Can Shunt Response in Patients with Idiopathic Normal Pressure Hydrocephalus Be Predicted from Preoperative Brain Imaging? A Retrospective Study of the Diagnostic Use of the Normal Pressure Hydrocephalus Radscale in 119 Patients.

Background And Purpose: The Normal Pressure Hydrocephalus Radscale is a combined scoring of 7 different structural imaging markers on preoperative brain CT or MR imaging in patients with idiopathic normal pressure hydrocephalus: callosal angle, Evans Index, Sylvian fissure dilation, apical sulcal narrowing, mean temporal horn diameter, periventricular WM lesions, and focal sulcal dilation. The purpose of this retrospective study was to assess the performance of the Normal Pressure Hydrocephalus Radscale in distinguishing idiopathic normal pressure hydrocephalus shunt responders from nonresponders.

Materials And Methods: The preoperative MR imaging and CT scans of 119 patients with idiopathic normal pressure hydrocephalus were scored using the Normal Pressure Hydrocephalus Radscale.

A method for modelling the oxyhaemoglobin dissociation curve at the level of the cerebral capillary in humans.

New Findings: What is the central question of this study? Can the change in haemoglobin's affinity for oxygen in the human cerebral circulation be modelled in vivo? What is the main finding and its importance? We provide a novel method for modelling the oxyhaemoglobin dissociation curve at the cerebral capillary level in humans, so that the cerebral capillary and mitochondrial oxygen tensions can reliably be estimated. This may be useful in future human-experimental studies on cerebral oxygen transport.

Abstract: We provide a method for modelling the oxyhaemoglobin dissociation curve (ODC) in the cerebral capillary in humans.

Transcerebral exchange kinetics of large neutral amino acids during acute inspiratory hypoxia in humans.

Hypoxaemia is present in many critically ill patients, and may contribute to encephalopathy. Changes in the passage of large neutral amino acids (LNAAs) across the blood-brain barrier (BBB) with an increased cerebral influx of aromatic amino acids into the brain may concurrently be present and also contribute to encephalopathy, but it has not been established whether hypoxaemia may trigger such changes. We measured cerebral blood flow (CBF) in 11 healthy men using the Kety-Schmidt technique and obtained paired arterial and jugular-venous blood samples for the determination of LNAAs by high performance liquid chromatography at baseline and after 9 hours of poikilocapnic normobaric hypoxia (12% O).

[Endovascular thrombectomy in ischaemic apoplexy treatment].

The goal when treating ischaemic apoplexy is a rapid, safe and effective recanalization. For some years, the main treatment has been the administration of IV thrombolysis, but due to several restrictions, lack of efficacy and a limited window of opportunity for treatment, an alternative method was needed. This formed the foundation for the develop-ment of endovascular thrombectomy.

Transcerebral net exchange of vasoactive peptides and catecholamines during lipopolysaccharide-induced systemic inflammation in healthy humans.

The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a 4-hour intravenous LPS infusion (0.3 ng·kg) induces any changes in the transcerebral net exchange of the vasoactive peptides endothelin-1 (ET-1) and calcitonin-gene related peptide (CGRP) and catecholamines in human volunteers.

A reassessment of the blood-brain barrier transport of large neutral amino acids during acute systemic inflammation in humans.

We reassessed data from a previous study on the transcerebral net exchange of large neutral amino acids (LNAAs) using a novel mathematical model of blood-brain barrier (BBB) transport. The study included twelve healthy volunteers who received a 4-h intravenous lipopolysaccharide (LPS) infusion (total dose: 0·3 ng/kg), a human experimental model of the systemic inflammatory response during the early stages of sepsis. Cerebral blood flow and arterial-to-jugular venous LNAA concentrations were measured prior to and after LPS, and the BBB transport and brain extracellular concentrations of LNAAs were calculated.

Mechanical Thrombectomy with the Embolus Retriever with Interlinked Cages in Acute Ischemic Stroke: ERIC, the New Boy in the Class.

Background And Purpose: The Embolus Retriever with Interlinked Cages (ERIC) device is a novel stent retriever for mechanical thrombectomy. It consists of interlinked cages and could improve procedural benchmarks and clinical outcome compared with classic stent retrievers. This study compares the rates of recanalization, favorable clinical outcome, procedural adverse events, and benchmarks between the ERIC device and classic stent retrievers.

Thrombectomy assisted by carotid stenting in acute ischemic stroke management: benefits and harms.

Extracranial carotid artery occlusion or high-grade stenosis with concomitant intracranial embolism causes severe ischemic stroke and shows poor response rates to intravenous thrombolysis (IVT). Endovascular therapy (EVT) utilizing thrombectomy assisted by carotid stenting was long considered risky because of procedural complexities and necessity of potent platelet inhibition-in particular following IVT. This study assesses the benefits and harms of thrombectomy assisted by carotid stenting and identifies factors associated with clinical outcome and procedural complications.

On the antioxidant properties of erythropoietin and its association with the oxidative-nitrosative stress response to hypoxia in humans.

Aim: The aim of this study was to examine if erythropoietin (EPO) has the potential to act as a biological antioxidant and determine the underlying mechanisms.

Methods: The rate at which its recombinant form (rHuEPO) reacts with hydroxyl (HO˙), 2,2-diphenyl-1-picrylhydrazyl (DPPH˙) and peroxyl (ROO˙) radicals was evaluated in-vitro. The relationship between the erythopoietic and oxidative-nitrosative stress response to poikilocapneic hypoxia was determined separately in-vivo by sampling arterial blood from eleven males in normoxia and following 12 h exposure to 13% oxygen.

Effects of lipopolysaccharide infusion on arterial levels and transcerebral exchange kinetics of glutamate and glycine in healthy humans.

