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PubMed1981

Heterotrophic potentials and hydrocarbon biodegradation potentials of sediment microorganisms within the athabasca oil sands deposit.

Techniques for the enumeration and the determination of the potential activity of disturbed sediment mixed populations at control sites and sites within the Athabasca oil sands formation were applied to August and December samples. These techniques included the determination of general heterotrophic potential for the assimilation and respiration of glutamate, which indicated no oil sand-related changes in the sediments but which indicated a significant seasonal change. Enumeration by epifluorescence direct counts, oil sand hydrocarbon plate counts, and most-probable-number determinations of [C]hexadecane and [C]-naphthalene degraders indicated that only the plate count was sensitive to increased numbers of oil sand-related hydrocarbon-oxidizing microorganisms within the oil sands deposit. Unlike the most probable number determinations of [C]hexadecane and [C]naphthalene degraders, however, the biodegradation potential results of these substrates indicated a significant increase in activity at oil sands sites. These biodegradation potentials also showed a marked seasonal fluctuation. Although the biodegradation potentials and the endogenous hydrocarbon plate counts indicated an oil sand-adapted mixed sediment population, the results of these techniques did not correlate well with the concentrations of bituminous hydrocarbons in the sediments. The results suggest that a general capability for hydrocarbon oxidation exists in the Athabasca River system and that this capability is enhanced within the natural bounds of the Athabasca oil sands.

Journal Article↗

PubMed1989

Survey of the anaerobic biodegradation potential of organic chemicals in digesting sludge.

The degradation potential of 77 organic chemicals under methanogenic conditions was examined with an anaerobic digesting sludge from the United Kingdom. Degradation was assessed in terms of net total gas (CH(4) plus CO(2)) produced, expressed as a percentage of the theoretical production (ThGP). The compounds tested were selected from various chemical groups and included substituted phenols and benzoates, pesticides, phthalic acid esters, homocyclic and heterocyclic ring compounds, glycols, and monosubstituted benzenes. The results obtained were in good agreement with published surveys of biodegradability in U.S. digesting sludges and other methanogenic environments. In general, the presence of chloro or nitro groups inhibited anaerobic gas production, while carboxyl and hydroxyl groups facilitated biodegradation. The relationship between substituent position and susceptibility to methanogenic degradation was compound dependent. The following chemicals were completely degraded (>/=80% ThGP) at a concentration of 50 mg of carbon per liter: phenol, 2-aminophenol, 4-cresol, catechol, sodium benzoate, 4-aminobenzoic acid, 3-chlorobenzoic acid, phthalic acid, ethylene glycol, diethylene glycol, triethylene glycol, sodium stearate, and quinoline. 3-Cresol, 4-chlorobenzoic acid, dimethyl phthalate, and pyridine were partially degraded. Although the remaining chemicals tested were either persistent or toxic, their behavior may differ at more environmentally realistic chemical-to-biomass ratios. Our findings suggest that biodegradability assessments made with sludge from one source can be extrapolated to sludge from another source with a reasonable degree of confidence and should help in predicting the fate of an organic chemical during the anaerobic digestion of sewage sludge.

Journal Article↗

PubMed1989

Biodegradation of Natural and Synthetic Humic Acids by the White Rot Fungus Phanerochaete chrysosporium.

Biodegradation of natural and synthetic (melanoidin) humic acids by Phanerochaete chrysosporium BKM-F 1767 was demonstrated by decolorization in batch culture, reduction in molecular weight, and CO(2) production from labeled melanoidin. This biodegradation occurred during secondary metabolism of the fungus in nitrogen-limited cultures; experimental results suggest that all or a part of the lignin-degrading system of BKM-F 1767 plays a part in biodegradation.

Journal Article↗

PubMed1990

Die-away kinetic analysis of the capacity of epilithic and planktonic bacteria from clean and polluted river water to biodegrade sodium dodecyl sulfate.

