Biomedical subjects

M Schumacher

Publications and source records attributed to M Schumacher.

At least 19 recordsLinked to original sources

PubMed2006

Measurement of the Gerasimov-Drell-Hearn Integrand for 2H from 200 to 800 MeV.

A measurement of the helicity dependence of the total inclusive photoabsorption cross section on the deuteron was carried out at MAMI (Mainz) in the energy range 200<Egamma<800 MeV. The experiment used a 4pi detection system, a circularly polarized tagged photon beam and a frozen-spin target which provided longitudinally polarized deuterons. The contribution to the Gerasimov-Drell-Hearn sum rule for the deuteron determined from the data is 407+/-20(stat)+/-24(syst) mu b for 200<Egamma<800 MeV.

Journal Article↗

PubMed2006

[Microcatheter in neuroradiology].

The application of neuroradiologic microcatheters may be beneficial for the patient as well as preoperative intervention or as sole therapeutical procedure. However, it is associated with a relatively high procedural risk, which is also supported by critical dimensions of the microcatheter. It is regrettable, that to some extent, the performance of manufacturers of microcatheters stay below today's technical possibilities. Conducted investigations of ruptured catheters could not prove, that ruptures could have been avoided by using better manufacturing techniques, however, it should be expected, that manufacturers ensure the highest possible technical performance. Attempts to re-process those products, because of their high price show, that not all technical problems and resulting risks are well understood by all parties concerned. The demand for re-processing is not congruous with current medical responsibility.

Catheterization↗

PubMed2006

Use of multistate models to assess prolongation of intensive care unit stay due to nosocomial infection.

BACKGROUND: Reliable data on the costs attributable to nosocomial infection (NI) are crucial to demonstrating the real cost-effectiveness of infection control measures. Several studies investigating this issue with regard to intensive care unit (ICU) patients have probably overestimated, as a result of inappropriate study methods, the part played by NIs in prolonging the length of stay. METHODS: Data from a prospective study of the incidence of NI in 5 ICUs over a period of 18 months formed the basis of this analysis. For describing the temporal dynamics of the data, a multistate model was used. Thus, ICU patients were counted as case patients as soon as an NI was ascertained on any particular day. All patients were then regarded as control subjects as long as they remained free of NI (time-to-event data analysis technique). RESULTS: Admitted patients (n=1,876) were observed for the development of NI over a period of 28,498 patient-days. In total, 431 NIs were ascertained during the study period (incidence density, 15.1 NIs per 1,000 patient-days). The influence of NI as a time-dependent covariate in a proportional hazards model was highly significant (P< .0001, Wald test). NI significantly reduced the discharge hazard (hazard ratio, 0.72 [95% confidence interval, 0.63-0.82])--that is, it prolonged the ICU stay. The mean prolongation of ICU length of stay due to NI (+/- standard error) was estimated to be 5.3+/-1.6 days. CONCLUSIONS: Further studies are required to enable comparison of data on prolongation of ICU length of stay with the results of various study methods.

Aged↗

PubMed2006

A marker for Stevens-Johnson syndrome ...: ethnicity matters.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions, which can be caused by a certain number of specific drugs among which is carbamazepine, an antiepileptic agent. A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population. Here in, we report preliminary results from a European study (RegiSCAR) of 12 carbamazepine-induced SJS/TEN cases (nine French and three German). Among these only four had a HLA-B*1502 allele. Remarkably, these four patients had an Asian ancestry, whereas the others did not as far as we have ascertained. This shows that although the HLA region may contain important genes for SJS, the HLA-B*1502 allele is not a universal marker for this disease and that ethnicity matters.

Adult↗

PubMed2006

Injury elicited increase in spinal cord neurosteroid content analyzed by gas chromatography mass spectrometry.

