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Biomedical subjects

P Braun

Publications and source records attributed to P Braun.

At least 19 recordsLinked to original sources

Ischemia: reperfusion injury and restenosis after coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is a very effective technology that allows, without surgery, successful mechanical revascularization of acutely or chronically obstructed coronary arteries. The success of PTCA in patients with acute myocardial infarction or unstable angina is questioned by early coronary reocclusion and by so-called reperfusion injury. In a biochemical context, reperfusion injury occurs as a very complex interaction between the different tissues that build heart muscle. Free radicals play a pivotal role and initiate a deleterious cascade of events after reperfusion. Protective mechanisms such as superoxide dismutase, glutathione peroxidase, and catalase are normally present in the cell to prevent damage by free radicals. Endothelial cells have a greater number of specific physiologic and metabolic functions and influence the microcirculatory flow. In the presence of exogenous glucose, coronary endothelial cells show a pronounced lactate production under well-oxygenated conditions. Low energy demand and high glycolytic activity may be the cause of why the coronary endothelium is less severely injured than the cardiomyocytes in the ischemic and anoxic heart. The success of PTCA in patients with chronically obstructed coronary arteries (stable angina) is questioned by vessel occlusion and restenosis. Restenosis is a very complex process involving clinical, morphological, procedural, regional flow-dependent, and biological determinants. Early platelet deposition, formation of mural thrombus, coronary vasospasm, and elastic recoil forces of stretched vessel wall may contribute to early restenosis in the first days after PTCA, but the peak incidence of restenosis occurs between two and three months after PTCA. Intimal hyperplasia or proliferation of smooth muscle cells is believed to be the fundamental process of restenosis. To solve the problem of restenosis, much effort has been expended, which includes several technical and pharmacological approaches. Pharmacological strategies, systemically or locally administered, aim at increased vasomotor tone, platelet function, smooth muscle cell proliferation/migration, and fibrocollagenous healing. Up to now none of the proposed drugs has been able to reduce the restenosis rate. There is experimental evidence for a claim that the antioxidant functions of vitamins (E, C, and beta-carotene) may prevent restenosis post-PTCA. Until recently, in most post-PTCA restenosis trials the angiographic analyses were not performed using computerized measurement methods. In order to assess the efficacy of acute or long-term interventions on the natural course or acute complications of coronary artery disease, quantitative measures have been introduced and validated that make use of digital coronary angiography and computerized image processing techniques.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary

Simultaneous measurement of coronary flow reserve by left anterior descending coronary artery Doppler and great cardiac vein thermodilution methods.

OBJECTIVES: The objective of this study was to compare left anterior descending coronary artery Doppler blood flow velocity and great cardiac vein thermodilution blood flow measurements of coronary flow reserve and submaximal coronary vasodilation in humans. BACKGROUND: Reported maximal coronary flow reserve values obtained with the coronary venous thermodilution method are lower than those obtained with other measurement methods. METHODS: Thermodilution measurements of great cardiac vein flow in 11 subjects were compared with simultaneous Doppler measurements of changes in left anterior descending coronary flow velocity after intracoronary administration of papaverine, nitroglycerin, iohexol and intravenous administration of dipyridamole. RESULTS: Coronary flow reserve (papaverine peak/rest flow ratio) was 3.7 +/- 1.7 (mean +/- SD) by the Doppler method and 2.0 +/- 0.7 by the thermodilution technique (p less than 0.001). Thermodilution flow changes were also smaller than Doppler-measured changes during submaximal vasodilation and during prolonged coronary dilation after dipyridamole administration. CONCLUSIONS: Coronary flow reserve and submaximal flow increases measured with the thermodilution method were consistently and substantially smaller than Doppler-derived measurements. This discrepancy has important implications for the comparison of coronary flow reserve measurements performed with the use of different techniques.

Blood Flow Velocity

An overview of the development and refinement of the Resource-Based Relative Value Scale. The foundation for reform of U.S. physician payment.

