Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Doppler echocardiography of 119 normal-functioning St Jude Medical mitral valve prostheses: a comprehensive assessment including time-velocity integral ratio and prosthesis performance index.

The purpose of this study was to provide, in a large number of patients, comprehensive Doppler echocardiographic assessment of normal St Jude Medical mitral valve prosthesis function using Doppler-derived hemodynamic variables, including the mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio and prosthesis performance index. The pressure half-time was less than 130 milliseconds in all patients, and all but one patient had either a peak early mitral diastolic velocity of 2 m/s or less or a mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio of less than 2.2. There was a significant (P < .001) negative correlation between the prosthesis performance index and prosthesis size. This negative correlation suggests that there is more efficient use of the in vitro geometric orifice area with smaller prostheses.     

Correlating digit span performance and event-related potentials to assess working memory.

Event-related brain potentials (ERPs) were recorded during a computerized and modified version of the Digit Span Backwards (DB) task from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). The modified DB version (ERP-DB task) was divided into two sections of 2, 4, 6 and 8 digits in length (Group 1) and 3, 5 and 7 digits in length (Group 2). Each trial had a study phase and a test phase. For the study phase, a series of digits was presented sequentially and aurally to 20 participants (10 for each group). For the test phase, a second series of digits was also presented sequentially and aurally that either corresponded to the reverse order of the digits in the study phase (correct condition) or had one digit in the sequence replaced by an incorrect digit (incorrect condition). The traditional DB task of the WAIS-III was also administered for comparison purposes. A prolonged positive slow wave (PSW) peaking between 450 and 750 ms was elicited to incorrect condition trials. For each participant, a derived measure was calculated from the ERP differentiation between correct and incorrect conditions. The derived measure was defined as the mean of the t-values obtained from the correct and incorrect waveform comparison, within the temporal interval that encompassed this component. The strongest statistical correlations between the derived measure and the traditional DB test scores were found at the Pz site (Group 1: r=0.79; Group 2: r=0.59). This statistical approach shows that it is possible to adequately relate an individual's performance on a traditional measure of working memory and ERP patterns. Overall, we believe that this kind of ERP approach holds promise as a technique for assessing quantitatively non-communicative patients.     

Asthma inhalers and subsurface enamel demineralisation: an in situ pilot study.

AIM: The purpose of this pilot study was to identify the subsurface enamel demineralising potential of two possible acidogenic lactose-based powders and their corresponding generic pump inhalers. METHODS: Ten healthy non-asthmatic adults participated in a 5- leg randomised crossover study including a 10% sucrose control. A twice-daily 400 microg dose of inhaler was applied in vitro to a demineralised enamel slab on the buccal flange of a mandibular removable appliance before in situ placement for 14 days each. Lesion parameters were determined using transverse microradiography and digitised image analysis. RESULTS: Minimal demineralisation occurred with sucrose, both pump and one powder inhaler. The remaining powder was associated with remineralisation (p = 0.29). Overall, mean lesion depth increased (p = 0.12). CONCLUSION: Asthma inhalers failed to demonstrate a significant acidogenic/cariogenic effect.     

Endometrial stromal neoplasms are immunoreactive with WT-1 antibody.

WT-1 positivity has previously been noted in nonneoplastic endometrial stroma. In this study we examined WT-1 expression in endometrial stromal neoplasms to ascertain whether these tumors are immunoreactive and whether this antibody might be of value in the diagnosis of these lesions. We also stained cases of cellular and highly cellular leiomyomas to investigate whether WT-1 might be of value in distinguishing these from an endometrial stromal neoplasm. We compared WT-1 staining with CD10, desmin, alpha smooth muscle actin, h-caldesmon, and AE1/3, many of these antibodies being commonly used to distinguish between an endometrial stromal and a smooth muscle phenotype. Cases of ESN (n = 5), low grade ESS (n = 14), and cellular or highly cellular leiomyoma (n = 14) were stained with the aforementioned antibodies. Cases were scored on a scale of 0 to 4+, with 4+ cases exhibiting positivity of >50% of cells. Sixteen of 19 endometrial stromal neoplasms were positive with WT-1, most (14 of 16) with 4+ positivity. Staining was nuclear (5 cases), cytoplasmic (5 cases), or combined nuclear and cytoplasmic (6 cases). All endometrial stromal neoplasms exhibited 4+ staining with CD10. Staining for alpha smooth muscle actin was present in most cases (14 of 19) and desmin and h-caldesmon were positive in a smaller number of cases (8 and 2 respectively). There was 4+ positivity with desmin in only 1 case. The 2 cases that were h-caldesmon positive both exhibited 1+ staining (<5% cells positive). Six cases were positive with AE1/3, 1 with 4+ staining. Leiomyomatous neoplasms always exhibited 4+ staining with desmin and alpha smooth muscle actin and in most cases (12 of 14) with h-caldesmon. The other 2 cases exhibited 2+ positivity. Most cases (12 of 14) were positive with WT-1 (7 of 14 with 4+ staining) and CD10 (5 of 14 with 4+ positivity). One case was positive with AE1/3. We conclude that diffuse WT-1 positivity is characteristic of endometrial stromal neoplasms and that this may be of value in diagnosis. However, WT-1 is of limited use in the distinction between an endometrial stromal and a cellular leiomyomatous neoplasm because many of the latter are also positive. This study confirms the value of h-caldesmon in the distinction between an endometrial stromal neoplasm (almost always h-caldesmon negative) and a cellular leiomyomatous neoplasm (h-caldesmon positive). Although CD10 is positive in endometrial stromal neoplasms, the commonly observed immunoreactivity of cellular and highly cellular leiomyomas with this antibody limits its diagnostic usefulness. Desmin is useful as all leiomyomatous neoplasms exhibited diffuse positivity, whereas only a small number of endometrial stromal neoplasms were focally positive and only 1 case exhibited 4+ positivity. Smooth muscle actin is of limited value since most neoplasms studied were positive. The overlapping immunophenotype of endometrial stromal and leiomyomatous neoplasms may reflect the origin of both cell types from a common progenitor within the uterus.     

Neural tube defects in rural Ireland.

The incidence of neural tube defects in a rural area of the west of Ireland from 1974 to 1985 was 2.96 per 1000. The prevalence was unchanged during the 11 years. When compared with a control group there was no increased incidence of anaemia in mothers of affected infants.     

Production of epidermal growth factor and transforming growth factor-alpha by the androgen-responsive LNCaP human prostate cancer cell line

Epidermal growth factor (EGF)-related polypeptides may be involved in the growth of human prostate cancer cells, and in the androgen stimulation of hormone-responsive prostatic carcinomas. We have shown that androgen-responsive LNCaP cells, like the autonomous DU 145 human prostate cancer cell line, synthesize and secrete EGF and related polypeptides, including immunoreactive transforming growth factor-alpha (TGF-alpha). As determined by radioimmunoassay, intracellular EGF levels were approximately 100 times those of TGF-alpha, but together these accounted for less than half of the total EGF-like polypeptides detected in a radioreceptor assay. Although LNCaP cell growth was stimulated by dihydrotestosterone (DHT), there was no evident effect on immunoreactive EGF levels in the medium after correction for cell number. Moreover, metabolic labeling experiments showed no effect of the androgen on EGF synthesis by LNCaP cells. Gel filtration chromatography of conditioned medium showed both high molecular weight species and the mature 6,000 dalton form of immunoreactive EGF. We conclude that although LNCaP prostate cancer cell growth is stimulated by DHT, it is unlikely that it is mediated directly via increased EGF synthesis by the tumor cells.     

Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.