[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.

[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.

[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.

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.

[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.

Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients.

The performance of two Aspergillus antigenemia systems, the sandwich enzyme-linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive aspergillosis were compared by testing 364 serum samples from 22 bone marrow transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were 60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients found positive with both methods, the ELISA test became positive earlier than the LA test or remained positive after the LA test had become negative. These results encourage further evaluation of the Platelia Aspergillus test, to assess its role in the management of invasive aspergillosis in BMT patients.

Longitudinal study of Aspergillus fumigatus strains isolated from cystic fibrosis patients.

The colonization over time of cystic fibrosis patients by Aspergillus fumigatus was investigated using a DNA fingerprinting method. Aspergillus fumigatus isolates collected sequentially for more than one year from six patients with cystic fibrosis were typed by Southern blot hybridization with a repetitive DNA sequence. Each cystic fibrosis patient harbored several strains of Aspergillus fumigatus that were isolated recurrently over time. Isolates collected from a cystic fibrosis patient with aspergilloma displayed the same genotype, suggesting that the infection was due to a single strain. Continuous isolation of the same genotype in another cystic fibrosis patient, however, was not correlated clinically with an Aspergillus infection.

Genetic diversity among clinical and environmental isolates of Aspergillus fumigatus.

To determine if cases of invasive aspergillosis (IA) were caused by strains of Aspergillus fumigatus with unique characteristics, strains from immunosuppressed patients with IA were compared to strains obtained from sputa of patients with cystic fibrosis and to strains from the environment. An extremely high genomic diversity was observed among the 879 strains typed by Southern blotting with a retrotransposon-like element from A. fumigatus (C. Neuvéglise, J. Sarfati, J. P. Latgé, and S. Paris, Nucleic Acids Res. 24:1428-1434, 1996). Analysis of Southern blot hybridization patterns showed the absence of clustering between environmental isolates and clinical isolates from patients with IA or cystic fibrosis. In addition, strains could not be clustered depending on their geographical location. This study implies that practically any strain of A. fumigatus is potentially pathogenic and can provoke a case of IA when it encounters a favorable environment in an immunosuppressed host.

Genotypic characterization of sequential Aspergillus fumigatus isolates from patients with cystic fibrosis.

Twenty-three sequential Aspergillus fumigatus sputum isolates, which had been collected over a period of 2 years, from two patients with cystic fibrosis were genotyped by random amplified polymorphic DNA PCR and restriction fragment length polymorphism analysis. In patient B, one genotype was predominantly present in the sputum samples, while in the other patient up to nine different genotypes were identified. This study suggests that different patterns of colonization with A.fumigatus exist in patients with cystic fibrosis.

Afut1, a retrotransposon-like element from Aspergillus fumigatus.

A repeated DNA sequence used for epidemiological studies of the human opportunistic pathogen Aspergillus fumigatus has been characterized. It is a retroelement of 6914 bp in length, bounded by long terminal repeats of 282 bp, with sequence and features characteristic of retroviruses and retrotransposons. A 5 bp duplication site was found at its borders. This element, designated Afut1, encodes amino acid sequences homologous to the reverse transcriptase, RNase H and endonuclease encoded by the pol genes of retroelements. Comparison of the peptidic sequences with other putative polypeptides of fungal LTR retrotransposons showed that Afut1 is a member of the gypsy group. This is the first report of a transposable element in A.fumigatus. Afut1 is a defective element: the putative coding domains contain multiple stop codons due exclusively to transitions from C:G to T:A.

Prospective sandwich enzyme-linked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis.

BACKGROUND: The delay between the onset of invasive aspergillosis and the start of antifungal therapy is crucial for the patient's recovery. Early diagnosis is difficult in cancer patients through lack of precocious specific signs. We have investigated the clinical usefulness of circulating Aspergillus antigen monitoring in pediatric hematology patients with a new sensitive sandwich enzyme-linked immunosorbent assay. METHODS: A prospective study was conducted by assessing circulating galactomannan levels in high risk patients. Thirty-seven patients studied during an 18-month period were evaluated twice weekly during neutropenic phases with the sandwich enzyme-linked immunosorbent assay for serum Aspergillus galactomannan. RESULTS: Twelve patients had one or more episodes of positive circulating galactomannan detection, 10 of whom developed presumptive invasive aspergillosis. The clinical and radiologic signs occurred at a mean of 13.4 days (range, 0 to 48) after circulating galactomannan detection and reversed in 6 patients treated with amphotericin B at the same time circulating galactomannan detection became negative. Reappearance of circulating galactomannan was observed during subsequent neutropenic periods in 3 patients. CONCLUSIONS: The detection of galactomannan at concentrations as low as 1 ng/ml can be useful for the early initiation of antifungal therapy and monitoring treatment in clinically documented lung aspergillosis. This technique coupled with chest computed tomography could help to restrict the need of invasive diagnostic procedures in fragile patients.

Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of invasive aspergillosis.

Aspergillus antigenemia was followed up in 215 consecutively observed bone marrow transplant (BMT) patients over a period of two years, using both a latex agglutination test and a sandwich immunocapture enzyme immunoassay (EIA) with a rat antigalactomannan monoclonal antibody as capture and detector antibody. For each patient, sequential sera (3 to 20) were obtained before and after BMT. No positivity was observed before BMT. After BMT, the EIA and latex agglutination test were positive in 19 and 4 patients respectively of 25 patients with confirmed aspergillosis and 14 and 7 of 15 patients with probable aspergillosis. In 19 of 25 patients with confirmed aspergillosis and 9 of 15 patients with probable aspergillosis, the EIA was more sensitive and detected infection earlier than the latex test. In all positive cases, antigenemia rapidly increased in sequential samples and remained strongly positive. In 31 of 169 (19%) BMT patients without clinical signs of aspergillosis, the EIA was occasionally positive in samples taken within the first month after BMT, giving a specificity of 81% in these patients. In non-BMT patients suffering from other diseases (n = 77), the specificity was 98.7%. The overall positive and negative predictive values for the EIA were 54% and 95% respectively. These results favour the use of EIA for early diagnosis and monitoring of aspergillosis in BMT patients, although the predictive value of transient positivity remains to be ascertained.

[Vocal retraining of teachers]. / Réadaptation vocale des enseignants.

A population of 90 teachers referred for vocal disorders is analyzed. In one third of the cases, no morphological anomaly was noted in the larynx. Pseudocysts and nodules were found in another third. Polyps (5 cases) were found in P.E. teachers, 8 epidermoid cysts and 3 sulcusglottidis were noted. For each professional category and for each type of lesion, the re-education of teachers presents predominant tendencies, but should remain the result of an individual assessment for each case.