Maternal deaths from indirect obstetric causes are the result of a pre-existing disease or condition that appeared during pregnancy without obstetric causes, but which was aggravated by the physiological effects of pregnancy. Twenty-six deaths from indirect causes related to a pre-existing pathology, excluding disease of the circulatory system or infection, were analysed by the committee of experts. Pre-existing pathology during pregnancy was documented in 13 women (asthma, n=3, genetic diseases, n=3, previous breast cancer, n=2, major sickle cell syndrome, n=2, epilepsy, n=1 and brain tumour, n=1). In 13 women, the pathology was not known before pregnancy (breast cancer, n=6, brain tumours, n=3, uterine sarcoma, n=1, cervical cancer, n=1, malignant melanoma, n=1 and acute myeloid leukaemia, n=1). For 16 women (61%), the death is related to a neoplastic pathology. Although the majority were considered inevitable for 11/16 women, 5 deaths were considered possibly preventable, the main preventable factor being a delay in diagnosis, and/or a delay in starting a specific treatment. For 10 women, the death is related to a chronic non-neoplastic pathology, known before pregnancy for 9 women, judged most often as possibly preventable, the main preventable factor being the failure of the medical team or the patient to take the pathology and/or its treatment into account. A preconception medical consultation with a specialist should be recommended to all patients with pre-existing disease. A clinical examination of the breasts is strongly recommended at the first visit and then during pregnancy.
Cardiovascular Diseases , Maternal Death , Stroke , Cardiovascular Diseases/epidemiology , Female , France/epidemiology , Humans , Maternal Death/etiology , Maternal Mortality , Pregnancy , Stroke/epidemiology
Amniotic fluid embolism remains the 3rd cause of maternal death in France, with a stable rate and 28 deaths in this triennium, representing 10.7% of maternal deaths and a maternal mortality ratio of 1.2/100,000 live births. Cases are characterized by the suddenness of symptoms: the median delay between symptoms and death was 4h [0.75-696] with 20/28 patients did not reach the intensive care unit. Initial circulatory failure or cataclysmic haemorrhage was the two modes of presentation. Prodromes were reported in 17 (63%) cases and induction of labour was present in 12/27 (44%). One or more factors of sub-optimal care were present in 72% of the cases, and 52% of deaths were considered possibly or probably preventable. This preventability most often concerned the content of care but also the organisation of care (including human resources, communication, sites of care and referrals). The delay in establishing a well-conducted cardio-circulatory resuscitation or the delay in setting up an optimal transfusion strategy were the most frequent elements of substandard care. Absence or delay at hysterectomy during haemorrhagic situations was reported in 15/20 cases. The experts suggest being on the alert to diagnose amniotic embolism at an early stage, initiating intense resuscitation "outside the walls", envisaging a hysterectomy without delay if the haemorrhage is intense. On an organisational level, a "vital emergency maternity care" plan, specific to each establishment could be proposed.
Embolism, Amniotic Fluid , Maternal Death , Maternal Health Services , Embolism, Amniotic Fluid/therapy , Female , France/epidemiology , Humans , Maternal Death/etiology , Maternal Mortality , Pregnancy
Polyoxometalates (POMs) are redox-active molecular oxides, which attract growing interest for their integration into nano-devices, such as high-density data storage non-volatile memories. In this work, we investigated the electrostatic deposition of the negatively charged [H7P8W48O184]33- POM onto positively charged 8-amino-1-octanethiol self-assembled monolayers (SAMs) preformed onto gold substrates or onto an array of gold nanodots. The ring-shaped [H7P8W48O184]33- POM was selected as an example of large POMs with high charge storage capacity. To avoid the formation of POM aggregates onto the substrates, which would introduce variability in the local electrical properties, special attention has to be paid to the preformed SAM seeding layer, which should itself be deprived of aggregates. Where necessary, rinsing steps were found to be crucial to eliminate these aggregates and to provide uniformly covered substrates for subsequent POM deposition and electrical characterizations. This especially holds for commercially available gold/glass substrates while these rinsing steps were not essential in the case of template stripped gold of very low roughness. Charge transport through the related molecular junctions and nanodot molecule junctions (NMJs) has been probed by conducting-AFM. We analyzed the current-voltage curves with different models: electron tunneling though the SAMs (Simmons model), transition voltage spectroscopy (TVS) method or molecular single energy level mediated transport (Landauer equation) and we discussed the energetics of the molecular junctions. We concluded to an energy level alignment of the alkyl spacer and POM lowest occupied molecular orbitals (LUMOs), probably due to dipolar effects.
