serological detection of Aspergillus galactomannan (GM), a europium-linked time-resolved fluoroimmunoassay was developed. This method was compared to an enzyme-linked immunosorbent assay using a peroxidase-conjugated detector antibody. No increase in the sensitivity of the detection of GM standards was seen with the europium-based fluoroimmunoassay.