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A Hartmann

Publications and source records attributed to A Hartmann.

At least 19 recordsLinked to original sources
PubMed2000

Few-particle effects in semiconductor quantum dots: observation of multicharged excitons

We investigate experimentally and theoretically few-particle effects in the optical spectra of single quantum dots (QDs). Photodepletion of the QD together with the slow hopping transport of impurity-bound electrons back to the QD are employed to efficiently control the number of electrons present in the QD. By investigating structurally identical QDs, we show that the spectral evolutions observed can be attributed to intrinsic, multi-particle-related effects, as opposed to extrinsic QD-impurity environment-related interactions. From our theoretical calculations we identify the distinct transitions related to excitons and excitons charged with up to five additional electrons, as well as neutral and charged biexcitons.

Journal Article↗
PubMed2000

Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease.

Caspase-3 is an effector of apoptosis in experimental models of Parkinson's disease (PD). However, its potential role in the human pathology remains to be demonstrated. Using caspase-3 immunohistochemistry on the postmortem human brain, we observed a positive correlation between the degree of neuronal loss in dopaminergic (DA) cell groups affected in the mesencephalon of PD patients and the percentage of caspase-3-positive neurons in these cell groups in control subjects and a significant decrease of caspase-3-positive pigmented neurons in the substantia nigra pars compacta of PD patients compared with controls that also could be observed in an animal model of PD. This suggests that neurons expressing caspase-3 are more sensitive to the pathological process than those that do not express the protein. In addition, using an antibody raised against activated caspase-3, the percentage of active caspase-3-positive neurons among DA neurons was significantly higher in PD patients than in controls. Finally, electron microscopy analysis in the human brain and in vitro data suggest that caspase-3 activation precedes and is not a consequence of apoptotic cell death in PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

[Cardiac pacemaker therapy for optimizing brain circulation. A possible prevention for cerebrovascular diseases?].

HISTORY AND CLINICAL FINDINGS: A 78-year-old patient experienced dizziness, impairment of mnemic and cognitive function, chronic fatigue and recurrent syncope. INVESTIGATIONS: Hypertensive heart disease, reduced left ventricular function, and ventricular ectopia classification Lown IVb was documented. Computed tomography showed minimal brain atrophia. Stenoses of the brain supplying arteries and of other intracranial diseases were excluded. A distinct correlation between cardiac output and cerebral blood flow in correspondence to changes of heart rate were found (cardiac output 4.2 l/min during sinus rhythm, 7.4 l/min during temporary atrial pacing--AAI-Mode with a pacing rate of 90/min; 4.8 l/min--AAI-Mode with a pacing rate of 120/min; cerebral blood flow: 70, 74 and 62 ml/100 g per minute, respectively). Thus, impairment of cerebral blood flow autoregulation can be assumed. TREATMENT AND COURSE: After implantation of a permanent pacemaker the patient was without any complaints. The mnemic and cognitive function improved, dizziness and fatigue disappeared. Synopsis did not occur. 14 months later a sudden onset of complaints occurred caused by atrial fibrillation (heart rate 120/min). Cardiac output and cerebral blood flow were now 4.0 l/min and 35 ml/100 g per minute. After antiarrhythmic drug therapy and restoration of sinus rhythm cardiac output and cerebral blood flow increased and the complaints disappeared again. CONCLUSION: In patients with impaired capacity of cerebral autoregulation a reduced cardiac function and output can induce a reduction of cerebral blood flow. Thus, impairment of mnemic and cognitive function as well as other unspecific neurological deficits can be caused. In these cases pacemaker therapy has to be discussed as an effective therapeutical concept.

Aged↗
PubMed2000

Interrater agreement for high grade carotid artery stenosis measurement and treatment decision.

