Acid waters in tank bromeliads: Causes and potential consequences.

PREMISE: The consequences of acidity for plant performance are profound, yet the prevalence and causes of low pH in bromeliad tank water are unknown despite its functional relevance to key members of many neotropical plant communities. METHODS: We investigated tank water pH for eight bromeliad species in the field and for the widely occurring Guzmania monostachia in varying light. We compared pH changes over time between plant and artificial tanks containing a solution combined from several plants. Aquaporin transcripts were measured for field plants at two levels of pH. We investigated relationships between pH, leaf hydraulic conductance, and CO2 concentration in greenhouse plants and tested proton pump activity using a stimulator and inhibitor. RESULTS: Mean tank water pH for the eight species was 4.7 ± 0.06 and was lower for G. monostachia in higher light. The pH of the solution in artificial tanks, unlike in plants, did not decrease over time. Aquaporin transcription was higher for plants with lower pH, but leaf hydraulic conductance did not differ, suggesting that the pH did not influence water uptake. Tank pH and CO2 concentration were inversely related. Fusicoccin enhanced a decrease in tank pH, whereas orthovanadate did not. CONCLUSIONS: Guzmania monostachia acidified its tank water via leaf proton pumps, which appeared responsive to light. Low pH increased aquaporin transcripts but did not influence leaf hydraulic conductance, hence may be more relevant to nutrient uptake.

Open for Bismuth: Main Group Metal-to-Ligand Charge Transfer.

The synthesis, characterization, and photophysical properties of 4- and 6-coordinate Bi3+ coordination complexes are reported. Bi(bzq)3 (1) and [Bi(bzq)2]Br (2) (bzq = benzo[h]quinoline) are synthesized by reaction of 9-Li-bzq with BiCl3 and BiBr3, respectively. Absorption spectroscopy, electrochemistry, and DFT studies suggest that 1 has 42% Bi 6s character in its highest-occupied molecular orbital (HOMO) as a result of six σ* interactions with the bzq ligands. Excitation of 1 at 450 nm results in a broad emission feature at 520 nm, which is rationalized as a metal-to-ligand charge transfer (MLCT) and phosphorescent emission resulting from bismuth-mediated intersystem crossing (ISC) to a triplet excited state. This excited state revealed a 35 µs lifetime and was quenched in the presence of oxygen. These results demonstrate that useful optoelectronic properties of Bi3+ can be accessed through hypercoordination with covalent organobismuth interactions that mimic the electronic structure of lead perovskites.

Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.

Nuclear-Mitochondrial interactions influence susceptibility to HIV-associated neurocognitive impairment.

HIV-associated neurocognitive impairment (NCI) is a term established to capture a wide spectrum of HIV related neurocognitive deficits ranging in severity from asymptomatic to dementia. The genetic underpinnings of this complex phenotype are incompletely understood. Mitochondrial function has long been thought to play a role in neurodegeneration, along with iron metabolism and transport. In this work, we aimed to characterize the interplay of mitochondrial DNA (mtDNA) haplogroup and nuclear genetic associations to NCI phenotypes in the CHARTER cohort, encompassing 1025 individuals of European-descent, African-descent, or admixed Hispanic. We first employed a polygenic modeling approach to investigate the global effect of previous marginally associated nuclear SNPs, and to examine how the polygenic effect of these SNPs is influenced by mtDNA haplogroups. We see evidence of a significant interaction between nuclear SNPs en masse and mtDNA haplogroups within European-descent and African-descent individuals. Subsequently, we performed an analysis of each SNP by mtDNA haplogroup, and detected significant interactions between two nuclear SNPs (rs17160128 and rs12460243) and European haplogroups. These findings, which require validation in larger cohorts, indicate a potential new role for nuclear-mitochondrial DNA interactions in susceptibility to NCI and shed light onto the pathophysiology of this neurocognitive phenotype.

Release from PI: An analysis and a model.

