Chemical sex (chemsex) in a population of French university students.

Introduction: Chemsex is defined by the use of psychoactive substances to facilitate or improve sexual relations. Our objectives were to assess the prevalence of the practice of 'chemsex' in a population of French university students and to identify socio-demographic and clinical factors associated with this practice. Material and methods: We have used an anonymous online questionnaire comprising 15 questions on socio-demographic characteristics, chemsex use, sexual satisfaction, the type of substances used in this sexual context and their route of administration. Results: A total of 680 people were included in our study. Among them, 22.5% reported chemsex behaviour in the past year. Using a multivariate analysis, factors associated with chemsex were dating application use (p = 0.049) and pornography use [viewing more than once per month (p = 0.002)]. Having a sexual partner involved in chemsex (p < 0.0001), celibacy (p = 0.007), sexual orientations other than heterosexual (p = 0.0013) and especially bisexuality (p = 0.0002) were also significantly associated with chemsex. Conclusion: This is the first study reporting a high prevalence of chemsex in a university student population. Further larger studies should be conducted to confirm these results showing a high prevalence of this at-risk behaviour.

[Transfusion and postpartum haemorrhage]. / Transfusion et hémorragie du post-partum.

Postpartum haemorrhage is the leading cause of maternal death in France and worldwide. Guidelines help to conduct a timed management and to reduce maternal morbidity and mortality. Rescue and surgical care, transfusion and monitoring have to be previously organized.

[Anaesthetic management for caesarean delivery and Creutzfeldt-Jakob disease]. / Anesthésie pour césarienne et maladie de Creutzfeldt-Jakob.

Variant Creutzfeldt-Jakob disease (vCJD) is the only form of prion diseases linked to bovine spongiform encephalopathy (BSE). The surgical and anaesthetic management in patients having Creutzfeldt-Jakob disease is rare. Maternofoetal and human transmission of Creutzfeldt-Jakob disease is still unknown. The principles for managing these new risks are not described in obstetric recommendations. We report the case of an 18-year-old woman, who developed the variant Creutzfeldt-Jakob disease during her pregnancy.

[Acute per-partum feto-fetal transfusion. A case study on two sets of twins]. / La transfusion foeto-foetale per-partum: à propos de deux observations.

Description of acute per-partum feto-fetal transfusion. The risk of twin-twin transfusion syndrome in monochorionic twin pregnancies is well known. This pathology starts in the second trimester and has a chronic course. Acute per-partum feto-fetal transfusion seems to be less frequent and has not been studied. In the study, we described two cases of acute per-partum feto-fetal transfusion. The outcomes of the pregnancies were as follows: following a successful delivery, the first set of twins presented hypovolemic shock at birth due to an acute anemia. The second set of twins was polyglobulic, but otherwise healthy at birth. The risk of hypovolemic shock seems to be unpredictable, even if the pregnancy is monitored. Obstetricians and pediatricians must keep this pathology in mind when dealing with this kind of pregnancy. Moreover, it would be interesting to obtain systematically a full blood count of each set of twins of monochorionic pregnancies, in order to detect every case of feto-oetal transfusion.

[What public health measures could reduce antenatal exposure to tobacco and improve the quality of perinatal care: the gynecologist-obstetrician's point of view]. / Quelles sont les mesures de santé publique susceptibles de réduire l'exposition anténatale au tabac et d'améliorer les indicateurs de qualité des soins périnatals? Le point de vue du gynécologue-obstétricien.

The progression of addiction to smoking among young women is particularly alarming. The fatal effects of the nicotine-poisoning on the pregnancy and on the child constitute a serious public health issue. For young women, the period of maternity plays an essential educational role. Contact with medical care during pregnancy offers a special opportunity to establish a sound basis for health. Clinicians must strive to help women become fully aware of the fatal effects of smoking, providing methods and support for abstinence through a global, structured strategy of health care. The "Maternity without tobacco" network was developed to achieve these objectives. Expired CO analysis can be an interesting tool to search for active or passive addiction to smoking, and more generally carbon monoxide poisoning.

[Postpartum hemorrhage: frequency, consequences in terms of health status, and risk factors before delivery]. / Hémorragies du post-partum: fréquence, conséquences en termes de santé et facteurs de risque avant l'accouchement.

