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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 253 records · Page 14Linked to original sources

Lidocaine prophylaxis for fatal ventricular arrhythmias after acute myocardial infarction.

OBJECTIVE: To compare the efficacy and safety of a 40-hour lidocaine infusion after completion of a 8-hour open-label infusion for prophylaxis of primary ventricular fibrillation in patients with uncomplicated acute myocardial infarction. METHODS: This was a double-blind, randomized placebo-controlled trial held in the coronary care unit of a large nonprofit hospital. We studied 200 patients with uncomplicated acute myocardial infarction in Killip class I or II who came to the hospital within 6 hours of onset of symptoms and 22 patients who had ventricular fibrillation before the start of the study. Intervention consisted of an 8-hour lidocaine infusion followed by placebo or lidocaine for an additional 40 hours. The infusion rate was adjusted in patients > or = 70 years old and in those < 50 kg or > or = 90 kg. Measurements recorded were baseline demographic characteristics, incidence of ventricular arrhythmias, adverse reactions, and death. RESULTS: New congestive heart failure developed during the randomized phase in 9% of patients receiving lidocaine and in 2% of patients receiving placebo (p = 0.03). Ventricular fibrillation did not occur during the treatment period, and sustained ventricular tachycardia developed in one patient receiving placebo. The in-hospital mortality rate was comparable in both groups (4% versus 2%; p = 0.68) but was much higher (13.6%) in patients with initial ventricular fibrillation not included in the randomized study. CONCLUSIONS: A 40-hour age- and weight-adjusted lidocaine infusion administered after an initial 8-hour infusion provoked more congestive heart failure than placebo. In view of the absence of ventricular fibrillation episodes with both infusions, caution should be used when lidocaine is administered for longer than 8 hours in patients with uncomplicated myocardial infarction.

Aged↗

Preliminary study of the effect of aging following irradiation on the wear of ultrahigh-molecular-weight polyethylene.

Several studies have indicated that degradation of ultrahigh-molecular-weight polyethylene following gamma irradiation in air adversely affects the mechanical properties of the material; however, it is not known how this subsequently affects its wear rate. Wear studies have therefore been performed on three groups of ultrahigh-molecular-weight polyethylene; unirradiated material, recently irradiated material (aged for 2 months), and aged irradiated material (aged for 5 years). The aging took place in sterile packaging on the shelf. The wear studies were carried out on a tri-pin-on-disk wear tester, with a pin from each type of material being studied in each test. In each test the wear rate of the nonirradiated material was slightly lower than the 2-month-aged, irradiated material. The 5-year-aged, irradiated material had the highest wear rate, and this was significantly greater than that of the unirradiated material (P < .05).

Acetabulum↗

Comparative study of the hydrodynamic function of six size 19 mm bileaflet heart valves.

The hydrodynamic function of six size 19 mm bileaflet mechanical heart valves was investigated in a pulsatile flow simulator. The St. Jude Standard, St. Jude Haemodynamic Plus, CarboMedics, Sorin Biomedica, Duromedics and ATS valves were studied. The mean pressure drop and effective orifice area during forward flow, regurgitant volumes and total energy loss were analysed. The St Jude Haemodynamic Plus and Sorin Biomedica valves had significantly lower forward flow pressure drops and total energy losses than the other four valves. Assuming that all six valves can be implanted in the equivalent size of aortic root, this should lead to improved in vivo performance.

Aortic Valve↗

Clinical trials of bispecific antibody MDX-210 in women with advanced breast or ovarian cancer that overexpresses HER-2/neu.

MDX-210 is a bispecific antibody (BsAb) that recognizes Fc gamma R1 on monocytes and macrophages and the cell surface product of the HER-2/neu oncogene, which is overexpressed on some breast and ovarian cancers. Clinical trials have demonstrated that treatment with MDX-210 is well tolerated and that MDX-210 is both immunologically and clinically active. Optimization of the dose and schedule of MDX-210 and development of combination treatments with cytokines that modulate immune effector cells will greatly enhance the efficacy of this novel BsAb construct for treatment of tumours that overexpress HER-2/neu. We envision that MDX-210 will be effective for treating patients with tumors that overexpress HER-2/neu, especially in the minimal disease setting.

Antibodies, Anti-Idiotypic↗

Small joint synovitis in rheumatoid arthritis: should it be assessed separately?

