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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 55 records · Page 3Linked to original sources

[Solid-pseudopapillary tumors in childhood].

We report on fife female patients with solid pseudopapillary tumors of the pancreas. The tumors are extremely rare in children. They occur mainly in adolescent and young adult females. The tumors are neoplasms of low malignancy with infrequent metastases, for instance, in the liver or the peritoneum. Although the tumors had reached a large diameter, all of them underwent complete tumor resection. After that the patients have a very good prognosis. Thus, so it is important to distinguish solid-pseudopapillary tumors from other tumors of the pancreas.

Child↗

[Simulation of coupling behavior of heart rhythms for study of phase synchronization].

Biological systems exhibit numerous rhythmic processes. In the human, rhythms produced by e.g. the cardiac and respiratory systems show signs of synchronisation, reflecting a physiological coupling of the underlying oscillating processes. When examining such rhythms for evidence of coupling, it is difficult to distinguish between epochs of coincidental (numerical) and real (physiological) synchronisation. The objective of this study was to simulate model rhythms in order to examine the conditions under which coupling may be recognised and the influence of noise on this recognition. Different model rhythms with adjustable noise were implemented. The synchronisation between pairs of such rhythms was examined with the help of synchrograms. Functions were used to simulate coupling. The results of the simulation were compared to real fetal-maternal cardiac rhythms. The simulation showed that heart rate variability may be an important factor in distinguishing between coincidental and real synchronisation.

Computer Simulation↗

High-yield expression of the recombinant, atrazine-specific Fab fragment K411B by the methylotrophic yeast Pichia pastoris.

In this report, we describe the high-yield secretory expression ( approximately 40 mg x l(-1)) of pure, atrazine-specific Fab fragments (K411B) from Pichia pastoris that was achieved by co-integration of the genes encoding the heavy and light chains (both under the control of the alcohol oxidase promoter) into the genome of the yeast cells. Antibody-expressing clones were selected by SDS-PAGE and ELISA and fed-batch fermentations were carried out in a 5-l scale. Both chains of the Fab were successfully expressed upon methanol induction and almost no other proteins were secreted into the media. Approximately 30% of the two chains formed the active Fab fragment containing the intermolecular disulphide bond, as determined by Western blot analysis under non-reducing conditions. Crude culture supernatant was used to study the binding properties of the Fab fragment toward different s-triazines by means of competitive ELISA: the IC50 value for the detection of atrazine was determined from the standard curve as 3 microg x l(-1), which is one magnitude higher than the value obtained with the parental mAb K4E7 but equals that obtained when the same Fab fragment was expressed in Escherichia coli cells. In addition, the cross-reactivity pattern of the Fab from Pichia is comparable to that of E. coli and to the parental mAb K4E7.

Atrazine↗

Cloning, functional expression, and characterization of recombinant pig liver esterase.

The N-terminal amino acid sequence of pig liver esterase (PLE) from a commercial sample was determined and shown to match closely to a published sequence encoding a proline-beta-naphthylamidase from pig liver. Next, mRNA isolated from pig liver was transcribed into cDNA and primers deduced from the N-terminal sequence were used to clone the 1698 base pairs of PLE cDNA. Initial attempts to express the cDNA in Escherichia coli and Pichia pastoris with different expression vectors and secretion signal sequences failed. Only after deletion of the putative C-terminal sequence His-Ala-Glu-Leu, usually considered as an endoplasmic reticulum retention signal, could heterologous expression of PLE be readily achieved in the methylotrophic yeast P. pastoris. Recombinant PLE (rPLE) was secreted into the medium and exhibited a specific activity of approximately 600 Umg(-1) and a Vmax/Km value of 139 micromolmin(-1)mM(-1) with p-nitrophenyl acetate as a substrate. Activity staining of renatured sodium dodecylsulfate-polyacrylamide gels gave a single band with esterolytic activity for rPLE, whereas several bands are visible in crude commercial PLE preparations. This was confirmed by native gels, which also show that rPLE is active as a trimer. Biochemical characterization of the recombinant enzyme and comparison with properties of commercial PLE preparations as well as with published data confirmed that we expressed a single PLE isoenzyme which showed a high preference for proline-beta-naphthylamide. This is a substrate specificity for the so-called gamma subunit of PLE. The optimum pH value and temperature for the recombinant PLE were 8.0 and 60 degrees C, respectively. The determined molecular weight of the secreted enzyme was approximately 61-62 kDa, which closely matches the calculated value of 62.419 kDa. The active site residues are located at Ser203, His448, and Asp97, and the typical consensus sequence motif for hydrolases was found around the active site serine (Gly-Glu-Ser-Ala-Gly).

