Search PubMedSearch

Biomedical subjects

J Kohn

Publications and source records attributed to J Kohn.

At least 19 recordsLinked to original sources

Assessment of the neurotoxicity of styrene, styrene oxide, and styrene glycol in primary cultures of motor and sensory neurons.

The neurotoxicity of styrene and its major metabolites, styrene oxide and styrene glycol, was investigated in dissociated primary cultures of murine spinal cord-dorsal root ganglia (DRG)-skeletal muscle using morphological and electrophysiological endpoints. Styrene and styrene oxide (but not styrene glycol) were acutely cytotoxic to both neuronal and non-neuronal cells in the cultures; concentrations in excess of 2 and 0.2 mM, respectively, induced blebbing, vacuolation, detachment from the substratum and cell death in neuronal and non-neuronal cells within 4 days. No effects on neuronal morphology were observed in cultures treated with sublethal concentrations of styrene or styrene oxide for up to 3 weeks. The results suggest that oxidation of multiple cellular macromolecules that underlies the toxicity of styrene in other organ systems may also be responsible for damage to cells in the nervous system. No changes in action potential production indicative of a 'solvent effect' on membrane electrical properties was apparent in cultures treated with up to 8 mM styrene or 10 mM styrene glycol.

Animals

Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials.

A series of four polycarbonates derived from the ethyl, butyl, hexyl, and octyl esters of desaminotyrosyl-tyrosine was prepared by condensation polymerization. The resulting polymers had weight average molecular weights ranging from 120,000-450,000, and their chemical structure was confirmed by elemental analysis, nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The polycarbonates were evaluated as degradable biomaterials. Their surface properties were determined by electron spectroscopy for chemical analysis, attenuated total reflectance-Fourier transformed infrared spectroscopy, and contact angle measurement. The degree of surface hydrophobicity was related to the length of the alkyl ester pendent chain. The tensile properties were dependent on the chemical structure of the polymers: For thin, solvent cast film specimens, the tensile modulus varied from 1.2-1.6 GPa, and the strength at break from 60-220 MPa. The degradation of polymeric films was followed in vitro by measuring changes in mechanical strength for up to 40 weeks, and the decrease in molecular weight and changes in surface chemistry for up to 80 weeks. The length of the pendent chain affected the degradation behavior and strength retention; the polymers with short pendent chains were more readily hydrolyzable. For sterilization, ethylene oxide treatment was less destructive, as judged by molecular weight retention, than gamma-irradiation. Spin-cast films of all tested polycarbonates were not cytotoxic toward cultured rat lung fibroblasts. The cell response was influenced by the chemical structure of the polymer. The least hydrophobic polycarbonate (having a short ethyl ester pendent chain) was a more stimulating substrate for cell growth than the more hydrophobic polymers (carrying longer alkyl ester pendent chains).

Animals

Detection of cleft lip by early second-trimester transvaginal sonography.

OBJECTIVE: To describe the detection of cleft lip in the early second trimester using transvaginal sonography. METHODS: We analyzed retrospectively 14,988 ultrasound examinations conducted for fetal malformations between 12-16 weeks' gestation. Seventy-five percent of the patients were at low risk for fetal anomalies and 25% were at high risk. RESULTS: Eleven cases of fetal cleft lip with or without cleft palate were detected by transvaginal sonography among 14,988 fetuses (0.07%). In nine cases, no risk factors for cleft lip or palate existed. In six cases, the cleft lip represented an isolated malformation, with no other associated anomaly; in five of these six cases, the pregnancy was terminated. One additional case of a small cleft lip was not detected, for a false-negative rate of 8%. CONCLUSIONS: The fetal lips can be scanned by transvaginal sonography in the early second trimester, and fetal cleft lip can be detected in most cases. Early second-trimester detection of cleft lip by transvaginal sonography allows informed parental choice regarding continuing or terminating the affected pregnancy.

Abnormalities, Multiple

Tyrosine-derived polycarbonates: backbone-modified "pseudo"-poly (amino acids) designed for biomedical applications.

