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Biomedical subjects

C Beckmann

Publications and source records attributed to C Beckmann.

At least 19 recordsLinked to original sources

Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease.

BACKGROUND: Budesonide is effective as initial therapy of mild to moderate Crohn's disease in adults. Superior tolerability to conventional corticosteroids might be attributed to extensive first-pass metabolism of budesonide by cytochrome P450 3A. AIM: To evaluate biotransformation and pharmacodynamic action of budesonide in children. METHODS: Drug disposition and effects on endogenous cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after first intake of 3 mg budesonide (single dose), and again after 1 week of thrice daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent metabolites were analysed in blood and urine. RESULTS: Pharmacokinetic parameters of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/-5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall systemic elimination of budesonide reflected by clearance and half-life was not different between children and adults. After 1 week of treatment reversible adrenal suppression was observed - most pronounced in children aged below 12 years. CONCLUSIONS: Disposition of oral budesonide appears to be similar between children and adults, but the doctor has to be aware of an increased risk for adrenal suppression in paediatric patients.

Administration, Oral↗

Towards understanding language organisation in the brain using fMRI.

Functional magnetic resonance imaging (fMRI), which allows non-invasive mapping of human cognitive functions, has become an important tool for understanding language function. An understanding of component processes and sources of noise in the images is contributing to increased confidence in the reproductability of studies. This allows clinical applications, e.g., for pre-surgical lateralisation of language functions in patients with temporal lobe epilepsy. fMRI is a sensitive method for mapping regions involved in language functions. We recently have applied it to study the effect of word surface form on reading with a comparison of responses to Chinese characters or alphabetical Pinyin. Interpretation of fMRI activations must be made with caution; fMRI suggests task-associated activation, but does not independently confirm that such activity is necessary. However, complementary studies can be performed using transcranial magnetic stimulation (TMS), which can be used to interfere with brain activity in a specific region transiently for characterisation of the behavioural effects. We describe how TMS combined with fMRI has confirmed a role for the left inferior frontal cortex in semantic processing.

Asian People↗

[Effect of body weight on plantar peak pressure in diabetic patients].

The goal was a better understanding of the correlation between body mass and plantar peak pressure in patients with diabetic neuropathy. A further aim was to obtain insight into the practicability of simulated weight increase and weight release and to delineate more clearly the indications for reducing body weight in order to lower the risk of ulcerations. Simulated change of body weight: (1) +20 kg by a waistcoat and (2)-20 kg by a movable overhead suspension. While normal forces and thus mean normal pressures depend directly on body mass, this does not necessarily apply to peak normal pressures. As shown in a transversal study by Cavanagh with pressure measurements in the bare foot, there is only a poor correlation between body mass and peak pressure. Therefore, peak pressure in heavy persons cannot be expected to be higher than in lighter weight persons. However, from these results it cannot be concluded that peak pressure is likely to remain unchanged irrespective of a change in body weight in a specific subject. Ten subjects were investigated: five controls and five patients suffering from diabetes without neuropathy or preceding ulcerations. All subjects wore the same kind of ready made shoes with ready made standard fitting insoles of cork. Each subject was measured in three modes of weight simulation: normal weight,20 kg weight increase (waistcoat with weight pieces), and 20 kg weight release. Weight release was effected by a modified rescue harness attached to an overhead suspension rail with 6m free walking distance. Individual alignment of the waistcoat and the suspension was checked by a force platform. In-shoe pressure measurement was done with the PEDAR in-shoe system (by Novel, Munich,Germany). For data analysis with the PEDAR standard software only peak pressures were considered. The foot was divided into six regions, particularly metatarsal region and heel. No significant difference between diabetics and controls was found. In the regions at highest risk (metatarsals and heel),peak pressure increased and decreased with weight. In the combined group (n=10), a simulated weight loss of 20 kg decreased metatarsal peak pressure by 5.4+/-1.9 N/cm(2), a 20 kg weight gain increased it by 7.4+/-5.1 N/cm(2). Therefore, without a significant deviation from linearity, peak pressure was found to be a linear function of weight. The results of this study show that weight increase or weight loss in the individual patient has an effect on the plantar peak pressure. The effect is significant in the metatarsal and heel regions. The linearity allows for a simple method of predicting the effect of weight loss by inverting the effect of simulated weight gain.