In the assessment of disease activity in rheumatoid arthritis (RA) small joint synovitis is traditionally included only as a component of active, tender or swollen joint counts. By contrast, in the assessment of disease damage in RA, the X-ray score of hands and feet represents one of the most common parameters used and is regarded as a major indicator of outcome. Data presented in this study lead us to hypothesize that the small joints require separate assessment in any study of disease activity or outcome in RA: (i) there is clear evidence that small joint synovitis often occurs in the absence of an abnormal acute phase response (ESR or C-reactive protein) and (ii) measured synovitis is an individual (PIP) joint has been shown to be reliable and to be related to subsequent X-ray changes in the same joint. Our findings show that, in a study of a treatment of RA, it is quite possible for disease activity measures to appear controlled while inflammation continues in the small joints causing radiological damage. This radiological damage is reflected as an adverse outcome. Hence the paradox of improving disease activity but not outcome. We argue that small joint inflammation and damage should be recognized as one aspect of the RA disease process offering unique information and as such should be assessed independently.

Adult↗

Evaluation of silicone-gel sheeting on early wound healing of linear incisions.

Topical silicone-gel sheeting has been shown to be beneficial in the treatment of established hypertrophic and keloid scars. Certain individuals and incisions in specific body sites appear to be at increased risk for the development of such scars. A simple, inexpensive, and preventive treatment in these individuals at increased risk could potentially minimize the extended period of pressure therapy and repeated steroid injections that are often required to optimize outcome. However, the effects of applying silicone-gel sheeting in the immediate postoperative period as a preventive measure have not been investigated to date. Because silicone-gel sheeting influences the remodeling and maturation phase of collagen formation, we believed it prudent to determine whether silicone-gel sheeting had any deleterious effect on early wound healing, as demonstrated by in vivo biomechanical testing of wound strength and histological assessment. To investigate the potential effects of silicone-gel sheeting on acute wound healing and its possible application for prevention of hypertrophic scars, a study was designed in the hairless guinea pig. In phase 1 of the study, bilateral dorsolateral incisions were made, allowing each guinea pig to serve as its own control. One wound was dressed with silicone-gel sheeting, and the control site was dressed with Nu-gauze dressing. Wounds were then assessed visually and with in vivo biomechanical analysis of wound strength at days 3, 5, and 7 postoperatively (n = 7 per group). Phase 2 of the study compared identical dressings in a similar animal model using a single dorsal midline incision, in which alternate halves of each wound served as the control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Abnormal TCR V beta repertoire in patients with chronic myeloid leukaemia.

We have used 25 sets of oligonucleotide primers specific for the 24 known major human T-cell receptor (TCR) V beta families in polymerase chain reactions to analyse the T-cell repertoire of the peripheral blood in seven patients with chronic myeloid leukaemia (CML). In contrast to normal healthy individuals, all seven patients exhibited variable degrees of TCR V beta-specific T-cell deletion, ranging from two to eight of the 24 major families. T cells bearing V beta 17 and 8 were most commonly deleted. These results suggest a superantigen effect associated with CML. The patterns of deletion did not appear to correlate with either of the two bcr-abl transcripts. The reason and aetiological agent responsible for the T-cell deletion remain speculative. Further work is ongoing to characterize this phenomenon in animal models and patients with CML.

Base Sequence↗

Flow cytometric determination of pre-transfusion red cell volume in fetuses and neonates requiring transfusion based on RhD+ dilution by transfused D- red cells.

We report a case of feto-maternal haemorrhage and describe a new flow-cytometric method of determining a fetus's or infant's pre-transfusion red cell volume (RCV). We validate this method against an established technique, employing fetal haemoglobin (HbF) dilution, for determining the RCV in fetuses and neonates requiring intravascular transfusion. We discuss advantages and other potential applications of this new method.

Blood Transfusion, Intrauterine↗

Regulation of corticotropin-releasing factor secretion and synthesis in the human neuroblastoma clones- BE(2)-M17 and BE(2)-C.

