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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 37 records · Page 2Linked to original sources
PubMed2002

Association between flupenthixol treatment and emergence of manic symptoms.

BACKGROUND: Flupenthixol is an antipsychotic drug with known mood-elevating properties. Its propensity to induce manic symptoms has not been investigated. METHODS AND RESULTS: We describe six patients, four with schizophrenia and two with bipolar disorder, in whom flupenthixol treatment was associated with emergence of manic symptoms. CONCLUSIONS: Patients treated with flupenthixol should be carefully monitored for the emergence of manic symptoms.

Adult↗
PubMed2002

The spectrum of allergic (cross-)sensitivity in clinical patch testing with 'para amino' compounds.

BACKGROUND: Allergic contact sensitization to 'para amino' compounds is frequent and the spectrum of cross-reactivity between members of this chemical group is variable. METHODS: A retrospective analysis of clinical patch test data obtained with a special test series in the centres of the Information Network of Departments of Dermatology (IVDK) between 1995 and 1999. RESULTS: In the 638 patients tested with the above test panel positive reactions were observed most often to p-aminoazobenzene (16.2%), p-phenylenediamine (14.1%), p-toluylenediamine (10.0%), followed by 4,4'-diaminodiphenylmethane (8.5%), Disperse Orange 3 (8.4%) and p-aminophenol (3.1%). Among the 544 patients tested with p-phenylenediamine and all seven additional 'para amino' compounds, concordance between reactions varied greatly. The stronger the positive test reaction to p-phenylenediamine, p-toluylenediamine or p-aminoazobenzene, the more frequently additional positive reactions to the other compounds were observed. CONCLUSIONS: A screening employing several 'para amino' compounds is necessary to describe the individual spectrum of allergic contact sensitization, as there is no reliable marker substance. Further research should aim at (i) establishing the mechanism of cross-reactivity to 'para amino' compounds and (ii) identifying exposures in the environment.

4-Aminobenzoic Acid↗
PubMed2002

[Hepatic transit time of an ultrasound echo enhancer indicating the presence of liver metastases - first clinical results].

AIM: This pilot study examines the question whether the transit time of an ultrasound echo enhancer, measured between the hepatic artery and the liver vein, can be used to differentiate between patients with and without liver metastases. METHOD: The hepatic transit time of an ultrasound echo enhancer (Optison(R)) was determined using the pulse-inversion mode in patients suffering from gastrointestinal tumours. A group with histologically verified liver metastases was compared to a group without liver metastases. RESULTS: 24 patients have been included in the study so far. 7 patients had liver metastases from a still existing primary tumour (group A). Five patients showed liver metastases after removal of the primary tumour (group B). Six patients had a primary tumour, but no liver involvement (group C), and six patients had neither a primary tumour nor any liver disease. The mean hepatic transit time in group A and B came to 7.4 seconds. Group C and D had a transit time of 16 and 15.5 seconds, respectively. This shows a significant difference in hepatic transit time between patients with liver metastases (groups A and B) compared to those without (groups C and D). The presence of a primary tumour did not influence hepatic transit time. CONCLUSION: In this first pilot study using the measurement of hepatic transit time it was possible to differentiate between patients with and without liver metastases.

Contrast Media↗
PubMed2002

[Treatment of a solitary adenoma of the parathyroid gland with ultrasound-guided percutaneous Radio-Frequency-Tissue-Ablation (RFTA)].

Radio-Frequency-Tissue-Ablation (RFTA) for the treatment of primary and secondary tumours of the liver has been used for several years, but this minimally invasive treatment is not limited to the liver. A patient suffering from symptomatic postmenopausal osteoporosis, additionally having primary hyperparathyroidism since 1995, refused a surgical resection of the adenoma of the parathyroid gland. Sonographically a 16 mm hypoechoic tumour dorsal of the right upper pole of the thyroid gland was detected. Osteodensitometry: severe osteoporosis of the lumbar spine (88 % of the norm for this age group). Blood check: Elevation of serum calcium level (3.1mmol/l) and serum parathormone level 274 pg/dl (N: 10-50). A percutaneous ultrasound guided RFTA of the adenoma of the thyroid gland was carried out. After RFTA the serum parathormone levels and the serum calcium levels dropped back to normal. The patient was followed-up for one year. For the first time a sufficient therapy for osteoporosis comprising calcium, etidronate and cholecalciferol could be carried out. The osteodensitometry carried out one year after treatment showed an increase in bone density. For the treatment of symptomatic primary hyperparathyroidism RFTA can be a therapeutic alternative for patients with contraindications for surgery.

Adenoma↗
PubMed2002

[Contrast enhanced ultrasound in the liver using low mechanical index--what is the difference?].