Amino Acid Sequence↗

[Physicians, internet and new knowledge. Utilization and efficiency of new continuing education media in the hospital].

BACKGROUND AND OBJECTIVES: The application of new information technologies will have a lasting impact on the physicians' working environment. Not only will classic learning methods change, but also ways of communication and strategies to find relevant information. This survey is designed to demonstrate current methods of and demand for continuing medical education and communication. METHODS: 110 participating physicians (26% female, 74% male) in nine different regional hospitals were asked regarding "continuing medical education", "communication" and "use of computerized technology". RESULTS: Most physicians regard their colleagues, scientific journals, textbooks and scientific meetings as most useful. The internet, scientific staff at research institutions and pharmaceutical representatives were valued as less useful. Physicians regarded scientific basis, speed and user-friendliness as the most important features of potential data and knowledge sources. Case specificity, German language and interactivity were viewed as less important. Most physicians expressed a growing need for education regarding use of e-mail as a communication tool and internet research techniques. CONCLUSION: Continuing medical education is in strong demand. The successful introduction of modern information technologies into physicians' daily work may and should be enhanced by specifically tailored training courses.

Adult↗

Ifosamide, epirubicin and granulocyte colony-stimulating factor: a regimen for successful mobilization of peripheral blood progenitor cells in patients with multiple myeloma.

In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3 g/m(2) on days 1 and 2 and epirubicine 80 mg/m(2) on day 1) and G-CSF (10 or 20 microg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79 x 10(6) CD34+ cells/kg BW (ranging from 0.94-26.36 x 10(6)) and 6.38 x 10(6) CD34+ cells/kg BW (ranging from 0.79-29.31 x 10(6)) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy.

Adult↗

Humoral immune parameters of cultured Atlantic halibut (Hippoglossus hippoglossus L.).

Several humoral immune factors were studied in a group of cultured halibut (Hippoglossus hippoglossus L.). The serum protein and IgM concentration was comparable to levels seen in other teleost species. A strong antibody activity against TNP-BSA was observed but not against other antigens tested. Lysozyme and anti-protease activity was detected and showed variable heat sensitivity. Unlike the anti-protease activity, the lysozyme activity of the sera was not sensitive to storage at -20 degrees C. No spontaneous haemolytic activity was observed and the sera had no bactericidal effect on any of the bacterial strains tested. Iron binding capacity of the sera was high. Individual variation was considerable in all the factors tested.

Animals↗

Factors affecting renal hydrogen ion excretion capacity in healthy children.

In 560 healthy German children and adolescents aged 2.8-22.0 years from the DONALD (Dortmund Nutritional and Anthropometric Longitudinally Designed) study, the relationship between urine pH and renal net acid excretion (mmol/day/1.73 m2) was analysed. A quadratic model showed the best fit (r2 = 0.608). Using logistic regression analysis three parameters (urinary phosphorus excretion, total protein intake and urinary ratio of potassium and sodium) had a significant effect on renal hydrogen ion excretion capacity characterised by the probability of high or low net acid excretion with respect to the urine pH value. Urinary osmolality, in contrast to what has been seen in a previous experimental study with low birth weight infants, along with sex and age had no significant independent effects on renal net acid excretion with respect to the urine pH value over the range of osmolalities observed. In healthy children and adolescents a low fluid intake with high urinary osmolality does not at least substantially decrease the renal capacity of hydrogen ion excretion.

Adolescent↗

The antisecretory factor: synthesis, anatomical and cellular distribution, and biological action in experimental and clinical studies.

