Biomedical subjects

S Schubert

Publications and source records attributed to S Schubert.

At least 19 recordsLinked to original sources

PubMed2006

Self-fabricated fenestrated Amplatzer occluders for transcatheter closure of atrial septal defect in patients with left ventricular restriction: midterm results.

To avoid left ventricular failure after transcatheter closure of atrial septal defects in elderly patients with restrictive left ventricular physiology, partial occlusion by fenestrated devices may be an option. If complete defect closure is not possible in these patients, significant reduction of left to right shunting usually results in clinical benefit. We report two patients in whom deterioration of left ventricular function could be avoided by implantation of self-fabricated fenestrated Amplatzer Septal Occluders (ASO) in patients with ongoing restrictive left ventricular physiology. We describe technical preparation of the standard occluder, the specific implantation technique, and the initial and the intermediate term results up to 24 months.

Aged↗

PubMed2006

Oligonucleotide-based antiviral strategies.

In the age of extensive global traffic systems, the close neighborhood of man and livestock in some regions of the world, as well as inadequate prevention measures and medical care in poorer countries, greatly facilitates the emergence and dissemination of new virus strains. The appearance of avian influenza viruses that can infect humans, the spread of the severe acute respiratory syndrome (SARS) virus, and the unprecedented raging of human immunodeficiency virus (HIV) illustrate the threat of a global virus pandemic. In addition, viruses like hepatitis B and C claim more than one million lives every year for want of efficient therapy. Thus, new approaches to prevent virus propagation are urgently needed. Antisense strategies are considered a very attractive means of inhibiting viral replication, as oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The ensuing targeted destruction of viral RNA should interfere with viral replication without entailing negative effects on ongoing cellular processes. In this review, we will give some examples of the employment of antisense oligonucleotides, ribozymes, and RNA interference strategies for antiviral purposes. Currently, in spite of encouraging results in preclinical studies, only a few antisense oligonucleotides and ribozymes have turned out to be efficient antiviral compounds in clinical trials. The advent of RNA interference now seems to be refueling hopes for decisive progress in the field of therapeutic employment of antisense strategies.

Animals↗

PubMed2006

Central diabetes insipidus in a patient with malaria tropica.

Up to 21% of severe cases of malaria tropica are associated with polyuria and are life-threatening. We describe a 39-yr-old man with malaria tropica who developed disseminated intravascular coagulation, polyuria, and a pituitary lesion. Empiric treatment with vasopressin improved the polyuria. This is the first case of malaria tropica in which central diabetes insipidus has been documented.

Adrenal Insufficiency↗

PubMed2006

[Indigenous helminthiasis].

Worldwide an estimated 1.5-2 billion people are infested with helminths. Over the last decades, in industrialized countries prevalence rates of human helminthic infections were decreased by means of wastewater and food control. In this article, we review the geographic distributions as well as the impact on the public health system of the most prevalent helminthiases. Special emphasis is given to Echinococcus, Enterobiasis, and Toxocariasis. Intestinal larvae or eggs of helminths can be detected in faeces. Pinworms are collected with a strip of cellophane tape with the sticky side towards the anus. Tissue helminthosis, like Toxocariasis or Trichinosis are associated with eosinophilia and can be diagnosed with sensitive immunological methods or by biopsy. Infection with Echinococcus multilocularis is the most serious parasitic disease in central Europe. Although current therapeutic options are limited, 5 year survival rates were markedly improved by the combination of medical and surgical treatment.

Demography↗

PubMed2006

[Tropical and subtropical helminthoses].

Human helminthic infestations are extraordinarily common in tropical regions and represent a significant burden for those countries and their populations. The risk of intestinal helminthoses is further increased by poverty. Particularly in children helminthoses lead to malnutrition (ascariasis etc) or iron and protein deficiency (ancylostomiasis). Tropical helminthoses like schistosomiasis and filariasis can cause severe organ damage, starvation, and early death. In contrast, returning travellers very rarely acquire tropical helminthoses, if they follow simple hygienic rules. Furthermore, the worm burden in returning travelers hardly ever is high enough to cause severe illness. Therefore, tropical helminthosis is more common in immigrants from endemic areas compared to returning travelers.

