From neglect to earlier diagnosis: a qualitative meta-synthesis of psycho-social factors associated with consultation delay in advanced basal cell carcinoma.

Local malignant potential of basal cell carcinoma (BCC) can lead at advanced stages to the destruction of underlying tissues and significant morbidity. The primary risk factor for progression of advanced basal cell carcinoma (aBCC) is the long duration of the tumour, which results from delay in seeking medical care. To assess the implication of psycho-social factors in the delay before the first medical consultation among patients with aBCC, in order to identify potentially targetable factors enabling earlier diagnosis. Three-step qualitative meta-synthesis: (1) systematic review of the literature; (2) structured qualitative analysis of these documents; (3) construction of a logical model. After screening, 81 articles were included. Self-neglect and denial in patients are roundly put forward as the main obstacles to consultation. We found that avoidance behaviour, mistaken interpretation and banalisation of symptoms, and fear of treatment all played a role. The strongest motivation to seek help comes from the realisation that new symptoms may be dangerous; the role of interpersonal surroundings is highlighted as helpful. Patient delay has multifactorial origins in aBCC, especially self-neglect ranging from denial of tumours to conscious refusal of treatment.

Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56.

PURPOSE: Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6-negative patients. METHODS: First, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients. RESULTS: 6.4% of ABCC6-negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE. CONCLUSION: CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.

Are there risk factors for false-positive malformation diagnoses on obstetric ultrasound? A nested case-control study.

INTRODUCTION: In a population-based study, we found an overall false-positive rate of 8.8% for the second and third trimester ultrasounds. Although numerous studies have been performed to examine factors which lead to false negatives, the same is not true for the factors associated with false positives. The principal objective of this study was to look for risk factors for false-positive diagnoses of fetal malformations on obstetric ultrasound scans. MATERIAL AND METHODS: In this nested case-control study, the case infants were those whose mother had a false-positive antenatal ultrasound diagnosis of a malformation during the second or third trimester (ultrasound false-positives) and who were live - or stillborn in Auvergne in 2006-2010. The control group comprised all children who were ultrasound true-negatives in 2005 and 2007. The study included 46 cases and 184 controls, matched according to the level of the maternity unit in which they were born. RESULTS: Most false-positive diagnoses were minor malformations. The mean term at this false-positive diagnosis was 27.7±5.4 weeks; in 46.8% of cases, the diagnosis was made during the second-trimester ultrasound. A single malformation was suspected in 95.7% of the cases. In 97.9% of cases, only one anatomical system was affected. In all, 49 malformations were identified among the 46 cases and their distribution differed according to anatomical system. The only risk factor identified was a body mass index (BMI)<25 (ORa=1.7; 95%CI: 1.2-2.4). DISCUSSION: A maternal BMI<25 was the only risk factor identified for a false-positive ultrasound diagnosis of a fetal malformation.

Preoperative Staphylococcus aureus Carriage and Risk of Surgical Site Infection After Cardiac Surgery in Children Younger than 1 year: A Pilot Cohort Study.

Surgical site infections (SSI) increase length of stay, morbidity, mortality and cost of hospitalization. Staphylococcus aureus (SA) carriage is a known risk factor of SSI in adults, but its role in pediatrics remains uncertain. The main objective of this pilot prospective monocentric cohort study was to describe the prevalence of SA colonization in children under 1 year old before cardiac surgery. The secondary objectives were to compare the incidence of SSI and other nosocomial infections (NI) between preoperative carriers and non-carriers. From May 2012 to November 2013, all children <1 year old undergoing cardiac surgery under cardiopulmonary bypass underwent preoperative methicillin-resistant (MRSA) and methicillin-sensitive SA (MSSA) screening using real-time PCR. The only exclusion criterion was invalid PCR. All patients were followed up to 1 year after the surgery regarding SSI and other nosocomial infections. Among the 68 studied patients, SA colonization prevalence was 26.5%, comprising 23.5% MSSA and 2.9% MRSA. There was no significant difference between colonized and non-colonized children regarding SSI rate (16.7 vs 20%; p = 0.53), but ventilator-associated pneumonia rate was significantly higher among the SA carriers (22.2 vs 2%; p < 0.05). The colonization rate was different depending on the age of the patients (p < 0.05). This pilot study highlights that colonization with MSSA is frequent whereas MRSA prevalence is low in our population. In this cohort, there was no association between SA colonization and SSI incidence but further studies are needed to analyze this association.

Phenotypic variability and diffuse arterial lesions in a family with Loeys-Dietz syndrome type 4.

