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Biomedical subjects

O Irion

Publications and source records attributed to O Irion.

At least 19 recordsLinked to original sources

Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort Study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV Study.

BACKGROUND: Therapies containing two reverse transcriptase inhibitors (RTI) with or without protease inhibitors are used with increasing frequency in pregnant HIV-infected women. OBJECTIVE: To assess the safety of antiretroviral therapy in pregnant women and their newborns. METHODS: All clinical events and laboratory abnormalities in pregnant women on RTI with or without protease inhibitors and in their newborns were collected through an observational study. RESULTS: A total of 37 HIV-infected pregnant women have given birth to 30 children (by 30 April 1998). All received RTI, which were combined with protease inhibitors in 16 cases. Twelve women became pregnant while on treatment. Drugs used were as follows: zidovudine (n = 33), lamivudine (n = 33), stavudine (n = 4), indinavir (n = 9), ritonavir (n = 4), nelfinavir (n = 2) and saquinavir (n = 2). Adverse events during pregnancy were anaemia (n = 15), elevation of transaminases (n = 4), nausea/vomiting (n = 4), glucose intolerance (n = 2), nephrolithiasis (n = 2), diarrhoea (n = 2), hypertension (n = 1), insulin-requiring diabetes (n = 1). Adverse events in neonates were prematurity (n = 10), anaemia (n = 8), cutaneous angioma (n = 2), cryptorchidism (n = 2), transient hepatitis (n = 1). Non-life-threatening intracerebral haemorrhage occurred in a premature baby (33 weeks gestation) exposed during fetal life to zidovudine-lamivudine-indinavir, and in a term baby exposed to stavudine-lamivudine-indinavir. Extrahepatic biliary atresia occurred in one newborn exposed to zidovudine-lamivudine-indinavir. Maternal viral load was below 400 copies/ml in 18 out of 30 patients who delivered. One case of mother-to-child HIV transmission was identified. CONCLUSIONS: In HIV-infected pregnant women treated with two RTI with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies. In newborns, frequent prematurity, one case of biliary malformation and one intracerebral haemorrhage in a term baby are of concern. These observations do not preclude combination therapies during pregnancy but emphasize the necessity to maintain updated registers on their safety.

Anti-HIV Agents

Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group.

OBJECTIVE: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. DESIGN: Prospective study. SETTING: Obstetric and paediatric clinics in Switzerland. PARTICIPANTS: Children of mothers with HIV infection identified before or at delivery. INTERVENTIONS: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. MAIN OUTCOME MEASURE: HIV infection status of children. RESULTS: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. CONCLUSIONS: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.

Abortion, Induced

A randomized trial comparing vaginal and cervical prostaglandin gel for cervical ripening and labor induction.

OBJECTIVE: To compare the effectiveness of intravaginal and intracervical prostaglandin E2 (PGE2) gel for cervical ripening, defined as an increase of 3 or greater in the Bishop score, and for induction of labor. METHODS: Women with Bishop score 4 or less were assigned randomly to receive either 2 mg PGE2 intravaginally (n = 125) or 0.5 mg intracervically (n = 122). If the Bishop score was 4 or less, another dose of PGE2 was given after 6 hours, and up to two additional doses were given 6 hours apart on the second day. An oxytocin infusion was begun when the Bishop score was 5 or greater in absence of spontaneous labor, or if labor had not begun on the third day. RESULTS: Baseline characteristics of the two groups were similar. Survival analysis showed that time from PGE2 application, to obtain an increase of 3 or greater in the Bishop score, to vaginal delivery was significantly shorter with intravaginal PGE2 (logrank test: P = .003 and < .001 after stratification for parity, respectively). Thirty-one percent of women in the intravaginal gel group required oxytocin for labor induction compared with 63% in the intracervical group (P < .001). There were no significant differences in relation to cesarean delivery rate, Apgar scores at 5 minutes, and arterial umbilical cord pH, although the power of our study was limited to detect differences in proportions of adverse outcomes. CONCLUSION: Vaginal PGE2 gel is more effective than intracervical gel for cervical ripening and labor induction.

Administration, Intravaginal

Prediction of preterm delivery by fetal fibronectin: a meta-analysis.

