Infections of intravascular bare metal stents: a case report and review of literature.

OBJECTIVE: The objective of the paper is to present a case of an infected bare metal stent in the left common iliac artery that was removed by an urgent operation, and to review the literature on diagnosis and outcome of infected coronary and non-coronary metal stents. METHODS: A systematic search of the Medline database was performed with the purpose of identifying risk factors, signs and symptoms, imaging strategies, and treatment modalities of bare metal stent infections, both coronary and peripheral. RESULTS: In total, 76 additional studies/case reports (48 non-coronary; 29 coronary) were included and analyzed. Intravascular bare metal stent infections are a rare but serious complication, often leading to emergency surgery (overall: 75.3%; non-coronary cases: 83.3%; coronary cases: 62.1%). In 25.0% of the non-coronary cases, infection led to amputation of an extremity or removal of viscera. Reported mortality was up to 32.5% of the cases (non-coronary: 22.9%; coronary 48.3%). Physicians should always be suspicious of a stent infection when patients present with aspecific symptoms such as fever and chills after stent placement. Additional imaging can be used to detect the presence of a pseudoaneurysm. A PET-CT is an ideal medium for identification of a stent infection. CONCLUSIONS: Intravascular stent infection is associated with a high risk of morbidity and mortality. Surgery is the preferred treatment option, but not always possible, especially in patients with a coronary stent. In selected cases, bare metal stent infections may be prevented by the use of prophylactic antibiotics at stent placement.

Infection of endovascular abdominal aortic aneurysm stent graft after urosepsis: case report and review of the literature.

Infection of endovascular abdominal aneurysm stent grafts is an uncommon but known complication. Inoculation with bacteria of the endovascular abdominal aneurysm stent graft during the actual implantation, in the periprocedural hospitalization or later due to an aortoenteric fistula, has been described in the literature. We report a case of endovascular abdominal aortic aneurysm stent graft infection occurring 40 months after implantation in a patient doing well up to an episode of urosepsis. In conclusion, we postulate that poor intraluminal healing of stent grafts, as observed in several explant studies, may result in a higher susceptibility to episodes of bacteremia than prosthetic vascular grafts inserted during open repair. We therefore consider the administration of prophylactic antibiotics in patients with endovascular stent grafts during periods with a likelihood of bacteremia.

DNA-Based Vaccination Primes Tumor-Rejecting T-Cell Responses.

DNA-based vaccination efficiently primes MHC-restricted T-cell responses. This technique specifically stimulates MHC-II-restricted CD4(+) T-cell responses and MHC-I-restricted CD8(+) T-cell responses against "strong" (immunodominant) or "weak" (subdominant or cryptic) epitopes of intracellular, secreted or membrane-associated protein antigens. In many experimental systems, T-cell-mediated effector functions have the potential to control tumor growth. In particular MHC-I-restricted cytotoxic T lymphocytes (CTL) can reject tumors. This has been shown using either defined tumor-associated antigens (TAA), or viral antigens containing well-defined, MHC-binding and CTL-stimulating epitopes that are expressed by transfected tumor cells.

Colitis-inducing potency of CD4+ T cells in immunodeficient, adoptive hosts depends on their state of activation, IL-12 responsiveness, and CD45RB surface phenotype.

We studied the induction, severity and rate of progression of inflammatory bowel disease (IBD) induced in SCID mice by the adoptive transfer of low numbers of the following purified BALB/c CD4+ T cell subsets: 1) unfractionated, peripheral, small (resting), or large (activated) CD4+ T cells; 2) fractionated, peripheral, small, or large, CD45RBhigh or CD45RBlow CD4+ T cells; and 3) peripheral IL-12-unresponsive CD4+ T cells from STAT-4-deficient mice. The adoptive transfer into SCID host of comparable numbers of CD4+ T cells was used to assess the colitis-inducing potency of these subsets. Small CD45RBhigh CD4+ T lymphocytes and activated CD4+ T blasts induced early (6-12 wk posttransfer) and severe disease, while small resting and unfractionated CD4+ T cells or CD45RBlow T lymphocytes induced a late-onset disease 12-16 wk posttransfer. SCID mice transplanted with STAT-4-/- CD4+ T cells showed a late-onset IBD manifest > 20 wk posttransfer. In SCID mice with IBD transplanted with IL-12-responsive CD4+ T cells, the colonic lamina propria CD4+ T cells showed a mucosa-seeking memory/effector CD45RBlow Th1 phenotype abundantly producing IFN-gamma and TNF-alpha. In SCID mice transplanted with IL-12-unresponsive STAT-4-/- CD4+ T cells, the colonic lamina propria, mesenteric lymph node, and splenic CD4+ T cells produced very little IFN-gamma but abundant levels of TNF-alpha. The histopathologic appearance of colitis in all transplanted SCID mice was similar. These data indicate that CD45RBhigh and CD45RBlow, IL-12-responsive and IL-12-unresponsive CD4+ T lymphocytes and lymphoblasts have IBD-inducing potential though of varying potency.

