Limitations to survival for infants with hypoplastic left heart syndrome before and after transplant: the Loma Linda experience

Untreated, hypoplastic left heart syndrome is a lethal cardiac defect. Heart transplant has become an accepted therapeutic option for this condition. However, significant limitations to survival remain for infants with this condition who are referred for heart transplantation. Attention to the prevention, early detection, and management of common problems occurring at each stage of the transplantation process is important for improving survival rates. This study retrospectively reviewed the cases of 195 infants with hypoplastic left heart syndrome registered for heart transplantation at Loma Linda University Medical Center between November 1985 and July 1996 to determine causes of death. During the waiting period, progressive cardiac failure and complications from interventional procedures were the leading causes. In the early postoperative period, technical issues and acute graft failure were most important, whereas late deaths (more than 30 days after transplant) were most often related to rejection and posttransplant coronary artery disease.     

The effect of sample freezing on proton magic-angle spinning NMR spectra of biological tissue

Magic-angle spinning (MAS) has recently been shown to enhance spectral resolution in NMR examinations of intact biological tissue ex vivo. This work demonstrates that freezing certain tissue samples before examination by 1H MAS NMR can have a marked effect on their spectra. Spectra of rat kidney after freezing in liquid nitrogen, compared with spectra before freezing, showed a significant increase in signal intensities from alanine (>100%), glutamine (>40%), and glycine (>100%), and a decrease in signals assigned to lipids and other macromolecules. Some resonances--such as from leucine, valine, isoleucine, and aspartate--only became visible after freezing the tissue. These observations suggest that low temperature storage of tissue necropsies or biopsies might affect the results of a MAS NMR analysis, possibly resulting in the misinterpretation of metabolite changes to pathogen or disease effects.     

Experimental tests of proton beam localization

The depth of penetration of heavy charged-particle therapy beams is sensitive to the density of tissues traversed. Maximum depth of dose contours will vary appreciably as the beam passes through bone, muscle, lung, and air or gas. Calculations suggest that beam activation of the short-lived positron-emitting isotope 15O in vivo will permit localization of proton therapy beams with resonable detected-event density and dose. Preliminary tests of this method indicate that the beam can be located at depth with a typical dose of 15 rad, using a large field-of-view positron camera on-ling. This technique is also applicable to other heavy charged-particle beams, negative pions, and heavy ions.     

Characteristics of neutron beam generated by 500 MeV proton beam

A neutron irradiation facility was constructed at PARMS, University of Tsukuba to produce an ultrahigh energy neutron beam with a depth dose distribution superior to an x-ray beam generated by a modern linac. This neutron beam was produced from the reaction on a thick uranium target struck by a 500 MeV proton beam from the booster synchrotron of the High Energy Physics Laboratory. The percentage depth dose of this neutron beam was nearly equivalent to that of x-rays around 20 MV and the dose rate was 15 cGy per minute. The relative biological effectiveness (RBE) of this neutron beam has been estimated using the cell inactivation effect and the HMV-I cell line. The survival curve of cells after neutron irradiation has a shoulder with n and Dq of 8 and 2.3 Gy, respectively. The RBE value at the 10(-2) survival level for the present neutron beam as compared with 137Cs gamma rays was 1.24. The results suggest that the biological effects of ultrahigh energy neutrons are not large enough to be useful, although the depth dose distribution of neutrons can be superior to that of high energy linac x-rays.     

A calculation of the relative biological effectiveness of 125I and 103Pd brachytherapy sources using the concept of proximity function

The clinical application of encapsulated radioactive sources in brachytherapy plays an important role in the treatment of malignancy. 125I and 103Pd sources have been widely used in the permanent implant of prostate cancer. An important consideration for the choice of brachytherapy sources is their relative biological effectiveness (RBE). Previous calculations of this quantity have used the dose-averaged lineal energy, yD, as a measure of biological effectiveness. In this approach, however, the selection of a relevant site size remains an open question. Here we avoid this problem by using the generalized theory of dual radiation action to calculate the initial slope, alpha, of the dose-effect curves using the proximity function, t(x), and the biological response function, gamma(x). At low doses and/or low dose rates (e.g., prostate implants) the parameter alpha determines the RBE. Proximity function, t(x), is the probability distribution function of distances between pairs of sublesions; and the biological function, gamma(x), is the probability that two sublesions at a distance x apart results in a lesion. Functions t(x) have been calculated for each source using the Monte Carlo transport codes PHOEL and PROTON5. The function gamma(x) has been taken from a published analysis. The RBE values thus obtained are: 1.5 for 125I and 1.6 for 103Pd. The question of whether an "effective" site size exists where yD approximates best the variation of alpha with radiation quality is also addressed.     