Recall decreases across a series of subspan immediate-recall trials but rebounds if the semantic category of the words is changed, an example of release from proactive interference (RPI). The size of the rebound depends on the semantic categories used and ranges from 0% to 95%. We used a corpus of novels to create vectors representing the meaning of about 40,000 words using the BEAGLE algorithm. The distance between categories and spread within categories jointly predicted the size of the RPI. We used a holographic model for recall equipped with a lexicon of BEAGLE vectors representing the meaning of words. The model captured RPI using a hologram as an interface to bridge information from episodic and semantic memory; it is the first account of RPI to capture release at the level of individual words in categorized lists.

A tale of two plasticities: leaf hydraulic conductances and related traits diverge for two tropical epiphytes from contrasting light environments.

We compared the effects of different light environments on leaf hydraulic conductance (Kleaf ) for two congeneric epiphytes, the tank bromeliads Guzmania lingulata (L.) Mez and Guzmania monostachia (L.) Rusby ex Mez. They occur sympatrically at the study site, although G. monostachia is both wider ranging and typically found in higher light. We collected plants from two levels of irradiance and measured Kleaf as well as related morphological and anatomical traits. Leaf xylem conductance (Kxy ) was estimated from tracheid dimensions, and leaf conductance outside the xylem (Kox ) was derived from a leaky cable model. For G. monostachia, but not for G. lingulata, Kleaf and Kxy were significantly higher in high light conditions. Under both light conditions, Kxy and Kox were co-limiting for the two species, and all conductances were in the low range for angiosperms. With respect to hydraulic conductances and a number of related anatomical traits, G. monostachia exhibited greater plasticity than did G. lingulata, which responded to high light chiefly by reducing leaf size. The positive plasticity of leaf hydraulic traits in varying light environments in G. monostachia contrasted with negative plasticity in leaf size for G. lingulata, suggesting that G. monostachia may be better able to respond to forest conditions that are likely to be warmer and more disturbed in the future.

BrachyView, a novel in-body imaging system for HDR prostate brachytherapy: Experimental evaluation.

PURPOSE: This paper presents initial experimental results from a prototype of high dose rate (HDR) BrachyView, a novel in-body source tracking system for HDR brachytherapy based on a multipinhole tungsten collimator and a high resolution pixellated silicon detector array. The probe and its associated position estimation algorithms are validated and a comprehensive evaluation of the accuracy of its position estimation capabilities is presented. METHODS: The HDR brachytherapy source is moved through a sequence of positions in a prostate phantom, for various displacements in x, y, and z. For each position, multiple image acquisitions are performed, and source positions are reconstructed. Error estimates in each dimension are calculated at each source position and combined to calculate overall positioning errors. Gafchromic film is used to validate the accuracy of source placement within the phantom. RESULTS: More than 90% of evaluated source positions were estimated with an error of less than one millimeter, with the worst-case error being 1.3 mm. Experimental results were in close agreement with previously published Monte Carlo simulation results. CONCLUSIONS: The prototype of HDR BrachyView demonstrates a satisfactory level of accuracy in its source position estimation, and additional improvements are achievable with further refinement of HDR BrachyView's image processing algorithms.

A new virtual ring-based system matrix generator for iterative image reconstruction in high resolution small volume PET systems.

A common approach to improving the spatial resolution of small animal PET scanners is to reduce the size of scintillation crystals and/or employ high resolution pixellated semiconductor detectors. The large number of detector elements results in the system matrix--an essential part of statistical iterative reconstruction algorithms--becoming impractically large. In this paper, we propose a methodology for system matrix modelling which utilises a virtual single-layer detector ring to greatly reduce the size of the system matrix without sacrificing precision. Two methods for populating the system matrix are compared; the first utilises a geometrically-derived system matrix based on Siddon's ray tracer method with the addition of an accurate detector response function, while the second uses Monte Carlo simulation to populate the system matrix. The effectiveness of both variations of the proposed technique is demonstrated via simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner featuring high-resolution DoI capabilities, which has previously been simulated and characterised using classical image reconstruction methods. Compression factors of 5 x 10(7) and 2.5 x 10(7)are achieved using this methodology for the system matrices produced using the geometric and Monte Carlo-based approaches, respectively, requiring a total of 0.5-1.2 GB of memory-resident storage. Images reconstructed from Monte Carlo simulations of various point source and phantom models, produced using system matrices generated via both geometric and simulation methods, are used to evaluate the quality of the resulting system matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM index image quality metrics. The Monte Carlo-based system matrix is shown to provide the best image quality at the cost of substantial one-off computational effort and a lower (but still practical) compression factor. Finally, a straightforward extension of the virtual ring method to a three dimensional virtual cylinder is demonstrated using a 3D DoI PET scanner.