The capacities of epilithic and planktonic river bacterial populations to degrade sodium dodecyl sulfate (SDS) in samples taken at two times during 1987 from one clean and four polluted sites in a South Wales river were estimated in die-away tests under simulated environmental conditions. There was a relatively slow disappearance of SDS in die-away tests for both planktonic and epilithic populations taken from the clean source site, as compared with those taken from the downstream polluted sites, for which the rate of biodegradation was accelerated, sometimes after an apparent initial lag period. The kinetic components contributing to the die-away curves were quantified by nonlinear regression analysis in which the experimental data were fitted to a variety of possible kinetic models. All samples except for one from the polluted sites best fitted a model which describes the biodegradation of SDS at concentrations well below its K(m) by bacteria whose growth is exponential and unaffected by the addition of a test substrate. Each sample from the clean source site fitted a different model, but there was generally little or no growth on endogenous carbon. A consideration of the numerical values of constants derived from the modeling of epilithic and planktonic populations from polluted sites indicated clearly that the biodegradative capacity of epilithic bacterial populations towards SDS is more stable than that of planktonic bacterial populations.

Journal Article↗

PubMed1997

Dehalogenation and biodegradation of brominated phenols and benzoic acids under iron-reducing, sulfidogenic, and methanogenic conditions.

The anaerobic biodegradation of monobrominated phenols and benzoic acids by microorganisms enriched from marine and estuarine sediments was determined in the presence of different electron acceptors [i.e., Fe(III), SO4(2-), or HCO3-]. Under all conditions tested, the bromophenol isomers were utilized without a lengthy lag period whereas the bromobenzoate isomers were utilized only after a lag period of 23 to 64 days. 2-Bromophenol was debrominated to phenol, with the subsequent utilization of phenol under all three reducing conditions. Debromination of 3-bromophenol and 4-bromophenol was also observed under sulfidogenic and methanogenic conditions but not under iron-reducing conditions. In the bromobenzoate-degrading cultures, no intermediates were observed under any of the conditions tested. Debromination rates were higher under methanogenic conditions than under sulfate-reducing or iron-reducing conditions. The stoichiometric reduction of sulfate or Fe(III) and the utilization of bromophenols and phenol indicated that biodegradation was coupled to sulfate or iron reduction, respectively. The production of phenol as a transient intermediate demonstrates that reductive dehalogenation is the initial step in the biodegradation of bromophenols under iron- and sulfate-reducing conditions.

Bromobenzoates↗

PubMed2001

Hepatic tissue engineering on 3-dimensional biodegradable polymers within a pulsatile flow bioreactor.

BACKGROUND: An optimal method for hepatocyte transplantation is not yet determined. With the principles of tissue engineering in vitro conditioning of hepatocytes on biodegradable polymer in a flow bioreactor before implantation forming spheroids may achieve increased cell mass and function to replace lost organ function in vivo. METHODS: Biodegradable poly-L-lactic (PLLA) polymer discs were seeded with rat hepatocytes in a concentration of 10 x 10(6) cells per ml and exposed to a medium flow of 24 ml/min for 1, 2, 4 and 6 days. The number and diameter of spheroidal aggregates was measured by phase-contrast microscopy. H&E histology was performed. Albumin production as hepatocyte specific function was determined by ELISA. RESULTS: Spheroids of viable hepatocytes of 50-200 microm in diameter were formed. Both the number and diameter of the spheroids increased during the first 2 days and then remained constant until day 6. Albumin production was maintained throughout the culture period. CONCLUSION: Short (2- 3 days) pre-transplant conditioning of hepatocytes in a flow bioreactor on biodegradable PLLA resulted in formation of spheroids with a liver-like morphology and preserved specific metabolic function. Tissue engineered hepatocyte spheroids on polymer may represent a functionally active and easy transplantable neotissue and may serve as an in vivo substitute for lost liver function.

Albumins↗

PubMed2001

A trial to prepare biodegradable collagen-hydroxyapatite composites for bone repair.

