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H Fernandez

Publications and source records attributed to H Fernandez.

At least 181 records · Page 10Linked to original sources

Successful chemotherapy including epirubicin in a pregnant non-Hodgkin's lymphoma patient.

We report a case of non-Hodgkin's lymphoma (NHL) successfully treated with combination chemotherapy during pregnancy. The histological diagnosis was large-cell B-type NHL. Four courses of chemotherapy with epirubicin, vincristine and prednisolone were given before delivery. The patient is in complete remission and her baby, now four years old, has developed normally. To our knowledge, this is the first reported case of epirubicin administration during pregnancy and in which chemotherapy was given safely to NHL patients during the second and third trimester of pregnancy.

Adult↗

Ultrasound-guided injection of methotrexate versus laparoscopic salpingotomy in ectopic pregnancy.

OBJECTIVE: To compare local injection of methotrexate (MTX) under sonographic control to laparoscopic salpingotomy for conservative management of ectopic pregnancy (EP). DESIGN: Prospective randomized study. PATIENTS: Forty patients were randomized into two groups using a random number table. Inclusion criteria were an EP visualized by ultrasound with a pretherapeutic score < or = 13 as assessed by six criteria graded from 1 to 3: gestational age, hCG level, P level, abdominal pain, volume of the hemoperitoneum, and diameter of the hematosalpinx. INTERVENTIONS: Group 1 patients injected transvaginally with 1 mg/kg MTX into the EP without anesthesia versus group 2 patients undergoing laparoscopic salpingotomy. MAIN OUTCOME MEASURES: Postoperative hospital stay, decrease of hCG levels, success rate. RESULTS: The success rates, defined by hCG levels returned to normal (< 10 mIU/mL [conversion factor to SI units, 1.00]), were 19 of 20 in both groups. Medical treatment was associated significantly with shorter postoperative stay (24 versus 46 hours) and a higher initial hCG level. Human chorionic gonadotropin returned to normal more quickly after laparoscopic treatment (14 versus 28 days). CONCLUSIONS: In selected cases of EP with a pretherapeutic score < or = 13, MTX treatment appeared to be as safe and efficient as was conservative treatment by laparoscopy.

Adult↗

Identification of genes overexpressed in tumors through preferential expression screening in trophoblasts.

Early trophoblastic cells share several features with neoplastic cells. Based on that observation, we attempted to identify genes overexpressed in tumors by analyzing genes preferentially expressed in trophoblasts. A subtracted library enriched in complementary DNA from early cytotrophoblasts was constructed, and the expression level of selected recombinants was analyzed on a large panel of normal and tumor tissues. The library was prepared using a polymerase chain reaction-based complementary DNA subtraction method with 6-week amenorrhea cytotrophoblast endoplasmic reticulum-bound RNA as target, and a mixture of complementary DNA prepared from terminal placenta and activated T-lymphocytes as driver. Two rounds of screening were performed to isolate clones preferentially expressed in early placenta. From a total number of recombinant clones estimated at 32,000 in the subtracted library, 594 inserts were analyzed by Southern blot and 21 sequences were isolated as corresponding to genes highly expressed in early placenta. Eleven encoded known molecules, such as carcinoembryonic antigen, human chorionic gonadotropin, and mitochondrial rRNAs. Ten sequences represented novel genes. Northern blot analysis confirmed that most of these genes were preferentially expressed in early trophoblast in comparison to terminal placenta. Three clones that gave detectable hybridization signals on total RNA were extensively studied and were found to be overexpressed in various tumors. Two of these clones, designated B9 and E4, were later identified as corresponding to genes coding for the putative ribosomal protein S18 and the bifunctional enzyme ADE2H1 involved in purine biosynthesis, respectively. Expression of the third clone, E9, was increased up to 10-fold in breast cancer tissues in comparison with normal counterparts. Present results confirm that many genes expressed in the trophoblast are overexpressed in malignant cells. This approach could provide a general targeted method for the identification of genes overexpressed in various neoplastic cell types.

Base Sequence↗

Treatment of unruptured tubal pregnancy with methotrexate: pharmacokinetic analysis of local versus intramuscular administration.

