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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 37 records · Page 2Linked to original sources

[Angiotensin converting enzyme (ACE, CD143) in the regular pulmonary vasculature].

Angiotensin I converting enzyme (ACE, CD143) is an endothelial transmembrane Zn2+-dipeptidylpeptidase. By formation of angiotensin II and degrading bradykinin it acts as a vasoconstrictor. We examined endothelial ACE expression in human pulmonary vessels in specimens from 20 female and 19 male patients (age: 34-76 years) by immunohistochemistry. In all specimens, capillary endothelial cells showed the strongest expression, followed by those in arterioles and arteries. Venules and veins showed next to no staining. The differences in staining intensities were significant ( P<0.001). Sex affected neither the expression intensity nor the expression pattern. Summarizing, we demonstrate the existence of a vessel-type specific ACE expression pattern for pulmonary vessels. The nearly exclusive endothelial ACE expression in capillaries and arterial vessels points to ACE as an immunohistochemical marker for these vessels in normal lung tissue.

Adult↗

Increased antisecretory factor reduces vertigo in patients with Ménière's disease: a pilot study.

It has been hypothesized that the symptoms of vertigo in patients with Ménière's disease somehow are related to impaired production and/or transport of endolymph. Antisecretory factor (AF) is a protein known to affect transport processes in the intestine and it has been shown that intake of specially processed cereals (SPC) can increase endogenous AF synthesis. In a prospective open pilot study, 24 patients with severe Ménière's disease (functional level scale 5-6 according to the criteria of AAO-HNS) received SPC for 14-30 days. AF levels in plasma increased by 83% in 20 of the 24 patients studied. The attacks of rotatory vertigo were reduced, to final AAO-HNS functional level scale 1-3, in 12 patients and in three of these hearing was normalized. Twelve patients had no or minor effects of the treatment. The correlation between AF activity after treatment and the final AAO-HNS functional level scale was -0.65, P<0.001. Studies in rats using immunohistochemistry methods showed that AF was localized to the cochlea and the vestibule of the inner ear. The present results suggest that AF might be a new regulator of the endolymph.

Adult↗

High prevalence of peripheral arterial disease and low treatment rates in elderly primary care patients with diabetes.

Representative data on peripheral arterial disease (PAD) in community-based office practice are scarce while at the same time of high interest. Thus, we aimed to determine the prevalence of peripheral arterial disease (PAD), comorbidity of atherothrombotic manifestations, and treatment intensity among elderly diabetic patients in primary care. In this monitored cross-sectional study, 344 general practitioners throughout Germany determined the ankle-brachial index (ABI) of 6880 consecutive, unselected patients aged 65 years or older with bilateral Doppler ultrasound measurements. PAD was defined according to the recent American Heart Association guidelines (using the higher of the 2 systolic ankle pressures: ABI < 0.9) or peripheral revascularisation, or amputation because of PAD. Coronary events (CAD) and cerebrovascular events (CVD) were taken from the patient's history without additional diagnostic measures. Diabetes was defined according to the clinical diagnosis of the physician and/or HbA1c > or = 6.5 % and/or intake of oral antidiabetic medication and/or application of insulin. 1.743 patients were classified as diabetics: the median disease duration was 6 years (1st; 3rd quartile: 2; 11), median HbA1c 6.6 % (5.9; 7.3), mean age 72.5 +/- 5.4 years, and 51.4 % were females. Diabetics had in comparison with non-diabetics a higher prevalence of PAD defined as ABI < 0.9 (26.3 % vs. 15.3 %, univariate odds ratio 2.0 [95 % confidence interval: 1.7; 2.3]), intermittent claudication (5.1 % vs. 2.1 %, OR: 2.5 [1.9; 3.4]), known CAD (16.1 % vs. 10.6 %, OR: 1.6 [1.4; 1.9]), and known CVD (6.8 % vs. 4.8 %; OR: 1.4 [1.2; 1.8]). 57.4 % of the diabetics with previously known PAD (as only atherothrombotic manifestation) received antiplatelet therapy (vs. 75.1 % with CAD and/or CVD only). The ABI was suitable as screening measure in the primary care setting. In elderly diabetics in comparison to non-diabetics, the prevalence of PAD was very high. Despite the known benefits of antiplatelet therapy, PAD patients were less intensively treated than patients with CAD or CVD.

