Showing papers by "University of Virginia published in 1990"

The International Cooperative Study on the Timing of Aneurysm Surgery. Part 1 Overall management results

Abstract: The International Cooperative Study on the Timing of Aneurysm Surgery evaluated the results of surgical and medical management in 3521 patients between December, 1980, and July, 1983. At admission, 75% of patients were in good neurological condition and surgery was performed in 83%. At the 6-month evaluation, 26% of the patients had died and 58% exhibited a complete recovery. Vasospasm and rebleeding were the leading causes of morbidity and mortality in addition to the initial bleed. Predictors for mortality included the patient's decreased level of consciousness and increased age, thickness of the subarachnoid hemorrhage clot on computerized tomography, elevated blood pressure, preexisting medical illnesses, and basilar aneurysms. The results presented here document the status of management in the 1980's.

Transplanted suprachiasmatic nucleus determines circadian period

Abstract: The pacemaker role of the suprachiasmatic nucleus in a mammalian circadian system was tested by neural transplantation by using a mutant strain of hamster that shows a short circadian period. Small neural grafts from the suprachiasmatic region restored circadian rhythms to arrhythmic animals whose own nucleus had been ablated. The restored rhythms always exhibited the period of the donor genotype regardless of the direction of the transplant or genotype of the host. The basic period of the overt circadian rhythm therefore is determined by cells of the suprachiasmatic region.

Three-dimensional magnetization-prepared rapid gradient-echo imaging (3D MP RAGE)

Abstract: A new three-dimensional imaging technique which is applicable for 3D MR imaging throughout the body is introduced. In our preliminary investigations we have acquired high-quality 3D image sets of the abdomen showing minimal respiratory artifacts in just over 7 min (voxel size 2.7 X 2.7 X 2.7 mm3), and 3D image sets of the head showing excellent gray/white contrast in less than 6 min (voxel size 1.0 X 2.0 X 1.4 mm3).

Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase

Abstract: MAP kinase (relative molecular mass, 42,000), a low abundance serine--threonine protein kinase, is transiently activated in many cell types by a variety of mitogens, including insulin, epidermal growth factor, and phorbol esters. In vitro, MAP kinase will phosphorylate and reactivate S6 kinase II previously inactivated by phosphatase treatment. Because many of the stimuli that activate MAP kinase are also stimulators of cell proliferation, and regulation of the cell cycle seems to involve a network of protein kinases, MAP kinase could be important in the transmission of stimuli eventually leading to the progression from G0 to G1 in the cell cycle. Activated MAP kinase contains both phosphotyrosine and phosphothreonine. We report here that MAP kinase can be deactivated completely by treatment with either phosphatase 2A, a protein phosphatase specific for phosphoserine and phosphothreonine, or CD45, a phosphotyrosine-specific protein phosphatase. We demonstrate that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggest therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.

The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results.

Abstract: A prospective, observational clinical trial was conducted by the International Cooperative Study on the Timing of Aneurysm Surgery to determine the best time in relation to the hemorrhage for surgical treatment of ruptured intracranial aneurysms. Sixty-eight centers contributed 3521 patients in a 2 1/2-year period beginning in December, 1980. Analysis by a prespecified "planned" surgery interval demonstrated that there was no difference in early (0 to 3 days after the bleed) or late surgery (11 to 14 days). Outcome was worse if surgery was performed in the 7 to 10-day post-bleed interval. Surgical results were better for patients operated on after 10 days. Patients alert on admission fared best; however, alert patients had a mortality rate of 10% to 12% when undergoing surgery prior to Day 11 compared with 3% to 5% when surgery was performed after Day 10. Patients drowsy on admission had a 21% to 25% mortality rate when operated on up to Day 11 and 7% to 10% with surgery thereafter. Overall, early surgery was neither more hazardous nor beneficial than delayed surgery. The postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery.

Family Ecologies of Ethnic Minority Children.