Echo-enhancing agents (EEA), also known as ultrasound contrast media, have improved the diagnostic potential of gastroenterologic ultrasound within the last years. Initially used to increase color-Doppler signals the potential to use harmonic waves being generated by the use of EEAs was established later. The effect was based upon the distraction of the EEA bubbles and the resulting pseudo-Doppler signal, the exam was carried out with high ultrasound energy and intermittent switching on and off of the ultrasound beam. Using this effect in real-time during continuous scanning is possible since the introduction of new EEAs with a flexible shell. This flexible shell oscillates during the scan process emitting harmonic signals. This new technology opens new possibilities for the detection of liver tumors including the possible characterisation. The detection rate for liver metastases can be increased by app. 40 % with this new technology. Correct sonographic characterisation of liver tumors can be achieved in nearly 100 % more cases.

Contrast Media↗
PubMed2002

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.

Allergens↗
PubMed2001

K(+) channel profile and electrical properties of Arabidopsis root hairs.

Ion channels and solute transporters in the plasma membrane of root hairs are proposed to control nutrient uptake, osmoregulation and polar growth. Here we analyzed the molecular components of potassium transport in Arabidopsis root hairs by combining K(+)-selective electrodes, reverse transcription-PCR, and patch-clamp measurements. The two inward rectifiers AKT1 and ATKC1 as well as the outward rectifier GORK dominated the root hair K(+) channel pool. Root hairs of AKT1 and ATKC1 loss-of-function plants completely lack the K(+) uptake channel or exhibited altered properties, respectively. Upon oligochitin-elicitor treatment of root hairs, transient changes in K(+) fluxes and membrane polarization were recorded in wild-type plants, while akt1-1 root hairs showed a reduced amplitude and pronounced delay in the potassium re-uptake process. This indicates that AKT1 and ATKC1 represent essential alpha-subunits of the inward rectifier. Green fluorescent protein (GFP) fluorescence following ballistic bombardment with GORK promoter-GFP constructs as well as analysis of promoter-GUS lines identified this K(+) outward rectifier as a novel ion channel expressed in root hairs. Based on the expression profile and the electrical properties of the root hair plasma membrane we conclude that AKT1-, ATKC- and GORK-mediated potassium transport is essential for osmoregulation and repolarization of the membrane potential in response to elicitors.

Acetylglucosamine↗
PubMed2001

Engineering of a glycosidase Family 7 cellobiohydrolase to more alkaline pH optimum: the pH behaviour of Trichoderma reesei Cel7A and its E223S/ A224H/L225V/T226A/D262G mutant.

The crystal structures of Family 7 glycohydrolases suggest that a histidine residue near the acid/base catalyst could account for the higher pH optimum of the Humicola insolens endoglucanase Cel7B, than the corresponding Trichoderma reesei enzymes. Modelling studies indicated that introduction of histidine at the homologous position in T. reesei Cel7A (Ala(224)) required additional changes to accommodate the bulkier histidine side chain. X-ray crystallography of the catalytic domain of the E223S/A224H/L225V/T226A/D262G mutant reveals that major differences from the wild-type are confined to the mutations themselves. The introduced histidine residue is in plane with its counterpart in H. insolens Cel7B, but is 1.0 A (=0.1 nm) closer to the acid/base Glu(217) residue, with a 3.1 A contact between N(epsilon2) and O(epsilon1). The pH variation of k(cat)/K(m) for 3,4-dinitrophenyl lactoside hydrolysis was accurately bell-shaped for both wild-type and mutant, with pK(1) shifting from 2.22+/-0.03 in the wild-type to 3.19+/-0.03 in the mutant, and pK(2) shifting from 5.99+/-0.02 to 6.78+/-0.02. With this poor substrate, the ionizations probably represent those of the free enzyme. The relative k(cat) for 2-chloro-4-nitrophenyl lactoside showed similar behaviour. The shift in the mutant pH optimum was associated with lower k(cat)/K(m) values for both lactosides and cellobiosides, and a marginally lower stability. However, k(cat) values for cellobiosides are higher for the mutant. This we attribute to reduced non-productive binding in the +1 and +2 subsites; inhibition by cellobiose is certainly relieved in the mutant. The weaker binding of cellobiose is due to the loss of two water-mediated hydrogen bonds.

Alkalies↗
PubMed2001

The Arabidopsis thaliana ABC transporter AtMRP5 controls root development and stomata movement.

In the present study, we investigated a new member of the ABC transporter superfamily of Arabidopsis thaliana, AtMRP5. AtMRP5 encodes a 167 kDa protein and exhibits low glutathione conjugate and glucuronide conjugate transport activity. Promotor- beta-glucuronidase fusion constructs showed that AtMRP5 is expressed mainly in the vascular bundle and in the epidermis, especially guard cells. Using reverse genetics, we identified a plant with a T-DNA insertion in AtMRP5 (mrp5-1). mrp5-1 exhibited decreased root growth and increased lateral root formation. Auxin levels in the roots of mrp5-1 plants were increased. This observation may indicate that AtMRP5 works as an auxin conjugate transporter or that mutant plants are affected in ion uptake, which may lead to changes in auxin concentrations. Experiments on epidermal strips showed that in contrast to wild type, the sulfonylurea glibenclamide had no effect on stomatal opening in mrp5-1 plants. This result strongly suggests that AtMRP5 may also function as an ion channel regulator.

