Thomas Schmitz
Charité
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Featured researches published by Thomas Schmitz.
European Journal of Obstetrics & Gynecology and Reproductive Biology | 2011
Christophe Vayssiere; Guillaume Benoist; Béatrice Blondel; Philippe Deruelle; Romain Favre; Denis Gallot; Paul Jabert; D. Lemery; Olivier Picone; Jean-Claude Pons; F. Puech; E. Quarello; L. J. Salomon; Thomas Schmitz; Marie-Victoire Senat; Loïc Sentilhes; Agnes Simon; Julien Stirneman; F. Vendittelli; Norbert Winer; Yves Ville
The rate of twin deliveries in 2008 was 15.6 per 1000 in France, an increase of approximately 80% since the beginning of the 1970s. It is recommended that chorionicity be diagnosed as early as possible in twin pregnancies (Professional Consensus). The most relevant signs (close to 100%) are the number of gestational sacs between 7 and 10 weeks and the presence of a lambda sign between 11 and 14 weeks (Professional Consensus). In twin pregnancies, nuchal translucency is the best parameter for evaluating the risk of aneuploidy (Level B). The routine use of serum markers during the first or the second trimester is not recommended (Professional Consensus). In the case of a choice about sampling methods, chorionic villus sampling is recommended over amniocentesis (Professional Consensus). Monthly follow-up by a gynaecologist-obstetrician in an appropriate facility is recommended for dichorionic pregnancies (Professional Consensus). A monthly ultrasound examination including an estimation of fetal weight and umbilical artery Doppler is recommended (Professional Consensus). It is recommended to plan delivery of uncomplicated dichorionic diamniotic twin pregnancies from 38 weeks and before 40 weeks (Level C). Monthly prenatal consultations and twice-monthly ultrasound are recommended for monochorionic twins (Professional Consensus). It is reasonable to consider delivery from 36 weeks but before 38 weeks+6 days, with intensified monitoring during that time (Professional Consensus). Prenatal care of monochorionic pregnancies must be provided by a physician working in close collaboration with a facility experienced in the management of this type of pregnancy and its complications (Professional Consensus). The increased risk of maternal complications and the high rate of medical interventions justify the immediate and permanent availability of a gynaecologist-obstetrician with experience in the vaginal delivery of twins (Professional Consensus). It is recommended that the maternity ward where delivery takes place have rapid access to blood products (Professional Consensus). Only obstetric history (history of preterm delivery) (Level C) and transvaginal ultrasound measurement of cervical length (Level B) are predictive factors for preterm delivery. No study has shown that the identification by transvaginal sonography (TVS) of a group at risk of preterm delivery makes it possible to reduce the frequency of such deliveries in asymptomatic patients carrying twins (Professional Consensus). It is important to recognize signs of TTTS early to improve the management of these pregnancies (Professional Consensus). Treatment and counseling must be performed in a center that can offer fetoscopic laser coagulation of placental anastomoses (Professional Consensus). This laser treatment is the first-line treatment (Level B). In the absence of complications after laser treatment, planned delivery is recommended from 34 weeks and no later than 37 weeks (Professional Consensus). For delivery, it is desirable for women with a twin pregnancy to have epidural analgesia (Professional Consensus). The studies about the question of mode of delivery have methodological limitations and lack of power. Active management of the delivery of the second twin is recommended to reduce the interval between the births of the two twins (Level C). In the case of non-cephalic presentation, total breech extraction, preceded by internal version manoeuvres if the twins position is transverse, is associated with the lowest cesarean rates for second twins (Level C). In the case of high and not yet engaged cephalic presentation and if the team is appropriately trained, version by internal manoeuvres followed by total breech extraction is to be preferred to a combination of resumption of pushing, oxytocin perfusion, and artificial rupture of the membranes, because the former strategy appears to be associated with fewer cesareans for the second twin (Level C).
