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Biomedical subjects

M Uzan

Publications and source records attributed to M Uzan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Nitric oxide (NO) metabolism in the cerebrospinal fluid of patients with severe head injury. Inflammation as a possible cause of elevated no metabolites.

BACKGROUND: This article investigates nitric oxide (NO) metabolism following severe head injury (SHI). We wished to clarify the alterations of NO metabolism end products that is associated with SHI, and to delineate the role of inflammation in this process. METHODS: In a prospective study, we simultaneously measured the concentrations of NO metabolites and interleukin-8 (IL-8) in the ventricular cerebrospinal fluid (CSF) of 11 patients who had suffered SHI. The CSF concentrations of nitrite (NO(-)(2)) and nitrate (NO(-)(3)) combined, and of IL-8 were measured during the following four time periods post-trauma: 6 to 10, 20 to 28, 40 to 56, and 64 to 74 hours. Levels were measured using the corresponding kits. RESULTS: Compared to the ventricular CSF control values, all of our SHI patients had significantly elevated CSF levels of NO(-)(2) plus NO(-)(3) (NO(-)(2) + NO(-)(3)) and IL-8 during all periods tested. CSF NO(-)(2) + NO(-)(3) and IL-8 concentrations reached their maximums simultaneously at 20 to 28 hours following trauma (Spearman's rank correlation = 0.609, p < 0.05), and NO(-)(2) + NO(-)(3) levels were significantly higher than those measured at 6 to 10, 40 to 56, and 64 to 74 hours. [Nitrite-nitrate concentrations: 6-10 hours: 19.22 +/- 6.75, 20-28 hours: 25 +/- 6.2 micromol/l, 40-56 hours: 19.82 +/- 4.47, and 64-74 hours: 19.72 +/- 4.61 micromol/l, (p < 0.05). IL-8 concentrations: 6-10 hours: 3,232 +/- 2,976.2, 20-28 hours: 3,458.45 +/- 3,048 pg/mL, 40-56 hours: 2,616.41 +/- 2,539.21, 64-74 hours: 1,388.88 +/- 1,216.7 pg/mL, (p < 0.001).]. This simultaneous surge in NO(-)(2) + NO(-)(3) and IL-8 in the initial 24 hours post-traumatic indicated that inflammation secondary to SHI increased the rate of NO metabolism, resulting in higher levels of metabolites in the CSF. CONCLUSION: In patients with SHI, CSF concentrations of the dominant metabolites of NO are elevated in the first 3 days after trauma. A similar concurrent spike in the CSF level of IL-8, a marker of acute inflammatory response, can also be demonstrated. These data indicate that the predominant cause of the higher CSF NO(-)(2) + NO(-)(3) concentrations observed in SHI is most likely inflammation.

Adolescent↗
PubMed2001

[Demons-Meigs syndrome: apropos of 1 case].

A 33-year-old patient presented with ascites and a right abdominal mass. Ultrasound and scannography showed it was probably a solid ovarian tumor measuring 175 mm x 115 mm. Serum Ca 125 was 752 UI/mL and ACE was normal. Surgical exploration revealed 3.2 liters ascites without any suspect peritoneal implant and a bulky ovarian fibrothecoma. The patient recovered quickly and serum Ca 125 was 43 UI/mL one month post-operatively. In this case report of Meigs' syndrome serum CA 125 level was particularly high. Preoperative diagnostic difficulties are discussed.

Adult↗
PubMed2001

Comparison of recombinant and urinary follicle-stimulating hormone preparations in short-term gonadotropin releasing hormone agonist protocol for in vitro fertilization-embryo transfer.

