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Biomedical subjects

P Bauer

Publications and source records attributed to P Bauer.

At least 19 recordsLinked to original sources
PubMed2006

Immunoadsorption in severe C4d-positive acute kidney allograft rejection: a randomized controlled trial.

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.

Adult↗
PubMed2006

Genetic characterization of the polycotyledon locus in tomato.

Developmental mutants serve as a useful material to unravel the mechanisms necessary for organ development. The polycotyledon (poc) mutant of tomato, with multiple cotyledons in the seedling and varied phenotypic effects in the adult plant is one such mutant. Studies using physiological and anatomical methods in our lab suggest that POC is involved in the negative regulation of polar auxin transport, which is likely the reason for the pleiotropic phenotype in the mutant. Because of the physiological significance of the polycotyledon mutant described in this paper and also being first of its kind in tomato and also other plant species, we are using a map-based cloning approach to map the polycotyledon gene. Molecular mapping of this locus using segregating interspecific F2 mapping population localized polycotyledon gene close to TG424 marker on the long arm of chromosome 9. The closest marker mapped was a PCR marker identified in this study, E8A2 at a distance of 7.4 cM from the poc locus. The absence of tightly linked RAPD markers and the non-availability of more mapped markers in this region led us to initiate chromosome walk to polycotyledon gene. Both the flanking markers TG248 and E8A2 were used to screen the BAC library and a contig was developed for TG248 marker. The BAC-end sequences were analyzed for their use as RFLP markers to enrich this region for markers. Analysis of the BAC-end sequences revealed that poc is localized in the region surrounded by copia-like retrotransposon elements explaining the absence of markers in the euchromatin region on long arm of chromosome 9. Further studies identified two BAC-end sequences which mapped around the poc locus and also indicated very low physical versus genetic distance ratio in this region. The double mutant analyses of poc with the other two known polycotyledon mutants of tomato, pct and dem revealed allelism with pct; therefore, the poc mutant was named as pct1-2, and also the original pct mutant was renamed as pct1-1.

Alleles↗
PubMed2006

Application of adaptive designs--a review.

A literature search has been performed to review applications of the adaptive design methodology based on the combination test or conditional error function approach. Some features of the 60 papers identified are summarized, e.g., the specific methodology used, calendar year, country, impact factor of the journal, number of planned and performed stages respectively, stopping for futility boundaries, type of adaptations and others. A selection of the ten recent publications in journals with the highest impact factors is discussed in more detail. Most applications up to now aim at sample size reassessment, the majority of papers is coming from Germany. Although we found that renowned journals allow for sufficient space to present the new statistical methodology in all its necessary details, the general impression is that the presentation of the adaptive designs methodology in applied papers has to be improved. Education and development of standards could help to achieve this.

Data Interpretation, Statistical↗
PubMed2006

Free peritoneal tumour cells are an independent prognostic factor in curatively resected stage IB gastric carcinoma.

BACKGROUND: Several studies have shown that the cytological detection of free peritoneal tumour cells (FPTCs) in patients with gastric cancer indicates the presence of metastatic disease. The immunocytochemical detection of FPTCs, especially in early-stage tumours, has not been examined comprehensively. METHOD: Peritoneal lavage was performed in 351 patients before curative resection of a gastric carcinoma between 1987 and 2001, and an adequate sample was obtained from 346 patients. FPTCs were detected immunocytochemically using Ber-EP4 antibody. Median follow-up time was 70 months. RESULTS: FPTCs were detected in the lavage fluid of 74 patients (21.4 per cent) and correlated with increasing pathological tumour depth (pT) and lymph node (pN) status (P < 0.001). The 5-year overall survival of patients with FPTCs was significantly worse than that of patients without FPTCs (35 versus 71.9 per cent; P < 0.001). FPTCs were present in 14 (8.5 per cent) of 164 patients with stage IA or IB tumours. Although the detection of FPTCs had no prognostic significance for stage IA tumours, the presence of FPTCs in those with stage IB tumours was associated with a worse prognosis (P < 0.001). Multivariate analysis identified the presence of FPTCs as an independent prognostic factor in the whole cohort and in the stage IB subgroup. CONCLUSION: Detection of FPTCs is associated with poor prognosis even in patients with early-stage gastric cancer and should be used for risk-group stratification.

Adult↗
PubMed2005

Quantitative analysis of the Ge concentration in a SiGe quantum well: comparison of low-energy RBS and SIMS measurements.

