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Biomedical subjects

M Scholz

Publications and source records attributed to M Scholz.

At least 127 records · Page 7Linked to original sources
PubMed1999

Analysis of principal component based quantitative phenotypes for alcoholism.

Principal component analysis was used to construct quantitative phenotypes for alcoholism. These were analyzed for linkage to genomic regions with a variance components approach. The four phenotypes considered were a factor describing medical symptoms of alcohol dependency, a factor describing a psychological profile correlated with susceptibility to alcoholism, monoamine oxidase B (MAOB) activity and an average measurement of the P3 component of event-related potentials (ERP) at the Fp electrode placements. One region (around marker GATA123C09 on chromosome 3) with suggestive evidence for linkage was detected for the P3 (Fp) measurement. For three of the four distinct phenotypes, modest evidence for linkage to a similar region (around marker ADH3 on chromosome 4) was found.

Alcoholism↗
PubMed1999

Treatment planning for light ions: how to take into account relative biological effectiveness (RBE).

A new treatment planning program was developed for the heavy ion therapy facility at GSI, which is tailored to the special needs for an active beam delivery using a magnetic raster scanner. It also includes a biological model for the estimation of biological effective dose for carbon ions and realizes a fully biological treatment planning. Biological effective dose distributions and RBE maps can be displayed and assessed from the graphical user interface.

Chondrosarcoma↗
PubMed1999

Time since vertebral fracture: an important variable concerning quality of life in patients with postmenopausal osteoporosis.

The aim of the study was to identify factors affecting patients with postmenopausal osteoporosis who had experienced one or more vertebral fractures. The overall hypothesis was that time after fracture would influence patients' perception of pain and well-being. The sample (50 patients) was split into two groups (group A, time after fracture < or > 24 months; group B, time after fracture >24 months). A fracture was defined as a vertebral height reduction of more than 20% or at least 4 mm. The assessment was carried out using the Spine Deformity Index and was confirmed by an experienced radiologist. To assess quality of life (QoL) the following measures were used: 'well-being scale' including social extroversion as a subscale, pain scale, and limitations in everyday life. The Sense of Coherence questionnaire developed by Antonovsky measures the ability of a person to see life meaningful, manageable and explicable. This questionnaire may reflect patients' coping abilities and was introduced to establish whether these influence the perception of pain and well-being after vertebral fracture. Variance and covariance analysis was carried out using SPSS (version 6.1). Differences between groups A and B were found for perception of average pain (p = 0.017), social extroversion (p = 0.003) and well-being (p = 0.024). No differences were found for limitations in everyday life (p = 0.607), Sense of Coherence (p = 0.638), the Spine Deformity Index (p = 0.171) and loss of height (p = 0.619). All analyses were corrected for age. Concurrent medication was not found to influence the results. Findings suggest that time after fracture is an important variable when considering QoL and well-being after vertebral fracture and should, therefore, be considered in future studies.

Aged↗
PubMed1999

Quality of life in patients with vertebral fractures: validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Working Party for Quality of Life of the European Foundation for Osteoporosis.

Vertebral fractures may be minor or lead to pain, decreased physical function, immobility, social isolation and depression, which together contribute to quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with vertebral fractures. This questionnaire, QUALEFFO, includes questions in the domains pain, physical function, social function, general health perception and mental function. QUALEFFO was validated in a multicenter study in seven countries. The study was done in 159 patients aged 55-80 years with clinical osteoporosis, i.e., back pain and other complaints with at least one vertebral fracture and lumbar bone mineral density T-score <-1. Patients with a recent vertebral fracture were excluded because of unstable disease. Controls were age- and sex-matched, and did not have chronic back pain or vertebral fractures. Subjects with conditions exerting a major influence on quality of life were excluded. The QUALEFFO was administered twice within 4 weeks and compared with a generic questionnaire, the Short Form 36 of the Medical Outcomes Study (SF-36). Standard spinal radiographs were made for assessment of vertebral height. Seven questions were removed from the analysis because of low response rate, linguistic ambiguities or redundancy. The 41 remaining questions were analyzed for repeatability, internal consistency and the capacity to discriminate between patients with vertebral fractures and controls. Comparison with the SF-36 was performed within similar domains by conditional logistic regression and by receiver operating characteristic (ROC) curves. The repeatability of QUALEFFO was good (kappa statistics 0.54-0.90) and 26 of 41 questions had a kappa score >/=0.70. The internal consistency of the five domains was adequate, with Crohnbach alpha around 0.80. All except five questions discriminated significantly between patients and controls. The median scores of QUALEFFO were significantly higher in patients with vertebral fractures than in controls in all five domain (p<0. 001), which is consistent with decreased quality of life in patients with osteoporosis. Spinal radiographs were assessed using the McCloskey-Kanis algorithm. According to this, 124 patients (78%) had vertebral fractures of >/=3 SD severity, in contrast with 7 controls (4%). Significant correlations existed between scores of similar domains of QUALEFFO and the SF-36, especially for pain, physical function and mental function. All five domains within each questionnaire discriminated significantly between fracture cases and controls. The odds ratios for pain and social function were greater for QUALEFFO, while general health perception was more discriminating using the SF-36. The ROC curve analysis of QUALEFFO indicated that all five domains were significantly predictive of vertebral fractures. When comparing similar domains of the two questionnaires, QUALEFFO domains demonstrated significantly better performance for pain, physical function and social function. The QUALEFFO total score and SF-36 physical composite score showed similar performance. In conclusion, QUALEFFO is repeatable, coherent and discriminates well between patients with vertebral fractures and control subjects. The results of this study confirm the decreased quality of life in patients with vertebral fractures.