Abstract: This article discusses a proposed interconnectedness between the ecologies of ethnic minority families, adaptive strategies, socialization goals, and child behavioral outcomes. The ethnic minority groups included are African American, American Indian/Alaskan Native, Asian Pacific Americans, and Hispanics. Demographic information on population size, geographic area of concentration, and preferred identity terms is provided. It is argued that adaptive strategies, including extendedness of families and role flexibility, biculturalism, and ancestral worldview, emerge from the ecological challenges of ethnic stratification status. These adaptive strategies foster the child-rearing goals of positive orientation to the ethnic group and socialization for interdependence, which in turn enhance the developmental outcomes of cognitive flexibility and sensitivity to discontinuities among ethnic minority children.

The expression and posttranslational modification of a neuron-specific β-tubulin isotype during chick embryogenesis

Abstract: Five β-tubulin isotypes are expressed differentially during chicken brain development. One of these isotypes is encoded by the gene cβ4 and has been assigned to an isotypic family designated as Class III (βIII). In the nervous system of higher vertebrates, βIII is synthesized exclusively by neurons. A βIII-specific monoclonal antibody was used to determine when during chick embryogenesis cβ4 is expressed, the cellular localization of βIII, and the number of charge variants (isoforms) into which βIII can be resolved by isoelectric focusing. On Western blots, βIII is first detectable at stages 12–13. Thereafter, the relative abundance of βIII in brain increases steadily, apparently in conjunction with the rate of neural differentiation. The isotype was not detectable in non-neural tissue extracts from older embryos (days 10–14) and hatchlings. Western blots of protein separated by two-dimensional gel electrophoresis (2D–PAGE) reveal that the number of βIII isoforms increases from one to three during neural development. This evidence indicates that βIII is a substrate for developmentally regulated, multiple-site posttranslational modification. Immunocytochemical studies reveal that while cβ4 expression is restricted predominantly to the nervous system, it is transiently expressed in some embryonic structures. More importantly, in the nervous system, immunoreactive cells were located primarily in the non-proliferative marginal zone of the neural epithelia. Regions containing primarily mitotic neuroblasts were virtually unstained. This localization pattern indicates that cβ4 expression occurs either during or immediately following terminal mitosis, and suggests that βIII may have a unique role during early neuronal differentiation and neurite outgrowth.

Schizophrenics Kill Themselves Too: A Review of Risk Factors for Suicide

Abstract: Suicide rates among schizophrenic individuals are disturbingly high. At present, suicide is the number one cause of premature death among schizophrenics, with 10 to 13 percent killing themselves. Recent studies place the risk of suicide for persons with schizophrenia at a level comparable to that for persons with affective disorder. Depression, especially the symptom of self-reported or perceived hopelessness, is an important comorbidity factor in assessing this risk. Young white schizophrenic men with high levels of premorbid functioning and high expectations are at particularly high risk. Schizophrenic women, unlike women in the general population, behave more like men when it comes to choosing suicide. This article reviews recent studies reporting suicide rates and risk factors for suicide among schizophrenic patients. Current issues concerning the prediction, prevention, and treatment of suicidality among persons with schizophrenia are also discussed.

Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases.

Abstract: Cellular transformation by oncogenic retroviruses encoding protein tyrosine kinases coincides with the tyrosine-specific phosphorylation of multiple protein substrates. Previous studies have shown that tyrosine phosphorylation of a protein of 120 kDa, p120, correlated with src transformation in chicken embryo fibroblasts. Additionally, we previously identified two phosphotyrosine-containing cellular proteins, p130 and p110, that formed stable complexes with activated variants of pp60src, the src-encoded tyrosine kinase. To study transformation-relevant tyrosine kinase substrates, we have generated monoclonal antibodies to individual tyrosine phosphoproteins, including p130, p120, p110, and five additional phosphoproteins (p210, p125, p118, p85, and p185/p64). These antibodies detected several of the same tyrosine phosphoproteins in chicken embryo fibroblasts transformed by avian retroviruses Y73 and CT10, encoding the yes and crk oncogenes, respectively. Protein substrates in mouse, rat, hamster, and human cells overexpressing activated variants of chicken pp60src were also detected by several of the monoclonal antibodies.