Adult↗

[Sociodemographic characteristics, risk factors and reproductive history in subjects with fibromyalgia--results of a population-based case-control study].

OBJECTIVES: According to recent studies, 1.3 to 4.8% of the population of Western industrialized nations suffer from fibromyalgia, with 80 to 90% of the affected persons being women. This preponderance of women, mostly in their reproductive years, suggests an association between fibromyalgia and sex hormones. METHODS: Within the framework of a population-based cross-sectional study of 3174 female residents of Bad Säckingen aged 35 to 74 years a stratified random sample of 653 women was clinically examined and surveyed. Thirty-six of these women fulfilled the ACR criteria of fibromyalgia. Forty-four women suffered from chronic widespread pain without having fibromyalgia (chronic pain group); 408 had no chronic pain (controls). RESULTS: Compared to the control group, subjects with fibromyalgia have a 3.6-fold risk, while compared to the chronic pain group, there is a 3.9-fold risk of having a lower social level. Subjects with fibromyalgia drink less alcohol than subjects from the chronic pain group and the control group. After adjusting for age, multivariate analyses demonstrated that, in comparison to controls, subjects with fibromyalgia have a significantly later menarche (OR=2.2 for >14 years) and had never been pregnant (OR=0.3). The comparison of the chronic pain group and controls did not demonstrate these associations. CONCLUSIONS: The associations with a low social level, low alcohol intake, late menarche and rare pregnancies are specific for subjects with fibromyalgia. These factors distinguish subjects with fibromyalgia from subjects with other chronic pain conditions as well as from subjects with no chronic pain. The same hormonal factors responsible for a delayed menarche and a reduced fertility may be relevant in the development of fibromyalgia.

Adult↗

Multifunctional g3p-peptide tag for current phage display systems.

We have previously described a monoclonal antibody (mAb), 10C3, directed against the gene-3 protein (g3p) of filamentous phage M13, which was produced to study g3p fusion protein expression in Escherichia coli and its incorporation in the phage capsid [Tesar, M., Beckmann, C., Röttgen, P., Haase, B., Faude, U., Timmis, K., 1995. Monoclonal antibody against pIII of filamentous phage: an immunological tool to study pIII fusion protein expression in phage display systems. Immunology 1, 53-54]. In this study we report mapping of the antigenic epitope of the mAb 10C3, by means of short overlapping peptide-sequences [Frank, R., Overwin, H., 1996. Spot synthesis. In: Morris, G.E. (Ed.), Methods in Molecular Biology, Vol. 66: Epitope Mapping Protocols. Humana Press, Totowa, NJ, pp. 149-169.] comprising the C-terminal half of the g3-protein. A minimal recognizable peptide was found which is represented in the 11 amino acid sequence from positions 292 to 302 of g3p [Wezenbeek van, P.M.G.P., Hulsebos, T.J.M., Schoenmakers, J.G.G., 1980. Nucleotide sequence of the filamentous bacteriophage M13 DNA genome: comparison with phage fd. Gene 11, 129-148]. In order to use the antibody also for detection and purification of recombinant proteins, such as single chain antibodies, the epitope was introduced as a tag sequence into the phagemid pHEN1 [Hoogenboom, H.R., Griffith, A.D., Johnson, K., Chiswell, D.J., Hudson, P., Winter, G., 1991. Multi-subunit proteins on the surface of the filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acid Res. 19, 4133-4137; Nissim, A., Hoogenboom, H.R., Tomlinson, I.M., Flynn, G., Midgley, C., Lane, D., Winter, G., 1994. Antibody fragments from a single pot phage display library as immunochemical reagents. EMBO J. 13 (3) 692-698]. Purified single chain antibodies containing this tag were detectable down to a concentration of 2 ng ml(-1) under non-denaturing conditions (ELISA) or 4 ng per lane on immunoblots. The high sensitivity of the antibody for the peptide tag was reflected in the antibody affinity constant K(D) of 6.80 x 10(-10) M, which was determined by real time biomolecular interaction analysis (BIA) based on surface plasmon resonance (SPR) [Karlsson, R., Fält, A., 1997. Experimental design for kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors. J. Immunol. Methods 200, 121-133]. Finally, recombinant proteins in E. coli periplasmic extracts could be purified in a single step by affinity purification using immobilized mAb 10C3. These studies demonstrated that the new peptide-tag and its corresponding mAb represents a versatile tool for the detection of recombinant proteins selected by phage display technology.

