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Biomedical subjects

R Koch

Publications and source records attributed to R Koch.

At least 37 records · Page 2Linked to original sources

GermOnline, a cross-species community knowledgebase on germ cell differentiation.

GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline's information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on approximately 700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics.

Animals↗

Quality of life and long-term results after ruptured abdominal aortic aneurysm.

OBJECTIVES: Quality of life as an endpoint of surgery and the long-term prognosis for patients who have survived surgery for a ruptured abdominal aortic aneurysm (RAAA) is not well-documented. PATIENTS AND METHODS: The records of all patients from 1993 to 2000 who underwent resection of RAAA were reviewed. Survival data were calculated from direct contact with the patients or follow-up records. All patients who were alive at the time of our study were invited to participate in follow-up investigations. They received the internationally comparable WHO-QOL-BREF-test. RESULTS: In a period of 7 years, 80 patients underwent surgery for RAAA. The average follow-up time was 5.1 years (1-7.9 years). Our data show that 51% of our patients died within 6 months postoperatively because of the complications of the aortic rupture (in-hospital mortality 39%). Patients who survived the first 6 months after surgery died for the same reasons as the normal population. However, patients who were younger than 75 at the time of RAAA had a higher relative survival rate than a matched sample of the population. There was no significant difference in the quality of life between the study group and the general population. CONCLUSIONS: RAAA survivors had no difference in long-term survival as compared to the general population and also had very few long-term complications. The WHOQOL-BREF-test suggests that the quality of life of survivors of RAAA is similar to the general population.

Aged↗

Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review.

Adult subjects with classical phenylketonuria (PKU) who were diagnosed and treated neonatally participated in this long-term follow-up study. Twenty-four subjects received neuropsychological (NP) assessment and a subset received magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to identify: (1) pattern of cognitive dysfunction; (2) effect of high blood phenylalanine (Phe) level at time of cognitive testing; and (3) treatment variables that may be associated with cognitive difficulties in adulthood. All subjects had average IQ except one subject in the borderline range. Diet was initiated by the 15th day of life. All subjects except one were on diet until age 6 years (mean years of treatment = 15). Blood Phe levels at cognitive testing ranged from 157 to 1713 micromol/L (mean = 1038); 11 subjects had levels < 1000 micromol/L and 13 subjects had levels >1000 micromol/L. Results suggest that adults with early-treated PKU demonstrate specific cognitive deficits, a number of which are associated with the frontal and temporal area of the brain. Deficits were noted in several domains including executive functioning, attention, verbal memory, expressive naming and verbal fluency. Self-report measures of depression and anxiety were generally in the normal/mild range. The group with a Phe level > 1000 micromol/L scored lower than the group with Phe level < 1000 micromol/L on measures of focused attention, verbal fluency, reaction time, verbal recognition memory, visual memory and naming. Tests of cognitive functioning were often correlated with measures of treatment during childhood rather than with Phe level at the time of cognitive testing. Subjects with abnormal MRI scored significantly lower on two cognitive tests (Trails A and CVLT Recognition Memory). We found no significant correlation between current brain Phe level obtained through MRS (n = 10) and neuropsychological functioning. Future longitudinal investigation with a larger sample size will assist in clarifying the aetiology of neuropsychological deficits and association with treatment history.

Adult↗

Maternal Phenylketonuria Collaborative Study (MPKUCS)--the 'outliers'.

Analysis of outcome data from 305 of the 414 offspring from the Maternal Phenylketonuria Collaborative Study (MPKUCS), plus 70 control offspring, revealed significant deficits in the IQ (intelligence quotient), as measured by the Wechsler Intelligence Scale for Children--Revised (WISC-R), when maternal metabolic control during pregnancy was delayed and/or inadequate. There were, however, 23 'outliers' (7.5% of the 305) in which the offspring's intellectual IQ was worse (n =10) or better (n =13) than expected. The aim of this study was to determine whether collection parameters were incomplete or whether these subjects were true biological variants influenced by other undetected factors or, perhaps, by modifier genes. Among the 10 offspring whose intellectual functioning was worse than expected, additional complications were uncovered that could explain the poor outcome. Four of the 13 offspring with higher than expected IQ had mothers with mild variants of PKU in which the insult to the fetus would not be expected to be as profound. For the other nine offspring whose intellectual performance was better than expected, there was no explanation, based on the parameters studied. We hypothesize that modifier genes will, at times, protect the fetus despite high maternal concentrations of phenylalanine. Not all offspring from the same (untreated) PKU mother may be similarly affected. Finding the source of these modifiers might effect the treatment of MPKU.

