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Biomedical subjects

B Seifert

Publications and source records attributed to B Seifert.

At least 19 recordsLinked to original sources

Clinical significance of cyclooxygenase-2 (COX-2) in multiple myeloma.

Several biological and clinical considerations suggest the involvement of cyclooxygenase-2 (COX-2), the key enzyme of prostaglandin (PG) synthesis, in the pathogenesis and progression of haematological malignancies. Despite the wealth of data concerning COX-2 expression, only limited information is available on multiple myeloma (MM). Using standard immunohistochemistry we therefore evaluated COX-2 protein expression in samples from 57 patients with a primary diagnosis of MM. Time to progression and a variety of clinicopathological features were evaluated by the Kaplan-Meier method and the Cox regression model. In addition, COX-2 expression was evaluated by staining bone marrow from healthy donors and 11 patients with MGUS. Overall, 31 MM samples (54%) expressed COX-2. Positivity for COX-2 was unrelated to stage or clinical or molecular features of the disease. However, patients with COX-2 positive tumours experienced a significantly shorter time to progression (17 vs 30 months, p = 0.037). In summary, COX-2 is frequently expressed in MM and correlates with shorter progression-free survival.

Adult↗

First clinical experience of tracheal intubation with the SensaScope, a novel steerable semirigid video stylet.

BACKGROUND: Problems with tracheal intubation are a major cause of anaesthesia-related morbidity and mortality. Difficulty with tracheal intubation is primarily a consequence of failure to see the vocal cords with conventional direct laryngoscopy. We report our experience with use of the SensaScope for tracheal intubation in routine clinical practice. METHODS: The SensaScope is a hybrid steerable semirigid S-shaped video stylet. Its handling and performance were assessed by anaesthetists with a minimum of 1 yr of experience. They performed four intubations each with the device in anaesthetized elective surgical patients. The view of the glottis with the Macintosh laryngoscope was compared with the view shown on the monitor by the SensaScope. The time taken to complete intubation, the final tracheal tube (TT) position and the degree of difficulty of the procedure were recorded. RESULTS: Thirty-two patients were studied. All Macintosh Cormack and Lehane grade 3 patients were converted to grade 1 or 2 with the SensaScope. Mean intubation time was 25 (12) s and correct mid-tracheal TT cuff position was achieved in all cases. The degree of difficulty was 3.0 (1.8) on a numerical scale ranging from 0 to 10. All operators rapidly became familiar with the device and mastered its technique of use. CONCLUSION: The SensaScope is a reliable and effective device for tracheal intubation under vision of the normal airway. It has great potential to facilitate management of difficult airway situations in anaesthetized and paralysed patients.

Adult↗

No sympatric speciation here: multiple data sources show that the ant Myrmica microrubra is not a separate species but an alternate reproductive morph of Myrmica rubra.

No aspect of speciation is as controversial as the view that new species can evolve sympatrically, among populations in close physical contact. Social parasitism has been suggested to yield necessary disruptive selection for sympatric speciation. Recently, mitochondrial DNA phylogeography has shown that the ant Myrmica microrubra is closely related to its host, Myrmica rubra, leading to the suggestion that sympatric speciation has occurred. We investigated the relationships between the two ant forms using mitochondrial and nuclear DNA sequences, microsatellite genotyping and morphometrics. Molecular phylogenetic and population structure analyses showed that M. microrubra does not evolve separately to its host but rather shares a gene pool with it. Probability analysis showed that mitochondrial DNA data previously adduced in favour of sympatric speciation do not in fact do so. Morphometrically, M. microrubra is most readily interpreted as a miniature queen form of M. rubra, not a separate species. Myrmica microrubra is not an example of speciation. The large (typical M. rubra) and small (M. microrubra) queen forms are alternative reproductive strategies of the same species. Myrmica microrubraSeifert 1993 is consequently synonymized here with M. rubra Linnaeus, 1758.

Animals↗

Simple criteria for differentiation of Fabry disease from amyloid heart disease and other causes of left ventricular hypertrophy.