Maternal deaths of indirect causes result of a preexisting disease or an affection appeared during the pregnancy without any relationship with obstetrical causes, but worsened by the physiological effects of pregnancy. Among the 23 deaths of indirect cause related to a preexisiting pathology, 22 (96 %) have been analyzed by the expert comity. A known or preexisting chronic disease was documented in 16 patients (sick-cell disorder, n=3, treated epilepsy, n=3, intracerebral carvenomas, n=1, multifocal glial tumor, n=1, breast cancer, n=1, systemic lupus, n=1, diabetes mellitus, n=3, antiphospholipid syndrome, n=1). For 6 women, the pathology was unknown before the pregnancy (glioblastoma, n=2, epilepsy, n=1, Ehlers-Danlos syndrome, n=1, sick-cell disorder, n=1, breast cancer, n=1). While 6 of these deaths has been evaluated as not avoidable, 13 deaths has been considered as possibly (n=12) or certainly (n=1) preventable. The main factor of avoidability was the patient's interaction with the health system (medically non advised pregnancy, lack of adherence to treatment, for example). A pre-pregnancy medical consultation with a specialist should be recommended to all patients with preexisting chronic disease, to allow a complete information about the risks of a pregnancy, treatment adaptation if needed, better adherence and multidisciplinary follow up.
Maternal Death/etiology , Pregnancy Complications/mortality , Adult , Cause of Death , Chronic Disease , Counseling , Female , France/epidemiology , Humans , Patient Compliance , Preconception Care , Pregnancy , Risk Factors
Amniotic fluid embolism (AFE) is an unpredictable, dreadful complication of pregnancy or childbirth. EA typically includes in the same lapse of time respiratory, haemodynamic, neurological and hemorrhagic symptoms (from early and severe coagulopathy). Immediate supportive treatment by a multidisciplinary team is the cornerstone of the management. Between 2010 an 2012 in France, 24 deaths were related to AFE giving a maternal mortality ratio of 1/100,000 live births (CI 95% 0.6-1.4). AFE ranks as the second leading cause of direct maternal death. Eight cases over 23 were classified as having some degree of substandard care. Substandard care included delays in performing aggressive surgical treatment or delays in the diagnosis and the treatment of the coagulopathy. Learning points focus on the importance to pay attention on premonitory symptoms, to early assess the clotting status and to train in multidisciplinary team.
Embolism, Amniotic Fluid/epidemiology , Maternal Death/etiology , Adult , Embolism, Amniotic Fluid/diagnosis , Embolism, Amniotic Fluid/therapy , Female , France/epidemiology , Humans , Maternal Mortality , Pregnancy , Quality of Health Care , Risk Factors
BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Asthma/physiopathology , Omalizumab/therapeutic use , Adult , Aged , Asthma/diagnosis , Female , Humans , Male , Middle Aged , Respiratory Function Tests , Retrospective Studies , Time Factors , Treatment Outcome
Covalent amphiphilic polyoxometalates generated from alkylphosphonic acids have been synthesized, characterized and monitored by multinuclear NMR spectroscopy. Among them, K3H[γ-SiW10O36(C12H25PO)2] has been successfully used as a surfactant for the stabilization of a Winsor I type microemulsion system.
