Left ventricular function and exercise capacity in patients with slow coronary flow

Background: Endothelial and microvascular dysfunction have been implicated in slow coronary flow (SCF). How and to what extent do these etiological factors affect left ventricular (LV) function and exercise capacity? Aim: The aim of the study was to evaluate LV systolic and diastolic function by pulsed tissue Doppler imaging (TDI) in SCF patients and their effects on exercise capacity. Subjects and methods: Sixty SCF patients and 20 control subjects were included in the study. Echocardiographic examination, treadmill exercise test, and TDI were performed. Isovolumic myocardial acceleration (IVA) and myocardial performance index (MPI) were measured. Results: TDI mean parameters for systolic and diastolic LV function were significantly impaired in SCF group with decreased Sa, IVA, Ea/Aa, and increased MPI (0.31 ± 0.06 vs. 0.26 ± 0.04, P < 0.01) compared to control. There was significant correlation between thrombolysis in myocardial infarction (TIMI) frame count and TDI mean parameters for LV systolic function (Sa & IVA, r =?0.53, P < 0.01 & r =?0.36, P < 0.05, respectively). Mean TIMI frame count was correlated with MPI and E/Ea. SCF patients had poorer peak exercise capacity than the controls (9.9 ± 1.9 METs vs. 12.7 ± 2.3, P < 0.01) with significant negative correlation with mean TIMI frame count (r =?0.46, P < 0.01). Conclusion: There is impairment of LV systolic and diastolic function in SCF patients with clinical impact on exercise capacity which emphasizes the importance of close follow‐up of these patients for risk stratification. (Echocardiography 2012;29:158‐164)     

Novel application of four-dimensional sonography with B-flow imaging and spatiotemporal image correlation in the assessment of fetal congenital heart defects

Aims: To evaluate the role of four‐dimensional (4D) ultrasound with B‐flow imaging and spatiotemporal image correlation (STIC) in the evaluation of normal fetal heart and congenital heart disease during pregnancy. Methods: Volume data sets of the fetal heart were acquired with automated transverse and longitudinal sweeps of the anterior chest wall. We studied 31 normal fetuses and 28 fetuses with congenital heart disease (6 with double‐outlet right ventricle, 5 with complete transposition of great arteries, 8 with tetralogy of Fallot, 3 with right aortic arch, 2 with persistent left superior vena cava, 3 with truncus arteriosus communis, and 1 with interruption of aortic arch) at gestation ages ranging from 18 to 39 weeks using transabdominal 4D B‐flow sonography with STIC (4D BF‐STIC). Results: Four‐dimensional BF‐STIC demonstrated dynamic angiographic features in both normal and abnormal fetal hearts. Four‐dimensional BF‐STIC images could not be obtained in two normal fetuses at 18.9 and 35.6 weeks because of the high fetal heart rate and inappropriate fetal position. Of the other 29 fetuses all extracardiac vessels such as aorta, pulmonary artery, ductus arteriosus, inferior vena cava, and ductus venosus could be detected on reconstructed images. In seven normal cases, a 4D image was recorded to allow simultaneous visualization of all four pulmonary veins. In the 28 fetuses with cardiac anomalies, 4D sonography with B‐flow imaging and STIC detected the “digital casts” of the outflow tracts, great arteries, and veins draining into the heart. These results demonstrate spatial relationship among these structures which provide important anatomical information. Conclusion: Four‐dimensional BF‐STIC provides a means of real time three‐dimensional evaluation of fetal extracardiac hemodynamics in the second and third trimesters. This novel technique assists in the evaluation of fetal cardiac hemodynamics and may play an important role in future fetal cardiac research and in the identification of anatomical features of different congenital cardiac anomalies. (Echocardiography 2012;29:614‐619)     

Cerebral blood flow and gray matter volume covariance patterns of cognition in aging

Advancing age results in altered cognitive and neuroimaging‐derived markers of neural integrity. Whether cognitive changes are the result of variations in brain measures remains unclear and relating the two across the lifespan poses a unique set of problems. It must be determined whether statistical associations between cognitive and brain measures truly exist and are not epiphenomenal due solely to their shared relationships with age. The purpose of this study was to determine whether cerebral blood flow (CBF) and gray matter volume (GMV) measures make unique and better predictions of cognition than age alone. Multivariate analyses identified brain‐wide covariance patterns from 35 healthy young and 23 healthy older adults using MRI‐derived measures of CBF and GMV related to three cognitive composite scores (i.e., memory, fluid ability, and speed/attention). These brain‐cognitive relationships were consistent across the age range, and not the result of epiphenomenal associations with age and each imaging modality provided its own unique information. The CBF and GMV patterns each accounted for unique aspects of cognition and accounted for nearly all the age‐related variance in the cognitive composite scores. The findings suggest that measures derived from multiple imaging modalities explain larger amounts of variance in cognition providing a more complete understanding of the aging brain. Hum Brain Mapp 34:3267–3279, 2013. © 2012 Wiley Periodicals, Inc.     

