Biomedical subjects

H Simon

Publications and source records attributed to H Simon.

At least 19 recordsLinked to original sources

PubMed2005

Potential activity of paclitaxel, vinorelbine and gemcitabine in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) has a rapidly fatal course in the mostly elderly patients with a median survival after diagnosis of 4-12 months. Activity of commonly used chemotherapy (doxorubicin) is low, thus more active compounds need to be introduced into the therapeutic concept of ATC. Recently, based on preclinical data Ain et al. conducted a clinical phase II study with paclitaxel 96 h infusion in ATC achieving a promising response rate of 53%. To further improve therapeutic options in ATC, we evaluated the activity of topotecan, oxaliplatin, vinorelbine, gemcitabine and paclitaxel in comparision to cisplatin and doxorubicin (1 and 96 h drug exposure) alone or in combination in the ATC cell lines SW1736 and 8505C. IC50 values were determined by the sulforhodamine B assay, potential clinical activity was estimated by relative antitumor activity (RAA) and drug interaction was analyzed using a parametric response surface approach (Greco model) of the Loewe additivity. Duration of drug effect was estimated by regrowth kinetics. We found paclitaxel, vinorelbine and gemcitabine active in ATC with RAA (1 h drug exposure) ranging from 86 to 454, 15 to 17 and 31 to 140, respectively. The activity of doxorubicin and cisplatin was moderate with RAA ranging from 1.4 to 2.2 and 0.2 to 0.3, respectively. Combined drug exposure of gemcitabine/paclitaxel and gemcitabine/vinorelbine was synergistic with a Loewe index > 0. However, these results did not reach statistical significance with p > 0.05. At clinically relevant drug concentrations paclitaxel, gemcitabine and vinorelbine but not oxaliplatin exerted a sustained growth inhibition after cessation of drug exposure for the complete assay time of 15 days. In conclusion, paclitaxel, gemcitabine and vinorelbine but not topotecan or oxaliplatin appeared to be active in anaplastic thyroid carcinoma based on RAA or growth delay at clinically relevant drug concentrations. Combinations of vinorelbine/gemcitabine and paclitaxel/gemcitabine exerted a trend to synergy. Thus, further evaluation of paclitaxel, vinorelbine and gemcitabine alone or in combination with ATC seems warranted.

Antineoplastic Agents↗

PubMed2005

Evidence for pygmy and giant dipole resonances in 130Sn and 132Sn.

The dipole strength distribution above the one-neutron separation energy was measured in the unstable 130Sn and the double-magic 132Sn isotopes. The results were deduced from Coulomb dissociation of secondary Sn beams with energies around 500 MeV/nucleon, produced by in-flight fission of a primary 238U beam. In addition to the giant dipole resonance, a resonancelike structure ("pygmy resonance") is observed at a lower excitation energy around 10 MeV exhausting a few percent of the isovector E1 energy-weighted sum rule. The results are discussed in the context of a predicted new dipole mode of excess neutrons oscillating out of phase with the core nucleons.

Journal Article↗

PubMed2005

"Safe" Coulomb excitation of 30Mg.

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient gamma spectrometer MINIBALL. Using 30Mg ions accelerated to an energy of 2.25 MeV/u together with a thin (nat)Ni target, Coulomb excitation of the first excited 2+ states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative deexcitation gamma-ray yields the B(E2;0(+)gs-->2(+)1) value of 30Mg was determined to be 241(31)e2 fm4. Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope 30Mg resides outside the "island of inversion."

Journal Article↗

PubMed2004

Shell structure of the near-dripline nucleus 23O.

Breakup reactions were used to study the ground-state configuration of the neutron-rich isotope 23O. The 22O fragments produced in one-nucleon removal from 23O at 938 MeV/nucleon in a carbon target were detected in coincidence with deexciting gamma rays. The widths of the longitudinal momentum distributions of the 22O fragments and the one-neutron removal cross sections were interpreted in the framework of a simple theoretical model which favors the assignment of Ipi = 1/2+ to the 23O ground state.

