InGaN islands and thin films grown on epitaxial graphene.

In this work, the growth of InGaN on epitaxial graphene by molecular beam epitaxy is studied. The nucleation of the alloy follows a three-dimensional (3D) growth mode in the observed temperature range of 515 °C-765 °C, leading to the formation of dendrite-like islands. Careful Raman scattering experiments show that the graphene underneath is not degraded by the InGaN growth. Moreover, lateral displacement of the nuclei during an atomic force microscopy (AFM) scan demonstrates weak bonding interactions between the InGaN and the graphene. Finally, a longer growth time of the alloy gives rise to a compact thin film in a partial epitaxial relationship with the SiC underneath the graphene.

Charge transfers and charged defects in WSe2/graphene-SiC interfaces.

We report on Kelvin probe force microscopy (KPFM) and density functional theory (DFT) investigations of charge transfers in vertical heterojunctions between tungsten diselenide (WSe2) layers and graphene on silicon carbide substrates. The experimental data reveal the existence of an interface dipole, which is shown by DFT to originate from the neutralization of the graphene n-doping by an electron transfer towards the transition metal dichalcogenide (TMD) layer. The relative vacuum level shift probed by KPFM between the TMD and the substrate stays constant when passing from monolayer to bilayer graphene, which confirms that the Schottky-Mott model can be rigorously applied to these interfaces by taking into account the charge transfer from the substrate to the TMD. DFT calculations show that the first TMD layer absorbs almost all the excess charges contained in the graphene, and that the second TMD layer shall not play a significant role in the electrostatics of the system. Negatively charged defect at the TMD edges contribute however to the electrostatic landscape probed by KPFM on both TMD layers.

Thesaurus for off-label indications for systemic antifungal agents.

OBJECTIVES: Following the removal of temporary treatment protocol procedures, we developed a thesaurus for off-label indications for systemic antifungals at our facility to update clinical practices and to control off-label prescriptions. MATERIALS AND METHODS: Clinical practice guidelines and literature data were analyzed. This work was part of an antifungal stewardship program. RESULTS: Off-label wording (prophylaxis, preemptive, empirical, curative) and corresponding antifungals and references were validated by the multidisciplinary group for antifungal agents under the aegis of the Commission for the use of drugs and sterile medical devices and of the anti-infective committee. CONCLUSION: Considering the complexity of invasive fungal infection management, this thesaurus needs to be shared and used as a helping tool to review off-label situations.

Producción publica de biosimilares en Argentina / Biosimilars public production in Argentina

Los biosimilares tendrían igual indicación terapéutica y menores costos dedesarrollo que los biofármacos originales. El aumento de su oferta mejoraríala eficiencia y accesibilidad, pero en Argentina este mercado define preciosiguales o superiores a las drogas originales. Una alternativa sería incentivar laoferta desde la producción pública, basada en desarrollos científicos institucionalesexistentes en Santa Fe, con sinergias entre empresas incubadas en laUniversidad Nacional del Litoral y el Laboratorio Industrial Farmacéutico paraabastecer al Ministerio de Salud y a la obra social provincial.ObjetivosEvaluar el impacto potencial de un programa de biosimilares de producciónpública, con alcance provincial o nacional, definiendo viabilidad presupuestaria,sinergia institucional, accesibilidad y regulación de mercado.MétodosSe realizó un análisis cuantitativo de impacto presupuestario basado en consumosy gastos de las coberturas citadas sobre eritropoyetina, interferón yfilgrastim. Se trabajó con distintos esquemas de sustitución, considerandoahorros y nuevos costos (inversión, seguimiento) con horizonte a cinco añospara escala provincial y nacional. Se complementó con encuestas/entrevistascualitativas a representantes de subsectores sanitarios.ResultadosLa eritropoyetina y el filgrastim se mostraron rentables a tasas de sustituciónactivas (>30%) a nivel provincial y nacional. Los sectores público, de seguridadsocial y académico/científico estimaron posible la implementación de estassinergias con distintos ajustes, con potencial impacto en la accesibilidad y elmercado, mientras que el sector privado desestimó su real alcance.ConclusionesLos modelos propuestos evidenciaron márgenes de factibilidad presupuestariasegún el alcance (provincial o nacional), el biofármaco considerado y lastasas de sustitución supuestas. Con excepción del sector privado, los demásrevelaron cualitativamente un impacto positivo de la propuesta estudiada.