OBJECTIVE: To assess the cervicovaginal fetal fibronectin test to predict preterm delivery. DATA SOURCES: We searched MEDLINE, Current Contents, Index Medicus, and proceedings of meetings for studies published between 1991 and June 1997. METHODS OF STUDY SELECTION: Inclusion criteria were prospective cohort study; test performed between 20 and 36 weeks' gestation; fetal fibronectin measured by a previously described assay, with a cutoff level set at 50 ng/mL; test results not disclosed to women or physicians; and fewer than 20% of study participants excluded from the analysis. TABULATION, INTEGRATION, AND RESULTS: Twenty-nine relevant studies were stratified according to the prevalence of preterm delivery, the number of tests performed, and delivery before 34, 35, or 37 weeks. Sensitivities, specificities, and likelihood ratios were calculated in each study. The summary estimates of the likelihood ratio for tests yielding positive results or tests yielding negative results along with their 95% confidence intervals (CIs) were computed in each stratum according to a random-effects model. All summary likelihood ratios for a test yielding positive results indicated a significant association with preterm delivery. The strongest association was found between a single test with positive results and delivery before 37 weeks in a low-risk population (likelihood ratio 7.5; 95% CI 4.6, 12.3). This association also was found in high-risk women (likelihood ratio 3.5; 95% CI 2.6, 4.6). In high-risk women, a test yielding negative results was associated with a reduction in risk of preterm delivery (likelihood ratio 0.4; 95% CI 0.3, 0.5). CONCLUSION: Fetal fibronectin in cervicovaginal secretions is associated with preterm delivery in both high-risk and low-risk women.

Cervix Uteri

Prediction of pre-eclampsia, low birthweight for gestation and prematurity by uterine artery blood flow velocity waveforms analysis in low risk nulliparous women.

OBJECTIVE: To assess the performance of four previously reported Doppler abnormalities of uterine artery velocity waveforms (presence of a protodiastolic notch, peak systolic over protodiastolic velocities (A:C ratio) > 2.5, peak systolic over end diastolic velocities (A:B ratio) > 90th centile, resistance index (RI) ([A-B]/A) > or = 0.58) in predicting pre-eclampsia, low birthweight and prematurity. DESIGN: Prospective cohort study. SETTING: Tertiary care university hospital in Quebec City. POPULATION: 1311 nulliparous women. METHODS: Evaluation of pulsed Doppler abnormalities of uterine artery velocity waveforms was carried out in 1000 and 1194 of women at 18.3 (SD 0.9) or 26.7 (SD 0.9) weeks of pregnancy. MAIN OUTCOME MEASURES: Pre-eclampsia, birthweight below the 10th centile for gestational age and spontaneous preterm birth (< 37 completed gestation weeks). RESULTS: Pre-eclampsia, low birthweight for gestation and prematurity occurred in 4%, 11% and 7% of the pregnancies, respectively. At 26 weeks all the abnormalities of the studied Doppler indices were significantly associated with pre-eclampsia and low birthweight for gestation as reflected by the 95% confidence intervals of the positive likelihood ratios which did not include the value 1. However, sensitivities (26% to 34%) and positive predictive values (7% to 28%) were low. No Doppler indices performed significantly better than the others. The abnormalities of the Doppler indices were not associated with spontaneous prematurity. The performance of the Doppler measurements performed at 18 weeks was poor. CONCLUSIONS: Uterine artery Doppler velocimetry waveform analysis does not qualify as a reliable screening test for pre-eclampsia or low birthweight for gestation in low risk pregnancies but may be useful in selected high risk populations.

Blood Flow Velocity

Planned vaginal delivery versus elective caesarean section: a study of 705 singleton term breech presentations.

OBJECTIVE: To compare neonatal mortality and neonatal and maternal morbidity in planned vaginal delivery versus elective caesarean section for breech presentation at term. To identify factors associated with the risk of caesarean section during labour. DESIGN: Cohort study. SETTING: University Hospital of Geneva. POPULATION: Seven hundred and five consecutive singleton term breech presentations: 385 planned vaginal deliveries and 320 elective caesarean sections. METHODS: Relative risk and risk difference with their 95% confidence intervals (95% CI) were calculated for neonatal and maternal morbidity. Prognostic factors for the risk of intrapartum caesarean section were analysed by multiple logistic regression. MAIN OUTCOME MEASURES: 1. Neonatal mortality 2. Neonatal morbidity (eg. fracture, haematoma with hyperbilirubinemia, paresis, paralysis, visceral trauma, respiratory distress, umbilical cord arterial pH < 7.0 with 5 minute Apgar score < 7), corrected neonatal morbidity was defined as morbidity after exclusion of major malformations. 3. Maternal morbidity (eg. endometritis, urinary infection, pulmonary infection, surgical complications, hysterectomy, anaemia, pulmonary embolism, cardio-respiratory arrest). RESULTS: There were significantly fewer maternal complications in the planned vaginal delivery group than in the elective caesarean section group (risk difference 10.5%, 95% CI 3.9 to 17.0). Five neonates with major malformations died. There was no difference in corrected neonatal morbidity between the planned vaginal delivery and the elective caesarean section groups (risk difference 1.9%, 95% CI -1.0 to 4.9). Nulliparity, maternal age > 30 years and a higher body mass index were independently associated with the risk (30%) of intrapartum caesarean section, but it was not possible to construct a predictive model useful for clinical practice. CONCLUSIONS: There is no firm evidence to recommend systematic elective caesarean section for breech presentation at term. Large unbiased studies are needed to determine whether a potential benefit for the newborns outweighs the increased risk for the mothers associated with elective caesarean section.