AIMS: Fabry disease may be difficult to differentiate from other causes of left ventricular hypertrophy such as other myocardial storage diseases (including amyloidosis), hypertrophic cardiomyopathy (HCM), or hypertensive heart disease (HHD). We sought to determine simple criteria to best differentiate the above mentioned cardiac diseases. METHODS AND RESULTS: All patients in a six-year time period with left ventricular hypertrophy due to Fabry disease (13 patients), biopsy proven cardiac amyloidosis (16 patients), non-obstructive HCM (17 patients), and 22 randomly selected patients with advanced HHD were compared. Retrospective analysis of clinical characteristics, findings of electrocardiogram (ECG) and echocardiography by blind review was performed. RESULTS: No single clinical characteristic or findings of ECG or echocardiography could reliably differentiate between the various diseases. Increased echogenicity/granular sparkling, valvular abnormalities, abnormal renal function, and diastolic function were not helpful discriminators. In a univariate analysis, four criteria (acroparesthesia, anhydrosis, absence of hypertension and presence of Sokolow criteria for left ventricular hypertrophy in the ECG) were significant for Fabry disease. By logistic regression analysis, the following most suitable discriminative parameters were identified: hypertension in HHD (specificity 82%), orthostasis and/or pericardial effusion for amyloidosis (specificity 93%), papillary muscle anomaly in non-obstructive HCM (specificity 92%), and Fabry disease if neither hypertension orthostatis, pericardial effusion nor a papillary muscle anomaly was present (specificity 87%). CONCLUSION: A combination of symptoms, echocardiographic findings and ECG in unexplained left ventricular hypertrophy may help to differentiate amyloidosis, non-obstructive HCM and hypertensive heart disease from Fabry disease. The results of this preliminary study will have to be confirmed in a prospective study.

Adult↗

Dose optimization of contrast-enhanced carotid MR angiography.

The purpose of this work was to compare the diagnostic performance of a single-contrast or a double-contrast dose of carotid contrast-enhanced MR angiography (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73 ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x 0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased-array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s, either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30 ml saline. Qualitative image analysis was performed on maximum intensity projections using a five-point scale. Signal intensities were measured at three different vascular levels on both sides to assess the contrast-to-noise ratios (CNRs). Image quality was rated as good or excellent in all cases. A double dose did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/-19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In both dose groups the mean CNRs were inversely related to bodyweight, despite adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA is not superior to single-dose MRA, as overall diagnostic performance and quantitative contrast enhancement are equal. Being more cost-efficient, a single-dose administration of contrast agent is recommended for MRA of the carotid arteries.

Adult↗

Complaints of sore throat after tracheal intubation: a prospective evaluation.

BACKGROUND AND OBJECTIVE: Sore throat and hoarseness rank, besides pain and nausea, among the most frequent subjective complaints after tracheal intubation for general anaesthesia. Our intention was to determine the incidence of postoperative sore throat from a large sample of patients and thus to identify the most important associated factors. METHODS: We prospectively followed up 809 adult patients who underwent elective surgical interventions and examined their history, the applied anaesthetic techniques, perioperative course and the occurrence, intensity and duration of postoperative throat complaints. The assignment and professional experience of the involved intubators were also assessed. The influence of a multitude of variables on postoperative throat complaints was statistically analysed. RESULTS: Postoperative sore throat was present in 40% overall being significantly higher in female than in male (44% vs. 33%; P = 0.001). The mean pain intensity in the affected patients (n = 323) was 28+/-12 mm on a visual analogue scale where 0 = no pain and 100 = extreme pain. The average duration was 16+/-11 h. Main factors associated with throat complaints were female sex; history of smoking or lung disease, duration of anaesthesia, postoperative nausea, bloodstain on the endotracheal tube and natural teeth. We could find no influence on the occurrence or intensity of throat complaints by the professional assignment or the length of professional experience of the personnel involved. CONCLUSIONS: Postoperative throat complaints frequently arise after tracheal intubation for general anaesthesia in the first 2 postoperative days, but they are of limited intensity and duration.

Adult↗

Membranes for biohybrid liver support: the behaviour of C3A hepatoblastoma cells is dependent on the composition of acrylonitrile copolymers.

