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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 91 records · Page 5Linked to original sources

Rationally and empirically derived dimensions of children's symptomatology: expert ratings and confirmatory factor analyses of the CBCL.

Expert ratings and confirmatory factor analyses were used to develop an alternative system for scoring the Child Behavior Checklist (CBCL; T. M. Achenbach, 1991) to measure specific dimensions corresponding to current conceptualizations of child symptomatology. Data were from a nonclinic and 2 independent clinic samples. Subscales measuring Anxiety, Attention Problems/Hyperactivity, Conduct Problems, Depression, Oppositional Defiant, Social Problems/Immaturity, and Somatization were created. Logistic regressions were conducted to evaluate the diagnostic efficiency and discrimination of the new and original approaches to scoring the CBCL. Some of the new subscales demonstrated better sensitivity, positive predictive power, and discriminant validity than the original CBCL subscales; however, subscales from both approaches demonstrated low sensitivity. Results support the use of the new subscales for specific research purposes.

Adolescent↗

The wear of oriented UHMWPE under isotropically rough and scratched counterface test conditions.

Unidirectional wear tests of UHMWPE against smooth counterfaces show that molecular chains at the surface of virgin material become oriented parallel to the sliding direction giving low wear rate. It is postulated that under more abrasive conditions and predominantly unidirectional motion as in knee prostheses, it may proof beneficial to provide molecular orientation of the bulk material. Therefore strips of UHMWPE were oriented by die drawing at elevated temperature and the resulting anisotropic material subjected to tensile tests, small punch tests and also unidirectional wear tests both parallel and perpendicular to the draw direction. The tensile tests showed that, in the parallel direction, the oriented UHMWPE became stiffer and less ductile compared to the virgin UHMWPE. In the perpendicular direction, there were reductions in yield stress, 5% proof stress and energy to failure compared to the virgin material. The small punch test showed that the oriented UHMWPE exhibited apparent hardening when tested in both parallel and perpendicular directions but the mechanical behaviour in the perpendicular direction was comparable to the virgin UHMWPE. The wear tests demonstrated that the oriented UHMWPE did not show any significant improvement of wear resistance for sliding against either isotropically rough or scratched counterfaces. There was no clear dependency between the mechanical properties and wear factors of the oriented UHMWPE.

Biocompatible Materials↗

Trisomy 12 mosaicism confirmed in multiple organs from a liveborn child.

This patient, in whom trisomy 12 mosaicism was confirmed in multiple organs, is the fifth case diagnosed postnatally and the first reported for whom a meiotic origin of the trisomy, maternal meiosis I, was determined. Mosaic aneuploidy was suspected because of pigmentary dysplasia, a frequent but non-specific finding in chromosomal mosaicism. The severe phenotype of this child, who died in infancy with a complex heart malformation, was probably a result of the high percentage of trisomic cells. Cytogenetic and interphase fluorescent in situ hybridization analyses showed a highly variable distribution of aneuploid cells in the nine tissues studied, from none in blood and ovary to 100% in spleen and liver. The trisomy arose meiotically with apparent post-zygotic loss of one of the chromosomes 12; uniparental disomy for this chromosome in the diploid cell line was excluded. The phenotype of the cases reported in living or liveborn individuals has been extremely variable, ranging from the present case, in which the child died in infancy with multiple malformations and pigmentary dysplasia, to a fortuitous finding in an adult studied for infertility. The variation in severity is probably determined by the proportion and distribution of the trisomic cells, which is linked to the timing of the non-disjunctional error.

Abnormalities, Multiple↗

Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13.

