Bovine pericardial bioprosthesis in mitral position. A ten-year follow-up

BACKGROUND: The pericardial bovine prosthesis Pericarbon should offer some advantages in comparison with the former generations, because its development is focused on solving previous problems and resulted in the variation of the pericardial fixation method, of valve structure and of stent coating. This hypothesis was evaluated through a retrospective follow-up. METHODS: Between 1985 and 1989, 78 Pericarbon prostheses O 29 were implanted in mitral position by the same surgeon. All patients received warfarin for the first three months to maintain an International Normalized Ratio between 2.5 and 3.5; after which they received antiaggregant therapy indefinitely. With an average follow-up period of 7.34 years for a total of 573 patient-years, we evaluated perioperative and late mortality, late morbidity (thromboembolic and haemorrhagic events, reoperations, primary tissue failures, endocarditic events) and patient clinical conditions. RESULTS: Perioperative mortality was 1.28% (1/78), late mortality was 11.6% (9/77) with 5 valve-related deaths. 5-year survival was 93% and 10-year survival 97%. Fifteen patients required reoperation for prosthetic replacement, fourteen for primary tissue failure. There were ten minor thromboembolic events, one major event, one haemorrhage and one prosthetic endocarditis (the last two with patient exitus). After 10 years (75% of patients were in New York Heart Association class I-II. CONCLUSIONS: Besides the known better haemodynamic performance, Pericarbon bioprosthesis seems to present a survival and redofreedom curve comparable to the best porcine prosthesis, with less incidence of endocarditis, thromboembolic events and prosthesis leakage.     

Activation of factor XI in plasma is dependent on factor XII [see comments]

The activation of factor XI initiates the intrinsic coagulation pathway. Until recently it was believed that the main activator of factor XI is factor XIIa in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface. Two recent reports have presented evidence that in a purified system factor XI is activatable by thrombin together with the soluble polyanion dextran sulfate. To assess the physiological relevance of these findings we studied the activation of factor XI in normal and factor XII-deficient plasma. We used either kaolin/cephalin or dextran sulfate as a surface for the intrinsic coagulation pathway, tissue factor to generate thrombin via the extrinsic pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is rapidly cleaved on incubation with kaolin. The kinetics appear to be exponential with half the maximum cleavage at 5 minutes. Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. Tissue factor (1:500) added to plasma did not induce cleavage of factor XI during a 90-minute incubation, although fibrin formation within 30 seconds indicated that thrombin was generated via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to 50% prothrombin activation) directly to factor XII deficient or normal plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to instantaneous fibrinogen cleavage, but again no cleavage of factor XI was observable. We conclude that in plasma surroundings factor XI is not activated by thrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable.     

A miRNA signature for defining aggressive phenotype and prognosis in gliomas

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA （miRNA） profile of 8 WHO grade II gliomas and 24 higher grade tumours （2 WHO grade III and 22 glioblastomas） by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method （RT-qPCR） with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas （TCGA） datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients＇groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme （GBM） and Lower Grade Glioma （LGG） datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses （ HR 1.19, P = O. 04, and HR 1.18, P = 0. 029 respectively）. Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.     

Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

Desmoplastic fibroma of the proximal ulna

A young man presented with desmoplastic fibroma in the proximal ulna. This rare tumour was treated by curettage and bone grafting.     

Postprandial hyperglycemia and hyperlipidemia-generated glycoxidative stress: its contribution to the pathogenesis of diabetes complications

Postprandial glucose and triglyceride increments after a mixed meal are more prolonged in people with type 1 and 2 diabetes or with impaired glucose tolerance than in normal individuals. Evidence in the literature suggests that these transient increases represent an additional and independent risk for chronic hyperglycemia to induce endothelial dysfunction, an important fact for the development of diabetic vascular complications. This article presents the more relevant mechanisms by which acute postprandial hyperglycemia and hyperlipidemia have been proved to determine the risk of reactive oxygen species overproduction, an increased synthesis of non enzymatic early-glycated and nitrated proteins, and a more atherogenic lipoprotein profile. Recent recommendations suggest that care for this transient glycoxidative stress should be associated with fasting glucose or HbA1c care, to reduce the risk of macro- and microvascular complications in people with diabetes.     

Role of interceptive orthodontics in early mixed dentition

Early orthodontic interventions are often initiated in the developing dentition to promote favourable developmental changes and remove or suppress those that are unfavourable. Early interceptive orthodontics can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. It also improves self-esteem in the subjects and parental satisfaction. Early detection and appropriate referral of cases requiring interceptive orthodontics are important. However, lack of awareness among school children, parents and primary-care personnel (dental nurses and dental officers) may result in patients not being referred for timely interceptive intervention. This article presents a general view of the scope of interceptive orthodontics that can be carried out in early mixed dentition, i.e. when the permanent incisors and molars are erupting into the oral cavity.