ATP-Binding Cassette Transporters↗
PubMed2001

From cell death to embryo arrest: mathematical models of human preimplantation embryo development.

Human preimplantation embryos exhibit high levels of apoptotic cells and high rates of developmental arrest during the first week in vitro. The relation between the two is unclear and difficult to determine by conventional experimental approaches, partly because of limited numbers of embryos. We apply a mixture of experiment and mathematical modeling to show that observed levels of cell death can be reconciled with the high levels of embryo arrest seen in the human only if the developmental competence of embryos is already established at the zygote stage, and environmental factors merely modulate this. This suggests that research on improving in vitro fertilization success rates should move from its current concentration on optimizing culture media to focus more on the generation of a healthy zygote and on understanding the mechanisms that cause chromosomal and other abnormalities during early cleavage stages.

Apoptosis↗
PubMed2001

Dynamic contrast-enhanced power Doppler sonography improves the differential diagnosis of liver lesions.

The aim of this paper was to investigate the diagnostic value of dynamic contrast-enhanced power Doppler sonography in the differential diagnosis of liver lesions. We prospectively examined 85 focal liver lesions in 71 patients by real-time gray-scale sonography, power Doppler sonography, and contrast-enhanced power Doppler using two ultrasound contrast agents (Levovist, Optison). Amount and architecture of lesion vascularity and the kinetics of contrast enhancement within the lesions were analyzed. Vascularity was detected in 61% of liver lesions (52/85) by conventional power Doppler, compared to 86% (73/85) by contrast-enhanced power Doppler sonography. Dynamic contrast-enhanced power Doppler identified arterial radial hypervascularity <16 s after contrast injection in 19/22 focal nodular hyperplasias (86%). Irregular hypervascularity was seen with contrast enhancement in the arterial phase in 14/15 hepatocellular carcinomas (93%). In 14/25 hemangiomas (56%), a circular vascularization pattern was noted. Specific lesion diagnosis based on B-scan and conventional and dynamic contrast-enhanced power Doppler sonography led to correct diagnosis in 86% (73/85, 95% confidence interval 78%-94%) compared to 57% (48/85, 95% confidence interval 47%-94%) by B-scan criteria and conventional power Doppler sonography. Contrast-enhanced power Doppler sonography improves diagnostic accuracy in the differential diagnosis of focal liver lesions.

Albumins↗
PubMed2001

Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction.

Previous studies have shown the implication of beta-defensins in host defense of the human body. The human beta-defensins 1 and 2 (hBD-1, hBD-2) have been isolated by biochemical methods. Here we report the identification of a third human beta-defensin, called human beta-defensin 3 (hBD-3; cDNA sequence, Genbank accession no. AF295370), based on bioinformatics and functional genomic analysis. Expression of hBD-3 is detected throughout epithelia of many organs and in non-epithelial tissues. In contrast to hBD-2, which is upregulated by microorganisms or tumor necrosis factor-alpha (TNF-alpha), hBD-3 expression is increased particularly after stimulation by interferon-gamma. Synthetic hBD-3 exhibits a strong antimicrobial activity against gram-negative and gram-positive bacteria and fungi, including Burkholderia cepacia. In addition, hBD-3 activates monocytes and elicits ion channel activity in biomembranes, specifically in oocytes of Xenopus laevis. This paper also shows that screening of genomic sequences is a valuable tool with which to identify novel regulatory peptides. Human beta-defensins represent a family of antimicrobial peptides differentially expressed in most tissues, regulated by specific mechanisms, and exerting physiological functions not only related to direct host defense.

Amino Acid Sequence↗
PubMed2001

Limits of body mass index to detect obesity and predict body composition.

Body mass index (BMI) is commonly used to identify obesity. In this study, we determined how accurately BMI could determine body composition and identify obese from non-obese individuals. Fat-free mass and body fat were determined with bioelectrical impedance. Adiposity was calculated as body fat per body mass and as body fat divided by body height (m2). Obesity was defined as a BMI of at least 30 kg/m2 or an amount of body fat of at least 25% of total body mass for men and at least 30% for women. Obesity as defined by percentage of body fat was always present with a BMI of at least 30 kg/m2. However, 30% of men and 46% of women with a BMI below 30 kg/m2 had obesity levels of body fat. The greatest variability in the prediction of percentage of body fat and body fat divided by height (m2) from regression equations using BMI was at a BMI below 30 kg/m2. In conclusion, using impedance-derived body-fat mass as the criterion, people with BMI of at least 30 kg/m2 are obese. However, significant numbers of people with a BMI below 30 kg/m2 are also obese and thus misclassified by BMI. Percent of body fat and body fat divided by height (m2) are predictable from BMI, but the accuracy of the prediction is lowest when the BMI is below 30 kg/m2. Therefore, measurement of body fat is a more appropriate way to assess obesity in people with a BMI below 30 kg/m2.

Adipose Tissue↗
PubMed2001

Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.

BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS AND METHODS: Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

Aged↗