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Biomedical subjects

D Schneider

Publications and source records attributed to D Schneider.

At least 19 recordsLinked to original sources
PubMed2006

Cetuximab combined with radiotherapy: an alternative to chemoradiotherapy for patients with locally advanced squamous cell carcinomas of the head and neck?

Radiotherapy remains the foundation of current treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). It has been shown that the addition of concurrent chemotherapy to radiotherapy (chemoradiotherapy, CRT, or chemotherapy-enhanced radiation therapy, CERT) results in improved clinical outcome in terms of both locoregional control and overall survival in some groups of patients. However, CRT is associated with severe, dose-limiting acute toxicities and, in some patients, a higher proportion of late toxicities. In addition, most CRT regimens are platinum-based and there is evidence that the maximum tolerable toxicity has been reached with the dose intensities currently used in bolus cisplatin regimens. Therefore, if we are to further improve outcomes through increased treatment compliance, more effective and more tolerable regimens are needed. Recent results from a phase III randomised study demonstrate that the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux)given concomitantly with radiotherapy yields a significant clinical benefit over radiotherapy alone without any increase in radiotherapy-associated toxicity. In this review, we explore the question of the degree to which adding cetuximab improves the efficacy of radiotherapy in locally advanced SCCHN and how the benefits of cetuximab plus radiotherapy compare with those achievable with CRT.

Antibodies, Monoclonal↗
PubMed2006

Bisphosphonate-related jaw necrosis--severe complication in maxillofacial surgery.

Bisphosphonates are used as potent inhibitors in metastatic bone lesions. They can reduce skeletal burden and prevent bony metastases. They are integral in the treatment of some tumours like breast cancer, prostate cancer and multiple myeloma. As a side effect, these drugs also may cause severe jaw necrosis. Twenty-four patients with bisphosphonate-related jaw necrosis were analyzed in a clinical study. These necroses mostly appeared after administration of aminobisphosphonates. Recurrent avascular necroses were found after changing from Pramidronate to Zoledronate. All patients were treated by resection of necrotic bone. Repeated surgical interventions were required with about 25% of the patients. The management of patients with bisphosphonate-related jaw necrosis remains extremely difficult and includes surgical procedures as well as the eradicating of the necrotic bone including antibiotic therapy. The prevention of such complications consists in a minimization of dental surgical interventions and an avoidance of ulcers by dental prosthesis.

Bone Neoplasms↗
PubMed2006

Neuroprotective effects of the P2 receptor antagonist PPADS on focal cerebral ischaemia-induced injury in rats.

After acute injury of the central nervous system extracellular adenosine 5'-triphosphate (ATP) can reach high concentrations as a result of cell damage and subsequent increase in membrane permeability. Released ATP may act as a toxic agent, which causes cellular degeneration and death, mediated through P2X and P2Y receptors. Mechanisms underlying the various effects of purinoceptor modulators in models of cerebral damage are still uncertain. In the present study the effect of P2 receptor inhibition after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats was investigated. Rats received either the non-selective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) or artificial cerebrospinal fluid (ACSF) as control by the intracerebroventricular route. First, these treatments were administered 10 min before MCAO and subsequently twice daily for 1 or 7 days after MCAO. The functional recovery of motor and cognitive deficits was tested at an elevated T-labyrinth. The PPADS-treated group showed a significant reduction of paresis-induced sideslips compared with ACSF-treated animals. Infarct volume was reduced in the PPADS group in comparison with the ACSF group. A significant decrease in intermediately and profoundly injured cells in favour of intact cells in the PPADS group was revealed by quantification of celestine blue/acid fuchsin-stained cells in the peri-infarct area. The data provide further evidence for the involvement of P2 receptors in the pathophysiology of cerebral ischaemia in vivo. The inhibition of P2 receptors at least partially reduces functional and morphological deficits after an acute cerebral ischaemic event.

Animals↗
PubMed2006

Clinical practice evaluation of atosiban in preterm labour management in six European countries.

