Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth

We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.     

Diazepam causes no adverse cardiocirculatory effects in cardiac patients

The effects of diazepam on hemodynamic measures and catecholamine levels were studied in 25 patients before administration of any other anesthetic or analgesic agent, for coronary artery bypass graft surgery. The patients were spontaneously breathing 40% oxygen in air, and no postural changes or surgical manipulations were allowed before or during the study. Before and ten minutes after completion of the intravenous infusion of 0.4 mg/kg of diazepam over five minutes, the following hemodynamic variables were determined: direct radial artery pressure, pulmonary artery pressure, central venous pressure, cardiac output by thermodilution in triplicate via a balloon-tipped pulmonary artery catheter and electrocardiograms. Norepinephrine, epinephrine, and dopamine levels were determined by liquid chromatography. Significant (P less than 0.05) reductions in pulmonary artery systolic pressure, systolic systemic blood pressure, and epinephrine levels were observed after diazepam administration. No other hemodynamic changes were statistically significant. Thus diazepam alone caused no adverse hemodynamic or endocrine effects in cardiac surgical patients. It is concluded that the use of diazepam is not contraindicated in cardiac patients with reduced myocardial oxygen supply as a consequence of coronary sclerosis.     

Midazolam causes no adverse hemodynamic effects in cardiac patients

The effects of midazolam on hemodynamic measures were evaluated in 30 patients scheduled for cardiac surgery. The patients were spontaneously breathing 40% oxygen in air and no postural changes or surgical manipulations were allowed before or during the study. Before and 10 minutes after completion of the intravenous infusion of 0.2 mg/kg of midazolam, the following hemodynamic variables were determined: direct radial artery pressure, pulmonary artery pressure, central venous pressure, cardiac output by thermodilution in triplicate via a Swan-Ganz pulmonary artery catheter, and electrocardiograms. Significant (P less than 0.05) reductions in systolic systemic blood pressure, systemic vascular resistance, systemic diastolic blood pressure, and left ventricular stroke work index were observed after midazolam administration. No other hemodynamic changes were statistically significant. Thus midazolam per se caused no adverse, but rather favorable, cardiocirculatory effects since it reduced cardiac work without altering cardiac contractility.     

Patients undergoing recurrent CT exams: assessment of patients with non-malignant diseases,reasons for imaging and imaging appropriateness

To determine percent of patients without malignancy and ≤ 40 years of age with high cumulative radiation doses through recurrent CT exams and assess imaging appropriateness. From the cohort of patients who received cumulative effective dose (CED) of ≥ 100 mSv over a 5-year period, a sub-set was identified with non-malignant disease. The top 50 clinical indications leading to multiple CTs were determined. Clinical decision support (CDS) system scores were analyzed using a widely adopted standard of 1–3 (red) as “not usually appropriate,” 4–6 (yellow) “may or may not be appropriate,” and 7–9 (green) “usually appropriate.” Clinicians reviewed patient records to assess compliance with appropriate use criteria (AUC). 9.6% of patients in our series were with non-malignant conditions and 1.4% with age ≤ 40 years. CDS scores (rounded) were 2% red, 38% yellow, 27% green, and 33% unscored CTs. Clinical society guidelines for CT exams, wherever available, were followed in 87.5 to 100% of cases. AUCs were not available for several clinical indications as also referral guidelines for serial CT imaging. More than half of CT exams were unrelated to follow-up of a primary chronic disease. We are faced with a situation wherein patients in age ≤ 40 years require or are thought to require many CT exams over the course of a few years but the radiation risk creates concern. There is a fair number of conditions for which AUC are not available. Suggested solutions include development of CT scanners with lesser radiation dose and further development of appropriateness criteria.     

Culture-negative endocarditis probably due to Chlamydia pneumoniae

A 59-year-old man had culture-negative endocarditis (clinical evidence compatible with endocarditis and histopathologic evidence of a recent episode of endocarditis) and serology compatible with a recent episode of Chlamydia pneumoniae infection. The conclusion was that this episode of culture-negative endocarditis was probably due to C. pneumoniae.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Clinical efficacy and cost effectiveness of intraoperative cell salvage in pelvic trauma surgery

Introduction

Pelvic acetabular injuries are associated with significant blood loss. This is compounded by multiple surgical interventions including definitive fracture fixation, which put patients at further risk of postoperative transfusion. We use intraoperative cell salvage routinely as a blood conservation strategy to address this issue. This is a prospective evaluation of the clinical efficacy and cost effectiveness of using intraoperative cell salvage in patients with pelvic acetabular injuries.

Methods

Data were collected prospectively for all the patients who underwent pelvic acetabular fracture fixation at our institution. A total of 30 patients (25 men, 5 women) with a mean age of 41 years (range: 31–79 years) were assessed over a period of 10 months.

Results

The mean preoperative and postoperative haemoglobin levels were 11.8g/dl and 9.9g/dl respectively. The mean intraoperative blood loss was 1,232.5ml (range: 150–2,693ml). The mean amount of blood salvaged and retransfused through a cell saver was 388ml. Of the 30 patients, 14 (47%) required transfusion after surgery and 26 units of blood were transfused. In terms of cost effectiveness, a total of £2,572 in 30 patients or £86 per patient were saved.

Conclusions

We found intraoperative cell salvage to be clinically efficacious and cost effective in patients with pelvic acetabular injuries.