PURPOSE: To determine if Biafine compared to Best Supportive Care (BSC) is effective in minimizing or preventing radiation-induced dermatitis in women undergoing breast irradiation. METHODS AND MATERIALS: Patients were randomized between Biafine (n = 83) vs. BSC (n = 89). The institutions identified preference for BSC at the time of randomization. A no-treatment arm was allowed (16% received no treatment). Patients were instructed to apply randomized product three times a day, but not within 4 h of their daily RT session. Application began following their first radiation treatment and continued 2 weeks postradiation. Skin dermatitis was scored weekly utilizing the RTOG and ONS (Oncology Nursing Society) skin toxicity scales, a weekly patient satisfaction and quality-of-life questionnaire. RESULTS: Using the RTOG toxicity scale there was no overall difference for maximum dermatitis during RT between Biafine and BSC (p = 0.77). There was no difference in maximum toxicity by arm or breast size. There was an interaction between breast size and toxicity, with large-breasted women exhibiting more toxicity. Large-breasted women receiving Biafine were more likely to have no toxicity 6 weeks post RT. CONCLUSION: There was no overall difference between BSC and Biafine in the prevention, time to, or duration of radiation-induced dermatitis.

Adult↗

Lewis A. Conner: Cornell's Osler.

Lewis A. Conner, MD (1867 to 1950), was a pioneer in public health cardiology, cardiac rehabilitation, and cardiac psychology. He helped establish the Burke Rehabilitation Hospital and was the founding president of the New York and American Heart Associations (AHA). Dr Conner was the founder of the American Heart Journal, America's first medical subspecialty journal, and the official publication of the American Heart Association until 1950, when CIRCULATION: was created. Conner spent more than a half-century on the staff of the New York Hospital and Cornell University Medical College and was Chairman of Medicine from 1916 to 1932. During this time, he created the innovative Cornell Pay Clinic and united the "old" New York Hospital with the new and scientifically-oriented Cornell University Medical College on a modern and inspiring urban campus. An extraordinary clinician and a humanist with great equanimity, Conner devoted his career to the Oslerian tradition of scholarship, leadership, and organization in the quest for improved patient care. This article contains newly discovered biographic material on Dr Conner and explores his professional and personal connection to Sir William Osler.

Cardiology↗

[Mitral valve repair in ischemic cardiomyopathy with severe left ventricular dysfunction].

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass. There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II. Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Aged↗

Cation-exchange high-performance liquid chromatography of recombinant adeno-associated virus type 2.

There has been much interest recently in the development of recombinant viruses as vectors for gene therapy applications. We have constructed a recombinant adeno-associated viral (AAV) vector containing the gene encoding CFTR (cystic fibrosis transmembrane chloride regulator). This vector is currently being used in clinical trials as a treatment for cystic fibrosis. In the course of scale-up and process optimization efforts, a variety of analyses have been developed to characterize yield and quality. Although these methods produce quantitative and highly reproducible results, most are very time intensive. For example, a standard bioassay requires a 72-h incubation period followed by an additional day of analysis. Other tests such as UV spectrophotometry are fast, but unable to distinguish between whole virus, free protein, and DNA. Here, we describe an analytical cation-exchange high-performance liquid chromatographic method utilizing a TSKgel SP-NPR strong cation-exchange column. Unlike the bioassay which requires a 96-h wait for information, this method yields data in less than 20 min. In addition to the quick assay turn-around, the material eluting in the single peak was found to be intact, infectious, nuclease resistant AAV particles. This offers a significant advantage over the limited information one gains from UV spectrophotometry. This demonstrates the utility of chromatography for analysis and purification of viral vectors.

Blotting, Western↗

Effect of size and dose on bone resorption activity of macrophages by in vitro clinically relevant ultra high molecular weight polyethylene particles.