This paper is a trial to prepare collagen-hydroxyapatite composites in vitro by an alternate immersion method. Collagen sponges of different biodegradabilities were prepared through chemical cross-linking of Type I collagen with glutaraldehyde (GA) at concentrations of 0.2, 1.0, and 2.0 wt%. The sponges were immersed at 37 degrees C in Tris-HCl-buffered solution containing 200 mM CaCl2 (pH 7.4) for 2 h and then in an aqueous solution of 120 mM Na2HPO4 (pH 9.3) for a 2 h further (one immersion cycle). The alternate immersion cycle was repeated for different times to obtain collagen-hydroxyapatite composites. The characterization of the resulting composites was performed by Fourier transform infrared spectroscopy (FT-IR). X-ray diffraction (XRD), and scanning electron microscopy (SEM). The weight of composites increased with an increase in immersion cycles and the rate of increase became greater with higher GA cross-linking levels for collagen sponge preparation. The pH of the phosphate solution decreased with the immersion cycle, which suggests H+ generation accompanied hydroxyapatite formation. Irrespective of the GA concentration and immersion cycle, every composite showed IR absorption bands attributable to phosphate and hydroxyl groups at 950-1100 or 550-650 and 3000-3500 cm(-1) and broad peaks specific to hydroxyapatite on the XRD charts. SEM study revealed small white clusters of hydroxyapatite interspersed uniformly on/in the collagen framework without any preferential orientation. The composite prepared from 0.2 wt% GA cross-linked collagen sponge which showed favourable characteristics was applied to a rat skull defect to evaluate its osteoconductivity as well as biodegradability. The formation of new bone tissue was histologically observed at the defect 12 weeks after application in marked contrast to the collagen sponge alone. The composite degraded without any inflammation reaction. It is concluded that the collagen-hydroxyapatite composite prepared by the present method is a biodegradable biomaterial of osteoconductivity applicable to bone repair.

Animals↗

PubMed2005

A microfabrication method of a biodegradable polymer chip for a controlled release system.

A simple microfabrication method for a controlled-release drug-delivery system has been designed using biodegradable polymeric microchips. Microholes were made in a poly(L-lactic acid) plate and dyes were cast in each well. After drying, the wells were sealed with polymers having different biodegradation rates using a mold that had hollows corresponding to the wells. The polymers were prepared by mixing polylactides with the co-polymers. The sealing was confirmed by ultrasonication. The plate was incubated in phosphate-buffered saline and the dye released from the plate as the degradation proceeded was detected spectrophotometrically. The higher the degradation rate of the polymer sealing, the faster the sealed dye was released. This biodegradable biochip is useful for the design of controlled-release drug-delivery systems.

Biocompatible Materials↗

PubMedDate not supplied

Comparison of initial fixation strength between biodegradable and metallic interference screws and a press-fit fixation technique in a porcine model.

The objective of this study was to evaluate the initial fixation strength of a biodegradable interference screw compared with press-fit fixation and a titanium interference screw in anterior cruciate ligament reconstruction using a bone-patellar tendon-bone graft. Porcine lower limbs were used. The specimens underwent 500 loading cycles between 60 and 250 N. This corresponds to loads in the graft during aggressive rehabilitation. Thereafter, intact specimens were loaded to failure. Failure mode was defined by visual analysis. Under cyclic loads none of the interference screw fixations failed. In the press-fit group (angle between load axis and tunnel axis 80 degrees), five specimens failed. The mean maximal load to failure was 945 N (+/- 87) for the titanium screw, 797 N (+/- 60) for the biodegradable screw, and 708 N (+/- 211) for the five press-fit specimens that did not fail during cyclic loading. With respect to primary fixation strength, biodegradable screws are a reasonable alternative to titanium interference screws. The press-fit fixation did not provide a secure fixation in all cases. Five press-fit specimens failed under cyclic loads comparable with those seen under conditions of accelerated rehabilitation.

Absorbable Implants↗

PubMed2000

Evaluation of the regenerative effect of a 25% doxycycline-loaded biodegradable membrane for guided tissue regeneration.

BACKGROUND: Biodegradable materials have been successfully utilized for guided tissue regeneration (GTR) and local delivery systems (LDS) because they are biocompatible, less cytotoxic, and do not require removal. Several studies have demonstrated that tetracyclines (TCs), when applied topically, stimulated osteogenesis in experimental bone defects. The purpose of this study was to evaluate the regenerative effect of a 25% doxycycline-loaded biodegradable GTR membrane (Doxy-M) in dogs. METHODS: Doxy-M was made by coating the inner surface of a biodegradable membrane (BD-M) with 25% doxycycline. Five male mongrel dogs with 20 created osseous defects were enrolled. The plain BD-M was used as the control membrane. Either Doxy-M or BD-M was applied in 20 randomly selected defects (10 Doxy-M, 10 BD-M) for 12 weeks with the GTR technique. The histometric analysis was evaluated with the following parameters: defect height (DH), apical extension of junctional epithelium (AEJP), new cementum height (NCH), new bone height (NBH), and new bone area (NBA). RESULTS: The Doxy-M-treated defects showed more pronounced new bone formation and less crestal bone resorption than the BD-M-treated defects. There were no statistically significant differences between the two groups in DH, AEJP, and NCH. Statistically significantly larger NBH (P <0.05) and NBA (P<0.005) were seen in the Doxy-M-treated defects. CONCLUSIONS: The results strongly suggest that Doxy-M may have a beneficial effect on osteogenesis to favor periodontal regeneration.

