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Variability of thrombotic disease among individuals homozygous for factor V Leiden has been described. It has been shown that some thrombotic patients carry an additional genetic risk factor such as protein C, protein S, antithrombin deficiency or the G20210A mutation on the prothrombin gene. The occurrence of a deep vein thrombosis during enoxaparin prophylactic treatment in a pregnant woman homozygous for factor V Leiden, without other known prothrombotic genetic factors, led us to investigate her thrombomodulin gene. We found that the patient was heterozygous for the previously described G 127 → A mutation, which results in an Ala 25 → Thr substitution. Furthermore, for this patient, the allelic combination at the 1418 polymorphic site was C/T, which predicts an Ala 455 → Val replacement. Although larger studies are required, this case report suggests that thrombomodulin gene mutations could be an additional genetic risk factor for thrombosis in carriers of the factor V Leiden mutation.

In order to reduce practice variations and offer cancer patients the best treatments according to reference guidelines, therapeutic decisions have to be taken, in France, by "multidisciplinary staff meetings'' (MSMs) as patient-specific care plans which are then implemented by cancer specialists. OncoDoc2 is a CDSS implementing CancerEst guidelines, a "local reference guideline'', on breast cancer management. The system has been assessed in a pragmatic before/after study. The intervention consisted in the routine use of OncoDoc2 during MSMs of Tenon hospital. The MSM decision compliance rate with the reference guideline was significantly higher in the after period, increasing from 79% to 93%. MSM decision analysis showed that missing steps in treatment plans were the main cause of noncompliance during the before period. This cause was drastically reduced in the after period.

Although the majority (about 90%) of cerebral palsies are related to antenatal or postnatal causes, search for acute fetal distress during labor remains one of the primary objectives of obstetrical surveillance. Acute fetal distress leads to hypoxemia which induced hypoxia and then asphyxia of most of the organs, including the noble organs such as the brain. Most of the parameters used for fetal monitoring have good sensitivity but low specificity. Furthermore, there is a weak correlation between the different parameters measured and the neonatal status which remains difficult to predict with certainty. The general "philosophy" behind fetal monitoring consists in detecting warning signs and, when warning signs are observed, to measure one or more other parameters to assess the state of hypoxia and its consequences. Fetal heart rate is a warning sign used by all teams. Irrespective of the method used to analyze fetal heart rate when anomalies are detected, metabolic acidosis induced by anoxia is an indispensable element for assessing severity. The development of fetal hypoxia is related to two essential phenomena: anaerobic glycolysis with lactate production and glycogenolysis to meet energy needs. Metabolic acidosis can be measured directly by scalp pH or lactate measurements, or indirectly by measuring its effect on heart conduction as expressed in the ST segment. The underlying physiological mechanisms and the methods used to evaluate acid base balance are described here.

The association of breast cancer with pregnancy is rare. It is defined as the occurrence of breast cancer during pregnancy or during the year following delivery. Patient management must be ensured by a multidisciplinary team including gynecologists, obstetricians and clinical oncologists.

Many reports suggested that the high rate of miscarriage in women with polycystic ovaries may be due to increased urine and/or plasma LH concentration. In fact, with the exception of pulsatile GnRH, any treatment likely to increase the plasma LH level results in unchanged or rather low miscarriage rates. Conversely, a reduction in this rate by GnRH agonists is not conclusive. Excess weight may also increase the risk of miscarriage. In women with incipient ovarian failure, the miscarriage rate is mainly linked to age. No stimulation has been found to be effective in these patients. There is a need for more extensive evaluation in GnRH analog microdoses, recombinant FSH and GnRH antagonists. Oocyte donations from younger women are difficult to obtain because of the lack of donors in France.

Defining elements leading to atypical hyperplasia's diagnosis, interpreting histological diagnosis of atypical hyperplasia and determining therapeutic strategy.

We assessed the accuracy with which stereotactic core biopsy of breast microcalcifications helps to justify follow-up or indicate required surgical planning. Eighty-nine patients underwent stereotactic breast biopsy performed with large core needles. Histopathologic findings of microbiopsies were correlated with radiological findings, with follow up and with surgical findings. Agreement between radiological and histopathologic findings on biopsies was obtained in 86% for benign results. Even in the case of benign radiological findings, the histological results of microbiopsies required a surgical biopsy justified in 10% of cases. Radiologically suspicious or malignant microcalcifications were correlated with 35% benign and 65% malignant histologies on biopsies. The positive predictive value, negative predictive value and accuracy were respectively 93%, 86% and 95%. Invasive lesions were found on microbiopsies in 39% of excised malignant lesions. Multifocal lesions were proved on microbiopsies in 50% of all excised carcinomas. Microbiopsies help to disclose malignant lesions undetected on radiological analysis, and may obviate diagnostic surgical biopsy in many cases.

