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Biomedical subjects

S Lange

Publications and source records attributed to S Lange.

At least 19 recordsLinked to original sources
PubMed2007

[Metabolic syndrome and peripheral arterial occlusive disease as indicators for increased cardiovascular risk].

BACKGROUND AND AIMS: The usefulness of the metabolic syndrome (MetS) or a low ankle brachial index (ABI), respectively, to identify patients with high risk for cardiovascular events has repeatedly been postulated. However, robust data on the prevalence and prognosis of such patients are missing in the primary care setting. PATIENTS AND METHODS: In the prospective, non-interventional "German epidemiological trial on Ankle Brachial Index (getABI) at total of 6880 unselected patients > or = 65 years were observed by their General Practitioners over 3 years. Death and cardiovascular events were recorded. The definition of MetS was similar to the one of NCEP ATP III (National Cholesterol Education Program--Adult Treatment Panel III). ABI (ratio of the systolic blood pressures measured at the distal part of the calf and at the upper arm) was measured with Doppler sonography. Peripheral arterial disease (PAD) was defined as ABI <0.9 or peripheral revascularization/amputation owing to PAD. Survival analyses were conducted with a Cox proportional hazard model. Hazard rate ratios (HRR, 95 % confidence intervals, CI) were multvariate adjusted. RESULTS: The observation time for the total cohort was more than 20,000 patient years (PY). Cardiovascular mortality in patients with MetS (n = 3040, 44 %) compared to patients without MetS (n = 3795; 55 %) was doubled (8.5 vs. 4.0 per 1,000 PY; HRR: 2.0; CI 1.3 - 2.9). Concomitant presence of MetS and PAD (n = 651; 9.5 %) increased the mortality risk compared to patients without both conditions (n = 3194; 46.4 %) drastically (21.1 vs. 3.0 per 1000 PY; HRR: 5.7; CI: 3.5 - 9.4). Similar significant risk increases also were noted for all-cause mortality or a combined endpoint of mortality and vascular morbidity. Further, in lower ABI categories cardiovascular event rates increased. CONCLUSIONS: Patients with MetS carry a substantially increased risk of premature death, especially cardiovascular death, and therefore require intensive treatment of their risk factors. This holds especially true if concomitant PAD is present.

Aged↗
PubMed2007

[Pseudoangiitis in bilateral ocular ischemia].

BACKGROUND: The term 'frosted branch angiitis' was initially used to describe an idiopathic form of vasculitis in association with panuveitis. It has since also been used to describe the angiographic phenomenon of diffuse leakage along retinal vessels against the background of other ocular and systemic diseases. METHODS: We describe a 57-year-old male patient with acute bilateral reduction of visual acuity, headaches and absence of any pulse at the temporal arteries. Fluorescence angiography showed bilateral diffuse leakage along all the retinal vessels, which resembled frosted branches. Laboratory parameters and histology were not indicative of vasculitis. Imaging showed complete occlusion of both common carotid arteries and a hypoplastic vertebral artery on the left. CONCLUSIONS: Ocular ischemia may imitate primarily inflammatory conditions in its angiographic appearance.

Angiography↗
PubMed2006

Non-parametric assessment of non-inferiority with censored data.

We suggest non-parametric tests for showing non-inferiority of a new treatment compared to a standard therapy when data are censored. To this end the difference and the odds ratio curves of the entire survivor functions over a certain time period are considered. Two asymptotic approaches for solving these testing problems are investigated, which are based on bootstrap approximations. The performance of the test procedures is investigated in a simulation study, and some guidance on which test to use in specific situations is derived. The proposed methods are applied to a trial in which two thrombolytic agents for the treatment on acute myocardial infarction were compared, and to a study on irradiation therapies for advanced non-small-cell lung cancer. Non-inferiority over a large time period of the study can be shown in both cases.

Computer Simulation↗
PubMed2006

[The role of randomised controlled trials in the medical evaluation of routine procedures].

If a demand exists for the evaluation of the favourable and adverse effects of a medical procedure, a comparison is required; this comparison should be fair. The only procedure that ensures a fair comparison is randomisation. Randomised controlled trials (RCTs) therefore represent the gold standard in the evaluation of medical procedures; the non-application of a randomisation process must be justified in detail in individual cases. Reasons presented for not conducting an RCT are mainly based on a misunderstanding of the term "randomisation". They may also be based on circumstances where the conduct of any simultaneous comparison is unsuitable (independent of the mode of allocation) or on situations where there is practically no hypothesis available for a comparison, or even for a study. These factors are taken into account by the current regulations valid in Germany on the approval of drugs and on the reimbursement eligibility of health care services by statutory health insurance.