OBJECTIVE: To evaluate the efficacy and safety of early administration compared with standard administration of atosiban, when predefined eligibility criteria were met. DESIGN: A prospective, open-label, randomised clinical trial. Women were randomised to receive atosiban either immediately (early) or when specified criteria, in terms of duration/frequency of uterine contraction or status of cervical dilation/effacement, were fulfilled (standard). SETTING: Carried out at 105 centres in six European countries. POPULATION: Pregnant women admitted to hospital in threatened preterm labour between 24 and 34 weeks of gestation, comprising a subgroup of women enrolled in the Tractocile Efficacy Assessment Survey in Europe (TREASURE) clinical experience review. MAIN OUTCOME MEASURES: Efficacy was defined as the successful delay of delivery with no alternative tocolytic agent for 48 hours. RESULTS: More women in the early group remained undelivered at 48 hours with no alternative tocolytic agent compared with those who received atosiban when specified criteria were fulfilled (88.9 versus 76.1%; P = 0.03). Safety was comparable between the groups. There were no statistical differences in maternal, fetal or neonatal adverse events between the early and standard atosiban arms. CONCLUSIONS: The use of atosiban was effective for the delay of preterm labour and presented no safety concerns irrespective of the time it was administered.

Adolescent↗
PubMed2006

Low systemic exposure in infants with atopic dermatitis in a 1-year pharmacokinetic study with pimecrolimus cream 1%*.

Systemic drug exposure following the application of topical agents is a very important safety consideration, particularly in infants, who have a significantly higher ratio of body surface area to body mass than older children and adults. Here, we report on drug exposure in five infants aged 5.7-11.9 months at baseline, with extensive, moderate-to-severe atopic dermatitis (AD). Patients were treated bid for 1 year, as needed, with pimecrolimus cream 1% in an open-label, non-controlled study. No indication of drug accumulation was found; pimecrolimus blood concentrations were consistently low, ranging from below the limit of quantitation (0.1 ng/ml) to 1.94 ng/ml. Treatment over this prolonged period was well tolerated, with no evidence of any treatment-related adverse events. The results of this 1-year study indicate that long-term management of AD with pimecrolimus cream 1% is associated with consistently very low systemic absorption, even in the youngest patients with extensive disease.

Administration, Cutaneous↗
PubMed2005

Ambient temperature affects mechanosensory host location in a parasitic wasp.

Certain parasitic wasps (Ichneumonidae, Pimplinae) use self-produced vibrations transmitted on plant substrate to locate their immobile concealed hosts (i.e. lepidopteran pupae). This mechanosensory mechanism, called the vibrational sounding, depends both on physical cues of the environment and physical activity of the parasitoid and is postulated to depend on ambient temperature. We analysed the influences of temperature on vibrational sounding by choice experiments using plant-stem models with hidden host mimics in the temperate species Pimpla turionellae. The results show a significant effect of temperature on host-location activity and on the success of this process. Outside an optimum range, the performance of the wasps decreased both at low and high temperatures. Below 10 degrees C and beyond 24 degrees C, the wasps displayed (1) substantial reduction in responsiveness, i.e. proportion of females showing ovipositor insertions, (2) reduction of quantitative activity with ovipositor insertions in the individuals, and (3) reduced precision of mechanosensory host location. Nevertheless, female wasps were able to locate their host over a surprisingly broad range of ambient temperatures which indicates that the wasps are able to compensate for temperature effects on vibrational sounding.

Animals↗
PubMed2005

Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats.

