Robert L. Berger

Effect of Coronary Bypass Surgery on Survival Patterns in Subsets of Patients With Left Main Coronary Artery Disease Report of the Collaborative Study in Coronary Artery Surgery (CASS)

The 3 year cumulative survival rate of 1,492 patients with left main coronary artery disease (50 percent or greater stenosis of luminal diameter) enrolled in the Collaborative Study in Coronary Artery Surgery (CASS) was 91 percent for the surgical group and 69 percent for patients treated medically (p less than 0.0001). Mortality was significantly greater in patients with impaired left ventricular function. The difference between medical and surgical therapy was significant for patients who had normal, moderately abnormal and severely impaired left ventricular function and for patients with stenosis of the left main coronary artery of 50 to 59, 60 to 69, 70 to 79 and 80 percent or greater. Aortocoronary bypass surgery did not significantly improve survival in patient subgroups who had (1) a nonstenotic dominant right or balanced coronary circulation, (2) a stenotic dominant right coronary artery and normal left ventricular function, and (3) left main coronary stenosis of 50 to 59 percent and normal or mildly abnormal left ventricular function. The Cox proportional hazards model was used to select baseline variables that were independent predictors of long-time mortality. The model selected left ventricular score, age, congestive heart failure score, hypertension, percent left main coronary arterial stenosis and coronary arterial dominance as the baseline variables most predictive of long-term survival. A clinical and angiographic prognostic risk index developed from these six baseline variables showed significantly improved survival for the surgical cohort in each of four risk categories. In the best and worst risk category, the 3 year survival rate was 97 and 82 percent, respectively, for the surgical group and 85 and 34 percent, respectively, for the medical group (p less than or equal to 0.0002). The data from this observational study show that coronary bypass surgery prolongs life in most patients with left main coronary artery disease, particularly those who have severe narrowing of the left main coronary artery or impaired left ventricular function. The results permit a better understanding of the natural history of left main coronary artery disease and permit a more accurate estimate of long-term survival for individual patients through the use of a clinical-angiographic risk index.

High resolution mixer for the study of the kinetics of rapid reactions in solution.

The turbulent wake of a spherical surface was utilized as part of a mixer for fast reaction studies. The mixer is capable of mixing two solutions within 100 μsec at a flow velocity of 30 m/sec. Optical and thermal methods were used to study the mixer. Highly efficient mixing was achieved for 120 cP solutions as well as aqueous solutions.

High Speed Optical Stopped‐Flow Apparatus

A stopped flow apparatus for the study of fast reactions in solution is described. The measured dead time was 270 μsec with an uncertainty in the measurement of 50 μsec. At 410 mμ and an optical density of about 0.09 a change of 0.0044 optical density units could be observed at a flow velocity of 30 m/sec through a 3.0 mm observation tube. Ten milliliters of each of the two reagents are required to fill the system, and less than 1.0 ml of each needs to be expended per experiment.

A chemical quenching apparatus for studying rapid reactions

Abstract A chemical quench-flow apparatus is described for studying enzymatic reactions with half-lives of 0.005 sec or longer. The syringe pistons are driven by a stepping motor which provides precise control over the volume and rate of flow of reactants. The drive mechanism also ensures a rapid approach to a steady flow velocity and thus minimizes the amount of material used per stroke. Improved mixing efficiency is accomplished by means of ball mixers which utilize the zone of turbulence in the wake of a sphere as the mixing mechanism. The instrument was used to follow the presteady state time course of phosphorylation and dephosphorylation of a microsomal preparation of (Na + + K + )-stimulated ATPase.

Continuous Determination of the Oxygen Dissociation Curve for Whole Blood

We report here the development of a new method that allows continuous determination of the oxygen dissociation curve for microsamples (600 mul) of whole blood under conditions of pH, pCO2, methemoglobin concentration, and 2,3-diphosphoglycerate content closely approaching those found in the circulatory system. The method consists of gradually oxygenating a blood sample by adding H2O2 in the presence of catalase (EC 1.11.1.6), to produce the reaction H2O2 leads to H2O + 1/2 O2. Because the total oxygen content of blood can be derived from the known rate of H202 addition and the pO2 is determined in the liquid phase by an oxygen electrode, the two functions (total O2 content) and (% oxygen saturation) vs. pO2 are simple to calculate. pCO2 and pH are controlled by adding base simultaneously with the gradual oxygenation of blood. The method described thus avoids the direct measurement of oxygen saturation of whole blood.

Thermal titrimetric evaluation of the heats of ionization of the commonly occurring amino acids and their derivatives.

Abstract By using instrumentation of relatively simple design it has been shown that calorimetric data of good precision can be obtained with rapidity and ease of operation. The heats of ionization of all the commonly occurring amino acids have been determined and, depending on the differences in ionization constants, heats of ionization of individual groups in a mixture can also be obtained.

Combined Calorimeter and Spectrophotometer for Observing Biological Reactions

A stopped‐flow fast reaction apparatus is described which permits chemical reactions with rate constants of 50 sec−1, or less, to be followed both spectrophotometrically and calorimetrically. The thermal detector is a single copper‐constantan thermocouple, 5μ thick, with a response time of 3 msec. Using a bandpass of 0 to 80 cps, the signal‐to‐noise ratio is 1:1 for a heat change of 100 μcal/ml. The apparatus is housed in a 30×30‐cm aluminum cylinder which is temperature stable to ±0.00001°C; reactants can be brought to within 0.001°C of equilibrium in less than 1 h. Acrylic light pipes are employed in the optical detection system to conduct a monochromatic light beam to the observation tube and to conduct the transmitted light to a photomultiplier. Solenoid valves control the mixer inputs; a third solenoid valve stops the flow in 2 msec. The thermal system and calorimeter were analyzed mathematically and two computer programs developed which make corrections for the response time of the system, correct t...

General Computer Method of Analysis of Conduction and Diffusion in Biological Systems with Distributive Sources

A method of analysis by use of the computer has been developed which permits the physical laws governing conduction, or diffusion, to be expressed in first‐order finite form. Solutions are obtained in the one‐dimensional case for rectangular, cylindrical, and spherical geometries without the use of transcendental functions or other conventional mathematical iterative methods. The case of the cylindrical calorimeter with concentric insulating and conducting layers of varying chemical properties and with distributive heat sources arising from biochemical reactions at the center is treated in the transient and steady‐state case.

Stopped-flow fluorometry with available instrumentation

Abstract Stopped-flow fluorescence experiments were conducted on a microscale in a spectrofluorometer by using an air-driven mixer attachment. All parts of the system employed, including the electronic components, are commercially available. There are many biochemical reactions of interest which take place in 0.05 to 10 seconds, that can be studied by fluorescence in this simple system. Examples shown are: ( 1 ) combination of carbonic anhydrase with a fluorescent sulfonamide; ( 2 ) reduction of α-ketoglutarate catalyzed by glutamate dehydrogenase at high concentration (1.5 mg/ml); and ( 3 ) formation of a ternary complex of lactate dehydrogenase. The mixing accessory is based on the design of R. Harvey and is compatible with a number of spectrometers.

Determination of the activity and concentration of immobilized and soluble enzymes by microcalorimetry

Abstract The relationship between activity and concentration of both soluble and immobilized lactate dehydrogenase and uricase was determined using the rate of heat production in a batch-type microcalorimeter. The results demonstrate the feasibility of using microcalorimetry for the determination of enzyme levels in biological fluids and for the determination of the activity of particle-bound enzymes.