The relationship between moral decision making and patterns of consolidation and transition in moral judgment development.

Following models that describe intraindividual correlates of stage transitions (S. S. Snyder & D. H. Feldman, 1984), this study assessed the relation between a measure of consolidation and transition in moral judgment development and the utility of moral concepts in sociomoral decision making. The study extends previous research in suggesting that individuals use moral concepts differently as they cycle through periods of consolidation and transition. With multiple cross-sectional and longitudinal samples, findings indicate that participants' reliance on a Kohlbergian moral framework as measured by the Defining Issues Test is highest during periods of consolidation and lowest during transitions. As participants move into periods of consolidation, the utility of moral stage information increases. Thus, this study indicates that the consolidation and transition model can be used to help identify individuals who are more or less likely to use Kohlberg's moral stages in their moral decision making.

Individual moral judgment and cultural ideologies.

Moral judgment cannot be reduced to cultural ideology, or vice versa. But when each construct is measured separately, then combined, the product predicts powerfully to moral thinking. In Study 1, 2 churches (N = 96) were selected for their differences on religious ideology, political identity, and moral judgment. By combining these 3 variables, a multiple correlation of .79 predicted to members' moral thinking (opinions on human rights issues). Study 2 replicated this finding in a secular sample, with the formula established in Study 1 (R = .77). Individual conceptual development in moral judgment and socialization into cultural ideology co-occur, simultaneously and reciprocally, in parallel, and not serially. Individual development in moral judgment provides the epistemological categories for cultural ideology, which in turn influences the course of moral judgment, to produce moral thinking (e.g., opinions about abortion, free speech).

A pancolitis resembling human ulcerative colitis (UC) is induced by CD4+ TCR alphabeta T cells of athymic origin in histocompatible severe combined immunodeficient (SCID) mice.

CD4+ TCRalphabeta+ T cells from the colonic lamina propria of athymic (nude) mice were adoptively transferred into histocompatible (SCID) mice homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of these extrathymic CD4+ T cells into SCID mice induced a pancolitis in the adoptive host. The histopathology of this inflammatory response was restricted to the colon and closely resembled human UC. CD4+ T cells infiltrating the colonic lamina propria of diseased SCID mice displayed the surface phenotype of mucosa-seeking memory/effector cells, expressed interferon-gamma (IFN-gamma), and lysed targets in a Fas (CD95)/FasL-dependent pathway. Massive accumulation of oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1 memory/effector T cells in the colonic lamina propria of a histocompatible, immunodeficient host elicits a pancolitis that morphologically mimics human UC.

T cell-mediated, IFN-gamma-facilitated rejection of murine B16 melanomas.

The murine melanoma cell line B16.F10 (H-2b) was used to study specific T cell responses that reject tumors. Stable B16 transfectants were established that express viral Ags, either the hepatitis B surface Ag (HBsAg) or the large tumor Ag (T-Ag) of SV40. B16 cells and their transfected sublines were CD40+ CD44+ but expressed no (or low levels of the) costimulator molecules CD154 (CD40L), CD48, CD54, CD80, and CD86. Surface expression of MHC class I (Kb, Db) and class II (I-Ab) molecules by B16 cells was low, but strikingly up-regulated by IFN-gamma. CD95 (Fas) and CD95 ligand (CD95L (FasL)) were "spontaneously" expressed by B16 cells growing in vitro in serum-free medium; these markers were strikingly up-regulated by IFN-gamma. B16 cells coexpressing CD95 and CD95L were irreversibly programmed for apoptosis. In vitro, noninduced B16 transfectants stimulated a specific IFN-gamma release response, but no cytolytic response (in a 4-h assay) in MHC class I-restricted CTL; in contrast, IFN-gamma-induced B16 targets were efficiently and specifically lysed by CTL. In vivo, B16 transfectants were specifically rejected by DNA-vaccinated syngeneic hosts through a T-dependent immune effector mechanism. The tumors showed evidence of massive apoptosis in vivo during the rejection process. The data suggest that CTL-derived IFN-gamma enhances an intrinsic suicide mechanism of these tumor cells in addition to facilitating lytic interactions of effectors with tumor targets.

