Showing papers by "Autonomous University of Barcelona published in 2006"

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

European phenological response to climate change matches the warming pattern

Abstract: Global climate change impacts can already be tracked in many physical and biological systems; in particular, terrestrial ecosystems provide a consistent picture of observed changes. One of the preferred indicators is phenology, the science of natural recurring events, as their recorded dates provide a high-temporal resolution of ongoing changes. Thus, numerous analyses have demonstrated an earlier onset of spring events for mid and higher latitudes and a lengthening of the growing season. However, published single-site or single-species studies are particularly open to suspicion of being biased towards predominantly reporting climate change-induced impacts. No comprehensive study or meta-analysis has so far examined the possible lack of evidence for changes or shifts at sites where no temperature change is observed. We used an enormous systematic phenological network data set of more than 125 000 observational series of 542 plant and 19 animal species in 21 European countries (1971–2000). Our results showed that 78% of all leafing, flowering and fruiting records advanced (30% significantly) and only 3% were significantly delayed, whereas the signal of leaf colouring/fall is ambiguous. We conclude that previously published results of phenological changes were not biased by reporting or publication predisposition: the average advance of spring/summer was 2.5 days decade � 1 in Europe. Our analysis of 254 mean national time series undoubtedly demonstrates that species’ phenology is responsive to temperature of the preceding

mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt

Abstract: Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent loss in insulin receptor substrate-1 expression leading to feedback down-regulation of signaling through the pathway. In model systems, tumors exhibiting mutational activation of phosphoinositide-3-kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR inhibitors, including rapamycin. Despite the activity in model systems, in patients, mTOR inhibitors exhibit more modest antitumor activity. We now show that mTOR inhibition induces insulin receptor substrate-1 expression and abrogates feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative, RAD001. IGF-I receptor inhibition prevents rapamycin-induced Akt activation and sensitizes tumor cells to inhibition of mTOR. In contrast, IGF-I reverses the antiproliferative effects of rapamycin in serum-free medium. The data suggest that feedback down-regulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation. Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity.

Novel ecosystems: theoretical and management aspects of the new ecological world order

Abstract: We e xplore the issues relevant to those types of ecosystems containing new combinations of species that arise through human action, environmental change, and the impacts of the deliberate and inadvertent introduction of species from other regions. Novel ecosystems (also termed ‘emerging ecosystems’) result when species occur in combinations and relative abundances that have not occurred previously within a given biome. Key characteristics are novelty, in the form of new species combinations and the potential for changes in ecosystem functioning, and human agency, in that these ecosystems are the result of deliberate or inadvertent human action. As more of the Earth becomes transformed by human actions, novel ecosystems increase in importance, but are relatively little studied. Either the degradation or invasion of native or ‘wild’ ecosystems or the abandonment of intensively managed systems can result in the formation of these novel systems. Important considerations are whether these new systems are persistent and what values they may have. It is likely that it may be very difficult or costly to return such systems to their previous state, and hence consideration needs to be given to developing appropriate management goals and approaches.

Oral Fingolimod (FTY720) for Relapsing Multiple Sclerosis

Abstract: Background Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis. Methods We randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg or 5.0 mg, or a placebo once daily, and we followed these patients for 6 months with magnetic resonance imaging (MRI) and clinical evaluations (core study, months 0 to 6). The primary end point was the total number of gadolinium-enhanced lesions recorded on T1-weighted MRI at monthly intervals for 6 months. In an extension study in which the investigators and patients remained unaware of the dose assignments (months 7 to 12), patients who received placebo underwent randomization again to one of the fingolimod doses. Results A total of 255 patients completed the core study. The median total number of gadolinium-enhanced lesions on MRI was lower with 1.25 mg of fingolimod (1 lesion, P<0.001) and 5.0 mg of fingolimod (3 lesions, P=0.006) than with placebo (5 lesions). The annualized re...

Comet 81P/Wild 2 under a microscope.

Abstract: The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.

Lymphoid neogenesis in chronic inflammatory diseases

Abstract: The frequent observation of organized lymphoid structures that resemble secondary lymphoid organs in tissues that are targeted by chronic inflammatory processes, such as autoimmunity and infection, has indicated that lymphoid neogenesis might have a role in maintaining immune responses against persistent antigens. In this Review, we discuss recent progress in several aspects of lymphoid neogenesis, focusing on the similarities with lymphoid tissue development, the mechanisms of induction, functional competence and pathophysiological significance. As more information on these issues becomes available, a better understanding of the role of lymphoid neogenesis in promoting chronic inflammation might eventually lead to new strategies to target immunopathological processes.

