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Objectives: Transcatheter Aortic Valve Implantation (TAVI) is an alternative to surgical valve replacement in high risk patients. Angiography of the aortic root, aorta and iliac arteries is required to select suitable candidates, but contrast agents can be harmful due to impaired renal function. We evaluated ECG-triggered high-pitch spiral dual source Computed Tomography (CT) with minimized volume of contrast agent to assess aortic root anatomy and vascular access., Methods: 42 patients (82 ± 6 years) scheduled for TAVI underwent dual source (DS) CT angiography (CTA) of the aorta using a prospectively ECG-triggered high-pitch spiral mode (pitch = 3.4) with 40 mL iodinated contrast agent. We analyzed aortic root/iliac dimensions, attenuation, contrast to noise ratio (CNR), image noise and radiation exposure., Results: Aortic root/iliac dimensions and distance of coronary ostia from the annulus could be determined in all cases. Mean aortic and iliac artery attenuation was 320 ± 70 HU and 340 ± 77 HU. Aortic/iliac CNR was 21.7 ± 6.8 HU and 14.5 ± 5.4 HU using 100 kV (18.8 ± 4.1 HU and 8.7 ± 2.6 HU using 120 kV). Mean effective dose was 4.5 ± 1.2 mSv., Conclusions: High-pitch spiral DSCTA can be used to assess the entire aorta and iliac arteries in TAVI candidates with a low volume of contrast agent while preserving diagnostic image quality.

Cytomegalovirus infection is associated with severe disease in immunocompromised individuals. Current antiviral therapy faces several limitations. In a search of novel drug candidates, we describe here the anti-cytomegaloviral properties of two compounds of the chemical class of quinazolines, gefitinib (Iressa) and Ax7396 (RGB-315389). Both compounds showed strong inhibitory effects in vitro against human and animal cytomegaloviruses with IC(50)s in a low micromolar range. Cytotoxicity did not occur at these effective concentrations. The antiviral mode of action was based on the inhibition of protein kinase activity, mainly directed to a viral target kinase (UL97/M97) in addition to cellular target candidates. This was demonstrated by a high sensitivity of the respective protein kinases in vitro and by infection experiments with viral mutants carrying genomic alterations in the ORF UL97/M97 modulating viral drug sensitivity. In a guinea pig model, gefitinib showed inhibition of cytomegaloviral loads in blood and lung tissue. Importantly, the rate of mortality of infected animals was reduced by gefitinib treatment. In contrast to the in vitro data, Ax7396 showed no significant antiviral activity in a mouse model. Further in vivo analyses have to assess the potential use of gefitinib in the treatment of cytomegalovirus disease.

Long-term function of vascularized human organ grafts is often limited by transplant arteriosclerosis and can lead to graft failure. Here, we have analyzed the impact of an initial rejection episode on the later development of transplant arteriosclerosis. Following transplantation of allogeneic abdominal aortic segments in mice, aortic grafts were retransplanted into either immunodeficient or syngeneic recipients. Retransplantation of grafts from immunocompetent into immunodeficient mice as early as 2 days after the primary transplant resulted in intimal proliferation and obstruction of the graft lumen 30 days after the primary transplant. In contrast, retransplantation of the grafts into donor syngeneic B10 recipients within 7 days did not result in the development of transplant arteriosclerosis. These data suggest that the adaptive immune system can induce intimal proliferation by an initial lethal hit that is sustained by the innate response. However our data demonstrate that development of chronic rejection can be inhibited, in this case by retransplantation into a syngeneic host., ((c) 2008 Wiley-Liss, Inc.)

Objective: To determine the incidence, risk factors, associated pathogens, and outcome of ventilator-associated pneumonia (VAP) in patients admitted to a coronary care unit (CCU)., Patients and Methods: This retrospective cohort study was performed in the CCU of a single tertiary medical center. Patients who were admitted to the CCU between March 23, 2002, and May 25, 2003, and who required invasive mechanical ventilation for more than 48 hours were included., Results: Of the 92 patients who met the study criteria, 17 (18.5%; 95% confidence interval, 11.9%-27.6%) developed VAP. The incidence of VAP was 36.3 (95% confidence interval, 21.1-58.1) per 1000 days of mechanical ventilation. There were no statistically significant differences in demographics, presence of chronic obstructive pulmonary disease, or use of continuous intravenous sedatives or neuromuscular blockers between patients with and without VAP. The most commonly isolated organisms were methicillin-sensitive Staphylococcus aureus, Sphingomonas paucimobilis, and Stenotrophomonas maltophilia. The median length of stay in the CCU for patients with VAP was 10 days compared to 6 days for patients without VAP (P < .01). Eight (47%) of the 17 patients with VAP died compared to 29 (39%) of 75 patients without VAP (P = .52)., Conclusions: The incidence of VAP in the CCU is similar to or higher than that reported in other intensive care units. The development of VAP in CCU patients is associated with a prolonged CCU stay but not with an increased hospital mortality.

