Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study.

OBJECTIVES: The purpose of this study was to evaluate left ventricular (LV) size and structure in elderly subjects with hypertension (HTN) and heart failure who have a normal ejection fraction (HFNEF) in a large population-based sample. BACKGROUND: The pathophysiology of HFNEF is incompletely understood but is generally attributed to LV diastolic dysfunction with normal or reduced LV diastolic chamber size despite greater than normal filling pressures. METHODS: In the Cardiovascular Health Study (n = 5,888), demographic and clinical characteristics and ventricular structure and function were compared in healthy normal subjects (healthy; n = 499), subjects with HTN but not heart failure (HTN; n = 2,184), and subjects with HTN and HFNEF (HFNEF; n = 167). RESULTS: Subjects with HFNEF were older, more obese, and more often African American than healthy and HTN subjects and had a higher prevalence of diabetes, coronary heart disease, and anemia than HTN subjects. Serum creatinine and cystatin-C were increased in HFNEF subjects. Average LV diastolic dimension was significantly increased in HFNEF subjects (5.2 +/- 0.8 cm) compared with healthy (4.8 +/- 0.6 cm) and HTN (4.9 +/- 0.6 cm) subjects. As a result, average calculated stroke volume (89 +/- 25 ml vs. 78 +/- 20 ml and 80 +/- 20 ml) and cardiac output (6.0 +/- 2.0 l/min vs. 4.8 +/- 1.3 l/min and 5.1 +/- 1.4 l/min) were increased in HFNEF compared with healthy and HTN subjects, respectively. CONCLUSIONS: As a group, HFNEF subjects have increased LV diastolic diameter and increased calculated stroke volume. They also have increased prevalence of multiple comorbidities, including anemia, renal dysfunction, and obesity, that can cause volume overload. These data suggest that extracardiac factors, via volume overload, may contribute to the pathophysiology of HFNEF in the elderly.     

Evidence for a rat granulocyte chalone effect on the proliferation of normal human bone marrow and of myeloid leukemias.

Evidence is presented that rat ascites cell extracts, acting as granulocyte chalone, temporarily inhibit the cell doubling of granulocytopoietic precursors in suspension cultures of human bone marrow. The extracts do not affect the proliferation of erythroblasts and do not show any cytotoxicity. In addition, a relative increase of granulocytic precursors capable of proliferation was found, suggesting an increase in the resting population of the granulocytopoietic proliferation pool due to extract treatment. However, the extract capable of depressing the proliferation of the normal granulocytopoiesis did not affect the granulocytopoiesis of 7 chronic myeloid and 2 chronic myelomonocytic leukemias at the same dose level. In contrast to these chronic leukemias, blast proliferation of 4 acute myeloid and monocytic leukemias was greatly depressed not only for 6 h but for the whole culture period of 48 h.     

Supported discharge service versus inpatient care evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm,functional impairment,and educational and clinical outcomes

Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. The aim of this study is to undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. 106 patients aged 12–18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomisation, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (five or more) of self-harm (OR = 0.18, 95% CI: 0.05–0.64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28.2–208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment.

     

Cold urticaria – What we know and what we do not know

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.     

Ultra-low-dose dual-source CT coronary angiography with high pitch: diagnostic yield of a volumetric planning scan and effects on dose reduction and imaging strategy

Objective:

To evaluate the role of an ultra-low-dose dual-source CT coronary angiography (CTCA) scan with high pitch for delimiting the range of the subsequent standard CTCA scan.

Methods:

30 patients with an indication for CTCA were prospectively examined using a two-scan dual-source CTCA protocol (2.0 × 64.0 × 0.6 mm; pitch, 3.4; rotation time of 280 ms; 100 kV): Scan 1 was acquired with one-fifth of the tube current suggested by the automatic exposure control software [CareDose 4D™ (Siemens Healthcare, Erlangen, Germany) using 100 kV and 370 mAs as a reference] with the scan length from the tracheal bifurcation to the diaphragmatic border. Scan 2 was acquired with standard tube current extending with reduced scan length based on Scan 1. Nine central coronary artery segments were analysed qualitatively on both scans.