Diarrhea in developed and developing countries: magnitude special settings and etiologies.

Abstract: Diarrheal diseases are major causes of morbidity, with attack rates ranging from two to 12 or more illnesses per person per year in developed and developing countries. In addition, diarrheal illnesses account for an estimated 12,600 deaths each day in children in Asia, Africa, and Latin America. The causes of diarrhea include a wide array of viruses, bacteria, and parasites, many of which have been recognized only in the last decade or two. While enterotoxigenic Escherichia coli and rotaviruses predominate in developing areas, Norwalk-like viruses, Campylobacter jejuni, and cytotoxigenic Clostridium difficile are seen with increasing frequency in developed areas; and Shigella, Salmonella, Cryptosporidium species, and Giardia lamblia are found throughout the world. The rational management of infectious diarrhea requires the highly selective use of laboratory tests for these varied etiologic agents, depending on the clinical and epidemiologic setting. The purpose of this review is to provide an overview of the magnitude, special settings, and etiologies of diarrhea endemic to developed and developing countries. This information permits a practical approach to the diagnosis and management of common diarrheal illnesses in different settings.

Two transpallidal pathways originating in the rat nucleus accumbens.

Abstract: The striatopallidal projection originating in the nucleus accumbens was investigated by using anterograde transport of PHA-L in combination with peptide immunohistochemistry in order to localize the injection sites and transported lectin with respect to neurochemically defined subterritories in the nucleus accumbens and subcommissural ventral pallidum. The results reported here supplement our previous observations, which indicated that the subcommissural ventral pallidum of the rat comprises two immunohistochemically defined subterritories (Zahm and Heimer, '88: J. Comp. Neurol., 272:516-535) which give rise to dichotomous downstream projection systems (Zahm, '89: Neuroscience, 30:33-50). The present data indicate that the neurotensin immunoreactivity-rich ventromedial district of ventral pallidum receives its accumbal input almost exclusively from the shell district of the nucleus accumbens. The accumbal core, alternatively, projects to the dorsolateral ventral pallidal subterritory that lacks appreciable neurotensin immunoreactivity and in many other respects more resembles the adjoining striatopallidal components of the caudate-putamen. In addition to direct topographic relationships in the frontal plane among the accumbal injection sites and ventral pallidal terminations, it was observed that more caudally placed core injections resulted in patches of striatopallidal terminations that were more caudally located in ventral pallidum. Shell injections, in contrast, produced columns of terminations that extended continuously from the rostralmost level that they appeared to the caudal end of ventromedial ventral pallidum. The accumbal shell, its exclusive projection to the ventromedial subterritory in the subcommissural ventral pallidum, and the previously reported, almost exclusive projection of that pallidal subdistrict to the mesencephalic ventral tegmental area are discussed in terms of a number of other neurochemical and hodological features that serve to distinguish them sufficiently to suggest that they represent a uniquely specialized part of the basal ganglia.

Evolution of EF-hand calcium-modulated proteins. I. Relationships based on amino acid sequences

Abstract: The relationships among 153 EF-hand (calcium-modulated) proteins of known amino acid sequence were determined using the method of maximum parsimony. These proteins can be ordered into 12 distinct subfamilies--calmodulin, troponin C, essential light chain of myosin, regulatory light chain, sarcoplasmic calcium binding protein, calpain, aequorin, Stronglyocentrotus purpuratus ectodermal protein, calbindin 28 kd, parvalbumin, alpha-actinin, and S100/intestinal calcium-binding protein. Eight individual proteins--calcineurin B from Bos, troponin C from Astacus, calcium vector protein from Branchiostoma, caltractin from Chlamydomonas, cell-division-cycle 31 gene product from Saccharomyces, 10-kd calcium-binding protein from Tetrahymena, LPS1 eight-domain protein from Lytechinus, and calcium-binding protein from Streptomyces--are tentatively identified as unique; that is, each may be the sole representative of another subfamily. We present dendrograms showing the relationships among the subfamilies and uniques as well as dendrograms showing relationships within each subfamily. The EF-hand proteins have been characterized from a broad range of organismal sources, and they have an enormous range of function. This is reflected in the complexity of the dendrograms. At this time we urge caution in assigning a simple scheme of gene duplications to account for the evolution of the 600 EF-hand domains of known sequence.

