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Biomedical subjects

J Paris

Publications and source records attributed to J Paris.

At least 37 records · Page 2Linked to original sources
PubMed2003

An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells.

The specific pharmacological profile of the 19-norprogestin nomegestrol acetate (NOMAC) is, at least in part, defined by its pattern of binding affinities to the different steroid hormone receptors. In the present study, its affinity to the progesterone receptor (PgR), the androgen receptor (AR) and the estrogen receptor (ER) was re-evaluated and compared to those obtained for progesterone (P) and several progestins. The characteristics of binding to the PgR in rat uterus were determined and Ki were found to be roughly similar with 22.8 and 34.3 nM for NOMAC and P, respectively. The binding characteristics of 3H-NOMAC were also determined and compared to that of 3H-ORG2058 with Kd of 5 and 0.6 nM, respectively for rat uterus and 4 and 3 nM, respectively for human T47-D cells. Structure-affinity and -activity relationships were studied on a variety of compounds related to NOMAC in order to assess its specificity as a progestin. The effects of NOMAC on the binding of androgen to the AR were investigated, using rat ventral prostate as target model. Contrary to what was observed for MPA, the RBA of NOMAC was found to decline with time, showing anti-androgenic rather than androgenic potential, a result that was confirmed in vivo. Regarding the ER, since none of the progestins were able to compete with estrogen for binding in rat uterus as well as in Ishikawa cells, the induction of alkaline phosphatase activity (APase) was used as an estrogen-specific response. It confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT), norethisterone acetate (NETA), levonorgestrel (LNG) or norgestimate (NGM) and others. In contrast, all P and 19-norP derivatives remained inactive. Finally, to complete this overview of NOMAC at the sex steroid receptor levels, the lack of estrogenic or estrogenic-like activity was checked out in different in vitro models. Data from this study have demonstrated that NOMAC is a progestin that has greater steroid receptor selectivity compared to MPA or some other synthetic progestins. It may provide a better pharmacological profile than those progestins currently in use in HRT and OC.

Animals↗
PubMed2003

Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo.

Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer.

Adolescent↗
PubMed2003

[Choanal atresia: therapeutic management and results].

OBJECTIVES: To assess and compare long term results after surgical correction (transnasal or transplatine approaches) of unilateral or bilateral choanal atresia, in children with or without associated anomalies. PATIENTS: During a 13-year period, 58 children were included in this retrospective study. Seventy-five choanas were operated on (41 unilateral and 17 bilateral). The transpalatine approach was performed in 41 children (56 choanas) while the transnasal approach was performed in 17 patients (19 choanas). Associated anomalies were reported in 28 children and corresponded to CHARGE association in 13 cases. RESULTS: With a mean follow-up of 7 years, perfect choanal permeability was reported in 90% of children operated on through a transpalatine approach and in 76% of children with a transnasal approach. A complementary therapeutic procedure was required in 54% of transpalatine approaches and 46% of transnasal approaches to yield these results. Postoperative choanal permeability was obtained in 93% of children without an associated anomaly and in 77% of those with associated anomalies, such as in 88% of unilateral atresias and 80% of bilateral ones. CONCLUSION: Initial success rate after surgery is similar for all surgical procedure insofar as nearly half choanas required a complementary therapeutic procedure. The endonasal procedure using the microdebrider appears hopeful and the KTP laser is interesting in fibrous residual stenosis. Associated anomalies are factors which lower general prognosis while inducing a higher surgical failure rate.

Abnormalities, Multiple↗
PubMed2003

[Choanal atresia: therapeutic management and results in a series of 58 children].

INTRODUCTION: An error of table being slipped during the publication of this article in number 1 (2003), the Review republishes it in entirety for a better comprehension. The preceding reference must be replaced by this one: Rev Laryngol Otol Rhinol 2003;124,3:139-143. OBJECTIVES: To assess and compare long term results after surgical correction (transnasal or transpalatine approaches) of unilateral or bilateral choanal atresia, in children with or without associated anomalies. PATIENTS: During a 13-year period, 58 children were included in this retrospective study. Seventy-five choanas were operated on (41 unilateral and 17 bilateral). The transpalatine approach was performed in 41 children (56 choanas) while the transnasal approach was performed in 17 patients (19 choanas). Associated anomalies were reported in 28 children and corresponded to CHARGE association in 13 cases. RESULTS: With a mean follow-up of 7 years, perfect choanal permeability was reported in 90% of children operated on through a transpalatine approach and in 76% of children with a transnasal approach. A complementary therapeutic procedure was required in 54% of transpalatine approaches and 46% of transnasal approaches to yield these results. Postoperative choanal permeability was obtained in 93% of children without an associated anomaly and in 77% of those with associated anomalies, such as in 88% of unilateral atresias and 80% of bilateral ones. CONCLUSION: Initial success rate after surgery is similar for all surgical procedure insofar as nearly half choanas required a complementary therapeutic procedure. The endonasal procedure using the microdebrider appears hopeful and the KTP laser is interesting in fibrous residual stenosis. Associated anomalies are factors which lower general prognosis while inducing a higher surgical failure rate.