Depression and executive dysfunction contribute to a metamemory deficit among individuals with methamphetamine use disorders.

OBJECTIVE: Chronic methamphetamine (MA) use is associated with moderate deficits in learning and memory, but the extend to which MA users are aware of such memory deficits (i.e., metamemory) is not known. METHODS: In the current study, 195 participants with lifetime MA use diagnoses (MA +) and 195 non-MA-using comparison subjects (MA -) underwent comprehensive neuropsychiatry research assessments, including performance-based and self-report measures of episodic memory. RESULTS: MA use disorders, major depressive disorder (MDD), and their interaction were uniquely associated with metamemory functioning, such that MDD increased the likelihood of a metamemory deficit among MA + participants. Within the MA group, individuals who over-estimated their memory abilities demonstrated greater executive dysfunction and lower cognitive reserve. CONCLUSIONS: Chronic MA use is associated with reduced awareness of objective deficits in memory acquisition and recall, which is particularly exacerbated by the presence of major depression. Efforts to enhance metamemory accuracy and deployment of compensatory mnemonic strategies may benefit substance abuse treatment outcomes.

Predictors of Attrition in a Cohort Study of HIV Infection and Methamphetamine Dependence.

Longitudinal cohort studies of HIV and substance use disorders play an important role in understanding these conditions, but high rates of attrition can threaten their integrity and generalizability. This study aimed to identify factors associated with attrition in a 5-year observational cohort study of 469 individuals with and without HIV infection and methamphetamine (MA) dependence. Rates of attrition in our four study groups were approximately 24% in HIV-MA-, 15% in HIV+MA-, 56% in HIV-MA+, and 47% in HIV+MA+ individuals. Predictors of attrition in the overall cohort included history of MA, alcohol, and other substance dependence, learning impairment, reduced cognitive reserve, and independence in activities of daily living (all ps < .05), but varied somewhat by clinical group. Of particular note, enrollment in a neuroimaging substudy was associated with significantly boosted rates of retention in the MA groups. Results from this investigation highlight the complexity of the clinical factors that influence retention in cohort studies of HIV-infected MA users and might guide the development and implementation of targeted retention efforts.

Radiation dose enhancement at tissue-tungsten interfaces in HDR brachytherapy.

HDR BrachyView is a novel in-body dosimetric imaging system for real-time monitoring and verification of the source position in high dose rate (HDR) prostate brachytherapy treatment. It is based on a high-resolution pixelated detector array with a semi-cylindrical multi-pinhole tungsten collimator and is designed to fit inside a compact rectal probe, and is able to resolve the 3D position of the source with a maximum error of 1.5 mm. This paper presents an evaluation of the additional dose that will be delivered to the patient as a result of backscatter radiation from the collimator. Monte Carlo simulations of planar and cylindrical collimators embedded in a tissue-equivalent phantom were performed using Geant4, with an (192)Ir source placed at two different source-collimator distances. The planar configuration was replicated experimentally to validate the simulations, with a MOSkin dosimetry probe used to measure dose at three distances from the collimator. For the cylindrical collimator simulation, backscatter dose enhancement was calculated as a function of axial and azimuthal displacement, and dose distribution maps were generated at three distances from the collimator surface. Although significant backscatter dose enhancement was observed for both geometries immediately adjacent to the collimator, simulations and experiments indicate that backscatter dose is negligible at distances beyond 1 mm from the collimator. Since HDR BrachyView is enclosed within a 1 mm thick tissue-equivalent plastic shell, all backscatter radiation resulting from its use will therefore be absorbed before reaching the rectal wall or other tissues. dosimetry, brachytherapy, HDR.

BrachyView, a novel inbody imaging system for HDR prostate brachytherapy: design and Monte Carlo feasibility study.