A new scenario for the Quaternary history of European beech populations: palaeobotanical evidence and genetic consequences

Abstract: Summary • Here, palaeobotanical and genetic data for common beech (Fagus sylvatica) in Europe are used to evaluate the genetic consequences of long-term survival in refuge areas and postglacial spread. • Four large datasets are presented, including over 400 fossil-pollen sites, 80 plant-macrofossil sites, and 450 and 600 modern beech populations for chloroplast and nuclear markers, respectively. • The largely complementary palaeobotanical and genetic data indicate that: (i) beech survived the last glacial period in multiple refuge areas; (ii) the central European refugia were separated from the Mediterranean refugia; (iii) the Mediterranean refuges did not contribute to the colonization of central and northern Europe; (iv) some populations expanded considerably during the postglacial period, while others experienced only a limited expansion; (v) the mountain chains were not geographical barriers for beech but rather facilitated its diffusion; and (vi) the modern genetic diversity was shaped over multiple glacial–interglacial cycles. • This scenario differs from many recent treatments of tree phylogeography in Europe that largely focus on the last ice age and the postglacial period to interpret genetic structure and argue that the southern peninsulas (Iberian, Italian and Balkan) were the main source areas for trees in central and northern Europe.

Who's who in networks. Wanted: the key player

Abstract: Finite population non-cooperative games with linear-quadratic utilities, where each player de- cides how much action she exerts, can be interpreted as a network game with local payocom- plementarities, together with a globally uniform payosubstitutability component and an own- concavity eect. For these games, the Nash equilibrium action of each player is proportional to her Bonacich centrality in the network of local complementarities, thus establishing a bridge with the sociology literature on social networks. This Bonacich-Nash linkage implies that aggregate equilibrium increases with network size and density. We then analyze a policy that consists of targeting the key player, that is, the player who, once removed, leads to the optimal change in aggregate activity. We provide a geometric characterization of the key player identi…ed with an inter-centrality measure, which takes into account both a player's centrality and her contribution to the centrality of the others.

EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria.

Abstract: This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).

The Lojasiewicz Inequality for Nonsmooth Subanalytic Functions with Applications to Subgradient Dynamical Systems

Abstract: Given a real-analytic function $f:\mathbb{R}^{n} \rightarrow \mathbb{R}$ and a critical point $a \in \mathbb{R}^{n}$, the Łojasiewicz inequality asserts that there exists $\theta\in\lbrack\frac{1}{2},1)$ such that the function $|f-f(a)|^{\theta}\,\Vert abla f\Vert^{-1}$ remains bounded around $a$. In this paper, we extend the above result to a wide class of nonsmooth functions (that possibly admit the value $+\infty$), by establishing an analogous inequality in which the derivative $ abla f(x)$ can be replaced by any element $x^{\ast}$ of the subdifferential $\partial f(x)$ of $f$. Like its smooth version, this result provides new insights into the convergence aspects of subgradient-type dynamical systems. Provided that the function $f$ is sufficiently regular (for instance, convex or lower-$C^{2}$), the bounded trajectories of the corresponding subgradient dynamical system can be shown to be of finite length. Explicit estimates of the rate of convergence are also derived.

The Epidermal Growth Factor Receptor Pathway: A Model for Targeted Therapy

Abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase receptor that is frequently expressed in epithelial tumors. The EGFR was the first receptor to be proposed as a target for cancer therapy, and after 2 decades of intensive research, there are several anti-EGFR agents available in the clinic. Recent advances in our understanding in the mechanisms of receptor activation and function, discovery of primary and secondary EGFR somatic mutations, as well as a new generation of anti-EGFR agents provide new leads on the clinical targeting of this receptor and may serve as a model for strategies aimed at targeting other receptors.

Measurement of neutrino oscillation by the K2K experiment

Abstract: We present measurements of {nu}{sub {mu}} disappearance in K2K, the KEK to Kamioka long-baseline neutrino oscillation experiment. One-hundred and twelve beam-originated neutrino events are observed in the fiducial volume of Super-Kamiokande with an expectation of 158.1{sub -8.6}{sup +9.2} events without oscillation. A distortion of the energy spectrum is also seen in 58 single-ring muonlike events with reconstructed energies. The probability that the observations are explained by the expectation for no neutrino oscillation is 0.0015% (4.3{sigma}). In a two-flavor oscillation scenario, the allowed {delta}m{sup 2} region at sin{sup 2}2{theta}=1 is between 1.9 and 3.5x10{sup -3} eV{sup 2} at the 90% C.L. with a best-fit value of 2.8x10{sup -3} eV{sup 2}.

Diazonium salts as substrates in palladium-catalyzed cross-coupling reactions.