Aim: Intra-aortic balloon pump (IABP) therapy before open heart surgery has been suggested for ''high risk'' patients., Methods: Records from patients undergoing open heart surgery at our institution between June 1999 and February 2002 were reviewed. Indication for IABP insertion was severely impaired left ventricular function, acute myocardial infarction (MI) or unstable angina., Results: Fifty-five patients were included in the study: 41 male, 14 female, age 64+/-9 years. Fifty-one (92.7%) required coronary artery bypass brafting (CABG) alone or as a combined procedure, 2 (3.6%) required mitral valve surgery, and 2 (3.6%) needed more complex cardiac procedures. Thirty-two patients (58%) underwent emergency cardiac surgery and 11 patients (20%) suffered from acute preoperative MI. The overall 30 days mortality was 9%. Mean intensive care unit (ICU) stay was 6+/-8 days. Four patients (7.2%) developed postoperative renal failure requiring temporary hemodialysis. Three patients (5.4%) developed IABP related peripheral vascular complications., Conclusions: Perioperative morbidity and mortality is increased despite preoperative IABP, particularly in patients with acute MI. In contrast to studies not using this approach, preoperative IABP reduces morbidity and mortality of high risk patients. IABP related complications are low. Our data suggest that high risk patients profit from preoperative IABP therapy, however, prospective studies are needed to confirm these findings.

Study Objectives: Previous studies have suggested that patients are more likely to die in the hospital if they are admitted on a weekend than on a weekday. This study was conducted to determine whether weekend admission to the ICU increases the risk of dying in the hospital., Design: Retrospective cohort study., Setting: ICU of a single tertiary care medical center., Patients: A total of 29,084 patients admitted to medical, surgical, and multispecialty ICUs from October 1994 through September 2002., Interventions: None., Measurements and Results: The weekend ICU admissions comprised 27.9% of all ICU admissions (8,108 ICU admissions). The overall hospital mortality rate was 8.2% (2,385 deaths). Weekend ICU admission was associated with a higher unadjusted hospital mortality rate than that for weekday ICU admission (11.3% vs 7.0%, respectively; odds ratio [OR], 1.70; 95% confidence interval [CI], 1.55 to 1.85). In multivariable analyses controlling for the factors associated with mortality such as APACHE (acute physiology and chronic health evaluation) III predicted mortality rate, ICU admission source, and intensity of treatment, no statistically significant difference in hospital mortality was found between weekend and weekday admissions in the overall study population (OR, 1.06; 95% CI, 0.95 to 1.17). For weekend ICU admissions, the observed hospital mortality rates of the medical, multispecialty, and surgical ICUs were 15.2%, 17.2%, and 6.4%, respectively, and for weekday ICU admissions the rates were 16.3%, 10.1%, and 3.5%, respectively. Subgroup analyses showed that weekend ICU admission was associated with higher adjusted hospital mortality rates than was weekday ICU admission in the surgical ICU (OR, 1.23; 95% CI, 1.03 to 1.48), but not in the medical or multispecialty ICUs., Conclusions: The overall adjusted hospital mortality rate of patients admitted to the ICU on a weekend was not higher than that of patients admitted on a weekday. However, weekend ICU admission to the surgical ICU was associated with an increased hospital mortality rate.

Background: It has recently been shown that treatment of animals with antibodies to CD154 (CD40L), allows for prolongation of cardiac allograft survival, but does not inhibit development of graft vasculopathy. CD8(+) T cells have been implicated in this effect. In this study we assess the role of CD40-CD154 interactions and CD40-independent CD8(+) T cells in the permanent and complete absence of CD40 by using donors and recipients genetically deficient in CD40., Methods: Hearts from BALB/c CD40(-/-) donors were transplanted into C57BL/6 CD40(-/-) recipients in the presence or absence of CD8(+) T-cell depletion. At Day 60, hearts were examined for vasculopathy using quantitative morphometry and numbers of infiltrating T cells were counted. The intragraft expression of interferon-gamma (IFN-gamma), transforming growth factor-beta1 (TGF-beta1), interleukin-4 (IL-4), eotaxin and CCR3 was assessed using competitive reverse transcription-polymerase chain reaction (RT-PCR)., Results: In the absence of CD8(+) T-cell depletion, the mean percent intimal occlusion was 28% (with 50% of vessels showing no intimal occlusion). This figure was reduced significantly to 12% and 80% of vessels showing no intimal occlusion in mice receiving anti-CD8 antibody. Depletion of CD8(+) T cells was associated with significantly reduced intragraft IFN-gamma, TGF-beta1 and CCR3 expression, whereas mRNA production of IL-4 and eotaxin was increased., Conclusion: Vascular intimal occlusion progresses in the complete absence of CD40-CD154 interactions, albeit to quite a small degree. The residual disease is significantly reduced by anti CD8(+) T-cell treatment, confirming the importance of CD40-CD154-independent CD8(+) T cells in the genesis of this disease.