PURPOSE: High dose rate (HDR) brachytherapy is a form of radiation therapy for treating prostate cancer whereby a high activity radiation source is moved between predefined positions inside applicators inserted within the treatment volume. Accurate positioning of the source is essential in delivering the desired dose to the target area while avoiding radiation injury to the surrounding tissue. In this paper, HDR BrachyView, a novel inbody dosimetric imaging system for real time monitoring and verification of the radioactive seed position in HDR prostate brachytherapy treatment is introduced. The current prototype consists of a 15 × 60 mm(2) silicon pixel detector with a multipinhole tungsten collimator placed 6.5 mm above the detector. Seven identical pinholes allow full imaging coverage of the entire treatment volume. The combined pinhole and pixel sensor arrangement is geometrically designed to be able to resolve the three-dimensional location of the source. The probe may be rotated to keep the whole prostate within the transverse plane. The purpose of this paper is to demonstrate the efficacy of the design through computer simulation, and to estimate the accuracy in resolving the source position (in detector plane and in 3D space) as part of the feasibility study for the BrachyView project. METHODS: Monte Carlo simulations were performed using the GEANT4 radiation transport model, with a (192)Ir source placed in different locations within a prostate phantom. A geometrically accurate model of the detector and collimator were constructed. Simulations were conducted with a single pinhole to evaluate the pinhole design and the signal to background ratio obtained. Second, a pair of adjacent pinholes were simulated to evaluate the error in calculated source location. RESULTS: Simulation results show that accurate determination of the true source position is easily obtainable within the typical one second source dwell time. The maximum error in the estimated projection position was found to be 0.95 mm in the imaging (detector) plane, resulting in a maximum source positioning estimation error of 1.48 mm. CONCLUSIONS: HDR BrachyView is a feasible design for real-time source tracking in HDR prostate brachytherapy. It is capable of resolving the source position within a subsecond dwell time. In combination with anatomical information obtained from transrectal ultrasound imaging, HDR BrachyView adds a significant quality assurance capability to HDR brachytherapy treatment systems.

Leaf hydraulic conductance for a tank bromeliad: axial and radial pathways for moving and conserving water.

Epiphytic plants in the Bromeliaceae known as tank bromeliads essentially lack stems and absorptive roots and instead take up water from reservoirs formed by their overlapping leaf bases. For such plants, leaf hydraulic conductance is plant hydraulic conductance. Their simple strap-shaped leaves and parallel venation make them suitable for modeling leaf hydraulic conductance based on vasculature and other anatomical and morphological traits. Plants of the tank bromeliad Guzmania lingulata were investigated in a lowland tropical forest in Costa Rica and a shaded glasshouse in Los Angeles, CA, USA. Stomatal conductance to water vapor and leaf anatomical variables related to hydraulic conductance were measured for both groups. Tracheid diameters and numbers of vascular bundles (veins) were used with the Hagen-Poiseuille equation to calculate axial hydraulic conductance. Measurements of leaf hydraulic conductance using the evaporative flux method were also made for glasshouse plants. Values for axial conductance and leaf hydraulic conductance were used in a model based on leaky cable theory to estimate the conductance of the radial pathway from the vein to the leaf surface and to assess the relative contributions of both axial and radial pathways. In keeping with low stomatal conductance, low stomatal density, low vein density, and narrow tracheid diameters, leaf hydraulic conductance for G. lingulata was quite low in comparison with most other angiosperms. Using the predicted axial conductance in the leaky cable model, the radial resistance across the leaf mesophyll was predicted to predominate; lower, more realistic values of axial conductance resulted in predicted radial resistances that were closer to axial resistance in their impact on total leaf resistance. Tracer dyes suggested that water uptake through the tank region of the leaf was not limiting. Both dye movement and the leaky cable model indicated that the leaf blade of G. lingulata was structurally and hydraulically well-suited to conserve water.

Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders.

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.

Defining neurocognitive impairment in HIV: deficit scores versus clinical ratings.