PURPOSE: To compare the efficiency and efficacy of two recombinant human FSH (r-FSH) and urinary (u-FSH) preparations in patients undergoing superovulation for IVF-ET using a short-term gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) protocol. METHODS: A total of 88 women undergoing IVF-ET were included in this prospective study. They were randomized to receive u-FSH (150 IU/d), follitropin-alpha (100 IU/d), or follitropin-beta (100 IU/d) for 2 days, and dosages were subsequently adjusted according to the ovarian response. RESULTS: The FSH dose required for the overall stimulation was significantly lower in patients treated with r-FSH than in those treated with u-FSH while serum FSH values were higher in the latter group. There were no statistically significant differences in ovarian response and IVF outcome between r-FSH preparations. CONCLUSIONS: Recombinant FSH preparations have a higher efficiency than urinary ones in patients undergoing IVF-ET using a short-term GnRH-a protocol. In this situation, the two recombinant follitropins have comparable effectiveness.

Adolescent↗
PubMed2001

Ultrasound assessment in a case of sialic acid storage disease.

A woman was referred to our unit at 25 weeks' gestation because of fetal ascites. Conventional and three-dimensional ultrasound examinations revealed coarse facies and micromelia which strongly suggested storage disease, despite the absence of an index familial case. Amniocentesis was performed and, in view of the poor prognosis, the pregnancy was terminated. Autopsy confirmed all the sonographic features and the cultured amniocytes confirmed the diagnosis of infantile sialic acid storage disease.

Abnormalities, Multiple↗
PubMed2001

Uteroplacental circulation development: Doppler assessment and clinical importance.

In the first weeks of pregnancy, columns of endovascular cytotrophoblastic plugs develop in the lumen of spiral arteries. Morphologic data show that these plugs become loosened as soon as the end of the second month and the intervillous circulation of maternal blood is likely to be established progressively between the 8th and 12th weeks. The disorganization of the musculo-elastic layers of these vessels provokes a dramatic decrease in vascular tone in the uteroplacental circulation. These modifications appear to govern the establishment of a low-pressure blood flow in the placenta, and hence determine the quality of uteroplacental circulation and normal fetal growth. Placental bed biopsies in women with pre-eclampsia and in a proportion of pregnancies with intrauterine growth retardation have shown that these physiologic changes were absent in the myometrial segments of spiral arteries. Recently, colour Doppler was used to assess intervillous and spiral artery flow in early pregnancy, confirming in vivo free intervillous flow at 12 weeks and a progressive significant decrease in spiral artery resistance with advancing gestation during the first trimester. However, certain data at an earlier gestational age are still contradictory. Particularly, the exact nature of the contents of the intervillous space before 8 weeks, and whether or not this fluid can be considered maternal blood, remains controversial.

Arteries↗
PubMed2001

Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results: a multicenter randomised controlled trial.

OBJECTIVES: To assess whether systematic screening with an uterine artery Doppler in low risk pregnant women followed by the prescription of low dose aspirin in cases with abnormal results reduced the incidence of intrauterine growth restriction and pre-eclampsia. DESIGN: A multicentre randomised trial. POPULATION: 3,317 low risk pregnant women. In the Doppler group, the uterine artery Doppler was performed between 20 and 24 weeks. Women with abnormal results received 100 mg of aspirin daily until the 35th week. MAIN OUTCOME MEASURES: Intrauterine growth restriction was defined as birthweight below the tenth and the third centile according to gestational age. Pre-eclampsia was defined as hypertension associated with proteinuria > 0.5g/L. RESULTS: Intrauterine growth restriction, whether defined by the third or tenth centile, did not differ significantly between the two groups (RR = 1.22 [0.73 - 2.04] and 1.18 [0.93 - 1.51] respectively). Screening with uterine artery Doppler did not affect birthweight or any of the criteria of perinatal morbidity. There was no effect on the incidence of pre-eclampsia (RR = 1.99 [0.97 - 4.09]) or hypertensive disorders. These results were the same for nulliparae and multiparae. CONCLUSIONS: There is no justification for screening with uterine artery Doppler in a low risk population, even if abnormal results are followed by aspirin treatment and increased prenatal surveillance. Future studies must assess predictive tests that can be performed early in pregnancy and can identify populations at very high risk of pre-eclampsia and intrauterine growth restriction. Only when all of these conditions are fulfilled, aspirin or other treatments may prove its efficacy.

Adult↗
PubMed2001

[Endometrial adenocarcinoma treated with combined radiotherapy and surgery: 437 cases].

