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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 19 recordsLinked to original sources

Exogenous chromophores for the argon and Nd:YAG lasers: a potential application to laser-tissue interactions.

Chromophore dyes can be employed to modify laser-tissue interaction. A number of dyes have been investigated for their effect on the absorption and transmission of argon and Nd:YAG laser energy by vascular tissue in vitro. Three histological dyes have been assessed as potential chromophores for the argon laser and four infrared dyes for the Nd:YAG. Segments of porcine coronary artery to which dye had been applied were lased (1,064 nm, 2.5 W, 83 W/cm2, 60 s and 488/514 nm, 400 mW, 10.5 W/cm2, 60s) and the tissue temperature measured remotely using an infrared thermometer. In addition, energy transmission was measured with a photodiode and tissue morphological changes assessed histologically. All three argon dyes significantly increased energy absorption (typically 60 degrees C v. 20 degrees C at 60 s, P less than 0.001, 2-way ANOVA). Three of the four infrared dyes behaved similarly (40-70 degrees C v. 20 degrees C, P less than 0.001). All dyes significantly increased the initial rate of rise in tissue temperature during lasing. A reduction in energy transmission was observed for each of the Argon dyes but not for the Nd:YAG dyes. Histological evidence of thermal damage in control tissue first occurred for the argon and Nd:YAG lasers at 800 mW and 7.5 W without chromophore and at 400 mW and 2.5 W with the chromophore, respectively. A number of effective chromophores have therefore been identified at each wavelength.

Absorption

Mechanical and optical anisotropy of bovine pericardium.

A Moiré fringe method was used to determine the shape of inflated disks of fresh bovine pericardium. The results suggested that the tissue was anisotropic and allowed the identification of the directions of the axes of elastic symmetry. Quantitative biaxial inflation and simple tension tests confirmed the anisotropy. In the circumferential direction the tissue was more extensible and had greater mean strength (18 MPa against 2.5 MPa) and mean terminal modulus (46 MPa against 14 MPa) than in the root-to-apex direction. The tissue was also optically anisotropic when viewed by transmitted polarised light and the directions of mechanical and optical anisotropy were related.

Animals

Assessment of the deformation of the Bateman bipolar hip prosthesis inner bearing due to moisture absorption and creep.

The mechanism of inner bearing stiffness of bipolar hip prostheses has been investigated. The Ultra-high Molecular Weight Polyethylene (UHMWPE) component of the Bateman bipolar hip prosthesis has been subjected to a series of static and dynamic tests to assess water absorption and creep. Although deformation of the UHMWPE occurred, this did not produce an increased resistance to movement in the inner bearing.

Biomechanical Phenomena

Analysis of regurgitant jets in natural and bio-prosthetic heart valves.

Artificial bio-prosthetic heart valves are prone to fatigue tearing, having a 50% failure rate in ten years. Tears in valves give rise to pulsing reverse flow back through the valve. This is termed regurgitant flow and the resultant jet of blood a regurgitant jet. The regurgitant volume of the jet during the pulsing cycle gives a measure of the severity of the valve defect and clinical significance. Hence, it is important for the cardiologists to be able to quantify this volume. Although the velocity of the regurgitant jet can be determined using Doppler ultrasound, the dimensions of the heart valve lesion cannot be measured directly; hence, the volumetric flow rate cannot be quantified accurately. At present the severity of the regurgitant jet is assessed qualitatively from the intrusion of the jet into the cardiac chamber. In the present study, classical mathematical theories of turbulent jets have been used to describe the velocity distributions for the types of jets expected in defective heart valves and these distributions have been verified experimentally. One of these models has been developed to enable the regurgitant volumetric flow through an axisymmetric orifice of unknown radius to be calculated from the velocity distribution of the jet. This relationship may be used in conjunction with ultrasound techniques to quantify the regurgitant volume within defective artificial heart valve implants. The present study shows that there is a significant difference in the velocity distributions in jets emanating from axisymmetric and high aspect ratio slots.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis

An improved method of in vivo wound disruption and measurement.