In the developing countries, postpartum hemorrhage is the leading cause of maternal death and affects approximately 1% of pregnant women. In developed countries like ours, maternal mortality is one hundred fold lower but remains the cause of maternal death for about 10 women per 100,000 births. In the last decade, French confidential inquiries show that the number of maternal deaths by postpartum hemorrhage are probably the double of the number in nearby countries, whereas hemorrhage should no longer be the leading cause of maternal death in our countries. Postpartum hemorrhage is defined as the loss of 500 ml or more blood in the 24 hours following delivery (5% of deliveries), but maternal tolerance is really threatened starting from 1,000 ml (1% of the women approximately). "Life-threatening" situations concern approximately one patient in one thousand so that obstetricians are rarely faced with this situation. For maternal morbidity or mortality, the risk factors of postpartum hemorrhage are nearly the same: maternal age, multiple pregnancies, uterine scars, abruptio placentae, cesarean section, poor social condition and absence of prenatal care constitute the main risk factors of postpartum hemorrhage. Maternal age must be kept in mind because it is the most related to mortality by hemorrhage, even if prevention is difficult. However, progress in delivery care which are applied to all the patients could make it possible to limit the harmful effects of this risk factor. A recent study showed that organizational factors also part of the factors of risk of maternal morbidity/mortality and could be studied for intervention.

Hip-flexed postures do not affect local anaesthetic spread following induction of epidural analgesia for labour.

Hip-flexed postures enlarging the pelvic diameter are used to improve the obstetric course of labour. Although most investigations show that lateral and sitting positions do not affect the spread of epidural analgesia, the effect of recently introduced hip-flexed postures has yet to be confirmed. This prospective randomised study included 93 parturients. Ropivacaine 0.1% 12 mL plus sufentanil 0.5 micrograms/mL was administered epidurally over a period of 6 min in one of four postures: sitting, right hip-flexed left lateral position, left hip-flexed right lateral position and supine 30 degrees lateral tilt as a control group. Left and right cephalad and sacral epidural spread were measured every 2 min over a period of 30 min. Pain relief, motor blockade and maternal and fetal side effects were noted. The total epidural spread was 15+/-0.3 dermatomes and the upper level of thermo-algesic blockade T7-T8 (range T3 to T10) in all groups. There were no differences between groups in left or right total spread or upper level of epidural blockade, time to maximal block or pain relief. There was no motor block nor any maternal or fetal side effects. The power of the study (1 - beta) was 93%. We conclude that, for the three hip-flexed postures tested, position does not influence local anaesthetic spread or symmetry of thermo-algesic blockade after induction of obstetric epidural analgesia.

[Marfan syndrome and pregnancy. Apropos of 4 cases]. / Syndrome de Marfan et grossesse. A propos de quatre cas.

OBJECTIVES: To create a follow-up protocol for pregnant patients with Marfan syndrome. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients who delivered in the Jeanne de Flandre University Hospital between June 1996 and June 1999. Four pregnant patients with Marfan syndrome were identified. RESULTS: Three of these patients had Bentall procedure. One of them had vaginal delivery and the two others underwent cesarean section. One of these two patients developed aortic valve thrombus at 14 weeks of amenorrhea. The fourth patient did not have surgery and had two vaginal deliveries. DISCUSSION: According to our results and after reviewing literature pregnant patients with Marfan syndrome were divided into two groups. The 1st group was comprised of patients who underwent Bentall procedure. The 2nd one was comprised of patients who did not undergo any surgical procedure. The possibility of vaginal delivery for patients who underwent Bentall procedure (one case) and the interest of Propanolol and anticoagulant treatment are emphasized. CONCLUSION: The multivariant approach of pregnant patients with Marfan syndrome is stressed out with special reference to the potential complications of this syndrome such as aortic dissection and to the problems related to the anticoagulant treatment.

High-performance liquid chromatography/mass spectrometry characterization of Ki4B-Ras in PSN-1 cells treated with the prenyltransferase inhibitor L-778,123.

Cellular transformation by Ras oncoproteins requires the posttranslation modification of farnesylation in a reaction catalyzed by farnesyl protein transferase (FPTase). Thus, inhibitors of FPTase have been developed as potential anticancer agents. However, recent studies with selective inhibitors of FPTase have shown that Ki4B-Ras retains its ability to transform cells by undergoing alternative prenylation by the related geranylgeranyl protein transferase I (GGPTase-I) in human tumor cells. We have developed a high-performance liquid chromatography/mass spectrometry assay for the detection and quantitation of the different processing states of Ki4B-Ras isolated from PSN-1 cells (a human pancreatic cell line with an activating Gly12 to Arg mutation) treated with the prenyltransferase inhibitor, L-778,123. Recently tested in the clinic, L-778,123 is a potent inhibitor of FPTase (in vitro IC50 = 2 nM) with some activity against GGPTase-I (in vitro IC50 = 98 nM). We find primarily farnesylated-Ki4B-Ras in vehicle-treated PSN-1 cells, a mixture of farnesylated- and geranylgeranylated-Ki4B-Ras in cells treated with nanomolar concentrations of L-778,123, and a mixture of unprocessed, farnesylated, and geranylgeranylated-Ki4B-Ras in cells treated with micromolar concentrations of compound. Of importance, this technique does not require metabolic labeling and may be used as a pharmacodynamic assay for Ki4B-Ras processing in mouse models.