The effects of spinal cord injury (SCI), combined with castration and adrenalectomy, and of progesterone (PROG) treatment on neurosteroid levels and steroidogenic enzyme expression were investigated in the adult male rat spinal cord (SC). Steroid levels were quantified by gas chromatography/mass spectrometry in SC and plasma, and mRNAs of enzymes by quantitative real-time RT-PCR. The levels of pregnenolone (PREG), PROG, 5alpha-dihydroprogesterone, 3alpha,5alpha-tetrahydroprogesterone increased in SC 75 h after transection without significant increase in the plasma. After combined adrenalectomy and gonadectomy, significant levels of PREG and PROG remained in the SC, suggesting their local biosynthesis. In the SC of adrenalectomized and gonadectomized rats, there was an increase of PREG 24 h after SCI, followed at 75 h by a concomitant increase in its direct metabolite, PROG. These observations are consistent with a sequential increase of PREG biosynthesis and its conversion to PROG within the SC in response to injury. However, no significant change in P450-side chain cleavage and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase mRNA levels was observed after SCI. Systemic PROG treatment after SCI, resulted in a very large increase in PROG, 5alpha-dihydroprogesterone, and 3alpha,5alpha-tetrahydroprogesterone in both plasma and SC. Furthermore, high levels of 3beta,5alpha-tetrahydroprogesterone were detected in SC, whereas their plasma levels remained barely detectable. Because the ratio of reduced metabolites to PROG was 65-times higher in SC than in the plasma, it appears likely that reduced metabolites mainly originated from local biosynthesis. Our results strongly suggest an important role for locally biosynthesized neurosteroids in the response of the SC to injury.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

[Lysis therapy vs. conservative therapy: randomised and prospective study on the treatment of acute central retinal artery occlusion (EAGLE study)].

In the prospective, randomised and multicenter EAGLE study, the therapeutic efficiency of local intra-arterial fibrinolysis (LIF) versus conservative treatment is being tested in patients with an acute central retinal artery occlusion (CRAO). The most important inclusion criteria are: (1) age between 18-75 years, (2) CRAO not older than 20 h, and (3) visual acuity <0.32. The primary study endpoint is the visual acuity before and 1 month after therapy. The study was started in 2002. To August 2006, 63 of the 200 required patients have been included in the study at 17 medical centers in Germany, Switzerland and Austria.

Europe↗

PubMed2006

[Radical prostatectomy in the treatment of organ confined prostate cancer].

Open radical prostatectomy represents one possible therapeutic option for treating patients with clinically localized prostate cancer Patient selection and the surgical management have undergone important changes during the last years, resulting in lower morbidity and probably in a better tumor control due to a better standardisation of the surgical technique. Long-term functional outcome regarding continence and potency are of increasing importance and influence mainly the quality of life in these patients. Open radical retropubic prostatectomy remains the gold standard in patients with localized prostate cancer, due to its low morbidity and excellent oncological and functional results. The value of laparoscopic and robotic radical prostatectomy is still discussed controversially. Due to the relative high morbidity during the so-called learning curve and the lack of long-term oncological and functional results, these techniques seem to show less favourable results.

Humans↗

PubMed2006

Neuroprotective effect of mifepristone involves neuron depolarization.

In several regions of the developing nervous system, neurons undergo programmed cell death. In the rat cerebellum, Purkinje cell apoptosis is exacerbated when cerebellar slices are cultured during the first postnatal week. To understand the mechanism of this developmental apoptosis, we took advantage of its inhibition by the steroid analog mifepristone. This effect did not involve the classical steroid nuclear receptors. Microarray analysis revealed that mifepristone down-regulated mRNA levels of the Na+/K+-ATPase alpha3 subunit more than three times. Consistent with the down-regulation of the Na+/K+-ATPase, mifepristone caused Purkinje cell membrane depolarization. Depolarizing agents like ouabain (1 microM), tetraethylammonium (2 mM), and veratridine (2 microM) protected Purkinje cells from apoptosis. These results suggest a role of excitatory inputs in Purkinje cell survival during early postnatal development. Indeed, coculturing cerebellar slices with glutamatergic inferior olivary neuron preparations allowed rescue of Purkinje cells. These findings reveal a new neuroprotective mechanism of mifepristone and support a pivotal role for excitatory inputs in the survival of Purkinje neurons. Mifepristone may be a useful lead compound in the development of novel therapeutic approaches for maintaining the resting potential of neurons at values favorable for their survival under neuropathological conditions.

Animals↗

PubMed2006

Are KISS data representative of German intensive care units? Statistical issues.