The effectiveness and relative importance of choice in the classroom.

This investigation examined the effects of providing choices among homework assignments on motivation and subsequent academic performance. Students were randomly assigned within classrooms either to receive a choice of homework options or to be assigned an option for all homework in one instructional unit. Conditions were reversed for a second instructional unit. Results revealed that when students received a choice of homework they reported higher intrinsic motivation to do homework, felt more competent regarding the homework, and performed better on the unit test compared with when they did not have a choice. In addition, a trend suggested that having choices enhanced homework completion rates compared with when no choices were given. In a second analysis involving the same students, the importance of perceived provision of choice was examined in the context of student perceptions of their teachers' support for autonomy more broadly defined. Survey data showed that the relationship between perceptions of receiving autonomy support from teachers and intrinsic motivation for schoolwork could be fully accounted for by students' perceptions of receiving choices from their teachers. The limitations and implications of the study for research and practice are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relative effectiveness of salt stimuli for the rat.

Determined the relative detectability of 8 salts over a molar concentration range of .0125-.80 in an experiment with 5 male hooded rats. The detectability of those salts, which have a strong sour or bitter quality, is substantially greater when compared with sodium chloride, than their relative effectiveness as determined by the size of the evoked response in the chorda tympani. It is suggested that, like quinine, these salts are more effective on the posterior tongue. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The efficacy and effectiveness of psychotherapy relative to medications.

A recent survey by Consumer Reports (1994) found that people who receive psychotherapy were generally pleased with their experience and that their satisfaction was unrelated to the type of treatment or the addition of medications. M. E. P. Seligman (1995) argued that these findings demonstrate the value of psychotherapy and suggested that such survey methodologies may be superior to randomized clinical trials in this regard because they study what occurs in actual clinical practice. Although such approaches provide important information, they are no substitute for controlled clinical trials when it comes to drawing causal inferences. However, the study does highlight the importance of defining outcome in the broadest possible fashion and of addressing the external validity of the findings obtained. Attention to such considerations has implications for the relative value of drugs and psychotherapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinct difference in relative biological effectiveness of 252Cf neutrons for the induction of mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila melanogaster

The relative biological effectiveness (RBE) of 252Cf neutrons was determined for two different types of somatic mutations, i.e., loss heterozygosity for wing-hair mutations and reversion of the mutant white-ivory eye-color, in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye color is due to an intragenic structural change in the white locus on the X-chromosome. For a quantitative comparison of RBE values for these events, we have constructed a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clones can be detected simultaneously in the same individuals. Larvae were irradiated at the age of 80 +/- 4 h post-oviposition with 252Cf neutrons or 137Cs gamma-rays, and male adult flies were examined under the microscope for the presence of the two types of clonal mosaic spots appearing. The induction of wing-hair spots per dose unit was much greater for 252Cf neutrons than for 137Cs gamma-rays, whereas the frequencies of eye-color reversion were similar for neutrons and gamma-rays. The estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant wing-hair spots and revertant eye-color spots, respectively. These results indicate that the RBE of neutrons is much greater for mitotic crossing over in comparison to the intragenic white-ivory reversion events. Possible causes for the difference in RBE are discussed.     

Within-compound associations modulate the relative effectiveness of differential and Pavlovian conditioned inhibition procedures.

