Biomedical subjects

M Schubert

Publications and source records attributed to M Schubert.

At least 19 recordsLinked to original sources

PubMed2006

Clinical experience with the new long-acting injectable testosterone undecanoate. Report on the educational symposium on the occasion of the 5th World Congress on the Aging Male, 9-12 February 2006, Salzburg, Austria.

This symposium report summarizes first extensive clinical findings with injectable testosterone undecanoate (Nebido) in hypogonadal patients showing clinical symptoms of androgen deficiency with or without erectile dysfunction (ED). This new testosterone formulation (1000 mg testosterone undecanoate in 4 ml castor oil) possesses nearly ideal long-term kinetics, i.e. sustained close mimicking of eugonadal testosterone serum levels without supra- or sub-physiological serum concentrations. The generally accepted administration scheme recommends the second injection 6 weeks after the first one followed by further injections every 12 weeks. Applying this regimen, administration intervals are drastically reduced in comparison to conventional i.m. testosterone preparations (e.g. about 16 injections of testosterone enanthate vs. 4-5 injections of testosterone undecanoate per year). Depending on the testosterone serum levels, individualized therapy is possible by shortening (every 10 weeks) or prolonging (every 14 weeks) the injection intervals. In hypogonadal patients with ED 58% respond to testosterone undecanoate alone. Best results are seen in diabetic hypogonadal patients. The regimen of injectable testosterone undecanoate administration ideally fits recommendations regarding pharmacokinetics, efficacy and safety monitoring.

Aged↗

PubMed2006

Characterization of a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12, associated with mental retardation and impaired speech development.

We report on a currently six-year-old patient with a de novo complex chromosome rearrangement (CCR) involving chromosomes 2 and 12. A translocation 2;12 that appeared to be reciprocal after standard banding turned out to be a complex event with seven breaks after molecular cytogenetic analyses. Array CGH analysis showed no imbalances at the breakpoints but revealed an additional microdeletion of about 80 kb on chromosome 11. The same deletion was also present in the phenotypically normal father. The patient showed relatively mild mental retardation, defined mainly as impaired speech development (orofacial dyspraxia) and psychomotor retardation. In addition, mild dysmorphic facial features like hypertelorism, a prominent philtrum and down-turned corners of the mouth were observed. We narrowed down all breakpoint regions to about 100 kb, using a panel of mapped bacterial artificial chromosome (BAC) clones for fluorescence in situ hybridization (FISH). BACs spanning or flanking all seven breakpoints were identified and no chromosomal imbalances were found consistent with the array CGH results. Our investigations resulted in the following karyotype: 46,XY,t(2;12)(2pter-->2p25.3::2p23.3-->2p25.2::2p23.3-->2p14::2q14.3-->2p14::2q14.3-->2q14.3::12q 12-->12qter;12pter-->12q12::2p25.3-->2p25.2::2q14.3-->2qter).

Child↗

PubMed2005

Corticosteroid status influences the volume of the rat cingulate cortex - a magnetic resonance imaging study.

Imbalances in the corticosteroid milieu result in reductions in hippocampal volume in humans and experimental rodents. The functional correlates of these changes include deficits in cognitive performance and regulation of the hypothalamic-pituitary-adrenal axis. Since other limbic structures which are intricately connected with the hippocampal formation, also play an important role in behavioural and neuroendocrine functions, we here used magnetic resonance imaging (MRI) to analyse how two of these areas, the anterior cingulate and retrosplenial cortex, respond to chronic alterations of adrenocortical status: hypocortisolism (induced by adrenalectomy, ADX), normocortisolism (ADX with low-dose corticosterone replacement), and hypercortisolism (ADX with high-dose dexamethasone supplementation). Hypercortisolism was associated with a significant reduction in the volume (absolute and normalized) of the left anterior cingulate gyrus as measured by MRI and confirmed using classical histological methods; a similar trend was observed in the right anterior cingulate region. In contrast, hypercortisolism did not influence the volume of the adjacent retrosplenial cortex. The volumes of the anterior cingulate gyrus and retrosplenial cortex were unaffected by the absence of adrenocortical hormones. These findings are the first to suggest that corticosteroid influences on the structure of the limbic system extend beyond the hippocampal formation, i.e., to fronto-limbic areas also.

Adrenal Cortex Hormones↗

PubMed2005

Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas.

