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D Meier

Publications and source records attributed to D Meier.

At least 19 recordsLinked to original sources
PubMed2000

Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer.

Preparations of stress protein gp96 from tumor cells are active as tumor vaccines by eliciting immune responses against mixtures of individual tumor peptide antigens which are complexed to gp96. Due to the individual antigenicity of tumors, a vaccine consisting of tumor-derived gp96 has to be prepared individually for each patient from autologous tumor tissue. So far, gp96 expression by human tumors has not been analyzed. Here, we report stable and mostly homogenous expression of gp96 by colorectal cancer, which was enhanced compared to surrounding tumor stroma in 70% to 80% of colorectal cancer specimens. Fewer non-metastatic than metastatic primary cancer specimens showed enhanced gp96 expression. Glucose deprivation increased gp96 protein and RNA expression in the human colon cancer cell line HT-29 in accordance with the role of gp96 as a glucose-regulated stress protein. Additionally, TNF-alpha, interferons and other cytokines induced an increase of gp96 RNA expression in HT-29 cells, suggesting that gp96 expression by colorectal cancer cells can be influenced by different methods of immunomodulation. The stable and homogenous expression of gp96 in 19 primary and metastatic colorectal cancer specimens and the up-regulation of gp96 in colon cancer cells by glucose deprivation point to an essential role of this stress protein in colorectal cancer, presumably by protecting against hostile conditions of the tumor micro-environment like glucose deprivation. In view of these results, loss of gp96 expression by colorectal cancer cells as an immune escape mechanism is unlikely.

Colorectal Neoplasms↗
PubMed2000

[Madelung disease and obstructive sleep apnea syndrome: apropos of a case].

Madelung's disease, or benign symmetric lipomatosis, is an uncommon disease. It is an unencapsulated fatty infiltration which in rare cases extends into the perilaryngeal space and mediastinum. The authors present a case complicated by an obstructive syndrome and sleep apnoea syndrome, which was successfully treated by continuous positive airway pressure. The literature is reviewed.

Humans↗
PubMed1999

Sulfidoleukotriene generation from peripheral blood leukocytes of horses affected with insect bite dermal hypersensitivity.

Sulfidoleukotrienes (sLT) generated in vitro after incubation of equine peripheral blood leukocytes (PBL) with different inducing agents were determined in 18 healthy and 16 insect bite dermal hypersensitivity (IDH)-affected horses. PBL from these 32 horses were stimulated with Concanavalin A, Parascaris equorum, Culicoides nubeculosus and Simulium extracts, and with a six-Grass mix. The cells of all but four horses generated sLT after incubation with Concanavalin A; these four horses did also not produce sLT with the other inducing agents. Of the 28 remaining horses (12 affected with IDH and 16 healthy), all but three generated sLT with the P. equorum extract. The six-Grass mix did not induce sLT production in any of the tested horses. sLT generation with Concanavalin A and Parascaris was statistically not different between IDH-affected and healthy horses. PBL of the diseased horses, however, produced significantly more sLT with the Culicoides (p < 0.01) and Simulium (p < 0.05) extracts than those of the healthy animals. Additionally, sLT generation with the Culicoides extract was measured at different times of the year in one IDH-affected animal and remained high even in winter, when the horse was asymptomatic. sLT and histamine release were determined in 10 horses in parallel. Positive correlations of 0.81 and 0.82 for Concanavalin A and Parascaris (p < 0.01 and p < 0.05, respectively), and of 0.95 and 0.94 for Culicoides and Simulium (p < 0.01) were found between sLT and histamine release. These results indicate that, alike in humans, sLT are released in vitro from equine basophils along with histamine in response to various stimuli and that immediate type hypersensitivity reactions to Culicoides and Simulium are often involved in the pathogenesis of IDH. Thus, sLT generation from equine basophils offers an in vitro diagnostic tool for IDH even in sensitised but asymptomatic horses.