OBJECTIVES: Randomized trials in North America (NASCET, ACAS) and Europe (ECST) have shown a beneficial effect of endarterectomy for patients with high grade carotid artery stenosis. The results of the NASCET and the ECST further suggest that the effect of endarterectomy differed by degree of stenosis, supporting the importance of stenosis measurement as a factor in the decision process regarding surgery. We investigated the interrater agreement for carotid artery stenosis measurements and treatment decision in a post hoc study on patients undergoing carotid surgery. METHODS: In a one-year series, 45 consecutive patients underwent preoperative conventional cerebral angiography followed by endarterectomy. Using a magnifying eyepiece and applying the two different measurement criteria of the randomized trials, angiograms were re-evaluated post hoc by three masked raters. Intra-class correlation coefficients (ICCs) with one-sided 95% confidence intervals (CIs) were calculated for the estimation of interrater agreement for degree of stenosis. Conger s kappa (k) statistics were used for the estimation of interrater agreement for a dichotomized stenosis evaluation, i.e. therapeutic decision on surgery (cut-off point for symptomatic stenosis: 70%, cut-off point for asymptomatic stenosis: 60%). RESULTS: ICCs were.74 (CI.63) for NASCET/ACAS criteria and.72 (CI. 59) for ECST criteria. k values were.55 (CI.42) for NASCET/ACAS criteria and.57 (CI.44) for ECST criteria. Disagreement for a therapeutic decision was seen in 6 of 23 symptomatic patients by NASCET criteria, in 2 of 23 symptomatic patients by ECST and in 4 of 22 asymptomatic patients by ACAS criteria. CONCLUSIONS: Overall, the interrater agreement for stenosis measurements was good. Agreement for therapeutic decisions on carotid surgery, however, was less strong. These findings suggest that accurate stenosis measurement may not suffice for reliable treatment decisions in patients with high grade carotid artery stenosis.

Aged↗
PubMed2000

A prospective trial of midwest breast cancer patients: a p53 gene mutation is the most important predictor of adverse outcome.

Several retrospective studies have suggested p53 gene mutation as an adverse prognostic indicator in breast cancer patients, based on a selective growth advantage of p53 mutant cancer cells and their presumed resistance to current adjuvant therapy regimens. A cohort of 90 Caucasian midwestern breast cancer patients was analyzed prospectively (60 months of follow-up) with a rigorous mutation detection methodology. The presence of a p53 gene mutation was the single most adverse prognostic indicator for recurrence (p = 0.0032) and death (p = 0.0001), and was associated with poor response to both adjuvant (p = 0.0001) and palliative (p = 0.006) therapy. Analysis of the p53 gene with appropriate mutation detection methodology markedly improves the prediction of early recurrence, treatment failure, and death in breast cancer patients.

Breast Neoplasms↗
PubMed2000

Effect of atenolol and celiprolol on acetylcholine-induced coronary vasomotion in coronary artery disease.

Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3x10(-7), 2.0x10(-6), and 6.3x10(-6) M) was given before and after double-blind celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3x12 patients. Vasomotion was investigated by quantitative coronary angiography in proximal and distal segments of epicardial coronary arteries, and by the determination of the coronary resistance index based on Doppler-flow measurements. The investigated drugs had no direct affect on the diameter of the epicardial coronary arteries. However, celiprolol, in contrast to atenolol, significantly reduced systemic vascular resistance (change after atenolol: from 1,855+/-308 to 2,161+/-550 dyne s cm(-5); celiprolol: 1,691+/-435 to 1,411+/-343 dyne s cm(-5); and placebo: 1,722+/-215 to 1,710+/-213 dyne s cm(-5), p<0.001) and the coronary resistance index (change after atenolol: 2.52+/-3.58 to 2.86+/-4.24; celiprolol: 2.70+/-1.55 to 2.49+/-2.26; and placebo: 1.97+/-1.35 to 1.92+/-1.25, p<0.01). Celiprolol, atenolol, and placebo did not have different effects on acetylcholine-induced coronary vasomotion of epicardial conductance vessels (diminution of proximal lumen diameter before/after atenolol: 0.42+/-0.39/0.44+/-0.39 mm; celiprolol: 0.32+/-0.26/0.30+/-0.24 mm; and placebo: 0.36+/-0.29/0.43+/-0.40 mm) and of coronary resistance vessels (reduction of coronary resistance index before/after atenolol: 1.95 +/-4.74/ 1.92+/-3.74; celiprolol: 0.98+/-0.73/1.41+/-1.50; and placebo: 1.16+/-1.29/1.16+/-1.04). In contrast to atenolol, celiprolol possesses vasodilative properties in systemic and coronary resistance vessels. There was no direct effect on the diameter of conductance vessels. Acetylcholine-induced coronary vasomotion both in conductance and resistance vessels was not influenced by the beta blockers that were studied. This suggests that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide related vasomotion.