Biomedical Technology↗
PubMed2006

[Mind-body medicine as a part of German integrative medicine].

Mind-body medicine (MBM) as a holistic approach to health and healing has been shaped by research into stress physiology and stress psychology, by psychoneuro(endocrino)immunology and by Antonovsky's salutogenetic paradigm. MBM seeks to acknowledge physical, psychological as well as social and spiritual aspects of human beings. MBM constitutes one of the traditions, which the emerging field of integrative medicine in Germany draws upon, others being mainstream medicine, traditional European naturopathy and non-European methods like traditional Chinese medicine. The article outlines historical aspects of MBM, gives a brief review of research evidence, and introduces clinical MBM institutes in Germany. Especially the Clinic and Chair of Complementary and Integrative Medicine, Alfried Krupp von Bohlen und Halbach Foundation at the University Duisburg-Essen has been integrating MBM into the concept of integrative medicine. Considering that a growing number of health issues arises due to maladaptive lifestyles, MBM is being identified as a development that supports a shift from increasingly expensive treatments to more cost-effective preventive approaches.

Delivery of Health Care, Integrated↗
PubMed2006

CRIT is expressed on podocytes in normal human kidney and upregulated in membranous nephropathy.

Complement C2 receptor inhibitor trispanning (CRIT) is a novel human complement regulatory cell surface receptor. It binds the human complement protein C2 and blocks the classical pathway of complement activation, thus protecting the cell against complement attack. CRIT expression in the kidney was analyzed by immunohistochemistry and in situ hybridization. Normal kidney and renal biopsies of patients with different nephropathies were studied. In glomeruli, CRIT protein was expressed only in podocytes. CRIT was also detected in endothelial cells of arterioles and arteries, but not of veins and peritubular and glomerular capillaries. A homogeneous and marked upregulation of CRIT was observed in podocytes in membranous nephropathy (MN). In focal and segmental glomerulosclerosis (FSGS) and minimal change disease, CRIT was downregulated in glomeruli with a loss of the staining in sclerotic lesions of FSGS. No specific changes were observed in the other nephropathies studied. However, podocytes showed in all pathologies a redistribution of CRIT in the cell bodies of 'activated' podocytes. The intensity of mRNA transcription correlated directly with the protein staining in the normal kidney and in MN. These data indicate that CRIT is expressed in the normal human kidney essentially by glomerular podocytes and arterial endothelial cells. The podocyte CRIT expression is upregulated in MN, which is in strong contrast with the known loss of podocyte complement receptor 1. CRIT might represent the last line of defense against complement aggression in MN, and the upregulation of CRIT in 'activated' podocytes might represent a similar self-defense mechanism.

Carrier Proteins↗
PubMed2006

Magnetic resonance imaging of the ovaries of healthy women: determination of normal values.

PURPOSE: To establish normal values for the volume and maximal diameter of ovaries and ovarian follicles and for the number of ovarian follicles in magnetic resonance imaging (MRI) based on menstrual cycle phase and age. MATERIAL AND METHODS: We performed MRI of the pelvis on 100 healthy women. Volume of the ovaries and largest ovarian follicles and the number of ovarian follicles were determined by menstrual cycle phase and age. RESULTS: The mean volume of the ovaries significantly increased with age and reached its peak between 31 and 40 years, and subsequently decreased. The mean volume of the largest ovarian follicles also significantly increased with age to reach its peak at 41-50 years. The highest mean numbers of ovarian follicles were found at 20-40 years. When the volumes of ovaries and of the largest ovarian follicles, and the number of ovarian follicles were compared between the first and second phase of the menstrual cycle, no significant differences were found. CONCLUSION: The volume and maximal diameter of ovaries and ovarian follicles and the number of ovarian follicles differ significantly with age, but not between the two phases of the menstrual cycle. Knowledge of MRI-related normal values can be expected to aid the early identification of ovarian pathologies.

Adult↗
PubMed2006

Immunostimulation of larvae and juveniles of cod, Gadus morhua L.

Cod larval culture is currently hampered by high mortalities in the first 2-3 weeks after hatching, often due to infectious diseases. The immune system of cod is not fully competent until 2-3 months after hatching. Conventional vaccination is, therefore, not of value before this time, and the larvae are wholly reliant on non-specific parameters for their defence against infection. A range of substances, generally derived from bacterial, fungal or plant origin, can activate these non-specific parameters. During three hatching seasons, 2001-2003, at the Marine Institute's Experimental Station, Stadur, Grindavik, Iceland, the effects of several immunostimulants on survival and disease resistance of cod larvae and juveniles were examined. Both bathing treatments and administration in the feed were used. One of these substances, lipopolysaccharide (LPS), isolated from the bacterium Aeromonas salmonicida (ssp. salmonicida or achromogenes), appeared in some instances to improve survival and have a beneficial effect on disease resistance. Other substances tested had limited effects. The results emphasize the need for further work in this field.

