Elevated endothelin-1 in heart failure and loss of normal response to postural change.

BACKGROUND. The possible contribution of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, to neurohumoral compensation for hemodynamic stress was examined in nine normal volunteers and six patients with severe congestive heart failure. METHODS AND RESULTS. Plasma levels of endothelin-1 were measured with a sensitive and specific radioimmunoassay. Venous blood samples were obtained after 90 minutes of supine rest and serially during 30 minutes of 60 degrees upright tilt. Endothelin-1 levels were compared with those of known neurohumoral mediators of compensation. In normal subjects, the resting levels of endothelin-1 were low (0.74 +/- 0.11 pg/ml), and there was a rapid increase to 1.37 +/- 0.07 pg/ml at 5 minutes of upright tilting (p less than 0.05). This increase was not sustained at 10 and 15 minutes of tilt, but there was a trend toward a second rise at 30 minutes (1.14 +/- 0.17 pg/ml; p = 0.06). This biphasic pattern of response was shared by dopamine and reflected the response of systemic blood pressure to postural change. In contrast, slower and more sustained increases in circulating levels were observed for norepinephrine, epinephrine, aldosterone, plasma renin activity, and vasopressin, whereas atrial natriuretic peptide tended to decrease progressively. Patients with congestive heart failure had markedly higher basal levels of circulating endothelin-1 than normal subjects (3.7 +/- 0.5 pg/ml; p less than 0.01), and there was no further increase on postural change. Similar patterns were observed for the other neurohumoral mediators measured, with the degree of blunting of the response to upright tilting in heart failure being inversely related to the magnitude of increase in basal levels. CONCLUSIONS. Alterations in plasma levels of endothelin in congestive heart failure and in response to postural change were qualitatively and quantitatively similar to the alterations of known mediators of neurohumoral compensation. In addition, the increase in plasma endothelin-1 during upright tilting in normal subjects preceded the increases in circulating levels of the other vasoconstrictor mediators, consistent with a role of endothelin-1 in neurohumoral compensation for hemodynamic stress.     

Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.     

Further specificity characterization of von Willebrand factor inhibitors developed in two patients with severe von Willebrand disease

Circulating inhibitors against von Willebrand factor (vWF) that show the properties of heterologous IgG antibodies have been described in a few patients with severe von Willebrand disease (vWD). The present study provides further characterization of inhibitors from two patients with severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected all sizes of multimers and the complex structure of each multimer from platelets and plasma of normal individuals as well as from plasma of patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF fragments that detected a higher relative proportion of 176-Kd fragment. Furthermore, all these antibodies recognized fragment III, although one inhibitor and rabbit polyclonal antibody reacted poorly and the other inhibitor did not react at all with reduced fragment II of vWF digested with Staphylococcus aureus V-8 protease. These data suggest that although human inhibitors from severe vWD patients may behave, to some extent, as polyclonal heterologous antibodies against native vWF, the former show striking differences in their target specificity as well as a much broader specificity than that described for human factor VIII inhibitors.     

Absence of late gadolinium enhancement on cardiac magnetic resonance imaging in ventricular fibrillation and nonischemic cardiomyopathy

Introduction

Cardiac magnetic resonance (CMR)‐identified late gadolinium enhancement (LGE), representing regional fibrosis, is often used to predict ventricular arrhythmia risk in nonischemic cardiomyopathy (NICM). However, LGE is more closely correlated with sustained monomorphic ventricular tachycardia (SMVT) than ventricular fibrillation (VF). We characterized CMR findings of ventricular LGE in VF survivors.

Methods

We examined consecutively resuscitated VF survivors undergoing contrast‐enhanced 1.5T CMR between 9/2007 and 7/2016. We excluded coronary artery disease, hypertrophic cardiomyopathy, amyloid, sarcoid, arrhythmogenic right ventricular cardiomyopathy, and channelopathy. Preexisting implantable cardioverter‐defibrillator (ICD) was a CMR contraindication. VF patients were divided into three groups: (1) NICM, (2) left ventricular (LV) dilatation with normal LV ejection fraction (LVEF), and (3) normal LV size and LVEF. Two groups of NICM patients with and without SMVT were examined for comparison.

Results

We analyzed 87 VF patients, and found that LGE was seen in 8/22 (36%) with NICM (LVEF 38 ± 11%, LV end‐diastolic volume index [LVEDVI] 134 ± 68 mL/BSA), 11/40 (28%) with LV dilatation and normal LVEF (LVEDVI 103 ± 17 mL/BSA), 4/25 (16%) with normal LV size and LVEF. Incidence of LGE in NICM patients without prior ventricular tachycardia/VF (LVEF 36 ± 12%, LVEDVI 141 ± 46 mL/body surface area [BSA]) was 117/277 and was not lower than those with VF and NICM (42% vs 36%; P = 0.59). By contrast, 22/37 NICM patients with SMVT (LVEF 42 ± 11%, LVEDVI 123 ± 48 mL/BSA) were LGE‐positive (59% NICM‐SMVT vs 36% NICM‐VF; P = 0.04).