Aged↗

Reproducibility and reliability of fetal cardiac time intervals using magnetocardiography.

We investigated several factors which may affect the accuracy of fetal cardiac time intervals (CTI) determined in magnetocardiographic (MCG) recordings: observer differences, the number of available recording sites and the type of sensor used in acquisition. In 253 fetal MCG recordings, acquired using different biomagnetometer devices between the 15th and 42nd weeks of gestation, P-wave, QRS complex and T-wave onsets and ends were identified in signal averaged data sets independently by different observers. Using a defined procedure for setting signal events, interobserver reliability was high. Increasing the number of registration sites led to more accurate identification of the events. The differences in wave morphology between magnetometer and gradiometer configurations led to deviations in timing whereas the differences between low and high temperature devices seemed to be primarily due to noise. Signal-to-noise ratio played an important overall role in the accurate determination of CTI and changes in signal amplitude associated with fetal maturation may largely explain the effects of gestational age on reproducibility. As fetal CTI may be of value in the identification of pathologies such as intrauterine growth retardation or fetal cardiac hypertrophy, their reliable estimation will be enhanced by strategies which take these factors into account.

Adult↗

Learning with computerized guidelines in general practice?: A randomized controlled trial.

BACKGROUND: Evidence-based guidelines are seen as an important instrument to transfer scientifically generated knowledge into daily clinical practice and to ensure high standards of clinical care. Despite wide promulgation, clinical guidelines so far have a limited impact on individual professional learning and on changing daily medical practice. OBJECTIVES: Our aims were (i) to study a potential knowledge increase among German GPs after implementation of web- and evidence-based guidelines and (ii) to identify and analyse potential barriers to individual professional learning with computerized guidelines. METHODS: A prospective, randomized controlled trial was conducted including 72 GPs (21% female, 79% male). The intervention group (n = 38) had access to clinical guidelines via the Internet or CD-ROM, the control group had not (n = 34). Both groups received a standardized two-part questionnaire. An increase of knowledge was measured with 25 multiple choice questions related to four different medical topics. In addition, reasons for using or not using computerized guidelines were analysed after access to guidelines was open to all participating physicians. RESULTS: There was no significant knowledge increase in the intervention group (P = 0.69). Twenty-two (58%) GPs of the intervention group had used the guidelines. Unspecified curiosity (76%) and a specific medical question (38%) were predominant motives for usage among physicians who had used the guidelines. Among 'non-users', 78% stated 'lack of time' as the main reason for not using guidelines. CONCLUSION: An efficient knowledge transfer through computerized guidelines was not achieved. Usage, individual learning and potential implementation depend on adequate incentives and pragmatic aspects of clinical practice: easy and quick access.

Adult↗

Modifications in cell cycle kinetics and in expression of G1 phase-regulating proteins in human amniotic cells after exposure to electromagnetic fields and ionizing radiation.

Low-frequency electromagnetic fields are suspected of being involved in carcinogenesis, particularly in processes that could be related to cancer promotion. Because development of cancer is associated with deregulated cell growth and we previously observed a magnetic field-induced decrease in DNA synthesis [Lange et al. (2002) Alterations in the cell cycle and in the protein level of cyclin D1p, 21CIP1, and p16INK4a after exposure to 50 HZ. MF in human cells. Radiat. Environ. Biophys.41, 131], this study aims to document the influence of 50 Hz, 1 mT magnetic fields (MF), with or without initial gamma-ionizing radiation (IR), on the following cell proliferation-relevant parameters in human amniotic fluid cells (AFC): cell cycle distribution, expression of the G1 phase-regulating proteins Cdk4, cyclin D1, p21CIP1 and p16INK4a, and Cdk4 activity. While IR induced a G1 delay and a dose-dependent G2 arrest, no discernible changes in cell cycle kinetics were observed due to MF exposure. However, a significant decrease in the protein expression of cyclin D1 and an increase in p21CIP1- and p16INK4a-expression could be detected after exposure to MF alone. IR-exposure caused an augmentation of p21CIP1- and p16INK4a- levels as well, but did not alter cyclin D1 expression. A slight diminution of Cdk4 activity was noticed after MF exposure only, indicating that Cdk4 appears not to act as a mediator of MF- or IR-induced changes in the cell cycle of AFC cells. Co-exposure to MF/IR affected neither cell cycle distribution nor protein expression or kinase activity additionally or synergistically, and therefore MF seems not to modify the mutagenic potency of IR.