Adolescent↗

CD34+ cell dose, conditioning regimen and prior chemotherapy: factors with significant impact on the early kinetics of donor chimerism after allogeneic hematopoietic cell transplantation.

The aim of this study was to define factors that significantly influence the early kinetics of donor chimerism after transplantation. In a retrospective study, the percentage of donor chimerism in peripheral blood measured with sex-chromosome-specific probes and fluorescence-in situ hybridization was analyzed in 184 recipients of allogeneic hematopoietic cells between days 1 and 30. Using a generalized linear model for longitudinal observations, the dose of CD34+ cells infused had a significant impact on the slope of donor chimerism. In multivariate analysis, cell doses of 2-8 x 10(6)/kg (P=0.001) and <2 x 10(6) CD34+ cells/kg (P<0.0001) were associated with slower increase of donor chimerism compared to >8.0 x 10(6) CD34+ cells/kg. In addition, fludarabine-based reduced-intensity conditioning resulted in a significant delay of donor cell increase compared to standard conditioning therapy (P=0.0001). The application of chemotherapy before the start of conditioning (P=0.0003) and the use of antithymocyte globulin (P=0.003) were associated with a faster increase of donor chimerism. The factors identified in this study can be used to predict the kinetics of early donor chimerism for an individual patient.

Adolescent↗

Changes in brain metabolism associated with remission in unipolar major depression.

OBJECTIVE: Functional brain correlates of remission in patients with major depressive disorder (MDD) are measured with positron emission tomography (PET) and 18F-fluorodeoxyglucose. METHOD: Glucose metabolism was measured in patients (n = 41) with moderate to severe MDD during acute depression and in the remitted state defined as a period of asymptomatic condition over 12 weeks. Data analyses used a region-of-interest (ROI) approach and statistical parametric mapping (SPM). RESULTS: There were significant decreases in metabolism upon remission with respect to the baseline scan in left prefrontal, anterior temporal and anterior cingulate cortex and bilateral thalamus (SPM analysis) and bilateral putamen and cerebellum (SPM and ROI analyses). There was a significant asymmetry in prefrontal and anterior cingulate cortex metabolism with lower metabolism in the left hemisphere that persisted despite clinical remission. CONCLUSION: These findings support the hypothesis that selective monoamine reuptake inhibition leads to an attenuation of a brain circuit that mediates depressive symptomatology.

Adolescent↗

Programmable computing with a single magnetoresistive element.

The development of transistor-based integrated circuits for modern computing is a story of great success. However, the proved concept for enhancing computational power by continuous miniaturization is approaching its fundamental limits. Alternative approaches consider logic elements that are reconfigurable at run-time to overcome the rigid architecture of the present hardware systems. Implementation of parallel algorithms on such 'chameleon' processors has the potential to yield a dramatic increase of computational speed, competitive with that of supercomputers. Owing to their functional flexibility, 'chameleon' processors can be readily optimized with respect to any computer application. In conventional microprocessors, information must be transferred to a memory to prevent it from getting lost, because electrically processed information is volatile. Therefore the computational performance can be improved if the logic gate is additionally capable of storing the output. Here we describe a simple hardware concept for a programmable logic element that is based on a single magnetic random access memory (MRAM) cell. It combines the inherent advantage of a non-volatile output with flexible functionality which can be selected at run-time to operate as an AND, OR, NAND or NOR gate.

Journal Article↗

Magnetologic with alpha-MnAs thin films.

Taking advantage of the spin information in present day computing is expected to yield an enormous increase in efficiency. A promising ferromagnetic material compatible with semiconductors for room temperature applications is MnAs. By sensitive cantilever beam magnetometry, we discovered that alpha-MnAs films on GaAs(001) exhibit an additional small out-of-plane component of the magnetization which is magnetically coupled with the dominant in-plane magnetization. We demonstrate that by regarding the two components as independent inputs, the alpha-MnAs layer can be utilized as a logic gate with nonvolatile output. The logic functionality of the layer can be preselected to be AND or OR at run time, thus offering the perspective for programmable magnetologic devices.

Journal Article↗

Ferromagnetism of MnAs studied by heteroepitaxial films on GaAs(001).

Thin epitaxial films of MnAs--promising candidates for the spin injection into semiconductors--are well known to undergo simultaneously a first-order structural and magnetic phase transition at 10-40 degrees C. The evolution of stress and magnetization of MnAs/GaAs(001), both measured quantitatively with our cantilever beam magnetometer at the coexistence region of alpha-MnAs and beta-MnAs, reveal an orthorhombically distorted unit cell of the ferromagnetic phase, which provides important clues on the origin of ferromagnetism in MnAs.