Four conditioned suppression experiments with 98 male albino rats compared the inhibitory strength of a Pavlovian conditioned inhibitory stimulus (CS–) and a differential CS– and identified some postconditioning manipulations that modulate the measured effectiveness of the CS–. In Exp I, more inhibition was detected to a differential inhibitor than to a Pavlovian inhibitor in summation and retardation tests. Exps II–IV provided evidence that some inhibition conditioned to the Pavlovian CS–, but not to the differential CS–, was masked by a within-compound association. In Exp II, postconditioning extinction presentations of the Pavlovian conditioned excitatory stimulus (CS+) increased the inhibition observed to its CS–. In Exp III, postconditioning pairings of the Pavlovian CS+ with a more powerful UCS than that used for conditioning reduced the inhibition observed to its CS–. In Exp IV, nonreinforced postconditioning presentations of the Pavlovian CS– increased the inhibition observed to that CS–. The unmasking and masking of inhibition conditioned to the Pavlovian CS– by operations that modulate the strength of the within-compound association also changed the relative effectiveness of the Pavlovian and differential procedures. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relative biological effectiveness of accelerated carbon ions with different LET for inducing mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila larvae

We previously described an expression cassette that relies on the tobacco etch virus (TEV) nuclear inclusion a (NIa) protease and leads to the coordinated accumulation of multiple proteins through self processing of a polyprotein [21]. However, low levels of proteins accumulated when the full-length protease was encoded within the polyprotein [22]. Studies were conducted to evaluate whether the disruption of NIa nuclear localization would affect the levels of proteins produced via the cassette. Modifications comprised either removal of its nuclear localization signals (NLSs), removal of the VPg domain (which includes the NLSs), and fusion to the 6 kDa protein, previously demonstrated to be a viral cytoplasmic anchor [28]. In in vitro translation reactions and in vivo protoplast experiments the modified NIa retained sequence-specific proteolysis. Moreover, the removal of the NLSs correlated with an increase in GUS reporter accumulation. The modified cassette, pPRO10, led to the synthesis of up to three viral coat protein (CPs) in addition to NIa. However, the accumulation of proteins in protoplasts depended upon the position of the CP coding sequence within the cassette as well as on the stability of the protein.     

The relative effectiveness of exposure to 131I at low doses

BACKGROUND: Reactive oxygen and nitrogen derived species produced by activated neutrophils have been implicated in the damage of mucosal proteins including the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the active inflammatory lesion in patients with inflammatory bowel disease (IBD). This study investigated the efficacy of currently used IBD therapeutics to prevent injury mediated by reactive oxygen and nitrogen derived species. METHODS: GAPDH activity of human colon epithelial cells was used as a sensitive indicator of injury produced by reactive oxygen and nitrogen derived species. HCT116 cells (10(6)/ml phosphate buffered saline; 37 degrees C) were incubated in the presence of 5-aminosalicylic acid (5-ASA), 6-mercaptopurine, methylprednisolone, or metronidazole before exposure to H2O2, HOCl, or NO in vitro. HCT116 cell GAPDH enzyme activity was determined by standard procedures. Cell free reactions between 5-ASA and HOCl were analysed by spectrophotometry and fluorimetry to characterise the mechanism of oxidant scavenging. RESULTS: GAPDH activity of HCT116 cells was inhibited by the oxidants tested: the concentration that produced 50% inhibition (IC50) was 44.5 (2.1) microM for HOCl, 379.8 (21.3) microM for H2O2, and 685.8 (103.8) microM for NO (means (SEM)). 5-ASA was the only therapeutic compound tested to show efficacy (p<0. 05) against HOCl mediated inhibition of enzyme activity; however, it was ineffective against H2O2 and NO mediated inhibition of GAPDH. Methylprednisolone, metronidazole, and the thiol-containing 6-mercaptopurine were ineffective against all oxidants. Studies at ratios of HOCl:5-ASA achievable in the mucosa showed direct scavenging to be the mechanism of protection of GAPDH activity. Mixing 5-ASA and HOCl before addition to the cells resulted in significantly greater protection of GAPDH activity than when HOCl was added to cells preincubated with 5-ASA. The addition of 5-ASA after HOCl exposure did not restore GAPDH activity. CONCLUSIONS: Therapies based on 5-ASA may play a direct role in scavenging the potent neutrophil oxidant HOCl, thereby protecting mucosal GAPDH from oxidative inhibition. These findings suggest that strategies for the further development of new HOCl scavenging compounds may be useful in the treatment of IBD.     

