Mechanism of action of hormonal preparations used for emergency contraception: a review of the literature.
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Biomedical subjects
Publications and source records attributed to M Durand.
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The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.
In higher vertebrates, the glycolytic enzyme enolase (2-phospho-D-glycerate hydrolase; EC 4.2.1.11) is active as a dimer formed from three different subunits, alpha, beta and gamma, encoded by separate genes. The expression of these genes is developmentally regulated in a tissue-specific manner. A shift occurs during development, from the unique embryonic isoform alphaalpha, towards specific isoforms in two tissues with high energy demands: alphagamma and gammagamma in the nervous system, alphabeta and betabeta in striated muscles. The alphaalpha remains widely distributed in adult tissues. Here we report the results of the first extensive study of beta enolase expression during human development. Indeed, the beta subunit is specifically expressed at early stages of human myogenesis. Immunocytochemical analyses demonstrated that it is first detected in the heart of 3-week-old embryos and in the myotomal compartment of somites from 4-week-old embryos. At this stage, the muscle-specific sarcomeric protein titin is expressed in this structure, which will give rise to all body skeletal muscles, but embryonic myosin heavy chain is not yet present. Analyses at the protein level show that, during human ontogenesis, myogenesis is accompanied by an increase in beta enolase expression and by a decrease in the expression of the two other alpha and gamma subunits. Furthermore, beta enolase subunit is expressed in proliferating myoblasts from both embryonic and post-natal muscles. In addition, clonal analysis of primary cell cultures, obtained from the leg muscle of a 7-week-old human embryo, revealed that the beta subunit is present in the dividing myoblasts of all four types, according to the classification of Edom-Vovard et al. [(1999) J Cell Sci 112: 191-199], but not in cells of the non-myogenic lineage. Myoblast fusion is accompanied by a large increase in beta enolase expression. Our results demonstrate that this muscle-specific isoform of a glycolytic enzyme (beta enolase) is among the earliest markers of myogenic differentiation in humans.
In spite of the widespread use of aerosols in respiratory diseases, very few studies have been performed in the field of ear, nose, and throat (ENT) disorders. The conditions for penetration of aerosols inside the sinus cavities are thus still not understood fully. The aim of this study was to investigate the penetration of aerosols inside maxillary sinuses in vitro, using plastinated models. Three plastinated specimens of the nose and sinuses were made from three different corpses. These specimens were validated by CT scans and were used to study deposition of aerosol in the maxillary sinuses. We performed scintigraphic images of the models in above, face, and profile views using a technetium (99mTc)-labelled solution to show aerosol deposition. We also counted the radioactivity deposited on gauze compresses placed inside the maxillary sinuses. In addition, we constructed a measuring unit with miniature humidity sensors placed inside the sinuses. We recorded the changes in relative humidity observed during nebulization. Results from these studies showed that scintigraphic images of the specimen, whatever the incidence of the views, were not accurate enough to differentiate the aerosol deposition in the maxillary sinuses from that in the nasal cavity. Using indirect counting on gauze compresses made possible the quantification of local aerosol deposition, and we found that aerosols entered into the sinuses. This confirmed that aerosols could reach the middle meatus, which is the main area for sinusitis disorders. The increased activity compared to background varied from 17 to 127%. The humidity sensors recorded changes in relative humidity during the nebulization. These humidity changes fitted a nonlinear model represented by the equation: y = b0 (1 - e(-b1t)), where b0 is the plateau and b1 is the speed to reach the plateau. These techniques may be useful in the future for in vitro characterization of aerosol penetration into the maxillary sinuses.
