PubMed HealthSearch

Biomedical subjects

R L Berger

Publications and source records attributed to R L Berger.

At least 19 recordsLinked to original sources

Safety and efficacy of autologous blood donation before elective aortic valve operation.

Although the use of preoperative autologous blood donations for patients undergoing elective cardiac operations has increased dramatically in recent years, patients awaiting elective aortic valve replacement have traditionally been denied access to preoperative autologous blood collection programs. We report our experience with 79 patients, each of whom donated 1 to 3 units of autologous blood before an aortic valve operation. All patients had serious aortic valve disease as evidenced by symptoms and preoperative catheterization data. The patients collectively made 129 blood donations. One patient had a syncopal episode within 2 hours of donation and recovered without difficulty. Of the patients who gave autologous blood preoperatively, 68% avoided any homologous blood donor exposure during their subsequent hospitalization for aortic valve replacement. In contrast, in a group of 298 patients who did not give autologous blood preoperatively, only 31% avoided homologous blood exposure during aortic valve replacement (p < 0.0001). Our experience suggests that preoperative autologous blood donation by patients awaiting elective aortic valve replacement is both safe and effective. Patients with aortic valve disease should not be routinely excluded from preoperative blood services.

Adult

Thoracic surgery and the war against smoking: Richard H. Overholt, MD.

Richard H. Overholt was born at the beginning of the twentieth century when thoracic surgery hardly existed. During the first 20 years of his life progress in the field was slow. The next 20 years, which coincided with Overholt's surgical training and his early years as a thoracic surgeon, saw a rapid and almost explosive growth. Overholt's contributions were legion. They included the world's first successful right pneumonectomy, advancements in surgical treatment of tuberculosis, development of segmental resection, and introduction of the prone operative position. He was a bold and creative pioneer thoracic surgeon with consumate technical skills. Sixty years ago, when Overholt started his career as a thoracic surgeon, the hazards of smoking were not appreciated, the habit was fashionable, and consumption of tobacco was rapidly rising. In the early 1930s Overholt was among the very few physicians who recognized the perils of smoking and initiated a long but initially unrewarding antismoking crusade. By the early 1950s evidence about the ill effects of tobacco use began to accumulate. Organized medicine, voluntary health groups, and governmental agencies joined in a concerted effort to educate and to contain smoking. During the ensuing 30 years the antismoking movement achieved ever-increasing success. Today, it is widely recognized that smoking is a major health hazard and tobacco consumption is on the decline. Richard Overholt issued the first warning signals about the perils of tobacco and served as an indefatigable leader of the antismoking crusade throughout his professional career.

History, 20th Century

Replacement of the thoracic aorta with intraluminal sutureless prosthesis.

A survey of the collective experience reveals that between 1976 and 1990, a sutureless intraluminal prosthesis was used to replace the ascending thoracic aorta, arch, and descending thoracic aorta in 122, 14, and 81 patients, respectively. During these 217 operations, at least 364 of the 434 anastomoses were performed by sutureless fixation. The underlying disease processes consisted of acute and chronic dissections; atherosclerotic, Marfan's, and mycotic aneurysms; and intraoperative disruptions of the ascending aorta. The data in the literature suggest that sutureless fixation shortens aortic cross-clamp time and reduces blood loss. Early graft-related complications were few and probably can be further reduced by improving surgical techniques. The incidence of paraplegia and renal failure after descending aortic grafting was identical at 2.5%. The operative mortality rate for ascending aortic, arch, and descending aortic replacement was 13.1%, 42.9%, and 14.8%, respectively. Long-term follow-up of 143 patients revealed satisfactory graft function with three possible device-related deaths and no other known complications attributable to the prosthesis. There are, however, anecdotal references to late complications from the intraluminal prosthesis. Most of these relate to faulty implantation techniques, but some could be due to flaws inherent in the concept of sutureless grafting. The collective experience suggests that grafting of the thoracic aorta is less hazardous with the sutureless than with the conventional sutured anastomosis technique. The implications of the anecdotal accounts about late complications remain to be determined.

Anastomosis, Surgical

Thermodynamic characterization of daunomycin-DNA interactions: microcalorimetric measurements of daunomycin-DNA binding enthalpies.

