Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses

We studied the association between CD34 cell dose and transplant outcomes in 359 bone marrow (BM) and 511 peripheral blood stem cell (PBSC) transplant recipients from human leucocyte antigen (HLA)-identical siblings, reported to the International Bone Marrow Transplant Registry (IBMTR). Transplants for leukaemia were performed between 1995 and 1998. Patients were divided into those receiving below or above the median CD34+ dose, for BM (3 x 106/kg) and PBSC (6 x 106/kg) grafts respectively. Cox proportional hazards regression was used to adjust for baseline patient-, disease- and transplant-related characteristics. Analysis of the BM recipients showed that high CD34 cell dose was associated with lower transplant-related mortality [relative risk (RR) = 0.60, P = 0.033] and treatment failure (inverse of leukaemia-free survival, RR = 0.69, P = 0.032). Among PBSC recipients, high CD34 dose was associated with faster recovery of neutrophils to > 0.5 x 109/l (RR = 1.38, P < 0.001) and platelets to > 20 x 109/l (RR = 1.34, P = 0.003), lower risk of relapse (RR = 0.62, P = 0.029) and treatment failure (RR = 0.74, P = 0.03). We conclude that higher CD34 cell doses decrease treatment failure in recipients of HLA-identical sibling BM and PBSC transplants.     

Transforming growth factor alpha may be a physiological regulator of liver regeneration by means of an autocrine mechanism.

We investigated whether transforming growth factor alpha (TGF-alpha) is involved in hepatocyte growth responses both in vivo and in culture. During liver regeneration after partial hepatectomy in rats, TGF-alpha mRNA increased; it reached a maximum (approximately 9-fold higher than normal) at the peak of DNA synthesis. The message and the peptide were localized in hepatocytes and found in higher amounts in hepatocytes obtained from regenerating liver. TGF-alpha caused a 13-fold elevation of DNA synthesis in hepatocytes in primary culture and was slightly more effective than epidermal growth factor. TGF-beta blocked TGF-alpha stimulation when added either simultaneously with TGF-alpha or a day later. TGF-alpha message increased in hepatocytes stimulated to undergo DNA synthesis by TGF-alpha or epidermal growth factor, and the peptide was detected in the culture medium by RIA. In the regenerating liver, the increase in TGF-alpha mRNA during the first day after partial hepatectomy coincided with an increase in epidermal growth factor/TGF-alpha receptor mRNA and a decrease (already reported) in the number of these receptors. We conclude that TGF-alpha may function as a physiological inducer of hepatocyte DNA synthesis during liver regeneration by means of an autocrine mechanism and that its stimulatory effects in this growth process are balanced by the inhibitory action of TGF-beta 1.     

Nonalcoholic fatty liver disease, adiponectin and insulin resistance in dipper and nondipper essential hypertensive patients

OBJECTIVE: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial, and the presence of insulin resistance is recognized as the pathophysiological hallmark of this condition. Arterial hypertension is referred as an insulin-resistant state, and insulin resistance may substantially contribute to the cardiovascular risk in this disorder. We examined the inter-relationship between insulin sensitivity, adiponectin levels, and NAFLD in hypertensive patients with different circadian blood pressure profiles. METHODS: Eighty never-treated patients with essential hypertension were selected for having a nocturnal decrement of blood pressure that was at least 10% (dippers, n=47) or less than 10% (nondippers, n=33) of daytime values. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for hepatic disease. The two groups were similar as to sex, age, and BMI. Abdominal fat distribution and NAFLD were assessed by ultrasonography. RESULTS: Hepatic steatosis was detected in 57.5% of all patients. Nondippers showed a higher prevalence of NAFLD than dippers (81.8 vs. 40.4%, P<0.005). Insulin and the homeostasis model of assessment index were higher (P<0.001) and adiponectin was lower (P<0.001) in nondippers than in dippers, whereas no difference was found in regional fat, liver enzymes, and other metabolic parameters. At multivariate analysis, factors independently associated with nondipping were insulin (P<0.05) and adiponectin (P<0.01) with the homeostasis model of assessment index being of borderline significance. CONCLUSION: In the absence of major risk factors for the development of NAFLD, a high prevalence of liver steatosis was associated with insulin resistance and low adiponectin levels in essential hypertensive patients with a nondipping profile.     