Acetylcholine↗
PubMed2000

Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing.

Atthe International Workshop on Genotoxicity Test Procedures (IWGTP) held in Washington, DC, March 25-26, 1999, an expert panel met to develop guidelines for the use of the single-cell gel (SCG)/Comet assay in genetic toxicology. The expert panel reached a consensus that the optimal version of the Comet assay for identifying agents with genotoxic activity was the alkaline (pH > 13) version of the assay developed by Singh et al. [1988]. The pH > 13 version is capable of detecting DNA single-strand breaks (SSB), alkali-labile sites (ALS), DNA-DNA/DNA-protein cross-linking, and SSB associated with incomplete excision repair sites. Relative to other genotoxicity tests, the advantages of the SCG assay include its demonstrated sensitivity for detecting low levels of DNA damage, the requirement for small numbers of cells per sample, its flexibility, its low costs, its ease of application, and the short time needed to complete a study. The expert panel decided that no single version of the alkaline (pH > 13) Comet assay was clearly superior. However, critical technical steps within the assay were discussed and guidelines developed for preparing slides with agarose gels, lysing cells to liberate DNA, exposing the liberated DNA to alkali to produce single-stranded DNA and to express ALS as SSB, electrophoresing the DNA using pH > 13 alkaline conditions, alkali neutralization, DNA staining, comet visualization, and data collection. Based on the current state of knowledge, the expert panel developed guidelines for conducting in vitro or in vivo Comet assays. The goal of the expert panel was to identify minimal standards for obtaining reproducible and reliable Comet data deemed suitable for regulatory submission. The expert panel used the current Organization for Economic Co-operation and Development (OECD) guidelines for in vitro and in vivo genetic toxicological studies as guides during the development of the corresponding in vitro and in vivo SCG assay guidelines. Guideline topics considered included initial considerations, principles of the test method, description of the test method, procedure, results, data analysis and reporting. Special consideration was given by the expert panel to the potential adverse effect of DNA degradation associated with cytotoxicity on the interpretation of Comet assay results. The expert panel also discussed related SCG methodologies that might be useful in the interpretation of positive Comet data. The related methodologies discussed included: (1) the use of different pH conditions during electrophoreses to discriminate between DNA strand breaks and ALS; (2) the use of repair enzymes or antibodies to detect specific classes of DNA damage; (3) the use of a neutral diffusion assay to identify apoptotic/necrotic cells; and (4) the use of the acellular SCG assay to evaluate the ability of a test substance to interact directly with DNA. The alkaline (pH > 13) Comet assay guidelines developed by the expert panel represent a work in progress. Additional information is needed before the assay can be critically evaluated for its utility in genetic toxicology. The information needed includes comprehensive data on the different sources of variability (e.g., cell to cell, gel to gel, run to run, culture to culture, animal to animal, experiment to experiment) intrinsic to the alkaline (pH > 3) SCG assay, the generation of a large database based on in vitro and in vivo testing using these guidelines, and the results of appropriately designed multilaboratory international validation studies.

Animals↗
PubMed2000

Each administration of cyclosporin A enhances skin microvascular reactivity in renal transplant recipients.