Aged↗
PubMed1999

Response of pig lung to irradiation with accelerated 12C-ions.

The response of pig lungs to irradiation with 12C-ions was assessed in two experiments to validate the procedures for heavy ion therapy planning at the Gesellschaft für Schwerionenforschung (GSI) and to explore their range of applicability. In both experiments, the target volume (spread-out Bragg peak, SOBP) was planned to be a 4 cm long cylinder with a diameter of 4 cm. Doses in the SOBP were prescribed to be equivalent to 5x4 Gy, 5x5.5 Gy and 5x7 Gy of x-rays in the first experiment, and to 5 fractions of 7 Gy and 9 Gy in the second experiment. The lung response in the first experiment was less than expected on the basis of earlier experiments with photons. Pneumonitis reaction and chronic fibrotic changes were observed outside the prescribed high-dose region. In the second experiment, the effects were more pronounced than had been expected on the basis of the first experiment. Changes were most intense in the high-dose region, but were also seen throughout the lung along the beam channel. Moreover, significant skin reactions were observed at the beam entrance site in all animals and - less pronounced - at the beam exit site in 3 of the 6 animals. In conclusion, the complex irradiation geometry of the pig lung, the changes of body weight between the two experiments, and insufficient accounting for a change in the relative biological effectiveness (RBE) computation led to substantial deviations of the observed reactions from expectations, the reasons for which could be identified in a subsequent analysis. The less pronounced lung reaction in the first experiment was due to an overestimation of RBE in a preliminary version of the algorithm for its determination. The extension of the fibrotic reaction resulted from the smear-out of the high-dose region due to density variations in tissue structures, respiratory movement, and limited positioning accuracy. The skin reactions at the entrance port reflect the different treatment geometry in the two experiments. The one unexplained observation is the mild skin reaction that was observed in the second experiment at the beam exit site.

Animals↗
PubMed1999

Tumor therapy and track structure.

The elevated relative biological effectiveness (RBE) of heavy ions like carbon is the main reason for their use in radiotherapy and is due to the microscopic distribution of dose inside each particle track. High local doses produce lesions that are expected to have a diminished possibility of repair. Thus, RBE depends on track structure and on the biological repair capacity of the tissue that is affected by the irradiation. For tumor treatment planning with heavy ions, the beam quality and the tissue sensitivity have to be taken into account. Using the dependence of radial dose distribution on particle energy and atomic number on the physical side and x-ray dose response for the repair capacity on the biological side, the response to particle irradiation can be calculated in the local effect model (LEM) and used for treatment planning. This article traces the route from electron emission as the basis of track structure to the RBE calculation and the application in treatment planning.

Electrons↗
PubMed1999

Human cytomegalovirus infection decreases expression of thrombospondin-1 independent of the tumor suppressor protein p53.