Mouse mammary tumor virus-Ki-rasB transgenic mice develop mammary carcinomas that can be growth-inhibited by a farnesyl:protein transferase inhibitor.

For Ras oncoproteins to transform mammalian cells, they must be posttranslationally modified with a farnesyl group in a reaction catalyzed by the enzyme farnesyl:protein transferase (FPTase). Inhibitors of FPTase have therefore been developed as potential anticancer agents. These compounds reverse many of the malignant phenotypes of Ras-transformed cells in culture and inhibit the growth of tumor xenografts in nude mice. Furthermore, the FPTase inhibitor (FTI) L-744,832 causes tumor regression in mouse mammary tumor virus (MMTV)-v-Ha-ras transgenic mice and tumor stasis in MMTV-N-ras mice. Although these data support the further development of FTIs, it should be noted that Ki-ras is the ras gene most frequently mutated in human cancers. Moreover, Ki-RasB binds more tightly to FPTase than either Ha- or N-Ras, and thus higher concentrations of FTIs that are competitive with the protein substrate may be required to inhibit Ki-Ras processing. Given the unique biochemical and biological features of Ki-RasB, it is important to evaluate the efficacy of FTIs or any other modulator of oncogenic Ras function in model systems expressing this Ras oncoprotein. We have developed strains of transgenic mice carrying the human Ki-rasB cDNA with an activating mutation (G12V) under the control of the MMTV enhancer/promoter. The predominant pathological feature that develops in these mice is the stochastic appearance of mammary adenocarcinomas. High levels of the Ki-rasB transgene RNA are detected in these tumors. Treatment of MMTV-Ki-rasB mice with L-744,832 caused inhibition of tumor growth in the absence of systemic toxicity. Although FPTase activity was inhibited in tumors from the treated mice, unprocessed Ki-RasB was not detected. These results demonstrate the utility of the MMTV-Ki-rasB transgenic mice for testing potential anticancer agents. Additionally, the data suggest that although the FTI L-744,832 can inhibit tumor growth in this model, Ki-Ras may not be the sole mediator of the biological effects of the FTI.

Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase.

Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1, 5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase.

Inhibitors of Ras protein farnesyltransferase are described which are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Reduction of the carbonyl groups linking the first three residues of the tetrapeptide leads to active inhibitors which are chemically unstable. Stability can be restored by alkylating the central amine of the tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with concomitant modification of the side chain of the third residue led to 2(S)-(2(S)-¿[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)- methylpentyl]naphthalen-1-ylmethylamino¿acetylamino)-4 -methylsulfany lbutyric acid (11), a subnanomolar inhibitor. The methyl ester (10) of this compound exhibited submicromolar activity in the processing assay and selectively inhibited anchorage-independent growth of Rat1 cells transformed by v-ras at 2.5-5 microM.

A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis.

The farnesyltransferase inhibitor L-744,832 selectively blocks the transformed phenotype of cultured cells expressing a mutated H-ras gene and induces dramatic regression of mammary and salivary carcinomas in mouse mammary tumor virus (MMTV)-v-Ha-ras transgenic mice. To better understand how the farnesyltransferase inhibitors might be used in the treatment of human tumors, we have further explored the mechanisms by which L-744,832 induces tumor regression in a variety of transgenic mouse tumor models. We assessed whether L-744,832 induces apoptosis or alterations in cell cycle distribution and found that the tumor regression in MMTV-v-Ha-ras mice could be attributed entirely to elevation of apoptosis levels. In contrast, treatment with doxorubicin, which induces apoptosis in many tumor types, had a minimal effect on apoptosis in these tumors and resulted in a less dramatic tumor response. To determine whether functional p53 is required for L-744,832-induced apoptosis and the resultant tumor regression, MMTV-v-Ha-ras mice were interbred with p53(-/-) mice. Tumors in ras/p53(-/-) mice treated with L-744,832 regressed as efficiently as MMTV-v-Ha-ras tumors, although this response was found to be mediated by both the induction of apoptosis and an increase in G1 with a corresponding decrease in the S-phase fraction. MMTV-v-Ha-ras mice were also interbred with MMTV-c-myc mice to determine whether ras/myc tumors, which possess high levels of spontaneous apoptosis, have the potential to regress through a further increase in apoptosis levels. The ras/myc tumors were found to respond nearly as efficiently to L-744,832 treatment as the MMTV-v-Ha-ras tumors, although no induction of apoptosis was observed. Rather, the tumor regression in the ras/myc mice was found to be mediated by a large reduction in the S-phase fraction. In contrast, treatment of transgenic mice harboring an activated MMTV-c-neu gene did not result in tumor regression. These results demonstrate that a farnesyltransferase inhibitor can induce regression of v-Ha-ras-bearing tumors by multiple mechanisms, including the activation of a suppressed apoptotic pathway, which is largely p53 independent, or by cell cycle alterations, depending upon the presence of various other oncogenic genetic alterations.

