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Biomedical subjects

M Krueger

Publications and source records attributed to M Krueger.

At least 19 recordsLinked to original sources

ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and elevated sICAM1 levels.

Intercellular adhesion molecule-1 (ICAM1) acts as ligand for beta2-integrin molecules and mediates leucocyte trafficking to the site of inflammation. Intercellular adhesion molecule-1-deficient mice show impaired lymphocyte recruitment to the lung, less airway hyper-responsiveness and less lung inflammation than healthy controls. Thus, the aim of the study was to test common ICAM1 polymorphisms for association with paediatric asthma. Furthermore, we were interested in whether soluble ICAM1 (sICAM1) serum levels were in correlation with genotypes. The following polymorphisms in ICAM1 were genotyped on 352 children with asthma and 270 controls: rs5491 (resulting in the amino-acid exchange K56M), rs5493 (G241S), rs5498 (K469E), rs5030400 (R478W) and rs885743 in the 3'-untranslated region. In addition, sICAM1 serum levels were measured. Only K469E and rs885743 were present in our populations. K469E showed association with asthma (P = 0.0037 with Armitage's trend test). Haplotype analysis by FAMHAP using both polymorphisms revealed association with asthma by P < 0.000001. In addition, serum sICAM1 levels were correlated with K469E genotypes (P = 0.009 by Kruskal-Wallis test). We conclude from our data that K469KE is associated with paediatric asthma in the German population. Furthermore, the same polymorphism is correlated with serum levels of sICAM1. Functional analyses have to further clarify the pathophysiological mechanism conferred by the polymorphisms.

3' Untranslated Regions↗

Thrombolytic therapy of acute ischemic stroke during pregnancy.

The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed.

Adult↗

Escherichia coli strain Nissle 1917: significant reduction of neonatal calf diarrhea.

Inappropriate daily use of antimicrobial drugs for the treatment of intestinal diseases is associated with an increased risk of antibiotic resistance. Thus, the establishment of new forms of therapy is still needed. Our objective was to examine the effect of the nonpathogenic Escherichia coli strain Nissle 1917 on the prophylaxis and treatment of neonatal calf diarrhea in a hypothesis-generating study (study I) and a subsequent confirmatory clinical study (study II) under field conditions. Both trials were designed as consecutive, placebo-controlled, single-blind comparisons of 2 groups of animals. Immediately after birth, healthy calves were assigned to either the E. coli Nissle 1917 or the placebo group. The study medication was administered orally 1/d before the first feeding. The treatment was continued for the first 10 to 12 d of life. For each animal, the studies ended on d 20 to 22 of life. In both trials, the number of calves developing diarrhea was defined as the primary target criterion. A total of 335 newborn calves were included in the studies (study I: n = 172; study II: n = 163). Study I showed that the incidence of diarrhea was 65.2% under placebo and 26.5% under E. coli Nissle 1917. In study II, the corresponding figures were 63.0% under placebo and 12.2% under E. coli Nissle 1917. It can be concluded that the administration of viable E. coli bacteria, strain Nissle 1917, has a clear beneficial effect on the prophylaxis and treatment of neonatal calf diarrhea.

Animals↗

C-reactive protein and antibacterial activity in blood plasma of colostrum-fed calves and the effect of lactulose.

Several milk proteins are very important for immunological defense and can be absorbed in the intestine of calves in the first hours after birth. The influence of colostrum intake and the effect of additional lactulose application on the concentration of C-reactive protein (CRP) in blood were investigated. The CRP is known as a mediator of innate immunity. Results were compared to the bovine acute phase protein haptoglobin, and to lactalbumin, lactoferrin, and immunoglobulins in plasma from calves. After colostrum intake, the concentration of most proteins were strongly increased. The data show, for the first time, a significant increase of CRP in the blood of calves 1 d after colostrum intake (nonlactulose group, n = 10), and an even more significant increase in CRP concentration (1 d postpartum) was measured in the group of animals with additional application of lactulose (lactulose group, n = 10) when compared to the nonlactulose group. In an in vitro assay with the plasma of these animals, an increased bactericidal activity was detected against Morganella morganii (1 d postpartum) in both groups, but again a higher activity occurred in the lactulose group. The results of these investigations emphasize the importance of colostrum intake during the first hours after birth for the defense potential of newborn calves. In addition, lactulose may have a positive effect in the period of passive transfer of colostrum proteins and in the immune defense.

