Radiofrequency ablation alters the microstructural organization of healthy and enzymatically digested porcine mitral valves.

BACKGROUND: Myxomatous mitral valve degeneration is a common cause of mitral regurgitation and is often associated with mitral valve prolapse. With no known targets to pharmacologically treat mitral valve prolapse, surgery is often the only treatment option. Recently, radiofrequency ablation has been proposed as a percutaneous alternative to surgical resection for the reduction of mitral valve leaflet area. OBJECTIVE: Using an in vitro model of porcine mitral valve anterior leaflet enlargement following enzymatic digestion, we sought to investigate mechanisms by which radiofrequency ablation alters the geometry, microstructural organization, and mechanical properties of healthy and digested leaflets. METHODS: Paired measurements before and after ablation revealed the impact of radiofrequency ablation on leaflet properties. Multiphoton imaging was used to characterize changes in the structure and organization of the valvular extracellular matrix; planar biaxial mechanical testing and constitutive modeling were used to estimate mechanical properties of healthy and digested leaflets. RESULTS: Enzymatic digestion increased leaflet area and thickness to a similar extent as clinical mitral valve disease. Radiofrequency ablation altered extracellular matrix alignment and reduced the area of digested leaflets to that of control. Additionally, enzymatic digestion resulted in fiber alignment and reorientation toward the radial direction, causing increased forces during ablation and a structural stiffening which was improved by radiofrequency ablation. CONCLUSION: Radiofrequency ablation induces radial extracellular matrix alignment and effectively reduces the area of enlarged mitral valve leaflets. Hence, this technique may be a therapeutic approach for myxomatous mitral valve disease and is thus an avenue for future study.

Facial emotion recognition and eye movement behaviour in conduct disorder.

BACKGROUND: Conduct Disorder (CD) is associated with impairments in facial emotion recognition. However, it is unclear whether such deficits are explained by a failure to attend to emotionally informative face regions, such as the eyes, or by problems in the appraisal of emotional cues. METHOD: Male and female adolescents with CD and varying levels of callous-unemotional (CU) traits and age- and sex-matched typically developing (TD) controls (aged 13-18) categorised the emotion of dynamic and morphed static faces. Concurrent eye tracking was used to relate categorisation performance to participants' allocation of overt attention. RESULTS: Adolescents with CD were worse at emotion recognition than TD controls, with deficits observed across static and dynamic expressions. In addition, the CD group fixated less on the eyes when viewing fearful and sad expressions. Across all participants, higher levels of CU traits were associated with fear recognition deficits and reduced attention to the eyes of surprised faces. Within the CD group, however, higher CU traits were associated with better fear recognition. Overall, males were worse at recognising emotions than females and displayed a reduced tendency to fixate the eyes. DISCUSSION: Adolescents with CD, and particularly males, showed deficits in emotion recognition and fixated less on the eyes when viewing emotional faces. Individual differences in fixation behaviour predicted modest variations in emotion categorisation. However, group differences in fixation were small and did not explain the much larger group differences in categorisation performance, suggesting that CD-related deficits in emotion recognition were not mediated by abnormal fixation patterns.

Serial testing for latent tuberculosis infection in transplant candidates: a retrospective review.

BACKGROUND: Accurately identifying latent tuberculosis (TB) infection (LTBI) in liver and renal transplant candidates is important because of the risks associated with both treatment of LTBI and reactivation of disease in this population. Many programs advocate yearly screening of patients awaiting organ transplantation. The reproducibility of serial interferon-gamma release assay (IGRA) testing in transplant candidates has not been studied. METHODS: We conducted a retrospective longitudinal study of patients listed for liver or kidney transplantation between January 1, 2005 and February 1, 2012 at the University of Illinois Medical Center at Chicago. Data collected included demographics, transplant type, IGRA results, treatment received, and mortality. RESULTS: The study population was comprised of 795 adults; 79 (10%) had at least 1 indeterminate result; indeterminate results were less common in men (P = 0.01) and more common in liver transplant candidates (P < 0.001). The reversion frequency was 27% with a rate of 158.1 reversions in 1000 person-years. A higher magnitude of initial TB response values was predictive of consistently positive results (P < 0.001). The conversion frequency was 15% with a rate of 82.6 conversions in 1000 person-years. Among those who converted, the values of the IGRA varied, with 48% having a TB response of <1 IU/mL, 41% 1-5 IU/mL, and only 10% >5 IU/mL. CONCLUSIONS: A significant number of conversions and reversions occur during serial IGRA testing of transplant candidates. Delineating true-positive converters from false-positives is an issue that warrants further study.

Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes.

BACKGROUND: The standard treatment of latent tuberculosis infection (LTBI) is associated with toxicities and data are limited on tolerability among patients with advanced organ disease listed for transplant. Alternate options are available, but they have yet to be studied in this population. METHODS: A retrospective review of the treatment of LTBI among kidney and/or liver transplant candidates was conducted to assess factors impacting therapy initiation, tolerability, and completion of therapy. RESULTS: Of 174 eligible patients, treatment of LTBI was initiated in 129, of which 91 were listed for kidney transplant and 38 were listed for liver or liver/kidney transplant. Infectious Diseases consultation was independently associated with treatment initiation when controlling for waitlisted organ and receipt of hemodialysis (odds ratio [OR] 81.14, 95% confidence interval [CI] 23.94-274.94, P < 0.001). Documented completion of first-line therapy was 47% overall, and 49% and 39%, respectively, among kidney and liver/kidney candidates (P = not significant). On multivariable analysis, controlling for baseline aspartate aminotransferase and waitlisted organ, first-line receipt of rifampin was associated with lower rates of treatment completion (OR 0.19, 95% CI 0.05-0.77, P = 0.02). CONCLUSION: Based on medical record documentation, completion of first-line therapy was <50% in this cohort, although this is likely an underestimate, as 34% of patients had no chart documentation that therapy was completed. Approximately 20% of patients did not complete first-line therapy because of adverse effects.

Exercise collapse associated with sickle cell trait (ECAST): case report and literature review.

Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and exercise-related sudden death in athletes and military warfighters. The mechanisms underlying ECAST remain controversial in the sports medicine community. Multiple case presentations and anecdotal reports postulate the role of extraordinary exercise intensity, but other risk factors including dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and dietary supplements have been cited as potential contributors. Others have hypothesized some of the aforementioned factors combining in a "perfect storm" to trigger ECAST with a resultant potentially fatal "metabolic crisis." This case report provides a brief review of SCT as it pertains to exercise in warfighters and athletes, identifies known and postulated risk factors associated with ECAST, and introduces the potential mechanistic role of the "double hit" as a contributor to ECAST.

A multicenter evaluation of pandemic influenza A/H1N1 in hematopoietic stem cell transplant recipients.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients have increased morbidity from respiratory viral infections. Pandemic influenza A - A(H1N1)/pdm09 - in 2009-2010 was associated with increased severity of illness in patients with underlying co-morbidities including HSCT, but the factors that contribute to severe disease in HSCT patients are not well characterized. METHODS: We conducted a multicenter review of microbiologically proven influenza A(H1N1)pdm09 in the HSCT population between April 2009 and April 2010 to determine factors that are associated with severe disease. RESULTS: We identified 37 adult patients (26 allogeneic and 11 autologous HSCT recipients). Median time from transplant to diagnosis was 411 days (range 4 days-14.9 years). Three cases were hospital acquired. Twenty-eight of 37 (75.7%) had confirmed A(H1N1)pdm09. Presumed viral lower respiratory tract infection was present in 12/37 (32.4%) patients. Antiviral therapy was given to 33/37 (89%) patients, primarily oseltamivir (n = 24) and oseltamivir before or after another antiviral (n = 8). Excluding those with nosocomial A(H1N1)pdm09, 18/34 (52.9%) were hospitalized and 6 (33%) required admission to an intensive care unit. Mortality within 30 and 60 days of symptom onset was 7/37 (18.9%) and 11/37 (29.7%), respectively. Factors associated with mortality included nosocomial acquisition (P = 0.023), receipt of mycophenolate mofetil (P = 0.001), or antilymphocyte antibody (P = 0.005) within the past 6 months, reduced-intensity conditioning (P = 0.027), and bacteremia (P = 0.021). CONCLUSIONS: A(H1N1)pdm09 infection was particularly severe in HSCT recipients, specifically among those receiving augmented immunosuppression for graft-versus-host disease. The high mortality of the nosocomial cases highlights the need for strict infection-control measures in hospitals during influenza outbreaks.

