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Biomedical subjects

Frank Schneider

Publications and source records attributed to Frank Schneider.

At least 19 recordsLinked to original sources
PubMed2025

Suppression of LKB1-mutant lung adenocarcinoma by natural killer cells from females.

BACKGROUND: This study addressed the enigma of sex differences in smoking-related lung cancer, particularly focusing on the low LKB1 mutation frequency in female patients with lung adenocarcinoma. METHODS: Sex bias was studied with a genetically engineered mouse model and various tail-vein injection models. Immune cells were analyzed by antibody-depletion study, flow cytometry, and immunofluorescence. The relevance of our findings to human disease was validated by evaluating various lung adenocarcinoma datasets. All statistical tests are 2-sided. RESULTS: A statistically significant percentage of females are resistant to LKB1-mutant tumor formation in our models, reflecting this sex difference in humans. Natural killer (NK) cells were identified as a critical factor in this sex-biased response. This sex difference was observed primarily in LKB1-mutant lung adenocarcinoma, probably due to their low major histocompatibility complex class I level, making them the ideal target for NK cells through the missing-self recognition. Although females resistant to LKB1-mutant lung adenocarcinoma formation did not have enhancement of any specific NK subpopulation, our immunofluorescence analysis revealed high numbers of NKs in female lungs even with the presence of LKB1-mutant lung adenocarcinoma. Our gene set enrichment analysis of The Cancer Genome Atlas-lung adenocarcinoma dataset also showed that female LKB1-mutant lung adenocarcinoma patients have a stronger NK-mediated response after adjusting for other male-female differences using the LKB1 wild-type lung adenocarcinoma dataset. CONCLUSION: Females have a stronger NK-mediated response against LKB1-mutant lung adenocarcinoma, which was present in our mouse model and the human lung adenocarcinoma dataset. This study revealed a novel role of NK cells in suppressing LKB1-mutant lung adenocarcinoma in females, which should be assessed in the clinical setting in the future.

Killer Cells, Natural↗
PubMed2006

Optimization of extracranial stereotactic radiation therapy of small lung lesions using accurate dose calculation algorithms.

BACKGROUND: The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. METHODS: A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron) and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. RESULTS: The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. CONCLUSION: The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction.

Algorithms↗
PubMed2006

Laboratory benchmarking: the College of American Pathologists' experience.

Benchmarking is an important part of performance evaluation in the clinical laboratory. When used effectively, benchmarking can lead to significant changes and performance improvement. This article reviews the experience of the College of American Pathologists (CAP) with benchmarking clinical laboratory expenses and presents data that summarizes recent laboratory trends identified through CAP's benchmark data.

Benchmarking↗
PubMed2006

A special role of negative emotion in children and adolescents with schizophrenia and other psychoses.

Emotional impairments are apparent at an early stage in schizophrenia. While emotion processing has been studied intensively in adult patients, investigations focusing on children and adolescents with psychoses are rare. Emotion probes for mood induction and emotion discrimination that have been standardized in healthy subjects and applied to adult schizophrenia patients were evaluated in young patients (11-20 years). Twenty children and adolescents with schizophrenia and other psychotic disorders as well as twenty healthy volunteers matched for age, gender and parental education were examined. Results reveal successful mood induction in both patients and healthy volunteers, but with more negative affect prominent in patients. While a reduced ability to discriminate negative emotional faces emerged in patients than in controls, this difference failed to reach statistical significance. The similarities between test results of children and adolescents compared with those of adults demonstrate that both tests proved to be useful when applied to younger ages. Negative affect seems to be differentially affected, a finding that which may be already evident in the early course of schizophrenia.

Adolescent↗
PubMed2006

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study.

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Adolescent↗
PubMed2006

Interaction of negative olfactory stimulation and working memory in schizophrenia patients: development and evaluation of a behavioral neuroimaging task.

Negative affect plays a crucial role in the psychopathology of schizophrenia. Although it is known that negative emotion has a strong effect on cognitive performance, this interaction has mainly been studied in healthy volunteers. Hence, working memory was assessed in 24 schizophrenia patients and 24 matched comparison subjects with a 0-back/2-back continuous performance test. Simultaneously, negative emotion was induced by olfactory stimulation. Although subjective ratings confirmed that stimulation with a negative odor was associated with a significant increase in negative affect in patients and healthy volunteers, working memory performance was affected differentially in healthy volunteers and schizophrenia patients. Whilst a similar trend of a reduced behavioral performance during negative odor stimulation was observed in patients, only controls demonstrated a significantly higher response time and a reduced number of correct reactions during higher working memory demands (2-back). Patients, on the other hand, revealed an increase in false alarms during both conditions. The present data indicate a differential effect of negative mood induction on working memory performance in schizophrenia patients and healthy subjects.