Demography↗

PubMed2006

Advantages of C2 monitoring to avoid acute rejection in pediatric heart transplant recipients.

BACKGROUND: Inadequate cyclosporine (CsA) blood levels are a major risk factor for acute rejection in transplant recipients. The CsA trough level (C0 level) measured just before the next dose is commonly used to adjust the oral dosage. However, the 2-hour post-CsA dose concentration (C2 level) is favored as the best single-point correlate of CsA area-under-the-curve concentration and may better reflect the immunosuppressive effect of CsA. Because an adequate C2 level has not yet been defined, this study was performed to assess the value of C2 monitoring for the prevention of acute rejection and to define target levels in pediatric heart transplant recipients. METHODS: C2 levels were assessed in 50 pediatric heart transplant patients with oral CsA therapy and compared with trough C0 levels using full blood sampling, mass spectrometry and a blinded analysis. Acute graft rejection was detected using intramyocardial electrocardiogram (IMEG) and serial conventional and tissue Doppler echocardiography (TDE). Rejection was confirmed or excluded by endomyocardial biopsy. RESULTS: C2 and not C0 levels were significantly reduced in patients with acute graft rejection (ISHLT Grade > or =2). Patients with a C2 level <600 ng/ml had a significantly higher risk of developing acute rejection (100% sensitivity and 82% specificity). Patients with impaired CsA absorption were identified with C2 monitoring and switched to another calcineurin inhibitor. CONCLUSIONS: Monitoring of the C2 rather than the C0 level better reflects immunosuppressive efficiency and identifies patients at increased risk of acute rejection. A C2 level of >600 ng/ml should be the target to prevent acute rejection.

Adolescent↗

PubMed2006

CD9-dependent regulation of Canine distemper virus-induced cell-cell fusion segregates with the extracellular domain of the haemagglutinin.

Antibodies to CD9, a member of the tetraspan transmembrane-protein family, selectively inhibit Canine distemper virus (CDV)-induced cell-cell fusion. Neither CDV-induced virus-cell fusion nor cell-cell fusion induced by the closely related morbillivirus Measles virus (MV) is affected by anti-CD9 antibodies. As CDV does not bind CD9, an unknown, indirect mechanism is responsible for the observed inhibition of cell-cell fusion. It was investigated whether this effect was restricted to only one viral glycoprotein, either the haemagglutinin (H) or the fusion (F) protein, which form a fusion complex on the surface of virions and infected cells, or whether it is dependent on both in transient co-transfection assays. The susceptibility to CD9 antibodies segregates with the H protein of CDV. By exchanging portions of the H proteins of CDV and MV, it was determined that the complete extracellular domain, including the predicted stem structure (stem 1, barrel strand 1 and stem 2) and globular head domain, of the CDV-H protein mediates the effect. This suggests that interaction of the CDV-H protein with an unknown cellular receptor(s) is regulated by CD9, rather than F protein-mediated membrane fusion.

Amino Acid Sequence↗

PubMed2006

A mouse model of persistent brain infection with recombinant Measles virus.

Measles virus (MV) nucleocapsids are present abundantly in brain cells of patients with subacute sclerosing panencephalitis (SSPE). This invariably lethal brain disease develops years after acute measles as result of a persistent MV infection. Various rodent models for MV infection of the central nervous system (CNS) have been described in the past, in which the detection of viral antigens is based on histological staining procedures of paraffin embedded brains. Here, the usage of a recombinant MV (MV-EGFP-CAMH) expressing the haemagglutinin (H) of the rodent-adapted MV-strain CAM/RB and the enhanced green fluorescent protein (EGFP) is described. In newborn rodents the virus infects neurons and causes an acute lethal encephalitis. From 2 weeks on, when the immune system of the genetically unmodified animal is maturating, intracerebral (i.c.) infection is overcome subclinically, however, a focal persistent infection in groups of neurons remains. The complete brain can be analysed in 50 or 100 microm slices, and infected autofluorescent cells are readily detected. Seven and 28 days post-infection (p.i.) 86 and 81% of mice are infected, respectively, and virus persists for more than 50 days p.i. Intraperitoneal immunization with MV 1 week before infection, but not after infection, protects and prevents persistence. The high percentage of persistence demonstrates that this is a reliable and useful model of a persistent CNS infection in fully immunocompetent mice, which allows the investigation of determinants of the immune system.