Co-polymers based on acrylonitrile, N-vinylpyrrolidone, aminoethylmethacrylate and sodium methallylsulfonate were used to prepare flat membranes by phase inversion. The surface properties of membranes were characterised by water contact angle measurements, atomic force microscopy and X-ray photoelectron spectroscopy (XPS). Membrane permeability was estimated by porosity measurements with water as test liquid. Human C3A hepatoblastoma cells were plated on these materials. Cell-material interaction was characterised by overall cell morphology, formation of focal adhesion contacts and intercellular junctions. Furthermore, cell proliferation was measured and compared with the functional activity of cells as indicated by 7-ethoxycoumarin-O-deethylation. More hydrophilic materials reduced spreading of cells, formation of focal adhesion and subsequent proliferation while homotypic cell adhesion was facilitated in correlation with stronger expressions of intercellular junctions and improved functional activity. In contrast, membranes with stronger adhesivity enhanced cell proliferation but reduced the functional activity of cells. It was concluded that the co-polymerisation of acrylonitrile with hydrophilic co-monomers, such as N-vinylpyrrolidone, could be used to tailor membrane materials for the application in biohybrid liver support systems.

Acrylonitrile↗

Development of polymer membranes with improved haemocompatibility for biohybrid organ technology.

Biomedical technology has opened up possibilities of treating the failure of internal organs like kidney and liver by artificial organ therapy. Most of these techniques are based on polymer membranes, which allow the removal of excess of water, salts and toxins from the circulation. However, haemodialysis for the replacement of kidney function results in an increased morbidity and mortality of patients after long-term application. Conventional therapy, such as haemofiltration for the treatment of acute liver failure does not improve significantly the survival rate of patients. Biohybrid organ support as a combination of the artificial organ therapy with the functional activity of immobilised cells seems to be a solution of the problem. Membranes applied in these devices have to face both tissue cells and blood. Organ cells in biohybrid organs have to make intimate contact with the surface of membrane but must also develop close cell-cell-connections as a prerequisite for their survival and high functional activity. Blood to be detoxified will contact the other side of membrane and may not become activated by the synthetic material. New polymer membranes based on acrylonitrile were developed to address these requirements by tailoring the composition of copolymers and to be applied in a specific hollow fibre bioreactor with an outer fibre for blood contact, and an inner fibre for tissue contact or vice versa.

Animals↗

[Evaluation of gastroenterology procedures by general practitioners in the Czech Republic--contribution to interdisciplinary cooperation].

BACKGROUND: The understanding of different management strategies in primary and secondary care is important for cooperation between specialists and general practitioners in clinical practice. The Institut of General Practice at First Faculty of Medicine carried out a survey for gastroenterologists concerning their opinions on general practitioners and their current knowledge, competence and management of GI disorders as a contribution to interdisciplinary communication. METHODS AND RESULTS: Questionnaires were sent to 552 gastroenterologists in the country. There was a response rate of 31% without any reminder, 170 questionnaires were included in a study. The most of gastroenterologists (92%) support practical guidelines development. There is an insufficient confidence that these guidelines are implemented in practice. Four from five gastroenterologists consider knowledge of their colleagues GPs in gastroenterology as average. In particular cases (irritable bowel syndrome, step up and step down approach) are specialists rather sceptic. There is a low support for the increase of GP competence in gastroenterology, as for urea breath test availibility, particularly in private gastroenterologists (p=0,04). CONCLUSIONS: Results of the survey could facilitate the interdisciplinary communication in gastroenterology, contribute to CME programs development and may serve as an example for other specialities.

Adult↗

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors or non-steroidal anti- inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side-effects. COX-2-selective inhibitors may have a more favourable side-effect profile. This study tested the hypothesis that the COX-2-selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side-effects of the two drugs were compared. METHODS: In this single-centre, prospective, double-blind, active controlled study, women undergoing vaginal hysterectomy (n=25) or breast surgery (n=25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid-stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side-effects were also recorded. RESULTS: In the rofecoxib group, stimulated platelet aggregation was disturbed less (P=0.02), and estimated intraoperative blood loss (P=0.01) and the decrease in haemoglobin were lower (P=0.01). At similar pain ratings, the use of anti-emetic drugs was less in the rofecoxib group (P=0.03). CONCLUSION: Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti-emetics and less surgical blood loss in gynaecological surgery compared with diclofenac.

Adult↗

[Environmental Survey for Children-- the environmental module of KiGGS. I. Design and research program].