[Management of outpatient medications in care units: An audit of clinical practices]. / Traitement personnel du patient hospitalisé : audit de pratiques.

OBJECTIVES: To assess the outpatient medication management in care units two years after the release of an institutional procedure. To assess the patients' satisfaction with their treatment and with the information transmitted by healthcare professionals. METHODS: An audit of clinical practices was conducted in 23 units of our universitary hospital - general, surgery, emergency departments. Questionnaires were developed and validated by an institutional working group and were composed of three themes: management of the outpatient medication at the admission, awareness of tools and information transmission. Two physicians (a senior and a resident), a registered nurse, a head nurse and a patient were interviewed. RESULTS: Eighty-one medical and paramedical team members and 21 patients were interviewed for the study. According to statements collected, the procedure was unknown by 100% of the interviewed surgeons and 69% of the interviewed physicians. The practices being used by the medical units were more in line with recommendations than the surgery units. Among the patients interviewed, 19 (86%) were satisfied with the information they received during their hospitalization and 4 (19%) managed their own medication treatment with the help of a nurse in only 36% of the cases according to their statements. CONCLUSIONS: The management of outpatient medications during hospitalization is representative of the difficulties to master the continuity of pharmaceutical care at the various transition points. Coordination and cooperation between the different healthcare professionals and patients are the major key success to ensure an optimized healthcare procedure.

[Integration of a hospital pharmacist in the ICU]. / Intégration d'un pharmacien hospitalier en service de réanimation.

The French regulatory system strongly encourages strict regulation of health products' production and distribution, especially concerning risk management and economic aspects. An ICU is an unusual environment for a local pharmacy practice (a nurse for every 2.5 patients, continuous adaptation of therapeutics…). However, a literature review reports interesting data concerning risk management and economics. This article aims to relate the experience of a pharmacist integration in a French teaching hospital ICU (half-time position).

[Sonographic cerebral sulcal pattern in normal fetuses]. / Repères échographiques de gyration cérébrale foetale normale.

PURPOSE: Define normal sulcation patterns and their chronological order of appearance on transabdominal ultrasound by comparing them with brain maturation references available in fetopathological studies and MRI findings. PATIENTS AND METHODS: By means of a prospective study, 158 normal fetal brains aged 21 to 34 gestational weeks have been analyzed with standardized data by transabdominal ultrasound in eleven different views using axial, coronal and sagittal orientation. RESULTS: The sequential development of cerebral sulci has been described according to the gestational age. This chronology was consistent with anatomo-pathologic references presenting a mean late period of one week and with MRI but without any late period. This study is available on the following website: CONCLUSION: This ultrasound study provides accurate landmarks and imaging features of normal fetal brain sulcation. The analysis and the knowledge of this sulcation provide better understanding of the brain cortex maturation and may be helpful in diagnosing brain diseases.

Prenatal diagnosis of trisomy 21 by i(21q): a rare case of fetoplacental chromosomal discrepancy.

OBJECTIVE: A study was conducted to explain the mechanism of an unusual discrepancy between short- and long-term culture examination methods of chorionic villus sampling (CVS). METHOD: In a 29-year-old Caucasian woman, transabdominal CVS was carried out at 12 weeks of gestation. Non-mosaic karyotype 46,XX,i(21q) was found on long-term CVS culture but number and morphology of chromosomes were normal on short-term culture, amniocyte culture, hygroma colli fluid and fetal fibroblast. RESULTS: Chromosomal aberration probably appeared after the trophoblast cell line differentiation, four days after fertilization, by means of a 21 centromere misdivision and formation of a i(21q) with secondary positive selection of the 46,XX,i(21q) cell line and loss of the 46,XX in the fetus. CONCLUSION: The restricted number of cases with this type of discrepancy limits the possibility of drawing generalised conclusions. In case of discrepancy, we recommend confirmation by amniocentesis or by fetal blood combined with sonographic examination to provide a more definitive diagnosis.