Animal Nutritional Physiological Phenomena↗

Effects of lactulose on the intestinal microflora of periparturient sows and their piglets.

The periparturient period of animals (and humans) is very stressful and influenced by the microecosystem of the gastrointestinal tract (GIT). Performance and productivity of animal husbandry depend on the health of animal mothers and their offspring. We investigated the influence of prebiotic amounts of lactulose in sows and their piglets. Two experimental trial sows received daily 30 ml lactulose, 71 field trial sows received daily 45 ml lactulose during their periparturient period (10 days before until 10 days after parturison). The weaners of trial sows received 15 ml lactulose per 1 kg baby food 10 days before and 10 days after weaning.The effect of lactulose was recorded by performance parameters like number of piglet born alive, losses until weaning, body mass of piglets, daily weight gain of weaners until 35 days after weaning. The effect of lactulose on GIT microflora was estimated by bacterial counts of faeces of sows (total aerobic bacteria, Gram-negative bacteria, Clostridium (C.) perfringens). In order to show a previously unknown effect of lactulose we investigated the levels of antibodies to phospholipase C (PLC) of C. perfringens in plasma of experimental sows and in colostral and ripe milk of field sows. Lactulose influenced the performance parameters of sows in a non-significant way. In case of weaners we recorded significant daily weight gains. Lactulose significantly influenced total aerobic bacterial counts, C. perfringens counts in faeces of sows 20 days after parturison. Under experimental conditions it was shown that trial sows and their piglets had higher IgG-antibody levels to C. perfringens PLCs than the control animals. Similar results were found under field conditions. Trial sows had significant higher IgG-anti LPS (J5) antibodies in milk 10 days after birth.

Animal Feed↗

Floating thrombus on an ASD occluder device in a patient with hemophilia A.

The case presented is that of a 29-year-old man with a history of hemophilia A who was admitted with recurrent onsets of transient cerebrovascular ischemia; he had undergone a transvenous closure of an atrial septal defects with an occluder device (Cardioseal Starflex) two months ago. Due to a factor-VIII deficiency, no further anticoagulation therapy was initiated. On admission, transesophageal echocardiography revealed a floating thrombus on the left atrial side of the umbrella. The device was explanted via a right minithoracotomy, and the atrial septal defect was closed. The patient had an uneventful recovery.

Adult↗

Taxonomic studies of predatory bdellovibrios based on 16S rRNA analysis, ribotyping and the hit locus and characterization of isolates from the gut of animals.

The aim of our study was to obtain data for the molecular characterization of bdellovibrio bacteria, which were recently split into the genus Bdellovibrio and the newly designated genus Bacteriovorax. We determined the 16S rDNA sequences of five reference strains and performed a phylogenetic analysis including published 16S rRNA sequences of bdellovibrios. A comparison of the secondary structure showed significant differences in two regions of the 16S rRNAs of the species Bdellovibrio bacteriovorus, Bacteriovorax starrii, and Bacteriovorax stolpii. In addition, ribotyping techniques gave specific hybridization patterns and revealed that two rRNA operons are present in the investigated strains. A hybridization probe derived from the genetic locus hit, associated with the host independent (HI) phenotype of B. bacteriovorus, was found to be specific for this species. Sequence comparison of the hit locus revealed few base pair changes between host independent (HI) and host dependent (HD) strains. Ribotyping and hybridization experiments using the hit probe were applied to characterize bdellovibrio strains isolated from the gut of animals and humans and one isolate from sewage.

Animals↗

Synthetic aperture-based beam compression for intravascular ultrasound imaging.

In this paper, intravascular ultrasound (IVUS) images acquired with a 64-element array transducer using a multistatic acquisition scheme are presented. The images are reconstructed from a collection of pulse-echo measurements using a synthetic aperture array imaging technique. The main limitations of IVUS imaging are a poor lateral resolution and elevated grating lobes caused by the imaging geometry. We propose a Synthetic Aperture Focusing Technique (SAFT), which uses a limited number of A-scan signals. The focusing process, which is performed in the Fourier domain, requires far less computation time than conventional delay-and-sum methods. Two different reconstruction kernel functions have been derived and are compared for the processing of experimental data.

Computer Simulation↗

Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of early-onset infection in premature infants.

