Biomedical subjects
Publications and source records attributed to H Fernandez.
We describe a case of spontaneous twin ectopic pregnancy, managed with the combination of local injection under ultrasound control and intramuscular administration of methotrexate. We describe a difference between the area under the curve of declining plasma concentration of methotrexate after intramuscular and local injection.
Previous reports have demonstrated a gastric emptying effect of erythromycin due to a motilin-like mechanism. We studied 50 patients, scheduled for daycase laparoscopy, randomly assigned to one of two groups: Group P patients received 30 min before induction of anaesthesia, in a double-blind manner an infusion of 250 ml dextrose 5% while patients in Group E (n = 25) received 500 mg of erythromycin diluted in 250 ml dextrose 5%. An orogastric tube was inserted to measure both gastric pH using a pHmeter and residual gastric volume (RGV) using the phenol red dilutional technique. Six patients were excluded for surgical reasons. More patients in Group P (6/22) than in Group E (0/22) had RGV > 25 ml and more patients in Group P (17/22) presented with a gastric pH < 2.5 than in Group E (5/22), P < 0.05. Since coma and respiratory depression have been reported recently after midazolam and alfentanil administration in patients having received erythromycin, recovery conditions were assessed and were found to be comparable between groups. In conclusion, the administration of iv erythromycin before outpatient laparoscopy decreased residual gastric volume and increased gastric pH without affecting recovery from general anaesthesia.
The most common adverse outcome associated with vaginal delivery is endometritis. It plays a significant role in postpartum morbidity and mortality. There is considerable evidence to support the idea that a single dose of antibiotic after vaginal delivery might decrease the incidence of postpartum endometritis. In this study the evaluation of the efficacy of antibiotic prophylaxis was based upon comparison of a group of patients given a single dose of Amox-CA (Augmentin) with a group of patients without treatment. The study was performed in the Department of Obstetrics and Gynecology of the A. Béclère Public Hospital, Clamart, France (Paris-Sud University). The patients who were the subject of the study had delivered vaginally during the period of 1 year, and were free of any clinical diagnosis of chorioamnionitis or other extragenital infection, had a maternal temperature of less than 38 degrees C during labor and 1 h after delivery, and had no history of allergy to penicillins or cephalosporins. After application of exclusion criteria, 1373 patients were randomized and 1291 included 610 in Group I given Amox-CA and 681 in Group II without any antibiotic. A single dose of 1.2 g of Amox-CA was given by intravenous injection, 1 h after delivery, in Group I. Patients of Group II received no injection. Postpartum status was evaluated before the patient left hospital and 2 weeks later. The two groups were similar in terms of demographic and clinical parameters. Four patients developed endometritis in Group I (4/610, 0.66%). Sixteen patients in Group II developed endometritis (16/680, 2.38%) (P = 0.013; 95% confidence interval (CI), 0.36-3.08%).(ABSTRACT TRUNCATED AT 250 WORDS)
Early amniocentesis (before 13 weeks' gestation) using a per-urethral transvesical route is studied. Eight samples were obtained in eight patients scheduled for elective termination of pregnancy. The volume of amniotic fluid averaged 12.5 +/- 7.8 ml. Culture was successful in all samples. In one case, culture was achieved with only 2 ml of amniotic fluid. The amniotic fluid can be easily obtained via the per-urethral transvesical route. We conclude that early per-urethral amniocentesis before 13 weeks amenorrhea may be an alternative to the transabdominal route. A clinical trial should be carried out in order to evaluate both techniques.