Six hundred seventy-six patients with ductal carcinoma in situ of the breast (DCIS) from 1971 to 1995 were included in the study. Computerized patient files were retrospectively analyzed. Clinical findings were less frequently reported to reveal DCIS after 1989. Positive mammographic findings were obtained in 87% of patients and were mainly represented by microcalcifications (79.4%). Treatment procedures were breast-conserving surgery (BCS) alone (37.5%), BCS followed by radiation (BCSR) (25.5%), or mastectomy (M) (37%). The actuarial local recurrence was 2.6% in the M group (94 months of follow-up), 14.5% in the BCS group (85,7 months of follow-up), and 7.5% in the BCSR group (78.8 months of follow-up). Predictive factors of recurrence in all patients were invaded margin status and age. In the BCS group, grade was also a predictive factor. The analysis per decade shows that the lesions currently diagnosed are less serious than those of the past. All the recurrence in patients with positive margins was in the same quadrant as the original lesion. This further emphasizes the need for clear margins.
PURPOSE: To report a case of explosive fungal endophthalmitis after penetrating keratoplasty and to review additional published and unpublished cases to consider possible strategies for prevention. METHODS: Records of this patient with postkeratoplasty candidal endophthalmitis and previously reported cases of postkeratoplasty candidal endophthalmitis were reviewed. Additional information of 26 unpublished cases was obtained from the Eye Bank Association of America. RESULTS: After standard keratoplasty, the patient developed precipitous endophthalmitis on the second postoperative day. Abundant contamination with Candida was found in the residual donor corneoscleral rim, and Candida albicans was isolated from the aqueous humor of the recipient. Despite therapy with local antimicrobial agents, intraocular amphotericin B, and systemic fluconazole, the patient had a poor outcome with hand-motion visual acuity. Of the 44 collected cases of postkeratoplasty candidal endophthalmitis, 40 (91%) had the same organism cultured from the donor rim or medium. Forty-three donor corneas had been preserved in cold storage medium at 4 degrees C. Of 15 cases in which the outcome was available, 9 (60%) resulted in visual acuity of 20/200 or worse. CONCLUSION: Case reports confirm the occurrence of donor-to-host transmission of postkeratoplasty candidal endophthalmitis. Despite the low reported incidence, the poor prognosis of the affected eye in the ajority of these cases suggests the need for antifungal supplementation of cold preservation media and other preventative strategies.
For a long time, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors permeable to calcium have been considered to be either non-existent or as "atypical". There is now ample evidence that these receptors exist in numerous regions of the nervous system and in many neuronal as well as non-neuronal cell populations. This evidence has been accumulated by several methods, including electrophysiological recording, calcium imaging and cobalt-loading. Functional AMPA receptors permeable to calcium are already expressed at very early stages of embryonic development, well before the onset of synaptogenesis. They are probably involved in the paracrine signaling necessary for construction of the nervous system before becoming involved in synaptic transmission. In immature cells, cyclothiazide strongly increases the steady-state level of responses not only to AMPA, but also to kainate. Ingestion, during pregnancy, of food or drug substances that can cross the placental barrier and act upon the embryonic receptors may constitute a risk for normal development. In the adult nervous system, synaptic as well as non-synaptic (paracrine) AMPA receptors permeable to calcium are probably widely expressed in both glial and neuronal cells. They may also participate in controlling some aspects related to adult neurogenesis, in particular the migration of newly formed neurons.
For extra-oral implants, the difficulty is not simply the surgical technique, similar to that used for intra-oral implants. The real problem is to insert the implant at a specific position and with a proper alignment. The final cosmetic result is directly related to correct insertion of the implant and its anchors. We demonstrate the importance of a tight collaboration between the surgeon and the prosthesis, before, after and often during the intervention for obtaining a satisfactory result.