Absorbable Implants↗

PubMed2001

Polydioxanone biodegradable pins in the knee: MR imaging.

OBJECTIVE: Biodegradable solid implants have been developed as an alternative to metallic orthopedic fixation. In animal models, implants degrade within and are replaced by bone. This study documents the resorption of these devices in human patients with MR imaging. SUBJECTS AND METHODS: One hundred seventy-five 1.3-mm biodegradable pins made of polydioxanone were used to secure a total of 59 osteochondral allografts of the knee. Patients with the pins underwent scanning on a 1.5-T unit with 3.3- to 4-mm contiguous T1-weighted spin-echo (TR/TE, 600/15), fat-saturated proton density-weighted (3000/40), T2-weighted fast spin-echo (3000/63), and three-dimensional spoiled gradient-recalled (47/7; flip angle, 60 degrees ) sequences at 3, 6, 12, 24, or 36 months after surgery. Eighty-nine pins were imaged on multiple occasions. Two osteoradiologists interpreted the MR examinations. RESULTS: More than 80% of the pin channels were visible at 3 and at 6 months after surgery. By 24 months, only 20% of the pin channels were visible, with the remainder having been replaced by bone. At 3 months, nearly 40% of the pins were associated with adjacent marrow edema. Edema generally diminished, involving less than 20% of pins at later time points. Focal cartilage defects were evident at 32% of the pin insertion sites during the first 6 months, but these defects were present in only 4% of the insertion sites thereafter. CONCLUSION: Biodegradable polydioxanone pins usually resorb completely by 24 months. Marrow edema, presumably representing inflammation related to pin resorption, is infrequent and tends to resolve. Cartilage defects related to pin placement heal spontaneously.

Absorbable Implants↗

PubMed2000

Site-specific administration of antisense oligonucleotides using biodegradable polymer microspheres provides sustained delivery and improved subcellular biodistribution in the neostriatum of the rat brain.

Antisense oligonucleotides (ODNs) are being increasingly used in the central nervous system as biological tools, as drug-target validation agents and as potential therapeutic agents. Although the local delivery of naked ODNs to the brain can result in the desired biological effects, the duration of efficacy is relatively short lived due to the combined effects of rapid ODN degradation and elimination half-lives in vivo. In this study, we have examined the use of biodegradable polymer microspheres as a site-specific delivery system for targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide) (PLAGA) microspheres using a double emulsion-deposition method and the formulations characterised in terms of particle size, surface morphology, percent encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo-taxically administered to the neostriatum of the rat brain and biodistribution of ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to the neostriatum resulted in a punctate cellular distribution of ODNs after 24 h with little or no ODN remaining in the neostriatum after 48 h. In comparison, fluorescently-labelled ODNs delivered using polymer microspheres were intensely visible in cells after 48 h post-administration and the fluorescence appeared to be diffuse covering both cytosolic and nuclear regions. Dual-label immunohistochemical analyses suggested that ODNs were mainly distributed to neuronal cells. These data indicate that site-specific administration of ODNs using biodegradable polymer microspheres will not only provide sustained delivery of nucleic acids but can also improve the cellular distribution of ODNs to brain cells. Sustained or controlled-release biodegradable polymer formulations, therefore, represent an attractive strategy for improved local delivery of ODNs to the CNS.

Animals↗

PubMed1998

Development of a sustained-release biodegradable polymer delivery system for site-specific delivery of oligonucleotides: characterization of P(LA-GA) copolymer microspheres in vitro.