OBJECTIVES: Data collected within the German nosocomial infection surveillance system KISS are recommended as reference data for judging nosocomial infection rates in German intensive care units (ICUs). It is unknown whether the KISS data tend to under- or overestimate the true infection incidence rates. In this article, methodological aspects of the SIR1 study on the incidence of nosocomial infections are discussed, with the aim of estimating unbiased incidence rates of nosocomial infections in interdisciplinary German ICUs and examining whether the KISS data are representative. METHODS: We discuss the following methodological issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs. 3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates using a negative binomial regression model. 5) Comparison of weighted incidence rates with the standardized rate ratio (SRR). RESULTS: Random sampling proved difficult to realize in practice since many ICUs refused to participate, particularly those in small hospitals. Analysis was adjusted for hospital size. No seasonal trends were found in the KISS data. Due to marked differences between ICUs, the number of infections is over-dispersed compared to a Poisson model, so negative binomial regression was used. Fifty ICUs were observed for two consecutive months each, corresponding to 21,832 patient days, during which 262 infections occurred. Infections were more frequent in large hospitals. The incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20) times as large as those estimated by the KISS system. CONCLUSION: For estimating nosocomial infection incidence rates, random sampling and statistical modeling of over-dispersion were successfully performed. The study provides evidence that the KISS surveillance system tends to underestimate the true incidence rates of nosocomial infections in German ICUs.

Binomial Distribution↗

PubMed2005

Multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. EAGLE Study report no. 1 : EAGLE Study report no. 1.

BACKGROUND: The natural course of central retinal artery occlusion (CRAO) often leads to legal blindness in the affected eye. To date, none of the conservative therapies had proven effective in retrospective studies. In 1991, a new minimally invasive therapy was started in patients with an acute CRAO. This therapy, namely, local intra-arterial fibrinolysis, is comparable to the minimally invasive therapy in patients with an acute ischemic stroke. In pilot studies, it showed promising results in comparison with conservative treatments. The efficacy of this method is now being investigated in a randomized multicenter study. METHODS: The European Assessment Group for Lysis in the Eye (EAGLE) started a prospective and randomized multicenter study in 2002 to evaluate therapeutic efficacy. Inclusion criteria are age between 18 and 75 years and a CRAO not older than 20 h with a visual acuity less than 0.32. The most important exclusion criteria are branch retinal artery occlusion (BRAO), cilioretinal arteries supplying the macula, and serious general disease. After randomization the patient is treated by conservative or local intra-arterial lysis therapy. The conservative regime included bulbus massage, lowering intraocular pressure with topical beta-blocker and acetazolamide, acetylsalicylic acid, heparin, and-depending on the hematocrit-isovolemic hemodilution. In case of local intra-arterial fibrinolysis, a maximum of 50 mg rtPA is injected into the ophthalmic artery by the neuroradiologist. During the following 5 days, all patients are treated with heparin. Primary study end point is visual acuity 1 month after therapy in comparison with visual acuity before therapy. The calculated sample size is 100 patients per subtrial (a total of 200 patients). The study was started in June 2002. To April 2005, 47 patients were included. CONCLUSIONS: The EAGLE Study is the first randomized prospective clinical trial to compare conservative medical treatment and local intra-arterial fibrinolysis in patients with CRAO. The results of this study should enable ophthalmologists and neuroradiologists to improve the therapy of patients with acute CRAO. To April 2005, treatment is only justified in randomized multicenter studies because of the limited therapeutical visual outcome. We welcome new study centers to join.

Adolescent↗

PubMed2005

Measurement of helicity-dependent photoabsorption cross sections on the neutron from 815 to 1825 MeV.

Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat) +/- 4.5(syst)] microb is extracted.

Journal Article↗

PubMed2005

Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis.