The German Environmental Survey for Children (GerES IV) is the environment-oriented module of the National Health Interview and Examination Survey for Children and Adolescents (KiGGS) which is being performed nationwide in Germany. From 2003 to 2006, a random subsample of 1800 children aged 3-14 years is being studied with regard to their body burden and health impairments linked to housing conditions and the personal environment- and health-relevant behaviour. The basic study programme includes the analysis of blood, urine, tap water and house dust as well as the application of an extensive questionnaire. The data gained from this population sample, which is representative for Germany's children, are the basis for deriving reference values to characterise the background exposure of children aged 3-14 years. Trends over time can be detected and the success of environmental policies verified by comparing the data with those of the German Environmental Survey 1990/92 (GerES II), also conducted in close cooperation with the National Health Survey, which included children aged 6-14 years. By linking the data from the Environmental and the Health Surveys, health-relevant environmental exposures can be detected and different scientific hypotheses can be tested. The main subjects that are being dealt with using subcollectives of GerES IV are 'VOC and eye and nasopharynx irritation', 'indoor allergens and allergic diseases of the respiratory system', 'chromium, nickel, fragrances and contact allergens', and 'noise, hearing capacity and stress hormones'.

Adolescent↗

Baseline staging in cutaneous malignant melanoma.

BACKGROUND: Baseline staging in patients with primary cutaneous malignant melanoma (MM) is routine, but the diagnostic accuracy and the impact on clinical outcome are still unclear. OBJECTIVES: To evaluate the sensitivity and specificity of baseline staging in the early detection of regional lymph node metastases or distant metastases in patients with MM. METHODS: One hundred consecutive patients with MM of Breslow's tumour thickness over 1.0 mm were enrolled. All patients had an extensive baseline staging including physical examination, ultrasound (US) of the abdomen and regional lymph nodes, chest X-ray, whole-body positron emission tomography (PET) and sentinel lymph node biopsy. The sensitivity and specificity of detection of macroscopic or microscopic metastases in the regional lymph nodes or at distant sites were calculated for each method. RESULTS: Sentinel lymph node biopsy was positive in 26 patients. US detected two of 26 histologically tumour-positive sentinel nodes (sensitivity 8%, specificity 88%) and PET two of 26 (sensitivity 8%; specificity 100%). There were three lymph node metastases with a diameter > 4 mm. All of them were found suspect at physical examination. Two of them were detectable with US, two with PET, and all were identified with either US or PET. Nine patients had suspect findings at distant sites, which were all false positive on further investigation (specificity of the combined staging procedures 91%). At 18 (6-37) months' follow-up, five of 26 (19%) patients with a positive sentinel node and four of 74 (5%) of patients with a negative sentinel node had recurrent or progressive disease. CONCLUSIONS: The combination of physical examination and lymph node US detects the great majority of patients with macroscopic lymph node metastasis (approximately 3% of patients at baseline). Only 10% of patients who have a histologically tumour-positive sentinel node are macroscopically detectable. Altogether, approximately 25% of patients have a positive sentinel node biopsy, among 90% microscopic. The value of whole body staging at baseline remains limited, since distant metastases can hardly ever be detected. The survival benefit of baseline staging and surveillance in patients with cutaneous MM remains to be established by comparative prospective trials.

Abdomen↗

Limited phylogeographical structure across Eurasia in two red wood ant species Formica pratensis and F. lugubris (Hymenoptera, Formicidae).

The phylogeography and demographic history of two closely related species of the red wood ant (Formica pratensis and F. lugubris) were examined across Eurasia. The phylogeny based on a 1.5-kilobase mitochondrial DNA fragment, including the cytochrome b gene and part of the ND6 gene, showed one phylogeographical division in F. pratensis. This division (0.7% of nucleotide divergence) suggests postglacial colonization of western Europe and of a wide area ranging from Sweden on the west to Lake Baikal on the east from separate forest refugia. In two localities, mitochondrial DNA has been transferred from F. lugubris to F. pratensis and all the individuals of F. pratensis sampled from the Pyrenees had haplotypes clustering in the lugubris clade. No phylogeographical divisions were detected in F. lugubris. Comparison of species-wide phylogeography between the two sympatrically distributed species of ant demonstrates a difference in phylogeographical structure that implies different vicariant histories. However, over most of the species' distribution ranges, similar signs of demographic expansion predating the last glaciation and the lack of phylogeographical structure were found in both the eastern phylogroup of F. pratensis and F. lugubris. This finding is highly consistent with the results reported for all other boreal forest animal species studied to date in Eurasia. Contraction of the distribution range of each species to a single refugial area at different times during the late Pleistocene and a subsequent population expansion seem to be an explanation for the lack of phylogeographical structure across most of Eurasia in species that are ecologically associated with the boreal forest.