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis. It has been shown that promoter sequences of the TSP-1 gene can be transactivated by the wild-type tumor suppressor protein p53. As human cytomegalovirus (HCMV) infection inactivates wild-type p53 of various cell types, we investigated whether HCMV infection is associated with reduced TSP-1 production. We found, in conjunction with accumulated p53, that TSP-1 mRNA and protein expression was significantly reduced in HCMV-infected cultured human fibroblasts. To determine whether the observed TSP-1 suppression depends on p53 inactivation, the p53-defective astrocytoma cell line U373MG was infected with HCMV. In these cells TSP-1 expression was also significantly reduced by HCMV infection whereas expression of the p53 mutant variant remained unaltered. In both cell lines the decreased expression of TSP-1 mRNA occurred early after infection (4 hours), indicating that HCMV inhibits TSP-1 transcription during the immediate-early phase of infection before HCMV DNA replication. Inhibition of HCMV DNA synthesis by ganciclovir did not influence TSP-1 reduction whereas the antisense oligonucleotide ISIS 2922, complementary to HCMV immediate-early mRNA, completely prevented the HCMV-mediated TSP-1 suppression. These findings strongly suggest a novel role for HCMV in the modulation of angiogenesis due to p53-independent down-regulation of TSP-1 expression.

Antiviral Agents↗
PubMed1999

A model for the depth-dependence of receptive field size and contrast sensitivity of cells in layer 4C of macaque striate cortex.

A model of LGN-input to layer 4C of macaque primary visual cortex has been used to test the hypothesis that feedforward convergence of P- and M-inputs onto layer 4C spiny stellate neurons is sufficient to explain the observed gradual change in receptive field size and contrast sensitivity with depth in the layer. Overlap of dendrites of postsynaptic neurons between M- and P-input zones proved sufficient to explain change in the lower two-thirds of layer 4C, while more rapid change in upper 4C was matched by proposing two different M-inputs with partial overlap in upper 4C alpha.

Animals↗
PubMed1999

Effect of desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) on rat cytomegalovirus replication in vitro and in vivo.

Cytomegalovirus (CMV) infection is a major problem in the immunosuppressed patient. It is thought that besides direct CMV induced cell lysis, immunological damage is part of CMV pathogenesis. New antiviral drugs, which combine immunomodulating and antiviral qualities, could be beneficial. Recently, it has been described that desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) exhibit both properties. In this report the antiviral effects of both compounds against rat CMV (RCMV) are described in vitro and in vivo using a generalised and local infection model. In vitro, both compounds exhibited a significant antiviral effect, DTPA being more potent than DFO. However, in the generalised infection model no effect was seen on mortality, morbidity or presence of virus in internal organs. In rats infected subcutaneously in the hind paw, no effect was seen locally on paw thickness, presence of viral antigens and inflammatory response. In addition, these rats suffered from a generalised infection of low magnitude at 15 days post infection, although both DFO and DTPA were able to lower the level of viral replication. In conclusion, our data indicate that despite in vitro activity, in vivo usage of DFO or DTPA for acute CMV infection is not warranted.

Animals↗
PubMed1999

Results of a prospective multicenter study for evaluation of the diagnostic quality of an open whole-body low-field MRI unit. A comparison with high-field MRI measured by the applicable gold standard.

OBJECTIVE: To evaluate the diagnostic quality of an open whole-body low-field MRI scanner compared to high-field scanners. MATERIALS AND METHODS: Over a period of 3 months, 401 patients with diseases of the kidney (n = 78), the shoulder (n = 122), the spine (n = 105) and the cerebrum (n = 96) were prospectively evaluated in four participating centers. They all underwent clinical evaluation, low-field and high-field MRI examination and surgical or follow-up confirmation of diagnosis. Clinical, histopathologic, high-field and low-field MRI diagnoses were recorded in standardized questionnaires that were centrally evaluated. Statistical evaluation comprised two parts: ROC analysis assessed accuracy of MRI and clinical diagnoses; furthermore rates of concordance of high- and low-field MRI diagnosis were calculated. RESULTS: We found no statistically relevant difference in high-field MRI diagnosis compared to low-field MRI diagnostic accuracy measured by clinical or surgical gold standard in three of the four regions examined; in cerebral examinations there was a small yet significant advantage for the high-field systems (P = 0.01). CONCLUSION: We conclude that the open low-field scanner we evaluated using clinical and surgical gold standard as reference is able to achieve comparable diagnostic accuracy compared to high-field scanners at lower costs and greater patient comfort. Limitations due to field strength (signal-to-noise ratio, resolution, scan time) seem to be relevant only in a very small number of cases that warrant high-field examination.

Adult↗
PubMed1999

Impact of study quality on outcome in placebo-controlled trials of homeopathy.

