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Biomedical subjects

R L Berger

Publications and source records attributed to R L Berger.

At least 19 recordsLinked to original sources
PubMed2001

Backscatter reduction using combined spatial, temporal, and polarization beam smoothing in a long-scale-length laser plasma.

Spatial, temporal, and polarization smoothing schemes are combined for the first time to reduce to a few percent the total stimulated backscatter of a NIF-like probe laser beam (2x10(15) W/cm (2), 351 nm, f/8) in a long-scale-length laser plasma. Combining temporal and polarization smoothing reduces simulated Brillouin scattering and simulated Raman scattering (SRS) up to an order of magnitude although neither smoothing scheme by itself is uniformly effective. The results agree with trends observed in simulations performed with the laser-plasma interaction code F3D simulations [R. L. Berger et al., Phys. Plasma 6, 1043 (1999)].

Journal Article↗
PubMed2001

Thomson scattering measurements of saturated ion waves in laser fusion plasmas.

We have measured the characteristics of saturated ion-acoustic waves in inertial confinement fusion plasmas. A 263-nm probe laser has been applied to simultaneous Thomson scatter on both ion-acoustic waves excited by thermal electrostatic fluctuations and by stimulated Brillouin scattering of a kilojoule laser beam of varying intensity. The Thomson scattering spectra show saturated ion-wave amplitudes for intensities above 5x10(14) W cm(-2) consistent with three dimensional nonlinear wave modeling.

Journal Article↗
PubMed1997

An improved process for the production of sterile modified haemoglobin solutions.

The process for manufacturing bulk quantities of sterile solutions of human haemoglobin (Hb) cross-linked between the alpha chains (alphaalphaHb) with bis(3,5-dibomosalicyl) fumarate (DBBF) was modified to: (1) improve product purity; (2) increase product yield; (3) eliminate non-United States Pharmacopoeia materials; (4) reduce reagent costs; and (5) reduce production time. These process modifications were the result of increased scientific understanding of the Hb cross-linking chemistry and were in the form of engineering and procedure controls that reflect current good manufacturing practices (cGMP). Purity, as reflected in the fractional yield of the desired alphaalphaHb product, has increased from 60% to 90+% of total Hb, and uncross-linked Hb was virtually eliminated. Impurities such as pyrogens, methaemoglobin, phospholipid, and free iron were reduced. The net yield of alphaalphaHb was increased from 33% to 58% of starting Hb content. Production time, the use of overtime, the consumption of expensive reagents and filters, and losses because of contamination have all been reduced. As a result, cost per gram of alphaalphaHb produced has decreased 60%. With this improved process, efficient production of very pure alphaalphaHb is possible.

Chemistry, Pharmaceutical↗
PubMed1997

Hydrophobic properties of NAD glycohydrolase from neurospora crassa conidia and interaction with dioxane.

NAD glycohydrolase (NADase, EC 3.2.2.5) from Neurospora crassa conidia shows marked hydrophobic properties which are related to the self inhibition of the enzyme. Both aliphatic amines and carboxylic acids are able to inhibit noncompetitively the catalytic activity of the enzyme and the inhibition depends on the non-polar moiety of the substances. Also dioxane is an inhibitor of NAD glycohydrolase even though it apparently increases the specific activity of the enzyme. This effect can be explained by the fact that NADase is present as a dimer when the enzyme is concentrated or at high temperature, and dioxane binds the enzyme breaking the hydrophobic bonds in the dimeric enzyme and yielding the most active monomeric form which is only slightly inhibited by the organic solvent.

Amines↗
PubMed1994

Coronary artery bypass grafting in patients with transplanted livers.

Coronary artery bypass grafting was performed on 3 patients for refractory angina pectoris 48, 5, and 40 months after orthotopic liver transplantation. At the time of the cardiac operation, all 3 patients had drug-induced moderate renal dysfunction, and 1 of the 3 exhibited mild chronic rejection of the graft. Maintenance immunosuppressive therapy was continued during the cardiac operation and the perioperative period. Stress-dose steroids and standard prophylactic antibiotics were also employed. All 3 patients tolerated the cardiac surgical procedure without hepatic decompensation, excessive bleeding, infection, impaired wound healing, and other complications related to the transplanted organ or to the immunosuppressive therapy. Early postoperative liver function test results showed mild transient deterioration. One patient experienced a brief psychotic episode and massive upper gastrointestinal bleeding. Both complications were attributed to the steroids used in immunosuppressive therapy. Follow-up ranging from 2 to 24 months after coronary artery bypass grafting revealed that the patients were active and had no cardiac symptoms or manifestations of hepatic decompensation. It appears from this limited experience that cardiac operations can be performed safely in patients who have previously undergone liver transplantation.

Aged↗
PubMed1994

Heparin resistance after preoperative heparin therapy or intraaortic balloon pumping.