An imbalance between glutamate and glycine signalling may contribute to sepsis-associated encephalopathy by causing neuronal excitotoxicity. In this study, we therefore investigated the transcerebral exchange kinetics of glutamate and glycine in a human-experimental model of systemic inflammation. Cerebral blood flow (CBF) and arterial to jugular venous concentration differences of glutamate and glycine were determined before and after a 4-h intravenous infusion of Escherichia coli lipopolysaccharide (LPS, total dose of 0.

Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6.

Obesity and type 2 diabetes are associated with chronically elevated systemic levels of IL-6, a pro-inflammatory cytokine with a role in skeletal muscle metabolism that signals through the IL-6 receptor (IL-6Rα). We hypothesized that skeletal muscle in obesity-associated type 2 diabetes develops a resistance to IL-6. By utilizing western blot analysis, we demonstrate that IL-6Rα protein was down regulated in skeletal muscle biopsies from obese persons with and without type 2 diabetes.

Brain and skin do not contribute to the systemic rise in erythropoietin during acute hypoxia in humans.

Erythropoietin (EPO) preserves arterial oxygen content by controlling red blood cell and plasma volumes. Synthesis of EPO was long thought to relate inversely to renal oxygenation, but in knockout mice, brain and skin have been identified as essential for the acute hypoxic EPO response. Whether these findings apply to humans remains unknown.

Cerebral formation of free radicals during hypoxia does not cause structural damage and is associated with a reduction in mitochondrial PO2; evidence of O2-sensing in humans?

Cellular hypoxia triggers a homeostatic increase in mitochondrial free radical signaling. In this study, blood was obtained from the radial artery and jugular venous bulb in 10 men during normoxia and 9  hours hypoxia (12.9% O(2)).

Acute in vitro hypoxia and high-altitude (4,559 m) exposure decreases leukocyte oxygen consumption.

Hypoxia impairs metabolic functions by decreasing activity and expression of ATP-consuming processes. To separate hypoxia from systemic effects, we tested whether hypoxia at high altitude affects basal and PMA-stimulated leukocyte metabolism and how this compares to acute (15 min) and 24 h of in vitro hypoxia. Leukocytes were prepared at low altitude and ∼24 h after arrival at 4559 m.

High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability.

High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty-six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA).

Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans.

Introduction: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.

Methods: The BCAA/AAA ratio, the cerebral delivery, and net exchange of LNAAs and ammonia were measured before and 1 hour after a 4-hour intravenous infusion of Escherichia coli lipopolysaccharide (LPS) in 12 healthy young men.

Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle.

Objective: To test the hypothesis that free fatty acid (FFA) and muscle glycogen modify exercise-induced regulation of PDH (pyruvate dehydrogenase) in human skeletal muscle through regulation of PDK4 expression.

Research Design And Methods: On two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relative to the contra-lateral leg (CON) the day before the experimental day. On the experimental days, plasma FFA was ensured normal or remained elevated by consuming breakfast rich (low FFA) or poor (high FFA) in carbohydrate, 2 h before performing 20 min of two-legged knee extensor exercise.

Calprotectin--a novel marker of obesity.

Background: The two inflammatory molecules, S100A8 and S100A9, form a heterodimer, calprotectin. Plasma calprotectin levels are elevated in various inflammatory disorders. We hypothesized that plasma calprotectin levels would be increased in subjects with low-grade systemic inflammation i.

Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein and radial artery blood samples during normoxia and 9-h passive exposure to hypoxia (12.9% O(2)).

Transcerebral exchange kinetics of nitrite and calcitonin gene-related peptide in acute mountain sickness: evidence against trigeminovascular activation?

Background And Purpose: High-altitude headache is the primary symptom associated with acute mountain sickness, which may be caused by nitric oxide-mediated activation of the trigeminovascular system. Therefore, the present study examined the effects of inspiratory hypoxia on the transcerebral exchange kinetics of the vasoactive molecules, nitrite (NO(2)(*)), and calcitonin gene-related peptide (CGRP).

Methods: Ten males were examined in normoxia and after 9-hour exposure to hypoxia (12.

Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans.

Recent studies have shown that erythropoietin (EPO) offers protection against ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has been suggested that EPO has anti-inflammatory effects. With the aim of investigating the potential acute anti-inflammatory effects of EPO in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects.

Cerebral blood flow and oxygen metabolism measured with the Kety-Schmidt method using nitrous oxide.

Background: The Kety-Schmidt method is the reference method for measuring global cerebral blood flow (CBF), cerebral metabolic rates (CMR) and flux, especially where scanners are unavailable or impractical. Our primary objective was to assess the repeatability of the Kety-Schmidt method in a variety of different approaches using inhaled nitrous oxide (N2O) as the tracer, combined with photoacoustic spectrometry. A secondary objective was to assess the impact of this tracer on the systemic vascular concentration of nitrite (NO2(-)).

Association between interleukin-15 and obesity: interleukin-15 as a potential regulator of fat mass.

Objective: IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way regulate adipose tissue mass.

Design: The relation between skeletal muscle IL-15 mRNA expression, plasma IL-15, and adipose tissue mass was studied in 199 humans divided into four groups on the basis of obesity and type 2 diabetes.

Human endotoxemia as a model of systemic inflammation.

Systemic inflammation is a pathogenetic component in a vast number of acute and chronic diseases such as sepsis, trauma, type 2 diabetes, atherosclerosis, and Alzheimer's disease, all of which are associated with a substantial morbidity and mortality. However, the molecular mechanisms and physiological significance of the systemic inflammatory response are still not fully understood. The human endotoxin model, an in vivo model of systemic inflammation in which lipopolysaccharide is injected or infused intravenously in healthy volunteers, may be helpful in unravelling these issues.