The BE(2)-M17 and BE(2)-C human neuroblastoma cell lines have been shown to synthesize and secrete corticotropin-releasing factor (CRF) following retinoic acid treatment. It has been demonstrated that CRF secretion and intracellular synthesis increases in response to forskolin treatment. In this report, we have further characterized these cells in response to protein kinase C activators, dexamethasone, interleukin-1 alpha, as well as various neurotransmitters and peptides. Nanomolar concentrations of the phorbol ester--phorbol 12 myristate 13--acetate (TPA), increased intracellular CRF content in both cell lines while increasing secretion only in the BE(2)-M17 cell. Nanomolar concentrations of dexamethasone were not able to alter basal levels of secretion and content in either cell type. However, in the BE(2)-M17 cell but not the BE(2)-C cell, the same concentrations of dexamethasone added to 30 microM forskolin augmented levels of CRF secretion and content. Likewise, the same augmented response in CRF secretion and content was seen only in the BE(2)-M17 cell line when nanomolar concentrations of dexamethasone were added to 20 nM TPA. Furthermore, only in the BE(2)-M17 cell line were micromolar levels of the biogenic amine serotonin able to increase levels of CRF secretion and content. No effects on CRF in both cell lines were demonstrable with picomolar levels of interleukin-1 alpha as well as micromolar levels of acetylcholine, norepinephrine, arginine-vasopressin, oxytocin, and angiotensin-II. The potential usefulness of these cells as models of central nervous system or placental CRF-containing neurons is discussed.

Colforsin↗

Contact pressure prediction in total knee joint replacements. Part 1: General elasticity solution for elliptical layered contacts.

A general elasticity contact theory has been developed to predict the contact area and the contact pressure in total knee joint replacements with elliptical contacts where the thickness of ultra high molecular weight polyethylene (UHMWPE) is similar or less than the contact half width. The interfacial boundary condition between the UHMWPE component and the underlying metal substrate has been considered to be either perfectly bonded or perfectly unbonded in the model. Poisson's ratio for UHMWPE has been assumed to be 0.3 or 0.4. The effect of the thickness of the UHMWPE layer on the contact area and the contact pressure has been examined. The predictions of the maximum contact pressure and the contact area have been presented in non-dimensional forms and can readily be applied for typical design configurations of current total knee joint replacements. Furthermore, the present results can readily be applied to design considerations for total knee joint replacements to reduce contact stresses within the UHMWPE component.

Elasticity↗

Contact pressure prediction in total knee joint replacements. Part 2: Application to the design of total knee joint replacements.

The general elasticity contact theory for elliptical geometry developed in Part 1 (1) has been applied to the design of current total knee joint replacements. A two-step curve-fitting technique using cubic spline interpolation routines has been adopted to represent the full elasticity solutions. The curve fit results of the maximum contact pressure have been compared with the full elasticity solution for a specified elliptical geometry and different polyethylene thicknesses and good agreement has been demonstrated. The computing time required by the curve-fitting technique is very small compared with the full elasticity solution and therefore can readily be applied to the design of knee joint replacements. Furthermore, reasonable agreement has also been found for the contact area for a typical knee joint design between the present theoretical prediction and the experimental measurement using pressure-sensitive film. Predictions of the maximum contact pressure have been made for an existing knee joint replacement in order to illustrate the present analysis in the design cycle. It has been shown that the effect of the thickness of ultra high molecular weight polyethylene is relatively small on contact stress predictions provided a sufficiently large value is chosen. On the other hand, the effect of conformity has a much greater influence on the contact stress distribution, particularly in the direction of the smaller principal radius.

Elasticity↗

The influence of manufacturing methods on the function and performance of a synthetic leaflet heart valve.

There is considerable interest in polyurethane synthetic leaflet heart valves for both ventricular assist devices and direct implantation in the body. Two different manufacturing methods, thermal forming, and dip casting, of the leaflets have been investigated. There were only small differences in the hydrodynamic function of the valves made by the two methods. However, the durability of dip cast valves was far superior to the thermally formed film fabricated leaflets, with all of the dip cast valves reaching 160 million cycles without failure. This study indicates that a correctly designed and manufactured polyurethane synthetic leaflet heart valve has the potential for long-term implantation in the body.

Evaluation Studies as Topic↗

Cushion form bearings for total knee joint replacement. Part 1: Design,friction and lubrication.

Cushion knee prostheses have been designed and constructed that produce approximately equal initial contact areas and theoretical film thicknesses compared with a conventional UHMWPE (ultra-high molecular weight polyethylene) joint. These compliant bearings had a flat tibial component which imposed fewer biomechanical constraints and allowed a greater range of movement. Friction experiments have been carried out on a pendulum simulator apparatus. The results showed that the cushion knee joints operated just within the mixed lubrication regime, but that they benefited from a substantial measure of fluid film lubrication. Microelastohydrodynamic lubrication was effective in preserving low friction and thin but effective lubricating films.

Biomechanical Phenomena↗

Cushion form bearings for total knee joint replacement. Part 2: Wear and durability.