The renin-angiotensin system not only plays a critical role in blood pressure control but is also involved in learning and memory mechanisms. In addition to angiotensin (Ang) II, Ang-(1-7) may also have important biological activities in the brain. Here, we show for the first time that Ang-(1-7) enhances long-term potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1 receptor antagonists and selective Ang-(1-7) receptor antagonists demonstrate the existence of a distinct Ang-(1-7) receptor in the brain, the G-protein-coupled receptor Mas, encoded by the Mas protooncogene. We also show that the genetic deletion of this receptor abolishes the Ang-(1-7)-induced enhancement of LTP. Thus, we firstly demonstrate that Ang-(1-7) influences the induction of LTP in limbic structures implicating its distinct function in learning and memory mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1-7) in the brain.

Angiotensin I↗

PubMed2005

Autoimmune polyglandular syndrome associated with idiopathic giant cell myocarditis.

The autoimmune polyglandular syndrome (APS) is characterized by a variable coexistence of several autoimmune diseases, affecting predominantly endocrine glands. In general two types of APS are distinguished. Type 1 APS is an autosomal recessive disorder often leading to insufficiency of the adrenal cortex, the parathyroid glands, and/or the gonads. This type of APS often affects the skin in form of chronic mucocutaneous candidiasis and ectodermal dystrophies (vitiligo, alopecia, keratopathy, dystrophy of dental enamel and nails). The second form of APS is a polygenic disease which usually involves the adrenal gland, the thyroid and the pancreatic beta-cells. In rare cases APS type 2 is associated with myasthenia gravis, autoimmune thrombocytopenic purpura, Sjogren's syndrome or rheumatoid arthritis. Here we describe a case of APS with the unusual combination of type 1 diabetes, secondary adrenocortical insufficiency, growth hormone deficiency, and primary hypothyroidism associated with lethal idiopathic giant cell myocarditis. The combination of APS and idiopathic giant cell myocarditis which is a rare, frequently fatal autoimmune disorder of myocardium affecting most commonly young individuals has not been reported so far.

Adrenal Cortex Diseases↗

PubMed2005

Late-onset hypogonadism in the aging male (LOH): definition, diagnostic and clinical aspects.

Late-onset hypogonadism (LOH) is defined by reduced serum testosterone levels (either total testosterone or free testosterone) and the careful exclusion of any form of classical hypogonadism. When the androgen decline associated with advancing age causes detrimental physiological and mental effects, the syndrome is known as symptomatic LOH (SLOH). A detailed medical history and physical examination are the bases of the diagnosis, and should always precede any biochemical investigations. A general screening of men above a certain age for testosterone deficiency is not feasible. Questionnaires may assist in identifying men who suffer from LOH. Common clinical symptoms of SLOH are lethargy, fatigue, decreased sense of well-being, reduced physical and mental activity, diminished libido, increased sweating, depressive mood, reduced muscle and bone mass or even osteoporosis, erectile dysfunction, and mild anemia. When clinical symptoms are present, the laboratory work-up should focus on total testosterone serum levels. Total testosterone levels <200 ng/dl indicate hypogonadism. In cases of testosterone levels between 200 and 400 ng/dl, measurement should be repeated and supplemented by determination of free testosterone, either by appropriate laboratory methods or the calculation of free testosterone index. In case of very low testosterone levels, classical secondary hypogonadism needs to be considered and excluded. For the safety reasons to exclude contraindications of therapy with androgens, and for follow-up investigations during therapy prostate-specific antigen (PSA), hemoglobin and hematocrit are of interest.

Adult↗

PubMed2004

Integrated approach to the electronic interaction of swift heavy ions with solids and gases.

The two most prominent processes of ion-matter interaction are the energy loss and charge exchange, whereby the first depends on the charge state of the ion as determined by the latter. However, up to now there has existed no closed calculation of these two major processes. We herewith present, within an integrated approach, a Monte Carlo calculation which intrinsically entails target ionization/excitation, as well as charge exchange and projectile ionization/excitation on equal footing, especially extended to the situation of ion-solid interaction.

Journal Article↗

PubMed2004

The chordate amphioxus: an emerging model organism for developmental biology.

The cephalochordate amphioxus is the closest living invertebrate relative of the vertebrates. It is vertebrate-like in having a dorsal, hollow nerve cord, notochord, segmental muscles, pharyngeal gill slits and a post-anal tail that develops from a tail bud. However, amphioxus is less complex than vertebrates, lacking neural crest and having little or no mesenchyme. The genetic programs patterning the amphioxus embryo are also similar to those patterning vertebrate embryos, although the amphioxus genome lacks the extensive gene duplications characteristic of vertebrates. This relative structural and genomic simplicity in a vertebrate-like organism makes amphioxus ideal as a model organism for understanding mechanisms of vertebrate development.