OBJECTIVE: To determine the optimal dose and route of methotrexate (MTX) in the treatment of ectopic pregnancy (EP). DESIGN: Prospective randomized study. SETTING: Department of Obstetrics and Gynecology (A. Béclère Public Hospital, Clamart, France, Paris-Sud University). PATIENTS AND METHODS: Forty-eight patients with unruptured EP clearly visualized by ultrasound were randomly allocated into four groups of treatment (12 patients in each group): group 1, 1 mg/kg injected locally in the ectopic gestational sac and 1 mg/kg by IM administration 48 hours later; group 2, 1 mg/kg locally; group 3, 0.5 mg/kg locally; group 4, 1 mg/kg by IM administration. Inclusion criteria used a pretherapeutic score < or = 12. Blood samples were collected at time 0.25, 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after MTX administration. Pharmacokinetics of MTX plasma levels were measured by fluorescence polarization immunoassay. Kinetic parameters were compared by Wilcoxon test and Mann-Whitney test. Plasma hCG concentrations were assessed on days 2, 5, and 10 and then weekly until they returned to undetectable levels. RESULTS: Success rate was 12 of 12, 11 of 12, 10 of 12, and 10 of 12 in groups 1, 2, 3, and 4, respectively. Six patients in group 3 required an additional MTX IM injection because of an inadequate decrease of hCG plasma levels. Five patients underwent surgery for abdominal pain or inadequate decrease of hCG. Area under the curve decreased more rapidly after injection in the gestational sac alone than after IM injection and was similar in groups 1 and 2 after local injection and lower in group 3. Terminal half-life and mean residence time remained similar in the four groups. Systemic side effects of MTX therapy occurred in three cases in groups 1 and 4. The regression curve of hCG plasma levels appeared similar in the four groups with a decrease to pretreatment values between days 6 and 8 after an initial rise after MTX was given. CONCLUSION: Area under the curve found after injection in the ectopic sac may be related to a decrease in bioavailability of MTX that links to trophoblastic cells. Patients in group 3 were clearly undertreated by 0.5 mg/kg MTX and required additional therapy. Residual values of MTX plasma levels were always below the limit of detection of our assay and confirmed that citrovarum factor rescue is unnecessary. Injection of 1 mg/kg of MTX in the ectopic sac appears as effective as systemic (IM) injection with less side effects for the patients.

Chorionic Gonadotropin↗

[Antibiotic prophylaxis in cesarean section and voluntary termination in pregnancy].

Infection is the main complication after voluntary termination of pregnancy through vacuum aspiration, with an infection rate of 3.6% in the subsequent three weeks. This rate is comparable to that observed in the so-called clean surgical procedures. However the consequences on fertility remain unknown. Studies using systematic antibiotic administration in all vacuum aspirations (voluntary termination of pregnancy and spontaneous abortion) demonstrated the value of such a preventive measure. Factors of risk are difficult to identify and systematic bacteriological specimen collection in all patients undergoing a termination of pregnancy is quite impossible to do. Therefore, the best strategy consists in the oral administration of 200 mg of doxycycline before the aspiration and 200 mg 12 hours later. The incidence of operative-site infection and endometritis after Caesarean section without perioperative antimicrobial prophylaxis varies from 5 to 85%. A variety of risk factors have been identified such as low social category, rupture of membranes, the number of vaginal examinations, labour, and emergency sections. Most clinical trials have shown no significant difference in the efficacy of various antibiotic regimens. However, prophylactic antibiotics decrease significantly the rate of infections. We recommend one or three doses of intravenous prophylactic antibiotic, after clamping and section of the umbilical cord in high risk patients. Cephalosporin of 1st or 2nd generation or ampicillin associated with an inhibitor of beta-lactamases are recommended.

Abortion, Induced↗

Incidence of ectopic pregnancy. First results of a population-based register in France.

A population-based register of ectopic pregnancy was established in 1992 for two French departments, with the primary aim of monitoring the trend in ectopic pregnancy over a prolonged period. In this paper, data collected during the first year of registration (1992) are analysed. The rate of ectopic pregnancy was 20.2 per 1000 live births, 15.8 per 1000 reported pregnancies and 9.5 per 10,000 women aged 15-44 years. The ectopic pregnancy rate per 1000 live births increased steeply after the age of 30 years and especially after the age of 35 years, whereas rates per 10,000 women of reproductive age steadily increased until the age of 35 years and decreased thereafter. The rates of ectopic pregnancy were lower in spring and summer than autumn and winter. These results are discussed and comparisons with similar studies conducted in the USA and Scandinavia are attempted.

Adolescent↗

Mifepristone for labour induction after previous caesarean section.

OBJECTIVE: To evaluate the efficacy and tolerance of mifepristone in women undergoing induction of labour at term after previous caesarean section. DESIGN: A prospective double blind placebo controlled trial. SUBJECTS: Thirty-two women at term (after 37.5 weeks' amenorrhea) who had had a previous caesarean delivery with a low transverse uterine incision. All women had a clear clinical indication for induction of labour with unfavourable cervical conditions (Bishop's score < 4). They were randomised to receive either 200 mg of mifepristone or placebo on days one and two of a four-day observation period. RESULTS: Thirteen women entered spontaneous labour: 11 were treated with mifepristone and two were in the control group (P < 0.01). Thirteen women, still with an unfavourable cervix on day four needed cervical ripening with vaginal tablets of prostaglandins. Of these, four had received mifepristone and nine the placebo. Mean oxytocin requirements were lower in the mifepristone group (P < 0.01) and the mean time interval between day one and start of labour was also significantly shorter in this group. Mode of delivery and neonatal outcome were similar in both groups. CONCLUSIONS: Induction of labour is facilitated in term women with prior caesarean section by the use of mifepristone. This induction agent appears safe and useful with no adverse events on the fetus or mother.