Neutron induced recoil protons of restricted energy and range and biological effectiveness

Low energy neutrons (<2 MeV), those of principal concern in radiation protection, principally initiate recoil protons in biological tissues. The recoil protons from monoenergetic neutrons form rectangular distributions with energy. Monoenergetic neutrons of different energies (<2 MeV) will then produce overlapping recoil proton spectra. By overlapping the effects of individual deposition events, determined microdosimetrically for cell nuclear dimensions, from such neutron beams the biological effectiveness of recoil protons within defined energy and range bounds can be determined. Here chromosomal aberrations per cell have been quantified following irradiation of Vicia faba cells with monoenergetic neutrons of 230, 320, 430, and 1,910 keV. Aberration frequencies from cells from part of the cell cycle, thereby limiting nuclear dimensions, were linearly related to dose and to the frequency of proton recoils per nucleus. The 320 keV neutrons were the most biologically effective per unit absorbed dose and 430 keV neutrons most effective per recoil proton, with 21% of recoils inducing aberrations. After extraction of effectiveness per proton recoil within each energy and range bounds (0-230, 230-320, 320-430, and 430-1,910 keV), it was concluded that recoil protons with energies of about 200-300 keV, traveling 2.5-4 microm and depositing energy at about 80 keV micrometer(-1), are more efficient at aberration induction than those recoil protons of lesser range though near equivalent LET and those of greater range through lesser LET. This approach allows for assessment of the biological effectiveness of individual energy deposition events from low energy neutrons, the lowest dose a cell can receive, and provides an alternative to considerations of relative biological effectiveness.     

Determination of proton magnetization transfer rate constants in heterogeneous biological systems

Two procedures are currently in use for the determination of proton magnetization transfer rate constants between macromolecular tissue components and water. The first method assumes that there are only two spin baths (macromolecular plus solvent) and that during off-resonance irradiation complete saturation of the "immobile" proton spin bath occurs (S. H. Koenig, R. D. Brown, III, R. Ugolini, Magn. Reson. Med. 29, 311 (1993)). This approach neglects the possibility of incomplete saturation and polydispersity, and yields an apparent magnetization transfer rate constant, Kapp. The second approach utilizes a formalism which can account for polydispersity and incomplete saturation of the immobile spin bath (K. Kuwata, D. Brooks, H. Yang, T. Schleich, J. Magn. Reson., in press). In this work magnetization transfer rate constants derived by the use of both methods for two systems, ocular lens tissue and cross-linked bovine serum albumin (BSA) were compared. For both samples Kapp was dependent on B2 off-resonance irradiation frequency and power when the first method was used. The second method provided values of the magnetization transfer rate constant that were similar to the values obtained by the first method, as the limit of complete saturation was approached.     

Response of stem cells in the mouse testis to fission neutrons of 1 MeV mean energy and 300 kV x rays. Methodology, dose-response studies, relative biological effectiveness

Microelectrode recording in the thalamus of pigeons subjected to tilt and sinusoidal rotational stimuli around the vertical, longitudinal and transversal axes revealed vestibularly driven units in two thalamic nuclei, the nucleus posteroventralis and the nucleus principalis precommissuralis. Many of these units responded in a complex manner suggesting that inputs from contralateral and ipsilateral cupulae and maculae converged on them. A few units received additional visual or proprioceptive information. The homology relationship with a mammalian vestibular thalamic nucleus is discussed briefly.     

Relative biological effectiveness of negative pi mesons for the immune response in mice

Immunologically competent mouse spleen cells were exposed to negative pi mesons in the entrance plateau or at the peak of the dose distribution at a maximum dosage of 5 rads/min. or to 60Co gamma rays at 4.96 rads/min. Survival curves from cells irradiated in vitro but incubated in vivo yielded RBE values of 2.15 for the peak and 1.84 for the entrance plateau at a surviving fraction of 0.1. The dose-rate dependence of antibody-forming spleen cells for both 60Co gamma rays and the lot-LET components of the pion beam is discussed. The authors suggest that these RBE values constitute an upper limit for normal mammalian cells exposed to pions and tha the RBE with clinically useful dose rates may be significantly lower than those reported here.