The antisecretory factor (AF) is a 41-kDa protein that provides protection against diarrheal diseases and intestinal inflammation. Its cDNA has been cloned and sequenced. AF is highly potent, with 10(-12) mol of recombinant AF being sufficient to counteract experimentally induced diarrhea in rat. The antisecretory activity is exerted by a peptide located between positions 35 and 50 of the AF sequence. Synthetic peptides based on this sequence are promising candidates for drugs to counteract intestinal hypersecretion, as well as imbalances of fluid transport in other body compartments. AF probably exerts its effects via nerves; AF immediately and potently inhibits ion transport across isolated nerve membranes from Deiters' cells. Immunocytochemistry has shown that AF is present in most tissues in the body, and in situ nucleic acid hybridization has shown that cells that store AF are also capable of AF synthesis. The endogenous plasma level of AF is increased by enterotoxins and by certain food constituents such as hydrothermally processed cereals. These cereals significantly improve clinical performance in patients suffering from inflammatory bowel diseases. AF-enhancing food also protects domestic animals against diarrheal diseases, and such feed has been used successfully in Swedish swine farming for the past 10 years. Increased understanding of AF action might result in expanded clinical applications and confirm that AF is an important regulator of homeostasis.

Animal Feed↗

Adjusting for multiple testing--when and how?

Multiplicity of data, hypotheses, and analyses is a common problem in biomedical and epidemiological research. Multiple testing theory provides a framework for defining and controlling appropriate error rates in order to protect against wrong conclusions. However, the corresponding multiple test procedures are underutilized in biomedical and epidemiological research. In this article, the existing multiple test procedures are summarized for the most important multiplicity situations. It is emphasized that adjustments for multiple testing are required in confirmatory studies whenever results from multiple tests have to be combined in one final conclusion and decision. In case of multiple significance tests a note on the error rate that will be controlled for is desirable.

Bias↗

Reproducibility of two coronary calcium quantification algorithms in patients with different degrees of calcification.

PURPOSE: To evaluate the reproducibility of coronary calcium quantification algorithms by electron beam CT (EBT) in patients with different amounts of calcified plaque using the conventional (Agatston) score and an area score and to demonstrate a potential application of these results for evaluation of follow-up scans. METHODS: In 50 consecutive patients. the conventional calcium score (CCS = Agatston score) and the area score (AS) were summed for each artery and patient. Data were analyzed in four groups according to degrees of calcification: 0 (absent-minimal): CCS 0-9, I (mild): CCS 10-99, II (moderate): CCS 100-399, III (severe): CCS > or = 400. We determined and compared the reproducibility for each algorithm within and among groups. RESULTS: Median percent reproducibility improved with increasing amounts of calcified plaque for the CCS and the AS (p = 0.002 and p = 0.004, respectively). We demonstrate how these reproducibility values can be used to evaluate long-term follow-up studies. The reduction of median reproducibility per patient using the AS vs. the CCS was 32% (13 vs. 19%, respectively). On a vessel-by-vessel basis, the reduction of median reproducibility was 7% (24.3 vs. 22.6%, CCS vs. AS, p < 0.02), which was attributable to a 45% reduction in reproducibility in arteries with mild scores (46.1 vs. 25.5%, CCS vs. AS, p < 0.005). CONCLUSION: The AS has an improved reproducibility compared with the CCS, especially in patients with small amounts of coronary calcifications which may prove clinically useful. Different reproducibility values in different degrees of calcification can be used for an individual assessment of changes in amounts of coronary calcification.

Adult↗

[Are there certified indications for the use of antithrombin III in intensive care].

The serine-protease-inhibitor antithrombin III (AT III) has often been recommended for the therapy of septic patients as it provides anticoagulant and antiinflammatory actions. In animal studies the prophylactic treatment with AT III in a dose > 250 U/kg prevented the development of disseminated intravascular coagulopathy and vital organ dysfunction during sepsis and lowered the mortality rate. In clinical studies with septic patients therapy usually was started several hours after the start of the disease in dosages much lower than those used in animal studies. In these patients AT III-therapy improved laboratory changes of disseminated intravascular coagulopathy but was unable to lower the mortality rate. Hereditary AT III deficiency, lack of heparin effect due to low AT III levels, disseminated intravascular coagulation disorders are indications for the use of AT III while beneficial effects of AT III in patients suffering from SIRS, sepsis or septic shock have not yet been demonstrated.