Adult

Characterisation of the cytotoxic alloresponse of cord blood.

As compared to bone marrow, transplantation with cord blood (CB) is associated with a lower risk of GVHD. Although some cases of GVHD III have been reported, usually the grade of GVHD remains low, even when donor and recipient are not fully HLA matched. To investigate whether this is due to an intrinsic property of CB T cells, we studied the conditions under which CB CD8+ cells would be able to generate an alloresponse. In addition, we measured the cytokines secreted by the alloreactive cytotoxic T lymphocyte (CTL) clones generated. We show that: (1) the capacity of CB cells to generate alloreactive CTLs in vitro is diminished as compared to adult cells (AB); (2) in the presence of exogenous IL-2, CB cells do generate a normal alloreactive response; (3) although CB-derived CD8+ allospecific clones showed the same T1/T0 cytokine profile as the clones from AB, they secreted a lower amount of IFN-gamma; and (4) in addition, cloned CD4+ CB cells are mainly T2/T0 type, whereas AB CD4+ T cells were mainly of T1/T0 type. These data suggest that the reduced GVHD observed after transplantation with CB might be the result of the naiveness of CB T cells. After allostimulation, CB cytotoxic T cells differ from AB T cells by a higher activation threshold, a lower secretion of IFN-gamma by both CD4+ and CD8+ CB cells and their bias towards a T2 type CD4 response.

Adult

Peak systolic over protodiastolic ratio as an objective substitute for the uterine artery notch.

OBJECTIVE: To measure the inter-rater agreement for the identification of a uterine artery notch, as well as the association between an observed notch and the peak systolic over protodiastolic (A/C) ratio. DESIGN: Cohort study. SETTING: Tertiary care university hospital. POPULATION AND METHODS: Six hundred and sixty-five nulliparous women in whom 1022 examinations of uterine artery velocity waveforms were performed by pulsed Doppler at 18 and at 26 weeks of gestation. Agreement between two independent raters was analysed using Cohen's kappa statistics. A/C ratios of flow velocity waveforms with or without a notch were compared. The agreement between A/C values and the presence of a notch was estimated by measuring the surface under the receiver operating characteristic (ROC) curve. RESULTS: Inter-rater agreement for the identification of a notch was 0.74 (95% CI 0.64-0.83) at 18 weeks and 0.72 (95% CI 0.64-0.80) at 26 weeks. A/C ratios were higher when a notch was present (P < 0.0001). The area under the ROC curve was 0.86 (95% CI 0.81-0.91) for the placental uterine artery and 0.93 (95% CI 0.90-0.96) for the nonplacental artery. An A/C value > or = 2.5 in any uterine artery had a sensitivity of 88% and a specificity of 86% to detect a notch. CONCLUSION: Although there is no definitive definition of the notch, its detection is reproducible within a center. However, published prevalences between centers in unselected populations vary. The measure of the A/C ratio can serve as an objective substitute.

Adult

Is intrapartum vibratory acoustic stimulation a valid alternative to fetal scalp pH determination?

OBJECTIVES: To determine the association between fetal heart rate accelerations, whether spontaneous or induced by vibratory acoustic stimulation, and subsequent scalp pH values in presence of a suspicious intrapartum fetal heart rate tracing, and thereby assess the ability of accelerations to predict a concurrent normal fetal scalp blood pH. DESIGN: Prospective observational study of 253 labours involving 421 pH samples. SETTING: Tertiary care university hospital of Genoeva. INTERVENTION: Vibratory acoustic stimulation through the maternal abdominal wall for five seconds prior to fetal blood sampling. MAIN OUTCOME MEASURES: Spontaneous fetal heart rate reactivity (accelerations) in the 10 min preceding vibratory acoustic stimulation, vibratory acoustic-induced reactivity prior to fetal blood sampling, and scalp pH value. RESULTS: The positive predictive value of a reactive fetal heart rate response after vibratory acoustic stimulation was 78% (95% CI 73-84%) and 97% (95% CI 94-99%) for scalp pH values of > 7.25 and > or = 7.20, respectively. Similar observations occurred with spontaneous reactivity. Of concern, 7 out of 31 (23%) occasions where the scalp blood pH was less than 7.20 appeared to be associated with a normal fetal heart rate response to vibratory acoustic stimulation. CONCLUSION: Fetal heart rate acceleration induced by vibratory acoustic stimulation was significantly associated with a normal scalp blood pH higher than 7.25. However, vibratory acoustic stimulation offers no advantage over observation of spontaneous fetal heart rate tracings and cannot safely replace fetal blood sampling during labour.