This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in suspension on positively charged microcarriers (MCs). A tissue-engineered tubular scaffold, containing bundles of parallel nanofibers, was developed. Both the tube and the nanofibers were made of a biodegradable dextran sulphate-gelatin co-precipitate. The suturable scaffold anchored the implant at the site of injury and provided guidance for the regenerating axons. Implants of adult human NOM cells were implanted into eight rats, from which a 4 mm segment of the spinal cord had been completely removed. Another four rats whose spinal cords had also been transected were implanted with a composite implant of cultured human embryonic spinal cord cells. Eight other cord-transected rats served as a control group. Physiological and behavioral analysis, performed 3 months after implantation, revealed partial recovery of function in one or two limbs in three out of eight animals of the NOM implanted group and in all the four rats that were implanted with cultured human embryonic spinal cord cells. Animals of the control group remained completely paralyzed and did not show transmission of stimuli to the brain. The utilization of an innovative composite implant to bridge a gap resulting from the transection and removal of a 4 mm spinal cord segment shows promise, suggesting the feasibility of this approach for partial reconstruction of spinal cord lesions. Such an implant may serve as a vital bridging station in acute and chronic cases of paraplegia.

Animals↗
PubMed2005

A multicenter study of CA 125 level as a predictor of non-optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To provide a large database of pre-operative CA 125 levels which may predict inappropriate cytoreductive surgery in patients with advanced epithelial ovarian cancer. METHODS: A multicenter review of the records of 424 patients with FIGO stage III and IV epithelial ovarian cancer of patients who underwent primary cytoreductive surgery was performed. The validity of pre-operative CA 125 level measurement as a single predictor of the possibility to achieve only suboptimal cytoreduction was evaluated by calculating the sensitivity and the specificity of various cut-off values. The relative importance of different cut-off values in achieving the best predictive validity was assessed by a receiver operating characteristics (ROC) curve. RESULTS: Optimal cytoreduction (largest diameter of residual tumour < or =1 cm) was achieved in 242 patients. The median CA 125 level in optimally cytoreduced patients was lower than in those patients suboptimally debulked (304 vs 863 U/mL; p<0.001). The area under the ROC curve was 0.65 (95% confidence interval, 0.60-0.71) and the CA 125 threshold derived from the ROC was 400 U/mL. The accuracy of the test at this level was 62%. CONCLUSIONS: The clinical applicability of the ROC derived CA 125 threshold is limited. The data accrued in the study provides a basis for decision-making regarding the place of primary surgery various CA 125 levels.

Biomarkers, Tumor↗
PubMed2005

Ion translocation by the Escherichia coli NADH:ubiquinone oxidoreductase (complex I).

The energy-converting NADH:ubiquinone oxidoreductase, also known as respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of ions across the membrane. It was assumed that the complex exclusively works as a proton pump. Recently, it has been proposed that complex I from Klebsiella pneumoniae and Escherichia coli work as Na+ pumps. We have used an E. coli complex I preparation to determine the type of ion(s) translocated by means of enzyme activity, generation of a membrane potential and redox-induced Fourier-transform infrared spectroscopy. We did not find any indications for Na+ translocation by the E. coli complex I.

Biological Transport↗
PubMed2004

Ectopic pregnancies in a Caesarean scar: review of the medical approach to an iatrogenic complication.

Implantation of a pregnancy within a Caesarean fibrous tissue scar is considered to be the rarest form of ectopic pregnancy and a life-threatening condition. We conducted a computer search of the English literature of all studies since 2002 to gather updated data on the outcome of such pregnancies. Sixty-six new cases were reported since 2002, possibly reflecting the increasing number of Caesareans currently being performed as well as the more widespread use of the transvaginal scan allowing their earlier detection. Analysis of these women's obstetric history revealed that those at risk for pregnancy in a Caesarean scar appear to have a history of dilatation and curettage, placental pathology, ectopic pregnancy, and IVF. Twenty-one out of 39 for which this information was available (54%) had undergone multiple (> or =2) Caesareans and 13 had previous dilatation and curettage, which might also be an associated factor. We review and discuss the features of contemporary work-ups, including a high index of awareness, a detailed history and a skillful ultrasound examination for an early and accurate diagnosis. Healthcare professionals should be familiar with the possibility of untoward sequelae and how a modern work-up can help in guiding conservative options, thus reducing morbidity and preserving fertility.

Cesarean Section↗
PubMed2004

Childhood leukaemia incidence and the population mixing hypothesis in US SEER data.