Abstract: 2.1.4. Effect of Bases and Other Additives 4628 2.1.5. Improved Catalytic Systems 4629 2.1.6. Applications in Synthesis 4630 2.1.7. Mechanistic Studies 4632 2.1.8. Related Matsuda−Heck Reactions 4633 2.2. Suzuki−Miyaura Reaction 4634 2.2.1. Early Studies 4634 2.2.2. Modification of the Boronic Counterpart 4635 2.2.3. Improved Catalytic Systems 4637 2.2.4. Superior Reactivity of N2 as the Nucleofuge 4637

Long-Term Survival in Patients Presenting With Type B Acute Aortic Dissection Insights From the International Registry of Acute Aortic Dissection

Abstract: Background— Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival. Methods and Results— We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6±6.6%, 82.8±18.9%, and 76.2±25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR],1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a hist...

Rapid climate change-related growth decline at the southern range edge of Fagus sylvatica

Abstract: Studies on Fagus sylvatica show that growth in populations toward the southern limit of this species' distribution is limited strongly by drought. Warming temperatures in the Mediterranean region are expected to exacerbate drought where they are not accompanied by increases in precipitation. We studied levels of annual growth in mature F. sylvatica trees over the last half-century in the Montseny Mountains in Catalonia (northeast Spain). Our results show significantly lower growth of mature trees at the lower limit of this species' distribution when compared with trees at higher altitudes. Growth at the lower Fagus limit is characterized by a rapid recent decline starting in approximately 1975. By 2003, growth of mature trees had fallen by 49% when compared with predecline levels. This is not an age-related phenomenon, nor is it seen in comparable populations at higher altitudes. Analysis of climate-growth relationships suggests that the observed decline in growth is a result of warming temperatures and that, as precipitation in the region has not increased, precipitation is now insufficient to ameliorate the negative effects of increased temperatures on tree growth. As the climate-response of the studied forest is comparable with that of F. sylvatica forests in other southern European regions, it is possible that this growth decline is a more widespread phenomenon. Warming temperatures may lead to a rapid decline in the growth of range-edge populations and a consequent retreat of the species distribution in southern Europe. Assessment of long-term growth trends across the southern range edge of F. sylvatica therefore merits further attention.

Unexpected biodiversity loss under global warming in the neotropical Guayana Highlands: a preliminary appraisal

Abstract: The fully vegetated summits of the table mountains that form the Guayana Highlands (GH), in northern South America, hold amazing biodiversity and endemism levels, and unique vegetation types. In spite of their present-day healthy appearance, their biota is seriously threatened of habitat loss by upward displacement, because of the projected warming for the end of this century. Available data are still insufficient for a definite assessment, but preliminary estimations based on representative endemic vascular plant species show that roughly one-tenth to one-third of them would loss their habitat with the 2‐41C temperature increase predicted for the region by AD 2100. Given the underlying endemism, the eventual loss of biodiversity will be of global nature. Other mountain ranges around the world with similar characteristics of the GH, namely topographical isolation, high endemism and absence of nival stage because of the lower altitude, would be under similar unexpected risk, and should be urgently considered for conservation purposes.

Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis

Abstract: Administration of daclizumab, a humanized mAb directed against the IL-2Ralpha chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4(+) and CD8(+) T cells and significant expansion of CD56(bright) natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56(bright) NK cells and contraction of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.

Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment.

Abstract: OBJECTIVES. Infantile hemangiomas are the most common tumor of infancy. Risk factors for complications and need for treatment have not been studied previously in a large prospective study. This study aims to identify clinical characteristics associated with complications and the need for therapeutic intervention. PATIENTS AND METHODS. We conducted a prospective cohort study at 7 US pediatric dermatology clinics with a consecutive sample of 1058 children, aged ≤12 years, with infantile hemangiomas enrolled between September 2002 and October 2003. A standardized questionnaire was used to collect data on each patient and each hemangioma, including clinical characteristics, complications, and treatment. RESULTS. Twenty-four percent of patients experienced complications related to their hemangioma(s), and 38% of our patients received some form of treatment during the study period. Hemangiomas that had complications and required treatment were larger and more likely to be located on the face. Segmental hemangiomas were 11 times more likely to experience complications and 8 times more likely to receive treatment than localized hemangiomas, even when controlled for size. CONCLUSIONS. Large size, facial location, and/or segmental morphology are the most important predictors of poor short-term outcomes as measured by complication and treatment rates.

Bladder Cancer and Exposure to Water Disinfection By-Products through Ingestion, Bathing, Showering, and Swimming in Pools

Abstract: Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998-2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus 35 micro g/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.

Biomolecular modeling: Goals, problems, perspectives.