Animals↗
PubMed1999

Parenchymal cell proliferation in coronary arteries after percutaneous transluminal coronary angioplasty: a human tissue bank study.

PURPOSE: Restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains a limitation of this technique. Arterial wall cell proliferation is a component of restenosis preventable with intravascular brachytherapy. This study attempts to locate the sites of cellular proliferation after PTCA so as to aid the optimization of this therapy. METHODS AND MATERIALS: Autopsy records from January 1, 1985 through December 31, 1995 were reviewed, and 27 patients who received PTCA prior to death were identified who also had evidence of PTCA on histologic examination of the arterial sections. The sections were subjected to immunohistochemical staining for proliferating cell nuclear antigen (PCNA) to detect the proliferating cells in the arterial sections, followed by image analysis to determine the proliferative index (PI) of all regions and layers of the section. RESULTS: The PI did not differ significantly according to vessel region (plaque, plaque shoulder, or portion of vessel wall with lowest plaque burden), vessel layer (intima, media, adventitia), or evidence of prior PTCA. There was a trend toward a higher PI in young lesions. CONCLUSION: Cell proliferation in the vascular wall after PTCA was found throughout the treated arterial section's axial plane, not only in the periluminal region.

Angioplasty, Balloon, Coronary↗
PubMed1999

Transfer insensitive labeling technique (TILT): application to multislice functional perfusion imaging.

Cerebral blood flow can be studied in a multislice mode with a recently proposed perfusion sequence using inversion of water spins as an endogenous tracer without magnetization transfer artifacts. The magnetization transfer insensitive labeling technique (TILT) has been used for mapping blood flow changes at a microvascular level under motor activation in a multislice mode. In TILT, perfusion mapping is achieved by subtraction of a perfusion-sensitized image from a control image. Perfusion weighting is accomplished by proximal blood labeling using two 90 degrees radiofrequency excitation pulses. For control preparation the labeling pulses are modified such that they have no net effect on blood water magnetization. The percentage of blood flow change, as well as its spatial extent, has been studied in single and multislice modes with varying delays between labeling and imaging. The average perfusion signal change due to activation was 36.9 +/- 9.1% in the single-slice experiments and 38.1 +/- 7.9% in the multislice experiments. The volume of activated brain areas amounted to 1.51 +/- 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 +/- 0.72 cc in the ipsilateral M1 area, 1.27 +/- 0.39 cm3 in the contralateral and 1.42 +/- 0.75 cm3 in the ipsilateral premotor areas, and 0.71 +/- 0.19 cm3 in the supplementary motor area.

Artifacts↗
PubMed1999

Accuracy of MRI-guided stereotactic thalamic functional neurosurgery.

Our goal was to evaluate the accuracy of stereotactic technique using MRI in thalamic functional neurosurgery. A phantom study was designed to estimate errors due to MRI distortion. Stereotactic mechanical accuracy was assessed with the Suetens-Gybels-Vandermeulen (SGV) angiographic localiser. Three-dimensional MRI reconstructions of 86 therapeutic lesions were performed. Their co-ordinates were corrected from adjustments based on peroperative electrophysiological data and compared to those planned. MR image distortion (maximum: 1 mm) and chemical shift of petroleum oil-filled localiser rods (2.2 mm) induced an anterior target displacement of 2.6 mm (at a field strength of 1.5 T, frequency encoding bandwidth of 187.7 kHz, on T1-weighted images). The average absolute error of the stereotactic material was 0.7 mm for anteroposterior (AP), 0.5 mm for mediolateral (ML) and 0.8 mm for dorsoventral (DV) co-ordinates (maximal absolute errors: 1.6 mm, 2.2 mm and 1.7 mm, respectively; mean euclidean error: 1 mm). Three-dimensional MRI reconstructions showed an average absolute error of 0.8 mm, 0.9 mm and 1.9 mm in AP, ML and DV co-ordinates, respectively (maximal absolute errors: 2.4 mm, 2.7 mm and 5.7 mm, respectively; mean euclidean error: 2.3 mm). MRI distortion and chemical-shift errors must be determined by a phantom study and then compensated for. The most likely explanation for an average absolute error of 1.9 mm in the DV plane is displacement of the brain under the pressure of the penetrating electrode. When this displacement is corrected for by microelectrode recordings and stimulation data, MRI offers a high degree of accuracy and reliability for thalamic stereotaxy.