Polyethylene wear debris generated at the bearing surfaces of total artificial hip joints is thought to play an important role in the periprosthetic osteolysis and ultimately the aseptic loosening of these prostheses. The macrophage is believed to be central to this process by releasing various cytokines and other mediators of osteolysis upon phagocytosis of the polyethylene wear debris. This study evaluated the in vitro bone resorption response of C3H murine peritoneal macrophages to clinically relevant GUR 1120 polyethylene particles. Macrophages were co-cultured in vitro with GUR 1120 particles with a mean size of 0.24, 0.45, 1.71, and 7.62, and GUR 1120 polyethylene resin with a mean size of 88 microm at various particle volume (microm)(3): macrophage ratios (0.1:1; 1:1; 10:1; and 100:1). The conditioned supernatants were incubated with (45)calcium radio-labeled mouse calvariae, and bone resorption was measured as (45)calcium release. The results showed that the 0.24 microm particles stimulated the macrophages to generate bone resorbing activity at a ratio of 10(microm)(3) per macrophage. The 0.45 and 1.71 microm particles were active at a ratio of 100( microm)(3) per macrophage, and the 7.62 and 88 microm particles were inactive at all the doses tested. The co-culture supernatants were also assayed for TNF-alpha, IL-1beta, IL-6, and PGE(2). The results followed the same trend for particle size and volume dose to that observed for the bone resorbing activity. This study has demonstrated, for the first time, the importance of size and dose of clinically relevant polyethylene particles on the osteolytic response of macrophages in vitro.

Animals↗

Evaluation of the response of primary human peripheral blood mononuclear phagocytes to challenge with in vitro generated clinically relevant UHMWPE particles of known size and dose.

The response of primary human peripheral blood mononuclear phagocytes to challenge with clinically relevant ultra-high molecular weight polyethylene (UHMWPE) wear debris of known particle size and dose was evaluated. Particles with a mean size of 0.24, 0. 45, 1.7, 7.6, and 88 microm were cocultured with cells for 24 h before assessment of cell viability and production of the osteolytic cytokines interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha, and granulocyte macrophage colony-stimulating factor, and prostaglandin E(2). All particle fractions were evaluated at particle volume (microm(3)) to cell number ratios of 10:1 and 100:1, which had been previously identified as being the most stimulatory and clinically relevant. None of the test fractions had an effect on cell viability. Whereas the heterogeneity of human individuals was clearly evident in the responses of the donors evaluated in this study (the response of donor 3 was between 5 and 20 times greater than the other donors), the most biologically active particles were found to be submicrometer in size. Stimulation with phagocytosable particles (0.24, 0.45, and 1.7 microm) resulted in enhanced levels of cytokine secretion. Macrophages stimulated with particles outside this size range produced considerably less cytokines at the volumes tested. These results confirm earlier findings and suggest that the size and volume of UHMWPE particles are critical factors in macrophage activation. Furthermore, they suggest that the heterogeneity of human individuals may be another important factor in determining implant life.

Biocompatible Materials↗

The H(2)(18)O solvent-induced isotope shift in (19)F NMR.

The H(2)(16)O/H(2)(18)O solvent-induced isotope shifts ((18)O SIIS) of the (19)F NMR signals of a number of fluorine compounds have been measured. These isotope shifts are observed to be upfield, downfield, or zero, depending on the specific compound and the precise solution conditions. At 25 degrees C and with an (18)O enrichment of 86%, the (18)O SIIS of several fluorinated amino acids were in the range of 0.0014-0.0018 ppm downfield. 5-Fluorouridine displays a significantly wider range of (18)O SIIS values. A 5-fluorouridine-labeled 16-mer RNA also displayed observable (18)O SIIS values, but the characteristics of these were significantly modified from those of free 5-fluorouridine. The experimental observations are consistent with the (18)O SIIS being composed of upfield and downfield components, with the relative contributions of these determining the size and direction of the overall isotope shift. This is discussed in terms of a combination of van der Waals interactions between the fluorine atom and the solvent, electrical and hydrogen bonding effects, and the perturbations to these due to (18)O substitution in the solvent water. This isotope effect promises to be a highly useful tool in a range of (19)F NMR studies.

Animals↗

Further evidence of a decorin-collagen interaction in the disruption of cervical collagen fibers during rat gestation.