European Journal of Obstetrics & Gynecology and Reproductive Biology | 2013
Loïc Sentilhes; Christophe Vayssière; Gael Beucher; Catherine Deneux-Tharaux; Philippe Deruelle; Pierre Diemunsch; Denis Gallot; Jean-Baptiste Haumonte; Sonia Heimann; Gilles Kayem; Emmanuel Lopez; Olivier Parant; Thomas Schmitz; Yann Sellier; Patrick Rozenberg; Claude D'Ercole
The primary cause of uterine scars is a previous cesarean. In women with a previous cesarean, the risks of maternal complications are rare and similar after a trial of labor after cesarean (TOLAC) and after an elective repeat cesarean delivery (ERCD), but the risk of uterine rupture is higher with TOLAC (level of evidence [LE]2). Maternal morbidity in women with previous cesareans is higher when TOLAC fails than when it leads to successful vaginal delivery (LE2). Although maternal morbidity increases progressively with the number of ERCD, maternal morbidity of TOLAC decreases with the number of successful previous TOLAC (LE2). The risk-benefit ratio considering the risks of short- and long-term maternal complications is favorable to TOLAC in most cases (LE3). Globally, neonatal complications are rare regardless of the mode of delivery for women with previous cesareans. The risks of fetal, perinatal, and neonatal mortality during TOLAC are low. Nonetheless, these risks are significantly higher than those associated with ERCD (LE2). The risks of mask ventilation, intubation for meconium-stained amniotic fluid, and neonatal sepsis all increase in TOLAC (LE2). The risk of transient respiratory distress increases in ERCD (LE2). To reduce this risk, and except in particular situations, ERCD must not be performed before 39 weeks (grade B). TOLAC is possible for women with a previous cesarean before 37 weeks, with 2 previous cesareans, with a uterine malformation, a low vertical incision or an unknown incision, with a myomectomy, postpartum fever, an interval of less than 6 months between the last cesarean delivery and the conception of the following pregnancy, if the obstetric conditions are favorable (professional consensus). ERCD is recommended in women with a scar in the uterine body (grade B) and a history of 3 or more cesareans (professional consensus). Ultrasound assessment of the risk of uterine rupture in women with uterine scars has not been shown to have any clinical utility and is therefore not recommended during pregnancy to help decide the mode of delivery (professional consensus). Use of X-ray pelvimetry to decide about TOLAC is associated with an increase in the repeat cesarean rate without any reduction in the rate of uterine rupture (LE2). It is unnecessary for deciding mode of delivery and for managing labor during TOLAC (grade C). TOLAC should be encouraged for women with a previous vaginal delivery either before or after the cesarean, a favorable Bishop score or spontaneous labor, and for preterm births (grade C). For women with a fetus with an estimated weight of more than 4500 g, especially in the absence of a previous vaginal delivery and those with supermorbid obesity (BMI>50), ERCD must be planned from the outset (grade C). For all of the other clinical situations envisioned (maternal age>35 years, diabetes, morbid obesity, prolonged pregnancy, breech presentation and twin pregnancy), TOLAC is possible but the available data do not allow specific guidelines about the choice of mode of delivery, in view of the low levels of proof (grade C). The decision about planned mode of delivery must be shared by the patient and her physician and made by the 8th month, taking into account the individual risk factors for TOLAC failure and uterine rupture (professional consensus). TOLAC is the preferred choice for women who do not have several risk factors (professional consensus). The availability onsite of an obstetrician and anesthetist must be pointed out to the patient. If the woman continues to prefer a repeat cesarean after adequate information and time to think about it, her preference should be honored (professional consensus). Labor should be induced in woman with a previous cesarean only for medical indications (professional consensus). Induction of labor increases the risk of uterine rupture, which can be estimated at 1% if oxytocin is used and 2% with vaginal prostaglandins (LE2). Mechanical methods of induction have not been studied sufficiently. Misoprostol appears to increase the risk of uterine rupture strongly (LE4). Based on the information now available, its use is not recommended (professional consensus). Routine use of internal tocodynamometry does not prevent uterine rupture (professional consensus). The increased risk of uterine rupture associated with oxytocin use is dose-dependent (LE3). In the active phase, it is recommended that the total duration of failure to progress should not exceed 3h; at that point, a cesarean should be performed (professional consensus). Epidural analgesia must be encouraged. The simple existence of a uterine scar is not an indication for a routine manual uterine examination after VBAC (grade C).