Cushion knee prostheses have been designed and constructed to produce larger initial contact areas and thicker theoretical film thicknesses than a conventional UHMWPE (ultra-high molecular weight polyethylene) joint. The compliant bearing had a flat tibial component which imposed fewer biomechanical constraints and allowed greater range of movement. Wear tests were performed in a knee joint simulator and creep tests were carried out in a servo-hydraulic apparatus. Various failure modes of cushion joints that require further study were identified. However, the results showed that adequate durability was achieved from a 20 MPa polyurethane material in joint simulating tests carried out over 0.5, 1.0 and 5.0 million cycles. Most importantly, during these tests, no detectable wear debris was generated. It is believed that this is the first time that the full potential of cushion bearings has been demonstrated in a joint simulator over periods corresponding to about five years of service in vivo.

Friction↗

Determination of the curvatures and bending strains in open trileaflet heart valves.

The leaflets of trileaflet artificial heart valves manufactured from polyurethane, gluteraldehyde-treated porcine aortic valves and pericardial tissue are subject to cyclic stresses and strains which can reduce the lifetime of the implanted valves through leaflet calcification and fatigue failure. A detailed knowledge of the stress state within a valve leaflet throughout a cardiac cycle is desirable in order to improve the geometry of the valve leaflets and ultimately improve the valve performance. An experimental method to evaluate the radius of curvature at the free edge of the open valve leaflet is presented. The technique has been applied to polyurethane trileaflet heart valves manufactured within the authors' laboratory and to commercially available bioprosthetic valves in the fully open position under steady and pulsatile flow conditions. Simple bending theory has been applied to the polyurethane valves to calculate bending stresses and strains at the free leaflet edge based on the measured curvature. The results showed that in the fully open position the highest curvatures occurred at the commissural regions for all the valves analysed. Additional areas of high curvature were present along the free leaflet edge. Average curvatures as high as 0.85 mm-1 were observed at the leaflet commissures for the polyurethane valves with a resultant bending stress of 0.72 MPa. The porcine bioprosthetic valves showed average curvatures as high as 2.5 mm-1 which also occurred at the leaflet commissures. The results of the study have been compared to values of stress obtained from numerical analysis of closed polyurethane valve leaflets reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative analysis of bone stresses and strains in the Intoss dental implant with and without a flexible internal post.

The clinical success of any dental implant is dependent upon the maintenance of good-quality bone supporting it. Previous studies have shown high values of strain around the neck of an implant under lateral loading. These high values may lead to fatigue damage and resorption in lower strength cancellous bone. In this study, the finite element method has been used to study the bone strain distribution around the following implants: (a) an Intoss dental implant, referred to as the 'standard' implant; (b) a comparative Branemark implant and (c) a modified Intoss implant with a central flexible post, referred to as the 'modified' implant. Three different bone distributions have been investigated under axial and lateral loading: (a) implant surrounded by cortical bone; (b) implant tip supported by cortical bone with a thin layer of cancellous bone along the length and top of the implant; (c) implant tip and top supported by cortical bone with a thin layer of cancellous bone along the remaining length. For the standard implant, similar maximum equivalent strain values were predicted for the bone surrounding a comparable length Branemark-type implant. Modification of the standard implant design to include a flexible central post resulted in a decrease in the maximum von Mises stresses and equivalent strains in the cancellous bone. It is postulated that this will reduce the likelihood of bone fatigue failure and subsequent resorption in this bone. Thus the proposed design change is predicted to be highly beneficial in terms of bone load transfer.

Bone Resorption↗

Experimental and theoretical study of the contact mechanics of five total knee joint replacements.

The tibio-femoral contact area in five current popular total knee joint replacements has been measured using pressure-sensitive film under a normal load of 2.5 kN and at several angles of flexion. The corresponding maximum contact pressure has been estimated from the measured contact areas and found to exceed the point at which plastic deformation is expected in the ultra-high molecular weight polyethylene (UHMWPE) component, particularly at flexion angles near 90 degrees. The measured contact area and the estimated maximum contact stress have been found to be similar in magnitude for all of the five knee joint replacements tested. A significant difference, however, has been found in maximum contact pressure predicted from linear elasticity analysis for the different knee joints. This indicates that varying amounts of plastic deformation occurred in the polyethylene component in the different knee designs. It is important to know the extent of damage as knees with large amounts of plastic deformation are more likely to suffer low cycle fatigue failure. It is therefore concluded that the measurement of contact areas alone can be misleading in the design of and deformation in total knee joint replacements. It is important to modify geometries to reduce the maximum contact stress as predicted from the linear elasticity analysis, to below the linear elastic limit of the plastic component.

Anthropometry↗