61 research outputs found
Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study
Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage
hampers comparative studies and optimization of clinical management. The concept of persistent postpartum
haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common
definitions that are either based on estimations of blood loss or transfused units of packed red blood cells
(RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured
by these three types of definitions.
Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive
women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical
characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum
haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h
following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation
and intensive care unit admission.
Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the
definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h
following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying
the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal
outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent
postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line
treatment.
Conclusion: The definition persistent postpartum haemo
A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction
Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acidinduced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5dihydroxybenzoic acid to a range of 2,5substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholineinduced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF2 and H2DCFDA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RTPCR and western blotting were utilized to measure Akt, eNOS, Nrf2, NQO1 and HO1 expression. Results: Ex vivo endotheliumdependent relaxation was significantly improved by the glycomimetics under palmitateinduced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitateinduced oxidative stress and enhanced NO production. We demonstrate that the protective effects of preincubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROSinduced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease
Plasma Concentrations of Islet Amyloid Polypeptide After Glucagon Administration in Type 2 Diabetic Patients and Non‐diabetic Subjects
Islet amyloid polypeptide (IAPP) is the main constituent of pancreatic islet amyloid, observed in the pancreases from patients with Type 2 diabetes mellitus. IAPP is synthesized by the pancreatic β‐cells. In order to study the secretion characteristics of IAPP in Type 2 diabetes mellitus, plasma IAPP was measured during a provocation test with glucagon in 33 Type 2 diabetic patients and 18 non‐diabetic subjects. The median fasting IAPP level was 5.7 (range 1.1–13.1) pmol l−1 in the 27 patients treated with oral hypoglycaemic agents and 2.7 (1.9–5.9) in the 6 patients on insulin. In the non‐diabetic group fasting IAPP was 5.7 (2.2–10.1). Six minutes after glucagon administration median IAPP rose to 9.4 (1.7–31.0) and 6.1 (5.1–10.2) in the respective diabetic groups, and to 16.8 (4.0–41.0) in the non‐diabetic subjects (p 0.05). The correlation coefficient between change in IAPP and change in C‐peptide was 0.68 in the diabetic group. We conclude that intravenous administration of glucagon stimulates IAPP release from the β‐cell. This provocation test is easy to perform and can be used on a large scale in the study of IAPP secretion in Type 2 diabetes mellitus. 1993 Diabetes U
Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients
Objectives: New insights in the pathophysiology of lacunar stroke (LS) suggest that it is caused by increased permeability of the blood-brain barrier due to endothelial activation. Because endothelial cells are the major production and storage site of tissue factor pathway inhibitor (TFPI), this protein can be used as marker of endothelial activation. In this observational study we measured the different pools of TFPI, as a marker of endothelial function, in first-ever lacunar stroke patients. Methods: We determined antigen levels of total and free full-length (FL) TFPI using ELISA in 149 patients and 42 controls. Heparin-releasable free FL TFPI was determined in a random subset of 17 patients and 15 controls. By brain MRI, we classified LS patients as having isolated lacunar infarct (ILA) or silent ischemic lesions (SILs). Results: Plasma levels of total TFPI were highest in patients with SILs compared with those with ILA, but this association disappeared after correction for age and levels of low-density lipoprotein cholesterol. However, levels of heparin-releasable free FL TFPI were higher in patients than in controls. Conclusions: Although ambient plasma levels of total TFPI were not different in subtypes of LS, the increased levels of heparin-releasable TFPI in patients suggest a role of endothelial activation in the pathogenesis of LS. Neurology (R) 2012;78:493-49
- …