Biomechanical studies of wound strength are important because of new investigations in growth factors, cytokines, and fetal wounds. We compared two traditional methods of wound disruption measurement with a novel computerized model designed for in vivo experiments. An Instron tensiometer (INSTS) and an air insufflated positive pressure device (AIPPD) were compared with a vacuum-controlled wound chamber device (VCWCD). The VCWCD produced vacuum at the wound site and wound disruption was monitored with two video camera/recorders. Rats were marked with a template guide for a 2.5 cm, full-thickness, abdominal incisional wound. Rats were divided into three groups and studied at 2, 7, or 14 days after wounding. The recorded images were computer digitalized to generate wound strength curves from a three-dimensional model. A comparison of the wound disruption curves demonstrated that the VCWCD was comparable to the INST or AIPPD in normal wound healing (P greater than .40). The VCWCD provided data with less standard error at 2 days after wounding (P less than 05). In separate series of experiments, VCWCD was tested in the early phases of healing and was found to be sensitive to change at intervals of 48 hr after wounding (P less than .005). The INST or AIPPD methods could not perform this task because of an unacceptable level of random error after tissue manipulation. The VCWCD system was considered superior for evaluating early wound healing because it was an in vivo method which required minimal wound manipulation.

Animals

Prospective analysis of mental status progression in ethanol-intoxicated patients.

Distinguishing patients with uncomplicated ethanol intoxication from intoxicated patients with other causes of mental status depression is a common clinical dilemma. The authors serially tested mental status in a group of ethanol-intoxicated patients to determine the interval over which mental status changes could be attributed to uncomplicated intoxication. Study patients were identified by (1) admission breath ethanol greater than or equal to 100 mg/dL; (2) ethanol-related impairment necessitating further observation or treatment; and (3) not critically ill or exhibiting focal neurologic signs. Mental status scores (sums of specific indices of alertness, orientation, and agitation) were determined initially, 1 hour after arrival, then every 2 hours. Causes of mental status depression other than acute intoxication were diagnosed in 16 patients, while another 18 failed to completely normalize mental status by the time of emergency department discharge or hospital admission. The remaining 71 with uncomplicated ethanol intoxication required (mean +/- SD) 3.2 +/- 3.6 hours to normalize mental status scores. A large proportion, however, took considerably longer to normalize mental status: 15 (21%) took 7 or more hours, and three (4%) took as long as 11 hours. Although patients with ethanol-associated depression of mental status lasting 3 hours after emergency department admission should be carefully evaluated for other causes of mental status abnormalities, the authors' observations indicate considerable individual variation in the duration of mental status depression caused by uncomplicated ethanol intoxication.

Alcoholic Intoxication

Carbomedics and St. Jude Medical bileaflet valves: an in vitro and in vivo comparison.

The hydrodynamic and haemodynamic function of 29 mm mitral and 23 mm aortic St Jude Medical (SJM) and CarboMedics (CM) heart valves have been compared in a pulsatile flow simulator in the laboratory and by doppler ultrasound in vivo. The laboratory studies showed that there was no significant difference in the pressure drop across the valves. The valves also had similar regurgitant volumes. Doppler ultrasound confirmed these results with a mean pressure drop of 12.9 +/- 5.5 mmHg across the CM aortic valves and 12.6 +/- 5.5 mmHg for the SJM aortic valves. The mean mitral diastolic pressure drops were 3.8 +/- 1.8 and 4.6 +/- 1.4 mmHg for the CM and SJM valves, respectively. Mild aortic regurgitation was detected in 5 of 14 patients in the CM group and 1 out of 6 patients in the SJM group, though none of the cases were clinically significant. Both the in vitro and in vivo results show these valves to have acceptable and comparable function.

Aortic Valve

The hydrodynamic function and leaflet dynamics of aortic and pulmonary roots and valves: an in vitro study.

Fresh homograft aortic and pulmonary roots were tested in a pulsatile flow simulator to assess their hydrodynamic function and leaflet opening characteristics. Simultaneous flow and pressure measurements were obtained for a range of cardiac outputs. The effective orifice area and regurgitant volumes were calculated. The mean pressure difference across the pulmonary roots was obtained under both left and right side pressures. A video recording of valve leaflet function was also obtained for each valve. A comparison was made with four porcine bioprosthetic heart valves (21 and 23 mm). The mean pressure difference with respect to flow for the 21 mm Hancock II and Intact porcine bioprostheses was significantly higher than that for all aortic roots tested. The 24 mm aortic root showed significantly lower pressure drop compared to all porcine valves tested. The mean pressure difference across each pulmonary root at pulmonary pressures was significantly greater than at systemic pressures. At systemic pressures the fully open leaflets had a triangular orifice with low leaflet open bending strains at the commissures. At the lower internal pressures, with reduced dilation of the root, higher bending strains were noted. These were not as severe as seen in porcine valves.

Adult

Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32).

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal

How accurate is a computerized surgical audit when resident medical staff collect the data?

