Abstract
Background
There is increasing Interest in bio-prosthetic MVD as recent advances in transcatheter MV interventions, but there is limited data.
Objectives
The aim of this study was to ...identify the factors determining mitral valve (MV) dysfunction (MVD) in patients who underwent MV replacement with bio-prosthetic valves. Also, we sought to investigate clinical outcomes in patients with bio-prosthetic MVD.
Methods
A total of 233 patients underwent surgical bio-prosthetic MV replacement between June 1996 and May 2015. Finally, 226 patients (mean age 66.9±11.5 years, 74.3% of women) were analyzed, excluding patients who followed-up for less than 5 years and patients whose baseline or follow-up echocardiography could not be analyzed. Clinical, echocardiographic, and laboratory data were collected early after the surgery and during follow-up. MVD was defined as an increase in mean gradient ≥5 mmHg with leaflet motion limitation and/or newly developed MV regurgitation during follow-up. Clinical outcome was defined as a composite of cardiovascular death, redo MV surgery or intervention, and hospitalization for heart failure.
Results
During a median of 102.0 months (interquartile range 72.0 to 132.0 months), 65 patients (28.8%) revealed MVD. 8 (12.3%) patients revealed predominant MV obstruction, and 57 (87.7%) showed predominant MV regurgitation. Factors associated with bio-prosthetic MVD by multivariate regression analysis were young age at operation (hazard ratio 0.97, 95% CI 0.95–0.99, p=0.001), end-stage renal disease (hazard ratio 4.29, 95% CI 1.45–12.71, p=0.007), elevated mean diastolic pressure gradient>5.5 mmHg across the bio-prosthetic MV early after operation (hazard ratio 1.86, 95% CI 0.97–3.74, p=0.063) and anemia after operation (hazard ratio 0.84, 95% CI 0.74–0.95, p=0.007). However, the presence of hypertension, dyslipidemia, or porcine bio-prosthesis was not related to the bio-prosthetic MVD. Kaplan-Meier curves revealed significant differences in event-free survivals for the occurrence of bio-prosthetic MVD according to each factor (Figure 1). Patients with bio-prosthetic MVD showed significantly poor clinical outcomes compared with those without bio-prosthetic MVD (event-free survival 43.1% vs. 91.9%, log-rank p<0.001) during the follow-up.
Conclusions
Young age at operation, end-stage renal disease, elevated mean pressure gradient early after the operation, and anemia after operation were associated with bio-prosthetic MVD in patients who underwent bio-prosthetic MV replacement.
Funding Acknowledgement
Type of funding sources: None.
Epidermal growth factor receptor (EGFR) signaling has been implicated in the genesis and progression of cholangiocarcinoma. However, the characteristics of EGFR signaling in cholangiocarcinoma cells ...have not been characterized. Thus, we attempted to more fully characterize EGF/EGFR signaling in human cholangiocarcinoma cells.
EGFR phosphorylation and ubiquitination were evaluated using immunoblot techniques. EGFR internalization was analyzed by immunofluorescent staining of EGFR or by immunoblot analysis for biotinylated EGFR. Cell growth was assessed using the MTS assay.
EGFR activation was sustained following EGF stimulation in cholangiocarcinoma cells as compared to hepatoma cells. This prolonged EGFR activation resulted in extended p42/44 MAPK activation in cholangiocarcinoma cells. Despite ubiquitination, EGFR activation-dependent internalization was defective in cholangiocarcinoma cells. Cell growth was increased in cholangiocarcinoma cells following EGF stimulation as compared to hepatoma cells, and this was significantly attenuated by EGFR kinase inhibitors. The EGFR kinase inhibitors also significantly decreased COX-2 expression in cholangiocarcinoma cells, while this was not evident in hepatoma cells.
The results demonstrate that cholangiocarcinoma cells exhibit sustained EGFR activation due to defective receptor internalization. As EGFR kinase inhibitors effectively attenuated cellular growth, these agents may be therapeutically efficacious in human cholangiocarcinoma.
Piroxicam can be ionized as a zwitterion that has two pKa values (pKa
1
=
1.86 and pKa
2
=
5.46). Consequently, piroxicam has a low solubility in both polar and nonpolar media, and a low ...lipophilicity, which results in a low permeability. Three piroxicam-ethanolamine salts were prepared, which had a higher area under the curve (AUC) than piroxicam. There were minimal differences in the AUC among the salt forms. It was reported that the piroxicam triethanolamine salt had a lower permeability across the skin than piroxicam but it had a higher oral bioavailability. Piroxicam monoethanolamine showed the highest
C
max followed by piroxicam diethanolamine and piroxicam triethanolamine. The dissolution rates of piroxicam and its salts were similar at pH 1.2. Piroxicam monoethanolamine showed the highest dissolution rate at pH 6.8, which was followed by the piroxicam diethanolamine and piroxicam triethanolamine salts. The order of dissolution rate at pH 6.8 matched the order of
C
max or the AUC after oral administration.
The authors conducted an analysis of prognostic factors for patient survival and local control of brain metastases after gamma knife radiosurgery.