Heparin resistance, defined as failure of 500 IU per kilogram of body weight of heparin to prolong the activated clotting time (ACT) to 480 seconds or longer, was noted during 949 of 4,280 (22%) consecutive open heart surgical procedures performed on adults between 1986 and 1991. The total population was divided into the following four groups: group 1, preoperative intraaortic balloon support without concomitant heparin therapy (n = 138 patients); group 2, preoperative intravenous heparin therapy (n = 741 patients); group 3, intraaortic balloon support with concomitant intravenous heparin therapy (n = 137 patients); and group 4, controls, not receiving preoperatively the therapy given groups 1, 2, or 3 (n = 3,264 patients). The ACT response to an initial dose of 500 IU/kg of heparin and the incidence of heparin resistance were 596 +/- 203 seconds and 30% in group 1; 506 +/- 149 seconds and 50% in group 2; 520 +/- 159 seconds and 53% in group 3; and 705 +/- 234 seconds and 14% in group 4, respectively. These results indicate that preoperative intravenous therapy and intraaortic balloon support are associated with a decreased ACT response to intraoperative heparin. Baseline ACT levels and preoperative platelet counts were not predictive of heparin resistance. A reduced ACT response to the initial dose of heparin was associated with increased requirements for supplementary anticoagulant therapy during the ensuing period on cardiopulmonary bypass, indicating that the decreased sensitivity to heparin extends beyond the initial episode of heparinization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Ethics in scientific communication: study of a problem case.

The hypothermia experiments performed on humans during the Second World War at the German concentration camp in Dachau have been regarded as crimes against humanity, disguised as medical research. For almost 50 years, scientists maintained that the study produced valuable, even if not totally reliable, information. In recent years, the results from the Dachau hypothermia project were glamorized with life-saving potential and a heated ethical dialogue was activated about the use of life-saving but tainted scientific information. In the wake of the debate, an in-depth examination of the scientific rigour of the project was performed and revealed that neither the science nor the scientists from Dachau could be trusted and that the data were worthless. The body of medical opinion accepted the unfavourable determination but a few scientists and ethicists have continued to endorse the validity, of at least parts, of the Dachau hypothermia data. The conduct of the scientific communications about the Dachau hypothermia experiments by the scientific and ethical communities invites serious consideration of a possible ethical misadventure. It appears that for almost 50 years, the results of the study had been endorsed without careful examination of the scientific base of the experiments and that secondary citation of relevant original material may have been commonly employed. These infractions contributed to a myth that good science was practised by the Nazis at Dachau. The more recent emphasis on the life-saving potential of the Dachau data, without citation of credible supporting evidence, has also been misleading. Similarly, acceptance of a determination by an in-depth examination that the 'whole' Dachau project if flawed with simultaneous endorsement of the validity of 'parts' of the results, poses an ethical problem. It is advisable that before seeking ethical consultation about the use of unethically obtained data, scientists should examine the quality of science behind the controversial information and ethicists should verify the integrity of the material prior to engaging in a dialogue.

Biomedical Research↗
PubMed1994

Pack and close approach to persistent postcardiopulmonary bypass bleeding.

Persistent intraoperative hemorrhage after cardiopulmonary bypass was managed in three patients by packing the suspected bleeding sites with surgical sponges, leaving the packs in place and closing all layers of the sternal wound. The maneuver reduced the rate of bleeding to acceptable levels. The day after the primary operation the wounds were reopened and the surgical sponges were removed. Bleeding had ceased and the operative field remained dry in all three patients. Definitive closure of the sternotomy incisions was then performed. The method is proposed as a simpler alternative to the commonly used approach of leaving the mediastinum open for days and closing the wound after the bleeding stopped.

Adult↗
PubMed1993

Thermodynamic characterization of daunomycin-DNA interactions: comparison of complete binding profiles for a series of DNA host duplexes.

Using a combination of spectroscopic and calorimetric techniques, we have determined complete thermodynamic binding profiles (delta G degree, delta H degree, and delta S degree) for the complexation of daunomycin to a series of 10 polymeric DNA duplexes. We find the resulting drug binding data to be sensitive to the base composition and sequence of the host duplex, with the binding free energies ranging from -7.5 to -10.8 kcal/mol of bound drug and the binding enthalpies ranging from +4.11 to -10.76 kcal/mol of bound drug at 25 degrees C. The smaller range in the free energy term reflects the impact of large enthalpy-entropy compensations. We observe that the three synthetic duplexes which exhibit the highest daunomycin binding affinities all contain GC (or IC) base pairs as part of alternating purine/pyrimidine sequence motifs, with these high binding affinities being strongly enthalpy driven at 25 degrees C. Specific comparisons between the binding profiles for daunomycin complexation with select pairs of host duplexes lead to the following observations: (1) The presence or absence of a major-groove methyl group does not alter daunomycin binding thermodynamics. (2) The presence or absence of a minor-groove amino group does alter daunomycin binding thermodynamics. (3) Duplexes with different base compositions but identical minor-groove functionality exhibit similar daunomycin binding thermodynamics. (4) Homopolymeric duplexes composed of either AT or AU base pairs, but not GC base pairs, exhibit large enthalpy-entropy compensations in their daunomycin binding profiles. We propose interpretations of these and other features of our thermodynamic data in terms of specific daunomycin-DNA interactions deduced from available structural data.

