Ventricular Performance After Surgery for a Congenital Heart Defect as Assessed Using Advanced Echocardiography: From Doppler Flow to 3D Echocardiography and Speckle-Tracking Strain Imaging

A varying degree of impairment of ventricular performance is observed over the long-term after surgery for a congenital heart defect (CHD). Impaired ventricular performance has been shown to be of prognostic value for increased risk of cardiovascular events in adult CHD patients. This emphasizes the importance of delineating the timing and cause of this postoperative impairment. Impairment of ventricular performance could develop over time as a consequence of residua, sequelae and complications of the CHD or surgical procedure. Yet, impaired ventricular performance has also been observed immediately after surgery and can persist and/or worsen over time. This postoperative impairment of ventricular performance is the focus of this review. This article provides an overview of echocardiographic techniques currently used to assess ventricular performance. Furthermore, we review current literature describing ventricular performance, as assessed using echocardiography, after correction of a CHD. In general, a decrease in ventricular performance is observed directly after surgery for CHD’s. Subsequent follow-up of ventricular performance is characterized by a varying degree of postoperative recovery. A consistent observation is the persistent impairment of right-ventricular performance after repair in several different subgroups of CHD patients ranging from ventricular septal defect repair to surgery for Tetralogy of Fallot.     

Homologous Recombination Deficiency: Concepts,Definitions, and Assays

BackgroundHomologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.MethodsFriends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.ResultsThis publication provides findings from the group’s discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.ConclusionOverall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.     

The American College of Rheumatology 1990 criteria for the classification of Henoch-Sch?nlein purpura

Criteria for identifying Henoch-Sch?nlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%.     

Gender- and parity-specific reference charts for fetal size in low risk singleton pregnancies at the onset of the third trimester

OBJECTIVES: To determine fetal growth in low risk pregnancies at the beginning of the third trimester and to assess the relative importance of fetal gender and maternal parity. SETTING: Dutch primary care midwifery practice. STUDY DESIGN: Retrospective cohort study on 3641 singleton pregnancies seen at a primary care midwifery center in the Netherlands. Parameters used for analysis were fetal abdominal circumference (AC), fetal head circumference (HC), gestational age, fetal gender and maternal parity. Regression analysis was applied to describe variation in AC and HC with gestational age. Means and standard deviations in the present population were compared with commonly used reference charts. Multiple regression analysis was applied to examine whether gender and parity should be taken into account. RESULTS: The fetal AC and HC increased significantly between the 27th and the 33rd week of pregnancy (AC r2=0.3652, P<0.0001; HC r2=0.3301, P<0.0001). Compared to some curves, our means and standard deviations were significantly smaller (at 30+0 weeks AC mean=258+/-13 mm; HC mean=281+/-14 mm), but corresponded well with other curves. Fetal gender was a significant determinant for both AC (P<0.0001) and HC (P<0.0001). Parity contributed significantly to AC only but the difference was small (beta=0.00464). CONCLUSION: At the beginning of the third trimester, fetal size is associated with fetal gender and, to a lesser extent, with parity. Some fetal growth charts (e.g., Chitty et al.) are more suitable for the low-risk population in the Netherlands than others.     

5-fluorouracil metabolite patterns in viable and necrotic tumor areas of murine colon carcinoma determined by 19F NMR spectroscopy

High-resolution ¹⁹F NMR spectroscopy at 9.4 T was used to study the difference in the metabolite pattern of 5-fluorouracil (5-FU) between viable and necrotic tissues of C38 murine colon tumors grown in C57BI/6 mice. Studies were performed on perchloric acid extracts of these tumor fractions after 5-FU treatment. The ¹⁹F nuclear magnetic resonance spectra exhibited resonances representing 5-FU, the catabolites α-fluoro-β-ureidopropionic acid and α-fluoro-β-alanine, as well as several fluoronucleotide anabolites. The absolute concentrations of anabolites and catabolites and the anabolite-to-catabolite ratio were significantly lower in the necrotic fraction than in the viable tumor fraction 50 min after administration of 5-FU, whereas the absolute concentration of 5-FU was the same. Therefore, in 5-FU metabolism studies with NMR spectroscopy, it is important to consider the necrotic contribution to the tumor volume.     

trans‐resveratrol alone and hydroxystilbenes of rhubarb (Rheum rhaponticum L.) root reduce liver damage induced by chronic ethanol administration: a comparative study in mice

The hepatoprotective effects and pharmacokinetics of trans‐resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied. Ethanol was administered to male BALB/c mice for 35 days in an inhalation chamber. During this time vehicle, trans‐resveratrol (20 mg/kg per day) or R. rhaponticum extract was intraperitoneally (i.p.) administered and mice were sacrificed for the collection of liver and blood. In an additional experiment, the level of parent compounds and metabolites was estimated in the blood after acute i.p. administration of trans‐resveratrol or R. rhaponticum extract. The levels of hydroxystilbenes, their metabolites and fatty acid oxy‐metabolites (oxylipins) were studied by LC‐tandem DAD‐MS/MS. Ethanol induced hepatotoxicity, as evidenced by histological changes and accumulation of oxylipins in the blood. Both trans‐resveratrol and R. rhaponticum extract reduced the extent of these changes. The pharmacokinetics of trans‐resveratrol was characterized by a rapid removal from the blood and metabolism to sulfates and glucuronides. After the administration of R. rhaponticum extract, in addition to trans‐resveratrol glucoside and its metabolites, several other hydroxystilbenes were found. Inhibition of oxidation of polyunsaturated fatty acids is proposed as a basis of the hepatoprotective effect of both trans‐resveratrol and R. rhaponticum extract. Copyright © 2008 John Wiley & Sons, Ltd.     

Role of Sonography and Magnetic Resonance Imaging in Detecting Deltoideal Acromial Enthesopathy

The acromial origin of the deltoid is a target structure of ankylosing spondylitis and related spondyloarthritis, which are often overlooked and underdiagnosed as causes of posterior shoulder pain. The objective of this article is to review the roles of sonography and magnetic resonance imaging in detecting deltoideal acromial enthesopathy and their importance for optimizing management in individuals with posterior shoulder pain. Adequate awareness of such enthesopathy as a potential manifestation of inflammatory rheumatic disorders is critical for early diagnosis of spondyloarthritis.     

The added value of simultaneous EEG and amplitude-integrated EEG recordings in three newborn infants

Amplitude-integrated electroencephalograms (aEEGs) recorded by cerebral function monitors (CFMs) are used increasingly to monitor the cerebral activity of newborn infants with encephalopathy. Recently, new CFM devices became available which also reveal the original EEG signals from the same leads. To date it was unclear whether this single-lead EEG provides additional information towards interpreting the aEEG traces more accurately. Our report deals with three cases in which the single-lead EEG from the CFM device did indeed reveal important additional information not provided by the aEEG alone. In cases 1 and 3, the aEEGs showed drifting of the baseline to higher amplitudes. The single-lead EEG revealed that this was due to muscle artefacts, high-frequency oscillation ventilation and the electrocardiogram rather than to cerebral activity. Hence, without knowledge of the EEG, the aEEG trace might have been misinterpreted as being fairly normal. Case 2 showed paroxysmal elevation of the lower margin of the amplitude on the aEEG which looked like epileptic activity. However, additional information from the single-lead EEG revealed that it was due to muscle artefacts. Thus, simultaneously recorded EEG can help to interpret seizure-like episodes on the aEEG. CONCLUSION: Simultaneously recorded single-lead EEGs can help to interpret aEEG traces more accurately.