Adult↗

Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels.

Although progesterone and estrogens are essential to maintain human pregnancy after implantation, the localization of their specific receptors in different uterine cell types during pregnancy has not been investigated. We studied uteri (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late pregnancy (n = 9) as well as from women 5-14 weeks pregnant (n = 10) who had received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical dilation. Frozen tissues were processed for indirect immunocytochemical staining with specific monoclonal antibodies against estrogen receptors (ER; Abbott Laboratories) and progesterone receptors (PR; Li 417). Specific staining for steroid receptors was only detected in the nucleus. In the endometrium, PR staining remained fairly constant throughout pregnancy, whereas ER staining was initially weak and then undetectable. PR was widely expressed in stromal cells and in spiral arterial wall cells, whereas ER was expressed in scattered stromal cells and arterial cells. Both PR and ER were absent from glandular epithelium, contrasting with the secretory activity during the first trimester. Spiral arteries of the endometrium and myometrial smooth muscle cells showed intense PR and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486 (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked increase in ER staining and a smaller increase in PR staining in stromal cells, whereas the glandular epithelium remained negative for both ER and PR (except for one and two specimens, respectively). We conclude the following. 1) Stromal cells retain PR despite the high progesterone levels during pregnancy, in keeping with the role of progesterone in stromal decidualization. The absence of PR from the secretory glandular epithelium suggests a paracrine link between decidualized stromal cells and epithelial cells. 2) Significant PR down-regulation by progesterone during pregnancy occurs only in epithelial cells of the endometrium. 3) In contrast, the absence or low level of ER staining in the various cell types of the endometrium during gestation concurs with the known effect (down-regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER in human decidua after RU 38486 treatment indicates that the main cause of the low ER levels is progesterone secretion. 4) The intense PR staining in smooth muscle cells of spiral arteries during early pregnancy suggests that progesterone is essential for modulating blood flow during pregnancy.

Adult↗

Postoperative pain after local anesthetics for laparoscopic sterilization.

OBJECTIVE: To test the effectiveness of intraperitoneal local anesthesia in relieving postoperative pain after laparoscopic sterilization. METHODS: In a double-blind, placebo-controlled randomized study of two groups of 25 subjects each, women scheduled for tubal sterilization under general anesthesia received 80 mL of 0.5% lidocaine with 1/320,000 epinephrine intraperitoneally in the right subdiaphragmatic quadrant at the beginning of the procedure. At the end of the procedure, they received 10 mL of 2% lidocaine with 1/80,000 epinephrine injected into each mesosalpinx. Controls received saline instead of lidocaine. Shoulder and pelvic pain assessed by visual analogue pain scale, postoperative analgesic requirements, nausea or vomiting, and time to return to normal daily activities were evaluated in the ambulatory unit and after discharge during the first 48 postoperative hours. Blood samples were taken in ten subjects receiving lidocaine to evaluate peak plasma concentrations and time to peak plasma concentrations. RESULTS: Pain was significantly less in patients who received lidocaine, and the difference lasted for the duration of the study (P < .05). Analgesic requirements and time to return to normal daily activities were significantly reduced in patients who received lidocaine (P < .05). Blood samples revealed no toxic concentrations. The peak plasma concentration was 3.22 +/- 1.21 micrograms/mL, and the time to peak plasma concentration was 42 +/- 15 minutes. CONCLUSION: Intraperitoneal instillation of lidocaine-epinephrine combined with mesosalpinx infiltration of lidocaine during tubal sterilization produces effective, long-lasting analgesia and improves the postoperative course.

Adult↗

[Oncologic application of oocyte donation].