BACKGROUND: Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection. PATIENTS AND METHODS: Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns. RESULTS: Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml, and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226-514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). CONCLUSION: In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.

Apgar Score↗

Pharmacokinetics of oral talinolol following a single dose and during steady state in patients with chronic renal failure and healthy volunteers.

OBJECTIVE: The objective of this study was to investigate the effect of renal impairment on the pharmacokinetics of the selective beta1-receptor antagonist talinolol. METHODS: Pharmacokinetic data were obtained in 12 healthy volunteers, 12 patients with renal impairment and 8 patients with terminal renal insufficiency after the oral administration of 100 mg talinolol and under steady state conditions (100 mg talinolol daily). Concentrations of talinolol in plasma, urine and dialysate during hemodialysis were measured with a validated HPLC-method. RESULTS: Talinolol is absorbed quite rapidly from the gastrointestinal tract (tmax 2.5-4 h). Steady state conditions were reached within 3-4 days depending on renal function. The calculated mean elimination half-life (t(1/2z)) in healthy volunteers (11 male, 1 female) was about 12 h. After an oral dose of 100 mg, about 55% of the bioavailable talinolol is eliminated unchanged in the urine. This fraction is reduced to 25% in patients with moderate to severe renal failure. A strong correlation was found between the renal elimination of talinolol and creatinine clearance. In patients with renal failure, the delayed elimination leads to an increase in t(1/2z) and to a decrease in the apparent total body clearance. Steady state trough levels (c(min)ss) in these patients are about 2.2-fold higher than in volunteers. The hemodialysability of talinolol was low. CONCLUSION: The disposition of talinolol shows a strong dependence on the renal function. On the basis of the kinetic data for talinolol, dose reductions of 30-50% are recommended in subjects with moderate to severe renal impairment.

Adrenergic beta-Antagonists↗

A novel acute phase marker in cattle: lipopolysaccharide binding protein (LBP).

The host response to infection, the "acute phase response" is a highly conserved series of physiological reactions including marked changes in concentrations of plasma proteins. These proteins have been shown to participate in the immune response to infections. Several recent studies have elevated the role of acute phase proteins (APPs) as predictive markers in infection. APPs such as serum amyloid A and haptoglobin but not C-reactive protein (CRP) have been identified as markers of inflammation in cattle. In humans, lipopolysaccharide (LPS) binding protein (LBP) has certain biological functions in host defence and participates in acute phase reactions. We measured plasma levels of LBP in a group of 20 calves experimentally infected with Gram-negative Mannheimia haemolytica (Pasteurella) in comparison to haptoglobin, the most widely studied APP in cattle. In infected calves, LBP levels rose significantly 6 h after infection, reaching a maximum at 24 h. Haptoglobin concentrations significantly rose after 12 h, and peak responses were measured 48 h after infection. Thus, LBP may prove to be a diagnostic marker in cattle infection and is faster than haptoglobin in detecting sepsis.

Acute-Phase Proteins↗

Treatment of respiratory failure with inhaled nitric oxide and high- frequency ventilation in an infant with respiratory syncytial virus pneumonia and bronchopulmonary dysplasia.

In a 7-month-old infant with bronchopulmonary dysplasia and respiratory syncytial virus (RSV) pneumonia, we have shown an additive effect of high-frequency ventilation (HFV) and inhaled nitric oxide (iNO) in terms of improved oxygenation and the avoidance of extracorporeal membrane oxygenation. Apparently, the combined therapy of HFV and iNO is superior to either therapeutic modality alone in the treatment of hypoxemic respiratory failure due to RSV pneumonia. The mechanism of increased lung expansion and alveolar recruitment appears to be responsible for a favorable clinical outcome. We conclude that the combined therapy of HFV and iNO should be considered in hypoxemic respiratory failure in pediatric patients.

Administration, Inhalation↗

Deformability and stability of erythrocytes in high-frequency electric fields down to subzero temperatures.