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. PATIENTS AND METHODS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of RT was not randomized and depended on the usual practices of the surgical teams. Group I: 79 pts received preoperative uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50 Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5 weeks]). The mean follow-up was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivariate analysis showed that independent factors decreasing the probability of disease-free survival were: histologic type (clear cell carcinoma, p = 0.038), largest histologic tumor diameter > 3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.0055), and 1988 FIGO staging system (p = 9.10(-8)). In group II, the addition of EPRT did not seem to improve locoregional control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were FIGO stage (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. EPRT independently increased the 10-year rate for grade 3 and 4 late radiation complications (R.R.: 5.6, p = 0.0096). CONCLUSION: EPRT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in a subgroup of intermediate risk patients (stage IA grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with stage III tumor are not satisfactory.

Adenocarcinoma↗
PubMed2001

Myometrial maturation and labour.

The increased expression of contraction-associated proteins, including oxytocin receptors, connexin-43, and prostaglandin F2alpha receptors, in term pregnant myometrium is classically considered to be the concrete expression of myometrial activation. However, the decrease in prostaglandin E2 receptor subtype EP2 on one hand and the down-regulation of the nitric oxide (NO) pathway and various vasorelaxing peptides on the other hand probably also play a key role in the loss of quiescence, and, with the above-mentioned activation, in the maturation of the myometrium. Decidual activation and production of interleukin-1, tumour necrosis factor-alpha and epidermal growth factor enhance prostaglandin production in both the amnion and chorion, and also in the myometrium. A substantial increase of eicosanoids concentration in myometrial tissue is probably an important condition for the success of the ultimate step of myometrial stimulation and the onset of labour. During labour, prostaglandins and oxytocin seem to act in synergy, perhaps along with endothelin-1, to trigger contractility through an increase in intracellular Ca2+ concentration. An overall view of these phenomena in which myometrial cells are the common targets of uterorelaxant and uterotonic agents appears essential for a rational use of tocolytic therapies and labour inductors.

Endothelin-1↗
PubMed2000

Role of the substrate conformation and of the S1 protein in the cleavage efficiency of the T4 endoribonuclease RegB.

The T4 endoribonuclease RegB is involved in the inactivation of the phage early messengers. It cuts specifically in the middle of GGAG sequences found in early messenger intergenic regions but not GGAG sequences located in coding sequences or in late messengers. In vitro RegB activity is very low but is enhanced by a factor up to 100 by the ribosomal protein S1. In the absence of clear sequence motif distinguishing substrate and non-substrate GGAG-containing RNAs, we postulated the existence of a structural determinant. To test this hypothesis, we correlated the structure, probed by NMR spectroscopy, with the cleavage propensity of short RNA molecules derived from an artificial substrate. A kinetic analysis of the cleavage was performed in the presence and absence of S1. In the absence of S1, RegB efficiently hydrolyses substrates in which the last G of the GGAG motif is located in a short stem between two loops. Both strengthening and weakening of this structure strongly decrease the cleavage rate, indicating that this structure constitutes a positive cleavage determinant. Based on our results and those of others, we speculate that S1 favors the formation of the structure recognized by RegB and can thus be considered a "presentation protein."

Base Sequence↗
PubMed2000

Endoribonuclease RegB from bacteriophage T4 is necessary for the degradation of early but not middle or late mRNAs.

The RegB endoribonuclease from bacteriophage T4 cleaves early mRNAs specifically in the middle of the sequence GGAG. We show here that RegB is required for the degradation of bulk T4 early mRNA. In the absence of RegB, the chemical half-life of early transcripts is increased nearly fourfold, whereas their functional half-life is increased twofold. RegB also regulates the translation of several prereplicative genes. The synthesis of several early proteins is down-regulated, probably as a consequence of RegB cleavages in the Shine-Dalgarno sequence of these genes. The synthesis of several other proteins is up-regulated, suggesting that processing by RegB might improve translation by changing the conformation of a transcript. In contrast, RegB does not affect the average half-life of middle and late mRNA. An analysis of the susceptibility to RegB of many GGAG motifs carried by these mRNA species showed that most middle and all late GGAG-carrying mRNAs escape RegB processing in spite of the fact that the enzyme is acting at least until ten minutes post-infection. The sensitivity or resistance to RegB observed during phage infection could be reproduced in uninfected Escherichia coli cells and in vitro. This shows that the GGAG-carrying RNAs that are uncut during T4 infection are not substrates, whatever the period of the T4 cycle when the transcripts are made.