Gene flow and simulation of transgene dispersal from hybrid poplar plantations.

Gene flow is a primary determinant of potential ecological impacts of transgenic trees. However, gene flow is a complex process that must be assessed in the context of realistic genetic, management, and environmental conditions. We measured gene flow from hybrid poplar plantations using morphological and genetic markers, and developed a spatially explicit landscape model to simulate pollination, dispersal, establishment, and mortality in the context of historical and projected disturbance and land-use regimes. Most pollination and seed establishment occurred within 450 m of the source, with a very long tail. Modeled transgene flow was highly context-dependent, strongly influenced by the competitive effects of transgenes, transgenic fertility, plantation rotation length, disturbance regime, and spatial and temporal variation in selection. The use of linked infertility genes even if imperfect, substantially reduced transgene flow in a wide range of modeled scenarios. The significance of seed and vegetative dispersal was highly dependent on plantation size. Our empirical and modeling studies suggest that transgene spread can be spatially extensive. However, the amount of spread is highly dependent on ecological and management context, and can be greatly limited or prevented by management or mitigation genes such as those that cause sexual infertility.

Extra-pulmonary manifestations of sarcoidosis.

Although, the diagnosis and evaluation of sarcoidosis has traditionally remained confined to the chest, its multi-system nature has been widely recognized. Radiological features of pulmonary sarcoidosis are well known but extra-pulmonary manifestations can produce a plethora of non-specific imaging findings that can affect subcutaneous tissue, and the neurological, cardiac, gastrointestinal, urological, liver, spleen, and skeletal systems. In the literature, there are various case reports and specific system reviews but there are few reviews that encompass all the extra-pulmonary manifestations. In this paper, we comprehensively review the imaging features of extra-pulmonary sarcoidosis with characteristic features as well as atypical presentations. In addition, we discuss the emerging role of nuclear medicine in sarcoidosis.

Longitudinal medical needs for periviable NICU survivors.

OBJECTIVE: To evaluate the technologies required, medications needed, and early intervention services utilized from discharge to 12 months post-discharge for periviable infants (22 0/7 to 24 6/7 weeks gestational age) followed in a comprehensive NICU follow-up clinic. STUDY DESIGN: Information regarding medication use, technology requirement, and early intervention services was collected prospectively at one, six, and twelve months after discharge. Neurodevelopmental assessment was completed at 12 months corrected age. RESULT: 69 periviable infants were actively treated and survived to discharge during the study period. 54 infants were enrolled and followed in the comprehensive NICU follow-up clinic. Use of technology and prescribed medications decreased with a 46% reduction of infants requiring ≥1 technology device (74.1% vs. 40.4%, p < 0.01) and 64% reduction in infants requiring ≥1 medication (88.9% vs 31.9%, p < 0.01) 12 months post discharge. There was an increase in early intervention services with 83% of infants receiving services by 12 months post discharge. CONCLUSION: Technology and medication requirements were high at discharge but notably decreased in the first year after discharge concurrent with increased enrollment in early interventional services. Many periviable infants survive without severe short-term developmental delays.

Functional asymmetry for the active sites of linked 5-aminolevulinate synthase and 8-amino-7-oxononanoate synthase.

5-Aminolevulinate synthase (ALAS) and 8-amino-7-oxononanoate synthase (AONS) are homodimeric members of the α-oxoamine synthase family of pyridoxal 5'-phosphate (PLP)-dependent enzymes. Previously, linking two ALAS subunits into a single polypeptide chain dimer yielded an enzyme (ALAS/ALAS) with a significantly greater turnover number than that of wild-type ALAS. To examine the contribution of each active site to the enzymatic activity of ALAS/ALAS, the catalytic lysine, which also covalently binds the PLP cofactor, was substituted with alanine in one of the active sites. Albeit the chemical rate for the pre-steady-state burst of ALA formation was identical in both active sites of ALAS/ALAS, the k(cat) values of the variants differed significantly (4.4±0.2 vs. 21.6±0.7 min(-1)) depending on which of the two active sites harbored the mutation. We propose that the functional asymmetry for the active sites of ALAS/ALAS stems from linking the enzyme subunits and the introduced intermolecular strain alters the protein conformational flexibility and rates of product release. Moreover, active site functional asymmetry extends to chimeric ALAS/AONS proteins, which while having a different oligomeric state, exhibit different rates of product release from the two ALAS and two AONS active sites due to the created intermolecular strain.