Expression of selectin-binding epitopes and cytokines by CD4+ T cells repopulating scid mice with colitis.

Recruitment into the gut of CD4+ T cells and their activation in the colonic lamina propria (LP) are key events in the development of colitis in scid mice reconstituted with CD4+ T cells from immunocompetent, congenic donor mice. This study investigated the expression of cytokines and selectin-binding epitopes by CD4+ T cells repopulating different tissues of the adoptive scid host. Cells from the inflamed colonic LP of transplanted scid mice produced high amounts of IL-12, IFN-gamma and TNF-alpha but only low amounts IL-4 and IL-10. Intracellular cytokine staining confirmed the presence of large numbers of IFN-gamma- and TNF-alpha-producing effector CD4+ T cells in the colonic LP of scid mice with colitis but also in non-inflamed tissues [spleen (S), peritoneal cavity (PC) and mesenteric lymph nodes (mLN)] of the adoptive host. Cells from these tissues furthermore produced large amounts of IL-12. Ligands for endothelial selectins are involved in recruiting T cells into inflamed tissues. We have analyzed the expression of selectin-binding epitopes on CD4+ T cells repopulating different tissues of the adoptive scid host. We found that a large fraction of CD4+ T cells from inflamed colonic LP and from non-inflamed PC, mLN and S expressed high levels of P- and E-selectin-binding epitopes (P-Lhi) in transplanted scid mice, but not in congenic, immunocompetent control mice. Although P-Lhi CD4+ T cells were enriched in IFN-gamma-producing subsets from most (but not all) tissues, we also found large numbers of in vivo generated P-Llo CD4+ T cells producing pro-inflammatory cytokines. This was in contrast to in vitro generated Th1 CD4+ T blasts that were almost exclusively P-Lhi. In this mouse model, production of Th1-type pro-inflammatory cytokines and expression of surface epitopes binding endothelial selectins are hence strikingly up-regulated in CD4+ T cells residing in inflamed and non-inflamed tissues during the development of colitis.

Short-term effects of early-acting and multilineage hematopoietic growth factors on the repair and proliferation of irradiated pure cord blood (CB) CD34+ hematopoietic progenitor cells.

PURPOSE: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro or in vivo on the survival of hematopoietic stem and progenitor cells after accidental or therapeutic total body irradiation. METHODS AND MATERIALS: We studied the clonogenic survival and DNA repair of irradiated (0.36, 0.73, and 1.46 Gy) CD34+ cord blood (CB) cells after short-term incubation (24 h) with GFs. CD34+ cells were stimulated with basic fibroblast growth factor (bFGF), stem cell factor/c-kit ligand (SCF), interleukin-3 (IL-3), IL-6, leukemia inhibitory factor (LIF), and granulocyte-monocyte colony stimulating factor (GM-CSF) alone or in combination in short-term serum-free liquid suspension cultures (LSC) immediately after irradiation and then assayed for clonogenic progenitors. DNA repair was evaluated by analysis of DNA strand breaks using the comet assay. Survival of CFU-GM, BFU-E, and CFU-Mix was determined and dose-response curves were fitted to the data. RESULTS: The radiobiological parameters (D[0] and n) showed significant GF(s) effects. Combination of IL-3 with IL-6, SCF or GM-CSF resulted in best survival for CFU-GM BFU-E and CFU-Mix, respectively. Combinations of three or more GFs did not increase the survival of clonogenic CD34+ cells compared to optimal two-factor combinations. The D[0] values for CFU-GM, BFU-E, and CFU-Mix ranged between 0.56-1.15, 0.41-2.24, and 0.56-1.29 Gy, respectively. As for controls, the curves remained strictly exponential, i.e., all survival curves were strictly exponential without any shoulder (extrapolation numbers n=1 for all tested GF(s). DNA repair capacity of CD34+ cells determined by comet assay, was measured before, immediately after irradiation, as well as 30 and 120 min after irradiation at 1 Gy. Notably, after irradiation the 2-h repair of cytokine-stimulated and unstimulated CD34+ cells was similar. CONCLUSION: Our data indicate that increased survival of irradiated CB CD34+ cells after short-term GF treatment is mediated through proliferative GF effects on the surviving fraction but not through improved DNA repair capacity.

