Use of platelet glycoprotein IIb/IIIa inhibitors in saphenous vein graft percutaneous coronary intervention and clinical outcomes

Platelet glycoprotein (GP) IIb/IIIa inhibitors are widely used in percutaneous coronary intervention (PCI). Previous studies have suggested that they do not offer benefit in saphenous vein graft PCI. Nonetheless, their use remains widespread during vein graft angioplasty. We retrospectively analyzed 1,537 patients who underwent saphenous vein graft PCI. Patients who received a GP IIb/IIIa inhibitor (n = 941) were compared with those who did not receive any GP IIb/IIIa inhibitor (n = 596). The primary end point was myonecrosis after PCI (creatine kinase-MB level >3 times the upper reference limit). The incidence of myonecrosis after PCI was similar between the group that received GP IIb/IIIa and the group that did not (odds ratio for GP IIb/IIIa use 1.39, 95% confidence interval 0.97 to 2.00, p = 0.07). Propensity-adjusted analysis demonstrated no significant difference in myonecrosis after PCI, in-hospital mortality, Q-wave myocardial infarction, or bleeding (blood transfusion, retroperitoneal bleed, or hematoma) between the 2 groups. In an analysis restricted to patients who were treated with an emboli protection device, GP IIb/IIIa use was not associated with decreased myonecrosis after PCI (this was also the case for patients who were not treated with an emboli protection device). Unadjusted survival (mean follow-up 5.5 +/- 0.1 years) was similar between the group that received GP IIb/IIIa and the group that did not (log-rank test, p = 0.89). There was no difference in survival after adjusting for the propensity to receive a GP IIb/IIIa inhibitor (adjusted odds ratio for GP IIb/IIIa use 0.92, 95% confidence interval 0.69 to 1.23, p = 0.59). In conclusion, adjunctive use of platelet GP IIb/IIIa inhibitors in saphenous vein graft PCI does not appear to be associated with less myonecrosis or improved survival.     

Selective Tyrosine Kinase Inhibitor for the Platelet-Derived Growth Factor Receptor In Vitro Inhibits Smooth Muscle Cell Proliferation After Reinjury of Arterial Intima In Vivo

Summary. The long-term success of coronary angioplasty is limited by restonosis. This study was undertaken to investigate whether and to what extent the enhanced proliferative response observed in a balloon reinjury model of rat aorta is regulated by the PDGF receptor (PDGF-R). Balloon injury was performed to 14-day-old pre-existing neointimal lesion in rat aorta. PDGF receptor and ligand immunoreactivity were measured at several time points after the first and second injury, and PDGF-R signaling was blocked with a selective inhibitor of PDGF-R tyrosine kinase. In the neointima, after repeated injury, upregulation of PDGF-AA was seen to coincide with a prompt proliferative response of smooth muscle cells (SMC). Administration of the PDGF-R tyrosine kinase inhibitor in vivo, tested and found to inhibit the proliferation of SMC induced by PDGF-AA and PDGF-BB, but not by IGF-1, EGF, or bFGF, resulted in a 60% reduction in the absolute number and percentage of BrdU+ cells after the second balloon injury to pre-existing neointima, but had no significant effect on proliferation after the first injury. Endpoint lesion are was reduced by 50% in the treated group at 14 days after the second injury. The results suggest that systemic administration of a tyrosine kinase inhibitor specific for the PDGF-R can be useful in the prevention of restenosis.     

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested.     

Association of a pulsatile blood flow pattern on coronary arteriography and short-term clinical outcomes in acute myocardial infarction

OBJECTIVES: We hypothesized that recognition of systolic flow reversal (pulsatile flow) after thrombolytic administration on coronary angiography is associated with angiographic and electrocardiogram findings reflecting impaired myocardial perfusion, as well as poorer clinical outcomes. BACKGROUND: Reversal of systolic flow on Doppler velocity wire recordings has been associated with impaired tissue perfusion on myocardial contrast echocardiography in the setting of myocardial infarction (MI). METHODS: Patients (n = 1,062) with a patent infarct-related artery were drawn from the Thrombolysis In Myocardial Infarction (TIMI) 10, TIMI 14, and Integrillin and Tenecteplase acute MI trials. RESULTS: Pulsatile flow (systolic flow reversal with cessation of antegrade contrast-dye motion or frank reversal of contrast-dye motion during systole) at 60 min after fibrinolytic administration was present in 11.0% of patients. Pulsatile flow was associated with higher corrected TIMI frame counts (slower epicardial flow) (median 40.1 frames, IQ 30 of 63 vs. 30 frames, interquartile 22 of 42, p < 0.0001), a closed microvasculature (TIMI myocardial perfusion grades 0 of 1, 57.1% vs. 37.8%, p = 0.03) and less complete (> or =70%) ST-segment resolution (23.5% vs. 58.9%, p = 0.008). Patients with pulsatile flow had a higher risk of death or reinfarction at 30 days (10.3% vs. 5.0%, p = 0.019). After controlling for age, pulse, blood pressure, anterior MI location, epicardial flow, and creatine kinase, pulsatile flow remained associated with an increased risk of death/MI (odds ratio 3.1, p = 0.006). CONCLUSIONS: A pulsatile pattern of flow is associated with impaired myocardial perfusion and poorer clinical outcomes independent of the velocity of antegrade flow in the epicardial artery. This simple and easily identifiable angiographic flow pattern may be useful in clinical risk stratification.     