Our understanding of early human development has been impeded by the general difficulty in obtaining suitable samples for study. As a result, and because of the extraordinarily high degree of evolutionary conservation of many developmentally important genes and developmental pathways, great reliance has been placed on extrapolation from animal models of development, principally the mouse. However, the strong evolutionary conservation of coding sequence for developmentally important genes does not necessarily mean that their expression patterns are as highly conserved. The very recent availability of human embryonic samples for gene expression studies has now permitted for the first time an assessment of the degree to which we can confidently extrapolate from studies of rodent gene expression patterns. We have found significant human-mouse differences in embryonic expression patterns for a variety of genes. We present detailed data for two illustrative examples. Wnt7a, a very highly conserved gene known to be important in early development, shows significant differences in spatial and temporal expression patterns in the developing brain (midbrain, telencephalon) of man and mice. CAPN3, the locus for LGMD2A limb girdle muscular dystrophy, and its mouse orthologue differ extensively in expression in embryonic heart, lens and smooth muscle. Our study also shows how molecular analyses, while providing explanations for the observed differences, can be important in providing insights into mammalian evolution.
The descriptive anatomy of the cricoarytenoid articulation provides an essential foundation for understanding disorders of mobility of the larynx, especially in carcinology. Thirteen formaline-preserved anatomic specimens of the adult larynx were studied and 4 pathologic larynges with loss of mobility due to a malignant tumor. The cricoid and arytenoid articular surfaces showed major intra- and inter-individual variations, causing dynamic asymmetry at the glottic level. They were joined by a connective-elastic articular capsule bounding a cavity, characterized by a pseudo-meniscal synovial ridge and deep peripheral blind recesses, indicative of great articular mobility. The cricoarytenoid ligament shares in stabilizing the articulation. The posterior cricoarytenoid m. (abductor) and the lateral cricoarytenoid m. (adductor) have a motor innervation derived from the inferior laryngeal nerve, which forms an endolaryngeal arch with a ventral concavity, in contact with the lateral articular recess. The cricoarytenoid articulation thus appears as a diarthrosis possessing three degrees of liberty during movements of glottic abduction and adduction: an antero-posterior rocking movement, an antero-medial shift of the arytenoid on the cricoid, and a less marked axial rotation. Histological study of the cricoarytenoid articulation where mobility was reduced by carcinomatous infiltration showed that each articular component may be affected (muscles, cartilage, capsule, nerve), and that several components may be involved simultaneously to a minimal degree. The therapeutic implications are important, particularly in conservative laryngeal surgery.
A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.
Spontaneously Hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats differ in their emotional responses to stress and antidepressant administration. We have analysed different neurochemical and psychoneuroendocrine responses to repeated pretreatments with fluoxetine, imipramine or desipramine (10 mg/kg p.o. daily for 4 weeks) in SHRs and WKY rats exposed to a daily 2-h restraint episode for the last 5 days of antidepressant administration. Following a 24-h wash-out period, WKY rats displayed higher plasma antidepressant and antidepressant metabolite levels than SHRs. Fluoxetine pretreatment decreased [(3)H]citalopram binding at midbrain serotonin (5-HT) transporters, whereas tricyclic and/or fluoxetine decreased [(3)H]ketanserin binding at cortical 5-HT(2A) receptors, [(3)H]CGP-12177 binding at cortical ss-adrenoceptors, and [(3)H]nisoxetine binding at midbrain noradrenaline (NA) transporters in both strains. None of the antidepressants affected [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin binding at hippocampal 5-HT(1A) receptors. In WKY rats, repeated restraint triggered a desipramine-sensitive 140% increase in hypothalamus [(3)H]nisoxetine binding; moreover, plasma adrenocorticotropin-releasing hormone responses to a 5-min open field test were amplified by prior repeated restraint in both strains, but desipramine prevented such an amplification in WKY rats only. However, neither elevated plus-maze nor open field behaviors of SHRs and WKY rats were affected by desipramine pretreatment. Thus, the SHR and WKY rat strains may prove useful in understanding how genetic differences in noradrenergic responses to repeated stress and desipramine treatment impact on adaptive processes.
