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Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 37 records · Page 2Linked to original sources

[Management of pulmonary embolism].

Venous thromboembolism is often triggered by transient episodes of increased risk but may occur spontaneously in patients with permanently increased risk. Pulmonary embolism may cause impairment of respiratory and circulatory function which can vary in severity from silent to catastrophic. The diagnosis can be feasibly established by detecting vein thrombosis. If this approach fails, demonstration of pulmonary emboli by lung scans becomes necessary to establish the diagnosis. A D-dimer-test can select patients in whom imaging of pulmonary perfusion is required. Immediate therapeutic anticoagulation with heparins is mandatory in confirmed thromboembolism, and is followed by a vitamin K antagonist. In the initial work-up, patients also have to be evaluated for systemic thrombolytic therapy by hemodynamic parameters and echocardiography. In a triggered episode of venous thromboembolism, duration of anticoagulation is confined to several months while spontaneous or recurrent events require prolonged or indefinite treatment.

Anticoagulants↗

[Damage control orthopedics].

BACKGROUND: In the management of patients with multiple injuries, the concept of damage control orthopedics (DCO) is still a matter of controversy. Thus, the clinical value of DCO remains unclear and should be evaluated on an evidence-based level by a review of the current literature. RESULTS: The work of various authors has demonstrated an association between injury severity and the clinical immuno-inflammatory response and its prognostic relevance regarding organ dysfunction or organ failure and clinical outcome. Research data published by the authors and other investigators have clearly demonstrated an additional inflammatory response caused by surgical trauma which is significantly higher after primary intramedullary fracture treatment than after external fracture stabilization. In contrast, a generally minor inflammatory response seems to be associated with intramedullary nailing for secondary conversion osteosynthesis. Three retrospective cohort studies have shown a reduction of organ dysfunction and an improvement of survival with the DCO approach. Simultaneously, it was demonstrated that primary external fracture fixation and secondary conversion to definite osteosynthesis is not associated with an increased rate of local or systemic complications. CONCLUSIONS: The advocates of DCO claim that patients with multiple injuries including severe brain and chest injuries as well as those with an unstable cardiopulmonary or circulatory condition are at high risk of developing a severe systemic immuno-inflammatory reaction during early total fracture care. Therefore, they recommend primary minimally invasive external fracture stabilization in these patients to avoid additional surgical trauma and that definitive secondary fracture care should be performed after medical stabilization of the patient in intensive care.

Critical Care↗

Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study.

BACKGROUND: For many years topical progesterone has been prescribed by gynaecologists as an antiageing and skin-firming treatment, without any clinical scientific evidence of its effects, tolerability and safety when applied to skin. OBJECTIVES: To evaluate the influence of 2% progesterone cream on function and texture of the skin in peri- and postmenopausal women. METHODS: A double-blind, randomized, vehicle-controlled study was conducted in 40 subjects. Objective methods for measuring skin elasticity, epidermal hydration and skin surface lipids, clinical monitoring and self-assessment, and determination of blood hormone levels (luteinizing hormone, follicle-stimulating hormone, oestrogen and progesterone) were used to determine effects and side-effects of this treatment at four visits over a 16-week period. RESULTS: The study demonstrated a significant (P < or = 0.05) increase of the elastic skin properties in the treatment group, as demonstrated by objective measurements of three skin elasticity parameters, whereas in the control group no such effect was observed. This effect in the treatment group was further paralleled by the results of the clinical monitoring, where the 2% progesterone cream yielded consistent superiority over vehicle in counteracting different signs of ageing in the skin of peri- and postmenopausal women. Clinical monitoring showed a greater reduction in wrinkle counts (29.10% vs. 16.50%) and wrinkle depth (9.72% vs. 7.35%) around the right eye, a greater decrease in nasolabial wrinkle depth (9.72% vs. 6.62%) and a significantly higher (P < 0.05) increase in skin firmness (23.61% vs. 13.24%) in the treatment group. Epidermal hydration and skin surface lipids did not change significantly in either group during the study. Progesterone was well absorbed in the systemic circulation: mean blood levels rose minimally, but statistically significantly (P = 0.001), by 0.53 ng mL(-1). No serious side-effects of the treatment were observed. CONCLUSIONS: The results of this study demonstrate that topical 2% progesterone acts primarily in increasing elasticity and firmness in the skin of peri- and postmenopausal women. These effects in combination with good tolerability make progesterone a possible treatment agent for slowing down the ageing process of female skin after onset of the menopause.