[Pelvic trauma and pregnancy. Literature review and case report]. / Traumatisme du bassin et grossesse. Revue de la littérature à propos d'un cas.

The authors are dealing with a case of a pelvic fracture (right superior pubic ramus) after a road traffic accident to a patient who arise a pregnancy with twins at twenty five weeks pregnant. Seven per cent of a road traffic accident affect pregnancy with a maternal death rate from eight to sixteen per cent and a fetal death rate up to fifty seven per cent. Pelvic trauma are more deleterious during the pregnancy because of the gravide uterus, of the abdominal injuries binding more often, and of pregnancy secondary maternal physiology which lead to delay diagnosis and therapeutics. Blunt fetomaternal consequences are ruled by pelvic haematomas, uterine rupture, prematurity, acute fetal distress, fetal injuries and in utero death. At mid and long range arise the problem of child birth way and the risk of mechanical dystocy. Cesarean is store in case of vesical and urethral injuries, or perineal injury, several pelvic fractures or in case of the pelvic belt fracture moved and not reduced, bringing to a surgical unsymmetrical pelvis. In the other cases, the obstetrical prognoses will be done after a dialogue with all medical staff and a full synthesis of the file based on the fetopelvic comparisons (obstetrics previous, clinic, fetal biometry, pelvimetry X ray).

Potent, non-thiol inhibitors of farnesyltransferase.

The structure-activity relationship of a series of non-thiol CaaX analogs, which are inhibitors of farnesyltransferase, is described. These inhibitors contain a substituted phenyl group at the N terminus, which may occupy a novel binding domain on the Ras protein.

Plantar flap reconstruction for acral lentiginous melanoma.

BACKGROUND: Acral lentiginous melanoma continues to be difficult to diagnose despite an overall trend toward early identification of smaller and thin lesions. The insidious nature of this lesion often precludes primary closure of the surgical defect once it is excised, adding to the reconstructive complexity. Local flaps on the plantar foot offer an option for reconstruction when the defect is of intermediate size. METHODS: Eight patients (5 men and 3 women, with an average age of 58 years) who underwent plantar flap reconstruction for defects isolated to the weight-bearing heel were retrospectively reviewed. RESULTS: The average depth of the melanoma was 2.82 mm. Surgical margins were 2 cm or less in seven of the eight patients. Partial flap necrosis occurred in one patient, and loss of part or all of the skin grafts was noted in two patients. Currently five patients are alive with no evidence of disease. CONCLUSION: The plantar flap can provide local well-vascularized tissue for weight-bearing areas where skin grafting alone may not be appropriate. Coverage of these areas with well-padded flaps led to ambulation in all of the patients studied. We believe this flap offers durable coverage for medium-sized defects in acral lentiginous melanoma.

Selection of potent inhibitors of farnesyl-protein transferase from a synthetic tetrapeptide combinatorial library.

Inhibitors of farnesyl-protein transferase (FPTase) show promise as anticancer agents. Based on the sequence of the protein substrates of FPTase (the CAAX sequence), potent and selective peptidomimetic inhibitors have been developed; these compounds share with the peptide substrate a free thiol and a C-terminal carboxylate. We have used a synthetic tetrapeptide combinatorial library to screen for new leads devoid of these features: the peptides were C-terminally amidated, and no free thiol was included in the combinatorial building blocks. To compensate for this negative bias, an expanded set of 68 amino acids was used, including both L and D as well as many non-coded residues. Sixteen individual tetrapeptides derived from the consensus were synthesized and tested; all were active, showing IC50 values ranging from low micromolar to low nanomolar. The most active peptide, D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-gamma- carboxyglutamic acid (Ki = 2 nM), is also very selective showing little inhibitory activity against the related enzyme geranylgeranyl-protein transferase type I (IC50 > 50 microM). In contrast to CAAX-based peptidomimetics, D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-gamma-carboxyglut amic acid appeared to mimic the isoprenoid substrate farnesyl diphosphate as determined by kinetic and physical measurements. D-Tryptophan-Dmethionine-D-4-chlorophenylalanine-L-gamma- carboxyglutamic acid was a competitive inhibitor of FPTase with respect to farnesyl diphosphate substrate and uncompetitive with respect to CAAX substrate. Furthermore, we demonstrated that FPTase undergoes ligand dependent conformational changes in its circular dichroism spectrum and that D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-gamma- carboxyglutamic acid induced a conformational change identical to that observed with farnesyl diphosphate ligand.