Very little information is available concerning the pharmacokinetic behaviour and monitoring of cyclosporin A (CsA) during pregnancy, notably after liver transplant. Monitoring of blood levels of CsA is considered to be one of the best tools for evaluation of the efficacy of immunosuppressant treatment. The aim of this study was to bring together new information concerning pregnant women receiving immunosuppressant treatment with CsA and, in view of the special pathophysiological status of such patients, to compare pharmacokinetic profiles of changes in blood levels of CsA and of the combination of CsA plus metabolites. Specific (CsA-S kit) and a new non-specific (CsA-NS kit) assays of CsA were carried out in five hospitalized pregnant patients who had received liver transplants between the 6th and the 41st weeks of amenorrhea. The results of five cases investigated lead to the following conclusions: (1) The pharmacokinetic behaviour of native CsA in the pregnant woman between the 6th and 41st weeks of amenorrhea suggests no systemic accumulation nor any radical need for changes in dosage schedule as compared with a non-pregnant patient. (2) Monitoring based upon simultaneous use of the CsA-NS and CsA-S kits may be a source of analytical bias and hence confusion for the physician. (3) Determination of an experimental CsA-NS/CsA-S accumulation ratio (based upon analysis of single concentrations or processing of AUCs) is of interest only if specific assays involve not only CsA itself but also its principal metabolites. (4) Monitoring based upon single measurements of residual CsA levels only, is necessary and adequate. Furthermore, such an approach is less costly.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: Our aim was to evaluate the course and outcome of pregnancy in orthotopic liver transplant recipients. STUDY DESIGN: We report the course and outcome of 19 pregnancies in 19 orthotopic recipients since 1985, out of 775 patients who have undergone liver transplant in our center. Statistical analysis was based on the chi 2 test with a 95% confidence interval, when appropriate. RESULTS: There were four spontaneous abortions and three therapeutic abortions for impaired liver function. One current pregnancy is uncomplicated at 19 weeks' gestation. Eleven women have given birth to 11 healthy infants at 38 +/- 1.5 weeks' gestation. There were no preterm deliveries. Birth weight was normal for gestational age in 10 of the 11 cases, with a mean value of 2990 +/- 370 gm. The main complications in the 11 successful pregnancies were hypertension in three and graft dysfunction at 37 weeks' gestation in another. CONCLUSION: Pregnancy is successful in a large proportion of liver transplant recipients, but it must be planned and managed as a high-risk situation by both an obstetrician and a surgeon.
OBJECTIVE: To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH). DESIGN: A prospective randomized trial. SETTING: The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France. PARTICIPANTS: One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period. TREATMENT: Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression. MAIN OUTCOME MEASURES: Response to COH, pregnancy rate (PR), tolerance. RESULTS: In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups. CONCLUSIONS: We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.
OBJECTIVE: To evaluate safety and efficacy of intrasaccular methotrexate (MTX) for treatment of ectopic pregnancy (EP). DESIGN: Longitudinal nonrandomized trial of MTX treatment of EP. SETTING: Department of Obstetrics and Gynecology (A. Béclère Public Hospital, Clamart, France Paris-Sud University). PATIENTS: One hundred patients with an EP visualized by sonography. Patients were 31.4 +/- 4.8 years old, para 0 to 4, and gravida 0 to 7. Twelve patients had a past history of EP, and 18 had previously undergone tubal surgery. Inclusion score for proposed medical treatment used six criteria graded from 1 to 3: gestational age, initial hCG level, P level, existence of abdominal pain, size of hemoperitoneum, and diameter of hematosalpinx. Eleven patients had an EP with cardiac activity. Treatment consisted of MTX, 1 mg/kg, given locally under transvaginal sonographic control. RESULTS: Eighty-three of 100 patients were considered to be completely cured (return of hCG to < 10 mIU/mL). The success rate was 92.8% with an initial hCG level < 5,000 mIU/mL and 87% when the score was < or = 12. Seven of the 11 patients with an EP with cardiac activity were treated successfully, including 5 of 7 when the initial score was < or = 12, and all failures concerned cases with an initial score > 12. Twenty-eight of 83 patients treated successfully required more than one injection of MTX (additional doses being given intramuscularly) because of nonresolution of hCG levels. Follow-up hysterosalpingography was performed in 80 patients showing 90% tubal patency on the side of the treated EP. Of 58 patients wishing pregnancy, 34 pregnancies occurred, including 25 ongoing or delivered. We observed a low recurrence rate of EP (3 with 1 on the same side). CONCLUSION: Treatment by initial transvaginal injection of MTX under sonographic control appears to be simple and effective, with no demonstrable untoward effects. The tubal patency and subsequent fertility obtained appear satisfactory. The highest success rate is observed when hCG level is under 5,000 mIU/mL and/or a pretherapeutic score < or = 12 when EP is visualized by sonography.