Since July 1988 all eight general surgeons at Fremantle Hospital have used a computer-based surgical audit and discharge system. At the time of writing (September 1991) 10,919 computer-generated discharge letters have been produced by the system. This paper describes the system and reports a series of quality control assessments carried out between 1 July 1988 and 30 June 1990 during which 30 pre-registration surgical residents completed 5,716 data collection forms. It was found that: (1) data collection for 23 of 24 monthly surgical audits was at least 95% complete; (2) outstanding surgical discharge summaries were reduced by 89%; (3) the residents recorded 17/19 wound infections and identified 15 (79%) of these as a surgical complication; and (4) the residents tended to under-record complications in patients who had more than one complication during their hospital stay. It was concluded that the system was robust, and that resident staff collected data in such a way that good quality computer-generated discharge letters were produced in a timely manner. Closer attention to aspects of data collection will be required before the optimum surgical audits of the QX system can be generated.

Abstracting and Indexing

A model of the geometrical changes in aortic valve leaflets in response to leaflet extension and variable boundary conditions.

The function, deformation and performance of heart valve leaflets are dependent on the material properties and the geometry of the leaflet. As the leaflet acts as a constrained membrane the geometry is dependent on the boundary condition applied to the leaflet and any permanent extension of the leaflet. Both of these factors are varied during the preparation of frame-mounted porcine bioprosthetic heart valves and surgical insertion of free-sewn valves. This can result in abnormal geometry and function. A mathematical model has been developed which describes these changes in geometry of a cylindrical leaflet as a function of the diameter of the aortic root (boundary conditions) and the length (or permanent extension) of the leaflet. Both the angle of inclination and the radius of curvature of the cylindrical leaflet were reduced with increased leaflet length or decreased aortic diameter. Agreement was found between the model predictions and experimental observations in porcine bioprosthetic heart valves, where abnormal leaflet geometries are produced by non-physiological boundary conditions and permanent set of the leaflets by fixation with glutaraldehyde. The general solutions developed in this model allow leaflet geometries to be predicted for a range of conditions in free-sewn and frame-mounted valves.

Animals

The effect of porosity of articular cartilage on the lubrication of a normal human hip joint.

The effect of porosity of articular cartilage on the lubrication of a normal human hip joint has been studied. The poroelasticity equation of articular cartilage and the modified Reynolds equation for the synovial fluid lubricant have been successfully solved under squeeze-film motion and for the conditions experienced in a normal human hip joint. It has been shown that porosity of the articular cartilage depletes the lubricant film thickness, rather than increasing it, particularly when the lubricant film thickness becomes small. Furthermore, it has been shown that articular cartilage can be treated as a single-phase incompressible elastic material in the lubrication modelling under physiological walking conditions.

Cartilage, Articular

Finite element stress and strain analysis of the bone surrounding a dental implant: effect of variations in bone modulus.

The long-term clinical performance of a dental implant is dependent upon the preservation of good quality bone surrounding the implant and a sound interface between the bone and the biomaterial. Good quality bone is itself dependent upon the appropriate level of bone remodelling necessary to maintain the bone density and the avoidance of bone microfracture and failure. Both processes are governed by the stress and strain distribution in the bone. In this study, a dental implant which had the same geometry as the Branemark system, but with a bioactive surface coating added to produce a direct bond to the bone, was analysed. A finite element stress and strain analysis has been carried out for a range of bone density distributions under axial and lateral loading. The predictions indicated that there was no evidence of strain shielding around the neck of the implant. With lateral loading, high values of von Mises stresses (18 M Pa) were predicted around the neck of the implant. A reduction in the elastic modulus of the bone around the neck of the implant by a factor of 16 only produced a twofold reduction in the peak stress. This resulted in stress levels capable of inducing fatigue failure in this much weaker bone. This analysis has demonstrated that it is extremely important to have good quality dense bone around the neck of the implant to withstand the predicted peak stresses of between 9 and 18 M Pa. Failure to achieve this after implantation and subsequent healing may result in local fatigue failure and resorption at the neck upon resumption of physiological loading.

Bone Density

Defect reconstruction and cerebrospinal fluid management in neurotologic skull base tumors with intracranial extension.