Does washing medical devices before and after use decrease bacterial contamination?: An in vitro study

Surface treatment of medical devices may be a way of avoiding the need for replacement of these devices and the comorbidities associated with infection. The aim of this study was to evaluate whether pre- and postcontamination washing of 2 prostheses with different textures can decrease bacterial contamination.The following microorganisms were evaluated: Staphylococcus aureus, Staphylococcus epidermidis, Proteus mirabilis and Enterococcus faecalis. Silicone and expanded polytetrafluoroethylene vascular prostheses were used and divided into 3 groups: prostheses contaminated; prostheses contaminated and treated before contamination; and prostheses contaminated and treated after contamination. Treatments were performed with antibiotic solution, chlorhexidine and lidocaine. After one week of incubation, the prostheses were sown in culture medium, which was incubated for 48 hours. The area of colony formation was evaluated by fractal dimension, an image analysis tool.The antibiotic solution inhibited the growth of S epidermidis and chlorhexidine decrease in 53% the colonization density for S aureus in for both prostheses in the pre-washing. In postcontamination washing, the antibiotic solution inhibited the growth of all bacteria evaluated; there was a 60% decrease in the colonization density of S aureus and absence of colonization for E faecalis with chlorhexidine; and lidocaine inhibited the growth of S aureus in both prostheses.Antibiotic solution showed the highest efficiency in inhibiting bacterial growth, especially for S epidermidis, in both washings. Lidocaine was able to reduce colonization by S aureus in post-contamination washing, showing that it can be used as an alternative adjuvant treatment in these cases.     

Genetic variation within the ANGPTL4 gene is not associated with metabolic traits in white subjects at an increased risk for type 2 diabetes mellitus

Angiopoietin-like protein 4 (ANGPTL4) represents an adipokine with metabolic effects within adipose tissue, such as inhibition of lipoprotein lipase activity and stimulation of lipolysis. These effects were convincingly demonstrated in mice. Therefore, we asked whether genetic variation within the ANGPTL4 gene contributes to prediabetic phenotypes, such as dyslipidemia, insulin resistance, or beta-cell dysfunction, in white subjects at an increased risk for type 2 diabetes mellitus. We genotyped 629 subjects with and without a family history of diabetes for the 4 single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 and performed correlational analyses with metabolic traits. For metabolic characterization, all subjects underwent an oral glucose tolerance test; a subset was additionally characterized by hyperinsulinemic-euglycemic clamp. The 4 SNPs rs4076317, rs2278236, rs1044250, and rs11672433 cover 100% of common genetic variation (minor allele frequency>or=0.05) within the ANGPTL4 gene (r2>or=0.8). None of these SNPs revealed significant correlation with anthropometric data (sex, age, body mass index, body fat, and waist-hip ratio) or with family history of diabetes. Furthermore, no reliable correlations were found with fasting triglycerides, fasting nonesterified fatty acids, and area under the curve of nonesterified fatty acids during oral glucose tolerance test or with parameters of insulin sensitivity and insulin secretion. Finally, haplotype analysis revealed the existence of 8 common diplotypes. None of these, however, was significantly correlated with insulin sensitivity, insulin secretion, or plasma lipid measures. We conclude that common genetic variation within the ANGPTL4 gene may not play a major role in the development of prediabetic phenotypes in our white population.     