Conclusion

Most VF survivors with a diagnosis of NICM did not have LGE on CMR and would not have met primary prevention ICD criteria based on LVEF. Absence of LGE may not portend a benign prognosis in NICM. Novel strategies for determining SCD risk in this cohort are required.

     

Boarding out as an option for the care of elderly people

There has been some experiment in Ireland in recent years with boarding out of elderly persons. This comprises the placement, usually with a non-relative in a private household, of an elderly person, with the carer receiving some reward. This study assesses the cost of care for a small group of elderly persons in boarding-out care compared with a similarly dependent group of elderly persons in welfare home institutional care. The cost of boarding out care is less than half the cost of care in the welfare home. This result is encouraging given the feeling that quality of care in boarding out is not below that of institutional care.     

Consumption of animal source foods,especially fish,is associated with better nutritional status among women of reproductive age in rural Bangladesh

In rural Bangladesh, intake of nutrient-rich foods, such as animal source foods (ASFs), is generally suboptimal. Diets low in nutrients and lacking in diversity put women of reproductive age (WRA) at risk of malnutrition as well as adverse birth outcomes. The objective of this study was to assess the relationship between maternal dietary diversity, consumption of specific food groups and markers of nutritional status, including underweight [body mass index (BMI) < 18.5 kg/m²], overweight (BMI ≥ 23 kg/m²) and anaemia (haemoglobin < 120 g/dl) among WRA in Bangladesh. This analysis used data from the third round of a longitudinal observational study, collected from February through May of 2017. Dietary data were collected with a questionnaire, and Women's Dietary Diversity Score (WDDS) was calculated. Associations between WDDS, food group consumption and markers of nutritional status were assessed with separate adjusted logistic regression models. Among WRA, the prevalence of underweight, overweight and anaemia was 13.38%, 40.94% and 39.99%, respectively. Women who consumed dark green leafy vegetables (DGLV) or eggs were less likely to be anaemic or underweight, respectively, and women who consumed ASFs, particularly fish, were less likely to be underweight compared with women who did not consume these foods. WDDS did not show any consistent relationship with WRA outcomes. Interventions that focus on promoting optimal nutritional status among WRA in Bangladesh should emphasise increasing consumption of specific nutrient-rich foods, including ASFs, DGLV and eggs, rather than solely focusing on improving diet diversity in general.     

Changes in cell surface antigen expression during hemopoietic differentiation

Human bone marrow cells were separated on a fluorescence activated cell sorter (FACS) according to their binding of a series of monoclonal antibodies; the positive and negative fractions were cloned for erythroid burst and colony-forming units (BFU-E and CFU-E) and myeloid colony-forming units (CFU-GM), and cytocentrifuge slides were prepared for microscopy of maturing precursors. The pattern of antigen expression on hemopoietic progenitor and precursor populations has been established using antibodies defining blood group (A, I/i), HLA- associated (*A, B, C, DR, DC1), lineage specific, and transferrin receptor antigens. Like monomorphic HLA-DR, the antigen defined by monoclonal antibody OKT10 is expressed on the earliest progenitors and lost during differentiation, suggesting a role in interactions regulating the differentiation of these cells. The HLA-linked DC1 determinant, in contrast to HLA-DR, is not expressed at a detectable level on progenitor cells. Although a lineage-specific early antigen has not been identified, the transferrin receptor is expressed on the majority of erythroid progenitors, but only weakly on myeloid progenitors, and may provide an approach to isolating erythroid progenitors. These and earlier studies with monoclonal antibodies against HLA-DR and glycophorin now provide a detailed "map" of antigen expression during hemopoietic differentiation.     

Platelet dynamics following allergen challenge in allergic asthmatics

BACKGROUND: There is evidence that platelet activation occurs in allergic inflammation and asthma, but little is known about the role platelets play in airway inflammation associated with asthma. Objectives: In the present study, we have investigated the kinetics of platelet activation following allergen provocation of allergic asthmatics to determine the dynamics of platelet activation relative to changes in lung function and changes in airway inflammation. METHODS: Changes in platelet count and haematocrit from baseline were measured during the early asthmatic response (EAR), late asthmatic response (LAR; or at corresponding time points) and at 24 h were compared between allergen- and saline-challenged groups. A subgroup of allergen-challenged asthmatics, a group of 7 challenged asthmatics and 7 controls were bronchoscoped, and BAL fluid was collected and analysed for levels of histamine and eosinophil cationic protein. RESULTS: There was a fall in circulating platelet count, but not haematocrit after allergen challenge when compared with saline during the LAR or at 24 h. At 24 h FEV(1) had returned to within 20% of baseline in all subjects, although the thrombocytopaenia and airway inflammation persisted. CONCLUSIONS: Our results suggest that persistent thrombocytopaenia accompanies allergen exposure and persists beyond changes in airway obstruction at a time when airway inflammation is present. Our results provide further evidence that platelets may be involved in allergic disease.