Development of a Sustained-Release Biodegradable Polymer Delivery System for Site-Specific Delivery of Oligonucleotides: Characterization of P(LA-GA) Copolymer Microspheres In Vitro Antisense oligodeoxynucleotides (ODNs) can selectively inhibit individual gene expression provided they gain access to and remain stable at the target site for a sufficient period of time. Biodegradable sustained-release delivery systems may facilitate site-specific delivery and also prevent degradation of ODNs by nucleases whilst delivering the nucleic acid in a controlled manner to the desired site of action. In this study, we have characterized biodegradable poly (lactide-co-glycolide) (P(LA-GA)) 50:50 microspheres for the potential delivery of antisense oligonucleotides in vivo. Phosphodiester (PO) oligonucleotides complementary to either c-myc proto-oncogene or the tat gene in HIV-RNA were adequately incorporated within P(LA-GA) microspheres with entrapment efficiencies up to 60% depending on particles size. In vitro release profiles of antisense nucleic acids from 10-20 microm size microspheres over 56 days in physiological buffer were triphasic. Profiles were characterised by an initial burst effect during the first 48 hours (phase 1) of release followed by a more sustained release (phase 2) with an additional increased release (phase 3) being observed after 25 days which corresponded with bulk degradation of the copolymer matrix. The release profiles were influenced by microsphere size, copolymer molecular weight, ODN loading, ODN length and by the pH of release medium used. The serum stability of PO ODNs was significantly improved when entrapped within P(LA-GA) microspheres and the hybridization capability, as assessed by duplex melting (Tm) measurements, of released ODN was not impaired by the double-emulsion microsphere fabrication procedure used. Thus, P(LA-GA) microspheres appear to be promising candidates for improving site-specific delivery profiles for ODNs and are worthy of further evaluation in vivo.

Base Sequence↗

PubMed1999

Biodegradable dental implants of ciprofloxacin beta-cyclodextrin inclusion complex in the treatment of periodontitis.

Dental implants of ciprofloxacin beta-cyclodextrin inclusion complex were formulated using poly (epsilon-caprolactone), a biodegradable polymer and evaluated. Clinical evaluation was carried out in ten patients with acute peridontitis. Various clinical parameters, viz. gingival index, plaque score, attachment gain, reduction in pocket depth were evaluated at 10, 20, 30, 40 days of treatment and compared with placebo as control. A significant (P < 0.0001) improvement in the healing of periodontal pockets treated with ciprofloxacin beta-cyclodextrin implant was observed in most of the clinical parameters. Estimation of gingival crevicular fluids (GCF) for the drug content revealed that drug levels above the minimum inhibitory concentration (10.2 micrograms/mg) for many of the periodontal pathogens were maintained throughout the period of study (40 days). This confirms the clinical efficacy of the dose and the duration of the study. It was found that biodegradable carrier was better accepted than the non-biodegradable carriers reported earlier.

Adult↗

PubMed2000

Concentration of ofloxacin in canine prostate tissue and prostate fluid after intraprostatic injection of biodegradable sustained-releasing microspheres containing ofloxacin.

