Search PubMed⌕ Search

Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 19 recordsLinked to original sources
PubMed2001

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↗
PubMed2001

[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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

[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↗
PubMed2001

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↗
PubMed2000

[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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Changes of QT dispersion in patients with coronary artery disease dependent on different methods of stress induction.

BACKGROUND: Episodes of stress-induced myocardial ischemia in patients with coronary artery disease (CAD) may cause increases of QT dispersion (QTd). HYPOTHESIS: Aim of this study was to analyze the effect of increasing heart rates on QTd and to compare the effect of different methods of stress induction in patients with varying degrees of CAD when estimating QTd. METHODS: We studied 58 patients, 22 with prior myocardial infarction (MI), 25 without MI or wall motion disturbances at rest, and 11 patients without evidence of CAD. Prior to coronary angiography, standard 12-lead ECGs were obtained at rest as well as during dynamic exercise and pharmacologic stress using arbutamine simultaneously with echocardiography. QTd was determined at each stress level by subtracting minimal from maximal QT interval duration. RESULTS: QTd values at rest were not consistently higher in the patients with CAD. At maximal heart rate, QTd was statistically significantly higher in patients with CAD with a better discrimination between groups for pharmacologic stress (p < 0.005 for exercise, p < 0.0001 for arbutamine). Patients after MI had higher QTd values under all conditions than did the groups without MI. As in patients with CAD, the values of this group changed more radically as a result of pharmacologic stress. CONCLUSION: Patients with CAD can be identified on the basis of QTd under stress. These changes were not as marked in patients with MI as their rest values were already increased. Overall, drug-induced stress produced greater differences than dynamic exercise, suggesting that the ischemic threshold might be lower in the former.

Adrenergic beta-Agonists↗
PubMed2000

[Are children properly classified within the scope of expert assessment to determine need for services?].

This project deals with assessment directives issued by the leading statutory care insurance companies to define the need for care of children at certain ages in coping with the activities of daily life specified by the German Social Legislation. The ages in question relate to healthy, normally developed children. They are used as a measure of comparison for the assessment of diseased children. Besides, they have a decisive significance in defining the need for care. Only if a child is not able to perform a certain activity, although it is meant to be able to do so at that age, can we define the need for help and assistance, i.e. care. The project is divided into two sections. 1. Comparison of age mentioned in the assessment directives for each of the daily life activities of healthy and normally developed children aged 1 to 12 years with the age mentioned in technical literature. 2. Comparison of age mentioned in the assessment directives for each ot the daily life activities of healthy and normally developed children at the age of 1 to 12 years with those mentioned in retrospective interviews with the same group of children. In the first part of the project, an analysis of the literature dealing with the subject was done. The literature included the stock of technical literature in the German language. Studying the literature, ages for children could be isolated, that could be classed with the activities of daily life mentioned in the German Social Code. These ages were compared with those in the assessment directives. In a second part of the project, 81 mothers and fathers of healthy, normally developed children aged 1 to 12 years were asked via a questionnaire. They were asked to estimate retrospectively from what age on their child had been able to perform certain activities of daily life without any help. The comparison of ages mentioned in the assessment directives with those of the analysis of literature conformed only regarding daily life activity. Regarding the other activities of daily life the age for children was set higher in the assessment directives than in the literature. Comparing the age of children in the assessment directives with the results of the questionnaires the age was also set higher in the directives than shown by the results of the questionnaires. The results of the literature analysis and the inquiry by questionnaires show that the ages mentioned in the assessment directives for an independent performance of daily life activities do not correspond to the development according to the age of healthy normally developed children aged 1 to 12 years. As a result of this project it seems to be justified to be doubtful about an adequate assessment of children who are in the need of care. Due to this reason it would be desirable to reexamine the data of the assessment directives by means of a new representative prospective study.

Activities of Daily Living↗
PubMed2000

Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept.

BACKGROUND: Antisecretory factor (AF), a 41 kDa cloned and sequenced protein, suppresses intestinal inflammation and hypersecretion in animals. Endogenous AF production can be induced by dietary modifications in several animal species, and this feed has been shown to reduce the incidence of diarrhoeal disease in weaning piglets. The role of AF in intestinal disease in humans is not known. AIMS: To study the effects of hydrothermally processed cereals, optimised for AF induction in animals, added to the diet of patients with longstanding symptoms of inflammatory bowel disease (IBD). PATIENTS: Fifty three patients with IBD (ulcerative colitis and Crohn's disease) were entered into the study, and 50 completed follow up. The experimental group consisted of 16 females (mean age 50 (SEM 5) years) and 10 males (41 (4) years) and the placebo group of 12 women (41 (4) years old) and 12 men (51 (5) years). METHODS: Patients were randomised to receive either hydrothermally processed cereals (active treatment) or the same amount of ordinary cereals (placebo treatment) for four weeks in a double blind study design. Baseline diet and medications remained unchanged. Bowel symptoms, plasma levels of AF, and colonic biopsies were evaluated before and after treatment. RESULTS: The active treatment significantly improved subjective ratings of clinical symptoms and increased plasma AF levels compared with placebo. Plasma lipid levels were unaffected. CONCLUSION: Hydrothermally processed cereals can induce AF production in human IBD. This increase in endogenous AF activity is associated with clinical improvement. Further studies are warranted to clarify the exact role of AF in human intestinal disease.

Adult↗