OBJECTIVE: To evaluate nonsurgical management of heterotopic pregnancy. DESIGN: Retrospective case series. SETTING: Department of Obstetrics and Gynecology (Antoine Béclère Hospital, Clamart, France, Paris-Sud University). PATIENTS: Six women with heterotopic pregnancy who conceived in four cases after ovulation induction. INTERVENTION: Transvaginal ultrasound (US)-guided aspiration/injection of potassium chloride (KCl) was performed in three cornual pregnancies with alive embryo. Expectant management was realized in three other cases. The regression was followed by serial US examination. MAIN OUTCOME MEASURES: Early and late complications related to the procedure, outcome of intrauterine pregnancy (IUP). RESULTS: Five of six patients were treated successfully (3 with KCl and 2 after expectant management). Three of these five patients had a spontaneous vaginal delivery, and two abortions occurred in the remaining two patients. Salpingectomy had to be performed in one case 10 days after medical treatment. This twin pregnancy ended with an abortion at 23 weeks of amenorrhea. Four cornual heterotopic pregnancies were treated successfully. No complication occurred after the initial management. CONCLUSION: Ultrasound permits a reliable and early diagnosis of heterotopic pregnancy. In such cases nonsurgical management is an efficient alternative with a good IUP prognosis.
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This study was designed to investigate the use of oral mifepristone (RU 486) for the induction of natural expulsion of concepti in women with spontaneously interrupted pregnancy in the first trimester. It consisted of a double-blind placebo-controlled study of mifepristone (600 mg) against placebo. A total of 46 women consulting for interrupted pregnancy were diagnosed at ultrasound with no clinical sign of miscarriage. Measurements were made of the occurrence of natural expulsion, the frequency of complete expulsion, the need for subsequent surgical evacuation, analgesia and the need for transfusion. Natural expulsion occurred within 5 days in 82% of patients receiving mifepristone treatment versus 8% of placebo-treated patients (P < 0.001). All patients experienced bleeding after RU 486 and two needed emergency aspiration for haemorrhagic expulsion. The treatment failed in four patients, who underwent evacuation under local anaesthesia. In the control group, 19 patients underwent evacuation under local (n = 10) or general (n = 9) anaesthesia. It was concluded that a standard oral pilot dose of 600 mg of mifepristone induces natural expulsion in 82% of women with non-developing first trimester intrauterine pregnancies.
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The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years) whose gestational ages ranged from 28 4/7 to 40 5/7 weeks were included. The diagnosis of infection was established in all cases; i.e., four women had chorioamnionitis and five women had pyelonephritis. The following triple antibiotic therapy was infused with the aim of achieving cure: CTX, 2 g once every 24 h (constant rate over 60 min); tobramycin, 3 mg/kg of body weight once every 24 h; and ornidazole, 1 g/day. Two series of blood samples were collected, i.e., during the first day of treatment (on day 1), to establish the primary pharmacokinetic profile of CTX, and at the plateau (on day 7), to evaluate a possible accumulation of the drug. This was an open, noncompartmental study, with each patient serving as her own control. Concentrations of total and unbound CTX in serum were measured by a high-performance liquid chromatographic method. Pharmacokinetic analysis was done by a noncompartmental method. Data were compared by a Wilcoxon t test (a P value of < or = 0.05 was considered significant). Data were also compared with those obtained for healthy subjects who received similar treatments. (i) The tolerance to treatment was excellent, and in all cases patients had a complete remission without premature delivery. (ii) No accumulation of CTX was noted during the treatment, and the profiles of the drug determined at days 1 and 7 were not significantly different.(iii) The pharmacokinetic parameters measured in pregnant patients during the third trimester of pregnancy were similar to those measured in healthy subjects. (iv) Residual concentrations of total and unbound CTX measured at 24 h were greater than the MICs for allegedly susceptible organisms, both on day 1 and at steady state. (v) During the final 3 months of pregnancy, the dosage schedule of CTX (2-g infusion per day) required no particular adjustment (i.e., neither a loading dose nor any increase in the maintenance dose.)
OBJECTIVE: To study postpartum distribution and protein binding of ceftriaxone (CTX) between maternal blood and milk and to discuss risk factors and possible impact for the neonate. DATA SOURCES: Reference articles and books are identified in the text. DATA SYNTHESIS: CTX distribution and protein binding between maternal blood and milk postpartum were studied in a patient at term presenting with acute pyelonephritis caused by Escherichia coli. The antibiotic therapy prescribed pending bacteriology results consisted of CTX 2 g/d, ornidazole 1 g/d, and tobramycin 3 mg/kg/d. Pharmacokinetics of total CTX were studied after the first 2-g infusion. At plateau (i.e., two days after delivery; seventh infusion), pharmacokinetics and milk distribution of total and free CTX also were studied. No accumulation of CTX was noted in the plasma at plateau. When high dosages of CTX are used (approximately 2 g), its penetration into the milk is important (i.e., protein binding capacity is overwhelmed). No notable adverse reactions occurred in mother or child. Thus, an important diffusion into the milk (4.4 percent of the dose) appears not to be clinically important. Our knowledge of both metabolism and milk distribution of drugs with high protein binding (> or = 95 percent) and an acid characteristic should be expanded to better understand their use during both the pregnancy and postpartum periods. Finally, the child of the patient described here has normal initial growth and development at the present time. CONCLUSIONS: Caution should be taken when drugs such as CTX, which have both high protein binding (> or = 95 percent) and an acid characteristic are administered to breastfeeding women. Drugs of this type should be systematically investigated to better understand their use during pregnancy and postpartum.