Adjuvants, Immunologic↗
PubMed2005

[Comparison of different stool tests for the detection of cancer of the colon].

BACKGROUND AND OBJECTIVE: Colonoscopy is the gold standard for the diagnosis of colonic neoplasia. Because of the low compliance, the discomfort of bowel preparation and the procedure itself and the (albeit small) risk of perforation or bleeding alternative procedures such as stool tests are being focused on. PATIENTS AND METHODS: After informed consent stool samples of 116 patients (44 male, 72 female, median age 47 years), scheduled for colonoscopy and 22 patients (17 m, 5 f, 69 y) with known colorectal cancer stool samples were collected. The samples were investigated by three methods: a biochemical (Guajak) test for fecal occult blood, an immunological test for fecal occult blood and a test determining the dimer pyruvat kinase M2 (tumor M2-PK). RESULTS: Sensitivity for detection of colorectal cancer or polyps was 27 % and 10 % for the biochemical test, 91 % and 19 % for the immunological test and 77 % and 48 % for the M2-PK-test, respectively. Specificity was 89 %, 94 % and 72 %, respectively. CONCLUSIONS: Both methods for detection of occult blood had a similar specificity. The sensitivity of the immunological test for the detection of colorectal cancer was significantly higher. The M2-PK-test had a markedly lower specificity in diagnosing cancer. Because of the low sensitivity for polyps the usefulness of stool tests is questionable. Reducing incidence and mortality of colorectal cancer should be achieved by colonoscopy, a recommendation that requires specific communication to the public.

Aged↗
PubMed2005

Choice of delta: requirements and reality--results of a systematic review.

An essential problem in planning clinical non-inferiority or equivalence studies is the specification of the 'irrelevant difference' (irrelevance margin; delta). This quantifies the amount of non-inferiority or difference, respectively, between a new test therapy and an established standard treatment which is to be considered as tolerable. In the past, most recommendations and guidelines for clinical non-inferiority and equivalence studies contained only general statements and formulations concerning the specification of delta. The current unsatisfactory situation was the reason for performing a systematic review of published clinical non-inferiority and equivalence studies. It was the aim to gain an overview on the irrelevance margins used in such studies, and on reasons for choosing the particular margins. For the sake of comparability, the irrelevance margins were converted into standardized differences and odds ratios. Overall, there were 332 non-inferiority or equivalence trials obtained by means of an extensive literature search. The results of the systematic review show that current requirements on the choice of delta and the reality of recent clinical non-inferiority and equivalence trials differ substantially. In about one half of the trials a difference of 0.5 standard deviations or more was regarded as 'irrelevant' explicitly or implicitly. Estimates of standard-placebo differences formed the basis of the irrelevance margin in less than every tenth trial. Reasons for this very low proportion might be (1) the possibly resulting very small irrelevance margins, and (2) unsolved problems of the requirements themselves. Overall, it seems that a more global definition of 'irrelevance' might be warranted.

Biopharmaceutics↗
PubMed2005

Influence of gestational age, heart rate, gender and time of day on fetal heart rate variability.

From adult data, it is known that numerous factors, such as age, state of the autonomic nervous system, diurnal rhythms or mean R-R interval mRR, influence heart rate variability (HRV). The aim of this study was the examination of the influence of gestational age, mRR, gender and time of day on fetal HRV. The analysis was based on 66 fetal magnetocardiograms (FMCGs) of 22 healthy fetuses between the 16th and 42nd week. FMCGs were recorded for 5 min using a multichannel biomagnetometer. On the basis of the time series of fetal R-R intervals, mRR as well as the standard deviation sdRR, root mean square of successive differences rmssdRR and approximate entropy ApEn were calculated. The influence of gestational age, mRR and gender on sdRR, rmssdRR and ApEn was determined by regression analysis. The relationship between time of day and HRV was evaluated by visual inspection of scatterplots. The logarithmised HRV measures increased significantly with the logarithm of gestational age (regression coefficients: sdRR = 1.28, rmssdRR = 1.12, ApEn = 1.30) and mRR (regression coefficients: sdRR = 0.008, rmssdRR = 0.011, ApEn = 0.012) There was no significant influence of gender. With respect to time of day (between 0800 h and 1800 h), no dependency of the HRV measures was apparent. In summary, when fetal HRV is assessed, it is essential to take gestational age and mRR into account. In contrast, time of day, with respect to daytime, and gender need not be considered. In future studies, the influence of fetal activity state on HRV should be examined.