Removal of As(iii) and As(v) from water using green,silica-based ceramic hollow fibre membranes via direct contact membrane distillation

Arsenite [As(iii)] and arsenate [As(v)] removal by direct contact membrane distillation (DCMD) using novel hydrophobic green, silica-based ceramic hollow fibre membranes derived from agricultural rice husk was investigated in this work. The green ceramic hollow fibre membranes were prepared from amorphous (ASHFM) and crystalline (CSHFM) silica-based rice husk ash and modified to be hydrophobic via immersion fluoroalkylsilane (FAS) grafting of 1H,1H,2H,2H-perfluorodecyltriethoxysilane. Superhydrophobic contact angle values up to 157° and 161° were obtained for ASHFM and CSHFM, respectively. Remarkably, the membrane surface morphology mimicked a look-alike lotus-leaf structure with decrement in pore size after grafting via the silane agent for both membranes. The effect of arsenic pH (3–11), arsenic concentration (1–1000 ppm) and feed temperature (50–80 °C) were studied and it was found that feed temperature had a significant effect on the permeate flux. The hydrophobic CSHFM, with a flux of 50.4 kg m⁻² h⁻¹ for As(iii) and 51.3 kg m⁻² h⁻¹ for As(v), was found to be the best of the tested membranes. In fact, this membrane can reject arsenic to the maximum contaminant level (MCL) limit of 10 ppb under any conditions, and no swelling mechanism of the membranes was observed after testing for 4 hours.

Arsenite [As(iii)] and arsenate [As(v)] removal by direct contact membrane distillation (DCMD) using novel hydrophobic green, silica-based ceramic hollow fibre membranes derived from agricultural rice husk was investigated in this work.     

Lumbar instrumented posterolateral fusion in spondylolisthetic and failed back patients: a long-term follow-up study spanning 11–13?years

Introduction and materials

We examined lumbar transpedicular instrumented posterolateral fusion patients operated on between 1992 and 1997 presenting: degenerative spondylolisthesis with spinal stenosis; adult isthmic spondylolisthesis; failed back syndrome after one to five discectomies; and failed back syndrome after one to three laminectomy operations (Groups 1–4, respectively).

Methods

They were examined by an independent orthopedic surgeon, completed the Oswestry Disability Index (ODI) and visual analog scale (VAS) questionnaires and their outcome was evaluated.

Results

The overall patient satisfaction at follow-up (mean 11.7 years) was 82.1 %. The reoperation rate was 15.1 % (7.5 % due to adjacent segment disease).

Conclusion

Group 1 showed the greatest improvements in ODI and VAS values, Group 2 the lowest and Group 3 the highest preoperative values, and Group 4 the second highest improvements. Patient satisfaction scores were 90.3, 69.7, 63.6 and 80.0 %, respectively, and unplanned reoperation rates were 6.5, 9.1, 31.8 and 20.0 %. Thus, long-term outcomes of lumbar instrumented posterolateral fusion (rarely previously studied) were satisfactory for >80 % of patients, but varied among groups.     

Incidence of osteotomies around the knee for the treatment of knee osteoarthritis: A 22-year population-based study

Purpose

Both tibial and femoral osteotomies have been used for the treatment of knee osteoarthritis (OA). Due to the clinical success of total knee arthroplasty (TKA) the current role and incidence of osteotomies remains unknown. The aim of this population-based study was to assess the incidence of osteotomies and compare it with that of knee arthroplasties.

Methods

From the Finnish National Hospital Discharge Register, we identified all patients, aged 18 years or more, who had undergone osteotomy for the treatment of knee OA between 1987 and 2008. The number of arthroplasties was extracted from the Arthroplasty Register.

Results

A total of 6,004 osteotomies were performed for 5,734 patients. The average osteotomy incidence has steadily decreased by 6.2%, and TKA incidence has increased by 9.8% annually. However, in patients aged less than 50 years the osteotomy incidence has increased by 1.4% annually. The decline of osteotomy incidence has been steeper in females than in males (9.0% vs. 3.6%), and during the last decade osteotomies were more commonly performed in male patients.

Conclusion

Incidence of osteotomies for the treatment of knee OA has decreased during last two decades. However, in patients aged less than 50 years the osteotomy incidence has slightly increased. In a comparison by gender, females are more likely to undergo arthoplasty than osteotomy, and it would therefore appear that the current use of osteotomies is predominantly reserved for the treatment of knee OA in relatively young males.