We report the first direct determination of binding enthalpies for the complexation of monomeric daunomycin with a series of 10 polymeric DNA duplexes. These measurements were accomplished by using a recently developed stopped-flow microcalorimeter capable of detecting reaction heats on the microjoule level. This enhanced sensitivity allowed us to measure daunomycin-DNA binding enthalpies at monomeric drug concentrations (e.g., 10-20 microM), thereby precluding the need to correct for daunomycin self-association, as has been required in previous batch calorimetric studies [Remeta, D. P., Marky, L. A., & Breslauer, K. J. (1984) Abstracts of Pittsburgh Conference and Exposition on Analytical Chemistry and Applied Spectroscopy, 838a; Breslauer, K. J., Remeta, D. P., Chou, W. Y., Ferrante, R., Curry, J., Zaunczkowski, D., Snyder, J. G., & Marky, L. A. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8922-8926]. We correct the published daunomycin-DNA binding enthalpies measured by batch calorimetry at higher drug concentrations (e.g., 0.5-1.0 M) for the enthalpy contribution associated with the binding-induced disruption of drug aggregates. The requisite correction term was obtained from a van't Hoff analysis of temperature-dependent NMR measurements on daunomycin solutions. We find remarkable agreement between the net binding enthalpies derived from these corrected batch calorimetric data and the corresponding binding enthalpies measured directly by stopped-flow microcalorimetry. The enhanced sensitivity of the stopped-flow instrument also allowed us to evaluate the influence of drug binding density on the daunomycin-DNA binding enthalpies. This assessment was accomplished by conducting stopped-flow calorimetric measurements over a range of seven different drug-to-phosphate ratios (r). For most of the 10 DNA host duplexes studied, we find that the daunomycin binding enthalpies exhibit small but significant r dependencies. The sensitivity of the stopped-flow instrument also enabled us to detect significant dilution enthalpies for several of the drug-free DNA duplexes, a quantity generally assumed to be negligible in previous studies. We discuss the binding enthalpies, their dependence on binding density, and the duplex dilution enthalpies in terms of the influence of base composition, sequence, conformation/hydration, and binding cooperativity on the sign and the magnitudes of the daunomycin-DNA binding enthalpy data reported here.

Binding Sites

A stopped-flow mixer device for a batch microcalorimeter application to NAD-NADase reaction.

A new molded polypropylene, diamond-like carbon (DLC)-coated mixing cell has been developed for use in the batch microcalorimeter. Reagent volume can be varied from 25 microliters to 100 microliters. A 10 microcalorie reaction heat can be measured to 5%. Repeat reactions can be done as often as every 10 min for a fast reaction. Reactions can be started within 1 h or less after loading. A pre-equilibrator and a temperature-controlled syringe drive unit permit solutions to be stored at 4 degrees C while being run at any temperature from -20 degrees C to 40 degrees C. The kinetics and enthalpy of reaction of NAD-NADase have been measured. delta H is about 21 kcal/mol endothermic.

Calorimetry

A computer-controlled all-tantalum stopped-flow microcalorimeter with microjoule resolution.

A new all-tantalum differential stopped-flow heat-conduction microcalorimeter with microjoule resolution has been developed. The instrument consists of two matched channels, each of which has two reagent inlet lines. A computer is used to process the data and control the syringe drive system which runs the samples through the calorimeter. The reagents are mixed in 0.6 s in ratios of 1:1, 1:2, 1:2.5, 1:4, 1:5, or 1:10. The priming volume from the loading port to the mixer is 1 ml and the reaction volume of the detection tube is 160 microliters. The instrument has a sensitivity of 1.60 J/V.s and a differential baseline stability of 100 nJ/s (p-p) over a 4 h period. The sample size can be reduced to 27 microliters with only a 12% loss in sensitivity. With an electrical step power input, the 10-90% response is 40 s. By using a data decomposition scheme, the response time can be improved to 1 s which allows the direct measurement of moderately fast reaction kinetics. With water/water mixes, differential heats of mixing are typically (+/-) 2 microJ with a standard deviation of (+/-) 2.5 microJ. Reaction heats in the 20-50 microJ range can be measured with a standard deviation of (+/-) 3 microJ. A fast reaction, e.g. HCl dilution, can be completed in 150 s. When loading and priming times are included, 25 reactions can be completed in 120 min. A chilled water jacket is used to allow operation over a temperature range of 4 degrees C to 50 degrees C.

Calorimetry

Rupture of left ventricle following mitral valve replacement.