Antithrombin III↗

Growth tracks in early childhood.

AIM: Child growth is modulated by numerous factors and, particularly in infancy and early childhood, often tends to follow apparently irregular patterns, with many centiles crossed before the later growth channels are reached. The aim of this study was to visualize the diversity of individual growth. DESIGN: The study investigated 333 girls and 329 boys without chronic illnesses from four paediatric practices in Kiel, Germany. The children were measured on natural, i.e., on various occasions, when they were presented to their doctors for preventive care examinations and for minor illnesses, at the age of 0.25 (range +/- 0.08) y, 0.5 (range +/- 0.16) y, 0.75 (range +/- 0.16) y, 1.0 (range +/- 0.25) y, and at the ages of 1.5, 2, 3, 4 and 5 (range +/- 0.25) y. Each individual growth curve was converted into a series of height SDS (standard deviation scores) using one of the most reputable longitudinal German growth studies as background reference. Height SDS was then converted into residual height SDS (differences between height SDS of each measurement and average personal height SDS of the respective child). Cluster analysis was used to identify groups of children (clusters) with similarities in residual height SDS patterns (growth tracks). The clusters contained a minimum of at least 10 children. Single children or small sets of individuals below the minimum number were rejected from further analysis. RESULTS: In males, 10 growth tracks were identified, each consisting of 11 to 52 boys. Growth in 111 boys was so heterogeneous that they could not be assigned to growth tracks. In females, 11 growth tracks were identified, each consisting of 12 to 48 girls; 112 girls could not be assigned. Approximately 7% of boys and 15% of girls showed evidence of a mild intermittent growth spurt at the end of infancy. Some growth tracks were almost horizontal, or showed declining residual height SDS up to the age of 3 and 4 y, with no evidence of growth spurts during early childhood. Others showed sharply declining growth in early infancy, or irregular patterns. Similar results were obtained when using cross-sectional standards as background reference. CONCLUSION: Cluster analysis provides evidence that the substantial diversity in infant and early child growth, is limited to a small number of narrow but characteristic tracks of yet unknown biological significance.

Algorithms↗

[Increased procalcitonin level in bacteriogenic metabolic disturbances. A new possibility for diagnosis and treatment monitoring in sepsis].

Earlier observations of increased plasma concentrations of immunoreactive calcitonin (32 amino acids) in sepsis and other non-tumorous conditions may be explained by increased secretion of procalcitonin, the 116-amino acid prohormone. At present, the site(s) of origin of procalcitonin in sepsis, the factors regulating its biosynthesis and release, the route(s) of its elimination from blood as well as its biological function(s) are unknown. The rapid increase in procalcitonin concentration in sepsis--in some patients earlier than that of C-reactive protein--and decrease upon successful chemotherapy makes procalcitonin a potentially important biomarker in monitoring patients with suspected or confirmed sepsis.

Biomarkers↗

Lymphoma discrimination by computerized triple matrix analysis of list mode data from three-color flow cytometric immunophenotypes of bone marrow aspirates.