Adult↗
PubMed2006

Prevention of epidural scarring after microdiscectomy: a randomized clinical trial comparing gel and expanded polytetrafluoroethylene membrane.

A randomized clinical trial compared two materials used to prevent epidural scarring after microdiscectomy. To determine whether ADCON-L Gel (ALG) or Preclude Spinal Membrane (PSM) was more effective in preventing scarring, reducing pain, and improving quality of life postoperatively. Postdiscectomy syndrome may result from epidural scarring. Various materials have been used in attempts to prevent this problem, but none have provided optimal results. Previous laboratory and clinical studies have found ALG and PSM to be effective, but none compared the two materials. Thirty-one patients undergoing primary microdiscectomy were randomly assigned to receive either ALG or PSM. Postoperatively, patients were evaluated by magnetic resonance imaging (MRI), with contrast, for volume and rostral-caudal extent of scar tissue and nerve root involvement. Back and leg pain and quality of life were assessed by neurologic examinations and standardized patient surveys. Findings at any reoperations were recorded. Results in the PSM (n = 18) and ALG (n = 13) groups were compared statistically. No operative or postoperative complications occurred. Two patients in each group required reoperation. MRI at 6 months showed no, mild or mild-moderate scarring in most patients, with no significant differences between the ALG and PSM groups in scar volume and extent or nerve root involvement. Neurologic examinations and patient surveys showed substantial reductions in pain over time in both groups but no significant differences between groups. PSM was easy to see and remove at reoperation. PSM and ALG are equally effective in preventing epidural scarring associated with postdiscectomy syndrome.

Adult↗
PubMed2006

Enhanced plasma concentration by selective deuteration of rofecoxib in rats.

The plasma concentrations of BDD-11602 (4-[4- (methanesulfonyl)phenyl]-3-(pentadeuterophenyl)-5H-furan-2-one), a rofecoxib derivative in which the positions 2',3;4',5' and 6' of the phenyl ring were deuterated, and rofecoxib (4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one, CAS 162011-90-7) were compared in order to explore the effects of selective deuteration on the systemic availability. The COX-2 selectivity in vitro was also compared. Following oral gavage administration of 0.1, 1 or 10 mg/kg BDD-11602 to Sprague Dawley rats, AUCo-t, (area under the curve) and Cmax (maximum concentration) values were statistically significant higher than those of rofecoxib at the same doses. The overall increase in AUC0-t and Cmax for BDD-11602 over rofecoxib was 1.53-fold and 1.60-fold, respectively. BDD-11602 and rofecoxib inhibited COX-2-derived PGE(2) synthesis with IC50 values of 173 nmol/l and 169 nmol/l, respectively. IC50 values for inhibition of human platelet COX-1 were estimated to be above 1 micromol/l for both compounds. The substitution of hydrogen by deuterium on the positions 2: 3',4',5' and 6' in BDD-11602 leads to superior oral availability compared to the non-deuterated compound, whereas the COX-2 selectivity is not affected.

Administration, Oral↗
PubMed2006

Impairment in the specificity of emotion processing in schizophrenia.

OBJECTIVE: Deficits in emotion processing are a hallmark of schizophrenia, with consequences for social functioning and subjective well-being. However, their specificity and characteristics have not been ascertained psychometrically. The authors' purpose was to examine a differential deficit for processing emotional facets of the face compared to judgment of nonemotional features (age) and facial memory. The authors also sought to establish whether the deficit affects sensitivity or specificity of performance. METHOD: Participants were 20 patients with schizophrenia and 20 healthy subjects matched for age, gender, and parental education. The authors examined emotional discrimination abilities compared to age discrimination and recognition memory for faces with standardized faces displaying the universal emotions of happiness, sadness, anger, and fear. Percent correct in each condition and for each emotion were assessed as well as sensitivity (correct identification of a target emotion) and specificity (correct rejection of a nontarget emotion) for emotion recognition. RESULTS: Patients with schizophrenia were differentially impaired in the discrimination of emotional aspects of facial expressions compared to nonemotional aspects and memory. Within the emotional task, patients showed differential impairment in specificity and insensitivity to the emotion displayed. CONCLUSIONS: When identical stimuli were used across tasks, differential impairment was seen in patients with schizophrenia for processing emotional faces, although the nonemotional task proved harder for both groups. Impairment in the specificity of emotion identification may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia. Emotion discrimination tests could augment the neurobehavioral evaluation of patients.

Adult↗
PubMed2006

Childhood trauma, psychiatric disorders, and criminal behavior in prisoners in Germany: a comparative study in incarcerated women and men.

