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Biomedical subjects

E C Harrison

Publications and source records attributed to E C Harrison.

At least 19 recordsLinked to original sources

Application of a Bayesian method to monitor and adjust vancomycin dosage regimens.

A Bayesian method for monitoring vancomycin concentrations and adjusting regimens in patients with unstable renal function by using a two-compartment population model was evaluated with a personal computer. The population model was derived from data from 12 cardiac outpatients who received single doses of vancomycin. The performance of the method was then tested in 27 acutely ill patients who received multiple doses of vancomycin. Significant renal impairment was observed in 15 patients. Renal function changed in 15 patients. The vancomycin concentrations in the patients with changing renal function were not at steady state during the observation times. Two concentrations in serum (peak and then trough, or trough and then peak) were fitted along with the population model to individualize the parameter values for each patient. All the subsequent concentrations in serum for each patient were then predicted by using the parameter values for each patient. Future concentrations of 118 serum samples were predicted. The mean absolute prediction error was 3.6 +/- 4.5 micrograms/ml, and the mean prediction error was -0.7 +/- 5.3 micrograms/ml. These results confirm that a two-compartment pharmacokinetic model can be sufficiently individualized with the knowledge of just two concentrations of drug in patient serum; it is possible to predict closely subsequent concentrations in serum, and dosing regimens for individual patients can be well adjusted to achieve the chosen therapeutic goals.

Adult

Flow characteristics of bioprosthetic heart valves.

A review of the in vivo and in vitro fluid dynamic performance of three bioprosthetic heart valves is presented. Data on Hancock porcine valves (standard models 242 aortic and 342 mitral and modified orifice model 250 aortic), Carpentier-Edwards porcine valves (model 2625 aortic and 6625 mitral), and the Ionescu-Shiley pericardial valve are reviewed. These valves were chosen because of their past or present popularity in clinical use and because of the variation in fluid dynamic performance reported by different investigators. The flow parameters that are reported include in vivo and in vitro mean pressure drop, cardiac output or cardiac index, regurgitant volume, effective orifice area, and performance index. These data provide a framework for differentiation of normal and abnormal bioprosthetic valve function.

Animals

In vitro flow dynamics of four prosthetic aortic valves: a comparative analysis.

The velocity fields downstream of four prosthetic heart valves were mapped in vitro over the entire cross-section of a model aortic root using laser Doppler anemometry. THe Björk-Shiley 60 degrees convexo-concave tilting disc valve, the Smeloff-Cutter caged ball valve, the St. Jude Medical bileaflet valve, and the Ionescu-Shiley standard bioprosthesis were examined under both steady and pulsatile flows. Velocity profiles under steady flow conditions were a good approximation for pulsatile profiles only during midsystole. The pulsatile flow characteristics of the four valves showed variation in large scale flow structures. Comparison of the valves according to pressure drop, shear stress and maximum velocities are also provided.

Aortic Valve

An emergency physician's guide to prosthetic heart valves: identification and hemodynamic function.

We describe methods for identifying the type and size of seven commonly used prosthetic heart valves and how these features influence the hemodynamics of flow through the valve. The four mechanical heart valves reviewed are Starr-Edwards silicone rubber ball valves (Models 1200/1260 aortic and 6120 mitral valves), Bjork-Shiley tilting disc valves (60 degrees standard spherical model and the 60 degrees convexo-concave model), Medtronic-Hall (Hall-Kaster) tilting disc valve, and St Jude Medical bileaflet valve. The three bioprostheses reviewed are Hancock porcine valve, Carpentier-Edwards porcine valve, and Ionescu-Shiley bovine pericardial valve. These valves were chosen because of their past or present popularity and therefore are the ones most apt to be implanted in patients seen in the emergency department.

Bioprosthesis

An emergency physician's guide to prosthetic heart valves: valve-related complications.

Serious valve-related complications that occur in patients with prosthetic valves have been discussed. The emergency physician's role primarily is to recognize the high probability that one of these serious complications exists and hospitalize the patient so that rapid definitive diagnoses and therapeutic decisions are not delayed.

Anemia, Hemolytic

The pharmacokinetics of antiarrhythmic agents in pregnancy and lactation.

The pharmacokinetics of various drugs may be profoundly altered during different stages of pregnancy, parturition, and lactation. Gastrointestinal absorption or bioavailability of drugs may vary due to changes in gastric secretion and motility. Various haemodynamic changes such as an increase in cardiac output, blood volume, and renal plasma flow may affect drug disposition and elimination. The increase in blood volume and total body water which occurs during pregnancy can alter the volume of distribution for various drugs. Although exact quantifications are not easy, these changes in pharmacokinetic parameters should be considered when dosing antiarrhythmic agents in pregnant women. Plasma protein concentrations and drug binding capacity are altered in the mother and fetus as pregnancy advances. With highly protein bound drugs, these changes may be clinically significant, as the pharmacological efficacy and toxicity are presumed to be related to the concentration of free drug in both the mother and fetus. In some instances, the fetus may be susceptible to greater drug toxicity as free drug concentrations may be underestimated by measurement of total drug concentrations. Changes in maternal drug metabolism and metabolism by the fetoplacental unit also contribute to alterations in the pharmacokinetics of drugs. As the placenta contains many metabolising enzymes, biotransformation of drugs at this site could potentially convert a drug into an active metabolite, or prevent fetal exposure to a toxic drug. Placental transfer of drugs, leading to toxicity in the fetus, is a major concern in the pharmacological management of the pregnant patient. The passage of individual drugs will vary depending on their apparent volumes of distribution, degree of protein binding the rates of metabolic conversion and excretion within the placenta and fetus, the pH difference between the maternal and fetal fluids, and maternal haemodynamic changes. Drug properties such as lipid solubility, protein binding characteristics, and ionisation constant (pKa) also influence the placental passage of drugs. For weakly basic antiarrhythmic agents, the fetal drug concentration may potentially exceed the maternal plasma concentration when the fetal pH is lowered as in the case of fetal acidosis; this is due to 'ion trapping'. Additionally, higher free drug concentrations of these basic drugs may exist, due to decreased alpha 1-acid glycoprotein concentration and binding affinity in the fetus. Lignocaine (lidocaine) has been shown to enter fetal plasma rapidly with fetal-maternal concentration ratios in the range of 0.52 to 0.66.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Arrhythmia Agents

Flow characteristics of four commonly used mechanical heart valves.