The rat olfactory bulb is innervated by basal forebrain cholinergic neurons and is endowed with both nicotinic and muscarinic receptors. The development of this centrifugal cholinergic innervation occurs mainly in early postnatal stages. This developmental time-course and the demonstration that acetylcholine can modulate some aspects of neuronal proliferation, differentiation or death, suggests the possible involvement of cholinergic afferents in the morphogenesis and/or plasticity of the olfactory bulb. The purpose of the present work was to assess whether acetylcholine could modulate neuronal morphogenesis in the olfactory bulb. Toward this aim, we developed a primary culture model of rat olfactory bulbs. Three major cell types were identified on the basis of their morphological and immunocytochemical phenotype: neuronal-shaped cells expressing the neuronal markers neuron specific enolase, microtubule associated protein 2, neural cell adhesion molecule and beta-tubulin III; glial-like cells immunoreactive for glial fibrillary acidic protein and flattened cells immunolabelled with antibodies against beta-tubulin III and nestin, most likely neuronal precursors. After three to six days of treatment with 100-microM carbachol, a cholinergic agonist, significant increase in neuritic length was observed in cultured olfactory bulb neurons. The neurite outgrowth effect of carbachol was abolished by co-treatment with 1 microM alpha-bungarotoxin, an alpha 7 subunit nicotinic receptor antagonist, but was not affected by the addition of 10 microM atropine, a general muscarinic antagonist. The effect of carbachol was also mimicked by the nicotinic agonists, nicotine (100 microM) and epibatidine (10 microM). This pharmacological profile suggested the involvement of nicotinic receptors of the alpha 7-like subtype as confirmed using 125I-alpha-bungarotoxin receptor autoradiography.Taken together, these data argue for a role for nicotinic receptors in neuritic outgrowth in the rat olfactory bulb and provide a cellular support to the previously described effects of acetylcholine on olfactory bulb plasticity in vivo.
Transcripts of calpain3, the gene involved in limb girdle muscular dystrophy type 2A, appear in organs other than the skeletal muscle during human development, the first of which being the early embryonic heart. We examined more precisely the spatio-temporal transcription pattern of calpain3 during human cardiogenesis and the appearance of its protein in fetal tissues, and correlated it to titin expression. Different events of the heart's maturation can be recognized: (i) the presence of titin RNA or protein constitute very precocious developmental cardiac markers appearing before the fusion of the two lateral endocardial tubes; (ii) the disappearance of calpain3 RNA from the ventricular compartment later in the embryonic heart. Finally, although calpain3 transcripts are present in the heart, the corresponding protein is not detected elsewhere than in skeletal muscle.
UNLABELLED: The Van Nuys prognostic index (VNPI) was thought to be useful for predicting response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS). We applied the VNPI under the conditions defined by Silverstein et al., in 367 retrospective DCIS entirely sectioned into serial macroscopic 2 mm slices (155 patients had radiotherapy, median follow-up 71 months). The percentage of positive blocks with DCIS was also estimated for each specimen with cut-offs at 30% and 60% to obtain three scores. One hundred and ninety five lesions had a low VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local recurrences (half invasive, all in the group without radiotherapy) in the low VNPI group. The local recurrence rate increased with size (p = 0.001), with reduction of distance to margins (p = 0.05), with histologic grade (p = 0.02), with percentage of positive blocks (p = 0.0003) and with VNPI score (p = 0.03). The percentage of positive blocks was the only independent predictor for local recurrence (p = 0.0001). CONCLUSION: (1) The VNPI was a local recurrence rate predictor between the low and the intermediate groups but in our series the low VNPI group had a surprisingly high local recurrence rate. (2) Only prospective studies will assess the importance of margin width and the role of radiotherapy in maintaining local control. (3) Estimation of the percentage of positive blocks is simple, may be an alternative when measurement of DCIS is difficult and should be taken into account.
