Enhanced coagulation activation in preeclampsia: the role of APC resistance,microparticles and other plasma constituents

In the Second Northwick Park Heart Study, the activation peptides of factor IX (FIXpep) and factor X (FXpep) were measured in 1261 middle-aged men by double-antibody radioimmunoassay. During follow-up 147 men who had a first coronary heart disease (CHD) event were found to have had an increased FIXpep (p = 0.003) and a reduced FXpep (p = 0.05) at baseline compared with those remaining CHD-free (controls). Plasma FIXpep and FXpep were positively associated, but the rate of rise in FIXpep with increasing FXpep was higher in cases than controls (p for interaction = 0.01). In a sample of 87 controls, FIXpep was positively and independently related to the concentrations of a polymorphonuclear-specific fibrinogen degradation product (p = 0.036) and FXpep (p = 0.004), but in larger samples no statistically significant associations were found either with C-reactive protein or with fibrinogen concentration. The findings suggested that the increased FIXpep in men at high CHD-risk may have been partly due to the generation of factor IX inactivation peptides by inflammatory proteolysis and their recognition together with true FIXpep in the radioimmunoassay. Direct evidence for this hypothesis requires development of assays for human elastase-specific factor IX inactivation peptides.     

Intravitreal injection of adeno-associated viral vectors results in the transduction of different types of retinal neurons in neonatal and adult rats: a comparison with lentiviral vectors

Replication-deficient viral vectors encoding the marker gene green fluorescent protein (GFP) were injected into the vitreous of newborn, juvenile (P14), and adult rats. We tested two different types of modified virus: adeno-associated viral-2-GFP (AAV-GFP) and lentiviral-GFP vectors (LV-GFP). The extent of retinal cell transduction in different-aged animals was compared 7, 21, and 70 days after eye injections. At all postinjection times, LV-GFP transduction was mostly limited to pigment epithelium and cells in sclera and choroid. In contrast, transduction of large numbers of neural retinal cells was seen 21 and 70 days after AAV-GFP injections. AAV-GFP predominantly transduced neurons, although GFP-positive Müller cells were seen. All neuronal classes were labeled, but the extent of transduction for a given class varied depending on injection age. After P0 injections about 50% of transduced cells were photoreceptors and 30-40% were amacrine or bipolar cells. After adult injections 60-70% of transduced cells were retinal ganglion cells. In adults many GFP-positive retinal axons were traced through the optic nerve/tract and terminal arbors were visualized in central targets.     

The Delphic oracle: a multidisciplinary defense of the gaseous vent theory

Ancient historical references consistently describe an intoxicating gas, produced by a cavern in the ground, as the source of the power at the oracle of Delphi. These ancient writings are supported by a series of associated geological findings. Chemical analysis of the spring waters and travertine deposits at the site show these gases to be the light hydrocarbon gases methane, ethane, and ethylene. The effects of inhaling ethylene, a major anesthetic gas in the mid-20th century, are similar to those described in the ancient writings. We believe the probable cause of the trancelike state of the Priestess (the Pythia) at the oracle of Delphi during her mantic sessions was produced by inhaling ethylene gas or a mixture of ethylene and ethane from a naturally occurring vent of geological origin.     

Preclinical assessment of anti-CD40 Mab 5D12 in cynomolgus monkeys

Monoclonal antibody (Mab) 5D12 is a potent antagonist of the CD40-CD40L pathway. This cellular interaction has been validated in a large number of experimental animal models where dys-regulation of the immune system plays a role. Chimeric 5D12 (ch5D12) was constructed to reduce the potential immunogenicity and enhance the in vivo half-life when used in humans. ch5D12 is a molecularly engineered human IgG(4) antibody containing the variable domains of the heavy and light chains of the murine version of 5D12 (mu5D12). This new chimeric Mab was tested in a marmoset experimental autoimmune encephalomyelitis model and was shown to effectively prevent disease symptoms. The results of this in vivo evaluation supported clinical use of ch5D12 for immune targeted diseases. Therefore GMP material was prepared and a GLP-compliant tissue cross-reactivity study on human tissues (3 donors/37 tissues) and cynomolgus tissues (2 donors/37 tissues) was performed. ch5D12 stained on the surface of B cells and selected dendritic cells and no unexpected cross-reactivity was observed. The identical staining patterns in human and cynomolgus tissues justified the use of cynomolgus monkeys as a relevant model for humans. A GLP-compliant safety and tolerability evaluation for ch5D12 in cynomolgus monkeys was performed using the GMP produced material. Weekly administration of ch5D12 at two dose levels for 4 weeks was shown to be safe and without any side effects in all monkeys.     

Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors: a case-control study using spontaneous reports

The aim of this study was to assess whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with extrapyramidal syndromes (EPS). We analysed the spontaneous reports of adverse drug reactions (ADRs) collected by The Netherlands Pharmacovigilance Foundation Lareb in the period 1985-99 (n = 24,263). The study population comprised all patients using an antidepressant drug at the time the ADR occurred. We calculated ADR-reporting odds ratios (ADR-OR) to estimate the association between SSRI-use and EPS, relative to other antidepressants. We identified 61 patients with EPS. SSRI-use was associated with spontaneous reporting of EPS compared to other antidepressants (adjusted ADR-OR 2.2; 95% confidence interval 1.2-3.9). This risk estimate appeared to be higher in patients concurrently using antipsychotic medication (6.9, 0.7-68.0), although the confidence interval was very wide. In conclusion, SSRI-use seems only to be moderately associated with EPS compared to other antidepressants. However, those concurrently using antipsychotic drugs or presenting with other risk factors may be more susceptible and should be closely monitored.     

Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide

Etoposide is commonly used in a variety of malignancies. A well known but rare toxicity are hypersensitivity reactions, usually manifested by chest discomfort, dyspnoea, bronchospasm and hypotension. We report the details of a patient who developed hypersensitivity reactions to intravenous etoposide, but subsequently tolerated the administration of intravenous etoposide phosphate with no sequelae.     

Subclinical Legionella infection in workers near the source of a large outbreak of Legionnaires disease

A survey was conducted of exhibitors at a 1999 floral trade show, where a whirlpool spa on display caused a large outbreak of legionnaires disease (LD). In total, 742 exhibitors without LD returned a questionnaire on their whereabouts during the fair and their health afterward and supplied blood samples for the detection of IgM and IgG antibodies against Legionella pneumophila. The exhibitors had higher average antibody levels than did the general population. The closer to the whirlpool that the exhibitors worked, the higher their antibody levels. Both high-normal and high titer levels were found more frequently among workers with more exposure, suggesting that serosurveys among potentially exposed subjects are a valuable tool for outbreak investigation. Some differences in health complaints were observed between the more and less exposed groups, as estimated by the workplace location, but few differences were found between groups with different antibody levels.     

Problems with laparoscopic instruments: opinions of experts.

INTRODUCTION: Laparoscopic surgery is particularly known for its complex technique, which calls for operative analysis of laparoscopic instruments. This study investigates the opinion of experts about clinical problems with instruments occurring during laparoscopic surgery. METHODS: A questionnaire was used to obtain the opinions of expert laparoscopic surgeons about difficulties experienced operatively using laparoscopic instruments. RESULTS: The laparoscopic surgeons indicated that coagulators were especially prone to cause complications of the gastro-intestinal tract, vascular injuries, and bile duct injuries. Dissectors were considered to play a role in the occurrence of solid organ and bile duct injuries, and retractors to cause solid organ injuries. Insufficient functionality of the instruments and insufficient quality of the image were indicated to contribute to the instrument's risks. CONCLUSION: The questionnaire identified technological deficiencies prone to cause operative complications. The results provide a basis for the interaction between surgeons and engineers, and serve as pilot information on which to base an in-depth object evaluation of instrument problems.     

Extracorporeal membrane oxygenation before induction of anesthesia in critically ill thoracic transplant patients

Cardiorespiratory failure just before surgery in critically ill thoracic transplant patients can have catastrophic consequences. We judged the cardiorespiratory condition in three of 160 thoracic transplant procedures performed in our center too unstable for a safe induction of anesthesia. In these 3 patients, extracorporeal membrane oxygenation support was installed before induction of anesthesia to maintain an adequate cardiorespiratory state. This strategy was successful for all 3 patients, and long-term survival was achieved with a good quality of life. Guidelines for indications to follow this strategy are discussed.