Double-Blind Method↗

DNA methylation is not likely to be responsible for aggrecan down regulation in aged or osteoarthritic cartilage.

BACKGROUND: Expression of aggrecan is reduced during aging and osteoarthritic cartilage degeneration. CpG methylation may have a role in the down regulation of aggrecan transcriptions. OBJECTIVE: To investigate whether a correlation between gene methylation and expression of aggrecan in chondrocytes exists. METHODS: The human aggrecan promoter region was analysed computationally for CpG-rich regions. These were investigated for the methylation of C residues in normal (aged) and osteoarthritic chondrocytes by the bisulphite method for modifying DNA as well as sequence analysis using DNA directly extracted from normal and osteoarthritic cartilage tissue. Additionally, chondrocytic cell lines were investigated for methylation within the aggrecan promoter region. RESULTS: The CpG-rich promoter region of the human aggrecan gene contains a 0.6 kb region that meets the criteria of a CpG island as defined by prediction programmes. A significant correlation of aggrecan mRNA expression levels and methylation status in normal (aged) and osteoarthritic chondrocytes as well as in different chondrocytic cell lines was not found. CONCLUSIONS: Expression of aggrecan in normal cartilage and diseased states is not modulated by gross changes of CpG methylation of its promoter region. CpG methylation does not have a central role in the switch off of aggrecan promoter activity in human adult articular chondrocytes.

Aged↗

Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

BACKGROUND: The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. METHODS: In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). RESULTS: 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). CONCLUSIONS: This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.

Adult↗

Effect of splitting the dose of esomeprazole on gastric acidity and nocturnal acid breakthrough.

BACKGROUND: Twice-daily dosing is increasingly used to improve gastric acid control, although not all proton-pump inhibitors are more effective when doses are split. Standard dose esomeprazole provides better gastric acid control than other standard dose proton-pump inhibitors. AIMS: To compare the effect of standard dose esomeprazole (1 x 40 mg) with 20 mg b.d. on gastric acidity. METHODS: Thirteen healthy subjects participated in this crossover study, receiving esomeprazole 2 x 20 mg and 1 x 40 mg for 7 days in random order with a washout period of at least 7 days. Gastric 24-h pH was measured on days 1, 2 and 6. RESULTS: Median gastric 24-h pH was higher during 2 x 20 mg esomeprazole on day 2 (P < 0.01), no differences were detected on day 6. Night-time gastric acid suppression was significantly improved by 2 x 20 mg esomeprazole on all study days (P < 0.05). Nocturnal acid breakthrough was observed on all study days in subjects receiving 1 x 40 mg, but in only 85% (first night), 64% (second night), and 45% of subjects (sixth night) with 2 x 20 mg (P < 0.05). CONCLUSION: Splitting the esomeprazole dose improves initial acid suppression, this effect starts at the first night. Maximal benefit is achieved on day 2, while the effect on night-time acid control is detectable during the entire first week of treatment.

Adult↗

Detection of cell-free nucleic acids in bronchial lavage fluid supernatants from patients with lung cancer.

The aim of this study was to determine whether nucleic acids are detectable in cell-free bronchial lavage supernatants, and whether it is possible to find alterations in this DNA and RNA of genes known to be present in lung tumour cells. DNA was isolated from cell-free lavage supernatants from 30 and RNA from 25 lung cancer patients. The DNA was examined for microsatellite alterations (MA) and the RNA analysed for the expression of seven tumour-associated genes. Intact DNA and mRNA could be isolated from all cell-free bronchial lavage supernatants. MA were found in lavage supernatants of 12/30 patients and in lavage cells of 6/30 patients. Altogether alterations were found in 14/30 patients. Analyses of tumour-associated gene expression showed positive results, with at least one marker in the lavage supernatants of all 25 patients. Thus, we could demonstrate, for the first time, that it is possible to isolate intact DNA and RNA from cell-free bronchial lavage supernatants. Their quantity and quality is sufficient for further amplification by polymerase chain reaction (PCR)/reverse transcriptase (RT)-PCR. Altogether, tumour-associated changes were detected in DNA samples from 47% of the patients and in RNA samples from all of the patients analysed.

Aged↗

Degradation of the radioactive and non-labelled branched 4(3',5'-dimethyl 3'-heptyl)-phenol nonylphenol isomer by sphingomonas TTNP3.

