Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis

Septic shock is characterized by increased vascular permeability and hypotension despite increased cardiac output. Numerous vasoactive cytokines are upregulated during sepsis, including angiopoietin 2 (ANG2), which increases vascular permeability. Here we report that mice engineered to inducibly overexpress ANG2 in the endothelium developed sepsis-like hemodynamic alterations, including systemic hypotension, increased cardiac output, and dilatory cardiomyopathy. Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to develop hemodynamic alterations. Interestingly, the hemodynamic alterations associated with endothelial-specific overexpression of ANG2 and the loss of capillary-associated pericytes were reversed by intravenous injections of adeno-associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice, which rapidly developed hypotension, acute pericyte loss, and increased vascular permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to 61%. These data indicate that ANG2-mediated microvascular disintegration contributes to septic shock and that inhibition of the ANG2/TIE2 interaction during sepsis is a potential therapeutic target.     

Myxoid liposarcoma

Summary Liposarcoma is an important soft tissue sarcoma. It requires careful classification into types, since prognosis varies considerably with histological appearance. In this case a myxoid sarcoma is shown to contain cells resembling fetal fat with active pinocytosis, and some scanty signet-ring cells. Their ultrastructural appearances are described.The author is indebted to Priv.- Doz. Dr. K. Donath, Department of Pathology University Hamburg, for electron microscopic photographs     

Changes in psychological distress of women with breast cancer in long-term remission and their husbands

The purpose of this randomized, prospective study was to identify factors influencing the psychological distress of breast cancer patients and their husbands during remission. Background variables and distress levels of 172 couples in two locations (Graz, Austria, and Jerusalem, Israel) were assessed by using three standardized instruments in two interviews conducted 6-8 months apart. In both geographic-cultural groups, women whose partners refused to participate in the interview reported significantly less perceived family support. The global severity index (measuring total psychological distress) reflected minor changes in psychological distress of both patients and their husbands over time.     

The seismocardiogram as magnetic-field-compatible alternative to the electrocardiogram for cardiac stress monitoring

Seismocardiography (SCG) is a methodology derived from the field of seismology to measure non-invasively compression waves generated by myocardial motion. The use of SCG is proposed here as method to monitor cardiac function during stress testing and magnetic resonance imaging (MRI). It is shown that recording of the seismocardiogram in subjects undergoing an MRI study is not compromised by flow-induced electrical voltages that can severely distort the electrocardiogram. Electromagnetic compatibility of the seismocardiograph device with the MRI scanner hardware was tested. Experiments in an animal model proved that changes in the SCG waveform during different levels of LAD stenosis correlate with the changes seen in LV function with cine MRI. The changes in the SCG waveform characteristic for the onset of ischemia were observed almost immediately after the creation of a flow-limiting stenosis. This novel application of SCG to monitor changes in peak acceleration from cardiac blood flow and wall motion may represent a solution to the long-standing and important problem of monitoring patients for signs of myocardial ischemia during MRI.     

The seismocardiogram as magnetic-field-compatible alternative to the electrocardiogram for cardiac stress monitoring

Seismocardiography (SCG) is a methodology derived from the field of seismology to measure non-invasively compression waves generated by myocardial motion. The use of SCG is proposed here as method to monitor cardiac function during stress testing and magnetic resonance imaging (MRI). It is shown that recording of the seismocardiogram in subjects undergoing an MRI study is not compromised by flow-induced electrical voltages that can severely distort the electrocardiogram. Electromagnetic compatibility of the seismocardiograph device with the MRI scanner hardware was tested. Experiments in an animal model proved that changes in the SCG waveform during different levels of LAD stenosis correlate with the changes seen in LV function with cine MRI. The changes in the SCG waveform characteristic for the onset of ischemia were observed almost immediately after the creation of a flow-limiting stenosis. This novel application of SCG to monitor changes in peak acceleration from cardiac blood flow and wall motion may represent a solution to the long-standing and important problem of monitoring patients for signs of myocardial ischemia during MRI.     

Is dopexamine superior to dopamine in the treatment of multiple trauma patients—A prospective, double-blind, randomised study

Background

The goal of this prospective, randomised, double-blind clinical trial study was to assess the effects of dopexamine hydrochloride on organ failure, inflammatory mediators and splanchnic oxygenation in blunt multiple trauma patients at high risk of multiple organ dysfunction syndrome (MODS).

Methods

We performed a prospective randomised controlled trial on 30 consecutive blunt multiple trauma patients with ISS ≥ 16, age 18-60 years and initial blood pressure ≥120 mmHg initially admitted to our level I trauma centre. Patients were randomised to treatment with dopamine (n = 15) or dopexamine (n = 15) for 48 h after admission. Outcome in terms of mortality, MODS, splanchnic perfusion, complications, duration of stay was statistically analysed.

Results

Dopexamine treatment was associated with impaired organ function and an increased duration of ventilation and ICU stay compared with patients who received dopamine treatment. The acute inflammatory response was increased in the Dopexamine group while a decreased pHi and MEGX formation and increased serum lactate levels were measured.

Conclusions

The indication to use dopexamine hydrochloride appears questionable. In the absence of an antiinflammatory effect, dopexamine demonstrated a disadvantageous ICU course in regards to the organ function and the duration of treatment. In addition, a decreased pHi and MEGX formation suggested a deterioration of splanchnic oxygenation.     

Safety and adverse effects during 24 hours after contrast-enhanced MRI with gadobenate dimeglumine (MultiHance®) in children

Background

Gadolinium-based MR contrast agents have long been considered safe for routine diagnostic imaging. However, the advent of nephrogenic systemic fibrosis (NSF) among certain patients with severe renal insufficiency has brought the issue of safety into question. Nowhere is safety of greater concern than among children who frequently require multiple contrast-enhanced MRI examinations over an extended period of time.

Objective

To retrospectively evaluate the safety of gadobenate dimeglumine for contrast-enhanced (CE) MRI across a range of indications.

Materials and methods

Two hundred pediatric inpatients (age: 4 days to 15 years) underwent CE MRI as part of clinical routine. The children received a gadobenate dimeglumine dose of either 0.05 mmol/kg body weight (liver, abdominal imaging, musculoskeletal imaging, brain and other rare indications) or 0.1 mmol/kg bodyweight (cardiovascular imaging, MR-urography). Young (< 8 years) children with congenital heart disease were intubated and underwent MRA evaluation with controlled ventilation. Monitoring for adverse events was performed for at least 24 h after each gadobenate dimeglumine injection. Depending on clinical necessity, laboratory measurements and, in some cases, vital sign and ECG determinations were made before and after contrast injection. Safety was evaluated by age group, indication and dose administered.

Results

No clinically adverse events were reported among children who had one MRI scan only or among children who had several examinations. There were no changes in creatinine or bilirubin levels even in very young children.

Conclusions

No adverse events were recorded during the first 24 h following administration of gadobenate dimeglumine in 200 children.