Syndromic thoracic aortic aneurysm and dissection (TAAD) can suggest Marfan, vascular Ehlers-Danlos or Loeys-Dietz (LDS) syndromes. Several of the TGFß-pathway-related genes predispose to different types of LDS. Heterozygous loss-of-function variations in TGFß2 have been shown to be responsible for a novel form of syndromic TAAD associated with an impairment of the mitral valve and cerebrovascular disease called Loeys-Dietz syndrome type 4 (LDS4). We report the clinical characterization of a LDS4 French family with sudden deaths and diffuse vascular lesions, caused by a frameshift mutation in TGFß2 gene: c.[995del]; p.(Leu332TrpfsTer27). Clinical characteristics include aneurysm of aortic sinus, skeletal and cutaneous features compatible with a syndromic form of TAAD (joint hypermobility, scoliosis, and easy bruises), intracranial aneurysms and rare mitral valve involvement. Iliac aneurysms, systemic medium caliber arteries dissections, and mild developmental delay were present in the family, and have not been described in LDS4. Phenotypic variability was also an important finding, including absence of clinical vascular events at advanced age in one case. Our data expand the phenotype of LDS4: we confirm that TGFß2 mutations are responsible for true LDS syndrome with non-specific features of connective tissue disorders and diffuse vascular lesions. Adapted vascular follow up and prevention has to be proposed for these patients.

Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro.

STUDY QUESTION: Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER: Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY: Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE: The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION: Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.

[Comparison of two protocols of febrile urinary tract infection management in children]. / Comparaison de deux protocoles de prise en charge des infections urinaires fébriles de l'enfant.

PURPOSE: To compare two first febrile urinary tract infection (UTI) management protocols with regards to the diagnosis of high-grade vesicoureteral reflux (VUR) and cost. METHODS: This study compared two cohorts of children under 16 years of age, admitted for a first episode of febrile UTI. The first group (in 2005) was managed according to previous recommendations (IV treatment and cystography performed for all children under 3 years of age). The second group (in 2006) was managed according to age and procalcitonin level. High-grade VUR frequency, UTI recurrence, hospitalization rate, and cost were compared between the two cohorts. RESULTS: A total of 225 children were included in 2005 and 116 in 2006. High-grade VUR was found in 6.2 and 9.5% of the patients in 2005 and 2006, respectively (P=0.274). There was no statistically significant difference in the UTI recurrence rate between the two cohorts (5.3% in 2005 and 8.6% in 2006; P=0.237). The mean cost of an episode of febrile UTI was not significantly different in 2005 and 2006 (€2235 in 2005, €2256 in 2006; P=0.902), but was lower for children older than 6 months in 2006 (€1292 versus €1882 in 2005; P=0.0042). CONCLUSION: Our management protocol for a first febrile UTI episode in children based on procalcitonin levels seems to be suitable for the diagnosis of high-grade VUR. The hospitalization rate and the mean cost of management for children older than 6 months of age was significantly reduced in 2006. The management guidelines for a first occurrence of febrile UTI in children should be reconsidered.

Beclin 1 mRNA strongly correlates with Bcl-XLmRNA expression in human hepatocellular carcinoma.

Beclin 1 physically associates with Bcl-x(L) and is considered as a haploinsufficient tumor suppressor. As the role of Beclin 1 in hepatocellular carcinoma (HCC) is unknown, we determined Beclin 1 mRNA expression in 27 pairs of tumoral/nontumoral (T/NT) liver samples. The Beclin 1 mRNA T/NT ratio was less than 0.5 in 2 tumors and more than 2 in 1 tumor, and was positively correlated with the Bcl-X(L) mRNA T/NT ratio (P < 0.001), but not with the proliferating cell nuclear antigen mRNA T/NT ratio. Coregulation of Beclin 1 and Bcl-X(L) expression in HCC may suggest cooperation in the regulation of apoptosis.

A HUVEC line with a stable expression of the VEGF121 gene to achieve complete endothelialization of blood conduits.