Base Composition↗
PubMed1993

Mechanism of the oxidation reaction of deoxyhemoglobin as studied by isolation of the intermediates suggests tertiary structure dependent cooperativity.

The intermediates in the oxidation of deoxyhemoglobin by ferricyanide in 0.1 M KCl, at 20 degrees C and three pH values, were studied by cryogenic techniques. Data analysis was carried out according to a simple four rate constant model, ignoring the functional heterogeneity of the subunits, to simulate the time courses of the oxidation reaction, as studied by the stopped-flow technique [Antonini et al., (1965) Biochemistry 4, 345], which show anticooperativity at neutral pH and cooperativity at alkaline pH. Data analysis according to a 12 rate constant model indicated that the rate of oxidation of the beta subunit in the first oxidation reaction was 4 times faster than the rate of oxidation of the alpha subunit at pH 6.2 and 12 times faster at pH 8.5. The reactions involving the alpha subunit were noncooperative except for the last oxidation step at acid and neutral pH, but were cooperative at alkaline pH. The reactions involving the beta subunit were partly noncooperative and partly anticooperative. These complex mechanistic patterns suggest that a simple two-state model requiring the concerted transition of the tertiary structures of the subunits from the T to the R conformation is not adequate to interpret the oxidation reaction and that tertiary structures contribute, positively and negatively, to cooperativity. A structural hypothesis is suggested to explain the difference in the reactivities of the alpha and beta subunits.

Ferricyanides↗
PubMed1993

A differential heat-conduction microcalorimeter for heat-capacity measurements of fluids.

A heat-conduction calorimeter has been developed for measuring small changes in heat capacity of milligram samples of membrane lipid dispersed in water as a function of temperature. The operation of the instrument is based on the principle that the thermal response of the sample to a short (10 s), electrically generated heat burst is a function of the diffusivity of the sample. Modeling studies of the instrument's performance have revealed that the output response after the heat burst is a function of only the heat capacity, rho Cp. Calibration of the instrument experimentally confirmed this behavior. This feature obviated the need to measure the thermal conductivity in order to determine rho Cp from the diffusivity equation, eta = lambda/rho Cp. The calorimeter has the following characteristics: reproducibility of loading: +/- 400 microJ/C degrees.cm3; baseline stability: +/- 10 microJ/C degrees.cm3 per 36 h; resolution (+/- 1 S.D.): +/- 50 microJ/C degrees.cm3; sample size 600 microliters.

Calibration↗
PubMed1993

Critical temperature for unilamellar vesicle formation in dimyristoylphosphatidylcholine dispersions from specific heat measurements.

Using a heat conduction calorimeter with very high resolution (+/- 0.00005 J/degrees C.cm3), we have measured the specific heat CpL between 25 and 35 degrees C of dimyristoylphosphatidylcholine (DMPC) in aqueous dispersions. Previous studies of the temperature dependence of the chemical potential of DMPC in the L alpha phase (lamellar, liquid crystalline) indicated that a dispersion consisting only of unilamellar vesicles forms spontaneously at a critical temperature T* of 29.0 degrees C. Our present measurements show an anomaly in CpL between 28.70 and 29.50 degrees C: the curve for CpL versus T first decreases and then exhibits an inflection point at 28.96 degrees C before it flattens. This anomaly is attributed to the transformation from multilamellar dispersion to unilamellar vesicles at T* = 28.96 degrees C. Two independent properties of the CpL data also indicate T* is a critical point for the formation of unilamellar vesicles: (a) the time to reach equilibrium upon changing temperature increased dramatically between 28.7 and 28.96 degrees C, increasing as (T* - T)-1; at T > T* the dramatic "slowing-down" phenomenon was not observed. This slowing-down near T* is a general characteristic of critical phenomena. (b) The free energy change for the multilamellar-unilamellar transformation was obtained from the CpL-T data over this temperature interval and found to be 3.2 J/mol or 0.016 ergs/cm2 of bilayer, in agreement with other estimates of the interaction energy between neutral bilayers. We conclude with a discussion of the implications for membrane bilayer stability of these newly identified dynamic properties of the transformation.

Biophysical Phenomena↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