The physics of mechanical alloying: A first report

Abstract: In this paper, we present a first attempt to define the basic geometry, mechanics, and physics of the process of mechanical alloying. The geometry of the collision events which lead to particle fragmentation and coalescence is modeled on the basis of Hertzian contacts between the grinding media which entrap a certain amount of material volume between the impacting surfaces. This geometry essentially defines the volume of material affected per collision, and from this information and characteristics of the specific mill and the material being processed, impact times, powder strain rates and strains, powder temperature increase, powder cooling times, and milling times can be approximated.

The person-environment fit approach to stress: Recurring problems and some suggested solutions

Abstract: In recent years, the person-environment (P-E) fit approach to stress has become widely accepted among organizational stress researchers (Eulberg, Weekley and Bhagat, 1988) The P-E fit approach characterizes stress as a lack of correspondence between characteristics of the person (eg abilities, values) and the environment (eg demands, supplies) This lack of correspondence is hypothesized to generate deleterious psychological, physiological, and behavioral outcomes, which eventually result in increased morbidity and mortality This basic framework forms the core of many current theories of organizational stress, such as those presented by French and his colleagues (French, Rogers and Cobb, 1974; French, Caplan and Harrison, 1982), McGrath (1976), Karasek (1979), Schuler (1980), and others

Hands: A Pattern Theoretic Study of Biological Shapes

Abstract: The text develops a global shape model and applies it to the analysis of real pictures acquired with a visible light camera under varying conditions of optical degradation Computational feasibility of the algorithms derived from this model is achieved by analytical means The aim is to develop methods for image understanding based on structured restoration, for example automatic detection of abnormalities The limits of applicability of the algorithms are also traced by making the optical degradations more and more severe until the algorithms no longer succeed in their task This book is suitable for an advanced undergraduate or graduate seminar in pattern theory, or as an accompanying book for applied probability, computer vision or pattern recognition

Influence tactics used by subordinates: A theoretical and empirical analysis and refinement of the Kipnis, Schmidt, and Wilkinson subscales.

Abstract: The research of Kipnis, Schmidt, and Wilkinson (1980) is critiqued and their subordinate influence subscales examined in four studies. In the first, the subscale items were given to 34 judges, who rated each item for dimensionality. In the second, the 27 items plus several additions were administered to a sample of 251 employed MBA students, and exploratory and confirmatory factor analyses were conducted. A third study used a similar sample (N=281) and the same analyses

Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation.

Abstract: The nucleosome is the fundamental unit of assembly of the chromosome and reversible modifications of the histones have been suggested to be important in many aspects of nucleosome function. The structure-function relations of the amino-terminal domain of yeast histone H4 were examined by the creation of directed point mutations. The four lysines subject to reversible acetylation were essential for histone function as the substitution of arginine or asparagine at these four positions was lethal. No single lysine residue was completely essential since arginine substitutions at each position were viable, although several of these mutants were slower in completing DNA replication. The simultaneous substitution of glutamine for the four lysine residues was viable but conferred several phenotypes including mating sterility, slow progression through the G2/M period of the division cycle, and temperature-sensitive growth, as well as a prolonged period of DNA replication. These results provide genetic proof for the roles of the H4 amino-terminal domain lysines in gene expression, replication, and nuclear division.

On dividing reference data into subgroups to produce separate reference ranges.

Abstract: We consider statistical criteria for partitioning a reference database to obtain separate reference ranges for different subpopulations. Using general formulas relating population variances, sample sizes, and the normal deviate test for the significance of the difference between two subgroup means, we show that partitioning into separate ranges produces little reduction in between-person variability, even when the differences between means are highly significant statistically. However, when there is a clear physiological basis for distinguishing between certain subgroups, simulation studies show that partitioning may be necessary to obtain reference limits that cut off the desired proportions of low and high values in each subgroup. Guidelines based on these results are provided to help decide whether separate ranges should be obtained for a given analyte.