Abnormalities, Multiple↗
PubMed2003

[Multifactorial analysis of preoperative functional symptoms in nasal polyposis (report of 403 patients)].

PURPOSE: Nasal polyposis is an invading disease whose evolution is dominated by functional symptoms. The aim of this study was to evaluate in cortico-resistant patients with nasal polyps the pre-operative functional symptoms in order to define factors that might increase them. METHODS: 403 patients were included in this study. All of them met the inclusion criteria of follow-up and initial examination. Anosmia, pain, nasal obstruction, rhinorrhea and sneezing were evaluated by patients themselves. Radiological data, respiratory function test results and histological data were matched. RESULTS: In our series, functional symptoms were dominated by anosmia, nasal obstruction and rhinorrhea. Pain and sneezing appeared to be less frequent. Analysis of co-variables allowed us to define factors which increased pre-operative functional symptoms. Some of them are well known (such as Fernand-Widal triad or stage 3 nasal polyposis), while others appear new or surprising. The same is true for frontal sinus involvement on CT-scan and glandular hyperplasia on histological study. CONCLUSION: Analysis of the complete clinical, radiological and histological picture has allowed us to emphasise the importance of certain factors on the functional symptoms of 403 patients with polyps of the nose and sinuses, resistant to steroid treatment. The same is true for Widal's disease, for a higher endoscopic grading, for frontal sinus involvement, and for histological evidence of glandular hyperplasia.

Adolescent↗
PubMed2003

[Recurrences of pleomorphic adenomas of the parotid: changing attitudes].

OBJECTIVE: The real issue of parotid surgery for pleomorphic adenoma is its risk of recurrence. The aim of this study was to compare the changing attitudes towards the pathology and surgical treatment in order to better define prevention and management of pleomorphic adenoma recurrences. MATERIAL AND METHOD: Histological study was performed after reviewing of slides originating from 100 patients with pleomorphic adenomas of the parotid gland, treated in our institution during the period May 1992 - November 2002. Study of the diagnostic value of fine needle cytology aspiration and MRI for pleomorphic adenoma diagnosis was performed for 181 patients operated on for parotid tumors. RESULTS: Hypocellular pleomorphic adenomas often have a thin capsule and constitute the most frequently encountered subtypes of recurrence. Pseudopodia are considered as an additional risk of recurrence. In our series, cytological study gave excellent diagnostic value with a sensitivity of 92% and a PPV of 96%. MRI study had a sensitivity of 83% and a PPV of 89%. CONCLUSIONS: According to these findings, enucleation surgery on a pleomorphic adenoma should not be performed any more. Parotidectomy techniques (total or superficial) constitute the surgical treatment of choice. The management of recurrences is based on surgery, with total parotidectomy and facial nerve preservation. The rôle of radiotherapy is still indeterminate.

Adenoma, Pleomorphic↗
PubMed2002

[Pleomorphic adenoma of the nasal cavity: a case arising from the wall of the maxillary sinus].