Bacteriophage T4↗
PubMed2000

[Neonatal myasthenia gravis].

BACKGROUND: Myasthenia gravis, an autoimmune disease of young women, is due to the dysfunction of neuromuscular transmission. The newborn of a myasthenic mother inconstantly presents a transitory neonatal myasthenic syndrome. Maternal aggravation, or even myasthenic crisis with respiratory failure, can occur in the first three months post-partum. CASE REPORT: Mrs. S., para two without appreciable medical history, delivered normally a boy weighing 4 kg with an Apgar score of 10/10. At 3 h of life the newborn was admitted to the neonatal care unit for grunting and axial hypotonia. Diagnoses of maternal-fetal infection and fetal distress were excluded. The dissociated pattern of neurological disorders (refusal to drink, axial hypotonia, hypomimia, but good contact and normal alertness) led to search for neuromuscular causes or poison. Myasthenia gravis was then considered and confirmed by maternal electromyography, allowing the diagnosis of transient neonatal myasthenia gravis and early diagnosis and treatment of the maternal myasthenic crisis in a specialized care unit. The outcome of both mother and child was favorable under treatment. CONCLUSION: Lack of maternal myasthenia gravis history should not result in excluding the diagnosis of transitory neonatal myasthenia gravis when evocative neonatal neurological signs are present. The symptomatology in the newborn may indeed reveal maternal myasthenia gravis, allowing an early diagnosis in both the mother and the newborn.

Adult↗
PubMed2000

The bacteriophage T4 anti-sigma factor AsiA is not necessary for the inhibition of early promoters in vivo.

Bacteriophage T4 early promoters are utilized immediately after infection and are abruptly turned off 2-3 min later (at 30 degrees C) when the middle promoters are activated. The viral early protein AsiA has been suspected to bring about this transcriptional switch: not only does it activate transcription at middle promoters in vivo and in vitro but it also shows potent anti-sigma70 activity in vitro, suggesting that it is responsible for the shut-off of early transcription. We show here that after infection with a phage deleted for the asiA gene the inhibition of early transcription occurs to the same extent and with the same kinetics as in a wild-type infection. Thus, another AsiA-independent circuit efficiently turns off early transcription. The association of a mutation in asiA with a mutation in mod, rpbA, motA or motB has no effect on the inhibition of early promoters, showing that none of these phage-encoded transcriptional regulators is necessary for AsiA-independent shut-off. It is not known whether AsiA is able to inhibit early promoters in vivo, but host transcription is strongly inhibited in vivo upon induction of AsiA from a multicopy plasmid.

Bacterial Proteins↗
PubMed2000

Consequences on gonadotrophin secretion of an early discontinuation of gonadotrophin-releasing hormone agonist administration in short-term protocol for in-vitro fertilization.

Administration of gonadotrophin-releasing hormone (GnRHa) agonists, used in IVF short-term protocols to initiate follicular recruitment, may be restricted to the early follicular phase without any further risk of LH surge. However, consequences of an early discontinuation upon residual endogenous gonadotrophin secretion are still unknown. Here, the effects of early cessation of GnRH agonist upon gonadotrophin secretion and ovarian parameters of IVF cycles were investigated. A total of 230 normo-ovulatory women were prospectively allocated to one of the two regimens: decapeptyl-GnRH (100 microgram) was daily injected either from day 1 to the triggering of ovulation (group 1) or for the first 7 days (group 2). Exogenous gonadotrophins (150 IU) were administered on day 4 and 5 with a subsequent adjustment. Detections of free alpha subunit and dimeric LH were performed by highly specific 'two site' monoclonal immunoradiometric assays. The results show that early discontinuation of GnRH agonist administration was associated with a sharp decrease in both plasma free alpha subunit and dimeric LH concentrations while plasma oestradiol response to exogenous gonadotrophins was reduced. Other ovarian parameters and pregnancy rate were unchanged. These data indicate that endogenous LH secretion is maintained by a daily administration of GnRH agonist and may contribute to the final follicular maturation.