Journal Article↗

PubMed2004

Evidence for multiphonon giant resonances in electromagnetic fission of 238U.

Differential cross sections for electromagnetic fission of 238U projectiles (500 MeV/u) in C, Sn, and Pb targets are measured and analyzed in terms of single- and multiphonon giant resonance excitations as doorway states to fission. A novel experimental method exploits the linear relationship between neutron multiplicity and the primary 238U excitation energy. Multiphonon states contribute up to 20% of the cross section; a component at high excitation energies is indicated that may arise from three-phonon dipole and two-phonon GDR x GQRiv giant resonance excitations.

Journal Article↗

PubMed2004

Simultaneous bilateral laparoscopic adrenalectomy: a surgical option for multiple endocrine neoplasia (MEN 2) patients with bilateral pheochromocytomas.

Multiple endocrine neoplasia (MEN 2) is a rare disorder. Of this group, 42% develop a pheochromocytoma of which 60% will have bilateral involvement. Although the benefits of unilateral laparoscopic adrenalectomy have been well documented, fewer cases of simultaneous bilateral laparoscopic adrenalectomy have been reported. We present the cases of three patients with MEN 2 who underwent successful simultaneous bilateral laparoscopic adrenalectomy after their initial presentation with bilateral pheochromocytoma. Although the management of bilateral pheochromocytomas has traditionally been approached via open laparotomy or bilateral posterior incisions, the bilateral laparoscopic approach should be considered a viable alternative for patients requiring surgical intervention. Clinical outcomes and complications are similar to open laparotomy. Simultaneous bilateral laparoscopic adrenalectomy is a safe and effective procedure that results in a more rapid recovery and a shorter hospital stay for patients with bilateral pheochromocytomas originating from MEN 2.

Adrenal Gland Neoplasms↗

PubMed2004

Different origins of low- and high-frequency components (600 Hz) of human somatosensory evoked potentials.

OBJECTIVE: Human median nerve somatosensory evoked potentials (SEPs) contain a low-amplitude (<500 nV) high-frequency (approximately 600 Hz) burst of repetitive wavelets (HFOs) which are superimposed onto the primary cortical response 'N20.' This study aimed to further clarify the cortical and subcortical structures involved in the generation of the HFOs. METHODS: 128-Channel recordings were obtained to right median nerve stimulation of 10 right-handed healthy human subjects and in 7 of them additional to right ulnar nerve. Data were evaluated by applying principal component analysis and dipole source analysis. RESULTS: Different source evaluation strategies provided converging evidence for a cortical HFO origin, with two different almost orthogonally oriented generators being active in parallel, but with a phase shift of a quarter of their oscillatory period, while the low-frequency 'N20' is adequately modeled by one tangential dipole source. Median and ulnar derived low-frequency and HFO cortical sources show a somatotopic order. Additionally, generation of the HFOs was localized in subcortical, near-thalamic and subthalamic source sites. The near-thalamic dipole was located at significantly different sites in HFO and low-frequency data. CONCLUSIONS: The cortical HFO source constellation points to a 'precortical' source in terminals of thalamocortical fibers and a second intracortical HFO origin. Furthermore, HFOs are also generated at subcortical and even subthalamic sites. Near-thalamic, the HFO and low-frequency signals are generated or modulated by different neuron populations involved in the thalamocortical outflow.

Adult↗

PubMed2004

Impulsivity in youth predicts early age-related cognitive deficits in rats.