Responding to distortions in payment rates between services, policymakers in the United States have sought a systematic and rational foundation for determining physician fees. One such approach to paying physicians, the Resource-Based Relative Value Scale (RBRVS), determines fees by measuring the relative resource costs required to produce them. On January 1, 1992, the Medicare program implemented a new payment system for physician services based on the RBRVS. This article provides a brief history of the RBRVS and a summary of the methods and data used to derive it. This overview represents the culmination of 6 years of research by the Harvard RBRVS study team and provides a road map to the study's concepts and definitions. The overview also provides a context for the articles in this issue that describe five major studies undertaken since 1988. The study's overall results are presented in the last article of the series.

Data Collection

Predicting the work of evaluation and management services.

Physicians, carefully adhering to the definitions of Physicians' Current Procedural Terminology (CPT) billing codes, used the same CPT codes to denote evaluation and management services that varied widely in work and used different codes for services whose work was the same. As payment shifted to the Medicare Fee Schedule, it was important that the coding system be redefined so that codes consistently reflect the resource costs of these services. Redefining these codes for a resource-based payment system required an understanding of how verifiable predictors relate to physician work. Using data obtained from the Resource-Based Relative Value Scale (RBRVS) study regarding 377 services surveyed among physicians in 31 specialties, multiple regression analyses of the relationship of different variables to the mean values of work were performed. Intraservice time, which accounted for 90% of the variance, was the most important predictor of intraservice work. Specification of time, which previously had not been an element in the definitions of CPT codes for evaluation and management services, was useful in refining these codes so that their value corresponds more closely to resource costs. Other predictors of work were site of service or visit type, patient status (new/initial, established/subsequent), and referral status (consultation, nonconsultation).

Abstracting and Indexing

Results and impacts of the Resource-Based Relative Value Scale.

On January 1, 1992, the Health Care Financing Administration implemented the 1989 legislation reforming the Medicare payment system for physicians' services. The cornerstone of the new payment reform is the Medicare Fee Schedule (MFS), which is based on the Resource-Based Relative Value Scale (RBRVS). In this article, the major findings of the RBRVS study and its impacts on physician payment are summarized. The authors report the impacts of a RBRVS-based fee schedule on Medicare fees and physicians' income if it were fully implemented, assuming budget neutrality and absence of volume changes in services. Under this scenario, fees for evaluation and management services increase by 15% to 45%, while fees for invasive services and diagnostic tests decrease by 20% to 30%. These changes increase the Medicare income of family practitioners by more than 30% while decreasing the income of most surgical specialties by 10% to 20%.

Economics, Medical

Measuring the determinants of work values for psychiatrists' services in the resource-based relative value scale study.

OBJECTIVE: As part of the Harvard resource-based relative value scale study, the authors investigated how well the codes in the Physician's Current Procedural Terminology, 4th edition, or CPT-4, match psychiatric services to the work involved in evaluating and managing patients and how patient care characteristics affect different levels of psychiatric work. METHOD: A random sample of over 200 psychiatrists and subspecialists was asked to use 68 typical clinical examples or vignettes to evaluate services described by CPT codes. Data were analyzed by multivariate statistical methods. RESULTS: The survey showed that the existing coding system does not adequately describe the work that psychiatrists do. Within a single code (e.g., 90844, individual medical psychotherapy), there was wide (more than twofold) variation in the estimates, from multiple measurements based on different vignettes, of the amount of work represented. Estimates of work values varied significantly according to treatment setting and patient characteristics: psychiatric services in the hospital showed an average work value 25% greater than that for office services; treating new patients involved 18% more effort than treating established patients; and treating patients described as at risk of harming self or others increased the psychiatrists' work effort by 36%. CONCLUSIONS: Revisions in coding evaluation and management services in the new Medicare fee schedule for psychiatric services should be further refined and then implemented. These revisions would bring the coding system into line with psychiatric practice, making it a better way of accounting for the relative work involved in treating patients of varying difficulty.

Fee Schedules

Polypeptides and bacteriochlorophyll organization in the light-harvesting complex B850 of Rhodobacter sphaeroides R-26.1.

