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Biomedical subjects

B Jansen

Publications and source records attributed to B Jansen.

At least 73 records · Page 4Linked to original sources
PubMed1995

In vitro and in vivo efficacy of a rifampin-loaded silicone catheter for the prevention of CSF shunt infections.

Infection of cerebrospinal fluid (CSF) shunts is one of the major complications associated with their use and is usually managed by shunt removal, temporary insertion of an external drainage and implantation of a new shunt system. We have evaluated the efficacy of a rifampin-loaded silicone ventricular catheter to prevent bacterial colonization and infection in vitro and in an animal model. On the basis of an incorporation process a rifampin-loaded catheter was developed which is capable of releasing rifampin in bacteriocidal concentrations for 60 days and more. In a stationary bacterial adherence assay using S. epidermidis as test strain, the colonization resistance of the device was demonstrated. To assess the capability of the catheter to prevent CSF shunt infections, a rabbit model was developed which allowed the establishment of a reliable and reproducible CSF infection by implantation of silicone catheters into the ventricle and inoculating S. epidermidis (minimal dose 10(6) cfu) or S. aureus (minimal dose 10(3) cfu). Rifampin-loaded catheters (12 animals inoculated with S. epidermidis, 8 animals inoculated with S. aureus) were compared with non-loaded (14 animals inoculated with S. epidermidis, 19 animals inoculated with S. aureus) control catheters, and infection was documented by clinical, microbiological and histological methods. In contrast to the control group, none of the animals with rifampin-loaded catheters showed clinical signs of infection. Furthermore, in none of the materials obtained after sacrifice of the animals (catheter, brain tissue, CSF, blood) could the infecting bacteria be cultured, whereas in materials from animals with the unloaded catheter the infecting strains could always be cultured from the catheter and from surrounding brain tissue. The histological examination of catheter-adjacent tissue supported these findings. We conclude that a rifampin-loaded silicone ventricular catheter is capable of completely preventing bacterial colonization and infection by staphylococci as the main causative organisms in CSF shunt infections and should be further evaluated in clinical trials.

Animals↗
PubMed1995

Prevention of biofilm formation by polymer modification.

Bacterial biofilm formation on synthetic polymers plays an important role in industry and in modern medicine, leading, for example, to difficult-to-treat infections caused by colonized foreign bodies. Prevention of biofilm formation is a necessary step in the successful prophylaxis of such infections. One approach is to inhibit bacterial adherence by polymer surface modification. We have investigated polymer modification by glow discharge treatment in order to study the influence of the modified surface on bacterial adherence. Surface roughness, surface charge density and contact angles of the modified polymers were determined and related to the adherence of Staphylococcus epidermidis KH6. Although no influence of surface roughness and charge density on bacterial adherence was noticed, a correlation between the free enthalpy of adhesion (estimated from contact angle measurements) and adherence was observed. There seems to exist a certain minimum bacterial adherence, independent of the nature of the polymer surface. Modified polymers with negative surface charge allow for bacterial adherence close to the adherence minimum. These polymers could be improved further by the ionic bonding of silver ions to the surface. Such antimicrobial polymers are able to prevent bacterial colonization, which is a prerequisite for biofilm formation. It is suggested that modification of polymers and subsequent surface coupling of antimicrobials might be an effective approach for the prevention of bacterial biofilm formation.

Anti-Infective Agents, Local↗
PubMed1995

Polymer materials for the prevention of catheter-related infections.

Catheter-related infections are major problems in medicine because of severe consequences for the patient, prolongation of hospitalization, and increasing therapy costs. Beside progress in hygienic measures, development of catheters with antiinfective properties seems to be a promising approach to the prevention of such infections. Two approaches for infection-resistant catheter materials have been developed: materials with antiadhesive properties and materials with antimicrobial properties. Antiadhesive polymers shall prevent the adhesion of microorganisms to the medical device. However, up to now there has been no material which would lead to a complete inhibition of adherence ("zero adherence"). Materials with antimicrobial properties contain antimicrobial substances which are incorporated into the biomaterial or bound to the polymer surface. These devices seem to be effective in the prevention of "early onset infections". In this paper, an overview of the development and efficiency of antiadhesive or antimicrobial polymers is given.

Bacterial Adhesion↗
PubMed1995

Prevention of catheter-related infections by silver coated central venous catheters in oncological patients.