Income Level, Gender, Ethnicity, and Household Composition as Predictors of Children's School-based Competence

Abstract: In the United States, being black, male, or growing up in a low-income and/or single-parent household have all been identified as risk factors for maladjustment during childhood. Interpretation of these findings is, however, often difficult because of the well-known associations among these variables. In the present study, we compared predictions of 3 different forms of children's competence from each of these 4 variables. In a sample of 868 black and white elementary school children from 2-parent and mother-headed 1-parent homes, we studied 3 aspects of school-based competence: conduct, peer relations, and academic achievement. Results showed that although the independent variables accounted for different amounts of variance in each domain of competence, income level and gender were better overall predictors of children's competence in conduct and peer relations than were ethnicity or household composition. Income level and ethnicity were better overall predictors of academic achievement than were gender or household composition, although each of the 4 variables made a significant contribution. Overall, income level and gender were thus the strongest predictors of children's competence. Black children were, however, more likely than white children to live in low-income homes. Our results thus highlighted some correlates of the unequal distribution of economic resources among black and white children growing up in the United States today.

Observations on electrode-tissue interface temperature and effect on electrical impedance during radiofrequency ablation of ventricular myocardium.

Abstract: The purpose of this study was to correlate changes in electrical impedance with the electrode-tissue interface temperature and to characterize the associated events occurring at the catheter tip electrode. In a canine model, lesions were created in vitro (n = 49) and in vivo (n = 31) and radiofrequency power settings were varied. Electrode-tissue interface temperature, delivered current, and voltage were recorded, and impedance was calculated. A sudden rise in electrical impedance was seen in only two of 17 ablations in vitro and in one of 16 ablations in vivo with a peak electrode-tissue interface temperature of less than 100 degrees C compared with 29 of 32 ablations in vitro (p = 0.0001) and 12 of 15 ablations in vivo with a temperature of more than 100 degrees C (p = 0.0001). This phenomenon was associated with the observation of boiling and popping at the tip in in vitro preparations and tissue avulsion and thrombus formation on the catheter tip in in vivo studies. The lesion size was directly proportional to the peak temperature for all ablations but not to the peak power, current, or voltage during radiofrequency catheter ablation in the heart. Maintaining electrode-tissue interface temperature at less than 100 degrees C during radiofrequency catheter ablation in the heart may avoid the complications associated with the sudden rise in electrical impedance.

Critical exponents for the one-dimensional Hubbard model

Abstract: Using results on the scaling of energies with the size of the system and the principles of conformal quantum field theory, we calculate the asymptotics of correlation functions for the one-dimensional Hubbard model in the repulsive regime in the presence of an external magnetic field. The critical exponents are given in terms of a dressed charge matrix that is defined in terms of a set of integral equations obtained from the Bethe-Ansatz solution for the Hubbard model. An interpretation of this matrix in terms of thermodynamical coefficients is given, and several limiting cases are considered.

Child-Mother Attachment of Six-Year-Olds and Social Competence at School

Abstract: 89 children and their mothers participated in a study examining the association between attachment and peer social competence. During the summer following kindergarten, quality of attachment was assessed from reunion episodes following a 1-hour separation. In the fall, measures of sociometric status, peer behavior nominations, and peer liking ratings were collected. Teachers completed liking ratings and ratings of behavior problems and competence. Consistent with longitudinal studies of infant attachment and peer relations, insecurely attached boys were less well liked by peers and teachers, were perceived as more aggressive by classmates, and were rated by teachers as less competent and as having more behavior problems than were their secure counterparts. No such associations emerged for girls. Possible explanations for unanticipated differences in the pattern of results for boys and girls are discussed.

Interaction of cholesterol with various glycerophospholipids and sphingomyelin.

