Dextran/aspirin versus heparin/dihydroergotamine in preventing thrombosis after hip fractures

In a randomised trial we compared the effects of two different antithrombotic regimens on the incidence of venographically established deep venous thrombosis (DVT) in 83 patients undergoing surgery for fracture of the femoral neck. Group A received dextran 40 peroperatively plus 0.5 g aspirin a day beginning before operation and continuing for 10 days after. Group B received heparin calcium 5000 iu subcutaneously plus dihydroergotamine (DHE) 0.5 mg intramuscularly, given 8-hourly, beginning before operation and continuing for 10 days after. Two patients in Group A and three in Group B developed proximal DVT, while the incidence of all DVT was 33% in Group A and 29% in Group B, a difference which was not significant. Haemorrhagic complications were much more common in the dextran/aspirin group: the volume of drainage fluid, the number of patients transfused and quantity of blood transfused, and the drop in haemoglobin level were all significantly greater in Group A. We conclude that the DHE/heparin regime is preferable to dextran/aspirin because it is safer and no less effective.     

Characterization of an epithelial, nearly diploid liver cell strain, from Chinese hamster, able to activate promutagens

Epithelial liver cells of the Chinese hamster (CHEL cells) werepropagated in culture for 35 passages. At favourable cell densities,the population doubling time in normal medium, was 20 h. L-Tyrosineamino transferase activity was retained at a measurable level,but its enhancement by dexamethasone was detected solely incells of early passages. Pyruvate kinase was strongly activatedby fructose-1,6-biphosphate at low substrate concentrations.These enzymatic properties suggest that the CHEL cells are derivedfrom a sub-population of parenchymal hepatocytes or from cellsclosely related to parenchymal hepatocytes. With a lag periodof a few hours, CHEL cultures metabolized benzo[a]pyrene. Incell homogenates the various monooxygenase activities investigatedwere below the detection limits. However, other xenobiotic—metabolizingactivities, such as cytochrome P-450 reductase, glutathionetransferase and UDP-glucuronosyl-transferase were high, withlevels comparable to those observed in freshly isolated ratparenchymal cells. Epoxide hydrolase activity was also detected,but was lower than in the liver. The CHEL cells were able toactivate benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene andaflatoxin B₁ to mutagens, as shown in a co-culture assay withV79 cells, in which acquisition of resistance to 6-thioguaninewas studied. At early passages, the CHEL cells had a near diploidset of chromosomes. Then, gradually the frequency of cells withslight changes in the number of chromosomes and the frequencyof tetraploids were increased. During the observation period(up to passage 20) the modal number of chromosomes shifted from22 to 23. No gross morphological changes in the cultures werenoticed during the 20 passages. However, the cloning efficiencyin normal medium was increased from 1% initially to 9%. In conditionedmedium, CHEL cells, even those of early passages, showed enhancedgrowth rates and cloning efficiencies of up to 60%. The former,but not the latter, effect was partially mimicked by the additionof insulin and epidermal growth factor to normal medium. CHELcells may be useful as indicator cells in mutagenicity experimentsas they (i) have a relatively stable karyotype consisting of 22 chromosomes; (ii) grow well in culture, even at clonal densities(in conditioned medium) and (iii) have retained various xenobiotic—metabolizingactivities. They may also be potentially useful in the studyof regulatory phenomena in the hepatic metabolism of endogenouscompounds, as well as acting as a model system for malignanttransformation of epithelial cells. ²To whom correspondence should be addressed     

Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab

Rituximab is a chimeric monoclonal antibody reacting with the CD20 antigen on B cells. It has been proposed as treatment for the idiopathic nephrotic syndrome, recurrent idiopathic nephropathy, and focal segmental glomerulosclerosis refractory to steroids. Rituximab influences T-cell immunity and may predispose the patients to opportunistic infections, such as progressive multifocal leukoencephalopathy caused by the polyomavirus JC (JCV). The risk of latent viruses infections/reactivations in pediatric patients receiving monoclonal antibodies is not well known yet. In this longitudinal 6-month study, the effects of rituximab on JCV and BK virus (BKV) replication have been investigated. Blood, serum, and urine samples have been collected monthly from 11 pediatric patients (mean age: 11 years) with the idiopathic nephrotic syndrome and recurrent idiopathic nephropathy, under rituximab therapy. JCV and BKV real-time PCRs and sequencing of the viral protein 1 and the non-coding control region have been conducted. The same investigations have been undertaken on samples collected from eight pediatric patients (controls, mean age: 6 years), with idiopathic nephrotic syndrome or focal segmental glomerulosclerosis, treated with conventional chemotherapy. JCV was detected in the urine of one patient (9%), and one control (12.5%); BKV was found in the urine of 7/11 patients (63.6%) and 2/8 controls (25%) and in blood samples from four patients. No significant difference was found in the mean viral loads and in the viral molecular characterizations between the two groups. The polyomaviruses replication was not associated with rituximab therapy in children.     