Aspirin, an inhibitor of cyclo-oxygenase, is prescribed in a number of conditions related to abnormal production of prostaglandins including gravidic hypertension. Results of the most recent trials demonstrate that in patients with a past history of pre-eclampsia or intra-uterine growth retardation, a pathological Doppler examination of the uterus, a pathological angiotensin test or an antiphospholipid syndrome, prescription of aspirin at the dose of 100 mg/day can prevent recurrence or development of pre-eclampsia or intra-uterine growth retardation. Treatment should begin as soon as possible during pregnancy, certainly before development of clinical manifestations. After history taking and identification of possible contraindications, bleeding time (Ivy method) is recorded before and after prescription and should be lower than 8 minutes. In case bleeding time exceeds 10 minutes 10 to 15 days after initiating aspirin, doses may be reduced to 50 mg per day or even 50 mg every two or three days to reach the target level. Treatment should generally be continued up to 36 weeks gestation.

UTERINE DISORDERS: Because they can prevent implantation, anomalies within the uterine cavity play an important role in fertility. The uterine disorders most often observed during hysteroscopy and implicated in infertility are adhesions, septa, polyps, submucous myomas, adenomyosis, endometritis, anomalies of the cervical canal, and lesions of the uterotubal junction.Hysterosalpingography can be used to evaluate tubal permeability but provides inadequate information about the uterine cavity (numerous false-positives and false-negatives). Pelvic ultrasound is especially helpful for diagnosing interstitial anomalies in the uterus.Diagnostic hysteroscopy also has a place in infertility investigations, for it allows direct visualization of the uterine cavity, the endometrial mucus (endometritis, adenomyosis), and the cervical canal. The examination is practiced on a out-patient basis, without anesthesia, using appropriate small-caliber instruments and irrigation with physiological saline. Surgical hysteroscopy is used to treat these anomalies. Patients receive general anesthesia. A high-frequency, low-voltage electric current is used, and glycine for irrigation. This procedure allows resection of submucous myomas and polyps and of septa and adhesions. Some groups use laser beams and irrigation by physiological saline for these treatments. Coagulation of a superficial focal spot of adenomyosis is not useful in infertility therapy.As assessed by the percentage of patients with each indication who subsequently became pregnant, the results of surgical hysteroscopy have been satisfactory: 62 per cent (%) of cases after myomectomy, 66% after section of uterine septa, and 61% after treatment of complicated adhesions. A new exploration of the uterine cavity will be necessary sometime after the surgery to verify the absence of any iatrogenic disorders (adhesions, myomatous fragments).

Breast cancer during pregnancy is a rare eventuality. The mean age of women is 34 years. The same histological types (essentially ductal) are found, but there are more inflammatory forms and/or node involvement and general metastasis. The hormonal receptors are usually negative. The clinical diagnosis is often difficult and delayed. The mammography is perturbed because of breast congestion, giving reason for histological verification. The treatment must consider the fetus as much as possible. The traditional mastectomy associated to axillary nodes dissection is replaced most of the time by a large tumorectomy with axillary node dissection with the condition not to delay the complementary radiotherapy fore more than three months and to take in consideration the toxicity in relation to the gestational age, the site of impact and the doses given. Also, chemotherapy, if indicated, must begin in the month following the diagnosis. The pronostic is not as good in general as that in the non pregnant woman, because of the delayed diagnosis, the ganglionic metastasis, and the aggravation of the forms accelerated by pregnancy. The prevention consists of a clinical examination of the breast early in pregnancy (particularly after 30 years) and by histologic verification in cases where there is the slightest doubt.

The increase of mammographies has lead to the discovery of more frequent mammary microcalcifications. Presently, about 30% of breast tumors are discovered from infraclinics lesions. Instead of the different classifications, the microcalcifications are the omnious sign with bad specificity. It is in the aim to improve the diagnostic etiology and the choice of therapy, that the directed microbiopsies on microcalcifications had been realized. After an orthogonal location and under local anesthesia, we performed at least six biopsies with a 2.1 mm (14 gauge) needle. This allowed recovery of malignant lesions during the control of microcalcifications and permitted considerable early operative treatment. In fact, a diagnostic and therapeutic advancement of 12 months as compared to a clinical diagnosis, permitting a 30% reduction of metastasis.

During a retrospective study on 152 singles pregnancies obtained by in vitro fecondation at Tenon hospital, and followed in this department between January 1990 and December 1994, we have studied the influence of the IVF (tubal origin, masculine or idiopathic) and the type of stimulation (human menopausal gonadotrophin: hMG or follicle stimulating hormone: FSH) on the weight of the newborn and the pathologies that occurred during the pregnancy. No difference in the antecedents has been found in the different group of patients. This study shows a significative difference (p0.001) of the newborn's weight when the indication of IVF is tubal origin or masculine. Also, in all IVF indications, the weight is significantly (p0.01) higher after a follicular stimulation by FSH versus hMG. For the pregnancy pathologies, no significative difference has been noted, although arterial hypertension, fetal growth retardation and gestational diabetes appear to be more frequent in the group of women who had stimulation by hMG.