Abstract: The influence of cholesterol on the phase behavior of glycerophospholipids and sphingomyelins was investigated by spin-label electron spin resonance (ESR) spectroscopy. 4-(4,4-Dimethyl-3-oxy-2-tridecyl-2-oxazolidinyl)butanoic acid (5-SASL) and 1-stearoyl-2-[4-(4,4-dimethyl-3-oxy-2-tridecyl-2-oxazolidinyl)butanoy l]-sn- glycero-3-phosphocholine (5-PCSL) spin-labels were employed for this purpose. The outer hyperfine splitting constants, Amax, measured from the spin-label ESR spectra as a function of temperature were taken as empirical indicators of cholesterol-induced changes in the acyl chain motions in the fluid state. The Amax values of 5-PCSL exhibit a triphasic dependence on the concentration of cholesterol for phosphatidylcholines and bovine brain sphingomyelin. We interpret this dependence as reflecting the existence of liquid-disordered, ld, liquid-ordered, lo, and coexistence regions, ld + lo. The phase boundary between the ld and the two-phase region and the boundary between the lo and the two-phase region in the phosphatidylcholine-cholesterol systems coalesce at temperatures 25-33 degrees C above the main-chain melting transition temperature of the cholesterol-free phosphatidylcholine bilayers. In the case of bovine brain sphingomyelin, the ld-lo phase coalescence occurs about 47 degrees C above the melting temperature of the pure sphingomyelin. The selectivity of interaction of cholesterol with glycerophospholipids of varying headgroup charge was studied by comparing the cholesterol-induced changes in the Amax values of derivatives of phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylserine spin-labeled at the fifth position of the sn-2 chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Measurements using cascade impactor, liquid impinger, and a two-site monoclonal antibody assay for Fel d I.

Abstract: The recent development of a sensitive two-site monoclonal antibody immunoassay for the major cat allergen (Fel d I) has made it possible to make accurate measurements of airborne cat allergen using low volume samplers that do not disturb the room. Houses with cats had from 2 to 20 ng Fel d I/m3 air compared with less than 0.2 ng/m3 in houses without cats. Using a cascade impactor and a multistage liquid impinger, the particle size distribution of airborne Fel d I in nine houses was 75% on particle greater than or equal to 5 microns in diameter and 25% (range, 10 to 62%) on particles less than or equal to 2.5 microns. In a cat vivarium with 12 cats, the air contained 40 ng Fel d I/m3, but less than 2% was detected on particles less than or equal to 2.5 microns. The air exchange rate in the vivarium (approximately 15 changes/h) appears to be the major difference from domestic houses (less than 0.5 changes/h). Repeated studies in one house confirmed a very high proportion (approximately 60%) of Fel d I on small particles. During domestic cleaning, the levels of small particle allergen in this house approached those produced by a nebulizer for bronchial provocation, i.e., 40 ng/m3. These results show unequivocally that significant airborne Fel d I is associated with small particles, which remain airborne for long periods. These findings are strikingly different from previous results obtained with airborne dust mite allergen. The results provide an explanation for the distinctive rapid onset of asthma or rhinitis in patients allergic to cats and a basis for designing a policy to reduce airborne allergen in houses with cats.

Pharmacokinetics of fentanyl administered by computer-controlled infusion pump.