Catheter-related infection (CRI) is a serious complication of central venous catheterization. We have investigated the efficacy of a silver-coated polyurethane catheter (Pellethane, Fresenius AG, Germany) in preventing CRI in oncological patients receiving chemotherapy in a phase II study. From November 1992 through April 1994, 266 patients were assigned to receive single lumen catheters, either standard uncoated catheters (UC, n = 113) or silver-coated ones (SC, n = 120). Catheters were inserted into the internal jugular vein after institutional approval and informed consent. Duration of catheterization (UC vs. SC = 13.3 vs. 12.7 days) and leukopenia (< 1.0 x 10(9) WBC/l; 4.3 vs. 3.6 days) were similar in both groups demonstrating a comparable risk for infections. Skin reactions at the catheter entry site were recorded daily. CRI and colonization rates were studied by semiquantitatively culturing intradermal and intravascular segments. CRI were confirmed by blood cultures obtained via catheter and from peripheral veins in cases of suspected sepsis or at the end of catheterization. No adverse effects from the silver-coated catheter could be observed. The bacteriological results showed that SC were colonized (> 15 CFU) in 45.1% and UC in 44.2%. CRI developed in 21.2% of the UC patients but only in 10.2% of the SC patients (p = 0.011). We conclude that this new silver-coated central venous catheter is biocompatible and effective in reducing the incidence of catheter-related infections in oncological patients.

Adolescent↗
PubMed1995

Susceptibility of staphylococci and enterococci to glycopeptides comparison of 3 test methods.

The significance of grampositive bacteria, especially staphylococci and enterococci, as nosocomial pathogens has increased in the last decade. Furthermore, resistance to commonly used antibiotics like beta-lactams has also become more common and even resistance to glycopeptides has been observed. We evaluated the susceptibility of 150 staphylococcal clinical isolates (52 S. epidermidis, 52 S. haemolyticus, 10 S. saprophyticus, 10 S. hominis, 4 S. warneri, 4 S. simulans, 4 S. capitis and 14 S. aureus) and of 50 enterococci (49 E. faecalis, 1 E. faecium) to the glycopeptides, vancomycin and teicoplanin. The data from the agar dilution test used as reference method were compared with the results from the E test and the agar disk diffusion test. Concerning vancomycin, no resistance among all the staphylococcal isolates was observed whereas one single enterococcal strain (E. faecium) proved to be resistant. The overall resistance of staphylococcal isolates against teicoplanin was about 10.7% (15 S. haemolyticus, 1 S. epidermidis) being mainly due to the high proportion of S. haemolyticus strains (52 out of 150) among the staphylococcal isolates. Teicoplanin resistance among the enterococci was not detected. For vancomycin, a very close correlation between the MICs from the agar dilution test and the E test was noticed. As concerns teicoplanin, the MICs from the E-test were usually somewhat lower than those obtained by the agar dilution test. No correlation was found between the MICs of resistant and intermediate staphylococcal strains and the results from the teicoplanin agar disk diffusion test. For routine teicoplanin susceptibility testing of staphylococci, the determination of the MIC (e.g., by the E test) is much more reliable for detecting resistant strains than the agar disk diffusion test.

Anti-Bacterial Agents↗
PubMed1995

Phosphorothioate oligonucleotides reduce melanoma growth in a SCID-hu mouse model by a nonantisense mechanism.

In our efforts to investigate the biologic role of Ha-ras oncogenes in human melanoma by Ha-ras phosphorothioate antisense oligonucleotides, we observed that antisense, sense, and scrambled control oligonucleotides at a concentration of 10 microM all similarly and strongly inhibited growth of our human melanoma target cell line SK-2 in vitro but without specific decrease of the target protein. Cell numbers with respect to the untreated control were reduced by 84% +/- 4.2% (ISD), 82.9% +/- 3.6%, and 84% +/- 3%, respectively. In vivo studies in a SCID-hu mouse model confirmed these findings. Both antisense and sense control oligonucleotides administered through osmotic pumps significantly (p < 0.006) reduced the mean tumor weight (1.5 g +/- 0.4 g and 1.8 g +/- 0.8 g, respectively) in comparison with saline-treated (5.7 g +/- 0.7 g) or untreated control animals (5.8 g +/- 1.0 g). The vascularity of oligonucleotide-treated tumors was greatly reduced. Clinical signs of oligonucleotide-related toxicity were not observed, and there was no evidence of histopathologic alterations in a variety of mouse tissues. We could demonstrate that the antimelanoma effects can be abrogated in vitro by adding basic fibroblast growth factor (bFGF). In the context of the importance of bFGF in melanocyte biology and angiogenesis, we argue in favor of an interaction between polyanionic phosphorothioate oligonucleotides and bFGF in our melanoma system. These findings stress the notion that phosphorothioate oligonucleotides may be promising antineoplastic lead compounds capable of employing antitumor effects by mechanisms other than specific inhibition of gene expression.

Animals↗
PubMed1994

In-vitro efficacy of an antibiotic releasing silicone ventricle catheter to prevent shunt infection.