Amnion↗

Induction of anti-secretory factor in human milk may prevent mastitis.

AIM: The aim of the study was to try to induce anti-secretory factor (AF) in human milk and possibly prevent mastitis. METHODS: Forty mothers who had normal deliveries and healthy full-term infants were randomly divided into two groups, 3-7 days postpartum. The experimental group received a food inducing AF. The control group received the same type of food, without AF-inducing properties. Milk was tested for AF after the mothers had eaten the cereals for 4-5 wk. AF was determined by intravenous injection of milk samples into rats measuring their capacity to prevent secretion into a gut loop of the rat injected with cholera toxin. RESULTS: The median levels of AF differed between the experimental (n = 12) and control groups (n = 16): 1.1 (0.7-1.25) units vs 0.1 (0.0-0.25) units, Z = -4.492, p < 0.0001 (11 mothers dropped out and one milk sample is missing from one of the control mothers). The frequency of mastitis in the experimental compared with the control group was reduced (p = 0.0086, permutation test). The median AF levels in mothers with or without mastitis differed; 0.0 (0.0-0.1) vs 0.5 (0.2-1.1), Z = -2.399, p = 0.017. CONCLUSION: We suggest a specially treated cereal induces AF in human milk and protects against clinically manifested mastitis.

Adult↗

Identification of factors impeding the production of a single-chain antibody fragment in Escherichia coliby comparing in vivo and in vitro expression.

The atrazine-specific single-chain variable antibody fragments (scFv) K411B was produced by expression in either the cytoplasm or the periplasm of Escherichia coli BL21(DE3). For periplasmic production, the pelB leader was N-terminally fused to scFv, whereas the unfused variant resulted in cytoplasmic expression. The extent of protein accumulation differed significantly. Expression of scFv with leader was 2.3 times higher than that of the protein without leader. This was further investigated by generating the respective translation profiles using coupled in vitro transcription/translation assays, the results of which were in agreement. This comparative approach was also applied to functionality: Periplasmic expression and in vitro expression resulted in only 10% correctly folded scFv, indicating that the oxidizing environment of the periplasm did not increase proper folding. Thus, the data obtained in vitro confirmed the findings observed in vivo and suggested that the discrepancy in expression levels was due to different translation efficiencies. However, the in vivo production of scFv with enhanced green fluorescent protein (EGFP) fused C-terminally (scFv-EGFP) was only successful in the cytoplasm, although in vitro the expression with and without the leader rendered the same production profile as for scFv. This indicated that neither the translation efficiency nor the solubility but other factors impeded periplasmic expression of the fusion protein.

Antibody Specificity↗

Antisecretory factor counteracts secretory diarrhoea of endocrine origin.

BACKGROUND: Dietary induction of antisecretory factor (AF) can reduce diarrhoea in patients with inflammatory bowel disease. Patients with neuroendocrine tumours may suffer from diarrhoea with a prominent secretory component. We studied if AF-therapy could affect this type of diarrhoea. METHODS: Six patients with the midgut carcinoid syndrome and two with metastasizing medullary thyroid carcinoma (MTC) participated. Effects of intake of AF, in the form of AF-rich egg powder (AF-egg), and induction of endogenous AF-activity by intake of specially processed cereals (SPCs) were studied. In an initial open part of the study all patients received AF-egg for 4 weeks, followed by a double-blind crossover period with SPC and control cereals (CCs) for 6 weeks each. Daily number of bowel movements at the end of each treatment period was registered. RESULTS: Treatment with AF-egg resulted in a decrease of bowel movements in seven patients (P<0.01). Registrations of bowel movements from both SPC and CC diet periods were obtained from five patients. The daily number of bowel movements was lower during the SPC-period compared to the period with CC (P<0.05). All patients had low levels of AF-activity in serum at baseline. During treatment with AF-egg, the mean level increased slightly. AF-activity was higher (P<0.05) after SPC compared to the CC diet. CONCLUSIONS: In a group of patients with endocrine diarrhoea, AF-activity could be induced, and AF-therapy reduced the number of bowel movements.