Animals↗

Survival and prognostic factors in patients with brain metastases from malignant melanoma.

AIM: We wanted to determine the factors influencing survival in a retrospective review of patients with melanoma brain metastases to permit more specific recommendations regarding therapy. PATIENTS AND METHODS: We reviewed the data of 100 patients treated at the Department of Dermatology and Radiation Oncology, University of Zurich, and the Klinik im Park, Zurich. Information on potential prognostic factors (age, sex, location of the primary tumor, Clark level, Breslow index, histological type, number of brain metastases, stage at initial diagnosis, location of brain metastases, and therapy) was collected from the medical records of 100 patients treated between 1966 and 2002. Univariate and multivariate analyses were performed to identify significant prognostic factors. RESULTS: The overall median survival time was 4.8 months, with 6-month, 1-year and 2-year survival percentages of 36, 14 and 5%, respectively. Univariate analysis indicated that survival correlated significantly with radiotherapy (partial and whole brain), surgery, stereotactic radiosurgery, chemotherapy, Clark level and Breslow index. Treatment with temozolomide (p = 0.052) and number of brain metastases (p = 0.07) failed to be statistically significant. Multivariate analysis confirmed radiotherapy (partial and whole brain), surgery, stereotactic radiosurgery, chemotherapy and the location of brain metastases as independent and significant prognostic factors of survival. The remaining factors did not reach statistical significance in multivariate analysis. CONCLUSION: Radiotherapy, chemotherapy and especially surgery and stereotactic radiosurgery seem to significantly prolong survival, as shown by multivariate analysis. Treatment with temozolomide will possibly play an important role in the future management of patients with brain metastases from cutaneous melanoma, but further prospective studies to verify this assumption are urgently needed.

Adolescent↗

Normal gas exchange after 30-h ischemia and treatment with phosphodiesterase inhibitor PDI747.

OBJECTIVE: Phosphodiesterases (PDEs) negatively regulate the concentrations of cAMP and/or cGMP, which act as downstream second messengers to the prostaglandins. PDE type-4 (PDE4) is selective for cAMP and is found in high concentrations in endothelial, epithelial, and different blood cells. The aim of this study was to evaluate if PDI747, a novel selective inhibitor of PDE4, can restore pretransplant cAMP levels and thereby posttransplant organ function after prolonged cold ischemia. METHODS: Left lung transplantation was performed in pigs (25-31 kg). Donor lungs were flushed with low potassium dextran glucose (LPDG) solution only (control, n=5)or, in addition with 1 micromol of PDI747 (PDI747, n=5) and stored for 30 h at 1 degrees C. PDI747 animals further received a bolus of PDI747 (0.3 mg/kg) 15 min prior to reperfusion and a continuous infusion (0.3 mg/kg per hour) during the 5 h after reperfusion. After occlusion of the right pulmonary arteries and the right main bronchus, hemodynamic and gas exchange parameters and extravascular lung water (EVLW) levels of the transplanted lung were assessed. RESULTS: Two control animals died of severe lung edema leading to heart failure (control, n=3). One animal in the treatment group was excluded due to a patent ductus arteriosus (PDI747, n=4). Gas exchange at the end of the experiment was restored to normal levels in the PDI747 group (Pa, O(2) 47.6+/-11.2 kPa, Pa,CO(2) 6.4+/-1.8 kPa) but not in the control group (Pa, O(2) 7.7+/-2.9 kPa, Pa, CO(2) 11.9+/-3.0 kPa, P(PaO2)<0.0001, P(Pa, CO2)=0.06). Extravascular lung water (EVLW) was normal in the PDI747 group (8.5+/-1.1 ml/kg) and clearly elevated in the control group (16.2+/-5.6 ml/kg, P=0.007). Airway pressure in the PDI747 group was significantly lower than in the control group (7.8+/-0.5 cm H(2)O vs. 11.3+/-0.6 cm H(2)O, respectively, P<0.0001). The free radical mediated tissue injury measured by lipid peroxidation (TBARS) was significantly reduced (P=0.001) in the PDI747 group. CONCLUSIONS: With the inhibition of PDE4 with PDI747 we achieved normal gas exchange, no posttransplant lung edema, normal airway pressures, and a reduced free radical injury after 30 h of cold ischemia.

3',5'-Cyclic-AMP Phosphodiesterases↗