Glycosaminoglycan entrapment by fibrin in engineered heart valve tissues

Tissue engineered heart valves (TEHVs) may provide a permanent solution to congenital heart valve disease by permitting somatic valve growth in the pediatric patient. However, to date, TEHV studies have focused primarily on collagen, the dominant component of valve extracellular matrix (ECM). Temporal decreases in other ECM components, such as the glycosaminoglycans (GAGs), generally decrease as cells produce more collagen under mechanically loaded states; nevertheless, GAGs represent a key component of the valve ECM, providing structural stability and hydration to the leaflets. In an effort to retain GAGs within the engineered constructs, here we investigated the utility of the protein fibrin in combination with a valve-like, cyclic flexure and steady flow (flex–flow) mechanical conditioning culture process using adult human periodontal ligament cells (PLCs). We found both fibrin and flex–flow mechanical components to be independently significant (p < 0.05), and hence important in influencing the DNA, GAG and collagen contents of the engineered tissues. In addition, the interaction of fibrin with flex–flow was found to be significant in the case of collagen; specifically, the combination of these environments promoted PLC collagen production resulting in a significant difference compared to dynamic and statically cultured specimens without fibrin. Histological examination revealed that the GAGs were retained by fibrin entrapment and adhesion, which were subsequently confirmed by additional experiments on native valve tissues. We conclude that fibrin in the flex–flow culture of engineered heart valve tissues: (i) augments PLC-derived collagen production; and (ii) enhances retention of GAGs within the developing ECM.     

Common variable immunodeficiency in adults: current diagnostic protocol and laboratory measures

Common variable immunodeficiency (CVID) is one of the most common symptomatic primary immune defects in adults. Unfortunately, the diagnosis of CVID is often delayed because of its variable presentations and manifestations. Sincere efforts from experts in the field of primary immunodeficiency disorders all over the world have made us wiser regarding the clinical features, associated complications and long-term outcome of the disease. However, a systematic compilation of diagnostic protocols and laboratory measures is desirable. The present review highlights in brief the immunological and molecular defects characterizing adult CVID along with a comprehensive discussion on currently followed laboratory criteria and methods used to identify these cases. The article may benefit the clinicians, immunologists, infectious disease specialists, pulmonary medicine specialists, gastroenterologists, dermatologists and other physicians who are involved in the team management of the patients with CVID.     

Flow Cytometry Analysis with a New FITC-Conjugated Monoclonal Antibody-3E12 for HLA-B*57:01 Rapid Screening in Prevention of Abacavir Hypersensitivity in HIV-1–Infected Patients

Abstract

Background: Rapid screening for the detection of HLA-B*57:01 in the prevention of abacavir hypersensitivity in HIV-1–infected patients is a hallmark for clinical services. Objective: The aim of this work was to analyze the utility of flow cytometry with a new FITC-conjugated B-17 monoclonal antibody (mAb3E12) for HLA-B*57:01 screening in a Spanish cohort of 577 HIV-1+ individuals. Methods: Cryopreserved peripheral blood mononuclear cell samples from HIV-1+ individuals were analyzed by flow cytometry with the mAb 3E12 that recognizes both HLA-B*57 and HLA-B*58 alleles (members of the group specificity, HLA-B17). Patients’ DNA samples had been previously typed for HLA-B*57:01 with PCR-SSO or PCR-SSP and additional DNA sequencing (EPI Study). The results obtained by flow cytometry were compared with the results obtained by the DNA-PCR techniques. Results: By flow cytometry, 46 samples (7.97%) were positive for HLA-B17, 530 (91.86%) were negative, and 1 (0.17%) was undetermined. All samples found negative by flow cytometry were negative for HLA-B*57:01 by DNA-PCR. Of the HLA-B17 positive samples, 31 (67.4%) were positive for HLA-B*57:01, 2 (3.25%) were positive for HLA-B*57:03, 11 (26.1%) were positive for HLA-B*58, and 2 (3.25%) were negative for both HLA-B*57 and HLA–B*58 antigens. The undetermined sample was negative for HLA-B*57 and HLA-B*58 alleles by DNA-PCR. Conclusions: This study shows that flow cytometry with mAb3E12 is a highly sensitive method (no false negatives) to implement prior to DNA-PCR analysis for rapid screening of HLA-B*57:01. Additional confirmation by molecular HLA typing method would be required in less than 10% of the cohort of HIV-1–infected individuals.     

Effects of enamel and dentine thickness on laser doppler blood-flow signals recorded from the underlying pulp cavity in human teeth in vitro

Objective

To determine the effect of enamel and dentine thickness on laser Doppler blood-flow (LDF) signals recorded from dental pulp.

Design

Observations were made on 18 human premolars that had been extracted from young patients during orthodontic treatment. The apical 2/3 of the root was cut off and the remaining pulp removed. Blood flow signals were recorded from the buccal surface of the crown with a laser Doppler flow metre while dilute blood was pumped at 10 ml/min. through a cannula inserted into the pulp cavity. Recordings were made from the enamel surface and at 0.5 mm steps through the enamel and dentine.

Results

The blood flow signal increased significantly as the cavity depth increased and at 2.0 mm, the median flux signal was more than ten times greater than that obtained on the enamel surface. The backscattered light intensity did not change with cavity depth.

Conclusion

When recording pulpal blood flow from a human tooth with a laser Doppler flow metre, a substantially better signal-to-noise ratio should be obtained by placing the probe on dentine in the floor of a cavity than on the enamel surface.     

The Science behind Topical Negative Pressure Therapy

Topical negative pressure therapy (TNP) is an established part of modern wound healing. With an increasing choice in TNP providers, understanding the differing modes of action, the biochemical and biophysical effects on the wound at a microscopic and macroscopic level, plus the role of the interface dressings, will aid the clinician in planning a clear goal of therapy. This article reviews the scientific evidence for TNP to date and explores each mechanism of action and the implications for wound healing and patient outcomes.