Journal Article↗

Danger of high-protein dietary supplements to persons with hyperphenylalaninaemia.

A 16-year-old adolescent with mild hyperphenylalaninaemia was given a high-protein 'body building' supplement twice daily, causing headaches, decreased school performance and mild depression. All symptoms disappeared after cessation of the supplement. The phenylalanine hydroxylase mutation H170D/IVS1nt5G>T was found to be responsive to tetrahydrobiopterin with significant decrease in blood phenylalanine concentration and increase in tyrosine blood content. A brain phenylalanine level of 0.5 mmol/L was initially documented, which decreased to the normal carrier range of 0.2 mmol/L within one month of discontinuance of the protein supplement. At present, the patient is on a normal diet without phenylalanine restriction.

Adolescent↗

The use of small personal ultrasound devices by internists without formal training in echocardiography.

AIMS: Hand-held ultrasound devices will probably be used for bedside cardiac diagnoses by internists without formal training in echocardiography. We compared the accuracy of hand-held ultrasound devices studies performed by expert echocardiographers vs internal medicine residents with brief training in echocardiography. METHODS AND RESULTS: Three internal medicine residents participated in an organized training program in echocardiographic principles, image acquisition, and interpretation. Subsequently, these residents and three echocardiographers imaged 300 patients with a hand-held ultrasound device. Sensitivity, specificity, positive and negative predictive values for internist- and echocardiographer-performed studies for the detection of cardiac abnormalities were compared using a full-featured exam as the gold standard. Resident- and echocardiographer-performed scans had similar overall sensitivity and specificity. There was a higher positive predictive value for the echocardiographer-performed scans. For clinically important findings (likely to affect patient care), sensitivity was slightly but significantly higher for the echocardiographer-performed scans. Clinically important findings most often missed by residents included regional wall motion abnormalities, intra-cardiac thrombus, right ventricular dysfunction and non-trivial pericardial effusions. CONCLUSION: Hand-held ultrasound devices provide useful screening tools for cardiac disease but should not replace a standard platform study. Training guidelines and competency evaluation are needed if these devices are to be used by non-echocardiographers for clinical decision-making.

Aortic Valve Stenosis↗

The Kleine-Levin syndrome - effects of treatment with lithium -.

Kleine-Levin syndrome (KLS) is a rare disorder which affects mainly adolescents. Periods of extreme somnolence alternate with megaphagia, psychomental changes and behavioural symptoms. The cause and pathogenesis of KLS remains unknown. Several treatments have been tried and recently lithium has been proposed for a prophylactic use in single cases. In view of the rarity of KLS, long-term results of lithium therapy have not been described yet. We report the clinical course of five adolescents with KLS who were treated with lithium. All patients showed significant EEG and polysomnographic changes during the episodes and had normal results in the interval. All patients had relapses while being treated with lithium. But episodes of hypersomnia under lithium therapy were shorter and monosymptomatic with lack of behavioural symptoms. Statistical modelling showed that the risk for a relapsing episode under maintenance of lithium drops per months of therapy from 100 % to 93 %, and furthermore that the maintenance of lithium shortens the mean duration of episodes to 19 %. No severe side effects were observed. In conclusion, in KLS with a high frequency of episodes and severe behavioural changes lithium may become a treatment option.

Adolescent↗

[Perioperative risk assessment in surgery - an analysis in 10 395 patients].

UNLABELLED: The aim of this study was to perform a risk analysis on the basis of routinely documented variables (age, sex, ASA-classification, priority of operation, malignant disease, intraperitoneal or intrathoracic operation and duration of operation) to identify surgical patients who benefit from a more complex risk assessment. PATIENTS AND METHODS: In a prospective observational trial we analysed a consecutive series of 10 395 patients who were operated on in our General Surgical Department from January 1996 until December 2000 in respect to in-hospital mortality. The variables were examined in univariate tests. Factors with significant impact were subsequently included in a multiple logistic regression analysis. This was done for all variables and afterwards for each ASA-class separately. Predictive accuracy of the prediction model was calculated by the area under a receiver operating characteristic curve (AUC (ROC)). RESULTS: The overall mortality was 3.9 %. For ASA-classes 2 to 4 we were able to establish a prediction model by means of multiple logistic regression that identified ASA-classification (Odds Ratio [OR ] ASA-class 3 = 3.7; OR ASA-class 4 = 22.4), age (OR 1.019 per year), duration of operation (OR for duration > or = 240 min = 2.25), intraperitoneal/intrathoracic operation (OR = 4.6), emergency operation (OR = 3.1), and malignant disease (OR = 1.5) as independent predictive factors. Both risk group 1 and risk group 5 were excluded from the analysis because there was no mortality in risk group 1 and too few patients in risk group 5. We found an AUC (ROC) of 91.6 % for the considered ASA-classes. CONCLUSION: The ASA-classification is a good instrument for the assessment of perioperative mortality. Its predictive power can substantially be improved in the classes 2 to 4 by the variables age, duration of operation, intraperitoneal or intrathoracic operation, priority of operation, and malignant disease.