We evaluated the infectious aetiology hypothesis of childhood leukaemia that rapid population influx into rural areas is associated with increased risk. Using data from the US SEER program, we found that in changes in rural county population sizes from 1980 to 1989 were associated with incidence rates for childhood acute lymphocytic leukaemia (ALL). The observed associations were strongest among children 0-4 years of age, born in the same state as diagnosis, in extremely rural counties, and when counties adjacent to nonrural counties were excluded. Similar analyses for brain and central nervous system (CNS) cancer in children, a disease less linked to this infectious hypothesis, provide evidence against methodologic bias. Similar evaluations for other decades were not meaningful due to limited sample sizes and, perhaps, increased population mobility.

Adolescent↗
PubMed2004

Continuous measurements of cerebral tissue oxygen pressure during hyperbaric oxygenation--HBO effects on brain edema and necrosis after severe brain trauma in rabbits.

INTRODUCTION: Severe brain injury is one of the most frequent causes of severe disability in the young. In acute management of brain trauma, new approaches based on experimental animal investigations should be sought. METHODS: Twenty male, juvenile Chinchilla-Bastard rabbits received standardized cold-injury-induced-brain-trauma (CIBT). A metal probe (temperature -196 degrees C) was applied epidurally over 10 s. The hyperbaric oxygenation (HBO) group (n=10) underwent 90-min HBO sessions with 100% oxygen at 2.5 atmospheres absolute (1 h, 24+/-2 h, 48+/-2 h after CIBT). Cerebral tissue pO2-measurements were performed 60 min after CIBT, during the three HBO sessions and on day 4. The control group (n=10) underwent no treatment. Animals were sacrificed on day 4, and brains were analyzed histologically. RESULTS: In the HBO group, pO2 measurements showed a significant increase in pO2 between day 1 and day 4, whereas no significant changes were observed in the control group. During the first HBO session, mean pO2 was 169 mm Hg, during the second 305 mm Hg and during the third 420 mm Hg. The mean area of necrosis was 16.2 mm2 in the HBO group, in the control group 19.9 mm2. The areas of brain edema were significantly smaller in the HBO group. Mortality in the HBO group was 0%, in the control group 20%. CONCLUSION: HBO appears to be beneficial as an adjunct treatment of severe head trauma. To find optimal treatment protocols, further clinical studies must be developed.

Animals↗
PubMed2004

Search for extraterrestrial point sources of neutrinos with AMANDA-II.

We present the results of a search for point sources of high-energy neutrinos in the northern hemisphere using AMANDA-II data collected in the year 2000. Included are flux limits on several active-galactic-nuclei blazars, microquasars, magnetars, and other candidate neutrino sources. A search for excesses above a random background of cosmic-ray-induced atmospheric neutrinos and misreconstructed downgoing cosmic-ray muons reveals no statistically significant neutrino point sources. We show that AMANDA-II has achieved the sensitivity required to probe known TeV gamma-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and gamma-ray fluxes are equal.

Journal Article↗
PubMed2004

Hyperbaric and normobaric reoxygenation of hypoxic rat brain slices--impact on purine nucleotides and cell viability.

Hyperbaric oxygen treatment has been suggested as able to reduce hypoxia induced neuronal damage. The aim of the study was to compare the impact of different reoxygenation strategies on early metabolical (purine nucleotide content determined by HPLC) and morphological changes (index of cell injury after celestine blue/acid fuchsin staining) of hypoxically damaged rat neocortical brain slices. For this purpose slices (300 microm and 900 microm) were subjected to either 5 or 30 min of hypoxia by gassing the incubation medium with nitrogen. During the following reoxygenation period treatment groups were administered either 100% oxygen (O) or room air (A) at normobaric (1 atm absolute, NB-O; NB-A) or hyperbaric (2.5 atm absolute, HB-O; HB-A) conditions. After 5 min of hypoxia, both HB-O and NB-O led to a complete nucleotide status restoration (ATP/ADP; GTP/GDP) in 300 microm slices. However, reoxygenation after 30 min of hypoxia was less effective, irrespective of the oxygen pressure. Furthermore, administering hyperbaric room air resulted in no significant posthypoxic nucleotide recovery. In 900 microm slices, both control incubation as well as 30 min of hypoxia resulted in significantly lower trinucleotide and higher dinucleotide levels compared to 300 microm slices. While there was no significant difference between HB-O and NB-O on the nucleotide status, morphological evaluation revealed a better recovery of the index of cell injury (profoundly injured/intact cell-ratio) in the HB-O group. Conclusively, the posthypoxic recovery of metabolical characteristics was dependent on the duration of hypoxia and slice thickness, but not on the reoxygenation pressure. A clear restorative effect on purine nucleotides was found only in early-administered HB-O as well as NB-O in contrast to room air treated slices. However, these pressure independent metabolic changes were morphologically accompanied by a significantly improved index of cell injury, indicating a possible neuroprotective role of HB-O in early posthypoxic reoxygenation.