The purpose of this investigation was to establish monoclonal cell lines of HUVEC with the stable expression of the VEGF(121) gene. Such cells are likely to better adhere to the luminal surface of stents or grafts and to promote a complete endothelialization. The eukaryotic expression vector PCD(2)-VEGF(121) was transfected into cell lines of HUVEC mediated by lipofect AMINE. The positive clones were obtained by the screening of G(418). The transcription and expression of the VEGF gene were investigated by RT-PCR and immunocytochemistry, respectively. The experiment of Miles was applied for the assay of the biological activity of the protein of the VEGF produced by the HUVEC lines with transfected PCD(2)-VEGF(121). The growth curve was made for comparison with that of non-transfected HUVEC line cells. The positive clone cells from which transcripted the mRNA of VEGF(121) gene were obtained by RT-PCR. The positive results of the immunocytochemistry were found and the high biological activity of VEGF in the media was detected in the positive clone cells only. The time to achieve the multiplication of the positive clone cells by a factor of 2 was shorter than that of the non-transfected HUVEC line calculated from the growth curve. The HUVEC line of monoclonal cells with the stable expression of VEGF(121) gene has been established successfully and can be employed on the luminal surfaces of foreign blood conduits.

[Is entropy a monitor for the guidance of intraoperative analgesia?]. / L'entropie: un moyen d'apprécier le défaut d'analgésie?

OBJECTIVE: Comparison between BIS (Bispectral Index) and state (SE) and response (RE) entropy during laparotomy for inflammatory bowel disease patients (IBD) and evaluation of the variations of RE and SE during nociceptive stimulation. STUDY DESIGN: Prospective, observational study. PATIENTS AND METHODS: Fourteen IBD's patients undergoing laparotomy were included. Anaesthesia aimed to maintain BIS between 40 and 60 by isoflurane and nitrous oxide. Analgesia was performed by sufentanil bolus administrated according to an increase of 20% of systolic blood pressure (SBP) and heart rate compared with the baseline values. BIS, RE and SE were measured at each nociceptive stimulation. A variance analysis (Anova) was used to assess BIS, RE and SE variations throughout surgery (p<0.05 as significant). Relationship between BIS, RE and SE was assessed by Pearson correlation (p<0.01 as significant). The ability for SE and RE to predict depth of anaesthesia and intraoperative analgesia was performed by calculating area under the receiver operated curves (AUC). RESULTS: BIS and entropy parameters had strictly the same evolution during anaesthesia. SBP increased significantly during nociceptive stimulation while no variation of RE was observed. A significant correlation was shown between BIS, RE and SE. The evaluation of anaesthesia depth was good for RE (AUC: 0.932+/-0.26) and SE (AUC: 0.926+/-0.27). There was however no difference between RE and SE to predict analgesic requirement. CONCLUSION: Because RE includes muscular frequency analysis, it does not allow analgesic requirement evaluation in paralyzed patients.

MRI virtual biopsies: analysis of an explanted endovascular device and perspectives for the future.

Information that can be obtained by magnetic resonance imaging (MRI) of explanted endovascular devices must be validated as this method is non-destructive. Histology of such a device together with its encroached tissues can be elegantly performed after polymethymethacrylate (PMMA) embedding, but this approach requires destruction of the specimen. The issue is therefore to determine if the MRI is sufficient to fully validate an explanted device based upon the characterization of an explanted specimen. An AneuRx device deployed percutaneously 25 months earlier in a 75-year-old patient was removed en bloc at autopsy together with the surrounding aneurysmal sac and segments of the upstream and downstream arteries. Macroscopic pictures were taken and a slice of the cross-section was processed for histology after polymethylmethacrylate (PMMA) embedding. For the magnetic resonance imaging investigation, the device was inserted in a Biospec 4.7 T MRI system with a 20 mm diameter birdcage resonator used for both emission and reception. A Spin-Echo (SE) was used to acquire both T1 proton density (PD) and T2 weighted images. A gradient-echo (GE) sampling of a free induction decay (GESFID) was used to generate multiple GE images using a single excitation pulse so that four images at different TE were obtained in the same acquisition. The selected explanted device was outstandingly well-healed compared to most devices harvested from humans. No inflammatory process was observed in contact or at distance of the materials. In MRI T1 images display no specific contrast and were homogeneous in the different tissues. The contrast was improved on proton density weighed images. On the T2 weighed images, the different areas were well identified. The diffusion images displayed in the surrounding B region had the greatest diffusion coefficient and the greatest anisotropy. The MRI analysis of the explanted AneuRx device illustrates the possibilities of this technique to characterize the interaction of the endovascular graft with the surrounding tissues. MRI is a breakthrough to investigate explanted medical devices but it also can be advantageously used in vivo to obtain virtual biopsies, because real biopsies to determine the 3 Bs (biocompatibility, biofunctionality and bioresilience) cannot be carried out as they could obviously initiate infection and degradation of the foreign materials.

Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2.