Antimitotic chemotherapy and/or radiation therapy can induce a premature ovarian failure in women. The improvement of the prognosis of cancer and the increasing in long-term survival mean that preservation of fertility should be considered before initiating therapy. An embryo cryopreservation can be proposed if the circumstances allow that possibility. Ten young women were included in our program and benefited from an oocyte retrieval before cancer therapy. Nine of them had an embryo cryopreservation, and one without partner an oocyte cryopreservation. Three patients had an embryo replacement without success, and in one case, a spontaneous full-term pregnancy was obtained after ovarian detransposition through coelioscopy. In the future, oocyte cryopreservation could appear a more suitable answer. Actually, oocyte donation with estrogen and progesterone replacement therapy gives good results (in our experience, 23.2 per cent of ongoing pregnancies per transfer). Nevertheless, after treatment against cancer, a study of the uterus with its arteries, and a particular adaptation of the treatment are necessary because of the risks of tissue damage impairing the embryo implantation. Indeed, in fifteen patients included in this group, eight women had fourteen transfers unfortunately without success. Consequently, the seven other women underwent complementary examinations. Two embryos were replaced in one patient with a more adjustable treatment allowing a full-term pregnancy.

Adult↗

[Conservative management of extra-uterine pregnancy].

Expectant management was studied in 35 patients representing 4.9% of all ectopic pregnancies during an 8 year period. Laparoscopy was performed in a first period to define the inclusion criteria: hematosalpinx < or = 2 cm and hemoperitoneum < or = 50 ml. In a second period, inclusion criteria used a predictive pretherapeutic score < or = 11 with a sonographic visualization of the ectopic pregnancy. This score involved six criteria graded on a scale from 1 to 3: gestational age, hCG and P level, existence of abdominal pain, size of hemoperitoneum and diameter of hematosalpinx assessed sonographically. The patients were on out-patients basis. Success rate was 85.7% (30/35 patients). When the pretherapeutic score was < or = 11 and the initial hCG level < 1,000 mUl/ml the success rate increased to 96%. Thirteen patients (87%) had patent tubes evaluated by hysterosalpingography on the side of the ectopic pregnancy. Twelve patients delivered one miscarriage occurred and none ectopic pregnancy was observed. Expectant management is a useful form of treatment for ectopic pregnancy in selected cases.

Abdominal Pain↗

Free radicals in retinal and choroidal blood flow autoregulation in the piglet: interaction with prostaglandins.

PURPOSE: To study the role of free radicals in autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) and the contribution of the cyclooxygenase pathway in free radical formation during blood pressure changes in 1- to 3-day-old pigs. METHODS: Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and the aortic root to induce hypertension and hypotension, respectively. Blood flow was measured using the microsphere technique. Also, the effects of peroxides on retinal artery diameter were studied on eyecup preparations using time-frame photography processed by digital imaging. RESULTS: Blood gases and intraocular pressure (13 +/- 1 mm Hg) remained stable throughout the experiments. In control animals, RBF was constant only between 30 and 75 mm Hg of ocular perfusion pressure and ChBF increased as a function of ocular perfusion pressure (tau = 0.58, P < 0.01). Inhibition of peroxidation with the free radical scavenger 21-aminosteroid U74389F (2.5 mg/kg) widened the range of RBF and ChBF autoregulation (ocular perfusion pressure from 30 to 131 mm Hg). Hypertension caused an increase in the products of peroxidation, malondialdehyde, and hydroperoxides, as well as in prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in the retina and choroid of control animals; these changes were inhibited by the free radical scavengers U74389F (2.5 mg/kg) and high-dose allopurinol (140 mg/kg) as well as by the cyclooxygenase inhibitors ibuprofen (40 mg/kg) and indomethacin (5 mg/kg). In isolated eyecup preparations, H2O2 and cumene hydroperoxide dilated retinal vessels, and this effect was completely blocked by indomethacin. CONCLUSIONS: These findings indicate that free radicals play a major role in setting the upper limit of RBF and ChBF autoregulation of the newborn animal. In addition, there exists a positive feedback interaction between free radicals and cyclooxygenase activity in ocular tissues, such that during hypertension the cyclooxygenase pathway is an important producer of free radicals and in turn is also activated by them.

Animals↗

[A new therapeutic strategy using a ofloxacin-amoxicillin-clavulanic acid combination in the treatment of upper gynecologic infections. Apropos of 123 cases].

OBJECTIVE: To evaluate a new antibiotic strategy with a combination of ofloxacin + co-amoxiclav in the treatment of pelvic infectious diseases. DESIGN: An open-non-comparative multicentre (10) study. SUBJECTS: 123 patients (118 salpingitis and 5 endometritis) were included clinical, laparoscopic and bacteriological assessments were performed before treatment and a laparoscopic control was done in 35% of cases. Among positive bacteriological samples before treatment 48.7% C. trachomatis were isolated; 56.1% of salpingitis were considered as severe (COGIT score > 6). TREATMENT: Patients received at entry oral ofloxacin 200 mg bid in combination with parenteral co-amoxiclav 2 to 4 g following by oral route. Total duration of treatment was 21 days. RESULTS: With respectively 97.2% and 91.6% satisfactory clinical and bacteriological results, this combination should take a major place in the treatment of pelvic infectious diseases.

Adolescent↗