The follow-up bone scans (BS) of 158 women with breast cancer and without known bone metastases were reviewed and compared with serum CA 15-3 concentration. Ninety-three BS were systematic (normal serum CA 15-3) and 3 corresponded to proven bone metastases. Sixty-five BS were motivated:-by isolated bone pain (20 BS. 1 corresponding to metastases),-by bone pain and signs of progression of the disease (11 BS. 7 corresponding to metastases: elevated serum CA 15-3 except in one case), by known visceral metastases (20 BS. 6 corresponding to metastases with elevated serum CA 15-3), by an isolated increase of serum CA 15-3 (7 BS. 4 corresponding to metastasis) by local recurrence (7 BS. 1 corresponding to metastasis). These results show that bone metastases were diagnosed in 6 patients whose serum CA 15-3 concentration was normal. We conclude that the existence of normal tumor markers is not sufficient to exclude the possibility of bone metastases.

Hypertension is observed in 10 to 15% of pregnancies, but only 10% of affected women will suffer preeclampsia. The pathophysiology of preeclampsia is based on an early anomaly of placental implantation, leading to a cascade of events (secretion of vasopressive prostaglandins, anomalies of hemostatis) which can cause disseminated intravascular coagulation. The diagnosis of preeclampsia is based on hypertension and significant proteinuria (above 0.5 g/24 h), and paraclinical maternal and fetal examinations to follow the evolution and detect the appearance of maternal complications (retroplacental haematoma, Hellp syndrome and eclampsia) and (or) fetal complications (delayed growth, in utero fetal death, perinatal death). The aim of hypertensive treatment is to normalise blood pressure and to avoid maternal complications. Preventive treatment with aspirin reduces the frequency of recurrent preeclampsia and delayed growth of the fetus.

PATIENT-RELATED FACTORS: Multiparous patients with a past history of severe pre-eclampsia are a high risk population which should be identified early in pregnancy. Selection on this criterion alone is however insufficient for large scale screening and prevention because most of the susceptible women are nulliparous. Search for a particular familial or personal history of vascular disorders can be helpful. The usefulness of blood pressure measurements during the second trimester has not been proven.There is a significant association between pre-eclampsia and a large number of biological markers. No one assay can however fulfill the requirements for effective early screening because sensitivity is too low or the rate of false positives is too high, or because the examination is too invasive or costly.Doppler exploration of the uterine arteries at 20 to 24 weeks gestation offers satisfactory sensitivity and specificity but the positive predictive value is low. Persistence of a bilateral notch beyond 24 weeks considerably limits the number of false positives. More than half of the patients with this anomaly will develop hypertension during pregnancy. While no one marker fulfills all the prerequisites for effective screening, a combination of several tests may be useful. hCG assay during the second trimester in association with Doppler exploration of the uterine arteries appears to be a promising combination.Starting with these markers or risk factors, the goal is to develop a prevention scheme using low-dose aspirin, the only evidence-based preventive treatment to date. Further trials are required to test simultaneously the predictive value and impact (versus placebo) of proposed strategies.

Severe preeclampsia is a major contributor to maternal and perinatal morbidity and mortality. This review was performed to assess the fetal and maternal benefits of allowing women presenting with severe preeclampsia between 24 and 32-34 weeks of amenorrhea to continue their pregnancy following antihypertensive treatment. After ultrasound scanning to assess growth and biophysical state of the fetus, patients without deteriorating maternal conditions, were managed with volume expansion, antihypertensive drugs (as hydralazine, labetalol, nifedipine), anticonvulsants and prophylactic steroids to promote fetal pulmonary maturity. Previous studies have indicated that this conservative management is also possible with the HELLP syndrome, without an increase in maternal morbidity.

International audience; BACKGROUND: Polymorphic eruption of pregnancy (PEP) is a pruritic disease that usually occurs in primiparous women, most commonly in the last trimester of pregnancy. The origin and pathomechanisms still remain unknown. OBJECTIVES: We attempted to determine the parameters that may be associated with or complicate the course of PEP. METHODS: Data of 200 pregnant women (40 PEP and 160 control) were studied retrospectively and compared statistically using univariable and multivariable analysis. RESULTS: In multivariate analysis, pregnancy with male fetuses (P = .02) and delivery by cesarean section (P = .012) were overrepresented in the PEP group. A tendency toward more multiple gestation pregnancy in PEP was found (P = .07). The risk of PEP was not related to excessive maternal or fetal weight gain. LIMITATIONS: This was a retrospective study. CONCLUSION: This large case-control study confirms the already suspected association of PEP with male fetuses and cesarean deliveries in multivariate analysis. The higher rate of multiple gestation pregnancy was also established.