The germanium concentration and the position and thickness of the quantum well in molecular beam epitaxy (MBE)-grown SiGe were quantitatively analyzed via low-energy Rutherford backscattering (RBS) and secondary ion mass spectrometry (SIMS). In these samples, the concentrations of Si and Ge were assumed to be constant, except for the quantum well, where the germanium concentration was lower. The thickness of the analyzed quantum well was about 12 nm and it was situated at a depth of about 60 nm below the surface. A dip showed up in the RBS spectra due to the lower germanium concentration in the quantum well, and this was evaluated. Good depth resolution was required in order to obtain quantitative results, and this was obtained by choosing a primary energy of 500 keV and a tilt angle of 51 degrees with respect to the surface normal. Quantitative information was deduced from the raw data by comparing it with SIMNRA simulated spectra. The SIMS measurements were performed with oxygen primary ions. Given the response function of the SIMS instrument (the SIMS depth profile of the germanium delta (delta) layer), and using the forward convolution (point-to-point convolution) model, it is possible to determine the germanium concentration and the thickness of the analyzed quantum well from the raw SIMS data. The aim of this work was to compare the results obtained via RBS and SIMS and to show their potential for use in the semiconductor and microelectronics industry. The detection of trace elements (here the doping element antimony) that could not be evaluated with RBS in low-energy mode is also demonstrated using SIMS instead.

Journal Article↗
PubMed2005

Apparent velocity threshold in the electronic stopping of slow hydrogen ions in LiF.

The electronic energy loss of hydrogen ions (protons and deuterons) in thin supported films of LiF has been studied in backscattering geometry for specific energies from 700 eV/u to 700 keV/u, using Rutherford backscattering spectroscopy and time-of-flight low-energy ion scattering spectroscopy. For specific energies below 8 keV/u, our data confirm velocity proportionality for the stopping cross section epsilon (like in a metal) down to 3.8 keV/u, as observed previously for protons and antiprotons despite the large band gap (14 eV) of LiF. Below 3.8 keV/u, the present results indicate an apparent velocity threshold at about 0.1 a.u. for the onset of electronic stopping.

Journal Article↗
PubMed2005

Biochemical markers and genetic research of ADHD.

ADHD (attention hyperactivity disorder) is a polygenetic disorder with various candidate genes. At this time, more than thirty dopaminergic, noradrenergic, serotonergic and GABA-ergic genes are known. The research of only some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought relatively consistent results confirming the heredity of ADHD syndromes. The results of research of other genes (DRD2, DRD3, MAO, ADR2A, GABA A3, GABA B3) are not clear yet. This paper summarizes the most important genetic data in correlations with biochemical periphery parameters (especially for DBH, HVA, MHPG, serotonin). Hypothetically, certain subgroups of ADHD may be identified by correlation of biochemical characteristics and some candidate genes. The paper discusses some implications for future research. Review.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease.

BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels of the substantia nigra (SN) in patients with Parkinson disease (PD) and in control subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron metabolism have been linked to basal ganglia disorders. One of these is ceruloplasmin (Cp), which is vitally involved in iron transport across the cell membrane. METHODS: One hundred seventy-six patients with PD according to the UK Brain Bank criteria and 180 ethnically matched control subjects, who were previously examined for SN iron signal changes by transcranial ultrasound, were examined for mutations in the Cp gene using denaturing high-performance liquid chromatography and subsequent sequencing for verification of unequivocal signals. Immunohistochemistry of PD midbrains was performed to examine the presence of Cp in Lewy bodies. RESULTS: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E) was significantly associated with PD and the ultrasound marker for increased SN iron levels. Moreover, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients and control subjects. Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD. CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD) patient or associated with the ultrasound marker for increased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis of PD. Further functional analyses are warranted to investigate whether these variations are causally linked to the complex pathogenesis of PD in a subset of cases.

Aged↗
PubMed2004

Screening for mutations of the IRP2 gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra.

IRP2 plays an important role in brain iron metabolism. We recently identified an increased amount of iron in patients with Parkinson's disease (PD) and hyperchogenicity of the substantia nigra (SN). Therefore, the IRP2 gene was screened for mutations in 176 PD patients with increased echogenicity of the SN. We identified one non-synonymous polymorphism (I888V) in exon 21 and a -88C > T polymorphism in the promoter region of IRP2 at similar frequencies in patients and controls without increased SN iron levels. In one patient a -74C > T variation was found which was not present in the control group. Our data indicate that mutations in the IRP2 gene are not a common cause of PD associated with SN iron accumulation.

Aged↗
PubMed2004

[Chronic anoperineal pain: diagnosis and strategy for evaluation].

Chronic anoperineal pain may result from diverse causes; a precise and painstaking diagnostic approach is necessary to avoid inappropriate treatments which may aggravate the situation. Advances in imaging and neurophysiologic testing have improved the ability to diagnose and differentiate coccydynia, pudendal neuralgia, and the pyriformis muscle syndrome. Other etiologies including anismus, the descending perineum syndrome, and the levator ani syndrome are discussed as well as psychologic ans somatic interactions.

Anus Diseases↗
PubMed2003

Interventions for normal tension glaucoma.

