Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

BACKGROUND/AIMS: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. METHODS: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. RESULTS: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 +/- 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 +/- 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. CONCLUSION: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.

Outcome after proximal femoral fractures during primary total hip replacement by the direct anterior approach.

BACKGROUND: The literature suggests that intraoperative fractures of the greater trochanter and the metaphysis are increased with uncemented stems and the direct anterior approach. This study aims to determine the incidence and assess the functional and radiological outcome after such fractures. METHODS: 484 consecutive total hip replacements (THR) (64 ± 12 years) were analyzed. We treated trochanteric fractures conservatively without any further denuding, and secured metaphyseal fissures with cerclages. Postoperative X-rays and at the latest follow-up were compared to assess secondary fracture displacement and stem subsidence. Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores after 1 year were analyzed. For each patient sustaining a fracture, two patients without fractures were matched in terms of age, body mass index and gender. RESULTS: 13 (2.7 %, 5 male, 68 ± 9 years) patients with intraoperative fractures of the greater trochanter (n = 8) or the metaphysis (n = 5) were analyzed. Consolidation was observed in 7/8 patients sustaining a trochanteric fracture while secondary displacement of the fragment occurred in one case. Stem subsidence was observed in 2/5 cases (5 and 7 mm). Patients who sustained a fracture showed a trend towards poorer WOMAC scores at 1 year postoperatively, compared to patients without fractures. A significantly increased joint stiffness was also observed. CONCLUSION: The intraoperative fracture risk in this series of THR through a direct anterior approach was 2.7 %. Trochanteric fractures do heal without primary fixation. Metaphyseal fractures heal well if immediately stabilized with a cerclage.

Treatment of type B periprosthetic femur fractures with curved non-locking plate with eccentric holes: Retrospective study of 43 patients with minimum 1-year follow-up.

INTRODUCTION: Periprosthetic femur fracture (PFF) is a serious complication after total hip arthroplasty that can be treated using different internal fixation devices. However, the outcomes with curved non-locking plates with eccentric holes in this indication have not been reported previously. The objectives of this study were to determine: (1) the union rate; (2) the complication rate; (3) autonomy in a group of patients with a Vancouver type B PFF who were treated with this plate. HYPOTHESIS: Use of this plate results in a high union rate with minimal mechanical complications. MATERIALS AND METHODS: Forty-three patients with a mean age of 79 years±13 (41-98) who had undergone fixation of Vancouver type B PFF with this plate between 2002 and 2007 were included in the study. The time to union and Parker Mobility Score were evaluated. The revision-free survival (all causes) was calculated using Kaplan-Meier analysis. The average follow-up was 42 months±20 (16-90). RESULTS: Union was obtained in all patients in a mean of 2.4 months±0.6 (2-4). One patient had varus malunion of the femur. The Parker Mobility Score decreased from 5.93±1.94 (2-9) to 4.93±1.8 (1-9) (P=0.01). Two patients required a surgical revision: one for an infection after 4.5 years and one for stem loosening. The survival of the femoral stem 5 years after fracture fixation was 83.3%±12.6%. CONCLUSION: Use of a curved plate with eccentric holes for treating type B PFF led to a high union rate and a low number of fixation-related complications. However, PFF remains a serious complication of hip arthroplasty that is accompanied by high morbidity and mortality rates. LEVEL OF EVIDENCE: Retrospective study, level IV.

Distal and proximal influences on the use of business and moral frames in responsible decisions

We empirically contribute to the debate on business education in building on a decision frame perspective of decision making in corporate responsibility settings. Business schools have been accused to teach amoral theories, leading their students to behave less morally and engendering corporate responsibility scandals. Research has also pointed toward self-selection: business students would differ from non-business students before entering business school. We examine the role of socioeconomic status, core self-evaluations in this regard. Further, we investigate the belief in a free market as a distal influence triggering a business frame, and moral intensity as a proximal influence triggering a moral frame on responsible decision making by business and non-business students. Cross-sectional data obtained from 566 students on two decision making scenarios mostly supported our hypotheses. Socioeconomic status but not core self-evaluations explain the belief in a free market, and had indirect effects on the likelihood to make a less responsible decision. Importantly, the relationship between business studies and the belief in a free market remained significant after accounting for these variables. Our study thus contributes to the socialization and self-selection arguments. We discuss theoretical and practical implications for research on decision frames and for business education, respectively.