Abstract: Fentanyl was administered to 21 patients using a computer-controlled infusion pump (CCIP) based on a pharmacokinetic model. Eleven of the patients were dosed according to the pharmacokinetics described by McClain and Hug, and ten of the patients were dosed according to the pharmacokinetics described by Scott and Stanski. The authors measured the difference between the measured arterial fentanyl concentrations and the concentrations predicted by the CCIP for each pharmacokinetic parameter set. The median absolute performance error (MDAPE) in patients dosed according to McClain and Hug's parameters was 61%, and the MDAPE in patients dosed according to Scott and Stanski's parameters was 33%. The population pharmacokinetics in these 21 patients were analyzed using a pooled data technique. The pharmacokinetics of fentanyl in this population showed a smaller central compartment volume and a more rapid initial distribution half-life than previously estimated for fentanyl. The derived pharmacokinetic parameters described these patients well and also predicted the observed fentanyl concentrations from four previously published fentanyl studies with reasonable accuracy. Comparison of the parameters used by the authors with those of McClain and Hug demonstrated that dosing regimens designed from pharmacokinetic models can be fairly accurate at the times sampled in the original study but may not be accurate at time points not sampled in the original research. The authors concluded that although the pharmacokinetics of fentanyl administered by CCIP are the same as the pharmacokinetics of fentanyl administered by a bolus or constant rate infusion, a pharmacokinetic study using a CCIP may be particularly effective at characterizing the most rapid distribution pharmacokinetic parameters, and thus may provide parameters appropriate for subsequent use in a CCIP.

Adenosine for paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Assessment in placebo-controlled, multicenter trials. The Adenosine for PSVT Study Group.

Abstract: OBJECTIVE To assess the safety and efficacy of intravenous adenosine in terminating acute episodes of paroxysmal supraventricular tachycardia. DESIGN Two prospective, double-blind, randomized, placebo-controlled trials to evaluate dose response in patients receiving adenosine and to compare the effects of adenosine with those of verapamil. PATIENTS A total of 359 patients with a tachycardia electrocardiographically consistent with paroxysmal supraventricular tachycardia were entered into the two protocols. Patients subsequently found to have arrhythmias other than paroxysmal supraventricular tachycardia were excluded from the efficacy analysis. INTERVENTIONS The first protocol compared sequential intravenous bolus doses of 3, 6, 9, and 12 mg of adenosine to equal volumes of saline. In the second protocol, patients received either 6 mg and, if necessary, 12 mg of adenosine or 5 mg and, if necessary, 7.5 mg of verapamil. MEASUREMENTS AND MAIN RESULTS When data are expressed in terms of cumulative response in eligible patients, intravenous adenosine terminated acute episodes of paroxysmal supraventricular tachycardia in 35.2%, 62.3%, 80.2%, and 91.4% of patients who received maximum doses of 3, 6, 9, and 12 mg, respectively, in a four-dose sequence, whereas 8.9%, 10.7%, 14.3%, and 16.1% of patients responded to four sequential placebo doses (P less than 0.0001). In the second trial, cumulative response rates after 6 mg followed, if necessary, by 12 mg of adenosine were 57.4% and 93.4%, and after 5 mg followed, if necessary, by 7.5 mg of verapamil were 81.3% and 91.4%. The average time after injection to termination of tachycardia by adenosine was 30 seconds. Adenosine caused adverse effects in 36% of patients, but they lasted less than 1 minute and were usually mild. CONCLUSIONS Adenosine in graded doses up to 12 mg rapidly and effectively terminates acute episodes of paroxysmal supraventricular tachycardia in which the atrioventricular node is an integral part of the re-entrant circuit. The overall efficacy of adenosine is similar to that of verapamil, but its onset of action is more rapid. Adverse reactions to adenosine are common but are minor and brief.

Carbon isotope composition of individual amino acids in the Murchison meteorite

Abstract: A SIGNIFICANT portion of prebiotic organic matter on the early Earth may have been introduced by carbonaceous asteroids and comets1. The distribution and stable-isotope composition of individual organic compounds in carbonaceous meteorites, which are thought to be derived from asteroidal parent bodies, may therefore provide important information concerning mechanistic pathways for prebiotic synthesis2 and the composition of organic matter on Earth before living systems developed3. Previous studies11, 12 have shown that meteorite amino acids are enriched in 13C relative to their terrestrial counterparts, but individual species were not distinguished. Here we report the 13C contents of individual amino acids in the Murchison meteorite. The amino acids are enriched in 13C, indicating an extraterrestrial origin. Alanine is not racemic, and the 13C enrichment of its D- and L-enantiomers implies that the excess of the L-enantiomer is indigenous rather than terrestrial contamination, suggesting that optically active materials were present in the early Solar System before life began.