The degradation of the 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) nonylphenol isomer in cultures of Sphingomonas TTNP3 supplemented with the technical mixture of nonylphenol was first assessed. Then the radioactive and non-labelled form of these diastereomers were both synthesised. The radioactive isomers were synthesised using [ring-U-14C]-labelled phenol and 3,5-dimethyl-3-heptanol by Friedel and Crafts alkylation. The time-course of degradation was performed with and without 14C-p353NP; balancing of radioactivity was calculated from different soluble fractions (organic, aqueous), bacterial biomass, and 14CO2 evolved as mineralization product. The noticeable portion of 14C bound to biomass showed that at least the aromatic ring of 14C-p353NP was degraded and served as energy source and probably as carbon source for bacterial growth. In addition, the appearance of 3,5-dimethyl-3-heptanol, the nonanol corresponding with the side-chain of p353NP, was demonstrated in the bacterial media, and its concentration determined during the course of fermentation. Besides the parent 14C-p353NP, no other radioactive compounds, i.e. metabolites of 14C-p353NP were detected in the media.

Biodegradation, Environmental↗

A new approach in anti-epileptic drug evaluation.

Presurgical trials with video-electroencephalogram (EEG) monitoring for a couple of days provide the possibility to objectively and quantitatively analyze seizure activity during different drug treatments. Patients are provided with the optimal medical care and safety precautions when hospitalized. Hereby a method used in the antiepileptic drug (AED) trials called therapeutic intensive seizure analysis (TISA) has been recently introduced, by which AED efficacy on seizure activity can be objectively quantified by using continuous video-EEG monitoring. This could be used not only as a supplement to the traditional evaluation of AEDs' efficacy by treatment failure designs in large groups, but also can provide early individual information on the changes of seizure activity of each patient during the therapy. Data from TISA studies suggest that secondarily generalized tonic-clonic seizures (SGTCs) mostly occur in patients with a SGTC history after withdrawal of AED. The first 3 days of titration of a newly introduced AED was important for efficacy assessment; with a low risk of SGTCs. By using the TISA method an early recognition of first effects of a new AED on seizure activity and neuropsychological changes is possible, which can be correlated to serum concentration levels in a small sample size. The essentials of the proposed modification to the conventional presurgical trial are: (1) a complete withdrawal of AEDs should be avoided, if possible and (2) a titration phase limited to 3 days is suggested, using a condensed evaluation setting including the TISA method, serum concentration and neuropsychological monitoring. In addition long-term effects can be evaluated by repeated video-EEG monitoring.

Anticonvulsants↗

Chemical nociception in the jejunum induced by capsaicin.

BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. METHODS: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). RESULTS: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 microg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 microg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain thresholds during distensions were not different before and after capsaicin perfusion. CONCLUSION: Despite the similarities in abdominal localisation and perceptional quality of capsaicin and distension induced sensations, our results rule out the fact that abdominal discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an increase in phasic and tonic motor activity. Capsaicin evokes abdominal sensations by stimulation of chemoreceptors which proves the existence of chemonociception in the human small intestine.

Abdomen↗

Detection of tumor-specific mRNA in cell-free bronchial lavage supernatant in patients with lung cancer.

Bronchoscopy is a standard procedure in the workup of patients with suspicious pulmonary lesions. We wondered whether it is possible to isolate malignancy-associated mRNA from cell-free lavage supernatant. Extracellular mRNA from cell-free lavage supernatant of 25 patients with lung cancer (23 with non-small cell lung cancer, 2 with small cell lung cancer) was isolated, reverse-transcribed, and amplified by reverse transcriptase polymerase chain reaction. The quantity and quality of the isolated RNA were checked after cDNA synthesis by amplification with beta-actin-specific primers. Afterwards, a panel of eight genes known to be expressed in lung tumors was used for the detection of tumor-associated mRNA expression in lavage supernatant and serum. mRNA coding for beta-actin could be isolated from lavage supernatant of all 25 patients. In addition, the expression of at least one tumor-associated gene was detectable in all patients. These results show that intact mRNA can be isolated from cell-free lavage supernatant and that its quantity and quality are sufficient for the detection of tumor-associated gene expression alterations. This may open new possibilities for the diagnosis of lung cancer.