Sacral transcutaneous electrical nerve stimulation in the treatment of idiopathic faecal incontinence.

AIM: The aim of this study was to investigate the potential use of S3 transcutaneous electrical nerve stimulation (TENS) in the treatment of idiopathic faecal incontinence. METHOD: Seventeen patients were treated by S3 TENS 2 h a day for 3 months. The outcome was evaluated by faecal incontinence severity index (FISI), faecal incontinence quality of life scale (FIQOL), 7-day bowel diary, anorectal physiology, patients' self-reported impression of improvement, bowel control and satisfaction with treatment on a visual analogue scale. RESULTS: Seventeen patients (13 women) of mean age 67.2 years (52-80) were followed up for a mean of 19.7 months. The FISI improved in 69% after 3 months of TENS (P < 0.01), and all components of FIQOL improved. The number of incontinent episodes per week fell for incontinence to gas and stool (solid and/or liquid). There was no significant difference in the maximum resting pressure and squeeze pressure, but the mean rectal volume of first sensation (12.1 ml, P = 0.027) and first urge (25.0 ml, P = 0.054) fell, and the maximum tolerable volume (16.0 ml, P = 0.679) rose. The satisfaction score was ≥ 6/10 in all patients. Fifteen (88%) scored ≥ 6/10 for bowel control, and all patients scored ≥ 2 (scale: -5 to +5) for their impression of improvement. CONCLUSION: S3 transcutaneous electrical nerve stimulation seems to be a promising noninvasive method to treat faecal incontinence. However, further study is required.

An association between cerebral aneurysm re-bleed and CT angiography--more than a coincidence?

Rupture of cerebral aneurysm during CT angiogram is a rare occurrence. Here we present such a case where an aneurysmal re-rupture during CT angiogram was demonstrated.

High Schools Struggle to Adopt Evidence Based Practices for the Management of Exertional Heat Stroke.

CONTEXT: Exertional heat stroke (EHS) deaths can be prevented by adhering to best practices. OBJECTIVE: We investigated the adoption of policies and procedures for the recognition and treatment of EHS and the factors influencing the adoption of a comprehensive policy. DESIGN: Cross Sectional. SETTING: Online questionnaire. PATIENTS OR OTHER PARTICIPANTS: Athletic trainers (ATs) practicing in the high school (HS) setting. MAIN OUTCOME MEASURE(S): Using the NATA Position Statement: Exertional Heat Illness, an online questionnaire was developed and distributed to ATs to ascertain their schools' current written policies for the use of rectal temperature and cold-water immersion (CWI). The Precaution Adoption Process Model (PAPM), allowed for responses to be presented across the various health behavior stages ("Unaware if have the policy", "Unaware for the need for the policy", "Unengaged", "Undecided", "Decided Not to Act", "Decided to Act", "Acting", and "Maintaining"). Additional questions included perceptions of facilitators and barriers. Data are presented as proportions. RESULTS: A total of 531 ATs completed this questionnaire. Overall, 16.9% (n=62) report adoption of all components for proper recognition and treatment of EHS. The policy component with the highest adoption was "cool first transport second" with 74.1% (n=110) of ATs reporting "Acting" or "Maintaining." The most variability in the PAPM responses was for a rectal temperature policy, with 28.7% (n=103) of ATs reporting "Decided not to Act" and 20.1% (n=72) reporting "Maintaining." The most commonly reported facilitator and barrier for rectal temperature included state mandate from state HS athletics association (n=274,51.5%) and resistance or apprehension from parents or legal guardians (n=311,58.5%), respectively. CONCLUSIONS: ATs in the HS setting appear to be struggling to adopt a comprehensive EHS strategy, with rectal temperature continuing to appear as the biggest undertaking. Tailored strategies based on health behavior, facilitators and barriers may aid in changing this paradigm.

Population substructure in continuous and fragmented stands of Populus trichocarpa.