Infection due to implanted polymeric devices is a major problem in modern medicine. Microbial colonization of implants in neurosurgery, e.g. cerebrospinal fluid (CSF) shunts is the main reason for their failure, and often results in the consequent removal of the infected implants. In this paper we report on new approaches in the prevention of bacterial infections by incorporation of an antibiotic (rifampicin) into the polymer devices (silicone). Drug release characteristics are investigated, and the physico-chemical mechanism of the delivery is discussed. Measurements of killing kinetics and the bacterial adhesion to the antibiotic-loaded silicone in a static adhesion assay reveal that only the liberation of high antibiotic doses over a period of weeks can prevent the bacterial colonization of the polymeric surface.

Animals↗
PubMed1994

Outbreak of methicillin-resistant Staphylococcus aureus in a teaching hospital--epidemiological and microbiological surveillance.

An outbreak of methicillin-resistant S. aureus (MRSA) in a large university teaching hospital occurred between December 1991 and May 1992, involving 7 different wards and more than 30 patients. Epidemiological typing was performed to control the epidemic and to identify the MRSA carriers. By a combination of various classical methods (antimicrobial susceptibility, phage typing) and molecular typing procedures (SDS-PAGE of extracellular proteins, plasmid DNA profile, restriction enzyme fragment pattern of chromosomal DNA), three different clones of MRSA could be discriminated. The epidemic clone A was recovered from 30 patients and from 3 staff members. By strict microbiological monitoring together with hygienic measures, the epidemic could be successfully controlled. It is concluded that a combination of phenotypic markers and DNA-based epidemiological markers is extremely useful in the microbiological surveillance of MRSA outbreaks.

Disease Outbreaks↗
PubMed1994

In vitro evaluation of the antimicrobial efficacy and biocompatibility of a silver-coated central venous catheter.

Central venous catheter infection presents an important problem in modern medicine, leading sometimes to a life-threatening situation for the patient as well as contributing to prolonged hospital stay and to an increase in costs. We have evaluated the in vitro biocompatibility and antimicrobial activity of a silver-coated polyurethane catheter designed for use as a colonization-resistant, antiinfective catheter. Due to a comparatively low silver release, the catheter performed well in cell toxicity and blood compatibility tests as well as in acute toxicity tests done with mice. The antimicrobial activity was tested in stationary and dynamic bacterial adherence experiments using S. epidermidis, E. coli and P. aeruginosa as test strains. The silver-coated polyurethane catheter showed good ability to prevent microbial colonization of the catheter surface. Currently a clinical trial of the silver-coated catheter is under investigation.

Animals↗
PubMed1993

Foreign body associated infection.

One of the major complications associated with the use of medical devices and implants is foreign body associated infection. Its significance in modern medicine and its pathogenesis are discussed. Adherence to and colonization of a foreign body material and the interference of microbial products with the host defence are critical steps leading to foreign body infections. Therapy is difficult and hence the immediate administration of antibiotics and the removal of an infected device or implant is still preferred. New strategies for the prevention of foreign body infections are briefly introduced.

Anti-Bacterial Agents↗
PubMed1993

Localization of the ActA polypeptide of Listeria monocytogenes in infected tissue culture cell lines: ActA is not associated with actin "comets".

The ActA protein of the gram-positive pathogen Listeria monocytogenes is a 90-kDa polypeptide required for interaction of the bacteria with components of the host cell microfilament system to generate intra- and intercellular movement. To study the localization, distribution, and expression of the ActA polypeptide in L. monocytogenes grown either in broth culture or in infected tissue culture cells, we first isolated ActA by monoclonal antibody-based immunoaffinity chromatography. Polyclonal rabbit antisera raised against purified ActA revealed that ActA was associated with the cell wall and exposed on the surface of the bacteria, readily accessible to ActA antibodies. In contrast, a C-terminally truncated ActA1 polypeptide expressed by the isogenic actA1 mutant was detected only in the supernatant fluids. Immunofluorescence microscopy and electron microscopic studies using immunogold labeling showed that ActA was present on the surface of the bacteria infecting PtK2 and J774 cells at all stages of the infection cycle and was not found to be associated with the actin "tail" of individual bacteria. For the isogenic actA1 mutant strain, which grew as microcolonies within infected cells, only diffuse staining of the secreted ActA1 polypeptide in the host cytoplasm was observed. The ActA polypeptide therefore appears to be required in the initiation of actin accumulation by the bacterium and is apparently not directly involved in the generation of the actin tail. Analysis of strains of several L. monocytogenes serotypes indicated microheterogeneity in the molecular weights of the ActA polypeptides of individual strains and led to the detection of a serotype 3a strain that does not produce ActA.

Animals↗
PubMed1993

Effective immunochemotherapy of human t(4;11) leukemia in mice with severe combined immunodeficiency (SCID) using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin plus cyclophosphamide.