Age Factors↗

PubMed2005

Antibacterial essential oils in malodorous cancer patients: clinical observations in 30 patients.

Malodorous necrotic ulcers in cancer patients are of major concern as it leads to social isolation and poor quality of life. Current medications and topical therapies have proven inadequate in their ability to reduce foul smell to acceptable levels. We report the positive experience we have had in using antibacterial essential oils in patients with incurable head and neck cancer and associated malodorous necrotic ulcers. All patients received a standard course of therapy with oral or systemic antibiosis. In addition, we rinsed the ulcers with an antibacterial essential oil mix (mainly based on Eucalyptus oil) twice a day. All patients experienced complete resolution of the foul smell by only the third or fourth day of therapy. As a secondary effect we saw that besides smell reduction the oils had anti-inflammatory effects on neoplastic ulcers. In some patients ulcers started to heal and achieved complete re-epithiliazation. The patients experienced great personal relief upon resolution of their malodorous conditions. Quality of life improved significantly with the resulting reintroduction of social contact with friends and relatives.

Aged↗

PubMed2005

Activity of histone H1.2 in infected burn wounds.

OBJECTIVES: Infections with multidrug-resistant microorganisms (e.g. Pseudomonas aeruginosa and Staphylococcus aureus) cause immense complications in wound care and in the treatment of immunosuppressed patients. Like most antimicrobial peptides, histones are relatively small polycationic proteins located in each eukaryotic nucleus, which naturally supercoil DNA. The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity. METHODS: To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out. Haemolytic and cytotoxic properties were determined in human red blood cells and primary human keratinocytes. In vivo antimicrobial activity was tested in an infected rat burn model with P. aeruginosa (ATCC 27853). All results were compared with the naturally occurring broad-spectrum antimicrobial peptide protegrin-1 and with antibiotics clinically used against the corresponding bacteria. RESULTS: Human histone H1.2 exerted good antimicrobial activity against all tested microorganisms without significant haemolytic activity. Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes. The in vivo burn model data revealed a significant three-fold higher reduction in bacterial counts within 4 h compared with carrier control. CONCLUSIONS: These findings indicate that histone H1.2 is a potential candidate for use as a local and, because of its low haemolytic activity, systemic antimicrobial agent. However, further investigations are needed to specify the cytotoxicity and the dose-response relationship for histone H1.2.

Animals↗

PubMed2005

Left ventricular conditioning in the elderly patient to prevent congestive heart failure after transcatheter closure of atrial septal defect.

Transcatheter closure of atrial septal defects (ASDs) is a safe and effective treatment. Over the past years, an increasing number of elderly patients (age > 60 years) have been admitted for transcatheter closure to prevent ongoing congestive heart failure from volume overload. However, recent data point to the risk of serious acute left ventricular dysfunction leading to pulmonary edema immediately after surgical or transcatheter ASD closure in some patients. In this study, we used a technique described before to recognize in advance patients at risk of left heart failure after ASD closure. Those patients at risk were then treated with preventive conditioning medication for 48-72 hr before definitive transcatheter ASD closure was performed. Fifty-nine patients aged over 60 years (range, 60-81.8 years; median, 68 years) were admitted to our institution for transcatheter closure of an atrial septal defect. All patients received evaluation of atrial pressures before and during temporary balloon occlusion of the ASD. Patients with left ventricular restriction due to increased mean atrial pressures (> 10 mm Hg) during ASD occlusion received anticongestive conditioning medication with i.v. dopamine, milrinone, and furosemide for 48-72 hr before definitive ASD closure with an Amplatzer septal occluder was performed. In 44 patients without any signs of left ventricular restriction, ASD closure was performed within the first session. Fifteen (25%) out of 59 patients showed left ventricular restriction. In the majority of patients with LV restriction, the mean left atrial pressures with occluded ASD were significantly decreased after 48-72 hr of conditioning medication. Definitive ASD closure was then performed in a second session. Only two patients received a fenestrated 32 mm Amplatzer occluder due to persistent increased atrial pressures > 10 mm Hg even after conditioning medication. There were no significant differences in shunt, device size, or defect size between the two groups. Balloon occlusion of atrial septal defects identifies patients with left ventricular restrictive physiology before ASD closure. Intravenous anticongestive conditioning medication seems to be highly effective in preventing congestive heart failure after interventional closure of an ASD in the elderly patient with a restrictive left ventricle.