Caspases play important roles in apoptotic cell death and in some other functions, such as cytokine maturation, inflammation, or differentiation. We show here that the 5'-flanking region of the human CASP-2 gene contains three functional response elements for sterol regulatory element binding proteins (SREBPs), proteins that mediate the transcriptional activation of genes involved in cholesterol, triacylglycerol, and fatty acid synthesis. Exposure of several human cell lines to statins, lipid-lowering drugs that drive SREBP proteolytic activation, induced the CASP-2 gene to an extent similar to that for known targets of SREBP proteins. Adenoviral vector-mediated transfer of active SREBP-2 also induced expression of the CASP-2 gene and the caspase-2 protein and increased the cholesterol and triacylglycerol cellular content. These rises in lipids were strongly impaired following small interfering RNA-mediated silencing of the CASP-2 gene. Taken together, our results identify the human CASP-2 gene as a member of the SREBP-responsive gene battery that senses lipid levels in cells and raise the possibility that caspase-2 participates in the control of cholesterol and triacylglycerol levels.

[Perioperative management of asplenic patients]. / Prévention du risque infectieux postopératoire chez les patients splénectomisés.

OBJECTIVE: In 2003, asplenia had involved 250000 patients in France. These patients are at risk of severe infection, mostly with capsulated bacteria as pneumococci, meningococci and Haemophilus. The higher mortality and morbidity due to infection in asplenic patient led in June 2003 a French expert committee to propose preventive management based on vaccination and antibioprophylaxis. STUDY DESIGN: Update article. DATA SYNTHESIS: For vaccination, two vaccines against pneumococci are available. The first one, the antipolysaccharide (Pneumo 23) is recommended for adults. It is effective for the majority of the serotypes even if its efficacy can be variable. The second one a conjugated pneumococcal vaccine (Prenevar) is used for children under two years because it has higher activity on antibiotic resistant strains therefore increasing antibiotic prophylaxis efficiency. When splenectomy is required, vaccination against pneumococci, Haemophilus (b type) and C meningococci must be performed at least 15 days before surgery, in order to get better immune stimulation. In case of emergency, vaccines have to be administrated within 30 days after surgery. Antibioprophylaxis is based on cefazolin injection before splenectomy and by postoperative intravenous amoxicillin administration. As soon as oral intake is allowed, antibioprophylaxis is continued for at least two years in adults and five years in children. Both antibiotic and vaccination have been reported to reduce pneumococcus infections.

Study of the effects of interferon a on several human hepatoma cell lines: analysis of the signalling pathway of the cytokine and of its effects on apoptosis and cell proliferation.

BACKGROUND: Interferon alpha (IFNalpha), currently used for the treatment of chronic viral hepatitis, is also known to prevent the development of hepatocellular carcinoma (HCC), the mechanism of this action being still debatable. AIMS: To study thoroughly in human hepatoma cell lines (HHL)--Hep3B, HepG2, HuH7, SKHep1, and Chang-Liver--submitted to rhIFNalpha, the signalling pathway of IFNalpha, the binding activity of the cytokine on specific gamma-activated sequence (GAS) and interferon-stimulated regulatory element (ISRE) nuclear sequences, and its effects on apoptosis and cell proliferation. METHODS: The behaviour of signal transducer and activator of transcription (STAT)1, STAT2, p48(IRF9) and the binding of nuclear proteins were investigated by immunoblot and electro-mobility shift assay. Expression of some IFNalpha-dependent proteins--p21/(WAF1), inducible nitric oxide synthase, IRF1 and 2--were studied by immunoblot. Apoptosis and the cell cycle were studied by morphological and biochemical methods. RESULTS: Transduction of INFalpha was unaltered, although there were some variations in the different HHL. Nuclear protein binding to GAS or ISRE showed that ISRE was mainly involved. Apoptosis did not occur. The cell cycle was slightly modified in HuH7. Three GAS- and/or ISRE-dependent proteins increased, suggesting that IFNalpha may have some biological effects on HHL. CONCLUSIONS: The IFNalpha signalling pathway is functional in several HHL, but the cytokine has no apoptotic effect and a moderate anti-proliferative effect. This suggests that the preventive role of IFNalpha on HCC cannot be explained by an apoptotic and/or an anti-proliferative effect, but possibly by its action on several specific nuclear sequences that protect liver cells from transformation.

A histopathologic investigation of PGE(2) pathways as predictors of proliferation and invasion in urothelial carcinomas of the bladder.