Both impaired and enhanced microvascular function have been described in humans on cyclosporin A (CsA) therapy. In the present study we investigated the acute microvascular effects of a single CsA administration in renal transplant recipients on maintenance CsA therapy. Fourteen renal transplant recipients, median age 48 years (range 24-63 years), transplanted 4-12 weeks earlier, were included in this placebo-controlled, double-blinded, crossover study. All recipients had stable renal function; median serum creatinine was 116 micromol/L (range 80-184 micromol/L). Immunosuppressive therapy consisted of CsA, prednisolone, and either azathioprine or mycophenolate. Microvascular function was assessed by laser Doppler flowmetry in combination with acetylcholine (endothelium dependent) stimulation and the postocclusive reactive hyperemia test. Measurements were performed before (control) and 2.5 h following administration of CsA (Neoral) or matching placebo and repeated with reversed medication after at least 6 days. Vasodilative responses to acetylcholine stimulation were significantly higher following CsA ingestion compared with placebo. The mean change in AUC(1.5) (area under the flux versus time curve) from control to 2.5 h was 100 +/-145 for CsA and -292 +/- 140 AU x min for placebo (P = 0.047, n = 10). The postocclusive hyperemic response AUC(rh) was also significantly higher following CsA intake (39 +/- 4 AU x min) compared to placebo (30 +/- 4 AU x min) (P = 0.006, n = 12). This study shows that each dose of CsA induces a transient increase in skin microvascular reactivity in renal transplant recipients. We speculate that this might be due to the potentiation of one or several endothelial-dependent compensatory vasodilative mechanisms in the microvascular bed.

Adult↗
PubMed2000

Prognostic significance of DNA cytometry in thymoma.

PURPOSE: The aim of this work was to evaluate the prognostic significance of DNA image cytometry in thymoma. PATIENTS AND METHODS: Image cytometric studies with an automatic video-based analysis system (LEYTAS) were carried out on 47 archival specimens from 36 patients with thymomas who underwent operation at a single institution from 1954 to 1992. The significance of aneuploidy DNA-content (5c-exceeding events), and nuclear size on stage and survival were evaluated. The median follow-up was 52.7 (6-164) months. RESULTS: Masaoka's stage was predictive of aneuploidy (P < 0.01) and disease-free survival (P < 0.015). In stage I 18% of the tumors were aneuploid, in stage II 78%, in stage III 85% and in stage IV 100%. The occurrence of 5c-exceeding events was associated with both decreased disease-free survival (P < 0.01) and overall survival (P = 0.013). Nuclear size was not significantly correlated to stage. Under multivariate analysis, aneuploidy and DNA content failed to attain independent significance for stage, performance status, and histology. CONCLUSION: DNA image cytometry may provide additional information about the prognosis of resected thymoma.

Adult↗
PubMed2000

Predictive value of clinical lacunar syndromes for lacunar infarcts on magnetic resonance brain imaging.

OBJECTIVE: We prospectively investigated the predictive value of clinical and CT-supported lacunar syndromes for lacunar infarcts on magnetic resonance (MR) brain imaging. PATIENTS AND METHODS: The 54 prospective, consecutive patients had clinical lacunar syndromes of acute onset and early computed tomography (CT; on admission day, i.e. < or =48 h after onset of symptoms) showing either a small deep infarct or no corresponding lesion. Taking MR (at day 2 to 4 after admission) as the gold standard, the positive predictive value of the CT-supported clinical syndrome for corresponding lacunar lesions was calculated. RESULTS: In 27 (50%) patients, early CT showed a lacunar infarct corresponding to the clinical syndrome, a further 27 (50%) patients had no fresh ischemic lesion. In 51 patients (94%), MR showed a recent lacunar infarct (hyperintense lacune in T2-weighted scans, no demarcation on T1-weighted scans and/or positive gadolinium-enhancement) corresponding to the clinical syndrome (positive predictive value 0.94, 95%, CI: 0.88 to 0.98). In 3 (6%) patients MR was normal. Aside from old unrelated ischemic (macro- and/or microangiopathic) lesions, MR revealed no acute non-lacunar infarct. CT and MR sites of lacunar lesions were matching. Compared to gold standard MR, the sensitivity of early CT for suspected lacunar lesions was 0.53 (95% CI: 0.38 to 0.67). CONCLUSION: Lacunar syndromes were highly predictive for small deep infarcts on MR. Magnetic resonance brain imaging may be redundant in the setting of a lacunar syndrome supported by a CT that excludes non-ischemic causes of stroke; it may therefore be abandoned in order to reduce costs in the health care system.