High-frequency electric fields can be used to induce deformation of red blood cells. In the temperature domain T = 0 degrees to -15 degrees C (supercooled suspension) and for 25 degrees C this paper examines for human erythrocytes (discocytes, young cell population suspended in a low ionic strength solution with conductivity sigma(25 degrees) = 154 microS/cm) in a sinusoidal electric field (nu = 1 MHz, E0 = 0-18 kV/cm) the following properties and effects as a function of field strength and temperature: 1) viscoelastic response, 2) (shear) deformation (steady-state value obtained from the viscoelastic response time), 3) stability (by experimentally observed breakdown of cell polarization and hemolysis), 4) electrical membrane breakdown and field-induced hemolysis (theoretical calculations for ellipsoidal particles), and 5) mechanical hemolysis. The items 2-4 were also examined for the frequency nu = 100 kHz and for a nonionic solution of very low conductivity (sigma(25 degrees) = 10 microS/cm) to support our interpretations of the results for 1 MHz. Below 0 degrees C with decreasing temperature the viscoelastic response time tau(res)(T) for the cells to reach steady-state deformation values d(infinity,E) increases and the deformation d(infinity,E)(T) decreases strongly. Both effects are especially high for low field strengths. The longest response time of approximately 30 s was obtained for -15 degrees C and small deformations. For 1 MHz the cells can be highly elongated up to 2.3 times their initial diameter a0 for 25 degrees and 0 degrees C, 2.1a0 for -10 degrees C and still 1.95a0 for -15 degrees C. For T > or = 0 degrees C the deformation is limited by hemolysis of the cells, which sets in for E0(lysis)(25 degrees) approximately 8 kV/cm and E0(lysis)(0 degrees) approximately 14 kV/cm. These values are approximately three times higher than the corresponding calculated critical field strengths for electrically induced pore formation. Nevertheless, the observed depolarization and hemolysis of the cells is provoked by electrical membrane breakdown rather than by mechanical forces due to the high deformation. For the nonionic solution, where no electrical breakdown is expected in the whole range for E0, the cells can indeed be deformed to even higher values with a low hemolytic rate. Below 0 degrees C we observe no hemolysis at all, not even for the frequency 100 kHz, where the cells hemolyze at 25 degrees C for the much lower field strength E0(lysis) approximately 2.5 kV/cm. Obviously, pore formation and growth are weak for subzero temperatures.

Electric Conductivity↗

Cancer screening and prevention in rural Wisconsin: the Greater Marshfield Experience.

BACKGROUND: Providing medical services to rural residents results in unique challenges to providers and patients. Cancer screening (CS) and early detection services (EDS) are frequently underutilized with rural residents often presenting with advanced cancer at diagnosis. A comprehensive approach to determine barriers and overcome them constitutes "The Greater Marshfield Experience." METHODS: Focus groups with rural residents determined the greatest barriers to receipt of CS and EDS were distance, cost, time from work and self-reliant behavior. Directives to address these concerns were to keep information simple and provide services at the workplace. In response, Marshfield Clinic and its research division developed a collaborative research partnership with public health agencies (PHA), federally funded government programs and volunteer agencies. RESULTS: In-house activities to remove barriers for providing CS and EDS included the development of a separate screening unit for these activities. Reminder systems were employed to notify patients of the need and availability of preventative services. Co-payments for health screening services were eliminated from the clinic owned health plan. Area residents near poverty level were encouraged to enroll in federally subsidized health plans that promoted and paid for CS and EDS. Federally funded cancer screening studies were implemented that funded breast and cervical cancer screening and evaluated the benefits of screening for prostate, lung, colorectal and ovarian cancers (PLCO). Outreach activities included developing partnerships with local PHA and minority groups and providing mobile screening services to remote areas. CONCLUSION: Concentrated, collaborative efforts to develop in-house systems and outreach activities resulted in delivery of CS and EDS in remote areas.

Adult↗

Grammaticality judgments and sentence comprehension in Parkinson's disease: a comparison with Broca's aphasia.

In order to test the hypothesis that significant linguistic deficits could be associated with predominantly subcortical dopaminergic pathways which projected to the frontal lobes (in patients with Parkinson's Disease-PD), we compared language performance in PD patients to that of Broca's aphasics with linguistic deficits. On tests of grammaticality judgements and sentence comprehension, performance by patients with Parkinson's Disease did not vary with different types of sentence structure (as was the case with the aphasics) and was instead, uniformly high (about 75% correct). Comprehension performance, however, did significantly decline in a subgroup of patients with PD who were tested when withdrawn from their dopaminergic medications. We conclude that patients with treated Parkinson's Disease evidence no selective linguistic dysfunction. When, however, they are withdrawn from dopaminergic medication language functions suffer.

Adult↗