Abstract: Computation based on molecular models is playing an increasingly important role in biology, biological chemistry, and biophysics. Since only a very limited number of properties of biomolecular systems is actually accessible to measurement by experimental means, computer simulation can complement experiment by providing not only averages, but also distributions and time series of any definable quantity, for example, conformational distributions or interactions between parts of systems. Present day biomolecular modeling is limited in its application by four main problems: 1) the force-field problem, 2) the search (sampling) problem, 3) the ensemble (sampling) problem, and 4) the experimental problem. These four problems are discussed and illustrated by practical examples. Perspectives are also outlined for pushing forward the limitations of biomolecular modeling.

Search for neutral MSSM Higgs bosons at LEP

Abstract: The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have searched for the neutral Higgs bosons which are predicted by the Minimal Supersymmetric standard model (MSSM). The data of the four collaborations are statistically combined and examined for their consistency with the background hypothesis and with a possible Higgs boson signal. The combined LEP data show no significant excess of events which would indicate the production of Higgs bosons. The search results are used to set upper bounds on the cross-sections of various Higgs-like event topologies. The results are interpreted within the MSSM in a number of “benchmark” models, including CP-conserving and CP-violating scenarios. These interpretations lead in all cases to large exclusions in the MSSM parameter space. Absolute limits are set on the parameter cosβ and, in some scenarios, on the masses of neutral Higgs bosons.

Targeting Tyrosine Kinases in Cancer: The Second Wave

Abstract: One of the most exciting developments in cancer research in recent years has been the clinical validation of molecularly targeted drugs that inhibit the action of pathogenic tyrosine kinases. Treatment of appropriately selected patients with these drugs can alter the natural history of their disease and improve survival. The clinical validation of these "first-generation" tyrosine kinase inhibitors has been the prelude to a second wave of advances in molecular targeting that is expected to further change the way we classify and treat cancer. Efforts are now being directed at identifying the tumor subtypes and patients who will benefit the most from these drugs. In addition, new compounds that circumvent acquired resistance to the first-generation tyrosine kinase inhibitors are being tested in patients with refractory disease. Agents directed against new molecular targets are also being explored.

B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities.

Abstract: The present paradigm dictates that phagocytosis is accomplished mainly by 'professional' phagocytes (such as macrophages and monocytes), whereas B cells lack phagocytic capabilities. Here we demonstrate that B cells from teleost fish have potent in vitro and in vivo phagocytic activities. Particle uptake by B cells induced activation of 'downstream' degradative pathways, leading to 'phagolysosome' formation and intracellular killing of ingested microbes. Those results indicate a previously unknown function for B cells in the innate immunity of these primitive animals. A considerable proportion of Xenopus laevis B cells were also phagocytic. Our findings support the idea that B cells evolved from an ancestral phagocytic cell type and provide an evolutionary framework for understanding the close relationship between mammalian B lymphocytes and macrophages.

Neutrino-induced nucleosynthesis of A>64 nuclei: the nu p process

Abstract: We present a new nucleosynthesis process that we denote as the nu p process, which occurs in supernovae (and possibly gamma-ray bursts) when strong neutrino fluxes create proton-rich ejecta. In this process, antineutrino absorptions in the proton-rich environment produce neutrons that are immediately captured by neutron-deficient nuclei. This allows for the nucleosynthesis of nuclei with mass numbers A>64, , making this process a possible candidate to explain the origin of the solar abundances of (92,94)Mo and (96,98)Ru. This process also offers a natural explanation for the large abundance of Sr seen in a hyper-metal-poor star.

Microbubble Administration Accelerates Clot Lysis During Continuous 2-MHz Ultrasound Monitoring in Stroke Patients Treated With Intravenous Tissue Plasminogen Activator

Abstract: Background and Purpose— We sought to evaluate the effects of administration of microbubbles (MBs) on the beginning, speed, and degree of middle cerebral artery (MCA) recanalization during systemic thrombolysis and continuous 2-MHz pulsed-wave transcranial Doppler (TCD) monitoring. Methods— We evaluated 111 patients with acute stroke attributable to MCA occlusion treated with intravenous tissue plasminogen activator (tPA). Thirty-eight patients were treated with tPA plus continuous 2-hour TCD monitoring plus 3 doses of 2.5 g (400 mg/mL) of galactose-based MBs given at 2, 20, and 40 minutes after tPA bolus (MB group). These patients were compared with 73 patients who were allocated to receive tPA plus continuous 2-hour TCD ultrasound (US) monitoring (tPA/US group) or tPA plus placebo monitoring (tPA group), most of whom were enrolled in a previous study of US-enhanced thrombolysis. The beginning, degree, and time to maximum completeness of recanalization during the first 2 hours of tPA bolus were recorded. ...