A survey of the English language literature revealed 125 cases of left ventricular rupture following mitral valve replacement. In ten larger series, the incidence averaged 1.2%. Most of the ruptures were attributed either to technical maneuvers in the operation or to stretch injury produced by the untethering of the left ventricle through removal of the mural leaflet of the mitral valve. Preventive measures include modifications in operative techniques, containing pressure-volume work by the left ventricle, and probably retention of the posterior mitral leaflet. Surgical repair of the rupture with and without the aid of cardiopulmonary bypass resulted in 50% and 7% survival, respectively. With the use of cardiopulmonary bypass, external repair was followed by a 67% survival and the internal approach, by a 27% survival.

Heart Rupture

Tests and confidence sets for comparing two mean residual life functions.

The mean residual life function of a population gives an intuitive and interesting perspective on the aging process. Here we present new nonparametric methods for comparing mean residual life functions based on two independent samples. These methods have the flexibility to handle crossings of the functions and result in a new type of confidence set. We also discuss similar methods for comparison of median residual life functions.

Animals

The determination of binding constants with a differential thermal and potentiometric titration apparatus. II. EDTA, EGTA and calcium.

A differential pH and thermal titrimeter has been used to determine the ionization constants of EDTA and EGTA as well as their calcium complexes. The intrinsic heat of binding is a constant for the pH range 2-11.5 for both substances and is found to be -5.4 kcal mol for EDTA and -7.9 kcal mol-1 for EGTA. The binding constants evaluated by fitting to the potentiometric curves and expressed as the log are 10.25 and 11.0, respectively. These values compare reasonably well to those reported in the literature. We have proposed that the binding of calcium occurs even at acid pH based on the pH drop observed at pH 2 when calcium is added, the reversibility of the thermal and the potentiometric curves, the lack of hysteresis upon rapid titration, the constancy of the intrinsic heat of binding and fitting of the entire potentiometric curves using the appropriate binding constants.

Calcium

Mössbauer spectroscopic studies of hemoglobin and its isolated subunits.

Samples of 90% enriched 57Fe hemoglobin and its isolated subunits have been prepared. Mössbauer spectroscopic measurements have been made on three such samples. Sample one contained contributions of oxyhemoglobin, deoxyhemoglobin, and carbonmonoxyhemoglobin. This sample was studied from a temperature of 90 K down to 230 mK. Measurements were also made at 4.2 K using a small applied magnetic field of 1.0 T. In general, the measured quadrupole splittings and isomer shifts for each component agreed with previous measurements on single component samples in the literature, and thus demonstrated that chemically enriched hemoglobin has not been altered. The second and third samples were isolated alpha and beta subunits, respectively. We have found measurable Mössbauer spectral differences between the HbO2 sites in the alpha subunit sample and the beta subunit sample. The measured Mössbauer spectral areas indicate that the iron ion has the largest mean-square displacement at the deoxy Hb sites as compared to that at the oxy- and carbonmonoxy Hb sites. The mean-square displacement at the HbO2 sites is the smallest.

Cobalt Radioisotopes

Clinical temporary ventricular assist. Pathologic findings and their implications in a multi-institutional study of 41 patients.

Forty-one patients, distributed among four centers, had left (33 patients), right (five), or bilateral (three) temporary ventricular assistance with textured (24) or smooth (17) surfaced diaphragm pumps, during an evaluation supported by the National Institutes of Health. Cardiac failure had occurred in 39 postoperative patients (after aorta-coronary bypass [23], valve replacement [four], both [nine], or other [three]), with total cardiopulmonary bypass time mean 306 minutes (range 69 to 600). Two patients had cardiomyopathy. Death of 35 nonsurvivors was due to myocardial necrosis (14), hemorrhage (nine), cerebrovascular accidents (three), infection (three), and other (six). Mean duration of support in all patients was 62 hours. In 16 patients (40%) whose condition improved, cardiac assist duration was mean 127 hours (range 48 to 264), compared with mean 19 hours (range 1 to 120) in 25 who did not. Of 17 patients in whom duration of support exceeded 72 hours, 15 (88%) improved, 11 were weaned, and six survived long term. Tissue examination (in 33 patients) by biopsy at pump implantation or autopsy revealed coagulation or contraction band myocyte necrosis, with or without hemorrhage, in 26 patients; of these, 10 improved and six were long-term survivors. Pump-related complications (two) included pulmonary embolism, most likely related to a cannulation site thrombus, and an aortic cannulation site infection in one patient each. This study suggests that mechanical cardiac assist may be accomplished with a low complication rate; should not necessarily be denied to patients with existing necrosis, because myocardial necrosis does not preclude improvement or survival; and frequently leads to functional myocardial recovery if patients survive early noncardiac complications, often the result of long duration of cardiopulmonary bypass.

