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Biomedical subjects

J Beuth

Publications and source records attributed to J Beuth.

At least 19 recordsLinked to original sources

Thymosin alpha(1) application augments immune response and down-regulates tumor weight and organ colonization in BALB/c-mice.

The immunomodulatory and antimetastatic/antitumor activity of thymosin alpha(1) (Talpha(1)) was evaluated in BALB/c-mice. Daily subcutaneous application (7 consecutive days, 0.01-10 microg of Talpha(1)/injection per mouse) upregulated the number of thymocytes and peripheral blood cells in tumor bearing mice. To check the influence of Talpha(1) treatment on growth of experimental metastases, RAW H10 lymphosarcoma cells or L-1 sarcoma cells were intravenously injected into BALB/c-mice to establish liver or lung metastases. Local tumor growth was induced by subcutaneous injection of L-1 sarcoma cells. Talpha(1) was subcutaneously administered daily for 7 consecutive days starting 24 h after tumor cell challenge. Organ colonization, as well as local tumor growth, were investigated on day 14 after tumor cell inoculation, and demonstrated a statistically significant (P<0.05) reduction of experimental liver and lung metastases and local tumor growth for Talpha(1) treated mice.

Adjuvants, Immunologic↗

Measurement of ultrasonic-induced chlorhexidine liberation: correlation of the activity of chlorhexidine-silver-sulfadiazine-impregnated catheters to agar roll technique and broth culture.

The diagnosis of intravascular catheter-related infections continues to be a challenge to both the clinician and the microbiologist. To assess the antiseptic effects of silver-sulfadiazine-chlorhexidine-impregnated central venous catheters (SSC) on catheter culture systems, segments of fresh antiseptic- and non antiseptic-impregnated catheters as well as extracted catheters following five days of immersion in PBS were sonicated. The chlorhexidine liberated from the catheter material by ultrasonication was measured by HPLC. Fresh antiseptic-impregnated catheter segments rolled on seeded agar plates produced inhibition zones unlike catheters which had been extracted for >five days in phosphate buffered saline (PBS). Scanning electron microscopy (SEM) revealed that chlorhexidine-silversulfadiazine crystals were located in the superficial catheter matrix. Direct contact of superficially located drug particles with seeded agar plates probably caused the inhibition of bacterial growth. The study suggests that antiseptic compounds readily elute from fresh catheters during solid medium-based culturing processes and ultrasonication. The addition of inhibitors of silversulfadiazine-chlorhexidine to media may be prudent especially when culturing antimicrobial loaded catheters removed after short inwelling times.

Anti-Infective Agents, Local↗

The antimicrobial efficacy of a new central venous catheter with long-term broad-spectrum activity.

Indwelling vascular catheters are a major cause of nosocomial sepsis. Prevention of colonization of polymeric surfaces by continuous release of bactericidal, highly biocompatible antimicrobials incorporated into polymers has been investigated as a promising new approach. An antimicrobial polyurethane catheter was investigated by HPLC and various antimicrobial assays. Controlled drug delivery governed by the physico-chemical mass transfer from the polyurethane bulk provided long-term release of the antimicrobial substances from the material to the outer surface and catheter lumen. The in vitro activity of catheters coated with miconazole and rifampicin against 158 clinical isolates of catheter-associated infections was evaluated. Incubated in physiological NaCl at 37 degrees C, the half-life of inhibitory activity of catheters coated with miconazole or rifampicin exceeded 3 weeks. In static and dynamic adhesion assays, coated catheters were able to prevent colonization with Staphylococcus aureus, Staphylococcus epidermidis and enterococci. To produce catheters resistant to infection, a potent antimicrobial efficacy combined with an excellent biocompatibility over time is needed. The long lasting efficacy of the antimicrobial polyurethane alloy as well as the increased antifungal activity of miconazole combined with rifampicin may be regarded as a promising improvement for long-term central venous access.

Anti-Bacterial Agents↗

Keyhole limpet hemocyanin for carcinoma in situ of the bladder: a long-term follow-up study.

OBJECTIVE: Keyhole limpet hemocyanin (KLH) is a nonspecific immunomodulator, demonstrated to be clinically effective in superficial bladder cancer. The present study investigated the clinical efficacy of intravesical KLH in patients with carcinoma in situ (CIS) with a long-term follow-up. METHODS: Thirteen patients with CIS grade III were treated with intravesical instillations of KLH, 20 mg for 6 weeks, then monthly for 1 year and bimonthly for 2 subsequent years. Patients not responding to 2 courses of KLH were treated with bacillus Calmete-Guérin (BCG, 81 mg Connaught strain). RESULTS: The follow-up period ranged from 12 to 84 months. Two patients were free of tumor after KLH instillations with a follow-up of 66 and 82 months, respectively. All patients who did not respond to the primary KLH course, but to the 'rescue' instillation of BCG, experienced recurrences after 42, 48, 56 and 60 months after the first KLH instillation treatment. Three patients with recurrent CIS and who were not cystectomized had recurrences after prolonged remission (4-5 years). Patients progressing despite KLH and BCG instillations underwent cystectomy. CONCLUSIONS: KLH demonstrates efficacy and induces long- term remissions against CIS in a limited number of cases. In the present study, most patients with CIS progressed over time whatever the substance instilled, whether KLH or BCG. CIS remains a very aggressive neoplasm requiring a lifelong follow-up. Further studies are necessary to define the precise role of KLH in patients with CIS.