Artifacts↗
PubMed1999

Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal transplantation: impact on muscular phosphate content, mineral metabolism, and acid/base homeostasis.

Hypophosphatemia caused by renal phosphate loss occurs frequently after kidney transplantation. In assumption of systemic phosphorus depletion, the presumed deficit commonly is replaced by oral phosphate supplements. However, such treatment is debatable, because intracellular phosphorus stores have not been assessed in this setting and may not be accurately reflected by serum phosphate concentrations. Moreover, disturbances in mineral metabolism from chronic renal failure, such as hypocalcemia and hyperparathyroidism, may be prolonged with oral phosphate supplements. Conversely, a neutral phosphate salt might improve renal acid excretion and systemic acid/base homeostasis for its properties as a urinary buffer and a poorly reabsorbable anion. Twenty-eight patients with mild early posttransplantation hypophosphatemia (0.3-0.75 mmol/L) were randomly assigned to receive either neutral sodium phosphate (Na(2)HPO(4)) or sodium chloride (NaCl) for 12 weeks and examined with regard to (1) correction of serum phosphate concentration and urinary phosphate handling; (2) muscular phosphate content; (3) serum calcium and parathyroid hormone (PTH); and, (4) renal acid handling and systemic acid/base homeostasis. Mean serum phosphate concentrations were similar and normal in both groups after 12 weeks of treatment; however, more patients in the NaCl group remained hypophosphatemic (93% versus 67%). Total muscular phosphorus content did not correlate with serum phosphate concentrations and was 25% below normophosphatemic controls but was completely restored after 12 weeks with and without phosphate supplementation. However, the percentage of the energy-rich phosphorus compound adenosine triphosphate (ATP) was significantly higher in the Na(2)HPO(4) group, as was the relative content of phosphodiesters. Also, compensated metabolic acidosis (hypobicarbonatemia with respiratory stimulation) was detected in most patients, which was significantly improved by neutral phosphate supplements through increased urinary titratable acidity. These benefits of added phosphate intake were not associated with any adverse effects on serum calcium and PTH concentrations. In conclusion, oral supplementation with a neutral phosphate salt effectively corrects posttransplantation hypophosphatemia, increases muscular ATP and phosphodiester content without affecting mineral metabolism, and improves renal acid excretion and systemic acid/base status.

Acid-Base Equilibrium↗
PubMed1999

Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography.

A deficit in gamma-aminobutyric acid (GABA) levels in the brain or the cerebrospinal fluid (CSF) is found in many epilepsy patients. Frequency and severity of seizures may be reduced by treatment with GABA increasing medicaments as e.g. vigabatrin, an irreversible inhibitor of GABA-transaminase. For a better understanding of the associated effects, healthy volunteers were examined with magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) before and after intake of different doses of vigabatrin. For the MRS examinations, a dedicated localized spectral editing method was developed to determine GABA levels. The 11C-flumazenil (FMZ)-PET protocol allowed determination of GABA-A receptor binding. The results show a clear and dose-dependent increase in the brain GABA levels after the medication period as compared to the baseline values. The GABA-A receptor binding, on the other hand, did not change significantly.

Adult↗
PubMed1999

Recommendations for incorporating palliative care education into the acute care hospital setting.