[Tricuspid valve endocarditis. Demonstration of a rare disease exemplified with 3 case reports]. / Trikuspidalklappenendokarditis. Darstellung eines seltenen Krankheitsbildes anhand dreier Fallberichte.

BACKGROUND: Endocarditis of the tricuspid valve is a rare form of valvular endocarditis and occurs mainly in patients with special risk factors. CASE REPORTS: The three case reports demonstrate 3 young patients (age 30 to 37 years, 2 female and 1 male) with a typical history of those risk factors. The two women were intravenous drug addicts and one of them had suffered already an episode of tricuspid valve endocarditis several years ago. The man developed his infection after implantation of a pacemaker. In all of the three patients the endocarditis was due to infection with staphylococci twice staphylococcus epidermidis and once staphylococcus aureus. In two of the three patients the endocarditis could not be cured by intravenous antibiotics alone and these patients had to undergo cardiac valvular surgery. All patients left the hospital after several weeks without signs of infection. CONCLUSION: In clinical praxis the introduction of a special endocarditis service, a small team which has to be consulted in every suspected case of endocarditis, seems to be beneficial as well as the use of the Duke criteria for diagnosis in those cases.

Local venous thrombosis after cardiac catheterization.

Pulmonary embolism is a rare but life-threatening complication of cardiac catheterization. Underlying deep venous thrombosis (DVT) is often not detectable clinically. To determine the true incidence of DVT the authors prospectively studied 450 consecutive patients (29% women, 71% men, mean age: fifty-eight years) undergoing a diagnostic cardiac catheterization. Patients were examined clinically and by duplex sonography with a high-resolution (5 or 7.5 MHz) transducer before and twenty-four hours after catheterization before mobilization. Duplex sonography excluded complete proximal DVT in all patients. Only partial occluding thrombi (pDVT) were detected in 11 (2.4%) patients. The thrombi were always localized at the puncture site. In 2 patients a difference was found in the circumferences of the legs, but no other clinical signs of DVT were seen. With use of continuous wave (cw) Doppler sonography, only 3 of these 11 patients (27%) showed a spontaneous (s) sound. Phlebography was performed in 4/11 patients (36%). In 2 patients the diagnosis was confirmed; in 1 patient extravenous compression was assumed, and the other demonstrated a normal-appearing phlebography at the time of investigation. Logistic regression analysis yielded a 3.5 times higher risk for developing a pDVT if a venous puncture was performed in addition to arterial puncture. Furthermore a 9.8 times higher risk was found if more than one venous puncture was necessary. During the follow-up no patient developed clinical signs of pulmonary embolism. The results of this study demonstrate that DVT is a rare complication of cardiac catheterization (0/450 patients), but pDVT occurred in 2.4%. Risk factors for pDVT are the venous puncture itself and multiple puncture attempts. Clinical relevance of pDVT remains to be determined.

Pseudoaneurysm after cardiac catheterization: therapeutic interventions and their sequelae: experience in 86 patients.