Population substructure has important implications for both basic and applied genetic research. We used 10 microsatellite markers to characterize population substructure in two ecologically and demographically contrasting populations of the model tree Populus trichocarpa. The Marchel site was a continuous stand growing in a mesic habitat in western Oregon, whereas the Vinson site consisted of three disjunct and isolated stands in the high desert of eastern Oregon. A previous study revealed that pollen-mediated gene flow is extensive in both populations. Surprisingly, model-based clustering, principal components analysis and analyses of molecular variance provided overwhelming support for the existence of at least two intermingled sub-populations within the continuous Marchel population (F(ST)=0.026, P<0.001), which occupied an area with a radius of only about 250 m. Genets in these two sub-populations appeared to have different relative clone ages and phenologies, leading us to hypothesize that they correspond to different seedling cohorts, each established from seeds produced by relatively few mothers. As expected, substructure was stronger in the fragmented Vinson population (F(ST)=0.071, P=0.001), and this difference appeared to result from the more extensive family structure in this population. Using group-likelihood methods, we reconstructed multiple interconnected half-sib families in the Vinson population, with some genets having as many as eight putative siblings. Researchers involved in ongoing and future association studies in P. trichocarpa should account for the likely presence of subtle but practically significant substructure in populations throughout the range of this species.

Imaging of illicit drug use.

Illicit drug abuse is a continuing menace of epidemic proportions associated with serious medical and social problems. Drug abuse can have a wide variety of presentations some of which can be life-threatening. The clinical diagnosis can be challenging as the history is usually limited or absent. Radiologists need to be familiar with varied imaging presentations and the related complications of illicit drug abuse to ensure correct diagnosis and appropriate timely treatment. This review will illustrate the imaging spectrum of illicit drug abuse involving several organ systems and also discuss the pathophysiological consequences of drug abuse.

Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part II: two year clinical results.

OBJECTIVES: To determine the clinical effects of juvenile pubic symphysiodesis (JPS) treatment in hip dysplasia-prone puppies with comparison to similar untreated control puppies. DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies, of which six were part of the control group, with a positive Ortolani or hip distraction index (DI)≥0.40. PROCEDURES: The following eight clinical tests were evaluated preoperatively, and at one and two years postoperatively: Ortolani, hip reduction angle (HRA), gait evaluation, osteoarthritis, hip pain, and three Norberg angles (angle-extended mode [N-OFA], angle-compression mode [N-COM], and angle-distracted mode [N-DIS]). Juvenile pubic fusion (JPS) was performed by unipolar electro-cautery at 12 to 24 weeks of age; the control puppies received a sham operation. RESULTS: For the JPS puppies, the mean osteoarthritis level did not significantly increase (11%). There was a 74% reversal of preoperative positive Ortolani signs. Hip reduction angle, DI and N-DIS also improved significantly. Only N-DIS fully detected Norberg angle laxity. Within the control group, osteoarthritis increased significantly (55%) with no improvement in Ortolani incidence, N-OFA or N-COM angles. A decrease in HRA and DI was associated with increased osteoarthritis levels. Signs of hip pain increased by 33%, which was not significant. Dogs with initial severe hip laxity (DI≥0.70) experienced progressive osteoarthritis. CONCLUSIONS AND CLINICAL RELEVANCE: In JPS dogs with preoperative mild to moderate hip laxity (DI = 0.40-0.69), insignificant osteoarthritis occurred at two years. Juvenile pubic symphysiodesis surgery also improved other clinical criteria (Ortolani, HRA, hip pain, N-DIS). Osteoarthritis was generally not prevented by JPS in dogs with initial severely lax hips (DI≥0.70). Juvenile pubic symphysiodesis surgery at 12 to 24 weeks of age was an effective and safe pre-emptive bilateral treatment for mild to moderate hip dysplasia.

Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part I: two year results of computed tomography and distraction index.