Animals↗

PubMed2004

Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism.

In an open-label, randomized, prospective trial, we investigated pharmacokinetics and several efficacy and safety parameters of a novel, long-acting testosterone (T) undecanoate (TU) formulation in 40 hypogonadal men (serum testosterone concentrations < 5 nmol/liter). For the first 30 wk (comparative study), the patients were randomly assigned to receive either 10 x 250 mg T enanthate (TE) im every 3 wk (n = 20) or 3 x 1000 mg TU im every 6 wk (loading dose) followed by 1 x 1000 mg after an additional 9 wk (n = 20). In a follow-up study, observation continued in those patients who completed the comparative part and opted for TU treatment (8 x 1000 mg TU every 12 wk in former TU patients and 2 x 1000 mg TU every 8 wk plus 6 x 1000 mg every 12 wk in former TE patients) for an additional 20-21 months. Here we report only the pharmacokinetic aspects of the new TU formulation for the first approximately 2.5 yr of treatment. At baseline, serum T concentrations did not significantly differ between the two study groups. In the TE group, mean trough levels of serum T were always less than 10 nmol/liter before the next injection, whereas in the TU group, mean trough levels of serum T were 14.1 +/- 4.5 nmol/liter after the first two doses (6-wk intervals) and 16.3 +/- 5.7 nmol/liter after the 9-wk interval at wk 30. The mean serum levels of dihydrotestosterone and estradiol also increased in parallel to the serum T pattern and remained within the normal range. In the follow-up study, the former TU patients (n = 20) received eight TU injections at 12-wk intervals, and the TE patients (n = 16) switched to TU and initially received two TU injections at 8-wk intervals (loading) and continued with six TU injections at 12-wk intervals (maintenance). This regimen resulted in stable mean serum trough levels of T (ranging from 14.9 +/- 5.2 to 16.5 +/- 8.0 nmol/liter) and estradiol (ranging from 98.5 +/- 45.2 to 80.4 +/- 14.4 pmol/liter). The present study has shown that 1000 mg TU injected into male patients with hypogonadism at 12-wk intervals is well tolerated and leads to T levels within normal ranges, using four instead of 17 or more TE injections per year. An initial loading dose of either 3 x 1000 mg TU every 6 wk at the beginning of hormone substitution or 2 x 1000 mg TU every 8 wk after switching from the short-acting TE to TU were found to be a adequate dosing regimens for starting of treatment with the long-acting TU preparation.

Adolescent↗

PubMed2003

The role of vision in maintaining heading direction: effects of changing gaze and optic flow on human gait.

How is heading direction maintained in human gait? This question was investigated with respect to the role of optic flow and in the context of different movement strategies. While walking on a treadmill the deviation from the ideal straight path was measured in terms of lateral sway induced by a lateral gaze shift (by looking at a moving visual target). The role of the focus of expansion (FOE) within a radially expanding optic flow pattern was investigated by varying its relative velocity of expansion from 0- to 4-fold (the equivalent of walking speed), thus increasing the perceptibility of FOE. If FOE was a relevant cue for maintaining heading direction, a reduction of lateral sway amplitude was expected with increasing flow velocity. The presence of a radially expanding flow pattern did not reduce lateral sway. Lateral sway was least when the visual background remained stable without any flow pattern. Increasing the velocity of the flow pattern resulted in an increase in lateral sway. If the relative velocity of the flow pattern was raised beyond that corresponding to walking speed, lateral sway amplitude approached the maximal values observed in the dark. In all experiments, sway amplitude increased linearly with the increasing excursion of the visual target. Different strategies to perform the gaze shift (eye or head turns) only resulted in minor differences in lateral sway amplitude. The results show that gaze shifts during locomotion induce lateral sway, which depends upon the presence, and characteristics, of background optic flow. Under the present conditions, the FOE within the flow field seems not to be a dominant cue to control heading. However, the systematic increase in lateral sway induced by high flow velocities indicates that motion parallax has an effect on heading during locomotion.

Adult↗

PubMed2003

Spectrum of cognitive, behavioural and emotional problems in children and young adults with Down syndrome.