Adult↗
PubMed2000

Clonality and genetic divergence in multifocal low-grade superficial urothelial carcinoma as determined by chromosome 9 and p53 deletion analysis.

Multifocality and recurrence are clinically important features of urothelial carcinomas of the urinary bladder. Recent molecular genetic studies have suggested that multifocal urothelial carcinomas are monoclonally derived from an identical transformed progenitor cell. However, most of these studies investigated advanced and poorly differentiated tumors. The study presented focuses on early papillary tumors, including 52 superficial well-differentiated multifocal and recurrent bladder carcinomas from 10 patients. Microdissection separating urothelium from stromal cells was considered essential to obtain pure tumor cell populations. Genetic analysis was carried out by applying two different methods. Dual color fluorescence in situ hybridization (FISH) with centromeric probes for chromosomes 9 and 17 and gene-specific probes for chromosome loci 9q22, 9p21, and 17p13 was carried out in parallel to loss of heterozygosity (LOH) analyses applying 5 microsatellite markers on these chromosomes. Overall, deletions on chromosome 9p were found in 47 tumors (90%), at chromosome 9q in 36 tumors (69%) and at chromosome 17p in 3 tumors (6%). There was a very high correlation of the results between FISH and LOH analysis. Ten early superficial papillary tumors showed deletion of chromosome 9p without deletion of 9q, suggesting 9p deletions as a very early event in the development of papillary urothelial carcinoma. Although in four patients, all investigated tumors showed identical genetic alterations and one patient showed no genetic alterations at the loci investigated, in five patients, two or more clones with different deletions were found. In four of these patients, the results are compatible with clonal divergence and selection of different cell subpopulations derived from a common progenitor cell. However, in one patient different alleles in two markers at chromosome 9 were deleted, favoring an independent evolution of two recurring tumor cell clones. In summary, we could show that there is considerable genetic heterogeneity in early multifocal and recurring urothelial carcinoma and demonstrated the occurrence of two independent clones in at least one patient as an indicator of possible initial oligoclonality of bladder cancer.

Aged↗
PubMed2000

A trans-acting factor, isolated by the three-hybrid system, that influences alternative splicing of the amyloid precursor protein minigene.

Two clones were isolated in a three-hybrid screen of a rat fetal brain P5 cDNA library with an intronic splicing enhancer of the amyloid precursor protein (APP) gene as RNA bait. These clones represent the rat homologues of the previously described genes CUG-binding protein (CUG-BP) and Siah-binding protein (Siah-BP). Both interact in a sequence-specific manner with the RNA bait used for library screening as well as with the CUG repeat. In contrast, no interactions were observed in the three-hybrid assay with other baits tested. In two-hybrid assays, Siah-BP interacts with U2AF65 as well as with itself. EWS, an RGG-type RNA-binding protein associated with Ewing sarcoma, was identified as an interacting partner for the CUG-BP homologue in a two-hybrid assay for protein-protein interactions performed with various factors involved in RNA metabolism. Splicing assays performed by RT-PCR from cells cotransfected with certain cDNAs and an APP minigene, used as a reporter, indicate exclusion of exon 8 if the CUG-BP homologue is present. We conclude that clone AF169013 and its counterpart in human CUG-BP could be the trans-acting factors that interact with the splicing enhancer downstream of exon 8, and in this way influence alternative splicing of the APP minigene.