Insulin-like factor 3 (INSL3) serum levels were measured in 135 andrologically well-characterized normal men and 85 patients with testicular disorders to investigate how the hormone, which is a major secretory product of human Leydig cells, is related to testosterone (T), LH, and semen quality. INSL3 was measured by using a newly developed fluorescence immunoassay. Median (2.5-97.5 percentiles) INSL3 serum levels were as follows: normal men (n = 135), 0.99 (0.55-1.73) ng/ml; infertile men (n = 23), 1.11 (0.60-2.07) ng/ml; anorchid men (n = 21), nondetectable (ND); patients with 47, XXY, Klinefelter syndrome (n = 21), 0.12 (ND-0.78) ng/ml; men with hypogonadotropic hypogonadism and T substitution (n = 11), ND; and men with hypogonadotropic hypogonadism and human chorionic gonadotropin (hCG) treatment (n = 5), 0.36 (0.13-0.73) ng/ml. Before testicular biopsy, two infertile men had blood samples drawn directly from vena spermatica. Here, the serum INSL3 levels were 15-fold higher than in serum from peripheral blood samples (13.84 and 14.00 ng/ml, respectively). In two unilaterally orchiectomized former testis cancer patients, who underwent hCG stimulation test, INSL3 serum levels were unchanged 72 and 96 h after hCG stimulation. In conclusion, we provide a normal range for INSL3 serum levels in adult men and show that the majority, if not all, circulating INSL3 derives from the testes. Furthermore, our data strongly indicate that INSL3 secretion is dependent on the differentiating effect of LH on Leydig cells but independent of the steroidogenic LH-mediated action. Thus, even though T and INSL3 are both dependent on LH, these two Leydig cell hormones are regulated differently.

Adolescent↗

PubMed2005

[The role of pelvic lymphadenectomy in clinically localised prostate cancer].

Lymph node dissection remains the only reliable method for exact staging to date. Extended lymphadenectomy including tissue along the external iliac vein, the obturator fossa, and along the internal iliac vessels should be performed in all patients undergoing radical prostatectomy. There is an increasing amount of data suggesting that removal of all diseased nodes, which contain minimal metastatic disease, may have a positive impact on disease-free and, perhaps, on overall survival. Due to the relatively benign course of the disease, longer follow-up periods are still necessary to make a definitive statement.

Clinical Trials as Topic↗

PubMed2005

[Ganglion curage in prostate cancer].

In clinically Localized prostate cancers, the interest of pelvic Lymphadenectomy is debated. Nevertheless, this intervention provides important information on disease prognosis (number of positive lymph nodes, tumoural volume, and extracapsular perforation of the affected ganglions); information that previously no other technique could provide. However, no consensus exists concerning patients who should benefit from pelvic Lymphadenectomy and on the extent of this intervention. For most surgeons, decision making regarding ganglion curage is based on nomograms. According to these nomograms, patients with a level of prostate specific antigen (PSA) <10 ng/mL and a Gleason score <7 have a very low risk for ganglionic metastases; this is the reason why the benefit of pelvic Lymphadenectomy remains controversial. Besides, most of these nomograms are based upon the results of standard Lymphadenectomy (iliac vein and obturator fossa) with, subsequently, a related risk of imprecision. In addition, potential therapeutic benefit may be expected from extended ganglion curage, despite the fact that this is not clearly documented yet, due to the benign course of the disease. In other tumoural diseases (stomach cancer, breast cancer, colorectal cancer, blade cancer), on the contrary, survival and stage identification depend on the number of removed ganglions, thus on the extent of Lymphadenectomy.

Humans↗

PubMed2005

Progesterone increases oligodendroglial cell proliferation in rat cerebellar slice cultures.

We have previously demonstrated that progesterone significantly increases the rate of myelination in organotypic slice cultures of 7-day-old rat and mouse cerebellum. Here, we show that progesterone (20microM) stimulates the proliferation of oligodendrocyte precursors in cultured cerebellar slices of 7-day-old rats. The steroid increased the number of pre-oligodendrocytes (NG2(+), O4(+)) and to some extent of oligodendrocyte precursors, corresponding to an earlier developmental stage (nestin(+), PDGFalphaR(+), NG2(+), O4(-)). Progesterone stimulated the proliferation of both NG2(+) and O4(+) cells as shown by increased double-immunolabeling with the cell proliferation marker Ki67. The mitogenic effect of progesterone was inhibited by the progesterone receptor antagonist mifepristone (10microM) and could not be mimicked by its GABA-active metabolite 3alpha,5alpha-tetrahydroprogesterone (allopregnanolone), even at the high concentration of 50microM. Results indicate that progesterone first strongly and transiently stimulates the proliferation of oligodendrocyte precursors, and that it may thereafter accelerate their maturation into myelinating oligodendrocytes. Although oligodendrocyte precursors may be a direct target for the actions of progesterone, their number may also be indirectly influenced by the effects of the steroid on neurons and microglial cells, since treatment of the cerebellar slices with progesterone enhanced staining of the neuronal cytoskeleton marker microtubule-associated protein-2 and increased the number of OX-42(+) microglia. A small percentage (about 0.1%) of the NG2(+) cells transiently became OX-42(+) in response to progesterone. These results point to novel mechanisms by which progesterone may promote myelination in the CNS, specifically by stimulating the proliferation and maturation of oligodendrocyte precursors into myelinating oligodendrocytes.