In comparison to most other groups with intellectual disability individuals with Down syndrome are at lower risk for significant psychopathology, although relative to their typically developing peers they have higher rates of behavioural and emotional problems. A total of 43 Down syndrome patients (21 females and 22 males), who ranged in age from 5.33 to 30.58 years, were examined for the presence of age-related changes in the spectrum of externalizing and internalizing problems. Intelligence tests included Hamburg-Wechsler-Intelligenz Test für Kinder III (HAWIK-III), Hamburg-Wechsler-Intelligenz Test für Erwachsene (HAWIE-R) and Kaufman-Assessment-Battery for Children, German Version (K-ABC). Behavioural and emotional problems were assessed by the the Strengths and Difficulties Questionnaire for Parents, German Version (SDQ) and the Clinical Assessment Scale for Child and Adolescent Psychopathology (CASCAP). IQ was significantly inversly related to the age of patients. Externalizing behaviours (dominant, opposing/refusing, impulsiveness, inattention and increased motor activity) were significantly higher in the 5-10 years old group, whereas internalizing behaviours (shy/insecure, low self confidence, decreased motor activity) where more prevalent in adolescents and adults (10-30 years). Possible relationships between this age-related changes and increased risks of later-onset psychopathology (depression and dementia) are discussed.

Adolescent↗

PubMed2003

Lack of cytoprotective effect of amifostine following HLA-identical sibling transplantation for advanced myelodysplastic syndrome (MDS): a pilot study.

The objective of this prospective study was to determine whether amifostine (Ethyol) reduced conditioning-related toxicity following a regimen of busulfan (7 mg/kg) and fractionated total body irradiation (6 x 200 cGy). In all, 12 patients with advanced myelodysplastic syndrome transplanted from HLA-identical siblings were enrolled. Patients received 340 mg/m(2) amifostine i.v. twice daily during conditioning (days -7 through -1). All patients developed oropharyngeal mucositis. Six patients had evidence of sinusoidal obstruction syndrome of the liver. Six patients experienced pulmonary toxicity of grades II-III. A total of 11 patients died, one with relapse and 10 with infectious complications or regimen-related toxicity. Nonrelapse causes of death included invasive aspergillosis in three, multiorgan failure in three, and idiopathic interstitial pneumonitis in two patients. One patient each died of organizing pneumonia and CMV pneumonia. One patient is alive in complete remission 31 months after transplantation. These results were not superior to those in patients conditioned with busulfan plus fractionated total body irradiation and not given amifostine, and suggest that amifostine, as administered here, has no protective effect against toxicity from this myeloablative regimen.

Adult↗

PubMed2002

Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.

Blockade of tumor necrosis factor (TNF)alpha by a soluble TNF receptor fusion protein (etanercept; Enbrel) improved in vitro hemopoiesis from the marrow of patients with myelodysplastic syndrome (MDS). Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial. Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks). Among 12 evaluable patients, four had rises in hemoglobin by 1-1.5 gm/dl (three) or decreased transfusion requirements (one). Two patients had increased platelet counts (54% and 73%), and two increased neutrophils (63% and 120%). Baseline TNFalpha levels, determined in all patients, did not correlate with responses. Among eight marrows available for sequential in vitro assays, four showed increases in CFU-GM of 1.5- to 5-fold at 8 weeks, whereas three showed 3- to 10-fold decrements relative to baseline. Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others. Additional trials are needed to evaluate its clinical efficacy in MDS.

Adult↗

PubMed2002

Diurnal radon variations in the upper soil layers and at the soil-air interface related to meteorological parameters.

Measurements of the radon concentration in a column (1 m2 x 2 m) consisting of a homogeneous mixture of dry sand and uranium tailings have been performed to obtain information on the radon transport under well defined conditions. The dependence of the radon concentration has been exclusively studied on the soil/air temperature gradient and on the wind speed. The soil moisture content has been kept constant. Significant diurnal variations of the radon concentration were detected in the uppermost soil layer and at the soil/air interface. Such a behavior was not found in 30 cm and deeper soil layers. It is argued that the diurnal radon variation in the uppermost soil layer is mainly associated with the diurnal inversion of the soil/air temperature gradient giving rise to a convective soil gas migration additional to the common upward diffusion processes, whereas the diurnal variation of the radon concentration at the soil/air interface is caused by the interplay of the temperature gradient and the wind speed. No impact of atmospheric pressure variations on the radon migration has been observed.

Air↗

PubMed2001

Three amphioxus Wnt genes (AmphiWnt3, AmphiWnt5, and AmphiWnt6) associated with the tail bud: the evolution of somitogenesis in chordates.