Adolescent

An automated differential thermal and potentiometric titration apparatus for binding studies.

A differential pH-thermal titration apparatus is described which can detect pH differences with a sensitivity of +/- 0.0001 pH units and a thermal sensitivity of +/- 0.00002 degree C at a time constant of 0.1 s. With a reaction which yields 1 kcal mol-1, the current system can detect concentrations as low as 4 X 10(-6) M or, in a 2 ml volume, a total amount of 40 nmol. With a time constant of 0.1 s, the sensitivity is 20 +/- 4 micro degrees C. The experimental protocol is specified by a microprocessor and three modes of operation are possible: titration at constant rate of reagent addition, titration at variable rates of addition so that the contents of both cells are at either constant pH or at a constant temperature and variable rate when a rate of change is specified. Experimental data are collected in files, corrected for heat loss, initial baseline drift, and changes in volume. The final corrected data from the standardized run of 0.01338 M HCl in 0.2 M KCl at 25 degrees C calibrate the pH scale and yield the calorimetric conversion constants and pKw which are calculated and stored for subsequent corrections for the titration of an unknown acid or the measurement of binding constants and heats.

Calorimetry

Application of the finite element simulation method to the adiabatic and potentiometric corrections of calorimetric titration data.

A general numerical analysis procedure is described which has been applied to an automated differential pH-thermal titration apparatus operated isoperibolically to obtain thermal corrections for heat loss. It is based on the Direct Byte (D-B) finite element computer simulation technique (FEST) applied to the heat conduction behavior of the instrument with time. Thermal constants of the numerical model are determined, and the results of the correction for titration data obtained from acid-base runs show that a constant upper baseline is achieved using this technique for both fast and slow reactions to an accuracy of 2%. The method is equally valid for endothermic and exothermic reactions.

Calorimetry

Use of the twin-cell differential titration calorimeter for binding studies. I. EDTA and its calcium complex.

The use of a twin-cell differential titration calorimeter is described which utilizes small volumes (1-3 ml) of modest concentrations of materials (0.001-0.01 M) and yields data of good precision. Operation is controlled by a microprocessor which regulates and controls the addition of reagents and collects and displays the data as time, temperature in volts, and the pH. Corrections for the titration of water are applied to the potentiometric data, and the thermal data are corrected for the initial temperature-time baseline, the changes in heat capacity, and the heat loss (or gain) to the external environment. Finally, the thermal signal is corrected for the heat derived from the formation of water due to the free hydrogen or hydroxyl ions present. The corrected data as pH, groups titrated and delta HT (kcal/mol) can then be used to obtain the parameters pK' and delta Hi involved with the equilibria by curve-fitting the observed data. The system has been applied to the ionization of EDTA and its calcium complex. The ionization constants, the heats of ionization, the stoichiometry of binding and the heat of binding have been determined and demonstrated to be in agreement with published values.

Calcium

Long-term follow-up of postcardiotomy patients with profound cardiogenic shock treated with ventricular assist devices.

Success of ventricular assist devices in patients with postcardiotomy shock has provided enough survivors to allow evaluation of the length and quality of life. Fifteen survivors from 28 to 68 years (mean 53) old from four centers were followed for 6 to 77 months (mean 35) after discharge from the hospital. Four patients suffered perioperative myocardial infarctions. In three patients, ventricular function was normal before surgery and remained so afterward. Of 12 patients with moderate or severely impaired ventricular function, five improved, five were unchanged, and two were worse. One patient died 6 months after surgery of cardiomyopathy. Seven patients are employed full-time and one works part-time. Five patients are retired but active and one is moderately disabled. NYHA functional class improved in the patients as a group: 13 were in classes III and IV before surgery and 13 were in classes I and II after surgery. Two patients had noncardiac partial disability. Survivors of ventricular assist device support for postcardiotomy shock have an excellent chance for high-quality life and the risk of crippling cardiac disability is small.

Adult