Cardiotocography↗
PubMed2005

Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury.

Intestinal injury 4-48 hr after cytotoxic therapy (etoposide phosphate, 100 mg/kg body weight [bw], intravenously [i.v.]) was studied in rats using ligated intestinal loops. Chromium-51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) and rubidium-86 chloride ((86)RbCl) were deposited intraluminally to determine the extent of the increase in intestinal permeability and ion channel disruption. Evans Blue (EB) was used for detection of endothelial leakage. Intestinal morphology was documented. Endothelial dysfunction, as observed by an increased extravasation of EB, was evident already 4 hr after cytotoxic therapy. Intestinal epithelial injury, as observed by an increase in (51)Cr-EDTA permeation and a decrease in (86)Rb absorption, occurred after 48 hr. Finally, histology disclosed a reduced crypt cell proliferation, displayed as a decrease in Ki67-positive cells. The findings suggest that, in the development of intestinal injury after cytotoxic therapy, endothelial disruption is an early event, whereafter epithelial dysfunction and crypt stem cell arrest occur. This knowledge could be of importance in the design of future intervention trials.

Animals↗
PubMed2005

Ontogeny of humoral immune parameters in fish.

The first appearance of IgM in lymphocytes varies considerably among fish species. Generally, the first appearance of B-lymphocytes and immunoglobulins is late in marine species compared to fresh water species, and larvae have reached about 20-30 mm in length when IgM is first expressed. Rainbow trout and channel catfish show the first appearances of surface IgM at about 1 week after hatching. Marine species like the sea bass, spotted wolffish and cod show IgM positive lymphocytes 1-10 weeks after hatching. Transfer of maternal antibody to eggs and embryos has been demonstrated in several species. Examples are plaice, tilapia, carp, sea bass and salmon, but not cod. The ontogeny of complement component C3 has been studied in Atlantic halibut (Hippoglossus hippoglossus L.), Atlantic cod (Gadus morhua L.) and the spotted wolffish (Anarhichas minor O.). By Western blotting experiments C3 was found in unfertilised eggs in the spotted wolffish indicating a maternal transfer. RT-PCR analysis revealed C3 mRNA transcripts from 290 degrees in spotted wolffish eggs. Using immunohistochemistry and in situ hybridisation, C3 was found in liver, brain, kidney and muscle of cod larvae 2 days post-hatching and in intestines, pancreas, heart and gills at different stages of larval development. Also, C3 was detectable in halibut larvae in yolk sac, muscle, liver, brain, chondrocytes, spinal chord, eye, heart, intestines and kidney. These studies suggest that complement may play a role in generation of different organs, not only in the defence against invading pathogens. Lysozyme is a bactericidal enzyme present in mucus, lymphoid tissue and serum of most fish species, but not in cod and wolffish. The enzyme has been detected in oocytes, fertilised eggs and larval stages of fish species like coho salmon, sea bass and tilapia. The activity of other enzymes like the cathepsins has been described in eggs and larvae of sea bass, cod and salmonids. Cathepsins may have a bactericidal role in the skin of fish. Lectins are carbohydrate-binding proteins that interact with pathogenic surface structures that result in opsonization, phagocytosis or activation of complement. Lectins have been isolated from the eggs of various fish species.

Animals↗
PubMed2005

[Magnetocardiography--a possible supplementary method for early detection of fetal distress in high-risk pregnancies].

Ever since the first report on fetal magnetocardiography by Kariniemi in 1974 numerous studies have examined cardiac activity in healthy fetuses using this technique. Recently there has been an increase in reports on the identification of fetal pathological states, in particular in the diagnosis of fetal arrhythmias, using magnetocardiography. Other possible applications of this non-invasive method include the assessment of intrauterine growth retardation and fetal stress. In a patient with gestational hypertension and asymmetric growth retardation without pathological ultrasound findings, fetal magnetocardiography showed a reduced beat-to-beat heart rate variability indicating signs of fetal stress. On the day following the magnetocardiographic recording, fetal Doppler ultrasonography findings indicated an incipient brain sparing effect. The fetal growth retardation was reflected in the duration of the fetal cardiac time intervals. We conclude that fetal magnetocardiography non-invasively enables the timely identification of pathological fetal conditions.