The interaction of ethidium bromide (EB), a DNA intercalator, with two intramolecular triplexes 5'd(G4A4G4-[T4]-C4T4C4-[T4]-G4T4G4), 5'd(G4T4G4-[T4]-G4A4G4-[T4]-C4T4C4) ([T4] represents a stretch of 4 thymine residues) and their precursor duplexes has been investigated by circular dichroism, fluorescence and UV absorption spectroscopy. Binding of EB induces a circular dichroism band in the region around 310 nm which is positive for the duplex forms but negative for the triplex forms. We observed that the binding of EB to the duplex form does not induce the formation of the triplex structures. Thermal denaturation experiments demonstrate that EB stabilizes more the parallel triple helix than the antiparallel one. Analysis of the binding process from fluorescence measurements shows that binding constants to the triple helical forms and to the hairpin reference duplex [T4]-G4A4G4-[T4]-C4T4C4) are close. However the binding site size is larger for the triplexes (4-6 base triplets) than for the duplex (2 base pairs).
BACKGROUND: Distortion of the pressure wave by a liquid-filled catheter-transducer system leads most often to an overestimation in systolic arterial blood pressure in pulmonary and systemic circulations. The pressure distortion depends on the catheter-transducer frequency response. Many monitoring systems use either mechanical or electronic filters to reduce this distortion. Such filters assume, however, that the catheter-transducer frequency response does not change over time. The current study aimed to study the changes with time of the catheter-transducer frequency response and design a flush procedure to reverse these changes back to baseline. METHODS: An in vitro setup was devised to assess the catheter-transducer frequency response in conditions approximating some of those met in a clinical environment (slow flushing, 37 degrees C, 48-h test). Several flush protocols were assessed. RESULTS: Within 48 h, catheter-transducer natural frequency decreased from 17.89 +/- 0.36 (mean +/- SD) to 7.35 +/- 0.25 Hz, and the catheter-transducer damping coefficient increased from 0.234 +/- 0.004 to 0.356 +/- 0.010. Slow and rapid flushing by the flush device built into the pressure transducer did not correct these changes, which were reversed only by manual fast flush of the transducer and of the catheter. These changes and parallel changes in catheter-transducer compliance may be explained by bubbles inside the catheter-transducer. CONCLUSIONS: Catheter-transducer-induced blood pressure distortion changes with time. This change may be reversed by a manual fast flush or "rocket flush" procedure, allowing a con. stant correction by a filter.
BACKGROUND: Standard cytokine detection methods are unable to determine which cells are the producing cells. We report on the extent and under which conditions the multilabeling capability of flow cytometry (FCM) can bring new advances into the field. METHODS: Five different cytokines, interleukin-2 (IL-2), -4, -5, -10 and interferon-gamma (IFN-gamma), were assessed simultaneously under five ex vivo stimulation conditions in peripheral blood mononuclear cells from five healthy volunteers in a 5-day kinetic study. A second group of 35 volunteers was assessed for IFN-gamma and IL-2 production. RESULTS: This study showed that (a) intracytoplasmic cytokines were almost undetectable within unstimulated cells, (b) intracytoplasmic cytokines were detected only in CD69(+) T lymphocytes, and (c) intracytoplasmic IL-2 and IFN-gamma were dramatically upregulated after stimulation with phorbol myristate acetate (PMA)-ionomycin in a biphasic response or with PMA-phytohemagglutinin (one major peak only at 18 h) but to a lesser extent with other stimuli such as monoclonal antibodies. Th2 cytokines were detected at a later time point and at lower levels. PMA/ionomycin stimulation after 4 h and 18 h of culture in 35 other volunteers individualized several subgroups according to the frequency of IFN-gamma- or IL-2-producing cells--IFN-gamma delayed producers (n = 10/35), IFN-gamma low producers (n = 8/35), and IL-2 delayed producers (n = 16/35)--as opposed to IFN-gamma or IL-2 normal producers. CONCLUSIONS: FCM appears to be a good tool to examine cell cytokine status in pathology (allergy, autoimmune disease, etc.) provided that optimal stimulation conditions and multiple time-point cultures are used. It also seems to be a relevant method to define new Th subsets further.