Because HIV-related neurocognitive impairment is usually mild and variable, clinical ratings (CR) and global deficit scores (GDS) are recommended for detecting HIV-associated neurocognitive disorders (HAND). The CR approach requires impairment in at least two ability domains while the GDS considers number and severity of impairments across all measures. We examined classification agreement and clinical correlates of the two methods. Neurocognitive functioning of 1574 HIV-infected participants was assessed via a comprehensive, seven-domain neuropsychological battery. Global neurocognitive impairment was defined for each participant independently by CR and GDS. Participants were classified into four categories (Dually-normal, [impaired by] CR-only, [impaired by] GDS-only, or Dually-impaired). There was 83% concordance between CR and GDS classifications; in total, 56% of participants were deemed impaired by CR and 41% were classified as impaired by GDS. Impairment by GDS virtually guaranteed CR impairment, but 16% of participants were additionally classified as impaired only by CR. As compared to Dually-normal participants, those classified as Dually and CR-only impaired were more likely to have AIDS, have more severe co-occurring conditions, have more severe depressive symptoms, be unemployed, and have more everyday functioning complaints (ps < .05). Impairment classifications of the two methods were in high agreement; however, more people were classified as impaired using the CR approach compared to the GDS approach. Those impaired according to CR-only showed fewer neurocognitive and functional deficits than the Dually-impaired participants, but more of these deficits than Dually-normal participants. The CR approach may be most appropriate for detecting more subtle forms of neurocognitive impairment. Clinicians and researchers should recognize the strengths and weaknesses of each method when evaluating neurocognitive complications in HIV.

Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning.

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms.

HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study.

OBJECTIVES: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). METHODS: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). RESULTS: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups). CONCLUSIONS: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

Regression of proximal deep venous thrombosis is associated with fibrinolytic enhancement.

PURPOSE: Recanalization after acute lower limb deep venous thrombosis (DVT) is well documented, but the precise mechanism and timing of these events has not been well characterized. Regression of DVT has been presumed to result from activation of the endogenous fibrinolytic system. This study was performed to compare measurements of the enzymatic components of the intrinsic fibrinolytic system (tissue plasminogen activator [tPA], plasminogen activator inhibitor [PAI-1]) with the observed morphologic changes in thrombosed venous segments using venous duplex ultrasound scanning (VDUS) at intervals after diagnosis of acute DVT. METHODS: Nineteen patients with acute DVT underwent serial VDUS to assess regression of thrombus at intervals of 1 to 2 weeks, 3 to 6 weeks, 8 to 12 weeks, and 24 to 36 weeks. The extent of thrombus in each limb was quantitated at each interval by VDUS of the residual thrombus present in each of five major axial venous segments: the common femoral, superficial femoral, profunda femoris, popliteal, and tibial veins. Thrombus scores for the group at each interval were compared with baseline scores at diagnosis to calculate the percent residual thrombus. Endogenous fibrinolytic activity was determined at the same intervals by serologic assay of the biologic activities of tPA and its inhibitor PAI-1. RESULTS: Thrombus regression was evident by VDUS at 1 to 2 weeks and progressed such that only 26% of residual thrombus remained at 24 to 36 weeks. Complete resolution of thrombus occurred in 10 of 18 patients (56%) who completed the 9-month study. Baseline mean tPA activity was 0.60 +/- 0.07 IU/ml and increased to 1.31 +/- 0.26 IU/ml at 1 to 2 weeks (p = 0.014). tPA activity remained significantly elevated through the 8 to 12 week interval and returned to baseline at 24 to 36 weeks. PAI-1 activity was elevated relative to an age-matched population at baseline (23.1 +/- 1.8 AU/ml) but remained unchanged throughout the study period. Progression of thrombus was observed in three patients (15.8%). Patients who experienced propagation of thrombus did not have the increased tPA activity that appeared to mark activation of intrinsic fibrinolysis. CONCLUSIONS: Regression of acute DVT begins early and continues for at least 9 months. It is accompanied by significant enhancement of the endogenous fibrinolysis, which appears to be primarily mediated by increased tPA activity. Patients who have thrombus propagation in spite of standard antithrombotic therapy may have failure of activation of endogenous fibrinolysis.