Human mixed lineage leukemia cell line RS4;11 with the t(4;11)(q21;q23) translocation causes disseminated and invariably fatal leukemia in mice with severe combined immunodeficiency. Whereas an immunotoxin constructed from the murine anti-CD19(B43) monoclonal antibody and the plant toxin pokeweed antiviral protein (B43-PAP) has a potent in vitro anti-leukemic effect against clonogenic RS4;11 cells, its activity is further potentiated by the active cyclophosphamide congener mafosfamid. These intriguing observations prompted us to evaluate the in vivo antileukemic efficacy of combined immunochemotherapy employing B43-PAP immunotoxin plus cyclophosphamide against human t(4;11) leukemia cells in an RS4;11 severe combined immunodeficiency (SCID) mouse model system. Intravenous injections of B43-PAP or cyclophosphamide improved survival of SCID mice challenged with RS4;11 leukemia, as reflected by markedly prolonged median survival times. After intravenous inoculation of 5 x 10(7) RS4;11 leukemia cells, the median survival times were 41 days for saline-treated control mice (n = 12), 44 days for control mice treated with unconjugated B43 monoclonal antibody and PAP (n = 12), 56 days for mice treated with the control immunotoxin G17.2 (anti-CD4)-PAP (n = 6), 79 days for B43-PAP-treated test mice (n = 12), and 80 days for cyclophosphamide-treated test mice (n = 16). Notably, combined immunochemotherapy using B43-PAP plus cyclophosphamide was significantly more effective than either B43-PAP or cyclophosphamide alone. The median survival time for a total of 22 SCID mice undergoing combined immunochemotherapy with B43-PAP followed by cyclophosphamide (n = 12) or cyclophosphamide followed B43-PAP (n = 10) was > 150 days. The Kaplan-Meier estimates and standard errors of the probability of event-free survival at 5 months after inoculation of 5 x 10(7) RS4;11 cells were 21 +/- 13% for B43-PAP-treated mice, 7 +/- 6% for cyclophosphamide-treated mice, 90 +/- 10% for mice treated with B43-PAP followed by cyclophosphamide (n = 12), and 90 +/- 10% for mice treated with cyclophosphamide followed by B43-PAP (n = 10). Our results lead us to recommend that initial consideration be given to combined immunochemotherapy protocols using B43-PAP immunotoxin plus cyclophosphamide for treatment of refractory or relapsed t(4;11) leukemias.

Acute Disease↗
PubMed1992

Successful treatment of human acute T-cell leukemia in SCID mice using the anti-CD7-deglycosylated ricin A-chain immunotoxin DA7.

The study of new therapeutic approaches for refractory human leukemia has been hampered by the lack of relevant in vivo models with disseminated disease, particularly T acute lymphoblastic leukemia (T-ALL). In the present study we evaluated methods for establishing and therapy of a human T-ALL cell line (MT-ALL) in 73 SCID mice. MT-ALL is a T-cell receptor alpha/beta +, CD3+, and CD7+ leukemia cell line, derived from a patient with refractory disease and early death. Injection of 5 x 10(7) MT-ALL cells i.v. caused disseminated human leukemia in hematopoietic and nonhematopoietic organs in 100% of SCID mice (n = 9) leading to death or terminal disease at 65 to 70 days after a uniform clinical course. To study possible therapeutic approaches for disseminated leukemia we utilized an immunotoxin, DA7, constructed by chemically linking the mouse IgG2b anti-CD7(3A1E) monoclonal antibody which recognizes a pan-T-cell marker expressed on almost all T-cell leukemias to deglycosylated ricin A-chain, a catalytic plant toxin and inhibitor of protein synthesis. Administration of DA7 led to greater than 5 log kill of clonogenic MT-ALL cells in vitro and selectively inhibited protein synthesis. DA7 was administered to mice at a dose of 10 micrograms/mouse/day for 5 consecutive days starting 8 days after i.v. inoculation of leukemia. The immunotoxin therapy resulted in significant long term survival over 348 days compared to untreated or control mice treated with anti-CD7 antibody and deglycosylated ricin A-chain which were all dead by day 70 (P less than 0.001). Even after more than 11 months there was no evidence of disease in 82% of the DA7 treated animals. SCID mice given i.p. injections (n = 9) developed an i.p. tumor mass but demonstrated metastasis outside the peritoneum with disseminated leukemia in hematopoietic and nonhematopoietic organs, a finding different from most conventional nude mouse models. The leukemia was fatal in 100% and killed the animals at 68-95 days. SCID mice given i.p. injections of MT-ALL completely responded to therapy with DA7, resulting in survival of 100% of the animals (n = 10) at 216 days (P less than 0.001 compared to untreated animals). Anti-CD7 antibody, deglycosylated ricin A-chain, and a control anti-melanoma immunotoxin (IND1-RTA) showed no therapeutic effect. We conclude that DA7 is an effective in vivo therapeutic agent against human MT-ALL in the SCID mouse system, suggesting potential usefulness for therapy of humans with poor prognosis T-cell leukemia.

Animals↗