European Respiratory Journal | 2013
Ulrike Weichelt; Ruhuye Cay; Thomas Schmitz; Evelyn Strauss; Marco Sifringer; Christoph Bührer; Stefanie Endesfelder
In preterm human infants, briefly elevated concentrations of oxygen are associated with a prolonged increase in blood chemokine concentrations and the development of bronchopulmonary dysplasia (BPD). Caffeine given to preterm infants for the prevention or treatment of apnoea has been shown to reduce the rate of BPD. We tested the hypotheses that infant rats exposed to a combination of caffeine and hyperoxia would be less susceptible to lung injury than those exposed to hyperoxia alone and that caffeine decreases the pulmonary tissue expression of chemokines and leukocyte influx following hyperoxia. Using 6-day-old rat pups, we demonstrated that 24 h of 80% oxygen exposure caused pulmonary recruitment of neutrophils and macrophages. High levels of oxygen upregulated the expression of: the CXC chemokines, cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2; the CC-chemokine monocyte chemoattractant protein-1; the pro-inflammatory cytokines tumour necrosis factor-&agr; and interleukin-6, as measured by realtime PCR after the administration of caffeine (10 mg·kg−1 body weight); and attenuated chemokine and cytokine upregulation, as well as the influx of CD11b+, ED-1+ and myeloperoxidase+ leukocytes. These experiments suggest that protective effects of caffeine in the neonatal lung are mediated, at least in part, by reduction of pulmonary inflammation.
The Journal of Neuroscience | 2011
Thomas Schmitz; Jonathan Ritter; Susanne Mueller; Ursula Felderhoff-Mueser; Li-Jin Chew; Vittorio Gallo
Impaired neurological development in premature infants frequently arises from periventricular white matter injury (PWMI), a condition associated with myelination abnormalities. Recently, exposure to hyperoxia was reported to disrupt myelin formation in neonatal rats. To identify the causes of hyperoxia-induced PWMI, we characterized cellular changes in the white matter (WM) using neonatal wild-type, 2–3-cyclic nucleotide 3-phosphodiesterase–enhanced green fluorescent protein (EGFP) and glial fibrillary acidic protein (GFAP)–EGFP transgenic mice exposed to 48 h of 80% oxygen from postnatal day 6 (P6) to P8. Myelin basic protein expression and CC1+ oligodendroglia decreased after hyperoxia at P8, but returned to control levels during recovery between P12 and P15. At P8, hyperoxia caused apoptosis of NG2+O4− progenitor cells and reduced NG2+ cell proliferation. This was followed by restoration of the NG2+ cell population and increased oligodendrogenesis in the WM after recovery. Despite apparent cellular recovery, diffusion tensor imaging revealed WM deficiencies at P30 and P60. Hyperoxia did not affect survival or proliferation of astrocytes in vivo, but modified GFAP and glutamate-aspartate transporter expression. The rate of [3H]-d-aspartic acid uptake in WM tissue was also decreased at P8 and P12. Furthermore, cultured astrocytes exposed to hyperoxia showed a reduced capacity to protect oligodendrocyte progenitor cells against the toxic effects of exogenous glutamate. This effect was prevented by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide treatment. Our analysis reveals a role for altered glutamate homeostasis in hyperoxia-induced WM damage. Understanding the cellular dynamics and underlying mechanisms involved in hyperoxia-induced PWMI will allow for future targeted therapeutic intervention.
The Journal of Neuroscience | 2013
Jonathan Ritter; Thomas Schmitz; Li-Jin J. Chew; Christoph Bührer; Wiebke Möbius; Marzieh Zonouzi; Vittorio Gallo
The pathological mechanisms underlying neurological deficits observed in individuals born prematurely are not completely understood. A common form of injury in the preterm population is periventricular white matter injury (PWMI), a pathology associated with impaired brain development. To mitigate or eliminate PWMI, there is an urgent need to understand the pathological mechanism(s) involved on a neurobiological, structural, and functional level. Recent clinical data suggest that a percentage of premature infants experience relative hyperoxia. Using a hyperoxic model of premature brain injury, we have previously demonstrated that neonatal hyperoxia exposure in the mouse disrupts development of the white matter (WM) by delaying the maturation of the oligodendroglial lineage. In the present study, we address the question of how hyperoxia-induced alterations in WM development affect overall WM integrity and axonal function. We show that neonatal hyperoxia causes ultrastructural changes, including: myelination abnormalities (i.e., reduced myelin thickness and abnormal extramyelin loops) and axonopathy (i.e., altered neurofilament phosphorylation, paranodal defects, and changes in node of Ranvier number and structure). This disruption of axon–oligodendrocyte integrity results in the lasting impairment of conduction properties in the adult WM. Understanding the pathology of premature PWMI injury will allow for the development of interventional strategies to preserve WM integrity and function.