Adjuvants, Immunologic↗

"Difficult to treat infections" pharmacokinetic and pharmacodynamic factors--a review.

"Difficult to cure infections" are characterized by poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the vegetation, absence of adequate host defense/cellular response. These infections typically include endocarditis, urinary tract infections (infected urinary tract stones), abscesses, infected fibrin clots (septic thromboemboli, haematomas, catheter-related infections) and foreign body infections. Four main aspects are discussed for the influence on human therapy: 1. the kinetics of antibiotic diffusion into vegetations 2. the specificity of some pharmacodynamic aspects and pharmacokinetic regimes 3. fibrin as one of the main constituents associated with infectious processes and 4. synergistical activities of antibiotic combinations on bacterial vegetations.

Anti-Bacterial Agents↗

Sophisticated medical devices as local drug-delivery systems.

The sustained release of antimicrobial substances from catheters, endoprostheses, wound-dressings and arterial grafts may be prudent for the prevention of device-associated infections. The release of heparin, synthetic prostacycline, hirudin and anti-inflammatory dexamethasone and related compounds from stent coatings may further reduce the risk of thrombosis, intimal hyperplasia and the requirement for long-term anticoagulation treatments. The delivery of cytokines and growth factors from wound dressings and bone grafts may accelerate wound healing and implant integration.

Anti-Infective Agents↗

Antimicrobial substances and effects on sessile bacteria.

Biofilms occur in natural aquatic ecosystems and on surfaces of biomaterials. They are generally associated with clinical infections predominantly of prosthetic hip joints, heart valves and catheters. Sessile microorganisms may be intimately associated with each other and to solid substratum through binding to and inclusion into exopolymer matrices on biofilms. The establishment of functional colonies within the exopolymeric matrices generate physico-chemical gradients within biofilms, that modify the metabolism and cell-wall properties of the microorganism. A consequence of biofilm growth is an enhanced microbial resistance to chemical antimicrobial agents and antibiotics. Investigations on the antimicrobial efficacy of antibiotics, antiseptics and antimicrobial heavy ions, however, gave controversial results. No single antimicrobial substance has been developed for the efficient eradication of adherent bacteria. This review elucidates the mechanisms of microbial resistance in biofilms and strategies for the prevention of biofilm development. Pharmacokinetical and pharmacodynamical issues for the screening of biofilm-active drugs are presented. Combinations of antistaphylococcal antibiotics with rifampin may be advantageous for preventing and curing biomaterial infections.

Anti-Bacterial Agents↗

Killing effects of antibiotics and two-fold antimicrobial combinations on proliferating and non growing staphylococci.

Antimicrobial agents are generally tested against bacteria in the log phase of multiplication to produce the maximal bactericidal effect. In case of foreign body infections, bacteria may multiply less optimally. We examined the effects of several classes of lipophilic antistaphylococcal agents to determine their antimicrobial activity towards coagulase-positive and coagulase-negative staphylococci during the non-growing and slowly growing phases. Only two-fold combinations containing rifampicin were bactericidal (3-log kill) against Staphylococcus aureus. This was in contrast to growing bacteria in the log phase, in which a variety of antibiotics produced relevant killing. Concerning the staphylococci examined, antibiotic killing was greatly dependent on the growth rate. Most of the two-fold combinations containing rifampicin showed additive and synergistic antibacterial activity both in growth and stationary states as measured by the killing kinetics. The theoretical and clinical implications of delayed killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are discussed. Antimicrobial combinations including rifampicin and a second lipophilic antistaphylococcal drug may be most promising and appropriate as coating substances for intravascular devices or for clinical application in cases of implant infections.

Anti-Bacterial Agents↗

Microflora-associated defense stimulating factors.

Mucosal surfaces are habitats for the physiological microflora and are closely related to the mucosal immune compartment (mucosa-associated lymphoid tissue, MALT). Recently, considerable evidence has accumulated showing that various members of the physiological microflora liberate low molecular weight substances which, apparently, are essential for the adequate immune response of the host. Antibiotic decontamination (e.g. of the BALB/c mouse gastrointestinal tract) results in a lack of generation of immunopriming microbial substances leading to immunosuppression. Biochemical analysis of the microbial substances revealed reproducible chromatographic fractions which selectively influence maturation, proliferation and activation of mononuclear immune cells.

Animals↗