Antidiarrheals↗

Are elevated homocysteine plasma levels related to peripheral arterial disease? Results from a cross-sectional study of 6880 primary care patients.

BACKGROUND: It is still unclear whether the strength of the association between elevated plasma homocysteine (HC) levels and peripheral arterial disease (PAD), coronary artery disease (CAD) and cerebrovascular disease (CVD) is similar. METHODS: Fasting homocysteine plasma levels were measured in 6880 unselected primary care patients aged 65 years or older. Presence of PAD was determined with the ankle brachial index, and both CAD and CVD were recorded according to patient history. RESULTS: Median homocysteine levels in the total sample (58.0% females, mean age 72.5 years, mean body mass index 27.3 kg m-2) differed between patients with and without PAD: 15.2 micro mol L-1 (95% confidence interval [CI] 14.8; 15.7, vs. 13.9 micro mol L-1 (CI: 13.8; 14.1; P < 0.001). Peripheral arterial disease prevalence moderately increased from 13.0% in the lowest HC quintile to 24.3% in the highest quintile (crude odds ratio [OR], 2.1 [CI: 1.7; 2.6]). The frequency of atherothrombotic manifestations in the patients' history increased nearly linearly across the homocysteine quintiles in the univariate analysis. However, the association diminished substantially after adjusting for known interfering variables: the ORs between the HC highest fifth vs. lowest fifth (adjusted for age, gender, smoking status, diabetes, hypertension lipid disorders, and estimated glomerular filtration rate levels) for PAD decreased to 1.4, for CAD to 1.0 (NS), and for CVD to 1.1. (NS). CONCLUSIONS: Elevated HC is only slightly more related to PAD than to CAD and CVD. After adjustment for known risk factors, the effect size is small, and an association can no longer be observed between homocysteine and CAD and CVD.

Age Distribution↗

Protection against atypical furunculosis in Atlantic halibut, Hippoglossus hippoglossus (L.); comparison of a commercial furunculosis vaccine and an autogenous vaccine.

Atlantic halibut, Hippoglossus hippoglossus (L.), was shown to be sensitive to infection by three different isolates of Aeromonas salmonicida ssp. achromogenes in pre-challenge tests using intraperitoneal (i.p.) and intramuscular (i.m.) injections as well as bath challenges. A commercial furunculosis vaccine, Alphaject 1200, and an autogenous vaccine, AAS, based on the challenge strain, induced immune protection as shown in challenge tests 8 weeks post-immunization. The survival rate of vaccinated fish after i.p. challenge was 100%, whereas mortality of control fish was 61%. Employing i.m. challenge, relative percentage survival induced by the furunculosis vaccine and the AAS vaccine was 47 and 44, respectively. Mortality of i.m. injected controls was 68%. Vaccinated fish behaved normally following vaccination but the weight gain was significantly reduced in vaccinated fish 8 weeks post-vaccination compared with control fish receiving phosphate-buffered saline. At the same time, intra-abdominal adhesions were observed in fish injected with either of the two vaccines or adjuvant alone. Antibody response against A. salmonicida ssp. achromogenes was detected in sera from fish receiving either vaccine.

Aeromonas↗

[Nosocomial pneumonias in haematological malignancies in the medical intensive care unit].

30 patients with malignant haematological disorders and nosocomial pneumonia, treated during a three-year period in the medical intensive care unit (ICU) of a university hospital, were studied in retrospect. Twelve patients had received bone marrow or peripheral stem cell transplantations 90 +/- 143 (10 - 546) days prior to ICU admission. Six of these received cyclosporin A. 19 of 30 patients were on corticosteroids and 20 had received courses of chemotherapy within a period of one month prior to ICU admission. Patients presented with signs of pulmonary infection and respiratory failure. In 24 patients the likely causative pathogen for pneumonia could be identified. Gram-negative bacteria (n = 17) were in the majority, lead by Pseudomonas, Enterobacter, and Klebsiella species. Gram-positive bacteria (n = 5) were Streptococcus and Staphylococcus species. Infections with Chlamydiae species were diagnosed in two cases. Fungal infections were caused by Candida (n = 8) or Aspergillus species (n = 3) and viral infections by Cytomegalovirus (n = 6). Infections with more than one pathogen were common. Ten patients had pneumonia associated with signs of diffuse pulmonary parenchymal damage of varying degree. 26 patients received mechanical ventilation for 7 +/- 9 (1 - 32) days. The duration of stay in the ICU was 11 +/- 10 (1 - 43) days. 26 of the 30 patients (87 %) died. Patients with haematological malignancies and nosocomial pneumonias have despite medical intensive care treatment a poor prognosis with substantial mortality.