Early versus delayed application of Thomas splints in patients with isolated femur shaft fractures: The benefits quantified.

AIMS: To investigate and quantify the clinical benefits of early versus delayed application of Thomas splints in patients with isolated femur shaft fractures. MATERIALS AND METHODS: Level IV retrospective clinical and radiological analysis of patients presenting from January to December 2012 at a Level 1 Trauma Unit. All skeletally mature patients with isolated femur shaft fractures independently of their mechanism of injury were included. Exclusion criteria were: ipsilateral fracture of the lower limb, neck and supracondylar femur fractures, periprosthetic and incomplete fractures. Their clinical records were analysed for blood transfusion requirements, pulmonary complications, surgery time, duration of hospital stay and analgesic requirements. RESULTS: A total of 106 patients met our inclusion criteria. There were 74 males and 32 females. Fifty seven (54%) patients were in the 'early splinted' group and 49 patients (46%) were in the 'delayed splinted' group (P>0.05). The need for blood transfusion was significantly reduced in the 'early splinted' group (P=0.04). There was a significantly higher rate of pulmonary complications in the 'delayed splinted' group (P=0.008). All other parameters were similar between the two groups. CONCLUSION: The early application of Thomas splints for isolated femur fractures in non-polytraumatised patients has a clinically and statistically significant benefit of reducing the need for blood transfusions and the incidence of pulmonary complications.

CD8 kinetically promotes ligand binding to the T-cell antigen receptor.

The mechanism of CD8 cooperation with the TCR in antigen recognition was studied on live T cells. Fluorescence correlation measurements yielded evidence of the presence of two TCR and CD8 subpopulations with different lateral diffusion rate constants. Independently, evidence for two subpopulations was derived from the experimentally observed two distinct association phases of cognate peptide bound to class I MHC (pMHC) tetramers and the T cells. The fast phase rate constant ((1.7 +/- 0.2) x 10(5) M(-1) s(-1)) was independent of examined cell type or MHC-bound peptides' structure. Its value was much faster than that of the association of soluble pMHC and TCR ((7.0 +/- 0.3) x 10(3) M(-1) s(-1)), and close to that of the association of soluble pMHC with CD8 ((1-2) x 10(5) M(-1) s(-1)). The fast binding phase disappeared when CD8-pMHC interaction was blocked by a CD8-specific mAb. The latter rate constant was slowed down approximately 10-fold after cells treatment with methyl-beta-cyclodextrin. These results suggest that the most efficient pMHC-cell association route corresponds to a fast tetramer binding to a colocalized CD8-TCR subpopulation, which apparently resides within membrane rafts: the reaction starts by pMHC association with the CD8. This markedly faster step significantly increases the probability of pMHC-TCR encounters and thereby promotes pMHC association with CD8-proximal TCR. The slow binding phase is assigned to pMHC association with a noncolocalized CD8-TCR subpopulation. Taken together with results of cytotoxicity assays, our data suggest that the colocalized, raft-associated CD8-TCR subpopulation is the one capable of inducing T-cell activation.

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities.

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.

Endovascular thoracic aortic aneurysm repair without angiography.