OBJECTIVE: Our purpose was to determine the histologic distribution and expression of decorin in rat cervix throughout the course of rat gestation and to correlate the findings with the known progression of collagen fiber disruption and cellular turnover in this tissue. STUDY DESIGN: Cervices from pregnant animals at 5, 11, 18, and 21 days were studied. A proteoglycan of low molecular weight, decorin, was detected by sensitive and specific immunohistochemical analysis with a biotin-avidin horseradish peroxidase method. RESULTS: Decorin was not detected on day 5. By day 11 moderate decorin staining was detected in the subepithelial layer and in the deep stroma. Decorin staining progressed to a strong expression in the subepithelial layer and to a moderate expression in the deep stroma on day 18. On day 21 (term in rat) the staining was fairly homogeneous throughout the connective tissue stroma. CONCLUSION: These findings clearly demonstrate that decorin expression increased progressively throughout pregnancy and are consistent with the hypothesis that an excess of decorin near term is capable of initiating a decorin-collagen interaction that leads to collagen fibril disruption and decreased cervical tensile strength.

Animals↗

The effect of sizing on the hydrodynamic parameters of the Medtronic freestyle valve in vitro.

BACKGROUND: An in vitro model has been established to investigate the effect of sizing on the hydrodynamic characteristics and leaflet motion of the Medtronic Freestyle valve. METHODS: The valves were tested in fresh porcine aortic roots. Two or three different sizes of valves were implanted in the same aortic root one after the other. The compliance of the fresh aortic and the composite roots was measured in the pressure range of 0 to 120 mm Hg, and the composite roots were then tested in a pulsatile flow simulator. The transvalvular gradient and degree of regurgitation were measured and the effective orifice area and performance index were calculated. Leaflet motion was recorded on video. RESULTS: The fresh aortic roots dilated by average 39.4% as the hydrostatic pressure rose from 0 to 120 mm Hg. Implantation of the Medtronic Freestyle valve did not change the distensibility of the aortic root significantly. The sizing protocol did not affect significantly the hydrodynamic performance. However, a significantly lower open leaflet bending deformation was found in the undersized valves. Regurgitation was found only at 2-mm undersized valves. CONCLUSIONS: Leaflet motion of the Medtronic Freestyle valve in vitro was best if 1 mm undersized, and this may be beneficial to long-term durability.

Aorta↗

Comparison of the response of primary human peripheral blood mononuclear phagocytes from different donors to challenge with model polyethylene particles of known size and dose.

The response of primary human peripheral blood mononuclear phagocytes to challenge with polyethylene particles of known size and dose was evaluated. Particles with mean sizes of 0.21, 0.49, 4.3, 7.2, and 88 microm were co-cultured with cells for 24 h prior to the assessment of cell viability and production of the osteolytic mediators IL-1beta, IL-6, TNFalpha, GM-CSF and PGE2. All particle fractions were evaluated at particle volume (microm3) to cell number ratios of 10:1 and 100:1 which were previously identified as being the most biologically active and clinically relevant. The heterogeneity of human individuals was clearly evident both in the profile and the magnitude of the response of the donors evaluated in this study (the response of donor 5 being 2- to 15-fold lower than that of the other donors). Only the sub-micrometre particles stimulated significantly enhanced cytokine secretion at the ratios tested: mean particle sizes of 0.49 and 0.21 microm being the most biologically active. Macrophages stimulated with particles outside this size range produced considerably lower levels of mediator. These results compared favourably with the results of earlier studies, which demonstrated that particles within the phagocytosable size range (0.1-10 microm) were the most biologically active. These results, therefore, confirm earlier findings and suggest that the size and volume of polyethylene particles are critical factors in macrophage activation. Furthermore, they suggest that the heterogeneity of human individuals may be another important factor in determining implant life and could provide the basis for a valuable diagnostic tool to identify those patients most at risk of implant loosening.

Blood Donors↗