Adenosine Diphosphate↗
PubMed2004

Intracellular acidification by inhibition of the Na+/H+-exchanger leads to caspase-independent death of cerebellar granule neurons resembling paraptosis.

Potassium withdrawal is commonly used to induce caspase-mediated apoptosis in cerebellar granule neurons in vitro. However, the underlying and cell death-initiating mechanisms are unknown. We firstly investigated potassium efflux through the outward delayed rectifier K+ current (Ik) as a potential mediator. However, tetraethylammoniumchloride, an inhibitor of Ik, was ineffective to block apoptosis after potassium withdrawal. Since potassium withdrawal reduced intracellular pH (pHi) from 7.4 to 7.2, we secondly investigated the effects of intracellular acidosis. To study intracellular acidosis in cerebellar granule neurons, we inhibited the Na+/H+ exchanger (NHE) with 4-isopropyl-3-methylsulfonylbenzoyl-guanidine methanesulfonate (HOE 642) and 5-(N-ethyl-N-isopropyl)-amiloride. Both inhibitors concentration-dependently induced cell death and potentiated cell death after potassium withdrawal. Although inhibition of the NHE induced cell death with morphological criteria of apoptosis in light and electron microscopy including chromatin condensation, positive TUNEL staining and cell shrinkage, no internucleosomal DNA cleavage or activation of caspases was detected. In contrast to potassium withdrawal-induced apoptosis, cell death induced by intracellular acidification was not prevented by insulin-like growth factor-1, cyclo-adenosine-monophosphate, caspase inhibitors and transfection with an adenovirus expressing Bcl-XL. However, cycloheximide protected cerebellar granule neurons from death induced by potassium withdrawal as well as from death after treatment with HOE 642. Therefore, the molecular mechanisms leading to cell death after acidification appear to be different from the mechanisms after potassium withdrawal and resemble the biochemical but not the morphological characteristics of paraptosis.

Acidosis↗
PubMed2004

Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre.

BACKGROUND: Our aim was to supplement the mostly individual case reports on the rarely occurring and life-threatening condition of ectopic pregnancy developing in a Caesarean section scar. METHODS AND RESULTS: Eight of all the patients treated in our department between 1995 and 2002 had been diagnosed for ectopic pregnancy that developed in a Caesarean section scar. They comprised this case series group. Four of them underwent methotrexate treatment; one had expectant management, one transcervical aspiration of the gestational sac and two by open surgery. All the non-surgically treated women had an uneventful outcome. One underwent a term Caesarean hysterectomy and the other first trimester hysterotomy and excision of the pregnancy located in the scarred uterus. Analysis of all these women's obstetric history revealed that five of them (63%) had been previously operated because of breech presentation, one had a cervical pregnancy and one had placenta previa. Four of them (50%) had multiple (> or = 2) Caesarean sections. CONCLUSIONS: The women at risk for pregnancy in a Caesarean section scar appear to be those with a history of placental pathology, ectopic pregnancy, multiple Caesarean sections and Caesarean breech delivery. Heightened awareness of this possibility and early diagnosis by means of transvaginal sonography can improve outcome and minimize the need for emergency extended surgery.

Adult↗