Blockade of the CD40-CD154 pathway can inhibit CD4(+) T cell activation but is unable to prevent immune responses mediated by CD8(+) T cells. However, even in the absence of CD8(+) T cells, inhibition of the CD40-CD154 pathway is insufficient to prevent the development of transplant arteriosclerosis. This study investigated the mechanisms of transplant arteriosclerosis in the absence of the CD40 pathway. C57BL/6 CD40(-/-) (H2(b)) recipients were transplanted with MHC-mismatched BALB/c (H2(d)) aortas. Transplant arteriosclerosis was evident in both CD40(-/-) and CD40(+/-) mice (intimal proliferation was 59 +/- 5% for CD40(-/-) mice vs 58 +/- 4% for CD40(+/-) mice) in the presence or absence of CD8(+) T cells (intimal proliferation was 46 +/- 7% for CD40(-/-) anti-CD8-treated mice vs 50 +/- 10% for CD40(+/-) anti-CD8-treated mice), confirming that CD8(+) T cells are not essential effector cells for the development of this disease. In CD40(-/-) recipients depleted of CD8(+) T cells, the number of eosinophils infiltrating the graft was markedly increased (109 +/- 24 eosinophils/grid for CD40(-/-) anti-CD8-treated mice vs 28 +/- 7 for CD40(+/-) anti-CD8-treated mice). The increased presence of eosinophils correlated with augmented intragraft production of IL-4. To test the hypothesis that IL-4 was responsible for the intimal proliferation, CD8 T cell-depleted CD40(-/-) recipients were treated with anti-IL-4 mAb. This resulted in significantly reduced eosinophil infiltration into the graft (12 +/- 5 eosinophils/grid for CD40(-/-) anti-CD8(+), anti-IL-4-treated mice vs 109 +/- 24 for CD40(-/-) anti-CD8-treated mice), intragraft eotaxin, CCR3 mRNA production, and the level of intimal proliferation (18 +/- 5% for CD40(-/-) anti-CD8(+)-, anti-IL-4-treated mice vs 46 +/- 7% for CD40(-/-) anti-CD8-treated mice). In conclusion, elevated intragraft IL-4 production results in an eosinophil infiltrate and is an important mechanism for CD8(+) T cell-independent transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

Background: The CD40-CD154 receptor-ligand pair plays a critical role in allograft rejection by mediating the activation of endothelial cells, antigen-presenting cells, and T cells. Blockade of this interaction prevents acute allograft rejection and leads to prolonged allograft survival in numerous experimental models, but in most cases indefinite graft survival is not achieved due to evolving transplant arteriosclerosis. In this study, we have used a model of transplant arteriosclerosis to investigate whether CD4+ and CD8+ T cells are differentially affected by CD154 blockade., Methods: BALB/c (H2d) aortic grafts were transplanted into C57BL/6 (H2b) recipients treated with anti-CD154 monoclonal antibody in the presence or absence of CD8+ T-cell depletion. Histology and morphometric measurements were performed on day 30 after transplantation., Results: Only combined treatment with anti-CD154 and anti-CD8 monoclonal antibodies resulted in a significant reduction of intimal proliferation (33 +/-10% vs. 67+/-14%; untreated control). Administration of either antibody alone did not produce this effect. Thymectomy did not alter the degree of intimal proliferation observed in any of the treatment groups., Conclusions: Our data provide direct evidence that CD8+ T cells are not targeted effectively by CD154 blockade and that the transplant arteriosclerosis seen after CD154 blockade is not due to recent thymic emigrant T cells.

This study is a review of the psychiatric and neurological effects of solvent inhalation on a group of 22 patients with chronic histories of solvent abuse, primarily toluene-based solvents. The findings suggest that the chronic inhalation of toluene-based adhesives can produce a paranoid psychosis which may persist. Other findings were a high incidence of temporal lobe epilepsy and decrease in IQ. We suggest that the psychiatric and neurological sequelae of chronic solvent abuse are serious and potentially irreversible. Toluene is felt to be a major factor in the morbidity associated with chronic solvent abuse, and attention is drawn to the necessity for educational programs in this area. The burden caused by the resulting psychiatric problems resulting from solvent abuse may have implications for health care budgets.