UNLABELLED: Bacillus thuringiensis subsp. israelensis is a bioinsecticide used for larval mosquito control and it represents a safe alternative to chemical insecticides. Despite its environmental safety, it is less efficient and persistent than chemical insecticides. To bypass these limitations, we propose to combine the advantages of chemical and biological insecticides by producing Bti in a medium supplemented with a chemical insecticide (DDT, deltamethrin, permethrin, propoxur or temephos). Among the investigated insecticides, the addition of deltamethrin in the medium induced a higher toxicity (over 6.72-fold) of the composite deltamethrin-Bti towards mosquito larvae as compared to Bti alone. This was mainly due to the insertion of deltamethrin into the membranes of Bti spores, as evidenced by a quantification of membrane-extracted deltamethrin by HPLC. This composite larvicide is a promising tool to decrease the quantity of chemicals dispersed in the environment, to increase the efficacy of Bti and to facilitate its widespread use as a transition between chemical and biological insecticides. Further experiments are required to characterize the mechanisms that underline the incorporation of deltamethrin into Bti to optimize the production and the toxicity of this composite larvicide. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report of an increased efficacy of the mosquitocidal bioinsecticide Bacillus thuringiensis subsp. israelensis (Bti) when produced with a chemical insecticide. The results clearly demonstrate that deltamethrin is able to synergize the insecticidal activity of Bti through inclusion into spore membranes, reducing off-target and nonspecific toxicity occurring when the chemical is used alone as sprays. This new composite chemical-biological insecticide can become an invaluable tool as an intermediate between single chemical usage and the widespread use of Bti, notably in developing countries with limited financial resources for intensive mosquito control campaigns.
Bacillus thuringiensis , Biological Control Agents , Culicidae , Insecticides , Mosquito Control/methods , Nitriles , Pyrethrins , Aedes , Animals , Bacillus thuringiensis/growth & development , Developing Countries , Larva , Permethrin , Temefos
A new series of polyoxometalate-based hybrids has been synthesized. These covalently linked organic-inorganic materials represent valuable elementary building blocks ready for postfunctionalization, using classical organic reactions and couplings. This approach is exemplified by the grafting of an organic chromophore via a Sonogashira coupling.
The manganese(V)-nitrido polyoxometalate derivative [PW(11)O(39){Mn(V)N}](5-) has been synthesized by photochemical activation of the parent manganese(III)-azido derivative [PW(11)O(39)Mn(III)N(3)](5-). It was characterized by mass spectrometry, (31)P NMR, UV-vis, and IR spectroscopies. An electrochemistry study indicated that only the Mn(V) state was stable. The photoactivation of the manganese(III)-azido derivative proceeds through two competitive routes, yielding to the targeted product of photooxidation {Mn(V)N} or the undesirable product of photoreduction {Mn(II)L} (L = H(2)O, N(3)), depending on the photolysis conditions. A simplified photolysis mechanism involving two different excited states was proposed to account for the temperature and wavelength dependence.
Azides/chemistry , Manganese/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/chemical synthesis , Tungsten Compounds/chemistry , Photochemistry
OBJECTIVES: Inhibitor of differentiation 3 (Id3)-deficient mice show sicca symptoms, lymphocyte infiltration of exocrine glands and positive anti-Ro/SSA and anti-La/SSB antibodies, all hallmarks of primary Sjögren's syndrome (pSS). The impairment of Id3 in T cells and, possibly, in salivary glandular epithelial cells (SGECs) seems to be involved. This animal model prompted us to investigate the role of Id3 in human pSS. METHODS: Quantitative Id3 expression in peripheral T cells, cultured SGECs and in total minor salivary glands was assessed by RT-PCR in pSS patients and controls. After Id3 sequencing, we investigated two single nucleotide polymorphisms (SNPs) (c.313G>A and g.-156A>G) in a case-control study of 212 Caucasian pSS patients and 168 controls. RESULTS: Quantitative Id3 expression was not decreased in pSS patients nor in SGECs, in T cells or in minor salivary glands. As well, patients and controls did not differ in allele and genotype frequencies of Id3 SNPs (P = 0.67 and P = 0.71 for the c.313G>A and the g.-156A>G, respectively). Neither SNP was associated with a pattern of autoantibody secretion. CONCLUSION: Although the Id3-deficient mouse model represents an attractive model for human pSS, Id3 expression is not impaired in SGECs, peripheral T cells and in labial salivary glands in pSS patients and Id3-relevant SNPs do not give evidence of genetic predisposition in Caucasian pSS patients.