Free radicals have been implicated in the development of injury to the immature retina. Asphyxia increases free radicals as well as prostaglandins (PG) in neural tissues. We assessed whether in the retina the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, which in turn disrupts retinal function. Newborn pigs were treated with either saline, ibuprofen (194 mumol/kg i.v.), or allopurinol (1 mmol/kg i.v.), and retinal malondialdehyde (MDA), hydroperoxides, PGE2 and PGF2 alpha levels, and the amplitudes and implicit times of the a- and b-waves of the full-field electroretinogram were measured before and 1 h after a 5-min period of asphyxia. In saline-treated animals, asphyxia caused a marked increase (p < 0.01) in MDA, hydroperoxides, PGE2, and PGF2 alpha concentrations in the retina. This was associated with a significant decrease (p < 0.01) in the b-wave amplitude measured under scotopic and photopic conditions and an increase in the b-wave implicit times. Ibuprofen and another cyclooxygenase inhibitor, indomethacin (28 mumol/kg i.v.), decreased PGE2 and PGF2 alpha levels and prevented the increase in MDA and hydroperoxides after asphyxia. Allopurinol maintained low concentrations of MDA and hydroperoxides after asphyxia. Both ibuprofen and allopurinol prevented the postasphyxial changes in the b-wave amplitude and diminished the delay in implicit time observed after asphyxia in saline-treated pigs. Our findings suggest that in the retina after asphyxia free radicals appear to originate primarily from the cyclooxygenase pathway and contribute to the deterioration in retinal electrophysiologic function of the newborn animal. Cyclooxygenase inhibitors, like free radical scavengers, may protect retinal function from deteriorating after oxidative stresses.
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UNLABELLED: We investigated the use of oral mifepristone (RU486) for the induction of natural expulsion in women with spontaneously interrupted pregnancy in the first trimester in a double blind placebo controlled study against placebo. 46 women consulting for interrupted pregnancy diagnosed at ultrasound with no clinical sign of miscarriage were included in the trial. Main outcome measures were occurrence of natural expulsion, frequency of complete expulsion need for subsequent surgical evacuation, analgesia and need for transfusion. Natural expulsion occurred within 5 days in 82% patients receiving treatment versus 8% placebo treated patients (p < 0.001). All patients experienced bleeding after RU486 and 2 needed emergency aspiration for haemorrhagic expulsion. The treatment failed in 4 patients who underwent evacuation under local anesthesia. In the control group 19 patients underwent evacuation under local (n = 9) or general (n = 11) anesthesia. CONCLUSION: A standard oral pilot dose of 600 mg of Mifepristone induces natural expulsion in 82% women with non developing first trimester intra-uterine pregnancies.
Non surgical management of ectopic pregnancy has recently become an alternative to surgery. We have investigated a pretherapeutic score to define the indication for non-surgical and surgical treatment in 123 patients with ectopic pregnancy. The score was performed before the patients' inclusion in a non-surgical management scheme. The score used six criteria which were evaluated on a scale from 1 to 3: gestational age, human chorionic gonadotrophin (hCG) level, progesterone level, abdominal pain, haemoperitoneum volume and haematosalpinx diameter (estimated by laparoscopy or transvaginal ultrasound). Three scores, 10, 11 and 12 were studied in order to define a threshold beyond which surgical treatment should be performed. For each one, sensitivity, specificity and positive and negative predictive values were analysed. The success rate of non-surgical treatment was 82.1% (101/123). For patients undergoing medical treatment with a score < or = 12, the success rate was significantly higher compared with a success rate of 56% when the score was > 12. We conclude that a score < or = 12 permits non-surgical management with a success rate of 87%. A score > 12 indicates that laparoscopic surgery may be more suitable. The choice between different non-surgical approaches, did not influence the success rate. When ultrasound reveals embryo heart activity, medical treatment is always possible if the score is < or = 12.