The light-harvesting complex (LHC) B850 from Rhodobacter sphaeroides was dissociated into several fragments by treatment with sodium dodecyl sulfate. The molecular weight of each fragment was determined by using transverse polyacrylamide gel electrophoresis under nondenaturing conditions and gel filtration techniques. Four B850 LHCs were observed, having molecular weights of 60,000, 72,000-75,000, 105,000, and 125,000-145,000, and two small bacteriochlorophyll (Bchl)-polypeptide complexes having molecular weights of 6000-8000 and 12,000-14,000. Each of the B850 complexes contains ca. one Bchl a for each 6.5-kDa protein. The optical absorption and circular dichroism of the B850 LHCs recorded directly from the gels are similar to those measured previously for a 22-24-kDa B850 LHCs by Sauer and Austin [(1978) Biochemistry 17, 2011-2019]. These data, combined with studies of other groups, indicate that the smallest LHC in LH1 and LH2 is a Bchl-polypeptide tetramer. Each tetramer contains two Bchl dimers that probably have the structure of P-860, the primary electron donor in Rhodobacter sphaeroides, and two alpha-beta-polypeptide pairs. Interactions among the paired Bchls shift their individual Qy transitions from 780-800 to 850-860 nm, and interactions among two such pairs induce the circular dichroism signal of the LHCs. Three Bchl-polypeptide tetramers probably form a dodecamer having C3 symmetry, and six such dodecamers organize into a large hexagon that can accommodate one or two reaction center complexes.

Bacteriochlorophylls

Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity.

Activated T-lymphocytes may regulate the eosinophilic inflammation of bronchial asthma. In the present study, we investigated T cell activation and eosinophilia in blood and bronchoalveolar lavage (BAL) in 17 patients with asthma not receiving steroid treatment. Compared to normal individuals, BAL from patients with asthma contained significantly increased numbers of both lymphocytes and eosinophils (EOSs). The lymphocytosis consisted of increased numbers of both CD4+ and CD8+ T cells, and these T cell populations expressed elevated levels of T cell activation markers (interleukin-2 receptor [CD25], HLA-DR, and very late activation antigen 1). Close correlation was found between numbers of BAL CD4+ IL-2R+ T cells and numbers of EOSs. Moreover, the numbers of activated T cells and EOSs were related to the severity of asthma as measured by impairment of FEV1 and increased methacholine bronchial responsiveness. We demonstrate in both blood and BAL a close correlation between T cell activation, eosinophilia, and severity of asthma, suggesting that recruitment and activation of lymphocytes and EOSs are fundamental to the pathogenesis of bronchial asthma.

Adult

New enzymatic protecting group techniques for the construction of peptides and glycopeptides.

The use of non-proteases for the selective removal of protecting groups from peptides and glycopeptides is described. The N-terminal deprotection of peptides can be achieved by the hydrolysis of the phenylacetyl (PhAc) amide blocking group catalyzed by penicillin G acylase. On the other hand, the lipase-mediated hydrolysis of n-heptyl (Hep) and 2-bromoethyl esters allows for the liberation of the C-terminal carboxy group. The selective C-terminal deprotection can be applied advantageously for the construction of acid- and base-sensitive polyfunctional O-glycopeptides. In all cases the enzymatic reactions are completely selective and proceed under mildest conditions (pH 7-8, r.t. to 37 degrees C) without damaging the various other functionalities present in the complex substrates.

Amino Acid Sequence

[Doppler echocardiographic determination of the effective orifice area of mechanical heart valve prostheses in a flow model].

In a flow model the effective orifice areas (Ae) of 17 mechanical heart valve prostheses were determined. We measured the Ae-values of several sizes of three types of mechanical prostheses (Medtronic-Hall, St. Jude Medical, and Omnicarbon) under quasi-steady flow conditions using the continuity equation: Ae = flow/maximal transprosthetic velocity. The flow through the model could be determined exactly by directly measuring the decreasing fluid level within the feed tank, while the maximal velocities were calculated from CW-Doppler echocardiographic spectra. It was found that 1) over a range of 200-800 cm3/s Ae was constant for all prostheses and 2) in small aortic prostheses the Ae could be determined with only little scattering of the obtained values, while in large mitral prostheses there was a considerable variation within the results of repeated investigations. For example, in the 21- and 31-Omnicarbon-valves mean values of Ae were calculated as 1.41 and 4.03 cm2, respectively, with standard deviations of 0.05 and 0.49 cm2 as a result of about 70 single calculations in each valve. 3) The absolute values of Ae were smaller than those of comparable in vitro studies based on the Gorlin formula. We conclude that the effective orifice areas of prosthetic heart valves can be easily determined in a flow model by the combination of flow and Doppler echocardiographic measurements. As determinations are based on the same principle, the obtained values should clinically be referred to patients where the corresponding continuity equation for pulsatile flow is used as Ae = stroke volume/time integral of the maximal transvalvular velocity.