INTRODUCTION: Pleomorphic adenoma is a common and benign tumour, originating from sero-mucous glands. Location in the nasal cavity and particularly on the medial wall of the maxillary sinus is very rare. PATIENTS AND METHODS: One patient with a pleomorphic adenoma of the nasal cavity and a review of literature are reported in order to describe the diagnostic and therapeutic management of this tumour. RESULTS: A 63-year-old woman was referred to our institution for evaluation of an unilateral nasal tumour. Clinical and radiological studies revealed an intra-nasal tumour, slightly lytic in nature, arising from the mucosa of the medial wall of the maxillary sinus. More than 2 years after complete excision of the tumour using an endoscopic procedure, the nasal cavity was free of tumour. DISCUSSION: Pleomorphic adenoma of the nasal cavity is a rare and benign tumour, usually presenting as a unilateral nasal tumour. Prognosis of this tumour is mainly linked to recurrences in cases of incomplete resection and to possible metastasis, such as an eventual malignant evolution. The gold standard treatment is complete surgical resection. After a complete imaging study for patient selection (CT scan and MRI), endonasal endoscopic surgery seems to be a reliable therapeutic treatment. CONCLUSION: Intra-nasal pleomorphic adenoma originates from nasal seromucous glands. Radiological study reveals a slightly lytic tumour developed from the septum of the medial wall of the maxillary sinus. Resecton can be performed with endoscopic endonasal surgery as long as the orbital bony framework and the ethmoidal roof are free of tumour. Whatever technique is employed, long term follow-up has to be used to detect any recurrence.

Adenoma, Pleomorphic↗
PubMed2001

Prognostic factors of sudden hearing loss in children.

OBJECTIVE: Sudden hearing loss in children under 15 years old is rare and its pathophysiology remains unclear. The aim of this retrospective study was to define prognostic factors of sudden hearing loss in children under 15 years old. METHODS: Among the patients referred to our institution during the period 1990-1999 for sudden hearing loss, 12 children were considered eligible for this study (mean age=9.5 years old). Patients were divided into three groups according to hearing recovery and seven putative prognostic factors were analyzed. RESULTS: Total hearing recovery (group I: 90-100%) occurred in 28.5% of cases, partial hearing recovery (group II: 11-89%) occurred in 28.5% of cases and absence of recovery (group III: 0-10%) was reported in 43% of cases. Factors such as age, sex, and bilaterality of hearing loss were not correlated with hearing recovery. CONCLUSIONS: Initial severe hearing loss, associated vertigo and 'downward' audiometric curve were three negative prognostic factors of hearing recovery. Tinnitus has only been reported in children with partial or total hearing recovery.

Adolescent↗
PubMed2001

Association of serotonin and cortisol indices with childhood abuse in bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is reported to co-occur with childhood abuse and alterations in central serotonin (5-hydroxytryptamine [5-HT]) and cortisol mechanisms. However, findings also link childhood abuse to anomalous 5-HT and cortisol function, and this motivated us to explore relationships between childhood abuse and neurobiological variations in BN. METHODS: Thirty-five bulimic and 25 nonbulimic women were assessed for childhood physical and sexual abuse, eating symptoms, and comorbid psychopathological tendencies. These women provided blood samples for measurement of platelet hydrogen-3-paroxetine binding and serial prolactin and cortisol responses following oral administration of the partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP). RESULTS: Bulimic women showed markedly lower mean +/- SD density (B(max)) of paroxetine-binding sites (631.12 +/- 341.58) than did normal eaters (1213.00 +/- 628.74) (t(54) = -4.47; P =.001). Paroxetine binding did not vary with childhood abuse. In contrast, measures of peak change on prolactin levels after m-CPP administration (Delta-peak prolactin) indicated blunted response in abused bulimic women (7.26 +/- 7.06), nonabused bulimic women (5.62 +/- 3.95), and abused women who were normal eaters (5.73 +/- 5.19) compared with nonabused women who were normal eaters (13.57 +/- 9.94) (F(3,51) = 3.04, P =.04). Furthermore, individuals reporting childhood abuse showed decreased plasma cortisol levels relative to nonabused women who were normal eaters. CONCLUSION: Findings imply that BN and childhood abuse are both generally associated with reduced 5-HT tone but that childhood abuse may be somewhat more specifically linked to reduced cortisol levels (ie, hypothalamic-pituitary-adrenal axis) activity.

Adolescent↗
PubMed2001

Diagnosis and treatment of juvenile nasopharyngeal angiofibroma.