Animals↗

PubMed2005

Recruitment of the sensorimotor cortex--a developmental FMRI study.

INTRODUCTION: The growing mastery of motor tasks is one of the most visible changes in the developing child. The cortex is known to play a central role in learning, planning, and performance of motor tasks. We investigated the age dependency of motor cortex activation using functional magnetic resonance imaging (fMRI). METHODS: Thirty-two right-handed subjects were studied: 11 children (median age 9 years, range 6 - 10 years), 10 adolescents (median age 13 years, range 11 - 15 years), and 11 adults (median age 27 years, range 23 - 42 years). The subjects performed a simple, paced unilateral motor task (repetitive squeezing of a ball with the right hand). Also, we set up a control experiment (visual stimulation using an alternating checkerboard pattern) in which no age-related differences were expected. RESULTS: Compared to children, adults showed significantly increased activation of the bilateral sensorimotor cortex, parietal areas, the supplementary motor area, and the cerebellum. In the visual stimulation experiment there were no age-related differences. CONCLUSION: Children show a significant difference in the degree of cortical activation compared to adults when performing a simple motor task. The change in fMRI activation patterns may reflect a maturation process of primary and secondary motor areas.

Adolescent↗

PubMed2004

Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors.

Among the different steroids found in the brain, pregnenolone sulfate (3beta-hydroxy-5-pregnen-20-one-3-sulfate; PREGS) is known to enhance hippocampal-associated memory. The present study employs rat hippocampal slices to investigate the ability of PREGS to modulate long-term potentiation (LTP), a phenomenon considered as a model of synaptic plasticity related to memory processes. LTP (3 x 100 Hz/1 sec within 2 min), implicated essentially glutamatergic transmission, for which the different synaptic events could be pharmacologically dissociated. We show that PREGS enhances LTP in CA1 pyramidal neurons at nanomolar concentrations and exhibits a bell-shaped concentration-response curve. The maximal effect of PREGS on both induction and maintenance phases of LTP is observed at 300 nM and requires 10 min of superfusion. Although PREGS does not change the N-methyl-D-aspartate (NMDA) component of the field potentials (fEPSPs) isolated in the presence of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in Mg2+-free artificial cerebrospinal fluid, PREGS does enhance the response induced by NMDA application (50 microM, 20 sec). PREGS does not modify the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the fEPSPs isolated in the presence of 100 microM DL-2-amino-7-phosphopentanoic acid (DL-AP5) or its potentiation induced by a single tetanic stimulation and the response induced by AMPA application (10 microM, 10 sec). Furthermore, PREGS does not affect the recurrent inhibition of the fEPSPs mediated by gamma-aminobutyric acid type A (GABA(A)) receptor. In conclusion, this study shows the ability of PREGS to enhance LTP in CA1 by accentuating the activity of NMDA receptors. This modulation of LTP might mediate the steroid-induced enhancement of memory.

2-Amino-5-phosphonovalerate↗

PubMed2004

Experimental check of the Gerasimov-Drell-Hearn sum rule for 1H.

For the first time we checked the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the proton experimentally in the photon energy range from 0.2-2.9 GeV with the tagged photon facilities at MAMI (Mainz) and ELSA (Bonn). New data of the doubly polarized total cross section difference are presented in the energy range from 1.6 to 2.9 GeV. The contribution to the GDH integral from 0.2-2.9 GeV yields [254+/-5(stat)+/-12(syst)] microb with negative contributions in the Regge regime at photon energies above 2.1 GeV. This trend supports the validity of the GDH sum rule.

Journal Article↗