Aortic Valve

D1-D2-cytochrome b559 complex from the aquatic plant Spirodela oligorrhiza: correlation between complex integrity, spectroscopic properties, photochemical activity, and pigment composition.

A D1-D2-cyt b559 complex with about four attached chlorophylls and two pheophytins has been isolated from photosystem II of the aquatic plant Spirodela oligorrhiza and used for studying the detergent-induced changes in spectroscopic properties and photochemical activity. Spectral analyses (absorption, CD, and fluorescence) of D1-D2-cyt b559 preparations that were incubated with different concentrations of the detergent Triton X-100 indicate two forms of the D1-D2-cyt b559 complexes. One of them is photochemically active and has an absorption maximum at 676 nm, weak fluorescence at 685 nm, and a strong CD signal. The other is photochemically inactive, with an absorption maximum at 670 nm, strong fluorescence at 679 nm, and much weaker CD. The relative concentrations of the two forms determine the overall spectra of the D1-D2-cyt b559 preparation and can be deduced from the wavelength of the lowest energy absorption band: preparations having maximum absorption at 674, 672, or 670.5 nm have approximately 20, 60, or 85% inactive complexes. The active form contains two chlorophylls with maximum absorption at 679 nm and CD signals at 679 (+) and 669 nm (-). These chlorophylls make a special pair that is identified as the primary electron donor P-680. The calculated separation between the centers of these two pigments (using an extended version of the exciton theory) is about 10 A, the pigments' molecular planes are tilted by about 20 degrees, and their N1-N3 axes are rotated by 150 degrees relative to each other. The other two chlorophylls and one of the two pheophytins in the D1-D2-cyt b559 complex have their maximum absorption at 672 nm, while the maximum absorption of the photochemically active pheophytin is probably at 672-676 nm. During incubation with Triton X-100, the photochemically active complex is transformed into an inactive form with first-order kinetics. In the inactive form the maximum absorption of the 679 nm absorbing Chls is blue-shifted to 669 nm. The first-order decay of the photochemical activity suggests that the isolated D1-D2-cyt b559 complex is stable as an aggregate but becomes unstable on dissociation into individual D1-D2-cyt b559 units.

Chlorophyll

Myocardial preservation using lidocaine blood cardioplegia.

Prevention of ventricular fibrillation after aortic unclamping using lidocaine hydrochloride as an additive to cold potassium blood cardioplegia was studied prospectively in 46 patients undergoing elective myocardial revascularization. Patients were similar with respect to age, ventricular function, severity of coronary artery disease, cross-clamp time, completeness of revascularization, frequency of internal thoracic artery grafting, systemic temperature at the time of cross-clamp removal, and mean infusate volume and temperature. Patients receiving lidocaine blood cardioplegia (group 1, 23 patients) had a significant reduction in the incidence of ventricular fibrillation (22% versus 74%; p less than 0.0005) and in the mean number of cardioversion attempts required to defibrillate the heart (0.5 +/- 1.3 versus 1.9 +/- 0.97; p less than 0.0005) after cross-clamp removal compared with controls (group 2, 23 patients). There were no differences between the two groups postoperatively with regard to cardiac enzyme release, hemodynamic measurements, or clinical outcome. Patients receiving lidocaine blood cardioplegia tended to have a lower incidence of new postoperative atrial fibrillation (9% versus 26%). Ventricular function was preserved equally in both groups. We conclude that lidocaine is a safe additive to potassium blood cardioplegia and significantly reduces the incidence of ventricular fibrillation after aortic unclamping.

Aged

Cyclosporine and anti-interleukin 2 receptor monoclonal antibody therapy suppress accelerated rejection of rat cardiac allografts through different effector mechanisms.