The amphioxus tail bud is similar to the amphibian tail bud in having an epithelial organization without a mesenchymal component. We characterize three amphioxus Wnt genes (AmphiWnt3, AmphiWnt5, and AmphiWnt6) and show that their early expression around the blastopore can subsequently be traced into the tail bud; in vertebrate embryos, there is a similar progression of expression domains for Wnt3, Wnt5, and Wnt6 genes from the blastopore lip (or its equivalent) to the tail bud. In amphioxus, AmphiWnt3, AmphiWnt5, and AmphiWnt6 are each expressed in a specific subregion of the tail bud, tentatively suggesting that a combinatorial code of developmental gene expression may help generate specific tissues during posterior elongation and somitogenesis. In spite of similarities within their tail buds, vertebrate and amphioxus embryos differ markedly in the relation between the tail bud and the nascent somites: vertebrates have a relatively extensive zone of unsegmented mesenchyme (i.e., presomitic mesoderm) intervening between the tail bud and the forming somites, whereas the amphioxus tail bud gives rise to new somites directly. It is likely that presomitic mesoderm is a vertebrate innovation made possible by developmental interconversions between epithelium and mesenchyme that first became prominent at the dawn of vertebrate evolution.

Animals↗

PubMed2001

Muscle vibration and prefrontal repetitive transcranial magnetic stimulation.

We previously demonstrated that prefrontal subthreshold repetitive transcranial magnetic stimulation (rTMS) may reduce motor cortex excitability. We have now examined whether muscle vibration (MV) can compensate for this depression. We enrolled 25 healthy volunteers (aged 22 to 37 years) who received 5 HZ, 10% subthreshold prefrontal rTMS for 12 s. The extensor carpi radialis muscle was vibrated with an electromagnetic mechanical stimulator with a stimulation frequency of 120 HZ and 0.5 mm amplitude. Motor evoked potentials (MEPs) from the flexor carpi radialis muscle (FCR) following single-pulse transcranial magnetic stimulation (TMS) were recorded at baseline, and after 4, 8, and 12 s. During prefrontal rTMS, MEPs of the FCR exhibited a serial depression (P = 0.001). This effect did not occur during MV. We conclude that rTMS of the prefrontal cortex may inhibit the corticospinal system. This depression may be compensated by MV, suggesting that vibration changes motor cortex excitability. The underlying mechanism might be an input from Ia sensory afferents to the motor and prefrontal cortex.

Adult↗

PubMed2001

Characterization of Amphioxus AmphiVent, an evolutionarily conserved marker for chordate ventral mesoderm.

Structure and developmental expression are described for amphioxus AmphiVent, a homolog of vertebrate Vent genes. In amphioxus, AmphiVent-expressing ventral mesoderm arises at midneurula by outgrowth from the paraxial mesoderm, but in vertebrates, Vent-expressing ventral mesoderm originates earlier, at the gastrula stage. In other embryonic tissues (nascent paraxial mesoderm, neural plate, endoderm, and tailbud), AmphiVent and its vertebrate homologs are expressed in similar spatiotemporal domains, indicating conservation of many Vent gene functions during chordate evolution. The ventral mesoderm evidently develops precociously in vertebrates because their relatively large embryos probably require an early and extensive deployment of the mesoderm-derived circulatory system. The vertebrate ventral mesoderm, in spite of its strikingly early advent, still resembles the nascent ventral mesoderm of amphioxus in expressing Vent homologs. This coincidence may indicate that Vent homologs in vertebrates and amphioxus play comparable roles in ventral mesoderm specification.

Amino Acid Sequence↗

PubMed2001

MUSIC, selective pulses, and tuned delays: amino acid type-selective (1)H-(15)N correlations, II.

Amino acid type-selective experiments help to remove ambiguities in either manual or automated assignment procedures. Here we present modified triple-resonance experiments that yield amino acid type-selective (1)H-(15)N correlations. They are based on the MUSIC coherence transfer scheme which replaces the initial INEPT transfer and is selective for XH(2) or XH(3) (where X is either (15)N or (13)C). Signals of the desired amino acid types are thus selected based on the topology of the side chain. MUSIC is combined with selective pulses and carefully tuned delays to create experiments for Ser (S-HSQC); Val, Ile, and Ala (VIA-HSQC); Leu and Ala (LA-HSQC); Asp, Asn, and Gly (DNG-HSQC), as well as Glu, Gln, and Gly (EQG-HSQC). The new experiments are recorded as two-dimensional spectra and their performance is demonstrated by their application to two protein domains of 83 and 115 residues.

Algorithms↗