Starting from L-tyrosine (Tyr) and its metabolites desaminotyrosine (Dat) and tyramine (Tym), four structurally related model dipeptides were prepared: Dat-Tym (neither N- or C-terminus present), Z-Tyr-Tym (N-terminus protected by benzyloxycarbonyl), Dat-Tyr-Hex (C-terminus protected by a hexyl ester group), and Z-Tyr-Tyr-Hex (both N- and C-termini present, protected by benzyloxycarbonyl and hexyl ester, respectively). The model dipeptides were used as monomers in the synthesis of polycarbonates. The polymerization reaction in the presence of either phosgene or triphosgene proceeded via the phenolic hydroxyl groups. Polymers with molecular weights of 105,000-400,000 da (by gel permeation chromatography, relative to polystyrene standards) were obtained. The physicomechanical properties (solubility, mechanical strength, glass transition and decomposition temperature, processibility) of the polymers were determined, and an attempt was made to correlate the polymer properties with the nature of the N- and C-terminus protecting groups. The presence of the urethane bond at the N-terminus protecting group was found to reduce solubility, ductility, and processibility, probably due to interchain hydrogen bonding. The presence of a C-terminus alkyl ester group increased solubility and processibility. Thus, the most promising candidate polymer for biomedical applications was obtained from Dat-Tyr-Hex, the monomer carrying a C-terminus protecting group only. Since very similar results had recently been obtained for a series of structurally related polyiminocarbonates, the structure property correlations seem to be generally valid.

Carbonates

Trends in the development of bioresorbable polymers for medical applications.

The gradual shift from biostable prostheses to degradable, temporary implants represents one of the most significant trends in biomaterials research. In view of this trend, medical applications of degradable implant materials were reviewed with special emphasis on orthopedic polymeric implants. Among the polymeric implant materials derived from natural sources, collagen, various polysaccharides such as cellulose, and microbial polyesters have been intensively investigated. Among the synthetic, degradable polymers, aliphatic polyesters such as poly(glycolic acid), poly(lactic acid), poly(caprolactone) and polydioxanone, are most commonly investigated. Only recently, several new classes of polymers such as poly(ortho esters), polyanhydrides, and degradable polycarbonates have been introduced as potential implant materials. A particularly versatile group of new biomaterials with promising engineering properties are the "pseudo"-poly(amino acids), amino acid derived polymers in which conventional peptide bonds have been replaced by various chemical linkages.

Absorption

Physico-mechanical properties of degradable polymers used in medical applications: a comparative study.

The physico-mechanical properties of degradable polymers used for medical applications have been characterized. The following polymers were included in this study: three samples of poly(ortho esters) derived from 3,9-bis(ethylidene 2,4,8,10-tetraoxaspiro[5,5]undecane) and various ratios of 1,6-hexanediol and trans-cyclohexane dimethanol, poly(glycolic acid), six samples of poly(L-lactic acid) and poly(D,L-lactic acid) with mol wt from 21,000 to 550,000, poly(epsilon-caprolactone), poly(beta-hydroxybutyrate) and three copolymers of beta-hydroxybutyric acid and various amounts of hydroxyvaleric acid, one sample each of two different types of poly(anhydrides), poly(trimethylene carbonate) and two different poly(imino-carbonates). For each polymer, the thermal properties (glass transition temperature, crystallization, melting and decomposition points) were determined by differential scanning calorimetry and by thermogravimetric analysis. The tensile properties (Young's modulus, tensile strength and elongation at yield and break) were determined by tensile testing on an Instron stress-strain tester. The flexural storage modulus as a function of temperature was determined by dynamic mechanical analysis.

Anhydrides

Patient factors and the influence of nephrologists, social workers, and nurses on patient decisions to choose continuous peritoneal dialysis.

To determine which members of the health care team are viewed by ESRD patients as the most helpful in giving information and deciding on a dialysis modality, we surveyed 42 outpatients after they toured the dialysis facility. The tour included discussions with a social worker, PD and HD nurses, watching a videotape, and receipt of written materials. Nephrologists referred patients for tours. Multiple responses were accepted. Patients felt that social workers (70%) and nurses (71%) gave the most useful information. Fifty per cent of patients thought the nurse, 43% the social worker, 21% the nephrologist, and 21% family or friend most helpful in deciding on PD versus HD. Twenty-three patients chose PD, 16 chose in-center HD. Patients choosing PD were more likely to be white (20/29 versus 3/10, p less than 0.05) and employed (11/23 versus 3/16 choosing HD, p less than 0.10). Patients choosing PD were also better educated but this was not independent of race. No differences in gender, age, or the presence of diabetes were seen among those choosing PD versus HD. Social workers and nurses are more influential than nephrologists in helping patients select a dialysis modality. PD patient recruitment efforts should focus on social workers' and nurses' input.