We investigated the influence of indicators of methodological quality on study outcome in a set of 89 placebo-controlled clinical trials of homoeopathy in three different ways: (1) The results of studies meeting single criteria (explicit statement of random allocation, allocation concealment, double-blinding, completeness of follow-up) of methodological quality were compared with those of studies not meeting the criteria in univariate and multivariate analyses; (2) The results of studies scoring above and below predefined scores in two quality assessment scales were compared; (3) Primary studies were consecutively entered into a cumulative meta-analysis according to the summary scores derived from the quality assessment scales. All analyses were performed using meta-regression methods. Studies that were explicitly randomized and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria. In the cumulative meta-analyses, there was a trend for increasing effect sizes when more studies with lower-quality scores were added. However, there was no linear relationship between quality scores and study outcome. We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results. Because summarizing disparate study features into a single score is problematic, meta-regression methods simultaneously investigating the influence of single study features seem the best method for investigating the impact of study quality on outcome.

Analysis of Variance↗
PubMed1999

Drug-induced apoptosis in chronic lymphocytic leukemia.

Glucocorticoids and fludarabine are able to induce typical features of apoptosis in CLL lymphocytes. Cysteinyl aspartate specific proteases (caspases) play a key biochemical role in the apoptotic pathway. Caspase activation following cytotoxic stimuli leads to highly specific proteolytic cleavage of functionally important cellular enzymes. One of them is poly ADP-ribose) polymerase (PARP). To some extent caspase activation seems to be under the control of the Bcl-2 family of interacting proteins. We determined the role of Bcl-2-family proteins Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic), activation of caspase-3 (CPP32/Yama) and activation of PARP in CLL apoptosis. All 21 analyzed CLL samples expressed Bcl-2 and Bax. Four of 13 (31%) samples with a low Bcl-2/Bax ratio exhibited in vitro prednisolone resistance, whereas eight of nine (88%) samples with a high Bcl-2/Bax ratio were in vitro resistant (</=0.025). There was no significant correlation between clinical pre-treatment status and Bcl-2/Bax ratio. Caspase-3/CPP32 activity increase was registered after dexamethasone as well as after fludarabine treatment in CLL lymphocytes in vitro. Caspase inhibitor Z-VAD.fmk was only able to partially block dexamethasone-induced and spontaneous apoptosis but not fludarabine-induced apoptosis in CLL lymphocytes. PARP activity decreased after dexamethasone and fludarabine treatment. PARP inhibitor 3-aminobenzamide (3-AB) was able to partially inhibit dexamethasone-induced apoptosis but not fludarabine-induced and spontaneous apoptosis.

Aged↗
PubMed1999

Changes in central venous pressure and pulmonary capillary wedge pressure do not indicate changes in right and left heart volume in patients undergoing coronary artery bypass surgery.

The value of pulmonary artery catheterization is a matter for discussion. Previous studies suggest that direct measurements of intravascular volume distribution and cardiac volume indices may be of greater relevance than central venous and pulmonary capillary wedge pressure. We therefore used a thermo-dye dilution technique for the quantification of central blood volume, right ventricular end-diastolic volume and left heart volume in patients undergoing coronary artery bypass surgery. Measurements were performed after the induction of anaesthesia as well as 1, 6 and 24 h after surgery. Central venous pressure was significantly increased at 1 and 6 h, whereas right ventricular end-diastolic volume was increased only at 6 h post-operatively. Pulmonary capillary wedge pressure showed a tendency to increase whereas left heart and central blood volume decreased significantly after surgery. The results of the present study suggest that changes in cardiac filling pressure do not indicate changes in indices of cardiac volume in patients after coronary bypass surgery.

Blood Volume↗
PubMed1999

[Quantification of postoperative vigilance by evoked potentials].