OBJECTIVES: Previous studies indicate high rates of childhood trauma experiences as well as of mental disorders among prisoners. In this study, we investigate (1) the prevalence of different kinds of early traumatic experiences in female and male incarcerated prisoners, (2) their associations with mental disorders, and (3) their associations with characteristics of criminal behaviors. METHOD: The Childhood Trauma Questionnaire, Structured Clinical Interviews for DSM-IV Axis I and II Disorders, and Symptom Checklist-90-Revised (current psychopathology) were administered, and the subjects' criminal and arrest histories were obtained. All assessments were performed between May 1, 2002, and June 1, 2003. RESULTS: Comparable sample groups of 63 incarcerated women and 76 men participated. Apart from low rates of short stay prisoners and foreign nationals, the sample was comparable with all prisoners in North-Rhine Westfalia (largest state in Germany). A history of at least 1 type of moderate or severe childhood trauma was reported by 50.4% of the prisoners. In 86.3%, >/= 1 lifetime Axis I disorder was found (current, 83.5%), and a high mean number of comorbid diagnoses was found (mean +/- SD lifetime = 3.6 +/- 3.3, current = 2.9 +/- 2.7). In 53.2% of the sample, at least 1 Axis II (personality) disorder was diagnosed. The numbers of comorbid Axis I lifetime and current disorders as well as the number of lifetime Axis II disorders were significantly (p < .001) associated with the severity of childhood trauma history, indicating a dose-response relationship. Negative associations were observed between the severity of childhood trauma and age at first offense. CONCLUSION: Severity of childhood trauma experiences is associated with the presence and number of Axis I and Axis II mental disorders and may play a crucial role in the development of these disorders.

Adult↗
PubMed2006

Analysis of shrinkage of different gutta-percha types using optical measurement methods.

The aim of this study was to compare the shrinkage of alpha- and beta-gutta-percha of the Multifill-system with commercial gutta-percha. Ten gutta-percha blocks of each of the three types were used. Speckle pattern shearing interferometry was used to prove that no trapped air and material defects were present in the specimens. The optical triangulation method was applied to assess shrinkage. The three gutta-percha types were examined after heating up to 90 degrees C and cooling down to 35 degrees C. Commercial gutta-percha showed less shrinkage (6.5%) than alpha- (7.2%) and beta-gutta-percha (7.3%; p=0.0051 for both comparisons; Wilcoxon's signed rank test). There was a significant difference between alpha- and beta-gutta-percha (p=0.0093; Wilcoxon's signed rank test). In the range of 45 degrees C to 40 degrees C, alpha- and beta-gutta-percha revealed the highest shrinkage (2.2%/5 degrees C and 2.1%/5 degrees C, respectively). Commercial gutta-percha showed the highest shrinkage (1.1%/5 degrees C) in the range of 55 degrees C to 40 degrees C. Overall, shrinkage of all types of gutta-percha was higher than could be assumed from former studies.

Cold Temperature↗
PubMed2005

Differential brain activation according to chronic social reward frustration.

Neural correlates of reward frustration are increasingly studied in humans. In line with prediction error theory, omission of an expected reward is associated with relative decreases of cerebral activation in dopaminergic brain areas. We investigated whether a history of chronic work-related reward frustration influences this reward-dependent activation pattern by means of functional magnetic resonance imaging. Solving arithmetic tasks was followed by either monetary reward or omission of reward. Hyperactivations in the medial prefrontal, anterior cingulate and dorsolateral prefrontal cortex were observed in a group of healthy adults with high susceptibility to reward frustration as compared with a group with low susceptibility. Findings indicate a compromised ability of adapting brain activation among those suffering form chronic social reward frustration.

Adult↗
PubMed2005

Dependence of amygdala activation on echo time: results from olfactory fMRI experiments.

Echo time dependence of the BOLD sensitivity is an important topic in fMRI whenever brain regions are considered where the EPI data quality suffers from susceptibility gradients. Here, an fMRI study is presented showing that a reduced echo time EPI sequence significantly enhances the statistical inference in subcortical (limbic) brain regions, with special focus on the amygdala. As a consequence, to facilitate whole-brain fMRI with optimal echo times, a sequence with slice-dependent echo time is demonstrated with a focus on structures suffering from susceptibility changes. The applicability of this method is shown in a second fMRI study aimed at both, cortical, and limbic brain regions. The results are in good agreement with theoretical descriptions of the BOLD sensitivity under the influence of susceptibility gradients.

Adult↗
PubMed2005

Improving quality of care for depression: the German Action Programme for the implementation of evidence-based guidelines.