Adult↗

Effect of antisecretory factor in ulcerative colitis on histological and laborative outcome: a short period clinical trial.

BACKGROUND: The antisecretory factor (AF) is a 41 kD endogenously produced protein capable of mediating protection against diarrhoea diseases and intestinal inflammation. High concentrations of AF-like proteins are present in egg yolk, and AF can consequently be administrated in the form of egg yolk drinks. In this study, performed in patients suffering from acute onset of ulcerative colitis (UC), we evaluate the influence of orally administrated AF on the histological and clinical laboratory outcome. METHODS: A total of 20 patients fulfilled this prospective, double-blind and randomized protocol. The intake of AF was used as an additive treatment to conventional UC medication. Patient registrations were extended to two outward visits, performed 2-4 and 8-12 weeks after hospital discharge. RESULTS: During AF treatment, a reduction in the histological severity from mucosal biopsies received from the mid-rectum was found. In addition, a lowering in the inflammatory blood parameters ESR, CRP and orosomucoid was demonstrated. CONCLUSION: In the AF-treated group a late and significant lowering of various inflammatory parameters combined with a histological recovery was demonstrated. These findings suggest that administration of AF mediates a long-lasting anti-inflammatory effect in cases of acute UC.

Administration, Oral↗

Antisecretory factor peptide derivatives specifically inhibit [3H]-gamma-amino-butyric acid/36Cl- out-->in permeation across the isolated rabbit Deiters' neuronal membrane.

AIMS: Antisecretory factor (AF) is a 41-kDa protein, its main function being the regulation of intestinal ion/water transport, but it also inhibits chloride and gamma-amino-butyric acid transport across nerve cell membranes. The present experiments were designed to evaluate whether the same AF peptide sequence mediates the permeability effects seen at the nerve cell membrane and in the rat small intestine. METHODS: Four peptides were prepared by the solid phase technique with sequences derived from positions 1-51 of the full-length antisecretory factor AF and tested on nerve cell membranes isolated from rabbit Dieter cells. RESULTS: AF peptides containing the active 36-51 peptide exerted a blocking effect of the out-->in permeation of 36Cl- as well as of [3H]-gamma-amino-butyric acid. The minimal dose causing inhibition, however, varied between 10(-11) m (AF10) and 10(-7) m (AF13). The most potent peptides have been shown previously to be active in inhibiting experimental diarrhoea in vivo in small intestinal ligated loops in rats. The non-active sequence AF23-32 did not inhibit any of the two permeation markers in vitro, a result which supports the lack of activity found also in vivo. CONCLUSION: The results suggest that AF, or AF derivatives, counteract intestinal hypersecretion by blocking anion permeation across large anionic pores. Such a blocking effect could also influence the generation of action potentials in enteric nerve cells controlling the intestinal water and ion transport system.

Amino Acid Sequence↗

[Characterization of factor VIII antibody epitopes from haemophilia A patients using cellulose bound FVIII peptide libraries].

Approximately 30% of patients suffering from severe haemophilia A develop antibodies against factor VIII (FVIII) neutralizing the effect of the pro-coagulant activity of intravenously injected FVIII as a complication of replacement therapy. Generally, various epitopes on the FVIII molecule are bound by these antibodies. The detailed structure of such epitopes is unknown. In this study epitopes on the FVIII molecule are identified using solid phase bound peptide arrays carrying the whole amino acid sequence of FVIII as small oligopeptides. The binding of FVIII antibodies by specific peptide sequences on the array indicates potential epitopes. FVIII antibodies of inhibitor patients and healthy blood donors are currently investigated by this method. Identified epitopes may lead to new concepts in therapy aiming at avoidance of inhibitor formation or improvement of inhibitor eradication. As participant of the 'haemophilia A' consortium dealing with genotype/phenotype correlation in haemophilia A we investigate, if the site or type of the mutation correlates with the epitopes, and if there is any relation between epitopes and clinical course. Furthermore, the influence of epitopes on therapeutical effects and the outcome of immune tolerance induction is under scrutiny.