In the survival analysis, 53 consecutive patients ...with 121 lesions treated in the last 2 years were examined. Common primary sites were lung (26 patients), kidney (seven), breast (three), and colon (three). Patient age ranged from 28 to 75 years (median 58 years) and the female/male ratio was 1:0.9. The median tumor volume was 2.1 cm3 (range 0.02-45.5 cm3) and the average prescription dose was 15.4 Gy to the 50% isodose. The median follow up was 12 months (range 1-23 months) and the median survival was 46 weeks. Six-month and 1-year survival rates were 63% and 39%, respectively. Karnofsky Performance Scale score, tumor volume, and presence of extracranial disease were statistically significant prognostic factors (p < 0.05) for survival in multivariate analysis. Number of lesions, patient age, and adjuvant whole-brain radiation therapy were not statistically significant. Ninety-one of 121 lesions with follow-up images were included in the local control analysis. The 1-year actuarial local control rate was 48%. In multivariate analysis smaller volume was associated with better control (p = 0.0043), and, control period of renal cell carcinoma was shorter than that of the other tumor types (p = 0.0070).
Karnofsky Performance Scale score, tumor volume, controlled primary cancer, and absence of extracranial metastases were associated with longer survival in the present study. For local control, tumor volume was a statistically significant factor.
GATA4 and GATA6 are known to have potential roles in vascular regulation by affecting vascular smooth muscle cell differentiation and atrial natriuretic peptide levels. The aim of this retrospective ...study was to investigate the associations between
and
polymorphisms and bleeding complication risk at a therapeutic international normalized ratio (INR) in patients with mechanical heart valves.
Study patients were included from the Ewha-Severance Treatment (EAST) Group of Warfarin. It consisted of 229 patients who received warfarin therapy after undergoing mechanical heart valve replacement and maintained a stable INR (INR of 2.0-3.0 for at least three consecutive times). Twenty single-nucleotide polymorphisms including
, and
were analyzed. Multivariate logistic regression analysis was employed to investigate the independent risk factors for bleeding complications. To evaluate the potential clinical value of genotyping for preventing bleeding complications in patients with high-risk genotype, the number needed to genotype (NNG) was also calculated.
One hundred forty-two patients were included in this study, 21 of whom had bleeding complications. After adjusting covariates, TT genotype carriers of rs13273672 in
and CC genotype carriers of rs10454095 in
showed 5.0- (95% CI, 1.6-15.7) and 3.1-fold (95% CI, 1.1-8.7) higher bleeding complications than carriers of C allele and T allele, respectively. NNG for preventing one patient from experiencing bleeding complications in patients with TT genotype of rs13273672 and CC genotype of rs10454095 was 22.2 and 17.5, respectively. Patients with both TT genotype in rs13273672 and CC genotype in rs10454095 showed 8.7-fold (95% CI, 1.7-46.1) higher bleeding complications than those with other genotypes. NNG in patients having both TT genotype in rs13273672 and CC genotype in rs10454095 was calculated to be 40.0.
This study showed that
and
gene polymorphisms could affect bleeding complications during warfarin treatment in patients with mechanical heart valves.
We present a possible mechanism of intracerebral peritumoural haemorrhage in meningioma based on the clinical data of three of our cases. A meningioma manifesting intracerebral haemorrhage is ...uncommon and some sporadic case reports have been presented, but without any proven mechanisms. We are presenting three cases of convexity meningioma manifesting spontaneous intracerebral haemorrhage with apoplectiform onset. All three patients had no evidence of bleeding tendency or other predisposing factors for haemorrhage. Preoperative radiological studies showed a solid mass attached to the dura with intracerebral peritumoural haematoma. Total removal of the tumour and haematoma could be achieved in every case. Histological investigation revealed extensive tumour infarction in two cases and fibrosis related to pre-existing ischaemia in the other case. The diagnoses were atypical meningioma in two cases and transitional type in one case. We suggest that extensive tumour infarction might be a cause of spontaneous intracerebral peritumoural haemorrhage in our series of patients.
Biomedical applications of nisin Shin, J.M.; Gwak, J.W.; Kamarajan, P. ...
Journal of applied microbiology,
June 2016, Letnik:
120, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Summary
Nisin is a bacteriocin produced by a group of Gram‐positive bacteria that belongs to Lactococcus and Streptococcus species. Nisin is classified as a Type A (I) lantibiotic that is synthesized ...from mRNA and the translated peptide contains several unusual amino acids due to post‐translational modifications. Over the past few decades, nisin has been used widely as a food biopreservative. Since then, many natural and genetically modified variants of nisin have been identified and studied for their unique antimicrobial properties. Nisin is FDA approved and generally regarded as a safe peptide with recognized potential for clinical use. Over the past two decades the application of nisin has been extended to biomedical fields. Studies have reported that nisin can prevent the growth of drug‐resistant bacterial strains, such as methicillin‐resistant Staphylococcus aureus, Streptococcus pneumoniae, Enterococci and Clostridium difficile. Nisin has now been shown to have antimicrobial activity against both Gram‐positive and Gram‐negative disease‐associated pathogens. Nisin has been reported to have anti‐biofilm properties and can work synergistically in combination with conventional therapeutic drugs. In addition, like host‐defence peptides, nisin may activate the adaptive immune response and have an immunomodulatory role. Increasing evidence indicates that nisin can influence the growth of tumours and exhibit selective cytotoxicity towards cancer cells. Collectively, the application of nisin has advanced beyond its role as a food biopreservative. Thus, this review will describe and compare studies on nisin and provide insight into its future biomedical applications.
PDF