ISSUE: Depressive disorders are of great medical and political significance. The potential inherent in achieving better guideline orientation and a better collaboration between different types of care is clear. Throughout the 1990s, educational initiatives were started for implementing guidelines. Evidence-based guidelines on depression have been formulated in many countries. PURPOSE: This article presents an action programme for structural, educational, and research-related measures to implement evidence-based care of depressive disorders in the German health system. The starting points of the programme are the 'Guidelines Critical Appraisal Reports' of the 'Guideline Clearing House' and measures from the 'Competence Network on Depression and Suicidality' (CNDS) funded by the Federal Ministry of Education and Research. The article gives an overview of the steps achieved as recommended by the Guidelines Critical Appraisal Reports and the ongoing transfer process into the German health care system. RESULTS: The action programme shows that comprehensive interventions to develop and introduce evidence-based guidelines for depression can achieve benefits in the care of depression, e.g. in recognition, management, and clinical outcome. CONCLUSION: It was possible to implement the German Action Programme in selected care settings, and initial evaluation results suggest some improvements. The action programme provides preliminary work, materials, and results for developing a future 'Disease Management Programme' (DMP) for depression.

Depressive Disorder↗
PubMed2005

Heart rate variability and spontaneous baroreflex sequences in supine healthy volunteers subjected to nasal positive airway pressure.

To determine the dynamic effects of short-term nasal positive airway pressure (nPAP) on cardiovascular autonomic control, continuous recordings of noninvasively obtained hemodynamic measurements and heart rate variability (HRV) were obtained in 10 healthy subjects during frequency-controlled breathing (between 0.20 and 0.24 Hz) in supine posture under different pressures of nPAP ranging from 3 to 20 cmH(2)O. HRV was assessed using spectral analysis of the R-R interval. The slope of the regression line between spontaneous systolic blood pressure and pulse interval changes was taken as an index of the sensitivity of arterial baroreflex modulation of heart rate (sequence method). Application of nPAP resulted in a pressure-dependent decrease of cardiac output and stroke volume (P < 0.05, ANOVA) and in an increase in total peripheral resistance (P < 0.03, ANOVA). Hemodynamic changes under increasing nPAP were accompanied by a decrease in total power of HRV despite mean R-R interval remaining unchanged. The overall decrease in HRV was accompanied by a reduction across all frequency bands when absolute units were used (P < 0.01). When the power of low frequency and high frequency was calculated in normalized units, a diminished high frequency and an increased low-to-high frequency ratio were observed (P < 0.05). Compared with low levels of nPAP, pressure levels of >10 cmH(2)O were associated with a significant decline in the mean slope of spontaneous baroreceptor sequences (P < 0.04). These findings indicate that short-term administration of nPAP in normal subjects exerts significant alterations in R-R interval variability and spontaneous baroreflex modulation of heart rate.

Adult↗
PubMed2005

Same or different? Neural correlates of happy and sad mood in healthy males.

Emotional experience in healthy men has been shown to rely on a brain network including subcortical as well as cortical areas in a complex interaction, which may be substantially influenced by many internal personal and external factors such as individuality, gender, stimulus material and task instructions. The divergent results may be interpreted by taking these considerations into account. Hence, many aspects remain to be clarified in characterizing the neural correlates underlying the subjective experience of emotion. One unresolved question refers to the influence of emotion quality on the cerebral substrates. Hence, 26 male healthy subjects were investigated with functional magnetic resonance imaging during standardized sad and happy mood induction as well as a cognitive control task to explore brain responses differentially involved in positive and negative emotional experience. Sad and happy mood in contrast to the control task produced similarly significant activations in the amygdala-hippocampal area extending into the parahippocampal gyrus as well as in the prefrontal and temporal cortex, the anterior cingulate, and the precuneus. Significant valence differences emerged when comparing both tasks directly. More activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC), the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the superior temporal gyrus during sadness. Happiness, on the other hand, produced stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and positive moods reveal distinct cortical activation foci within a common neural network, probably making the difference between qualitatively different emotional feelings.

Adult↗
PubMed2005

Leg lengthening as part of gait improvement surgery in cerebral palsy: an evaluation using gait analysis.

Eleven children with hemiplegic or an asymmetric diplegic cerebral palsy who had a preoperative leg length discrepancy of more than 2.5 cm underwent gait improvement surgery which included leg length equalisation. Sagittal plane kinematics and kinetics before and about 3 years after surgery for the lengthened limb and contralateral limb were evaluated. Preoperatively the unaffected limb had excessive stance phase flexion at the hip and knee, and dorsal flexion at the ankle joint. These changes could be partially reversed to produce a kinematic gait pattern comparable to age matched normal controls on the uninvolved side after equalisation of leg length.

Adolescent↗