Chromosomal defects and associated malformations in fetal cleft lip with or without cleft palate.

OBJECTIVE: To describe the incidence, associated features including chromosomal defects in fetuses, with cleft lip and/or palate and assess the need for karyotyping. METHODS: Retrospective study of 62 cases of prenatally diagnosed facial cleft lip and/or palate in a tertiary fetal medicine unit between January 1991 and December 1999. Chromosome analysis was performed in all fetuses with associated ultrasound findings and in 14 (39%) fetuses with isolated facial clefts. RESULTS: Associated abnormalities were detected in 26 (42%) of the 62 fetuses of which 22 (35%) fetuses had multiple other abnormalities. Central nervous system abnormalities and limb malformations were the most common. Three fetuses had genetic syndromes confirmed after birth. All fetuses with isolated clefts were chromosomally normal, whereas 15 of the 26 with additional abnormalities (58 or 24% of the total group) had chromosomal defects (eight cases of trisomy 13, five of trisomy 18, one unbalanced translocation between chromosomes 7 and 8, and one deletion 4p-). All 22 women who chose not to undergo fetal karyotype analysis delivered phenotypically normal infants. There were five midline clefts; each of them was associated with additional sonographic findings and four were associated with holoprosencephaly. CONCLUSION: Isolated facial clefting is not associated with an increased risk for chromosomal defect. Amniocentesis is recommended when facial cleft is found in association with additional ultrasonographic abnormalities as it is unnecessary for isolated clefts.

[Problems posed by the diagnosis and prenatal management of facial clefts]. / Problèmes posés par le diagnostic et la prise en charge prénatale des fentes faciales.

OBJECTIVE: To identify the difficulties in relation to prenatal diagnosis of cleft lip and/or palate. To provide useful clue to the clinician in order to evaluate prognosis and for prenatal management of this malformation. PATIENTS AND METHODS: Retrospective study of all cases managed in our fetal medicine unit between January 1991 and December 1999. During this study period 64 cases of fetal cleft lip and/or palate were retrospectively reviewed. From June 1995, all cases were prospectively recorded, giving us the opportunity to compare the performance of three ultrasound signs for associated secondary cleft palate. RESULTS: The mean gestational age at diagnosis was 26 weeks. Associated ultrasound abnormalities were detected in 42% of cases. Chromosome analysis was performed in all fetuses with associated ultrasound findings and in 39% of fetuses with isolated facial clefts. All fetuses with isolated cleft were chromosomally normal, whereas 15 of the 26 with additional abnormalities had chromosomal defects. Prospective assessment of three ultrasound signs of associated secondary cleft palate was considered possible in 57% of facial clefts. Sensitivity of these signs was respectively 78% (interruption of the secondary palate midline linear echo in a sagittal view), 87% (abnormal oro-nasopharyngeal fluid flow with color Doppler imaging) and 31% for ancillary signs (amniotic fluid excess and non-visualized fetal stomach) for the prediction of associated cleft palate. Only the absence of the three signs to rule out secondary cleft palate. CONCLUSION: Prenatal diagnosis of cleft lip and/or palate must draw attention to associated sonographic malformations. When cleft lip and/or palate is isolated, amniocentesis is recommended apart from selected cases. Secondary palate involvement is difficult to ascertain during pregnancy.

Prenatal ultrasonographic diagnosis of the popliteal pterygium syndrome.