This article presents recommendations for improving the education of physicians about end-of-life care in the acute care hospital setting. The authors, who have a variety of backgrounds and represent several types of institutions, formulated and reached consensus on these recommendations as members of the Acute Care Hospital Working Group, one of eight working groups convened at the National Consensus Conference on Medical Education for Care Near the End of Life in May 1997. A recently published literature review on the status of palliative care education, a summary of recent research on education about end-of-life care, and expert opinion were helpful in developing the recommendations. The authors emphasize that the acute care setting offers many opportunities for education about care at the end of life. Faculty should support learners' appreciation of the importance of end-of-life care, and convey the meaning and privilege of attending to patients and families at this difficult time. Faculty should teach students and residents to provide care that embodies attention to the control of distressing physical, physiologic, and spiritual symptoms, appropriate awareness of patients' differing cultural backgrounds and their impact upon the experience of dying, excellent communication skills, the application of bioethical principles, timely referral and smooth transition to other care settings that meet patient and family goals, and the role of the interdisciplinary team in meeting the diverse needs of dying patients and their families.

Education, Medical, Continuing↗
PubMed1999

Thrombolysis in acute ischemic stroke: controlled trials and clinical experience.

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the National Institute of Neurological Disorders and Stroke (NINDS) showed a significant improvement in 3-month outcomes with rtPA despite a significant risk for symptomatic hemorrhage. Two other trials, the first and second European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary end point. An analysis of the risk/benefit profile of rtPA therapy based on the results of these three trials indicates that the treatment is effective and, when administered within 3 hours of symptom onset at a dose of 0.9 mg/kg, the benefits by far outweigh the risks for eligible patients. Even with the 6-hour time window of the two ECASS trials, a combined analysis of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.

Acute Disease↗
PubMed1999

From IgG monoclonals to IgM-like molecules.

One problem in blood group testing is that IgG monoclonal antibodies, in contrast to IgM, do not usually agglutinate erythrocytes. One of the reasons is the high zeta potential induced by the negative charge of the cell surface. During the last few years, we have produced a series of human monoclonal antibodies by the conventional fusion technique directed against antigens of the Rh blood group system. Some of these monoclonals, especially those directed against Rh-subgroups such as the c-antigen, were mainly of the IgG-subtype and unsuitable for agglutination tests. We have therefore tried to establish a molecular biological method to make IgM-like molecules from IgG monoclonals. From the c-antigen specific human hybridoma BS 240 (IgG subtype), we isolated mRNA that was transcribed into cDNA and then amplified by PCR using family specific primers. The heavy and light chain products were cloned into the pHen vector containing a DNA linker fragment, a myc-tag for identification and a His-tag for purification. After transformation in E.coli and phage rescue with helper phage, the culture supernatant was screened for antigen positive recombinant phage antibodies as a first control for specificity using c-antigen positive erythrocytes and anti-M13 antibodies as bridging antibodies (Coombs technique). Erythrocytes being negative for the c-antigen served as a negative control. After changing the culture conditions, soluble single chain fragments (scFv) were obtained from the periplasmatic extract. Specificity was shown using the c-antigen positive and negative erythrocytes and the 9E10 antibody (anti-myc) as a bridging antibody. To obtain IgM-like molecules, DNA coding for the specific scFv was cloned into the vector pSTE containing DNA coding for the monomer of core streptavidin. After expression, purification and refolding of the monomer, the core streptavidin combines to form tetrameric structures, termed scFv::strep, that are able to bind biotin as shown using ELISA plates coated with biotinylated BSA. Binding was detected with 9E10 and a peroxidase conjugated secondary antibody. In the agglutination assay, the construct was able to agglutinate c-antigen positive erythrocytes but not the negative erythrocytes. These experiments show that it is possible to construct IgM-like agglutinating molecules from cells containing secreting IgG antibodies. Experiments employing human antibody libraries instead of hybridoma cell lines are now in progress.

Amino Acid Sequence↗
PubMed1998

Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators.