Intracranial extension (ICE) is the spread of tumor into the subarachnoid space through dura or along cranial nerve roots. The single-stage removal of the skull base tumor with its ICE has been confounded by cerebrospinal fluid management and defect reconstruction. The purpose of this report is to review a current protocol for managing the cranial base tumor and its ICE as a unit. The ventricular shunting paper of 1987 is retracted. All tumors were managed at a single stage. Defect reconstruction was size dependent. Ninety-eight neurotologic skull base tumors with ICE were managed from 1971 to 1991. The new protocol was initiated in 1987. Results specific to this group are highlighted. For glomus tumors, cerebrospinal fluid leak rates have been dramatically reduced overall from 14.5% to 4%. The leak rates for nonglomus tumors, overall, have improved slightly. Complications are discussed. The development of this surgical approach protocol improves the functional outcome in patients of surgeons who aspire to disease "cure" rather than "control."

Adolescent

Job strain and prevalence of hypertension in a biracial population of urban bus drivers.

OBJECTIVES: In this study we tested the association between occupational stress--as measured by job demands, decision latitude, and job strain--and hypertension in a population of 1396 Black and White bus drivers. METHODS: Height, weight, blood pressure, and medical history were assessed by physical exam. Drivers completed a questionnaire assessing their work schedules, personal habits, and self-perceptions about job demands and decision latitude. RESULTS: Univariate analyses revealed significant inverse associations; lower levels of job demands and job strain were associated with a higher prevalence of hypertension for Blacks and Whites. After 12 confounding variables were controlled for, the association between these two measures of occupational stress and hypertension became nonsignificant. Decision latitude was also not significantly associated with hypertension. CONCLUSIONS: Our findings are inconsistent with previous studies' findings of a positive association between job strain and chronic diseases. The difference in results may be explained by our incorporation of individuals' perceptions in the measurement of occupational stressors and our use of individuals from a single occupation with comparable job responsibilities and income, thus controlling for potential confounding by social class.

Adult

Protein kinases and phosphatases are involved in erythropoietin-mediated signal transduction.

To study the role of protein phosphorylation in erythropoietin (EPO)-mediated signal transduction, we examined the effects of tyrosine phosphatase and tyrosine and serine-threonine kinase inhibitors as well as activators of serine kinases on DNA synthesis and cell proliferation in the murine EPO-dependent cell line HCD-57. HCD-57 cells were obtained synchronized in G0 by centrifugal elutriation, and DNA synthesis was measured by incorporation of labeled thymidine into DNA. Half-maximal DNA synthesis was stimulated by 0.001 U/ml of EPO. Sodium orthovanadate (Na3VO4), a tyrosine phosphatase inhibitor, at 5 microM potentiated a subsaturating concentration of EPO. Na3VO4 alone stimulated HCD-57 DNA synthesis at concentrations of 0.1-20 microM. Zinc chloride, another tyrosine phosphatase inhibitor, also stimulated HCD-57 DNA synthesis at concentrations of 50-100 microM. Genistein, a tyrosine kinase inhibitor, blocked the effect of EPO at a concentration of 5 micrograms/ml. Bryostatin, a protein kinase C (PKC) activator, stimulated DNA synthesis in HCD-57 cells at concentrations of 10(-9)-10(-10) M, whereas the phorbol ester, phorbol 12,13-dibutyrate (PDBu), was stimulatory only at a concentration of 10(-11) M. Staurosporine, a PKC inhibitor, blocked the effect of EPO at a concentration of 10(-7) M, and H-7, a nonspecific protein kinase inhibitor, was not inhibitory. These agents also had similar effects on the in vitro proliferation of HCD-57 cells. Taken together, the data indicate that the EPO-mediated transition from G0 to S phase in HCD-57 cells involves the activation of both tyrosine and serine-threonine kinases and is modulated by tyrosine phosphatase activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

A new approach to template purification for sequencing applications using paramagnetic particles.

A new method using traditional hybridization methodology, coupled with the new magnetic particle technology, has been developed for DNA purification, specifically for sequencing applications. The method is similar to the reverse hybridization blot system; however, a specific oligonucleotide probe was attached to the paramagnetic particle instead of a sheet membrane. The target DNA containing the complementary sequence of the probe hybridizes to the probe that is attached to the bead and is then magnetically removed from solution, washed and collected. This system eliminates the need of organic extractions and precipitation/concentration steps. The entire hybridization-purification system can be done in a 1.5-ml microcentrifuge tube making the method ideal for automation. M13 phage clones were purified with this method, both by manual means and by using the CATALYST 800 Molecular Biology LabStation fitted with a prototype magnetic station, and then sequenced. DNA sequencing results obtained with this system were reproducible and gave excellent length of read with low background.

Base Sequence