Actins↗

Microbial degradation of a single branched isomer of nonylphenol by Sphingomonas TTNP3.

The endocrine disrupting chemical nonylphenol (NP) is a technical product which consists of a complex mixture of nonylphenols with different alkyl side-chain isomers. Since the bio-degradation of each NP isomer may lead to its own range of metabolites, the isolation and identification of transformation products is very difficult. In order to overcome this difficulty, the nonylphenol isomer 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) was synthesized, and its degradation by an axenic culture of Sphingomonas TTNP3 was investigated with [ring-U-14C]-labelled and non-labelled p353NP including a time-course study. Radioactive mass balancing resulted in different polar soluble fractions, in insoluble radioactivity associated with biomass, and volatile radioactivity in the form of the mineralization product 14CO2. In the extracellular media, the presence of nonanol corresponding to the nonyl chain of the NP isomer was confirmed and its concentration was determined during the course of fermentation. No other radioactive compounds were detected beside the parent isomer. Radioactive metabolites were only found in the intracellular fraction of S. TTNP3.

Biodegradation, Environmental↗

Bioavailability of a nonylphenol isomer in dependence on the association to dissolved humic substances.

Humic substances are important environmental components since they represent a very large part of organic compounds on earth. According to many reports, dissolved humic substances are a determinant parameter for the bioavailability of xenobiotic compounds. For the present bioavailability studies, two kinds of dissolved humic substances, a commercially available humic acid and fulvic acids isolated from peat were used. As the relevant xenobiotic, a defined branched nonylphenol isomer, 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) was synthesised according to Friedel-Crafts alkylation. Equilibrium dialysis studies were implemented in order to investigate the association between 14C-labelled p353NP and dissolved humic substances. The biodegradability in the presence of dissolved humic substances was examined in experiments with the nonylphenol degrading bacterium strain Sphingomonas TTNP3 and with p353NP as sole carbon source. The results showed that p353NP-humic acid associates were formed in high amounts, whereas no adducts with fulvic acids occurred. In the degradation studies with Sphingomonas TTNP3, no effects of dissolved humic substances on the bioavailability of p353NP could be observed. It was assumed that the association between nonylphenol and humic acids occurs rapidly and is reversible. Thus, the formation of "labile" complexes did not influence biodegradation rates, which were quite low.

Biological Availability↗

Updated European recommendations for the clinical use of HIV drug resistance testing.

In most European countries, HIV drug resistance testing has become a routine clinical tool. However, its practical implementation in a clinical context is demanding. The European HIV Drug Resistance Panel was established to make recommendations to clinicians and virologists on this topic and to propose quality control measures. The panel recommends resistance testing for the following indications: i) drug-naive patients with acute or recent infection; ii) therapy failure, including suboptimal treatment response, when treatment change is considered; iii) pregnant HIV-1-infected women and paediatric patients with detectable viral load when treatment initiation or change is considered; and iv) genotype source patient when post-exposure prophylaxis is considered. In addition, for drug-naive patients with chronic infection in whom treatment is to be started, the panel suggests that resistance testing should be strongly considered and recommends testing the earliest sample for drug resistance if suspicion of resistance is high or prevalence of resistance in this population exceeds 10%. The panel does not favour genotyping over phenotype, however it is anticipated that genotyping will be used more often because of its greater accessibility, lower cost and faster turnaround time. For the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible. It is mandatory that laboratories performing HIV resistance tests take regular part in quality assurance programs. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and meet regularly to discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. The panel also encourages the timely collection of epidemiological information to estimate the impact of transmission of resistant HIV and the prevalence of HIV-1 non-B subtypes in the different European countries.

Anti-HIV Agents↗

Dynamics of multimode diode lasers with strong, frequency-selective optical feedback.

The dynamical behavior of a class of multimode semiconductor diode lasers with emission wavelength around 980 nm is investigated both experimentally and numerically in the presence of strong, frequency-selective optical feedback provided by a fiber Bragg grating. The focus is set on the switching between broad- and narrow-band optical spectra, on chaotic transitions, and on the loss of frequency locking between laser and grating. Laser and feedback parameters are chosen in the typical ranges pertaining to wavelength stabilization in erbium-doped fiber amplifiers for telecommunication applications. An improved set of rate equations, which allows for arbitrary feedback levels and includes experimentally measured gain and linewidth enhancement factor, is studied analytically and numerically.

Journal Article↗