After diagnostic cardiac catheterization in 8,715 patients, a pseudoaneurysm was diagnosed in 86 (1%) patients. Primary conservative management by repeated compression bandages (CB) or ultrasound guided compression (UGC) was attempted in all patients. Occlusion of the pseudoaneurysm was achieved significantly more often by UGC (41/47; 87%) than by CB (22/39; 56%; P = 0.016). Of 86 patients, 23 (27%) required surgical treatment. Major clinical acute complications occurred after surgery in 8/23 cases (35%) versus 4/63 (6%; P = 0.0004) following successful CB or UGC. However, intention-to-treat analysis showed no difference in the rate of acute complications in the CB or UGC group (15.4% versus 12.8%, P = 0.7272), because of a trend towards a higher complication rate following secondary surgery in the UGC (4/6 = 66.7%), as compared to the CB group (4/17 = 23.5%, P = 0.1589). During follow up, 22/64 (34%) patients reported persistent inguinal complaints, 9/15 (60%) after surgery and 13/49 (27%) after successful CB or UGC (P = 0.0169). However, according to the intention-to-treat analysis, there was no significant difference between the initial groups (CB: 26.1% versus UGC: 39.0%, P = 0.2958). Despite a higher effectiveness of UGC to achieve occlusion of a pseudoaneurysm compared to CB (87% vs. 56%), UGC is not superior to CB because of a higher rate of acute complications as well as long-term complaints in those patients requiring secondary surgery in the UCG group as compared to the CB group.

Processing of exogenous hepatitis B surface antigen particles for Ld-restricted epitope presentation depends on exogenous beta2-microglobulin.

Processing of exogenous hepatitis B surface antigen (HBsAg) particles in an endolysosomal compartment generates peptides that bind to the major histocompatibility complex (MHC) class I molecule Ld and are presented to CD8+ cytotoxic T lymphocytes. Surface-associated 'empty' MHC class I molecules associated neither with peptide, nor with beta2-microglobulin (beta2m) are involved in this alternative processing pathway of exogenous antigen for MHC class I-restricted peptide presentation. Here, we demonstrate that internalization of exogenous beta2m is required for endolysosomal generation of presentation-competent, trimeric Ld molecules in cells pulsed with exogenous HBsAg. These data point to a role of endocytosed exogenous beta2m in the endolysosomal assembly of MHC class I molecules that present peptides from endosomally processed, exogenous antigen.

Relationship between transepidermal water loss and temperature of the measuring probe.

BACKGROUND/AIMS: Transepidermal water loss (TEWL) is an important parameter for the determination of skin barrier function. The open chamber method has been established as the technique of choice in most dermatological laboratories for measurements of TEWL. However, the influence of the probe temperature on TEWL measurements has been the subject of recent controversial debates. In this study the relationship between TEWL measured with the Tewameter and temperature of the measuring probe was therefore investigated by comparing two different measuring techniques. METHODS: For one measurement, the probe was kept at room temperature (20°C) and for the other one, the probe was preheated to the actual temperature of the measuring object before obtaining the values. Measurements were performed on evaporative standards (EvSs) and healthy individuals. For the EvSs, semipermeable membranes were pulled over a petri dish filled with water, which could be heated. RESULTS: TEWL values were found to depend on the temperature of the probe. TEWL values were higher when measured with the preheated probe. However, long-term measurements revealed that TEWL values measured with the unheated probe reached those higher TEWL values after approximately 8 min measuring time. CONCLUSIONS: The final TEWL value was reached after shorter intervals for the preheated probe compared to the unheated probe (2.5 min vs. 4 min) for some measurements. However, preheating of the probe resulted in greater variability of the measurement values. Therefore, measurements with a preheated Tewameter probe is not be recommended.

Cytotoxic reactivity of gut lamina propria CD4+ alpha beta T cells in SCID mice with colitis.

Polyclonal, mucosa-seeking memory/effector CD4+ T cells containing a large fraction of blasts activated in situ accumulate in the gut lamina propria of severe-combined immunodeficient (SCID) mice developing colitis after CD4+ T cell transplantation. CD4+ T cells isolated from different repopulated lymphoid tissues of transplanted SCID mice proliferate in vitro in the presence of interleukin (IL)-2 + IL-7. CD3 ligation enhances this cytokine-supported proliferation in CD4+ T cells from the spleen and the mesenteric lymph node of transplanted SCID mice; CD3 ligation suppresses the cytokine-supported proliferation in CD4+ T cells from the gut lamina propria in a cell density- and dose-dependent manner. Almost all CD4+ T cells from repopulated lymphoid tissues of transplanted SCID mice express CD95 (Fas) on the cell surface, and a large fraction of CD4+ T cells from the gut lamina propria of transplanted SCID mice express the Fas ligand on the surface. Gut lamina propria CD4+ T cells show Fas-dependent cytotoxicity. A large fraction of gut lamina propria CD4+ T cells that infiltrate the inflamed colon in transplanted SCID mice are activated in situ and many CD4+ T cells are apoptotic. Hence, a large fraction of colitis-inducing CD4+ T cells undergo activation-induced cell death in situ and can damage other cells through Fas-dependent cytotoxicity.