Aged↗

PubMed2005

Rare case of pulmonary arteriovenous fistula simulating residual defect after transcatheter closure of patent foramen ovale for recurrent paradoxical embolism.

We report on a patient suffering from recurrent cerebrovascular events despite previous transcatheter closure of persistent foramen ovale (PFO) with a Helex occluder. There was evidence of persistent left-to-right atrial shunt shown by transesophageal contrast echocardiography and the patient was admitted to our institution for interventional closure of the supposed residual defect. However, the PFO was completely closed by the device and left pulmonary artery injections showed a pulmonary arteriovenous fistula in the left lower lobe. This rare malformation may well explain the recurrent paradoxical embolism. Transcatheter fistula closure with coils was performed successfully. This case underlines that the existence of an isolated pulmonary arteriovenous fistula as a right-to-left shunt in patients with cryptogenic stroke should not be overlooked, even if a PFO is present and pulmonary arteriovenous fistula is not suggested by the initial physical findings or chest X-ray.

Adult↗

PubMed2005

Kinetics and quantification of antibacterial effects of beta-lactams, macrolides, and quinolones against gram-positive and gram-negative RTI pathogens.

Traditionally, the in vitro activity of antibacterial agents is characterized by their minimal inhibitory concentrations. However, these endpoints are, by nature, discrete and do not provide information on time-dependent killing of the bacteria during the incubation period. Nevertheless, the pharmacodynamic characteristics of antibacterial agents are almost always defined by correlating a static endpoint describing the antibacterial activity of an agent with the pharmacokinetics, describing the time-dependent fluctuation of drug concentrations. This approach is basically a contradiction in itself. Therefore, it would be more logical to correlate pharmacokinetics to in vitro parameters describing the time- and concentration-dependent antibacterial action of an agent. Thus, experimental methods and mathematical models quantifying the decrease in growth rate of a bacterial population due to the action of an antibacterial agent as a function of time and drug concentration have been applied to quantitate their pharmacodynamics. The effect of nine antibacterial agents representing drug classes of penicillins, cephalosporins, penems, macrolides, and fluoroquinolones were mathematically analyzed by using three different but related models. The kill rate, maximal kill, the 50%-effective concentration (EC50), the Hill coefficient, and concentrations and times needed to obtain a 1,000-fold decrease of the initial number of viable counts were calculated. Both the phenotypic description of the time-kill curves and these five parameters mirror the bacteriostatic or bactericidal activity of all nine agents studied as a function of time and concentration. Therefore, it would be more logical to correlate a parameter quantifying the kinetics of antibacterial in vitro activity with the pharmacokinetics of the drug, thus, replacing static endpoints like minimal inhibitory concentrations.

Anti-Bacterial Agents↗

PubMed2005

Pharmacodynamics of moxifloxacin and levofloxacin simulating human serum and lung concentrations.

Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to integrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log(10) titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect.

Anti-Bacterial Agents↗

PubMed2005

Effect of pH on the in vitro activity of and propensity for emergence of resistance to fluoroquinolones, macrolides, and a ketolide.