Pediatric Research | 2007
Thomas Schmitz; Axel Heep; Floris Groenendaal; Dieter Hüseman; Susanne Kie; Peter Bartmann; Michael Obladen; Ursula Felderhoff-Müser
Posthemorrhagic hydrocephalus (PHHC) represents a major complication of preterm birth. The aim of this study was to determine whether cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines IL-1β, IL-18, and interferon (IFN)-γ are altered in the CSF of preterm infants with PHHC and may serve as a marker of white matter damage (WMD). Twenty-seven preterm infants with PHHC were included in the study; 13 of them had signs of cystic WMD (cWMD) on ultrasound examinations. CSF sample 1 was obtained at first ventriculostomy, sample 2 at shunt implantation. Results were compared with a control group of 20 age-matched patients without neurologic diseases. IL-1β concentrations were elevated in CSF sample 1 of PHHC patients without WMD and in sample 1 of patients with cWMD. Concentrations of IL-18 were increased in both samples of patients without WMD and in sample 2 of patients with cWMD. CSF levels of IFN-γ were elevated in sample 1 of PHHC patients with cWMD. The pro-inflammatory cytokine IL-1β and IL-18 levels in the CSF are elevated in patients with PHHC. Higher IFN-γ levels are detected in a subgroup of patients developing cWMD, indicating its involvement in the pathogenesis of cWMD in the context of PHHC.
Free Radical Biology and Medicine | 2014
Stefanie Endesfelder; Irina Zaak; Ulrike Weichelt; Christoph Bührer; Thomas Schmitz
Caffeine administered to preterm infants has been shown to reduce rates of cerebral palsy and cognitive delay, compared to placebo. We investigated the neuroprotective potential of caffeine for the developing brain in a neonatal rat model featuring transient systemic hyperoxia. Using 6-day-old rat pups, we found that after 24 and 48h of 80% oxygen exposure, apoptotic (TUNEL(+)) cell numbers increased in the cortex, hippocampus, and central gray matter, but not in the hippocampus or dentate gyrus. In the dentate gyrus, high oxygen exposure led to a decrease in the number of proliferating (Ki67(+)) cells and the number of Ki67(+) cells double staining for nestin (immature neurons), doublecortin (progenitors), and NeuN (mature neurons). Absolute numbers of nestin(+), doublecortin(+), and NeuN(+) cells also decreased after hyperoxia. This was mirrored in a decline of transcription factors expressed in immature neurons (Pax6, Sox2), progenitors (Tbr2), and mature neurons (Prox1, Tbr1). Administration of a single dose of caffeine (10mg/kg) before high oxygen exposure almost completely prevented these effects. Our findings suggest that caffeine exerts protection for neonatal neurons exposed to high oxygen, possibly via its antioxidant capacity.