Inhibitor of Differentiation Proteins/biosynthesis , Neoplasm Proteins/biosynthesis , Sjogren's Syndrome/metabolism , Autoantibodies/metabolism , Case-Control Studies , Cells, Cultured , Female , Gene Expression , Gene Frequency , Humans , Inhibitor of Differentiation Proteins/genetics , Male , Middle Aged , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Salivary Glands, Minor/metabolism , Sjogren's Syndrome/genetics , Sjogren's Syndrome/immunology
One-third of first-degree relatives of patients with primary Sjögren's syndrome (pSS) suffer from other autoimmune diseases, including type I diabetes, systemic lupus erythematosus and autoimmune thyroiditis. Recently, 1858 C/T polymorphism of PTPN22 gene was reported to predispose to these autoimmune diseases. We decided to investigate whether PTPN22 gene polymorphism was also involved in the genetic predisposition to pSS in a case-control study, including 183 patients with pSS and 172 healthy controls. No significant differences in allele (T allele frequency: 7.7% in patients with pSS vs 7.8% in controls, P=0.9) and genotype frequencies of PTPN22 polymorphism were detected between patients with pSS and controls. PTPN 22 gene polymorphism was not associated with a specific pattern of autoantibody secretion either. Thus, 1858 C/T polymorphism of PTPN22 gene is not involved in genetic predisposition to pSS.
Polymorphism, Single Nucleotide , Protein Tyrosine Phosphatases/genetics , Sjogren's Syndrome/genetics , Autoantibodies/blood , Female , Genetic Linkage , Genetic Predisposition to Disease/genetics , Humans , Male , Protein Tyrosine Phosphatase, Non-Receptor Type 22 , Sjogren's Syndrome/blood
Reaction of K7[A,alpha-PW9Mo2O39] with Na2MoO4.2H2O in a mixture of water/dioxane/hydrochloric acid and further precipitation with (Bu4N)Br provided (Bu4N)3[A,alpha-PW9Mo3O40](3). Analogous reaction with K7-xNax[alpha-PW11O39] is an alternative to the synthesis of (Bu4N)3[alpha-PW11O39{MoVIO}]2. Multinuclear NMR and ESI mass spectrometry have been used to interpret the reaction of (Bu4N)x[alpha-PW11O39{ReO}](x=3 1; x=4 1I), (Bu4N)x[alpha-PW11O39{MoO}](x=3 2; x=4 2I) and (Bu4N)3[A,alpha-PW9Mo3O40]3 by organohydrazines, arylamines, tolylisocyanate and tetraphenylphosphine imide.