Acoustic Stimulation

Nonclosure of the visceral and parietal peritoneum at caesarean section: a randomised controlled trial.

OBJECTIVE: To assess the short term morbidity of nonclosure of the peritoneum at caesarean section. DESIGN: Women undergoing a lower segment caesarean section were randomly allocated to either closure or nonclosure of the visceral and parietal peritoneum. SETTING: Tertiary Care University Hospital of Geneva. MAIN OUTCOME MEASURES: Length of post-operative hospital stay. Other outcomes include maternal pain as assessed by both a visual analogue scale and the amount of post-operative analgesics administered, post-operative ileus, and febrile morbidity. Operative time was recorded. RESULTS: We allocated 137 women to the nonclosure group and 143 to the closure group. Population characteristics were similar between groups. The mean length of hospital stay was 6.5 (SD 1.9) days for the nonclosure group and 6.8 (SD 2.2) days for the closure group (P = 0.21). No differences were found in the level of post-operative pain, the number of analgesic doses given, nor in the proportion with febrile morbidity. Post-operative ileus resolved later in the closure group (P = 0.006). The mean operative time was shorter by 6 min (P = 0.006) in the nonclosure group. CONCLUSIONS: Short term post-operative morbidity and maternal pain are not increased by a shorter and more simple surgical procedure in which the peritoneum is left unsutured.

Adult

[Value and limits of transabdominal cytogenetic amniocenteses during the first trimester of pregnancy].

OBJECTIVE: To assess the feasibility of amniotic fluid collection during the first trimester of pregnancy for caryotyping. METHODS: Echo-guided amniocenteses were performed prior to therapeutic abortions. Withdrawal of at least 5 ml of amniotic fluid for caryotyping was attempted. RESULTS: 55 amniocenteses were attempted in pregnancies between 8 to 12 weeks of gestation. Mean fluid sample was 8 +/- 4.7 ml, range 1-17. Less than 3 ml of amniotic fluid was obtained for cephalo-caudal lengths < 23 mm. At least 5 ml of amniotic fluid were collected in 68% of the pregnancies with a cephalo-caudal length of 23 to 35 mm and in 100% of those with a cephalo-caudal length > 35 mm. There was a correlation between cephalo-caudal length and volume of amniotic fluid sampled (r = 0.72, 95% CI: 0.56-0.83; p < 0.0001). Fourteen of the 45 samples cultured led to satisfactory carytotypes. No caryotypes could be obtained for embryos with a cephalo-caudal length < 27 mm, while the rate of success was 100% in those > 45 mm. Cephalo-caudal lengths were different in cases with successful and unsuccessful caryotypes (p < 0.001). CONCLUSIONS: This preliminary study indicates that it is difficult to obtain adequate amniotic fluid sample when the cephalo-caudal length is < or = 35 mm. A caryotype could be obtained in only 31% of these cases. Success rate was proportional to gestational age. Based on these findings and a review of the literature, it appears difficult to obtain a fetal caryotype by amniocentesis or choriocentesis before 10 weeks gestation.

Abortion, Therapeutic

Successful term pregnancy after Mustard operation for transposition of the great arteries.

Transposition of the great arteries is a complex cardiac malformation with poor prognosis without surgical correction. Since the introduction of surgical procedures such as the intra-auricular reorientation of the venous return (Mustard procedure), an increasing number of patients may reach adulthood and experience pregnancy. Because long-term complications after the Mustard operation include systemic heart failure, arrhythmias, venous return stenosis and pulmonary edema, hemodynamic changes during pregnancy and delivery may potentially engender life-threatening complications in these patients. We report the case of a 24-year-old primigravida who underwent a Mustard procedure at the age of 2 years for transposition of the great vessels, and who carried out a full-term pregnancy. The pregnancy was uneventful until the 34th week, when the woman developed signs of moderate right ventricular failure and frequent episodes of accelerated junctional rhythm. Digitalisation improved symptoms and elicited return to normal sinus rhythm. The patient delivered at term by elective cesarean section, under close hemodynamic monitoring.

