The Cryolife-O''Brien Stentless Aortic Porcine Xenograft Valve

BACKGROUND: The advantageous design of the Cryolife-O'Brien stentless porcine aortic valve permits specific quick, easy, supravalvular implantation using single layer continuous 3-0 polypropylene suture. The advantages, contraindications, and implantation errors to avoid are detailed. The use of this valve for aortic valve replacement in the elderly population has been directed to proving its efficacy and establishing its grounds for durability while maintaining all of the advantages of a stentless tissue valve. METHODS: From December 1992 to September 1998, this valve was used in 240 patients (mean age 73 years: 15% > 80 years), 45% receiving associated coronary artery grafting (2.4 grafts per patient). Left ventricular (LV) myomectomy was necessary in 12% of patients. Detailed postoperative follow-up (100%) analysis included 650 serial echocardiographic studies. RESULTS: The 30-day mortality was low at 1.2% (3 deaths of 240 elderly patients). Ten patients had late mortality (1.5 months to 5 years), all nonvalve related. No structural failure and one only explant for endocarditis have occurred. Echocardiographic analyses have shown low mean transvalvular gradients in relationship to time (8.18 mmHg at 18 months) and to valve size (8.52 mmHg for a 23-mm host aortic annulus). Incompetence has been zero or a trace in 97% of the patients at 21/2 years. No patient over the 6 years shows valve deterioration. CONCLUSION: Six years of experience with this stentless valve in 240 elderly patients has revealed the many advantages of this safe, composite, and truly stentless device that is assembled without the need for Dacron support. Excellent sustained hemodynamics with low gradients, minimal regurgitation, and a good effective orifice have been coupled with low immediate mortality, no intrinsic valve failure, and one explant for endocarditis. Marked LV regression and minimal late valve-related complications confirm the safety and advantages of this stentless valve.     

Innate resistance of mice to Salmonella typhi infection.

The basis for the natural resistance of mice to Salmonella typhi was examined. In contrast to Salmonella typhimurium, the virulence of S. typhi for mice was independent of the mouse strain and was not affected by inactivation of murine macrophages with silica. However, mice were more susceptible to S. typhi when given iron alone or iron and an iron chelator. The results suggest that the failure of S. typhi to undergo net growth in murine tissues reflects an inability of the bacterium to multiply rather than rapid killing by resident macrophages.     

Hodgkin''s disease: a flow cytometric study.

Flow cytometry was performed on paraffin embedded tissue from 115 cases of Hodgkin's disease. Thirteen (11%) tumours were aneuploid with no significant difference between the histological subgroups. The median proliferative index was 14%, and the highest values were found in the NS2 (16.4%) and lymphocyte depleted (16.0%) subgroups. The difference in proliferative index approached significance when the NS2 subgroup was compared with the NS1 subgroup (p less than or equal to 0.11) and when the lymphocyte depleted and NS2 subgroups combined were compared with the mixed cellularity, lymphocyte predominance, and NS1 subgroups combined (p less than or equal to 0.07). There was a trend towards better survival for patients with aneuploid tumours and those cases with a proliferative index below 15%, but neither of these trends was significant.     

Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness

Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G>C and p.Gln589ArgfsX55 [NM_144672.3]) . The pathogenic potential of c.1320 + 5 G>C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild‐type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol‐specific phospholipase C‐induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI‐anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI‐anchorage.     

Effects of palladium addition on emission of mercury vapor from dental amalgam

OBJECTIVES: The purpose of this investigation was to test the hypothesis that palladium causes a reduction in mercury emission when added to dental amalgam during condensation. METHODS: Mercury vapor release was measured in a closed bottle system and an Intraoral Flow device(IOF). Conventional amalgam restorations were modified by addition of various palladium pellets. 1.57 mm diameter palladium pellets with different porosities were fabricated. These pellets were then placed in amalgam restoration using typical condensation and carving procedures. The samples were stored in a closed bottle and mercury measurements were taken from the bottles at 30 min, 1, 3, 5, 24 and 48 h and 7 days after trituration using a Jerome 411 Mercury Vapor Analyzer (Arizona Instrument Corp., Jerome, AZ). The palladium pellets identified as the most effective in mercury vapor reduction were further tested in an IOF device. Data were analyzed by two-way ANOVA followed by Tukey HSD pairwise analysis for significant findings (alpha = 0.05). RESULTS: The palladium containing amalgams when tested in the closed bottle system yielded significantly lower (p < 0.05) mercury vapor release than the controls. Pellets fabricated with the highest porosity yielded the greatest reduction in overall mercury vapor release. In the IOF device the overall amount of mercury vapor released from the palladium containing amalgams was also significantly less than the control (p < 0.05). SIGNIFICANCE: Mercury vapor emission from dental amalgam was greatly reduced by adding palladium pellets to amalgam during condensation. These techniques require only slight modifications of the standard operative procedures.     

INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis

AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep~(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep~(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH.     

DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith–Wiedemann syndrome

Tierling S, Souren NY, Reither S, Zang KD, Meng‐Hentschel J, Leitner D, Oehl‐Jaschkowitz B, Walter J. DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith–Wiedemann syndrome. Beckwith–Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood‐specific hypomethylation phenotype most probably caused by a feto‐fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome.     

Young and vulnerable: Spatial-temporal trends and risk factors for infant mortality in rural South Africa (Agincourt), 1992-2007

Background

By 2025, it is estimated that approximately 1.8 million Australian adults (approximately 8.4% of the adult population) will have diabetes, with the majority having type 2 diabetes. Weight management via improved physical activity and diet is the cornerstone of type 2 diabetes management. However, the majority of weight loss trials in diabetes have evaluated short-term, intensive clinic-based interventions that, while producing short-term outcomes, have failed to address issues of maintenance and broad population reach. Telephone-delivered interventions have the potential to address these gaps.

Methods/Design

Using a two-arm randomised controlled design, this study will evaluate an 18-month, telephone-delivered, behavioural weight loss intervention focussing on physical activity, diet and behavioural therapy, versus usual care, with follow-up at 24 months. Three-hundred adult participants, aged 20-75 years, with type 2 diabetes, will be recruited from 10 general practices via electronic medical records search. The Social-Cognitive Theory driven intervention involves a six-month intensive phase (4 weekly calls and 11 fortnightly calls) and a 12-month maintenance phase (one call per month). Primary outcomes, assessed at 6, 18 and 24 months, are: weight loss, physical activity, and glycaemic control (HbA1c), with weight loss and physical activity also measured at 12 months. Incremental cost-effectiveness will also be examined. Study recruitment began in February 2009, with final data collection expected by February 2013.

Discussion

This is the first study to evaluate the telephone as the primary method of delivering a behavioural weight loss intervention in type 2 diabetes. The evaluation of maintenance outcomes (6 months following the end of intervention), the use of accelerometers to objectively measure physical activity, and the inclusion of a cost-effectiveness analysis will advance the science of broad reach approaches to weight control and health behaviour change, and will build the evidence base needed to advocate for the translation of this work into population health practice.

Trial Registration

ACTRN12608000203358     

Predictors of successful labor induction with oral or vaginal misoprostol

Objective: To identify independent predictors of successful labor induction with oral or vaginal misoprostol.

Methods: Women enrolled in four previous randomized trials involving oral or vaginal misoprostol for cervical ripening and labor induction were included in the present cohort study, with dosing of 25–50?μg every 4 to 6?h vaginally (n?=?574) or 50?μg every 4?h orally (n?=?207). Multiple logistic regression was performed to identify factors independently associated with successful labor induction – defined as vaginal delivery within 12?h, vaginal delivery within 24?h and spontaneous vaginal delivery. Predictors of Cesarean birth and the need for only one dose of misoprostol were also identified. Variables included in the models were maternal age, weight, height, parity, gravidity, membrane status, route of misoprostol, gestational age, birth weight, and Bishop score and its individual components.

Results: Maternal age, height, weight, parity, birth weight, dilatation, effacement and cervical station were associated with vaginal delivery within 24?h of induction. Maternal age, height, weight, nulliparity, birth weight and route of misoprostol were associated with Cesarean birth, with oral misoprostol being associated with a lower rate of Cesarean birth. The need for only one dose of misoprostol was predicted by maternal height, weight, parity, gestational age, Bishop score and route of misoprostol.

Conclusion: Characteristics of the woman (height, weight, parity), the fetus (birth weight) and some of the individual components of the Bishop score, were associated with successful labor induction, with oral misoprostol being associated with a lower rate of Cesarean birth.