Alternative Splicing↗
PubMed2000

Middle cerebral artery (MCA) susceptibility sign at susceptibility-based perfusion MR imaging: clinical importance and comparison with hyperdense MCA sign at CT.

PURPOSE: To describe the radiologic findings of susceptibility changes in acute middle cerebral artery (MCA) thromboembolism detected with three-dimensional (3D) susceptibility-based perfusion magnetic resonance (MR) imaging and to compare the detectability and clinical value of this sign with those of the hyperdense MCA sign at computed tomography (CT). MATERIALS AND METHODS: Twenty-three patients (mean age, 55 years) underwent CT and MR imaging within the first 6 hours after the onset of acute MCA stroke. The hyperdense MCA sign at CT and the presence of susceptibility changes in acute thromboembolism as depicted on T2*-weighted 3D perfusion MR images were assessed. The presence of each sign was correlated with clinical presentation. RESULTS: The sensitivity of the hyperdense MCA sign at CT was 54% (negative predictive value, 71%) compared with 82% (negative predictive value, 86%) for the susceptibility changes at MR imaging. There were no false-positive CT or MR readings. The presence of the MCA susceptibility sign correlated positively with the initial clinical presentation (chi(2) = 7.987, P =.009, Spearman rho = 0.589). However, neither of the signs was a predictor for clinical outcome in cases of spontaneous MCA stroke. CONCLUSION: In addition to the information traditionally provided with reconstructed perfusion parameter maps, 3D susceptibility-based perfusion MR images allow the identification of acute MCA thromboembolism with a sensitivity higher than that of CT.

Acute Disease↗
PubMed2000

Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy.

We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rifampicin for 2 months. Due to pharmacokinetic interaction with rifampicin, the prednisolone dose was doubled, and the dose of tacrolimus had to be tripled for maintenance of adequate trough concentrations. Five months following cessation of antibiotic treatment, the patient has regained normal strength and function in her left-sided extremities and has a serum creatinine level of about 160 micromol/l (1.8 mg/dl).

Anti-Bacterial Agents↗
PubMed2000

Determinants of neurological outcome after surgery for brain arteriovenous malformation.

BACKGROUND AND PURPOSE: We sought to define determinants of neurological deficit after surgery for brain arteriovenous malformation (AVM). METHODS: One hundred twenty-four prospective patients (48% women, mean age 33 years) underwent microsurgical brain AVM resection. Patients were examined by 3 study neurologists immediately before surgery, postoperatively in-hospital, by in-person long-term follow-up, and with a structured telephone follow-up. They were classified according to the 5-point Spetzler-Martin grading system, with its 3 elements: size, venous drainage pattern, and location. The functional neurological status was classified with the modified Rankin scale. Multivariate logistic regression models were applied to test the effect of patient age, gender, and the 3 Spetzler-Martin elements on early and long-term postoperative neurological complications. RESULTS: Twelve patients (10%) were classified as Spetzler-Martin grade 1; 36 (29%) as grade 2; 47 (38%) as grade 3; 26 (21%) as grade 4; and 3 (2%) as grade 5. Postoperatively, in-hospital, 51 patients (41%) showed new neurological deficits (15% disabling [ie, Rankin scale score >2] and 26% nondisabling [ie, Rankin 1 or 2]). At long-term follow-up (mean follow-up time 12 months), 47 patients (38%) revealed surgery-related neurological deficits (6% disabling; 32% nondisabling). The rate of neurological complications increased by Spetzler-Martin grade. Female gender, AVM size, and deep venous drainage were significantly associated with neurological deficits at in-hospital and long-term evaluation. For patient age and AVM location, no significant association was found. CONCLUSIONS: The findings suggest that female gender, AVM size, and AVM drainage into the deep venous system may be determinants of neurological deficit after microsurgical AVM resection.

Adolescent↗