The aim of this retrospective study was to compare clinical and radiological findings and discuss optimal surgical approach in patients with juvenile nasopharyngeal angiofibroma (JNA). Forty-three cases of JNA were treated at our institution from 1975 to 1999. Thirty-three male patients aged between 8 and 25 years (mean 15.3) were included. Twenty-nine patients underwent primary surgical treatment at our institution and four were treated for recurrence following primary surgery elsewhere. Tumors were staged according to Fisch's staging. Preoperative embolization was performed in 22 cases. Surgical techniques consisted of the transantral approach, lateral rhinotomy approach, transmaxillary via midfacial degloving approach, and the subtemporal preauricular infratemporal fossa approach. Tumors were classified stage I in seven cases, stage II in 11, stage III in 13 and stage IV in two. The mean delay between the initial symptom and surgery was 14 months overall, 18 months for stage I, 14 for stage II, 13 for stage III and 12 for stage IV. The transantral approach was used in 11 patients, lateral rhinotomy approach in 11 cases, transmaxillary via midfacial degloving approach in three patients, and pre-auricular infra-temporal approach in eight patients. Mean follow-up after surgery was 56 months. Six patients had recurrent tumors. Surgery is the gold standard for treatment of JNA. Modern imaging techniques allow accurate diagnosis and staging of JNA. Our experience and a review of the literature shows that the surgical approach should be selected according to tumor stage.

Adolescent↗
PubMed2001

Cross-tolerance to otherwise lethal N-methyl-D-aspartate and oxygen-glucose deprivation in preconditioned cortical cultures.

In vitro ischemic preconditioning induced by subjecting rat cortical cultures to nonlethal oxygen-glucose deprivation protects against a subsequent exposure to otherwise lethal oxygen-glucose deprivation. We provide evidence that attenuation of the postsynaptic N-methyl-D-aspartate (NMDA) receptor- and Ca(2+)-dependent neurotoxicity underlies oxygen-glucose deprivation tolerance. It is demonstrated that extended tolerance to otherwise lethal NMDA or oxygen-glucose deprivation can be induced by either of their sublethal forms of preconditioning. These four pathways are linked, since NMDA receptor blockade during preconditioning by oxygen-glucose deprivation eliminates tolerance. These results suggest that NMDA tolerance, induced by nonlethal activation of these receptors during oxygen-glucose deprivation preconditioning, underlies oxygen-glucose deprivation tolerance. Several neurotoxic downstream Ca(2+)-dependent signaling events specifically linked to NMDA receptor activation are attenuated during otherwise lethal oxygen-glucose deprivation in preconditioned cultures. Specifically, calpain activation, as well as degradation of microtubule-associated protein-2 and postsynaptic density-95, are attenuated 2 h following otherwise lethal NMDA treatment alone or oxygen-glucose deprivation in preconditioned cultures. Formation of microtubule-associated protein-2-labeled dendritic varicosities is also attenuated in preconditioned cultures within 1 h of lethal oxygen-glucose deprivation or NMDA application. Intracellular Ca(2+) levels, measured using the high- or low-affinity dyes Fluo-4 (K(d) approximately equal 345 nM) or Fluo-4FF (K(d) approximately equal 9.7 microM) respectively, are markedly attenuated during lethal oxygen-glucose deprivation in preconditioned cultures.Collectively, the results suggest the attenuation of the postsynaptic NMDA-mediated component of otherwise lethal oxygen-glucose deprivation through the suppression of Ca(2+)-dependent neurotoxic signaling, a mechanism that is initially induced by transient nonlethal activation of this receptor during ischemic preconditioning.

Aniline Compounds↗
PubMed2001

Implications of impulsive and affective symptoms for serotonin function in bulimia nervosa.

BACKGROUND: Bulimic, impulsive and depressive syndromes have all been associated with abnormalities in brain serotonin (5-hydroxytryptamine; 5-HT) mechanisms. METHODS: We had 26 bulimic women and 22 normal-eater women report impulsive, affective, self-destructive and bulimic symptoms, and then provide serial blood samples for measurement of: [3H]-paroxetine binding in platelets; and, prolactin (PRL) responses following oral meta-chlorophenylpiperazine (m-CPP). RESULTS: Bulimic status was associated with markedly reduced density of paroxetine-binding sites, modest blunting of m-CPP stimulated PRL response, and greater nausea following m-CPP. Biological variables did not co-vary with most psychopathological or eating-symptom indices. However, there were inverse associations (in bulimic women only) between scores indicating impulsivity (largely 'unreflectiveness') and density of platelet 5-HT uptake sites. CONCLUSIONS: Our observations link bulimia nervosa to altered 5-HT functioning, and suggest that there may be a relatively symptom-specific association between impulsivity and reduced 5-HT reuptake.

Adult↗
PubMed2001

Attenuation of neurotoxicity in cortical cultures and hippocampal slices from E2F1 knockout mice.