Lymphoid enhancer binding factor-1 (LEF1) expression as a prognostic factor in adult acute promyelocytic leukemia

Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/ β-catenin signaling pathway. High LEF1 expression has been reported as a prognostic marker in hematologic malignancies. We evaluated the prognostic significance of LEF1 expression in 78 adult acute promyelocytic leukemia (APL) patients. APL samples were dichotomized at the median value and divided into: LEF1^low and LEF1^high. LEF1^high patients had lower WBC counts at baseline and were less likely to carry a FLT3 -ITD than LEF1^low patients. Early death occurred only in the LEF1^low group. Moreover, LEF1^low expression was associated with a high Sanz score. Survival analysis of 61 APL patients < 60 years revealed that the LEF1^high group had a significantly longer overall survival (OS). Cox analysis for OS confirmed only LEF1 expression as an independent prognostic factor. Of the 17 patients over the age of 60, those in the LEF1^high group showed a higher median survival. In silico analysis identified 9 differentially expressed, up-modulated genes associated with a high expression of LEF1; the majority of these genes is involved in the regulation of apoptosis. Our study provides evidence that LEF1 expression is an independent prognostic factor in APL, and could be used in patients risk stratification.     

Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence

The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We have shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR_84-95), drives cell migration and angiogenesis in a protease-independent manner. This study is aimed at defining the contribution of uPAR_84-95 sequence to invasion of ovarian cancer cells. Now, we provide evidence that the ability of uPAR-expressing ovarian cancer cells to cross extra-cellular matrix and mesothelial monolayers is prevented by specific inhibitors of PAR_84-95 sequence. To specifically investigate uPAR_84-95 function, uPAR-negative CHO-K1 cells were stably transfected with cDNAs coding for uPAR D2 and D3 regions and exposing (uPARD2D3) or lacking (uPARΔD2D3) the 84–95 sequence. CHO-K1/D2D3 cells were able to cross matrigel, mesothelial and endothelial monolayers more efficiently than CHO-K1/ΔD2D3 cells, which behave as CHO-K1 control cells. When orthotopically implanted in nude mice, tumor nodules generated by CHO-K1/D2D3 cells spreading to peritoneal cavity were more numerous as compared to CHO-K1/ΔD2D3 cells. Ovarian tumor size and intra-tumoral microvessel density were significantly reduced in the absence of uPAR_84-95. Our results indicate that cell associated uPAR promotes growth and abdominal dissemination of ovarian cancer cells mainly through its uPAR_84-95 sequence.     

C-reactive protein as a marker for cardiac ischemic events in the year after a first, uncomplicated myocardial infarction

The prognostic role of C-reactive protein levels in patients with a first acute myocardial infarction, an uncomplicated in-hospital course, and the absence of residual ischemia on a predischarge ergometer test and with an echocardiographic ejection fraction ≥50% has not been described. C-reactive protein was determined during hospitalization in 64 patients (55 men, mean age 64.6 ± 10.4 years). The patients were followed up for 13 ± 4 months and the following cardiac events were recorded: cardiac death, new-onset angina pectoris, and recurrent myocardial infarction. Patients who developed cardiac events during the follow-up period had significantly higher C-reactive protein values than patients without events (3.61 ± 2.83 vs 1.48 ± 2.07 mg/dl, p <0.001). The probability of cumulative end points was: 6%, 12%, 31%, and 56% (p = 0.006; RR 3.55; confidence interval 1.56 to 8.04), respectively, in patients stratified by quartiles of C-reactive protein (<0.45, 0.45 to 0.93, 0.93 to 2.55 and >2.55 mg/dl). In the Cox regression model, only increased C-reactive protein levels were independently related to the incidence of subsequent cardiac events (chi-square 9.8, p = 0.001). Thus, increased C-reactive protein levels are associated with a worse outcome among patients with a first acute myocardial infarction, an uncomplicated in-hospital course without residual ischemia on the ergometer test, and with normal left ventricular function.     

Nutraceuticals and Prevention of Atherosclerosis: Focus on ω‐3 Polyunsaturated Fatty Acids and Mediterranean Diet Polyphenols

Nutraceuticals are potentially healthful foods that play a role in maintaining human well being, enhancing health and preventing, or even treating, specific diseases. More than for any other diseases, cardiovascular diseases occur in association with risk factors that are amenable to prevention or treatment by nutraceutical interventions. Several ingredients marketed for use in dietary supplements address such risk factors. The ability of nutraceuticals to favorably influence cardiovascular risk factors and atherosclerotic vascular disease should be recognized as an enormous opportunity for the prevention or treatment of this common condition. In this review, we attempt at summarizing some of the recent research findings on ω‐3‐polyunsaturated fatty acids and antioxidant polyphenols that have beneficial cardiovascular effects to update the practicing clinicians on the potential benefits of nutraceuticals in this area.