OBJECTIVE: Patients will be discharged from the postoperative recovery room mostly on subjective clinical assessment. In this study an approach to a more quantitative judgment of postoperative vigilance is made by recording the P300-latency and neuropsychological tests. METHODS: 22 adult patients undergoing a disc operation were examined. For induction of anesthesia thiopental (4-5 mg/kg), fentanyl (0.1 mg) and a musclerelaxant (atracurium 0.4 mg/kg or succinylcholine 1-2 mg/kg after precurarisation with atracurium 5 mg) were given. Anesthesia was then continued with enflurance (1.0-1.2 MAC) in a mixture of 67% nitrous oxide in oxygen. If postoperative analgesia was needed, piritramid was injected in boli à 3-6 mg. The P300 was acoustically stimulated with an oddball-paradigm and recorded at Fz and Cz. Afterwards the latencies were measured and compared with a vigilance score composed of clinical parameters and neuropsychological tests. Recordings were done preoperatively and every 30 minutes up to 2 hours postoperatively. A correlation between P300-latencies and vigilance score was made with the coefficient of Spearman. Comparison of pre- and postoperative values was managed by using Wilcoxon test for matched pairs with Bonferroni-correction. RESULTS: Immediately after operation, P300 was obtained only in 8 patients (36%). The latencies were delayed (394 +/- 35 ms versus 326 +/- 12 ms preoperatively). During follow-up patients recovered and 2 hours postoperatively only one patient had no P300. At the end of the examination period P300-latencies of most patients had not yet reached the preoperative levels. The vigilance score in parallel showed decreases immediately after the operation and increases later on. However there were discrepancies between P300 latencies and neuropsychological findings, in some cases possibly due to the sedative effects of postoperative analgetics. CONCLUSION: Recording of P300-latencies showed remarkable cognitive deficits because of subclinical anesthesia hangover even 2 hours after a routine inhalational anesthesia. It is a good quantifiable method for assessment of postoperative vigilance. In some cases P300-latency is a more sensitive parameter for vigilance phenomena than clinical and neuropsychological scores.

Adult↗
PubMed1999

Surgical treatment of recurrent trigeminal neuralgia.

In this retrospective investigation 7 patients operated on for recurrent trigeminal neuralgia via a suboccipital enlarged burr hole trepanation were evaluated. The intraoperative findings indicate that neo-compressive effects due to foreign material used during prior surgery are more important than adhesions around the nerve. Furthermore, the results of recurrent operations are encouraging as 6 of the 7 patients were painfree without additional neurological deficits.

Adult↗
PubMed1999

RBE for carbon track-segment irradiation in cell lines of differing repair capacity.

PURPOSE: The LET position of the RBE maximum and its dependence on the cellular repair capacity was determined for carbon ions. Hamster cell lines of differing repair capacity were irradiated with monoenergetic carbon ions. RBE values for cell inactivation at different survival levels were determined and the differences in the RBE-LET patterns were compared with the individual sensitivity to photon irradiation of the different cell lines. MATERIAL AND METHODS: Three hamster cell lines, the wild-type cell lines V79 and CHO-K1 and the radiosensitive CHO mutant xrs5, were irradiated with carbon ions of different energies (2.4-266.4 MeV/u) and LET values (13.7-482.7 keV/microm) and inactivation data were measured in comparison to 250 kV x-rays. RESULTS: For the repair-proficient cell lines a RBE maximum was found at LET values between 150 and 200 keV/microm. For the repair-deficient cell line the RBE failed to show a maximum and decreased continuously for LET values above 100 keV/microm. CONCLUSIONS: The carbon RBE LET relationship for inactivation is shifted to higher LET values compared with protons and alpha-particles. RBE correlated with the repair capacity of the cells.

Animals↗
PubMed1999

Cytomegalovirus-induced transendothelial cell migration. a closer look at intercellular communication mechanisms.

A variety of cells such as leukocytes and tumor cells may adhere to endothelial cells and subsequently transmigrate into the solid tissue by involving specific intercellular molecular pathways. One important prerequisite for transendothelial migration is the loosening of endothelial cell-to-cell contact sites, which can be triggered by extravasating cells. Cytomegalovirus (CMV) has obviously evolved the ability not only to influence host cells floating in the blood stream to adhere to endothelial cells, but also to induce the formation of intercellular gaps within the endothelium, resulting in transendothelial migration. These features allow the virus to disseminate and evade the immune system. In coculture experiments with human endothelial monolayers and human CMV (HCMV)-infected neuroblastoma cells or leukocytes, changes in the integrity of the monolayer were observed and further analyzed on the molecular level. For example, HCMV may activate the integrin beta1alpha5 (VLA-5) that triggers adhesion to endothelial cells with subsequent focal disruption of endothelial cell-to-cell connections. It is hypothesized that a Ca(2+)-independent pathway following VLA-5 binding disconnects the cadherin-catenin-actin complex within the endothelial cells. The loss of cadherin function causes the loss of contact to the neighboring endothelial cells and thus could represent an important mechanism in HCMV-induced cellular transendothelial migration and disruption of the endothelial integrity.

Cell Adhesion↗