Autoantibodies↗

Factors influencing the prognostic role of oestrogen and progesterone receptor levels in breast cancer--results of the analysis of 670 patients with 11 years of follow-up.

In the last two decades, the prognostic role of the steroid hormone receptors has been the subject of a myriad of publications. Nevertheless, its relevance after long-term follow-up is still not clear. The confusion about the prognostic value is mainly due to the difficulty in comparing analyses. Despite different study-designs and statistical approaches, oestrogen (ER) and progesterone (PR) receptors are widely accepted as prognostic factors. Data from 670 breast cancer patients with a median follow-up of 11.4 years were analysed retrospectively. ER and PR were measured by the dextran-coated charcoal (DCC) assay. To investigate the time dependence of the prognostic relevance of ER and PR, separate analyses were done for follow-up shorter and longer than 5 years. Special focus was directed at patients < or =50 and >50 years, node-negative women, in particular those without adjuvant therapy. Univariate and multivariate analyses were performed. In univariate analysis, ER and PR were associated with a significantly longer overall survival at the cut-off levels 10, 20 or 100 fmol/mg protein. The significant survival benefit occurred in the first 5 years of follow-up and remained unchanged in the following period. In the multivariate analyses, only the PR was of significant prognostic value (for PR> or =20 fmol/mg P=0.036, for PR> or =100 P=0.01, Cox analysis). In patients younger than 51 years, only PR was an independent prognosticator at the cut-off level of 100 fmol/mg protein, while in patients >50 years both hormone receptors were not significant. In N0 patients, only the PR reached long-term prognostic independence at a cut-off point of > or =100 fmol/mg (P=0.018). In addition, in the group of node-negative women < or =50 years without adjuvant therapy the PR level reached prognostic significance. The hormone receptor status was a prognostic factor only during the first 5 years of follow-up. Our data suggest that age, lymph node status, length of follow-up and probably the ER/PR assay are important for the evaluation of ER and PR as prognostic variables. In most analyses, PR appeared to be superior to ER in predicting the prognosis of primary breast cancer patients.

Adult↗

Multicentre study of fetal cardiac time intervals using magnetocardiography.

OBJECTIVE: A database with reference values of the durations of the various waveforms in a magnetocardiogram of fetuses in uncomplicated pregnancies is assessed. This database will be of help to discriminate between pathologic and healthy fetuses. A fetal magnetocardiogram is a recording of the magnetic field in a location near the maternal abdomen and reflects the electric activity within the fetal heart. It is a non-invasive method, which can be used with nearly 100% reliability from the 20th week of gestation onward. DESIGN: Durations of the waveforms were assembled from averaged magnetocardiograms and statistically processed. SETTING: Fetal magnetocardiograms were measured with different magnetocardiographs. All measurements were carried out in magnetically shielded rooms. SAMPLE: Fetal magnetocardiograms were obtained for 582 healthy patients. METHOD: The durations of the waveforms were extracted from fetal magnetocardiograms measured at the cooperating centres. The variables collected included the duration of the P-wave, the PR interval, the PQ interval, the QRS complex, the QT interval and the T-wave and QTc value. The results were compared with values extracted from electrocardiograms of fetuses measured via electrodes attached to the maternal abdomen, from electrocardiograms measured during labour using a scalp electrode, and from electrocardiograms recorded in newborns, that were found in the literature. MAIN OUTCOME MEASURES: Values of the durations are given as a function of gestational age including the regression line as well as the bounds marking the 90%, 95% and 98% prediction interval. RESULTS: The durations of the P-wave, the PR interval, the QRS complex, the QT interval and QTc value increase linearly with gestational age. The durations of the PQ interval and the T-wave are independent of fetal age. CONCLUSION: The values found agree with those found in the literature. The scatter of the data is wide due to the variation in normal physiology, the measuring system and signal processing and the subjectivity of the researcher. However, the system can define normal ranges and may be used in diagnosis.

Analysis of Variance↗