Adult↗
PubMed2005

Patterns of hormone replacement therapy in a population-based cohort of postmenopausal German women. Changes after HERS II and WHI.

In July 2002, data from the Women's Health Initiative (WHI) trial provided strong evidence for an increased risk of cardiovascular disease with use of combined estrogen plus progestogen in postmenopausal women. These unexpected results triggered a large and ongoing discussion about the role of hormone replacement therapy (HRT). We investigated the frequency of HRT before and after the publications of the WHI trial and the Heart and Estrogen/Progestin Replacement Study II (HERS II) in a population-based random sample of German women aged 45 - 65 years. A total of 8380 women completed a questionnaire on menopausal status, hysterectomy and HRT. 75 % were postmenopausal. Mean age was 56.1 years; mean age of natural menopause 49.9 years; mean duration of postmenopause was 11 years; 27 % of the women had undergone hysterectomy. The percentage of current HRT users dropped by 16 % (35.4 % to 29.8 %, p = 0.004), past users increased from 19.8 % to 23.5 % (p = 0.03). Among current HRT users, the share of combined conjugated estrogen/progestogen decreased by 41 % (p = 0.008). We observed a decreased prevalence of HRT among German women 7 months after publication of the HERS II and WHI results. The decline was, however less pronounced than reported from other countries. The use of conjugated estrogen/gestagen combinations declined disproportionately compared to other formulations.

Aged↗
PubMed2004

Cloning, recombinant expression and biochemical characterisation of novel esterases from Bacillus sp. associated with the marine sponge Aplysina aerophoba.

Two novel esterases (EstB1 and EstB2) were isolated from a genomic library of Bacillus sp. associated with the marine sponge Aplysina aerophoba. EstB1 shows low identity (26-44%) with the published hydrolases of the genus Bacillus, whereas EstB2 shows high identity (73-74%) with the carboxylesterases from B. cereus and B. anthracis. Both esterases were efficiently expressed in Escherichia coli under the control of T7 promoter using the vector pET-22b(+). Recombinant EstB1 was purified in a single step to electrophoretic homogeneity by IMAC. A method for the refolding of inclusion bodies formed by the recombinant EstB2 was established to obtain active enzyme. Substrate specificity of the two enzymes towards p-nitrophenyl and methyl esters and the respective kinetic parameters K(m) and V(max) were determined. The temperature optima of EstB1 and EstB2 were determined to be in the range of 30-50 degrees C and 20-35 degrees C, respectively. The pH optima were found to be in the range of 6.5-7.5 and 6.5-8.0, respectively. Both enzymes showed the highest stability in up to 50% (v/v) DMSO followed by methanol, ethanol and 2-propanol. The influence of high NaCl and KCl concentrations was tested. The inhibition effect of 10-50 mM Zn(2+) and 50 mM Mg(2+) and Ca(2+) ions was observed for both esterases. One to five millimolar PMSF deactivated the enzymes, whereas beta-mercaptoethanol, DTT and EDTA had no effect on the enzymes activity.

Animals↗
PubMed2004

Assessment of fetal growth on the basis of signal strength in fetal magnetocardiography.

Fetal magnetocardiography has shown that fetal P wave and QRS complex durations increase with gestational age, reflecting change in cardiac muscle mass. The latter should, in principle, be associated with an increase in signal strength. We examined two approaches for determining QRS signal strength in a healthy fetus on a weekly basis in the second and third trimester. Twenty-two fetal magnetocardiograms of the same fetus were obtained using a 61 channel Magnes 1300 biomagnetometer (20th-42nd week of gestation). In the signal averaged fetal beat produced at each week, signal strength was assessed on the basis of 1) peak-to-peak QRS signal amplitudes and 2) strength of an equivalent current dipole (ECD) computed at R peak. The results were assessed on the basis of correlation to week of gestation and by comparison to changes in QRS interval duration. All values increased with advancing gestation and regression analysis suggested a nonlinear dependency on age. ECD strength reflected gestational age slightly more reliably (r2=0.93) than signal amplitude values (mean, median, maximum: r2=089, 0.88, 0.85, respectively). ECD strength and mean signal amplitude also correlated well (r=0.97, p<0.0005) Values calculated from QRS complexes determined immediately before and after a clear change in fetal position (acquisition week 24) demonstrated a certain instability in both approaches. Nonetheless, the overall correlation of the amplitude to gestational age compared favorably with that of QRS complex duration. This indicates that not only magnetocardiographically determined fetal cardiac time intervals but also signal strength may be used to assess fetal growth.

Cardiotocography↗