The E2F1 transcription factor modulates neuronal apoptosis induced by staurosporine, DNA damage and beta-amyloid. We demonstrate E2F1 involvement in neuronal death induced by the more physiological oxygen-glucose deprivation (OGD) in mouse cortical cultures and by anoxia in mouse hippocampal slices. E2F1(+/+) and (-/-) cultures were comparable, in that they contained similar neuronal densities, responded with similar increases in intracellular calcium concentration ([Ca(2+)]i) to glutamate receptor agonists, and showed similar NMDA receptor subunit mRNA expression levels for NR1, NR2A and NR2B. Despite these similarities, E2F1(-/-) cultures were significantly less susceptible to neuronal death than E2F1(+/+) cultures 24 and 48 h following 120-180 min of OGD. Furthermore, the absence of E2F1 significantly improved the ability of CA1 neurons in hippocampal slices to recover synaptic transmission following a transient anoxic insult in vitro. These results, along with our finding that E2F1 mRNA levels are significantly increased following OGD, support a role for E2F1 in the modulation of OGD- and anoxia-induced neuronal death. These findings are consistent with studies showing that overexpression of E2F1 in postmitotic neurons causes neuronal degeneration and the absence of E2F1 decreases infarct volume following cerebral ischemia.

Animals↗
PubMed2001

Synthesis and antiproliferative activity of [2-(phthaloylamino)alkyl]triphenyl phosphonium derivatives against K562 cell line.

Given the reported cytotoxicity of phthaloylaminoethyltriphenylphosphonium bromide 2a in the P-388 cell line, we have developed new [2-(phthaloylamino)alkyl]phosphonium derivatives 2b-e and evaluated their cytotoxic activity. These compounds have been synthetized from N,N-phthaloylaminoalcohols and triphenylphosphonium hydrobromide via a one-pot reaction. 2a was found inactive in the K562 cell line, but 2c-e exhibited a cytotoxic activity with IC50 values about 1 microM.

Antineoplastic Agents↗
PubMed2001

Diatheses and stressors in borderline pathology of childhood: the role of neuropsychological risk and trauma.

OBJECTIVE: To determine the relative contributions of neuropsychological deficits and psychosocial stressors to the presence of borderline pathology in children. METHOD: The subjects were 86 school-age children (75 males, 11 females) referred for psychiatric day treatment. Thirty-five of the children met criteria for borderline pathology. Data on psychosocial risk factors were obtained for each child from a questionnaire completed by members of the child's clinical team and were based on interviews with parents and children, as well as reports from schools and social agencies. Neuropsychological measures included computerized versions of the Wisconsin Card Sorting Test and the Continuous Performance Test. RESULTS: Both deficits in executive function and psychological trauma made significant and independent contributions to the variance in borderline pathology. Inclusion of both sets of risk factors produced a model that explained 48% of the variance in borderline diagnosis. CONCLUSIONS: Both environmental risks and neurobiological vulnerability should be taken into account to understand the etiology of borderline pathology in children.

Borderline Personality Disorder↗
PubMed2001

Brain Regional alpha-[11C]methyl-L-tryptophan trapping in impulsive subjects with borderline personality disorder.

OBJECTIVE: Neurotransmission of serotonin (or 5-hydroxytryptamine [5-HT]) is thought to be disturbed in patients exhibiting impulsive behaviors. However, until recently it has not been possible to test this hypothesis in the brains of living humans. METHOD: Unidirectional trapping of the 5-HT precursor analog alpha-[(11)C]methyl-L-tryptophan (alpha-[(11)C]MTrp) has been proposed as an index of 5-HT synthesis capacity. The authors measured brain regional alpha-[(11)C]MTrp trapping with positron emission tomography in medication-free subjects with borderline personality disorder (N=13) and a healthy comparison group (N=11). Impulsivity was assessed by using a laboratory measure of behavioral disinhibition, go/no-go commission errors. RESULTS: Compared to healthy men, the men with borderline personality disorder had significantly lower alpha-[(11)C]MTrp trapping in corticostriatal sites, including the medial frontal gyrus, anterior cingulate gyrus, superior temporal gyrus, and corpus striatum. In the women with borderline personality disorder, significantly lower alpha-[(11)C]MTrp trapping was seen in fewer regions, but in both men and women, negative correlations with impulsivity scores were identified in the medial frontal gyrus, anterior cingulate gyrus, temporal gyrus, and striatum. CONCLUSIONS: Low 5-HT synthesis capacity in corticostriatal pathways may contribute to the development of impulsive behaviors in persons with borderline personality disorder.

Adult↗