Angiographic and intravascular ultrasound findings of the late catch-up phenomenon after intracoronary beta-radiation for the treatment of in-stent restenosis

We report one-year angiographic and intravascular ultrasound (IVUS) outcomes of in-stent restenosis (ISR) patients treated with intravascular brachytherapy (IVBT). The benefit of IVBT for treating ISR is well documented. However, few data exist on significant angiographic and intravascular ultrasonic in-stent lumen deterioration beyond the habitual 6-month analysis after the index radiation procedure or so-called late catch-up process in the treatment of ISR. Twenty-five consecutive patients with ISR were treated with IVBT using the Beta-Cath System (a 40 mm 90 Sr per 90 gamma source). Quantitative angiographic and IVUS analysis was performed in all of them at 6 and 12 months. IVBT was successful in all patients. Four patients (16%) developed recurrent angiographic binary restenosis at 6-month follow-up, all located within the adjacent reference segments, with 2 being associated with geographical miss. An additional 4 patients (16%) presented with recurrent ISR at 12-month follow-up, all within the stented segment. Significant in-stent lumen loss (0.16 +/- 0.42 mm to 0.34 +/- 0.46 mm; p = 0.008) and in-stent intimal hyperplasia growth (+11.2 +/- 0.48 mm3; p = 0.03) was observed between 6 and 12 months. Intracoronary beta-radiation for the treatment of ISR was associated with significant luminal deterioration (late catch-up) within the stents between 6 and 12 months due to an important late progression of in-stent intimal hyperplasia.     

IMPACT Trial: angiographic and intravascular ultrasound observations of the first human experience with mycophenolic acid-eluting polymer stent system.

The purpose of the study was to examine the safety and efficacy of two different formulations of mycophenolic acid (MPA)-eluting Duraflex stents on coronary de novo lesions. Recent data indicate that local delivery of MPA in the porcine overstretch coronary model significantly reduces neointimal hyperplasia (NIH). Patients were divided into three consecutive groups. The first (n=50) and second (n=55) groups received moderate- and slow-release MPA-eluting Duraflex stent, respectively. The last group (n=50) received the bare metal Duraflex stent. Clinical, angiographic, and intravascular ultrasound analysis were performed at 6-month follow-up. All stents were successfully deployed and patients were discharged home without clinical events. Compared to controls, 6-month in-lesion and in-stent minimum luminal diameter as well as late lumen loss were not significantly different in the moderate- and slow-release treatment groups. At follow-up, percentage obstruction and NIH volume were also similar between the three groups. At 30 days and 6 and 12 months, there were no differences noted between the three groups with respect to major adverse cardiac events as well as the individual rates of mortality, myocardial infarction, or repeat revascularization. There were no cases of subacute or late thrombosis. In this feasibility trial, the MPA-eluting Duraflex stents in either slow- or moderate-release formulations were well tolerated, but showed no benefit for treatment of coronary lesions when compared to controls. Further testing with different drug dosing or delivery rate might improve these results.     

Detection of myocardial iron overload by two-dimensional speckle tracking in patients with beta-thalassaemia major: a combined echocardiographic and T2* segmental CMR study

We aimed to evaluate the role of two-dimensional speckle tracking imaging (2DSTI) in detecting early changes of myocardial deformation in patients affected by thalassemia major (TM) and its relation with myocardial iron overload (MIO) detected by T2* cardiovascular magnetic resonance (CMR). We studied 28 TM patients (15 males, 37.4?±?10 years). All patients underwent CMR and echocardiography in the same day. Segmental and global T2* values were measured. Values of global longitudinal strain (GLS) were derived from the three apical views, while radial and circumferential strain were obtained as average strain from the short axis views at basal, mid and apical level. Six patients (21.4%) showed significant MIO (global heart T2*?<?20 ms). GLS showed a significant correlation with T2* values (R?=??0.49; P?=?0.001) and it was significantly lower in patients with a significant MIO than in those with no significant MIO (?18.3?±?2 vs. ?21.3?±?2.7, P?=?0.02). No significant difference was found for radial and circumferential strain in relation to the severity of MIO. Patients with impaired GLS (<?19.5%) had a significant higher risk of showing significant MIO (Odds-ratio-OR?=?17; 95%). GLS is related with global T2* in TM patients. Moreover, GLS can identify TM patients with severe MIO detected by CMR.     

Temporal Trends Between 2010 and 2015 in Intensity of Care at End-of-Life for Patients With Chronic Illness: Influence of Age Under vs. Over 65 Years

Context

Recent analyses of Medicare data show decreases over time in intensity of end-of-life care. Few studies exist regarding trends in intensity of end-of-life care for those under 65 years of age.