Antibodies, Monoclonal↗

Utility of green fluorescent nucleic acid dyes and aluminum oxide membrane filters for rapid epifluorescence enumeration of soil and sediment bacteria.

High background fluorescence and unspecific staining hampered the epifluorescence enumeration of bacteria in 45% of the tested soil and sediment samples with 4',6-diamidino-2-phenylindole (DAPI) and polycarbonate membrane filters. These problems of the determination of total cell counts can be circumvented by using green fluorescent high-affinity nucleic acid dyes and aluminum oxide membrane filters. Due to the bright staining of cells, we recommend SYBR Green II as dye.

Aluminum Oxide↗

Monoclonal antibody against pIII of filamentous phage: an immunological tool to study pIII fusion protein expression in phage display systems.

UNLABELLED: A monoclonal antibody directed against the gene 3 product (pIII) of filamentous phage M13 was produced to study pIII-fusion protein expression in E. coli and its incorporation in the phage capsid. The protein was gel-purified from E. coli expression cultures harboring the genetic information of pIII under the control of an inducible lac promoter. To study pIII-fusion protein expression, phage display systems were applied in which either the whole pIII or the C-terminal half was used (McCafferty et al. (1990) Nature (London) 348, 552-554; Szardenings and Collins (1990) Gene 94, 1-7; Barbas and Lerner (1991) In: METHODS: Companion to METHODS in Enzymology, Combinatorial Immunoglobulin Libraries on the Surface of Phage (Phabs): Rapid Selection of Antigen-Specific Fabs, Vol. 2, Academic Press, Orlando, pp. 119-124). In all cases, the monoclonal antibody was able to detect the native and the recombinant protein in E. coli and on the phage tip using non-denaturing (ELISA) and denaturing (SDS-PAGE, immunoblot analysis) conditions. All selected pIII-specific monoclonal antibodies were found to be directed against epitopes within amino acids 198 to 406 of pIII, which is necessary for capsid incorporation and therefore included in all pIII-mediated phage display designs.

Animals↗

Radioactive contamination of soils in lower Saxony, Germany, after the Chernobyl accident.

The horizontal and spatial distribution of artificial and natural radionuclides in soils, and the vertical migration velocity of 0.8-2.0 cm per annum for caesium were examined in order to determine whether caesium is still in the root zone of major plants and, therefore, part of the food-chain. The vertical distribution patterns of caesium are dependent on the different physico-chemical soil properties. The soil samples were analysed with a pure Ge detector. In south-eastern Lower Saxony, the maximum gamma-activity for 137Cs of 33.3 kBq m-2 was found in a depth range of 0-20 cm (January 1, 1989). This was correlated with areas that had received heavy rainfall on May 4, 1986. On January 1, 1989 approximately 60% of the Chernobyl caesium was still in the top 0-2 cm of the topsoil.

Accidents↗

[Microbiological studies in children in nurseries (Study A)].

From 1986 to 1988 76 children, aged from 13 to 36 months, being in 8 créches of a large town were tested microbiologically in the phases: healthy (0), initial phase of acute respiratory disease (A), 2nd and 4th week of convalescence (R2, R4). It was possible to proof bacteria 253 times. 17 various kinds of bacteria were found. Bacteria of catarrhal group (30.8%) and streptococcus pneumoniae (28.4%) dominated among other bacteria. In phase 0 they were isolated in 24% of the children, in phase A in nearly 50%, in phase R2 and R4 in 21 and 14%, respectively in 26 and 25%. Most kinds of bacteria followed this trend. This was not the case with the virological and mycological results. 14 isolations of viruses with 10 various kinds and 30 viro-serological proofs of 8 various kinds did not reflect the actual situation with only 2 quadruple increases of titre during the disease. The detection rate of Candida albicans (24% in healthy) is situated in value expected. Conclusions are drawn.