BACKGROUND: Thrombolysis for acute ischaemic stroke has been investigated in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0.9 mg/kg bodyweight) within 6 h of stroke onset. METHODS: This non-angiographic, randomised, double-blind, trial enrolled 800 patients in Europe, Australia, and New Zealand. Computed tomography was used to exclude patients with signs of major infarction. Alteplase (n=409) and placebo (n=391) were randomly assigned with stratification for time since symptom onset (0-3 h or 3-6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0-1) and unfavourable (score 2-6) outcome. Analyses were by intention to treat. FINDINGS: 165 (40.3%) alteplase-group patients and 143 (36.6%) placebo-group patients had favourable mRS outcomes (absolute difference 3.7%, p=0.277). In a posthoc analysis of mRS scores dichotomised for death or dependency, 222 (54.3%) alteplase-group and 180 (46.0%) placebo-group patients had favourable outcomes (score 0-2; absolute difference 8.3%, p=0.024). Treatment differences were similar whether patients were treated within 3 h or 3-6 h. 85 (10.6%) patients died, with no difference between treatment groups at day 90+/-14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8.8%) alteplase-group patients and 13 (3.4%) placebo-group patients. INTERPRETATION: The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0.9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.

Adolescent↗
PubMed1998

Quantitative 1H MRS of the human brain in vivo based on the stimulation phantom calibration strategy.

Normal metabolite concentrations were determined in five different brain regions of healthy adult volunteers using proton magnetic resonance spectroscopy (1H MRS) in vivo. The absolute in vivo concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cre), and choline containing compounds (Cho) were quantified from measurements obtained with a head-shaped simulation phantom. Scanner performance and calibration accuracy were assessed by phantom experiments. Localized spectra were acquired on clinical 1.5 T systems using the PRESS localization sequence with frequency selective water suppression. Comparison of the results obtained from phantom experiments and human brain in vivo strongly suggests that reproducibility in vivo mainly depends on the topologic metabolite heterogeneity of brain tissue in combination with relative volume dislocalization.

Adolescent↗
PubMed1998

Heuristic optimization algorithms applied to the quantification of spectroscopic data.

The quantification of in vivo MR spectra imposes severe problems because of low spectral resolution and poor signal-to-noise ratio. Maximum likelihood methods are often applied. However, with conventional spectrum analysis procedures, the search for a global minimum in a multidimensional space often terminates in only a local minimum. Heuristic optimization procedures are able to circumvent this difficulty. Two approaches, the genetic algorithm and the simulated annealing, have been adapted to the quantification of MR spectra. For evaluation purposes, the procedures have been applied to synthetic and in vivo spectra with different noise levels. They both allowed a reliable spectrum quantification. The areas of most peaks were quantified reproducibly, although in some cases, the discrimination between spectroscopically almost identical metabolites (e.g., glutamate and glutamine) was not completely satisfactory. The two algorithms are found to be valuable alternative methods in the quantification of in vivo MR spectra.

Algorithms↗
PubMed1998

A new correlation-based fuzzy logic clustering algorithm for fMRI.

Fuzzy logic clustering algorithms are a new class of processing strategies for functional MRI (fMRI). In this study, the ability of such methods to detect brain activation on application of a stimulus task is demonstrated. An optimization of the selected algorithm with regard to different parameters is proposed. These parameters include (a) those defining the pre-processing procedure of the data set; (b) the definition of the distance between two time courses, considered as p-dimensional vectors, where p is the number of sequential images in the fMRI data set; and (c) the number of clusters to be considered. Based on the assumption that such a clustering algorithm should cluster the pixel time courses according to their similarity and not their proximity (in terms of distance), cross-correlation-based distances are defined. A clear mathematical description of the algorithm is proposed, and its convergence is proven when similarity measures are used instead of conventional Euclidean distance. The differences between the membership function given by the algorithm and the probability are clearly exposed. The algorithm was tested on artificial data sets, as well as on data sets from six volunteers undergoing stimulation of the primary visual cortex. The fMRI maps provided by the fuzzy logic algorithm are compared to those achieved by the well established cross-correlation technique.

Algorithms↗
PubMed1998

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo.

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy (1H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.

Adult↗