Decision Making

Structure-property relationships for the design of polyiminocarbonates.

Structure-property relationships for the design of new polyiminocarbonates were established, based on the investigation of thermal stability and processibility, morphology, tensile strength, hydrolytic degradation and drug release profiles of 15 different polyiminocarbonates. The results indicated that some polyiminocarbonates were among the mechanically strongest, bioerodible polymers currently available. The iminocarbonate bond was highly unstable under physiological conditions, facilitating the design of rapidly degrading devices. The drug-release profiles of certain polyiminocarbonates exhibited lag periods, facilitating the design of pulsed-release or delayed-release devices. Possible limitations of the practical applicability of polyiminocarbonates as biomaterials were the low thermal stability of the iminocarbonate linkage and the complicated, two-phase degradation mechanism that led to the formation of slowly degrading residues of low molecular weight. To identify non-toxic diphenols as monomers for the synthesis of polyiminocarbonates, derivatives of tyrosine dipeptide were systematically explored. Using structure-property relationships as design guidelines, desaminotyrosyl-tyrosine hexyl ester was identified as a promising, tyrosine-derived diphenol. The corresponding poly(desaminotyrosyl-tyrosine hexyl ester iminocarbonate) formed amorphous, transparent films and was mouldable at about 70 degrees C. It had a tensile strength of 400 kg/cm2 and a tensile modulus of 16,300 kg/cm2. Under physiological conditions in vitro, a thin film made of high molecular weight poly(desaminotyrosyl-tyrosine hexyl ester iminocarbonate) degraded to low molecular weight oligomers within 5 d. The results indicated that polyiminocarbonates and in particular poly(desaminotyrosyl-tyrosine hexyl ester iminocarbonate) might be of interest in a variety of biomedical applications.

Animals

Single-step immunization using a controlled release, biodegradable polymer with sustained adjuvant activity.

The use of a biodegradable polymer for antigen delivery based on poly(CTTH-iminocarbonate) (IUPAC nomenclature: poly[oxyimidocarbonyloxy-p-phenylene [2-(hexyloxycarbonyl)ethylene]imino[2-[1-(benzyloxy)formamido]- 1-oxotrimethylene]-p-phenylene]) was investigated. This polymer was selected since its primary degradation product, N-benzyloxycarbonyl-L-tyrosyl-L-tyrosine hexyl ester (CTTH) was found to be as potent an adjuvant as complete Freund's adjuvant and muramyl dipeptide, when measuring the serum antibody response to bovine serum albumin (BSA) in male CD-1 mice over 56 weeks. BSA released from subcutaneously implanted polymeric antigen delivery devices made of poly(CTTH-iminocarbonate) resulted in significantly higher (P less than 0.006) anti-BSA antibody titers than devices made of poly(bisphenol A-iminocarbonate).

Adjuvants, Immunologic

Poly(iminocarbonates) as potential biomaterials.

Poly(iminocarbonates), based on diphenols such as hydroquinone or Bisphenol A were synthesized. Poly(iminocarbonates) degraded under physiological conditions. Compression moulded discs of poly-(hydroquinone-iminocarbonate) showed near zero-order release for low loadings (1%, w/w) of Eosin Y. Poly(Bisphenol A-iminocarbonate) formed transparent films and strong fibres. It is a tough polymer with high tensile strength. Under physiological conditions complete erosion of a thin film of poly(Bisphenol A-iminocarbonate) required about 200 d. The release profile for p-nitroaniline from solvent cast films of poly(Bisphenol A-iminocarbonate) was characterized by a lag period (20 d), followed by near zero-order release for 90 d. Initial toxicological studies revealed no inflammatory cell response after implantation in the corneas of rabbits or subcutaneously in mice.

Animals