Impulsivity is a feature of psychiatric disorders such as mania, addictive behaviors or attention deficit-hyperactivity disorder (ADHD), which has recently been related to complaints of forgetfulness in adults. We investigated whether impulsiveness exerts a long-term influence on cognitive function in rats in a longitudinal study. Impulsivity, assessed by the ability to complete a sequence of presses to obtain food (conditioning box), spatial working memory (8-arm radial maze) assessed with varying degree of attentional load and recognition memory (Y-maze) were tested at different ages. Marked individual differences in impulsivity were observed at youth and remained stable at middle-age despite a general decline in the trait. Working memory scores of impulsive and non-impulsive rats did not differ in youth, whereas by middle-age the impulsive group had impaired working memory and was more sensitive to a higher attentional demand. Thus, impulsiveness in youth predicts cognitive performance in middle-age. These findings may help refine the search for early biological substrates of successful aging and for preventive follow-up of subjects at risk of impaired cognitive aging.

Age Factors↗

PubMed2003

The t+n+n system and 5H.

The one-proton knockout channel from 6He (240 MeV/u) impinging on a carbon target has been investigated. The triton fragments originating from this channel were detected in coincidence with the two neutrons. A broad structure, peaked at 3 MeV above the t+2n threshold, is observed in the t+n+n-relative energy spectrum. It is shown that this structure is mainly due to a I(pi)=1/2(+) resonance as expected for the 5H ground state, and from the observed angular and energy correlations, being used for the first time in 5H studies, that the neutrons to a large extent occupy the p shell.

Journal Article↗

PubMed2002

Evidence for a new low-lying resonance state in 7He.

Low-lying resonance states in 7He(6He+n), formed after fragmentation reactions of a 227 MeV/nucleon 8He beam on a carbon target, have been studied. Coincidences between 6He nuclei and neutrons, corresponding to the one-neutron knockout channel in 8He, were selected. The relative energy spectrum in the 6He+n system shows a structure, which is interpreted as the 7He ( Ipi = 3/2(-)) ground state, unbound with 0.43(2) MeV relative to the 6He+n system and a width of Gamma = 0.15(8) MeV overlapping with an excited ( Ipi = 1/2(-)) state observed at 1.0(1) MeV with a width of Gamma = 0.75(8) MeV.

Journal Article↗

PubMed2002

DNA sequence recognition of thiazole-containing cross-linked polyamides can be favored.

The binding ability of cross-linked thiazolated polyamides (containing the base sequence-reading elements thiazole(Th)-pyrrole(Py)-pyr-role(Py) and thiazole(Th)-imidazole(Im)-pyrrol(Py) to various DNA dodecamers has been investigated. CD titration experiments at high salt concentration demonstrate that the dimers with a heptanediyl linker (C7 dimer) show a significantly higher sequence specificity than their corresponding monomers. The dimer of Th-Py-Py primarily prefers binding to pure AT sequences and that of Th-Im-Py to the dodecamer sequences containing a GC pair within the central sequence (e.g. AACGTT). Surprisingly, the sequence binding ability is strongly influenced by the presence of a T-A step: e.g. Th-Py-Py has a similar affinity to the sequences TTTAAA and ATCGTA; likewise Th-Im-Py shows a preference for these sequences. The CD results correlate with footprinting data. Related biochemical studies on the effect of polyamides on DNA gyrase activity in vitro show that the C7 dimers most effectively inhibit the enzyme activity compared with the monomers and the natural reference minor groove binder distamycin. The highest inhibitory potency is observed for the Th-Py-Py-dimer. The role of the T-A step in binding of the cross-linked dimer to the minor groove is discussed in light of the sequence recognition of the TATA box binding protein.

AT Rich Sequence↗

PubMed2001

Photoneutron cross sections for unstable neutron-rich oxygen isotopes.

The dipole response of stable and unstable neutron-rich oxygen nuclei of masses A = 17 to A = 22 has been investigated experimentally utilizing electromagnetic excitation in heavy-ion collisions at beam energies about 600 MeV/nucleon. A kinematically complete measurement of the neutron decay channel in inelastic scattering of the secondary beam projectiles from a Pb target was performed. Differential electromagnetic excitation cross sections d sigma/dE were derived up to 30 MeV excitation energy. In contrast to stable nuclei, the deduced dipole strength distribution appears to be strongly fragmented and systematically exhibits a considerable fraction of low-lying strength.