Hydrazines/chemistry , Isocyanates/chemistry , Tungsten Compounds/chemistry , Electron Spin Resonance Spectroscopy , Magnetic Resonance Spectroscopy , Polyelectrolytes , Polymers/chemistry , Quaternary Ammonium Compounds/chemistry , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared
Reaction of [Ru(arene)Cl(2)](2) (arene = benzene, toluene, p-cymene, hexamethylbenzene) with K(7)[PW(11)O(39)].14H(2)O provided two series of organometallic derivatives of heteropolytungstates: type-1 and type-2 complexes of general formulas [PW(11)O(39){Ru(arene)(H(2)O)}](5-) and [{PW(11)O(39){Ru(arene)}}(2){WO(2)}](8-), respectively. All compounds were characterized by infrared and multinuclear NMR ((1)H, (31)P, (183)W) spectroscopies. The crystal structures of Na(4)K(4)[{PW(11)O(39){Ru(benzene)}}(2){WO(2)}].6H(2)O (NaK-2a.6H(2)O), K(7)H[{PW(11)O(39){Ru(toluene)}}(2){WO(2)}].4H(2)O (K-2b.4H(2)O), and Cs(3)K(2)[PW(11)O(39){Ru(p-cymene)(H(2)O)}].4H(2)O (CsK-1c.4H(2)O) were obtained and revealed that the {Ru(arene)} fragment is supported on the oxometallic framework. Photochemical reactivity of [PW(11)O(39){Ru(arene)(H(2)O)}](5-) (arene = toluene, p-cymene) in the presence of various ligands L (L = H(2)O, dimethyl sulfoxide, tetramethylene sulfoxide, and diphenyl sulfoxide) was investigated, and led to the formation of [PW(11)O(39){Ru(L)}](5-), in which the ruthenium is incorporated into the lacunary [PW(11)O(39)](7-) anion.
The family of two siblings with severe hereditary spherocytosis was investigated. The decrease was evident on both the alpha- and the beta-chains. The parents were haematologically normal. The mother was heterozygous for the low-expression polymorphic allele alphaLEPRA. The father was heterozygous for a novel combination in which one allele showed the alpha-spectrin low expression polymorphic allele alphaLELY, while his other allele showed the alphaLELY polymorphism in cis with a G-->A substitution, named Bicêtre, found at the extreme 3' end of exon 51. This combination was designated alpha(LELY-Bicêtre). The children were compound heterozygotes for alleles alphaLEPRA and alpha(LELY-Bicêtre). Reverse transcription polymerase chain reaction detected only trace amounts of the mRNA coding for alpha(LELY-Bicêtre). Mutation is therefore an essentially null mutation with no functional protein product. The lack of disease in the alphaLELY/(LELY-Bicêtre) father compared with the marked haemolysis in the alphaLEPRA/alpha(LELY-Bicêtre) children showed that expression of allele alphaLELY is not low enough to expose null alpha-spectrin alleles on the other chromosome. Quantitative estimations from these findings suggest that, to evoke spherocytosis, it is necessary that alpha-spectrin expression must be reduced to less than 25% of normal, while a reduction to 8% is sufficient.
Spectrin/genetics , Spherocytosis, Hereditary/genetics , Alleles , Female , Humans , Infant, Newborn , Male , Mutation , Pedigree , Spherocytosis, Hereditary/blood
OBJECTIVE: to assess the effects of an educational program in asthmatic patients, following treatment readjustment. METHODS: moderate to severe asthmatic adults underwent a run-in period (up to 45 days) in order to optimize their treatment. Patients were then randomized to an educational or control group over a one-year period. Education consisted of five individual sessions covering: pathophysiology of asthma, role of medication and side-effects, asthma triggers and their avoidance, detection of an asthma flare-up, and self-management plan based on symptoms and peak-flow monitoring. MAIN OUTCOME CRITERION: symptom-free days over the study period (SFD). RESULTS: a total of 72 patients were enrolled (36 in the "education group" and 36 in the "control group"), 54 of whom completed the study. Mean SFD was comparable in the two groups (88% in the education group and 89% in the control group, respectively). When the analysis was restricted to the education group, those patients who complied perfectly with the action plan (n = 5) exhibited a higher SFD, compared to the others (97% vs. 87%, p = 0.009). CONCLUSION: both education and control groups showed high and comparable percentages of SFD. Compliance with self-management plans appears to be an important determining factor in educational programs.
Asthma/therapy , Patient Education as Topic , Self Care , Adolescent , Adult , Aged , Asthma/epidemiology , Female , Follow-Up Studies , Forced Expiratory Volume/physiology , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Morbidity , Patient Compliance , Prospective Studies , Quality of Life