The in vivo and in vitro fluid dynamic performance of 4 mechanical heart valves was reviewed: Starr-Edwards silicon-rubber ball valves (models 1200/1260 aortic and 6120 mitral valves), Björk-Shiley tilting disc valves (standard spherical model, modified and unmodified convexo-concave [60 degrees and 70 degrees C-C] models), the Medtronic-Hall (Hall-Kaster) tilting disc valve and the St. Jude Medical bileaflet valve. These valves were chosen because of their past or present popularity in clinical use and because they encompass most of the basic mechanical valve designs used during the past 2 decades. The flow measurements reported include in vivo and in vitro mean pressure drop, cardiac output or cardiac index, regurgitant volume, effective orifice area and performance index.

Cardiac Output

Regurgitation of prosthetic heart valves: dependence on heart rate and cardiac output.

Prosthetic heart valves exhibit closure and leakage backflow; however, no well-controlled study to evaluate the influence of factors such as cardiac output and heart rate on backflow has been reported to date. Four clinically used prosthetic aortic valves (size 27 mm)--St. Jude Medical, Björk-Shiley Spherical Disc, Björk-Shiley Convexo Concave, and Starr-Edwards model 1260--were studied in the aortic chamber of a pulse duplication system at heart rates of 50, 80, 110, and 140 beats/min, cardiac output of 2, 4, 6, and 8 liters/min, and mean aortic pressure of 100 mm Hg. Regurgitation was calculated in percentage and found to vary directly with heart rate and inversely with cardiac output. The range of values obtained were 5.5% for the Starr-Edwards model 1260 valve at 110 beats/min and 8 liters/min, to 37.5% for the Björk-Shiley Convexo Concave valve at 140 beats/min and 2 liters/min. Regurgitation was also calculated in milliliters/stroke and ranged from 3.4 ml/stroke for the Starr-Edwards model 1260 valve at 140 beats/min and 2 liters/min, to 17.3 ml/stroke for the Björk-Shiley spherical disc valve at 50 beats/min and 2 liters/min. Regurgitation associated with prosthetic heart valves may present a problem clinically, particularly under conditions of low cardiac output and tachycardia.

Cardiac Output

In vitro fluid dynamic characteristics of Ionescu-Shiley and Carpentier-Edwards tissue bioprostheses.

In the study reported here, the in vitro fluid dynamic characteristics of the Ionescu-Shiley (calf pericardial) and Carpentier-Edwards (porcine) aortic tissue valves were studied. The experiments conducted were pressure drop measurements, leaflet photography, flow visualization, and velocity measurements. The pressure drop studies indicated that both types of tissue valves created relatively large pressure drops. These pressure drops were larger than those observed with the corresponding sizes of Bjork-Shiley, Hall-Kaster, and St. Jude aortic prostheses. The photographs of the opening of the valve leaflets indicated that the tissue valves do not open as ideally as do the natural valves. It was also observed that the Ionescu-Shiley aortic valves opened more symmetrically and with reproducibility than the corresponding Carpentier-Edwards aortic valves. Velocity and shear stress measurements made with a laser-Doppler anemometer indicated that the flow that emerged from the leaflets for both types of tissue valves was like a jet and could lead to turbulent shear stress on the order of 1,000-3,000 dynes/cm2. Such turbulent shear stresses could be harmful to blood components. The jet-type flow could also damage the endothelial lining of the wall of the ascending aorta. The velocity measurements also indicated an annular region of stagnant fluid between the outflow surfaces of the leaflets and the flow channel wall. Such a region could lead to the build-up of thrombotic, fibrotic, and/or calcific material on the outflow surfaces of the leaflets. Both types of valve designs, however, created relatively low wall shear stresses and regurgitant volumes.

Animals

In vitro fluid dynamic characteristics of the Medtronic-Hall pivoting disc heart valve prosthesis.

The need for better low-profile mechanical valves led to the design and development of the Medtronic-Hall (formerly known as the Hall-Kaster valve) pivoting disc heart valve prosthesis in 1976. In vitro flow studies indicate that it has improved pressure drop characteristics compared to the Lillehei-Kaster and convexoconcave Björk-Shiley (60 degrees model) tilting disc valves. It does, however, have a somewhat larger regurgitant volume compared to the Björk-Shiley valve design. Velocity measurements with a laser-Doppler anemometer in the immediate downstream vicinity of the Medtronic-Hall valve indicate no region of stagnation near the outflow face of the disc. Regions of stagnation were, however, observed adjacent to the two titanium "pivot stops" situated on either side of the disc in the major orifice and along the pivot post in the minor orifice, together with a region of flow separation adjacent to the sewing ring of the minor outflow region. The results of the present in vitro study indicate a small but significant improvement in the overall fluid dynamic performance of the Medtronic-Hall valve, compared to the convexo-concave Björk-Shiley (60 degrees model) and Lillehei-Kaster tilting disc prostheses in current clinical use.

Aortic Valve