Do 5-F-catheters reduce the incidence of a pseudoaneurysm?

Femoral artery pseudoaneurysm is a major problem in patients undergoing cardiac catheterization. This study describes our experience with 5 French (5 F) and 7 French (7 F) introduction sheaths and 7 investigators at our institution regarding the incidence of pseudoaneurysms. During 54 months (1/1990-6/1994) 8715 consecutive patients after diagnostic cardiac catheterization were first clinically checked for pseudoaneurysm and in case of suspicion a duplex sonography was performed. In 86 (1%) patients, 44 (52%) women and 42 (48%) men, mean age 63 +/- 9.7 years we observed this complication by duplex ultrasound. 54 (62%) patients had arterial hypertension, 18 (20%) diabetes and only 3 (3.6%) had peripheral arteriosclerosis. An antithrombotic medication was used in 60% (52 patients). As compared to a control group of 450 consecutive patients a pseudoaneurysm was significantly more likely to occur in patients with a history of hypertension (63% vs 25%, p < 0.0001). Women are also at higher risk representing 51% of all pseudoaneurysms as compared to 29% in the control group (p < 0.0001). Using 7-F catheters more pseudoaneurysms occurred (82/7183; 1%) than using 5 F (4/1532; 0.2%) introduction sheaths (p = 0.0005). There were also significantly more pseudoaneurysms caused by investigator 1 (21/787; 2.7%) as compared to the other investigators (65/7829; 0.8%), (p = 0.0002). Investigator 1 had a more distal puncture technique than the others. Pseudoaneurysms complicating cardiac catheterization occur 5-times more frequent using 7 F (1%) as compared to 5 F catheters (0.2%). Moreover distal puncture site is associated with a higher frequency of pseudoaneurysms.

Surface antigen expression on CD34+ cord blood cells: comparative analysis by flow cytometry and limiting dilution (LD) RT-PCR of chymopapain-treated or untreated cells.

Expression of antigens coexpressed on cord blood (CB) CD34+ cells was evaluated by flow cytometry analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Antigen expression was also comparatively analyzed by flow cytometry and limiting dilution (LD) RT-PCR to investigate effects of chymopapain on epitopes of several cell surface markers: LD RT-PCR allows detection of the expression of antigens degraded by chymopapain which are not identified by flow cytometry. Monoclonal antibodies (MoAbs) that recognize chymopapain resistant epitopes on several coexpressed cell surface markers were identified: these included MoAbs directed against CD11a, CD13, CD18, CD38, CD45RO, CD51, HLA-DR, Thy-1, c-kit, flt-3 (STK-1), and mdr-1. Interestingly, chymopapain treatment caused enhanced staining with MoAbs against HLA-DR, Thy-1, flt-3, mdr-1, and CD51. The frequency (LD RT-PCR) of CD18, CD38, Thy-1, and c-kit RT-PCR signals on pure sorted CD34+ CD18-, CD34+ CD38-, CD34+ Thy-1-, and CD34+ c-kit- cells, respectively, was similar in corresponding subsets treated or not with chymopapain. In contrast, the frequency of CD33 RT-PCR signals on sorted CD34+ CD33- cells was higher in chymopapain-treated samples than in untreated samples and thus confirmed at the transcriptional level that the epitope recognized by anti-CD33 is chymopapain sensitive. Our findings extend data on the phenotypic profile of CB CD34+ cells and show that several key cell surface markers of hematopoietic progenitor cells are chymopapain resistant. In addition, the results of the present study demonstrate that the RT-PCR can be applied to the analysis of multiple RNA species in small numbers of hematopoietic progenitor cells and show that LD RT-PCR allows the identification and frequency determination of rare cells which are undetectable by flow cytometry.