Adolescent↗

HLA typing and Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.

Adult↗

[Predictive value of thyrotropin receptor antibodies using the second generation TRAb human assay after radioiodine treatment in Graves' disease].

UNLABELLED: The detection of TSH-receptor antibodies (TRAb) in patients with Graves' disease is routinely used in nuclear medicine laboratories. This determination has been possible for approximately 3 years with a second generation human TRAb assay. Studies showed that this TRAb determination is diagnostically more sensitive compared to established, porcine TRAb assays. OBJECTIVE: The aim of our study was to investigate, based on a ROC analysis, whether TRAb determination with the new, second generation assay allows a dependable statement about probability of occurrence of relapse after radioiodine therapy in patient suffering from Graves' disease. METHODS: 57 patients were examined with the DYNOtest TRAKhuman (BRAHMS Diagnostica AG, Hennigsdorf) directly before and six months after therapy with radioiodine (dose: 150 Gy). A ROC-analysis was performed to determine positive/negative predictive values depending on different cut-off values. RESULTS: Whereas 21/57 patients became eu- or hypothyroid after six months, 36/57 patients relapsed. Non-relapsed patients showed a significant lower median TRAb titer (4.2 IU/l vs. 19.2 IU/l; p <0.05) compared to relapsed patients. But the positive predictive value conducted 63 and 66, 62 and 66 as well as 63 and 69% (before and after therapy) linked with the cut-offs 1.0, 1.5, and 2.0 IU/l. So it was in areas also achieved by the first generation porcine radio receptor assay. CONCLUSION: An increased sensitivity is achieved undoubtedly with the new DYNOtest TRAKhuman in the diagnostic of Graves' disease. It is not held over the established radio receptor assay concerning the positive predictive value for relapsing patients.

Follow-Up Studies↗

Butterfly hysteresis loop at nonzero bias field in antiferromagnetic molecular rings: cooling by adiabatic magnetization.

At low temperatures, the magnetization of the molecular ferric wheel NaFe6 exhibits a step at a critical field B(c) due to a field-induced level crossing. By means of high-field torque magnetometry we observed a hysteretic behavior at the level crossing with a characteristic butterfly shape which is analyzed in terms of a dissipative two-level model. Several unusual features were found. The nonzero bias field of the level crossing suggests the possibility of cooling by adiabatic magnetization.

Journal Article↗

[Collagenase 3 mRNA expression in squamous epithelial carcinomas of the oropharynx].

BACKGROUND: Metalloproteinases (MMP) are endopeptidases, which are able to degrade extracellular matrix. It is assumed that MMP play an important role in invasion and metastasis of malignomas. The expression of collagenase-3, also named MMP-13, was already detected in squamous cell carcinoma of the head and neck, but the significance in the process of metastasis is still unclear. PATIENTS AND METHODS: 36 tumor biopsies of oropharyngeal squamous cell carcinoma (10 cases N0, 26 patients N+) and 12 biopsies of normal oropharyngeal mucosa were analysed with reverse transcriptase-PCR and Northern Blot for their mRNA-expression of MMP-13 and TIMP-1, the physiological inhibitor of MMP-13. RESULTS: In 30 of 36 (83.3%) tumor biopsies a MMP-13-mRNA-expression was detected. In 9 of 10 (90%) cases with N0-status and 21 of 26 (80.7%) cases with N(+)-neck the mRNA-expression could be shown. There was no correlation between MMP-13-mRNA-expression and N-status. In 34 tumor biopsies (94.4%) a TIMP-1-expression was detected. MMP-13-mRNA was not detected in normal oropharyngeal mucosa. CONCLUSIONS: It seems that MMP-13-mRNA-expression is not a prognostic factor for metastatic behavior of oropharyngeal cancer and therefore not helpful for further decisions on the therapy.

Adult↗