Antibiotic activity against common respiratory pathogens can be affected by the pH of the medium (in vitro) or the bodily fluid (in vivo) in which bacteria are present. The ionized fraction of an antibiotic is not able to efficiently penetrate bacterial or mammalian membranes, reducing the quantity of molecules able to exert their antibacterial effect resulting in elevated MIC values This study shows that the activity of macrolide antibiotics is particularly sensitive to acidic conditions, whereas a ketolide and fluoroquinolones are much less affected. Furthermore, induction of spontaneous and multistep macrolide resistance is greatly increased in acidic medium. In contrast, telithromycin and moxifloxacin did not induce resistance at any pH. Antibiotics which are less likely to induce resistance in vitro may also be less likely to induce the development of resistance in patients with respiratory tract infections.

Anti-Bacterial Agents↗

PubMed2005

The CP stent--short, long, covered--for the treatment of aortic coarctation, stenosis of pulmonary arteries and caval veins, and Fontan anastomosis in children and adults: an evaluation of 60 stents in 53 patients.

OBJECTIVE: To evaluate the feasibility and usefulness of the Cheatham platinum (CP) stent in a broad spectrum of lesions. METHODS: Retrospective analysis of 60 implanted CP stents (11-80 mm lengths, 12 covered) between September 2001 and March 2004. PATIENTS: 53 patients aged 2.5-68 years (median 17 years). Body weight ranged from 12-95 kg (median 52 kg). Thirty six patients had aortic (re)coarctation; seven of them had functionally interrupted aortic arches. Thirteen patients had pulmonary artery stenosis and four had stenosis of caval veins or conduits in a total cavopulmonary connection (TCPC). RESULTS: Arterial pressure gradients dropped from 33 mm Hg (range 20-80 mm Hg) to 5 mm Hg (range 0-10 mm Hg) and pressure gradients in TCPC or caval veins dropped from 4 mm Hg (range 4-20 mm Hg) to 0 mm Hg (range 0-3 mm Hg). All stents were placed in the target lesion without complications. Three stent fractures without clinical instability were noted. CONCLUSIONS: The CP stent is suitable for the treatment of vessel stenosis in congenital heart diseases from childhood to adulthood. Whether these good results will be stable in the long term needs to be investigated.

Adolescent↗

PubMed2004

Induction of pathogen resistance in barley by abiotic stress.

Enhanced resistance of barley (Hordeum vulgare L. cv. Ingrid) against barley powdery mildew (Blumeria graminis f. sp. hordei race A6) was induced by abiotic stress in a concentration-dependent manner. The papilla-mediated resistance was not only induced by osmotic stress, but also by proton stress. Resistance was directly correlated with increasing concentrations of various salts in the nutrient solution. Resistance induced by proton stress also depended on the stress intensity. Resistance induction occurred even at low stress intensities. Any specific ion toxicity affecting the fungal growth directly, and therefore leading to enhanced pathogen resistance, can be excluded because of the independence of resistance induction of the ion used and of the time course of sodium accumulation in the leaves. BCI-4, a marker for benzo[1,2,3]thiadiazolecarbothioic acid S-methyl ester (BTH)-induced resistance was not induced by these abiotic stresses. However, resistance was induced in the same concentration-dependent manner by the application of the stress hormone ABA to the root medium. During the relief of water stress, resistance did not decrease constantly. On the contrary, after a phase of decreasing resistance for 24 h the pathogen resistance increased again for 48 h before decreasing finally to control levels.

Ascomycota↗

PubMed2004

Ribozyme- and deoxyribozyme-strategies for medical applications.

Ribozymes are catalytically active nucleic acids capable of site-specific cleavage of target mRNAs. They have widely been employed as tools in functional studies and for therapeutic purposes. Different classes of ribozymes distinguished by size and mechanism of action have been discovered in natural systems or obtained by in vitro selection. After an introduction to different types of ribozymes with a special focus on the hammerhead and hairpin ribozyme, major challenges in the process of developing ribozymes for medical purposes will be described in the present review. Subsequently, examples of ribozyme applications in animal models for various diseases including cancer, viral infections, rheumatoid arthritis and cardiovascular diseases will be given. The course of phase I and II clinical trials with ribozymes designed to treat patients with virus infections or cancer will be outlined. Finally, the current significance of ribozymes will be discussed in the light of the emergence of new powerful anti-mRNA strategies, particularly RNA interference (RNAi).

Animals↗