OBJECTIVES: To measure one and two year effects of juvenile pubic symphysiodesis (JPS) in puppies defined as 'at-risk' for canine hip dysplasia (CHD) using the following objective hip conformation criteria: Acetabular angle (AA), dorsal acetabular rim angle (DARA) and hip laxity (PennHIP© distraction index (DI). DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies (six controls). PROCEDURES: The dogs were anaesthetised and acetabular angle, DARA, and DI values were obtained by computed tomography and radiography preoperatively. Electro-cautery fusion of the pubic symphysis was performed between 12 - 24 weeks of age. The imaging was repeated at one and two years of age. RESULTS: Significant hip improvements were seen at the two-year follow-up appointments for: AA (JPS dogs 31% increase, control 3%), DARA (JPS 38% decrease, control 15%) and DI (JPS 41% decrease in laxity, controls 20%) for all postoperative versus preoperative values. Pubic fusion occurred with minor morbidity. CONCLUSION: Juvenile pubic symphysiodesis resulted in significant improvements in hip conformation (AA and DARA), especially in mild to moderately lax hips (DI = 0.40-0.69). Most dogs with DI≥0.70 increased in osteoarthritis grade by two years of age. CLINICAL RELEVANCE: Juvenile pubic symphysiodesis surgery at 12-24 weeks of age significantly improved hip conformation and decreased laxity in at-risk CHD dogs. Early-age (12 to 16 week) recognition of hip laxity offered greater JPS benefits than surgery performed at 19- to 24-weeks-old. Dogs with severe laxity (DI≥0.70) continued to increase in osteoarthritis. An early (12-16 weeks) positive laxity test (Ortolani) should alert one to obtain objective laxity determinations (PennHIP© DI).

Extensive pollen flow in two ecologically contrasting populations of Populus trichocarpa.

Pollen-mediated gene flow was measured in two populations of black cottonwood using direct (paternity analysis) and indirect (correlated paternity) methods. The Marchel site was an area with an approximate radius of 250 m in a large continuous stand growing in a mesic habitat in western Oregon. In contrast, the Vinson site was an area with a radius of approximately 10 km and consisted of small, disjunct and isolated stands in the high desert of eastern Oregon. Pollen immigration was extensive in both populations, and was higher in the Marchel site (0.54 +/- 0.02) than in the substantially larger and more isolated Vinson site (0.32 +/- 0.02). Pollen pool differentiation among mothers was approximately five times stronger in the Vinson population (Phi FT = 0.253, N = 27 mothers) than in the Marchel population (Phi FT = 0.052, N = 5 mothers). Pollen dispersal was modelled using a mixed dispersal curve that incorporated pollen immigration. Predicted pollination frequencies generated based on this curve were substantially more accurate than those based on the widely used exponential power dispersal curve. Male neighbourhood sizes (sensu Wright 1946) estimated using paternity analysis and pollen pool differentiation were remarkably similar. They were three to five times smaller in the Vinson population, which reflected the substantial ecological and demographic differences between the two populations. When the same mathematical function was used, applying direct and indirect methods resulted in similar pollen dispersal curves, thus confirming the value of indirect methods as a viable lower-cost alternative to paternity analysis.

Isolation and characterization of low density structures from orotic acid-induced fatty livers.

Centrifugation of a sucrose homogenate of the livers of female albino rats fed a 1.5% orotic acid diet for 3 wk yielded a pellicle containing low density structures. In morphology and biochemical properties these structures resembled those portions of endoplasmic reticulum which accumulated lipid. Electron microscopy indicated large droplets of lipid bounded by a membrane with attached ribosome-like particles. The presence of ribosomes in these structures was established by treatment with deoxycholate and centrifugation. The proportion of 18S and 29S RNA was the same as that found in the ribosomes from normal liver; however, the distribution of radioactivity between the 18S and the 29S RNA after injection of 8-(14)C-adenine was distinctly different. The RNA isolated from these structures contained a higher guanylic acid to cytidylic acid ratio than that found in the microsomes of the normal liver. It is proposed that these low density structures may be those portions of the endoplasmic reticulum in which there exists a defect responsible for the block in the assembly or secretion of plasma lipoprotein.

Atypical pulmonary thrombosis caused by a toxic cyanobacterial peptide.

Parenteral injection into mice of a toxic pentapeptide isolated from the cyanobacterium Microcystis aeruginosa induced thrombocytopenia, pulmonary thrombi, and hepatic congestion. The lethality of the toxin was unaffected by several anticoagulants. The acute liver damage that follows injection of the toxin has been attributed to direct action on liver cells but may be due to hypoxemia, heart failure, and shock.