Journal Article↗

PubMed2001

Investigation of the physicochemical basis of enantiomeric enrichment: The example of alpha-phenylethylamine with achiral dicarboxylic acids.

We investigated the enantiomeric enrichment of enantiomeric mixtures of alpha-phenylethylamine by achiral dicarboxylic acids. As achiral agents oxalic, malonic, fumaric, and phthalic acids were used. The results of the enantiomeric enrichment via partial salt formation followed by distillation were compared with enantiomer separation via crystallization of the neutral salt. Without the presence of a solid phase, enantiomeric separation is impossible. Our results show that the properties of the solid phase determine the separation. It is also confirmed by our observation that the eutectic points, which are observed on the 3-phase solubility diagrams of the solid neutral salts, can be found at the same initial enantiomeric composition as the point of intersection of distillate and residue of the distillation curves and the point of intersection of precipitated salt and mother liquor of the crystallization curves. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

PubMed2001

Chronic treatment with Delta(9)-tetrahydrocannabinol enhances the locomotor response to amphetamine and heroin. Implications for vulnerability to drug addiction.

Cannabis sativa preparations are some of the most widely used illicit recreational drugs. In addition to their direct addictive potential, cannabinoids may influence the sensitivity to other drugs. The aim of the present study was to determine if a cross-sensitization between Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and other drugs (amphetamine and heroin) could be demonstrated. We examined the effects of a chronic treatment with Delta(9)-THC (0.6, 3 and 15mg/kg, ip) on the locomotor response to amphetamine (1mg/kg, ip) and heroin (1mg/kg, ip). Chronic treatment with Delta(9)-THC resulted in tolerance to the initial hypothermic and anorexic effects. Pre-treatment with Delta(9)-THC increased the locomotor responses to amphetamine and heroin. This cross-sensitization was time-dependent as it was observed three days after the last injection of Delta(9)-THC for amphetamine, and a relatively long time after the end of chronic treatment (41 days) for heroin. Moreover, the enhanced response to amphetamine or heroin was noted in some individuals only: the high-responder rats (HR). These animals have previously been shown to be vulnerable to drug taking behaviors. It is hypothesised that repeated use of Cannabis derivates may facilitate progression to the consumption of other illicit drugs in vulnerable individuals.

Amphetamine↗

PubMed2001

Enhancement of place and object recognition memory in young adult and old rats by RS 67333, a partial agonist of 5-HT4 receptors.

There is recent evidence that activation of central 5-hydroxytryptamine (5-HT)4 receptors enhances cognitive processes such as learning and memory. In the present study, we assessed the effects of a selective 5-HT4 receptors agonist, RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone], in a two-trial recognition task designed to test place or object recognition memory.RS 67333 was injected in young adult (0.0001, 0.01, 1 mg/kg, i.p.) and old (0.0001, 0.01, 1, 10 mg/kg, i.p.) rats before the acquisition phase, immediately after it, or before the retrieval phase, to determine the stage of information processing affected by the compound. When injected before the acquisition phase, RS 67333 (1 mg/kg) enhanced place and object recognition in young adult rats. In old rats, RS 67333 (10 mg/kg) improved place recognition when injected before the acquisition phase, and object recognition when injected before the acquisition or in the consolidation phase of information processing. The beneficial effects of RS 67333 were abolished by prior treatment with a selective 5-HT4 receptors antagonist, GR 125487 [(1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate); 10 mg/kg, i.p.]. These results support the view that selective 5-HT4 receptors agonists may be of value in the treatment of cognitive disorders related to normal aging or neurodegenerative conditions such as Alzheimer's disease.

Aging↗

PubMed2001

[Gastroduodenal metastases: an unusual manifestation of lung cancer. Study of two cases and review ot the literature].