BACKGROUND: Normal tension glaucoma is a clinical condition in which the optic nerve is pathologically excavated and the visual field is disturbed. Nevertheless it has been assumed that intraocular pressure plays a role in the progression of visual field defects in this disease, but other, mainly vascular factors, have been discussed as well. OBJECTIVES: The objective of this review is to assess the effects of medical and surgical treatments for normal tension glaucoma. SEARCH STRATEGY: Trials were identified from the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register), MEDLINE, EMBASE and BIOSIS Previews. Bibliographies of identified trials were searched to find additional trials. In addition, investigators and pharmaceutical companies were contacted. Date of last search: January 2001. SELECTION CRITERIA: This review includes randomised controlled trials in which medical or surgical interventions were compared to no treatment, placebo or other treatment in people with normal tension glaucoma. Two reviewers independently assessed the full text copies of the possibly relevant trials. Trial quality was assessed according to the methods set out in Section 6 of the Cochrane Reviewers' Handbook (Clarke 2000). DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and results were compared for differences. Discrepancies were resolved by discussion. The heterogeneity of interventions, follow-up periods and outcomes did not allow for statistical combinations of the study results. MAIN RESULTS: According to the selection criteria on visual field loss, eight studies were included in this review. Only three studies focussed on patient relevant outcomes. In one trial a beneficial effect of lowering intraocular pressure was found, but only if data were corrected for cataract development. In two small studies a beneficial effect on visual field loss of brovincamine, a calcium antagonist was reported. REVIEWER'S CONCLUSIONS: In one study the effect of intraocular pressure lowering on visual field outcome was only significant when data were corrected for cataract development. The results for calcium antagonists are promising, but larger trials have to be performed. Studies that focussed on reduction of intraocular pressure or haemodynamic variables are not necessarily relevant for the outcome in people with normal tension glaucoma.

Antihypertensive Agents↗
PubMed2003

Niemann-Pick disease type A and B are clinically but also enzymatically heterogeneous: pitfall in the laboratory diagnosis of sphingomyelinase deficiency associated with the mutation Q292 K.

This study describes a diagnostic pitfall in the laboratory diagnosis of patients with sphingomyelinase deficiency (SMD; Niemann-Pick disease types A and B; NPA and NPB), in cases where sphingomyelinase activity was not determined with sphingomyelin as the natural enzymic substrate. Four of 24 SMD patients studied had falsely normal or enhanced activity, when a so-called artificial sphingomyelinase substrate, 2-N-(hexadecanoyl)-amino-4-nitrophenyl phosphorylcholine (HNP), was used, whereas SMD was clear with the sphingomyelin substrate. Those four patients had the Q292 K mutation of the acid sphingomyelinase gene (SMPD1) on at least one allele. Three of the four patients (no data available from one) experienced only late-infantile or juvenile, though distinct, neurological involvement, where learning disabilities, hypo- or areflexia or mild ataxia were initial signs. The laboratory pitfall with HNP substrate, which is used in many laboratories, raises the risk that some SMD patients are overlooked, and it prevents the consideration of a late-manifesting neurological course in some patients as well as the planning of enzyme substitution therapy in non-neurological SMD (NPB) patients. Since classical NPB is very rare, it is suggested that SMD patients with late- or mild-manifesting neurological symptoms should better be assigned to additional SMD subgroups than grouped with NPB.

Adolescent↗
PubMed2003

Remifentanil and nitrous oxide reduce changes in cerebral blood flow velocity in the middle cerebral artery caused by pain.

BACKGROUND: Cerebral blood flow is affected by painful stimuli, and analgesic agents may alter the response of cerebral blood flow to pain. We set out to quantify the effects of remifentanil and nitrous oxide on blood flow changes caused by experimental pain. METHODS: We simulated surgical pain in 10 conscious volunteers using increasing mechanical pressure to the tibia. We measured changes in cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)) caused by the pain, using transcranial Doppler sonography. We gave increasing doses of remifentanil (0.025, 0.05 and 0.1 micro g kg(-1) min(-1)) or nitrous oxide [20%, 35% and 50% end-tidal concentration (FE'(N(2)O))] and compared these effects on blood flow changes. RESULTS: Nitrous oxide increased CBFV(MCA) only when given at 50% FE'(N(2)O). Remifentanil did not affect CBFV(MCA). Pain increased CBFV(MCA). Both agents attenuated this pain-induced change in CBFV(MCA) with the exception of nitrous oxide at 20% FE'(N(2)O). CONCLUSIONS: Inhalation of nitrous oxide or adminstration of remifentanil attenuated pain-induced changes in CBFV(MCA).

Adolescent↗
PubMed2003

Sequential tests for noninferiority and superiority.

The problem of simultaneous sequential tests for noninferiority and superiority of a treatment, as compared to an active control, is considered in terms of continuous hierarchical families of one-sided null hypotheses, in the framework of group sequential and adaptive two-stage designs. The crucial point is that the decision boundaries for the individual null hypotheses may vary over the parameter space. This allows one to construct designs where, e.g., a rigid stopping criterion is chosen, rejecting or accepting all individual null hypotheses simultaneously. Another possibility is to use monitoring type stopping boundaries, which leave some flexibility to the experimenter: he can decide, at the interim analysis, whether he is satisfied with the noninferiority margin achieved at this stage, or wants to go for more at the second stage. In the case where he proceeds to the second stage, he may perform midtrial design modifications (e.g., reassess the sample size). The proposed approach allows one to "spend," e.g., less of alpha for an early proof of noninferiority than for an early proof of superiority, and is illustrated by typical examples.

Humans↗