INTRODUCTION AND OBJECTIVES: The pattern of arachidonate acid (AA) transformation in tumor cells has been shown to play a role in determining tumor cell invasiveness. AA is released from membrane phospholipids by cPLA(2). Then it is metabolized into prostaglandins and PGE(2) especially via cyclooxygenase pathways. PGE(2) production seems to be necessary for rendering the cells invasive. We aimed to characterize cPLA(2), cyclooxygenase 2 (COX2) and prostaglandine E synthase (PGES) expression in human transitional carcinoma (TCC) of the urinary bladder and correlate with the Ki-67 proliferating marker. METHODS: Formalin-fixed human TCC tissues (n=54) obtained from TURB or cystectomies were evaluated for cPLA(2), COX2, PGES and Ki-67 expression using specific antibodies. There were 6 CIS, 9 pTaG1, 9 pTaG3, 10 pT1G3 and 10 pT2G3. 10 normal bladder tissues were also evaluated. Control slides were incubated without primary antibodies and treated in a similar way. RESULTS: cPLA(2), COX2 and PGES were not expressed in the 10 normal tissues. In the same normal tissues, Ki-67 expression was observed only in 1% of the cells. However, cPLA(2) was expressed in 1/6 CIS, 1/9 pTaG1, 3/9 pTaG3, 6/10 pT1G3 and 2/10 pT2G3. COX2 was expressed in 0/6 CIS, 0/10 pTaG1, 2/9 pTaG3, 3/10 pT1G3 and 1/10 pT2G3. PGES was expressed in 4/6 CIS, 0/9 pTaG1, 4/9 pTaG3, 2/10 pT1G3 and 5/10 pT2G3. Ki-67 expression was 39.5% for CIS, 6.5% in pTaG1, 37% in pTaG3, 34.5% in pT1G3 and 55% in pT2G3. If we consider it a positive result when at least one enzyme was expressed, there were 5/6 CIS positive, 1/9 pTaG1 positive, 9/9 pTaG3 positive, 10/10 pT1G3 positive and 10/10 pT2G3 positive. Also the Ki-67 is more often expressed in cells with high grade tumor. CONCLUSIONS: These results suggest that (i). not only COX2 is involved in the tumorogenesis of the TCC but also cPLA(2) and PGES, (ii). there is relationship between the AA metabolic PGE(2) pathway expression and the aggressiveness of the TCC of the urinary bladder.

Impaired mitochondrial pyruvate importation in a patient and a fetus at risk.

The patient was the first child of healthy consanguineous parents. She presented at birth with hypotonia, mild facial dysmorphism, periventricular cysts, marked metabolic acidosis, hyperlactacidemia with normal lactate/pyruvate molar ratios, normoglycemia, and normal ammonia. Hyperlactacidemia was severe (5-14 mmol/l) and not corrected with bicarbonate, thiamine (10 mg/d), 2-chloropropionate (100 mg/kg/d) and a ketogenic diet. Pyruvate dehydrogenase (PDHC) activity was normal in lymphocytes and fibroblasts. Functional assays were performed in digitonin-permeabilized fibroblasts to measure oxidation rates from radiolabeled pyruvate and malate. The production of [14C]acetylcarnitine or [14C]citric cycle intermediates derived from [2-14C]pyruvate as well as the release of 14CO(2) from [1-14C]pyruvate was severely impaired, whereas decarboxylation of [U-14C]malate was normal. With increasing concentrations of [1-14C]pyruvate, the patient's fibroblasts behave like control fibroblasts incubated in the presence of alpha-cyano-4-hydroxycinnamate, a specific inhibitor of mitochondrial pyruvate uptake: a progressive increase in 14CO(2) production was observed, likely due to passive diffusion of [1-14C]pyruvate through the mitochondrial membranes. Our results are consistent with a defect of mitochondrial pyruvate transport in the patient. Mutational analysis was precluded as the cDNA sequence of the pyruvate carrier has not been identified as yet in any organism. An affected fetus was recognized in a subsequent dichorionic twin pregnancy using the coupled assay measuring [2-14C]pyruvate oxidation rates on digitonin-permeabilized trophoblasts. After selective feticide, the pregnancy was uncomplicated with delivery at 37w of a healthy female, who is currently 2-month old.

Solid-state 1H and 27Al NMR studies of amorphous aluminum hydroxides.