Adult↗
PubMed2000

Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation.

UNLABELLED: The adaptation of vascular tone in early pregnancy precedes and probably triggers blood volume and cardiac output increase. Because the endothelium is known to regulate vascular smooth muscle action, the role of nitric oxide (NO) in the setting up of adequate uteroplacental and renal blood flow during normal pregnancy was investigated. The persistence of abnormally high uteroplacental resistance is a strong predisposing factor for intrauterine growth retardation and preeclampsia and can be screened by second trimester Doppler assessment of the uterine arteries. Current hypotheses suggested by experimental and clinical data concerning preeclampsia confirm the crucial role played by the endothelium and vascular tone adaptation. The analysis of these data leads to consider apart early-onset preeclampsia affecting pregnancies with growth retarded fetuses and associated with high vascular resistance. Lastly, NO donors seem to significantly decrease the impedance in the uteroplacental circulation and to improve fetoplacental hemodynamics assessed by Doppler measurements, and their therapeutic use in some forms of preeclampsia might be promising. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to summarize the events that regulate vascular tone in pregnancy, specifically the role of nitric oxide and other vasoactive prostaglandins in the regulation of vascular tone and to describe the various hypotheses concerning the mechanism and the mediators responsible for initiating endothelial damage in the various disorders of vascular tone in pregnancy.

Adult↗
PubMed1999

Sylvian fissure lipomas: case reports and review of the literature.

Two patients with Sylvian fissure lipoma are reported. One of them was operated on because of an increased frequency of epileptic seizures in spite of high dose carbamazepine treatment. A review of the literature regarding the surgical experience with Sylvian lipomas revealed only four cases, and in none of them was the lipoma removed totally. One of ours is the first case in which total removal of the lipoma was achieved. The postoperative course was uneventful and carbamazepine dose was gradually lowered without further epileptic activity. If these exceedingly rare lesions cause symptoms then surgical intervention is indicated. With microsurgical techniques, Sylvian fissure lipomas can be removed totally without complication and symptomatic improvement may result.

Adult↗
PubMed1998

Virological and biological characteristics of cervical intraepithelial neoplasia grade I with marked koilocytotic atypia.

The aim of this study was to evaluate virologic and biological significance of marked koilocytotic atypia observed in some cases of grade I cervical intraepithelial neoplasia (CIN I). Thirty-one CIN I cervical biopsy specimens with marked koilocytotic atypia, defined by the presence of meganuclei in the superficial epithelial layers, were compared to 37 CIN I biopsy specimens with usual koilocytes for (1) the human papillomavirus (HPV) type and signal pattern as detected by nonisotopic in situ hybridization (ISH); (2) the proliferation index assessed by Ki 67 immunostaining and (3) the p53 labeling pattern. Interobserver agreement for meganuclei was excellent (k = 0.9). Twenty-five out of 68 biopsies (37%) were positive by ISH for the 6 of 11 HPV probe, 30 (44%) for the 16-18 probe, and 7 (10%) for the 31/33 HPV probe, 6 (9%) were negative for ISH. The presence of meganuclei was strongly related to high and intermediate risk HPV type (P = 0.0001). The sensitivity and specificity of meganuclei for the detection of high or intermediate risk HPV in CINI were 73 and 87%, respectively. Loss of p53 immunostaining in the lower third of the epithelium was also related to the presence of meganuclei (P < .05), but the MIB-1 index and ISH labeling pattern were not. In conclusion, marked koilocytotic atypia in CIN I is a reliable and sensitive marker for infection by high or intermediate-risk HPV, and might be a guide to therapy.

Antigens, Nuclear↗