INTRODUCTION: Diagnosis of gastroduodenal metastases is rare. Primary tumors are essentially melanomas and breast cancer, and exceptionally lung cancer. EXEGESIS: We report two patients who have a diagnosis of gastroduodenal metastases as initial manifestation of lung cancer. In one case, the patient died 3 weeks after the diagnosis. In the other case, chemotherapy was performed and complete response was obtained for the gastric metastasis. After a few months, node recurrence was diagnosed and the patient died 8 months after the diagnosis. CONCLUSION: We review the endoscopic and non-endoscopic literature and discuss the different histological types and therapeutic strategies concerning these unusual manifestations of lung cancer.

Abdominal Pain↗

PubMed2001

A prospective multicenter study of cervical spine injury in children.

OBJECTIVE: Pediatric victims of blunt trauma have developmental and anatomic characteristics that can make it difficult to assess their risk of cervical spine injury (CSI). Previous reports, all retrospective in nature, have not identified any cases of CSI in either children or adults in the absence of neck pain, neurologic symptoms, distracting injury, or altered mental status. The objective of this study was to examine the incidence and spectrum of spine injury in patients who are younger than 18 years and to evaluate the efficacy of the National Emergency X-Radiography Utilization Study (NEXUS) decision instrument for obtaining cervical spine radiography in pediatric trauma victims. METHODS: We performed a prospective, multicenter study to evaluate pediatric blunt trauma victims. All patients who presented to participating emergency departments underwent clinical evaluation before radiographic imaging. The presence or absence of the following criteria was noted: midline cervical tenderness, altered level of alertness, evidence of intoxication, neurologic abnormality, and presence of painful distracting injury. Presence or absence of each individual criterion was documented for each patient before radiographic imaging, unless the patient was judged to be too unstable to complete the clinical evaluation before radiographs. The decision to radiograph a patient was entirely at the physician's discretion and not driven by the NEXUS questionnaire. The presence or absence of CSI was based on the final interpretation of all radiographic studies. Data on all patients who were younger than 18 years were sequestered from the main database for separate analysis. RESULTS: There were 3065 patients (9.0% of all NEXUS patients) who were younger than 18 years in this cohort, 30 of whom (0.98%) sustained a CSI. Included in the study were 88 children who were younger than 2, 817 who were between 2 and 8, and 2160 who were 8 to 17. Fractures of the lower cervical vertebrae (C5-C7) accounted for 45.9% of pediatric CSIs. No case of spinal cord injury without radiographic abnormality was reported in any child in this study, although 22 cases were reported in adults. Only 4 of the 30 injured children were younger than 9 years, and none was younger than 2 years. Tenderness and distracting injury were the 2 most common abnormalities noted in patients with and without CSI. The decision rule correctly identified all pediatric CSI victims (sensitivity: 100.0%; 95% confidence interval: 87.8%-100.0%) and correctly designated 603 patients as low risk for CSI (negative predictive value: 100.0%; 95% confidence interval: 99.4%-100.0%). CONCLUSIONS: The lower cervical spine is the most common site of CSI in children, and fractures are the most common type of injury. CSI is rare among patients aged 8 years or younger. The NEXUS decision instrument performed well in children, and its use could reduce pediatric cervical spine imaging by nearly 20%. However, the small number of infants and toddlers in the study suggests caution in applying the NEXUS criteria to this particular age group.

Adolescent↗

PubMed2000

Enoate reductases of Clostridia. Cloning, sequencing, and expression.

The enr genes specifying enoate reductases of Clostridium tyrobutyricum and Clostridium thermoaceticum were cloned and sequenced. Sequence comparison shows that enoate reductases are similar to a family of flavoproteins comprising 2,4-dienoyl-coenzyme A reductase from Escherichia coli and old yellow enzyme from yeast. The C. thermoaceticum enr gene product was expressed in recombinant Escherichia coli cells growing under anaerobic conditions. The recombinant enzyme was purified and characterized.

Amino Acid Sequence↗