BACKGROUND: The goal of this study was to evaluate a self-learning algorithm for the computer classification of information extracted from flow cytometric immunophenotype list mode files from high-grade non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). Materials and Methods Bone marrow aspirates (BMA) were obtained from untreated NHL (n = 51), HD (n = 9), or MM (n = 13) patients. Bone marrow aspirates were not infiltrated in NHL and HD patients as confirmed by thorough histologic and cytologic investigation; however, MM patients showed an infiltration rate >50% by malignant myeloma cells. Peripheral blood leukocyte (PBL) samples were taken from age-matched healthy volunteers (n = 44) as easily available control material. A second control group of 15 healthy volunteers, from whom BMA and PBL samples were available, allowed us to differentiate whether the observed classification results on malignant samples were due to the malignant process or simply to the inherent differences between BMA and PBL. Bone marrow aspirates and PBL were analyzed by the same immunophenotyping antibody panel (CD45/14/20, CD4/8/3, kappa/CD19/5, lambda/CD19/5). The acquired list mode data files were analyzed and classified by the self-learning triple matrix classification algorithms CLASSIF1 following a priori separation of the data into a learning set and unknown test set. After completion of the learning phase, known patient samples were reclassified and unknown samples prospectively classified by the algorithm. RESULTS: Highly discriminatory information was extracted for the various lymphoma entities. The most discriminating information was encountered in antibody binding, antibody binding ratios, and relative antibody surface density parameters of leukocytes rather than in percentage frequencies of discrete leukocyte subpopulations. Samples from healthy controls were classified as normal in 97.2% of the cases, whereas those of NHL, HD, and MM patients were on average correctly classified in 80. 8% of the cases. CONCLUSIONS: Although no detectable lymphoma cells were present in BMA of NHL and HD patients, the CLASSIF1 classification of the immunophenotypes of morphologically normal cells provided a surprisingly good disease discrimination equal or better than that obtained by examining pathological lymph nodes according to the respective literature. The results are suggestive for a lymphoma-related and disease-specific antigen expression shift on normal hematopoietic bone marrow cells that can be used to discriminate the underlying disease (specificity of unspecific changes), i.e., in this case NHL from HD. Multiple myeloma patients were discriminated by changes on malignant as well as on normal bone marrow cells.

Algorithms↗

Extrapyramidal motor signs in degenerative ataxias.

BACKGROUND: Extrapyramidal motor signs (EPS) are well-known symptoms of degenerative ataxia. However, little is known about frequency and appearance of EPS in subtypes of ataxia. METHODS: We characterized 311 patients with ataxia clinically and genetically. Course of the disease and EPS were investigated according to a standardized protocol. Diagnostic and prognostic impact of EPS in subtypes of ataxia was analyzed by Kaplan-Meier plots. RESULTS: Extrapyramidal motor signs occurred in all forms of ataxia, but frequency and type of EPS varied between genetically and clinically defined subtypes. Postural tremor in hereditary ataxias was typical for spinocerebellar ataxia type 2 (SCA2). Dystonia was generally rare in ataxias, but, if present, suggested SCA3. We observed a parkinsonian variant of SCA3 in which parkinsonism was present in the beginning of the disease and responded well to levodopa therapy, leading to diagnostic confusion. Parkinsonism in SCA3 was independent of CAG repeat length but ran in families, suggesting modifying genes. In idiopathic sporadic cerebellar ataxia (ISCA), EPS are more frequent in late-onset than in early-onset forms. In 50% of ISCA patients with parkinsonism, the diagnosis of multiple system atrophy remained questionable because of normal autonomic function. CONCLUSIONS: Extrapyramidal motor signs can help to predict the genetic subtype of ataxia. Extrapyramidal motor signs were more frequent in genetic subtypes in which basal ganglia affection has been demonstrated by postmortem studies. However, no type of EPS was specific for an underlying mutation. In ISCA, EPS are an adverse prognostic factor. Parkinsonism is especially associated with a more rapid course of the disease. Arch Neurol. 2000;57:1495-1500

Aged↗

Mechanistic aspects of dihydrogen activation and transfer during asymmetric hydrogenation in supercritical carbon dioxide.

A new "CO2-philic" chiral rhodium diphosphinite complex was synthesized and applied as catalyst precursor in the asymmetric hydrogenation of dimethyl itaconate in scCO2, scC2H6 and various liquid organic solvents. Deuterium labeling studies and parahydrogen-induced polarization (PHIP) NMR experiments were used to provide the first detailed mechanistic insight into the activation and transfer of the dihydrogen molecule during hydrogenation in scCO2. Chemical interactions between CO2 and reactive intermediates of the catalytic pathway could be excluded as possible explanations for the experimentally verified difference in the catalytic behavior in scCO2 and hexane.

Carbon Dioxide↗