PURPOSE: Excellent treatment results in chronic prostatitis by direct intra-prostatic injection of antibiotic were reported several decades ago with only minimal scientific background. We examined the distribution, in prostatic tissue and fluid, of the antibiotic in canines after intra-prostatic injection of biodegradable sustained-releasing microspheres containing 12 mg. of ofloxacin. MATERIALS AND METHODS: A total of 36 male dogs, 12 controls and 24 experimental, older than 2 years, were used. Experimental dogs were given biodegradable sustained releasing microspheres containing ofloxacin 12 mg. and poly(D,L-lactic) acid 28 mg., designed to release over more than a 4 week period. The 12 control animals were divided into 2 groups, and oral ofloxacin 100 mg. was given twice a day for 2 and 4 weeks. The 24 experimental animals were divided into 4 subgroups of 6 dogs each, 4 for prostatic tissue and 2 for prostatic fluid level of ofloxacin determination. Anesthesia was initiated with ketamine HCl and xylazine, and maintained with intermittent ketamine HCl. In the experimental groups, 1 ml. of resolved formula was injected into one lobe of surgically exposed prostates. The concentration of ofloxacin was measured by high performance liquid chromatography (HPLC) of blood, prostatic tissue and prostatic fluid. Pilocarpine 0.5 mg./kg. was used for the collection of the prostatic fluid. RESULTS: The total ofloxacin of controls were 2,800 (2 weeks) and 5,600 (4 weeks) mg. In control groups, tissue concentrations of ofloxacin were relatively even at all segments of prostate, 7.4 +/- 0.8 (2 weeks) and 9.2 +/- 1.1 microg./ml. (4 weeks). The blood level ranged between 3.6 to 5.1 microg./ml. The prostatic fluid level ranged from 3.1 to 5.7 microg. /ml. In the experimental groups, the tissue levels of ofloxacin were 10.5 +/- 3.0 (1 week), 13.8 +/- 4.5 (2 weeks), 7.1 +/- 0.9 (3 weeks) and 7.7 +/- 3.0 microg./ml. (4 weeks) in the injected lobe. The opposite lobes were 8.0 +/- 1.1 (1 week), 10.2 +/- 4.2 (2 weeks), 5. 1 +/- 1.4 (3 weeks) and 7.6 +/- 0.8 (4 weeks) microg./ml. The blood level in the experimental groups ranged between 0.16 to 0.59 microg./ml. The prostate fluid level ranged from 2.9 to 6.1 microg./ml. in 8 dogs. Upon pathologic examination, the microspheres were interposed between prostate stroma and their size was reduced over time. CONCLUSIONS: Our study indicates that there is communication between the right and left prostate lobes. Direct injection of biodegradable sustained releasing ofloxacin formula into the prostate may be a substitute for long term antibiotic medication in humans for chronic prostatitis in the future without hurting the minimal inhibitory concentration(MIC)90.

Animals↗

PubMed2001

Biodegradable interference screw augmentation reduces tunnel expansion after ACL reconstruction.

This study assessed 40 patients who underwent anterior cruciate ligament reconstruction with hamstring autografts using our standard technique. Twenty patients underwent tibial fixation augmentation with a biodegradable interference screw, and the remaining 20 patients did not. Patient groups were compared using radiographic evaluation of bone tunnel diameter, physical examination, and arthrometer measurements. The two groups differed in only one way: the placement of the tibial biodegradable interference screw. Biodegradable interference screw augmentation resulted in decreased distal tibial and some femoral tunnel diameters at both 3- and 12-month follow-up. There was no significant difference in the Lachman and arthrometer testing in either group of patients at the termination of this study. These results indicate that although distal tibia tunnel diameter reduction is significant, it does not appear to have any clinical significance in the first year.

Absorbable Implants↗

PubMed2004

[Development of biodegradable and bioabsorbable bone-repaired materials].

This paper reviews recent work on biodegradable and bioabsorbable materials, including macromolecular, inorganic, and compound materials which have been used as bone-repaired devices. The properties and uses of poly(lactic acid), chitin and tricalcium phosphate are expounded. At the same time, we discuss the trend in the development of biodegradable and bioabsorbable bone-repaired materials. In our opinion, the development of biodegradable and bioabsorbable bone-repaired materials forcuses on the composite of different materials, especially the composite of BMP and MSCs; on the improvement of the mechanical properties of materials; and on the search for new suitable materials.

Absorbable Implants↗

PubMed2004

[Treatment of recurrent malignant brain gliomas by surgical excision combined with biodegradable polymers of interstitial chemotherapy].

OBJECTIVE: To investigate the effectiveness of treatment of recurrent malignant brain gliomas by surgical excision combined with biodegradable polymers of interstitial chemotherapy. METHODS: In 30 patients with recurrent malignant brain gliomas, the tumor was surgically removed and Vp-16 biodegradable polymers were implanted during operation in the tumor bed at a dose of 100 - 150 mg. The patients were followed up for 3 - 24 months, and the results were compared with 46 cases with the recurrent malignant brain gliomas who received operation only. RESULTS: At 3, 6, 12, 24 months after treatment, the recurrent rate was 16.7%, 30%, 50% and 83.3%, respectively; the mortality rate was 6.67%, 20%, 40% and 70%, respectively. All the patients had no apparent side-effects of chemotherapy. CONCLUSION: Surgical treatment combined with interstitial chemotherapy with biodegradable Vp-16 polymers improves the treatment result of recurrent malignant brain gliomas compared to surgery alone.

Adult↗