Adult

[Pregnancies in HIV infected women in Switzerland].

In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively followed up between January 1, 1990, and October 30, 1993. 69.8% were infected by intravenous drug abuse and 91.5% were asymptomatic (CDC classes II and III) in early pregnancy. 48 (21.0%) were first discovered to be HIV-infected during the index pregnancy: 46 of these had risk factors. The present epidemiologic development does not seem to warrant a general HIV-screening in pregnancy at this time. 71 pregnancies (31%) were terminated; 158 children were born, 17 (23.3%) of the 73 definitely classified are HIV-infected. An asymptomatic HIV infection with a sufficiently high (> 200/microliters) CD4 cell count has no proven influence on the pregnancy. Otherwise, however, maternal infectious diseases can lead to prematurity. For mothers with i.v. drug abuse, there is a significantly higher incidence of prematurity and fetal growth retardation. The maternal HIV infection can be transmitted to the child either during pregnancy or at delivery. The incidence of vertical transmission in our study was 23.3%; the most predictive parameter for a prenatal HIV transmission is a low anti-p24 antibody titre. The risk of intrapartum transmission seems to be somewhat, but not significantly, reduced for primary Caesarean sections. Recently, prophylaxis with Zidovudin during pregnancy, beginning after the 14th GW, was found to reduce vertical HIV-transmission by 66%. Since the virus can also be transmitted through mothers' milk, HIV-positive mothers should not nurse their babies. Maternal infections are significantly more frequent in HIV-positive women, and are a risk factor for prematurity.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced

[Prediction of prematurity by oncofetal fibronectin. Prospective cohort study].

OBJECTIVE: To evaluate the association between cervical oncofoetal fibronectin and prematurity as well as the interval between sampling and delivery in symptomatic women. METHODS: Cervical fibronectin was measured with an immunoassay in a cohort of 64 women at the University Hospital of Geneva. Subjects with positive and negative fibronectin were then compared using the relative risk and the incidence rate ratio of premature delivery as well as the survival tables. Performance of the test to predict premature delivery or delivery within one week of the test were expressed in terms of sensitivity, specificity, predictive values and likelihood ratios with their 95% confidence intervals. RESULTS: Thirty-four percent of women delivered prematurely. The presence of fibronectin was significantly associated with premature delivery and with a shorter interval to delivery. The likelihood ratio for a positive test was 2.6(95% CI: 1.45-4.66). A negative test had a 100% predictive value to exclude delivery within one week of the test. CONCLUSION: Oncofoetal fibronectin appears to be the best marker currently available to predict premature delivery. A randomized trial is needed to confirm its clinical usefulness.

Adult

Alterations of calcium and phosphate metabolism in primary hyperparathyroidism during pregnancy.

Primary hyperparathyroidism (PHP) is rare during pregnancy and has been claimed to be associated with significant increase of neonatal morbidity and mortality. Whether the well recognized changes in calcium (Ca) and phosphate (Pi) homeostasis occurring in pregnancy might influence the biochemical expression of PHP is unclear. We evaluated biochemical parameters of calcium and phosphate metabolism in two cases of PHP in pregnancy diagnosed in the third trimester (patient 1) and in the second trimester (patient 2). Both patients displayed increase in protein-adjusted plasma Ca, bone resorption evaluated by the fasting urinary Ca-to-creatinine ratio, renal tubular reabsorption of Ca, urinary cAMP excretion and decrease in renal tubular reabsorption of Pi. These alterations were identical to those found in 12 non-pregnant women with PHP. The biochemical expression of PHP did not change after delivery in patient 1. This patient underwent the excision of a 1 g parathyroid adenoma on the 13th day after delivery, which led to normalization of all biochemical parameters. The lowest plasma Ca of the newborn of patient 1 was 2.02 mM 72 hours after birth. Thus, the results indicate that these two pregnant women with PHP displayed biochemical alterations of calcium and phosphate metabolism similar to those observed in non-pregnant women with primary hyperparathyroidism.

Adult

Pregnancy in a patient with treated Wilson's disease: a case report.

Pregnancy should have a successful outcome in a patient with treated Wilson's disease if complications are excluded before conception. Chelating treatment must be maintained, although there is some concern about its teratogenicity. We describe the course of pregnancy in a patient followed up in our department.

Adult