Bacteria↗

[Microbiological studies on nursery children susceptible to infections].

In a microbiological paper from 1986 to 1988 dealing with 76 children aged from 13 to 36 months in 8 crèches of a large town, it could be found that 24 of these children were susceptible to infections and it is established that there were 3-9 bacteria per child. The most important bacteria were: Staphylococcus aureus, Streptococcus pneumoniae, haemolytic streptococci. But bacteria of the catarrhal group played a certain role, too. In 8 of these children dispositional factors and factors caused by exterior conditions of life (risk factors) could be shown, in 50% out of them a prolonged convalescence and in 50% after 4 weeks a reinfection after acute respiratory disease (ARD). The course of phases of ARD (initial phase, 2. and 4. week of convalescence) is introduced from microbiological view at all children. We point out the meaning of microbiological diagnostics with subsequent aiming sanitation by children susceptible to infections with risk factors.

Bacteria↗

Retention of intrauterine fetal bone increases menstrual prostaglandins.

Intrauterine retention of fetal bone is a rare complication of abortion that can cause secondary infertility by an unknown mechanism. We report such a case in which menstrual fluid prostanoids were measured to elucidate the possible pathophysiology. The pattern of prostanoid increases was similar to that seen in intrauterine device users.

6-Ketoprostaglandin F1 alpha↗

[Thorotrast kidney as a precancerous condition].

9 cases of "thorotrast kidney" after retrograde pyelography with reflux are presented. In 6 patients carcinoma of the renal pelvis developed 47--31 years after thorotrast pyelography. Because of this high rate of carcinoma induction, thorotrast kidney must be classified as a precancerous condition with high-rate tumor manifestation. Thorotrast kidney is diagnosed on X-ray by very opaque linear densities following the calices and pyelon. Early ureteronephrectomy is the treatment of choice in unilateral thorotrast kidneys. If uretero-nephrectomy is not possible, the patient should be followed up regularly with urinary cytologic examinations for early detection of malignancy.

Aged↗

[Proceedings: Evaluation of the plasma-phenolred test as a simple kidney function test].

The phenolsulphthalein 60/60 plasma test (PSP 60/60) was evaluated in 30 control subjects (mean value 51 micrograms/100 ml +/- 49 micrograms/100 ml) and 60 patients with chronic renal disease with varying degrees of renal insufficiency. PSP 60/60 proved to be superior to determination of serum creatinine and urea nitrogen. PSP 60/60 correlated well with endogenous creatinine clearance and 131I-iodohippurate clearance in over 80% of cases. Of various exogenous and endogenous factors interfering with the test, drugs influencing renal excretory mechanisms are most important. Due to its technical simplicity, PSP 60/60 is a useful screening test for evaluation of renal function, especially as an office procedure.

Adult↗

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors].

The new semisynthetic epipodophyllotoxin VP 16-213 has been tested for antitumor activity and toxicity in a non-randomized phase II trial. The study included 33 patients with solid tumors and acute leukemias. The drug was given in 5-day courses every 3 weeks, parenterally for the first 2 courses and thereafter orally. Subjectively VP 16-213 was well tolerated in both i.v. and oral administration, but almost universally induced leukothrombopenia and hair loss. The best results were achieved in 12 patients with oat cell carcinoma of the lung (4 good and 4 less good responses). Remissions of lesser quality were also observed in anaplastic lung cancer, ovarian carcinoma and acute myelomonocytic leukemia. VP 16-213 possesses proven, clinically valuable cytostatic activity against various human neoplasms. Complementary studies to establish its optimum dosage and administration, and its place in combination chemotherapy, are in progress.

Adenocarcinoma↗