Experimental Neurology | 2014
Thomas Schmitz; Grietje Krabbe; Georg Weikert; Till Scheuer; Friederike Matheus; Yan Wang; Susanne Mueller; Helmut Kettenmann; Vitali Matyash; Christoph Bührer; Stefanie Endesfelder
Poor neurological outcome in preterm infants is associated with periventricular white matter damage and hypomyelination, often caused by perinatal inflammation, hypoxia-ischemia, and hyperoxia. Minocycline has been demonstrated in animal models to protect the immature brain against inflammation and hypoxia-ischemia by microglial inhibition. Here we studied the effect of minocycline on white matter damage caused by hyperoxia. To mimic the 3- to 4-fold increase of oxygen tension caused by preterm birth, we have used the hyperoxia model in neonatal rats providing 24h exposure to 4-fold increased oxygen concentration (80% instead of 21% O2) from P6 to P7. We analyzed whether minocycline prevents activation of microglia and damage of oligodendroglial precursor cell development, and whether acute treatment of hyperoxia-exposed rats with minocycline improves long term white matter integrity. Minocycline administration during exposure to hyperoxia resulted in decreased apoptotic cell death and in improved proliferation and maturation of oligodendroglial precursor cells (OPC). Minocycline blocked changes in microglial morphology and IL-1β release induced by hyperoxia. In primary microglial cell cultures, minocycline inhibited cytokine release while in mono-cultures of OPCs, it improved survival and proliferation. Long term impairment of white matter diffusivity in MRI/DTI in P30 and P60 animals after neonatal hyperoxia was attenuated by minocycline. Minocycline protects white matter development against oxygen toxicity through direct protection of oligodendroglia and by microglial inhibition. This study moreover demonstrates long term benefits of minocycline on white matter integrity.
Journal of Neuroscience Research | 2012
Thomas Schmitz; Stefanie Endesfelder; Li-Jin Chew; Irina Zaak; Christoph Bührer
Ischemic brain injury is widely modeled in vitro with paradigms of oxygen‐glucose deprivation (OGD), which leads to cell death. The prevention and attenuation of brain injury by the tetracycline antibiotic minocycline has been attributed largely to suppression of microglial activation, but its benefits in oligodendrocyte cells have not been well characterized. Using primary cultures of rat oligodendroglial precursor cells (OPC) exposed to OGD, we investigated the direct effects of minocycline on the survival, proliferation, and maturation of oligodendroglial lineage cells. OGD for 2 hr caused a decrease in the total number of OPC and the amount of proliferating progenitors by 50%, which was attenuated by inclusion of minocycline. The reduced numbers of immature oligodendroglial cells at 72 hr and of mature oligodendrocytes at 120 hr after OGD were partially restored by minocycline. In OPC, OGD caused an increase of reactive oxygen species (ROS) and production of TUNEL‐positive cell numbers, which was abolished by minocycline. Minocycline preferentially increased the expression of superoxide dismutase under OGD but not in control OPC. Minocycline also prevented the OGD‐induced downregulation of the transcription factors Sox10 and Olig2 and of myelin‐specific genes 2′3′ cyclic nucleotide phosphodiesterase (CNP) and myelin basic protein (MBP) in response to OGD. These studies demonstrate direct protective actions of minocycline on oligodendroglial‐lineage cells, suggesting potential benefit in white matter injury involving OGD.
Experimental Neurology | 2012
Thomas Schmitz; Stefanie Endesfelder; Marie-Christine Reinert; Florian Klinker; Susanne Müller; Christoph Bührer; David Liebetanz
In preterm infants, the risk to develop attention-deficit/hyperactivity disorder is 3 to 4-fold higher than in term infants. Moreover, preterm infants exhibit deficits in motor coordination and balance. Based on clinical data, higher oxygen levels in preterm infants lead to worse neurological outcome, and experimental hyperoxia causes wide-ranging cerebral changes in neonatal rodents. We hypothesize that hyperoxia in the immature brain may affect motor activity in preterm infants. We subjected newborn mice from P6 to P8 to 48 h of hyperoxia (80% O(2)) and tested motor activity in running wheels starting at adolescent age P30. Subsequently, from P44 to P53, regular wheels were replaced by complex wheels with variable crossbar positions to assess motor coordination deficits. MRI with diffusion tensor imaging was performed in the corpus callosum to determine white matter diffusivity in mice after hyperoxia at ages P30 and P53 in comparison to control animals. Adolescent mice after neonatal hyperoxia revealed significantly higher values for maximum velocity and mean velocity in regular wheels than controls (P<0.05). In the complex running wheels, however, maximum velocity was decreased in animals after hyperoxia, as compared to controls (P<0.05). Decreased fractional anisotropy and increased radial diffusion coefficient were observed in the corpus callosum of P30 and P53 mice after neonatal hyperoxia compared to control mice. Hyperoxia in the immature brain causes hyperactivity, motor coordination deficits, and impaired white matter diffusivity in adolescent and young adult mice.