Results:

Scan 2 (105.1 ± 10.1 mm) was significantly shorter than Scan 1 (127.0 ± 8.7 mm). Image quality scores were significantly better for Scan 2. However, in 5 of 6 (83%) patients with stenotic coronary artery disease, a stenosis was already detected in Scan 1 and in 13 of 24 (54%) patients with non-stenotic coronary arteries, a stenosis was already excluded by Scan 1. Using Scan 2 as reference, the positive- and negative-predictive value of Scan 1 was 83% (5 of 6 patients) and 100% (13 of 13 patients), respectively.

Conclusion:

An ultra-low-dose CTCA planning scan enables a reliable scan length reduction of the following standard CTCA scan and allows for correct diagnosis in a substantial proportion of patients.

Advances in knowledge:

Further dose reductions are possible owing to a change in the individual patient''s imaging strategy as a prior ultra-low-dose CTCA scan may already rule out the presence of a stenosis or may lead to a direct transferal to an invasive catheter procedure.In recent years, dramatic advances in CT technology have led to the establishment of CT coronary angiography (CTCA) as a non-invasive imaging modality with robust image quality for the detection of coronary artery stenosis.^1,2 A major drawback of CT is the radiation exposure, which may be as high as 20 mSv.^3,4 Several techniques are available to reduce the radiation dose to the patient, including electrocardiography (ECG)-based tube current modulation, automatic exposure control and prospective ECG gating.^5–7 State-of-the-art dual-source CT scanners, which use two radiation sources and detectors, provide markedly better resolution and, in conjunction with fast table advancement, enable image acquisition of the entire heart in a single heartbeat.⁸ This technique requires no overlapping acquisition and—under ideal conditions, that is, in patients with low heart rates—can reduce radiation exposure to <1 mSv.⁹While these techniques can already substantially lower the radiation exposure of patients undergoing CTCA, there is potential for further reduction by optimally planning the scan length in the z-axis. An anteroposterior view acquired for localization of the imaging volume provides only a general idea of the course of the coronary arteries within the cardiac silhouette. Therefore, in order to ensure coverage of the entire coronary system, most examiners define the scan length using the tracheal bifurcation as the upper limit and the lateral diaphragmatic recess as the lower limit.¹⁰ In many cases, this strategy results in a longer scan and higher radiation exposure than is actually needed. An option for more accurate delimitation of the scan length is to use the axial slices of a prior calcium scan for orientation.^11,12 Alternatively, an accurate definition of the necessary scan length is achieved by acquiring a contrast-enhanced ultra-low-dose planning scan that might allow for a simultaneous diagnostic evaluation of at least the larger, proximal coronary artery segments, that is, those segments that are potentially amenable to a catheter-based intervention. We hypothesized that an ultra-low-dose planning scan can reduce the overall radiation exposure of CTCA: patients in whom the planning scan already excludes a stenosis would not need the subsequent diagnostic scan and patients in whom the planning scan detects at least one stenosis can directly undergo invasive cardiac catheterization.The aim of our study was to investigate the use of a high-pitch ultra-low-dose dual-source CTCA scan for delimiting the scan range of the subsequent diagnostic CTCA, and to assess how such a scan might reduce radiation exposure and modify the imaging strategy in an individual patient.     

Interleukin 4 promotes expression of mast cell ICAM-1 antigen.

Cell recognition molecules play a crucial role in the regulation of immune cells. We recently found that mast cells (MCs) express leukocyte recognition molecules, including ICAM-1 antigen, a natural ligand of LFA-1. We here report that interleukin 4 (IL-4), a pleiotropic cytokine and mast cell differentiation factor, selectively promotes expression of surface ICAM-1 antigen and ICAM-1 mRNA in human MCs. IL-4 also up-regulates ICAM-1 antigen in cells of monocyte/macrophage lineage but has no effect on ICAM-1 antigen expressed on basophils, fibroblasts, or lymphocytes. The increase in expression of mast cell/macrophage ICAM-1 antigen induced by IL-4 may contribute to the accumulation of leukocytes and facilitate cell-contact-dependent regulation of immune cells in inflamed tissues.