Two kinds of amorphous aluminum hydroxides, a sample precipitated from admixing AlCl3 and NaOH aqueous solutions and the commercial product, were measured by 27Al and 1H solid-state NMR spectroscopy. Pentahedral and tetrahedral coordinations, as well as octahedral coordination of oxygen atoms for aluminum, are observed in 27Al magic angle spinning (MAS) spectra of both amorphous samples. In contrast, octahedral coordination is only observed in gibbsite, bayerite, and boehmite. According to 1H MAS-NMR spectra under conditions of high spinning rate (35 kHz) and high field (14.09 T), free waters and OH groups coupled with aluminum for amorphous samples are observed at approximately 5 and approximately 4.5 ppm, respectively, the latter peak being broader. This is consistent with the differential spectra between spin echo and transfer of populations in double resonance. We conclude that the subunits of AlO4, AlO5, and AlO6 in amorphous aluminum hydroxides are bound through hydrogen bonds with a wide distribution of bonding strength.

[The pneumology department]. / Le Service de Pneumologie.

The department of pneumology of the Erasme hospital exists since 25 years. The basic clinical activities include pulmonary function testing (7,500 patients per year), endoscopy, including interventional endoscopy (1,500 patients per year), thoracic oncology, allergology, rehabilitation and aid to smoking cessation. The following expertise fields have been largely developed: lung transplantation, treatment of cystic fibrosis in collaboration with the children's hospital Reine Fabiola, occupational.

Interleukin-1, tumor necrosis factor alpha, and interleukin-17 synergistically up-regulate nitric oxide and prostaglandin E2 production in explants of human osteoarthritic knee menisci.

OBJECTIVE: In osteoarthritis (OA), a combination of biochemical and biomechanical factors may damage both menisci and articular cartilage. Nitric oxide (NO) and prostaglandin E2 (PGE2) have been implicated as mediators of inflammation in OA. The goals of this study were to determine if menisci from patients with OA produce NO and PGE2, and if the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor a (TNFalpha), and IL-17 augment NO and PGE2 production by these tissues. METHODS: Menisci were obtained from 17 patients (age 47-75 years) undergoing total knee replacement for OA. Tissue explants were cultured alone or with IL-1beta, IL-17, or TNFalpha, and the release of NO and PGE2 from the tissue as well as the presence of type 2 nitric oxide synthase (NOS2) and cyclooxygenase 2 (COX-2) antigens were measured. RESULTS: All menisci constitutively produced NO, and significant increases in NO production were observed in the presence of IL-1beta, TNFalpha, or IL-17 (P < 0.05). The combination of IL-17 and TNFalpha significantly increased NO production compared with either cytokine alone. Basal and cytokine-stimulated NO synthesis was inhibited by the NOS inhibitors NG-monomethyl-L-arginine or N-3-aminoethylbenzylacetamidine (1400W). IL-1beta significantly increased PGE2 production. The combination of IL-1beta and TNFalpha had an additive effect on PGE2 production, while addition of IL-17 to TNFalpha or IL-1beta synergistically enhanced PGE2 production. Inhibition of NO production by 1400W significantly increased IL-1beta-stimulated PGE2 production, and inhibition of PGE2 production by the COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide significantly increased IL-17-stimulated NO production. CONCLUSION: Menisci from humans with OA spontaneously produced NO and PGE2 in a manner that was synergistically or additively augmented by cytokines. NO and PGE2 exhibited reciprocal regulatory effects on one another, suggesting that pharmaceutical agents designed to inhibit NOS2 or COX-2 production may in fact be influencing both pathways.

Plasma progesterone kinetics following surgical treatment of ectopic pregnancies.

OBJECTIVES: Comparative study of plasma progesterone and betaHCG kinetics following surgical treatment of ectopic pregnancy. STUDY DESIGN: Prospective study involving 62 patients with tubal ectopic pregnancies. Study of the kinetics of plasma progesterone and betaHCG, and the correlation coefficient between plasma progesterone and betaHCG levels during post-operative follow-up. RESULTS: Thirty-nine patients were treated by salpingostomy and 23 by salpingectomy. Analyzing the betaHCG kinetics according to treatment revealed that both curves were convergent on day 2. Progesterone kinetics differed greatly in that they appeared "parallel and confused". Analyzing the correlation between betaHCG and progesterone levels proved the absence of a significant link. CONCLUSIONS: Studying the kinetics of plasma progesterone after surgical treatment of ectopic pregnancies revealed a fast decrease in progesterone. Statistical analysis of the progesterone concentration showed that post-operative kinetics is fully independent from that of betaHCG. Progesterone therefore cannot be substituted to betaHCG for post-operative follow-up.