The prenatal ultrasound identification of a cleft lip and palate, equinovarus feet with severe lower limb malposition and genital abnormalities led to the prenatal diagnosis of popliteal pterygium syndrome in a pregnant mother suspected to have a mild expression of this autosomal dominant condition. However, in sporadic cases with lack of a family history for this rare syndrome, prenatal diagnosis may be difficult to ascertain.

[Prevalence and distribution of congenital heart diseases in Indre-et-Loire. Evaluation of prenatal diagnosis (1991-1994)]. / Prévalence et répartition des cardiopathies congénitales en Indre-et-Loire. Evaluation du diagnostic anténatal (1991-1994).

UNLABELLED: Congenital heart diseases are the most frequent malformation at birth. New technologies have improved diagnosis procedures (echocardiography and Doppler). The aim of our study was to evaluate the prevalence of congenital heart diseases, their different types, and the detection rate of antenatal diagnosis. METHODS: A retrospective study was performed for all infants with congenital heart disease (CHD), born between January 1st 1991 and December 31st 1994, and for all fetuses which died after disruption of pregnancy, in Indre-et-Loire (a French country). In all cases, CHD diagnosis was confirmed with echocardiography and Doppler. RESULTS: CHD prevalence in newborns was 9.8% and 10.4% for the total population including dead fetal material. A high proportion of septal defects (64.8%) was observed with muscular, isolated and small forms (< 3 mm) in 70.2% of cases. The prevalence of great vessels transposition (0.15%), left ventricular hypoplasia (0.11%), and atrioventricular septal defect (0.11%), were lower than in previous studies. The performance of antenatal diagnosis was estimated at 40.5% for the four years; the prevalence of detectable CHD was only 1.4/1000. The atrioventricular septal defect was the most frequently detected. CONCLUSION: Relative high prevalence of congenital heart disease in this French county is due to the high level of small septal defects. Prevalence of detectable CHD remains low, which explains in part the difficulties of improving the antenatal diagnosis.

Cellular signalling and free-radical modulating activities of the novel peptidomimetic L-glutamyl-histamine.

A novel histamine-containing peptidomimetic, L-glutamyl-histamine (L-Glu-Hist), has been synthesized and characterized as a possible cytokine mimic which might lead to cellular responses of improved specificity. The energy-minimized 3-D conformations of L-Glu-Hist derived from its chemical structure stabilize Fe2+-chelating complexes. L-Glu-Hist concentration-dependently accelerates a decrease in ferrous iron in ferrous sulfate solution and shows ferroxidase-like activity at concentrations less than 3 mM in the phenanthroline assay, whereas in the concentration range 3-20 mM it restricts the availability of Fe2+ to phenanthroline by chelation of iron ions. At low concentrations (less than or about 1 mM), L-Glu-Hist stimulates peroxidation of phosphatidylcholine in liposomes catalyzed by a superoxide anion radical (O2)-generating system (Fe2+ + ascorbate) and, at high concentrations (*10 mM), it suppresses lipid peroxidation (LPO) in liposomes. The stimulation of LPO by L-Glu-Hist is related to its ability at low concentrations (*0.05 mM) to release O2 free radicals as determined by the superoxide dismutase-inhibitable reduction of cytochrome c. The release of O2 by L-Glu-Hist might result from its ferroxidase-like activity, while its inhibition of LPO is due to chelation of Fe2+, prevention of the formation of free radicals, and degradation of lipid hydroperoxides at 5-20 mM L-Glu-Hist concentrations. L-Glu-Hist releases O2 at concentrations which stimulate [3H]thymidine incorporation into DNA and proliferation of mouse spleen lymphocytes and also of mononuclear cells from human blood. The induction of lymphocyte proliferation by L-Glu-Hist is dose-dependent in the 0.01-0.05 mM concentration range, although the maximal stimulation of LPO in the O2-dependent system is observed at higher L-Glu-Hist concentrations (*1 mM). Thus, low concentrations of oxygen free radicals released by L-Glu-Hist may provide a very fast, specific, and sensitive trigger for lymphocyte proliferation and immunoregulation.