OBJECTIVE: : Intravascular ultrasound (IVUS) generates high definition circumferential cross-sectional images and provides real-time readout of vascular dimensions, including visualization of vessel branches. We have used it as an alternative to angiography in the endovascular thoracic aneurysm repair work-up. METHODS: : Out of consecutive 203 patients with descending thoracic aortic aneurysm, 89 (43.8%) received endovascular treatment [mean age, 68 ± 8 years; range, 29-82; male, 79 (88.7%); female, 10 (11.3%)] without using angiography during the endovascular procedure. IVUS (6 F, 12.5 MHz probe or 10 F 9 MHz) coupled with fluoroscopy for the placement of radiopaque markers was used for target site identification, landing zone measurement, device positioning, and assessment of endovascular repair. RESULTS: : Hospital mortality was 4/89 (4.5%). Number of devices implanted in each patient was 1.2 (range, 1-3). X-ray exposure time was 12 ± 8 minutes. Median procedure time was 63 ± 20 minutes. Conversion to open surgery was necessary in one patient (1.1%) because of aortic dissection. In nine patients (10.1%) left subclavian artery was covered because of a short neck. Two patients (2.2%) had vascular access lesions and required surgical repair. One patient developed paraplegia (1.1%). Early endoleak was observed in eight patients (8.9%) and 4 (4.5%) required additional procedures (proximal or distal extensions). Late conversion was necessary in one patient (1.1%). CONCLUSIONS: : IVUS provides all information necessary for device selection, target site identification as well as safe and correct deployment of thoracic endoprostheses and makes periprocedural angiography unnecessary, thus avoiding the risk of renal failure because of contrast medium.

Biofilm formation by staphylococci on fresh, fresh-frozen and processed human and bovine bone grafts.

Biofilm formation is a multi-step process influenced by surface properties. We investigated early and mature biofilm of Staphylococcus aureus on 4 different biological calcium phosphate (CaP) bone grafts used for filling bone defects. We investigated standardised cylinders of fresh and fresh-frozen human bone grafts were harvested from femoral heads; processed humanand bovine bone grafts were obtained preformed. Biofilm formation was done in tryptic soy broth (TSB) using S. aureus (ATCC 29213) with static conditions. Biofilm density after 3 h (early biofilm) and 24 h (mature biofilm) was investigated by sonication and microcalorimetry. After 3 h, bacterial density was highest on fresh-frozenandfresh bone grafts. After 24 h, biofilm density was lowest on freshbone grafts (p < 0.001) compared to the other 3 materials, which did not differ quantitatively (p > 0.05). The lowest increase in bacterial density was detected on fresh bone grafts (p < 0.001). Despite normal shaped colonies, we found additional small colonies on the surface of the fresh and fresh-frozen samples by sonication. This was also apparent in microcalorimetric heat-flow curves. The four investigated CaP bone grafts showed minor structural differences in architecture but marked differences concerning serum coverage and the content of bone marrow, fibrous tissue and bone cells. These variations resulted in a decreased biofilm density on freshand fresh-frozenbone grafts after 24 h, despite an increased early biofilm formation and might also be responsible for the variations in colony morphology (small colonies). Detection of small colony variants by microcalorimetry might be a new approach to improve the understanding of biofilm formation.

The dynamics of yeast telomeres and silencing proteins through the cell cycle.

Genes integrated near the telomeres of budding yeast have a variegated pattern of gene repression that is mediated by the silent information regulatory proteins Sir2p, Sir3p, and Sir4p. Immunolocalization and fluorescence in situ hybridization (FISH) reveal 6-10 perinuclear foci in which silencing proteins and subtelomeric sequences colocalize, suggesting that these are sites of Sir-mediated repression. Telomeres lacking subtelomeric repeat elements and the silent mating locus, HML, also localize to the periphery of the nucleus. Conditions that disrupt telomere proximal repression disrupt the focal staining pattern of Sir proteins, but not necessarily the localization of telomeric DNA. To monitor the telomere-associated pools of heterochromatin-binding proteins (Sir and Rap1 proteins) during mitotic cell division, we have performed immunofluorescence and telomeric FISH on populations of yeast cells synchronously traversing the cell cycle. We observe a partial release of Rap1p from telomeres in late G2/M, although telomeres appear to stay clustered during G2-phase and throughout mitosis. A partial release of Sir3p and Sir4p during mitosis also occurs. This is not observed upon HU arrest, although other types of DNA damage cause a dramatic relocalization of Sir and Rap1 proteins. The observed cell cycle dynamics were confirmed by direct epifluorescence of a GFP-Rap1p fusion. Using live GFP fluorescence we show that the diffuse mitotic distribution of GFP-Rap1p is restored to the interphase pattern of foci in early G1-phase.