Increasing numbers of sensitized patients are either precluded from receiving an allograft or experience accelerated rejection which may be refractory to conventional therapy. Using a rat model, we have shown that accelerated (24 hr) rejection of LBN cardiac Tx in LEW rats sensitized with BN skin grafts 7 days earlier, could be prevented by treatment with cyclosporine (15 mg/kg/day x7 days, Tx survival about 42 days) or ART-18, an anti-IL-2R mAb (300 micrograms/kg/day x10 days i.v., Tx survival about 16 days). In this study, we evaluated intragraft mechanisms responsible for these effects by immunoperoxidase localization of relevant humoral mediators (IgG, IgM, C3, cross-linked fibrin), graft infiltrating cells (GIC), and associated cytokines (IL-2, IFN-g, tumor necrosis factor [TNF], or cytokine receptors (IL-2R). Tx rejected in fulminating fashion by 24 hr in sensitized hosts showed extensive and progressive endothelial deposition of IgG, C3, and fibrin from 2 hr, followed by an influx of neutrophils at 3 hr, and peak numbers of GIC by 18 hr (88.8 +/- 20.3 leukocytes/field). At 18 hr, GIC consisted of neutrophils (26%), T cells (20%, greater than 90% of which were OX-8+), and monocytes/macrophages (53%), whereas B cells were absent. By 18 hr, up to 20% of GIC were IFN-g+, 10% were IL-2R+, and 10% were IL-2+, consistent with labeling of 20% of cells with OX-22. Widespread endothelial and mononuclear cell labeling for TNF and the procoagulant molecular tissue factor (TF) were also noted. In contrast to untreated grafts, CsA treatment essentially abolished intragraft Ig, C3, and fibrin deposition. Moreover, despite dense cell infiltration at 24 hr (total GIC 55.3 +/- 13.4/field), analysis of CsA-treated Tx showed markedly decreased neutrophils (0.5%), with increased T cells (35%) and similar proportions of macrophages (66%). In addition to the reduction in neutrophils, Ig and C3, fewer IL-2R+ (6%) and OX-22+ (3%) cells, considerably less TNF and TF, and almost no IL-2+ or IFN-g+ GIC (less than 1%) were detected. Surprisingly, ART-18 treatment also greatly decreased but did not abolish endothelial deposition of C3, IgG, or IgM, whereas widespread endothelial and mononuclear labeling for fibrin, TNF, and TF remained. In addition, GIC (about 54.8 +/- 16.1/field) contained only moderately reduced numbers of neutrophils (31%) and the proportions of T cells (27%) and macrophages (49%) were generally comparable to those of rejecting Tx in untreated rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Refinement and expansion of the Harvard Resource-Based Relative Value Scale: the second phase.

The Harvard resource-based relative value scale (RBRVS) for physician services has assumed a critical role in physician payment reform. We have demonstrated that the relative resource costs of providing physician services can be defined and measured in a rational and systematic way and that the results are reliable and valid. Consequently, the RBRVS is a viable basis for national payment policy and could be used for establishing a national fee schedule for physician services or to identify "mispriced" physician procedures. Since the release of the final report of the first phase of the Harvard RBRVS study in September of 1988, there has been extensive review, discussion, and criticism of the RBRVS. Dr. Laurence F. McMahon, Jr., in the accompanying article, provides a further critique of our research. In this paper, we review the RBRVS study and results and respond to the major criticisms that have been raised by Dr. McMahon and others. We then describe the tasks we are currently undertaking to expand and validate our research and address the important criticisms and limitations.

Data Interpretation, Statistical

Panic disorder among American Indians: a descriptive study.

Little is known about panic disorder among American Indians. In a pilot project involving two Northwest Coast Indian villages, community health representatives screened the population for panic disorder, substance abuse, and major depression using DSM-III criteria. Accompanying the screening were subsequent patient education and further evaluation by a psychiatrist, a social worker, and primary care physicians. Of fifty community residents who agreed to take the screening examination, seven were found who met diagnostic criteria for panic disorder. Four of the seven had symptoms of alcohol abuse which complicated the course and diagnosis of panic disorder, and individuals with panic disorder reported more than twice the lifetime prevalence of depression in comparison with other community members. Limitations of the study and refinements of study design are needed in future study discussions.

Adult