[Prenatal diagnosis of anomalies of the corpus callosum with ultrasound: the echographist's point of view]. / Diagnostic prénatal des anomalies du corps calleux par les ultrasons: le point de vue de l'échographiste.

Ultrasonography can identify agenesis of the corpus callosum (excluding holoprosencephaly which an be detected earlier on) in the second trimester of pregnancy (18-20 weeks gestation). Diagnosis of corpus callosum agenesis is difficult but is important as a risk factor for neurological or genetic malformations. The characteristic signs suggestive of corpus callosum agenesis are: moderate distension of the occipital ventricle and the ventricular communications; absence of the spectrum giving rise to an upward displacement of the third ventricle shown in the anterior coronal section (especially in transvaginal ultrasonography); radial position of the fissures on the internal side of the cerebral hemisphere seen on the sagittal section; the absence in color coded Doppler of the pericallosal artery normally characterised by a semicircular vessel observable on the median sagittal section. At present, color coded Doppler should give the diagnosis of corpus callosum agenesis. MRI can provide further information especially in case of late detection around 28-30 weeks gestation as is most frequently the case. The development of 3D echographic imaging should allow an even more sophisticated approach to this diagnosis giving even more precise prognosis. Isolated corpus callosum agenesis is compatible with normal intellectual development an raises an important problem with regard to pregnancy continuation and infant development. Each individual case should be discussed during the pluridisciplinary prenatal diagnostic discussion.

Diagnosis of photosensitivity to flupenthixol by photoprick testing.

We report the case of a 38-year-old patient with an erythematous eruption, initially confined to photo-exposed areas and then becoming more generalized, which was attributable to flupenthixol, a thioxanthene derivative used for its neuroleptic properties. The compound has the same polycyclic aromatic hydrocarbons as phenothiazines, but without any cross-reaction in our patient. A photoallergic cause for the eruption was verified on clinical, histological and photobiologic grounds. Photopatch tests were negative, but photoprick testing was positive after UV irradiation of the test site. Photopatch test methods using better skin penetration have been already reported for testing drug photosensitivity. Photoprick testing combines better penetration with greater ease of use.

Etiology, prognosis and management of nuchal cystic hygroma: 25 new cases and literature review.

OBJECTIVE: To develop an algorithm for the prenatal management of patients when a cystic hygroma is diagnosed by ultrasonography. METHODS: We report a personal series of 25 cases diagnosed between 10 and 23 weeks gestation and a review of the literature comprising a total of 999 cases. We focused on the etiologies and the value of various prognostic factors in the management of cystic hygromas. These include karyotype, alpha-fetoprotein levels, sonographic findings in the fetus and within the hygroma itself, and natural history. RESULTS: According to the literature, fetal chromosomal abnormalities were associated with cystic hygromas in 62% of the cases. Turner's syndrome remains the most common (33%) but Down's syndrome, Trisomy 18 and Trisomy 13 are not rare (15, 7 and 2%). Others have Mendelian abnormalities. The prognosis remains gloomy. The literature reports that only 9% of cases result in healthy children with normal karyotypes. The remaining 91% are either terminated (89%) or liveborn (2%), but with chromosome abnormalities or various malformations. CONCLUSION: The prognostic factors associated with a poor outcome are an abnormal karyotype and associated structural malformations. Resolution of the hygroma by 20 weeks gestation suggests a good prognosis, but is not definitive. All other factors evaluated do not appear to be of prognostic value at this time. Careful analysis of these prognostic factors is very important to identify the small percentage of normal children and to advise parents effectively for a future pregnancy.

Prenatal diagnosis of trisomy 8 mosaicism in CVS after abnormal ultrasound findings at 12 weeks.

We describe a case of trisomy 8 mosaicism in which fetal chromosome analysis was prompted by ultrasound abnormalities, i.e., hygroma colli and dilatation of the renal pelves. Chorionic villus sampling (CVS) was performed, with a false-negative result on direct karyotype analysis, although cultured trophoblasts revealed trisomy 8 mosaicism. Fetal autopsy confirmed the abnormalities found on ultrasound examinations and fetal tissue examination showed different levels of trisomy 8 mosaicism. To our knowledge, this is the first prenatal diagnosis of trisomy 8 made on ultrasound findings.

[Fetal cerebral accident due to massive fetomaternal hemorrhage. A case report]. / Accident cérébral foetal par hémorragie foetomaternelle massive. Un cas.

Massive fetomaternal haemorrhage (FMH) occurs in 0.12 to 0.5% of pregnancies. It is most often spontaneous and involves uncomplicated near-term pregnancies. It causes fetal anaemia, with or without fetal distress and hydrops fetalis. To our knowledge only one paper has reported a neurological complication (hemiplegia). We describe one case of FMH (maximal Kleihauer test = 6.5%) at 28 weeks gestation, which was spontaneous, reversible, associated with sinusoidal fetal heart rare (FHR) and hydrops fetalis; and complicated by an intraventricular antenatal haemorrhage at 30 weeks gestation. Echographic abnormalities decreased. The infant was born at 40 weeks gestation. Clinical examination was normal during the first week of life. At the age of 4 1/2 months, examination showed axial hypotonia and moderated dilatation of intracerebral lateral ventricules without any other brain damage. At the age of 24 months, the child had retarded walking and hypotonia. The outcome was spontaneously favourable with disappearance in utero of the intraventricular haemorrhage (HIV), without hydrocephalia or ischaemic lesions. Three cases of similar FMH have been reported but none of them described cerebral complications. Intrauterine intravascular transfusion should be proposed early. No single pathophysiological mechanism of FMH has been universally accepted and there is no aetiological treatment. The risk of recurrence of FMH in later pregnancies requires careful follow-up.

[Ethical problems raised by the current French practice of therapeutic abortions. Part I: prospective study for 24 months at the University Hospital of Tours (76 cases)]. / Problèmes éthiques soulevés par les pratiques françaises actuelles de l'interruption médicale de grossesse. 1re Partie: Etude prospective sur 24 mois au CHU de Tours (76 cas).

OBJECTIVE: Determine the circumstances and conditions concerning ethical problems raised by medical abortions treated in a University hospital. METHODS: Prospective study for 2 years (1 Sept 1991--31 Aug 1993) conducted with a consulting Committee for the antenatal diagnosis and fetal medicine at the University Hospital at Tours. Each discussion of the medical file for proposed medical abortions, the conditions leading to the decision and the ethical recommendations formulated were registered as well as the outcome of the pregnancy and for the infant. RESULTS: There were 76 cases raising ethical problems. They were divided into 3 categories of recommendations: medical abortion (55 cases), abstention with acceptation of possible fetal death in utero (11 cases), conservation of the pregnancy (10 cases). CONCLUSION: A practical attitude could usually be decided after discussion between parents and physicians. A few cases of disagreement were observed which led to uncertainty [correction of incertainty] and diverging opinions concerning the diagnosis and prognosis for the fetal pathology.

Inflammatory linear verrucous epidermal naevus with auto-immune thyroiditis: coexistence of two auto-immune epithelial inflammations?

We report a patient with an inflammatory linear verrucous epidermal naevus (ILVEN) coexisting with an auto-immune lymphocytic thyroiditis. The occurrence of two epithelial inflammatory processes could be linked and raises the question of auto-immune involvement in the inflammatory part of ILVEN. Moreover, expression of a membrane antigen, OKM5, usually assigned to antigen-presenting cells, especially macrophages, has been demonstrated on keratinocytes in some dermatological diseases including ILVEN. These data suggest that keratinocytes in ILVEN could present some antigens and perhaps auto-antigens modified by the hamartomatous process, leading to an (auto-immune?) inflammatory reaction.