Heating Lyophilised Factor VIII Does Not Alter Its Recognition by Specific Antibodies

Background and objectives: Alterations of factor VIII (FVIII) during preparation procedures can potentially affect its immunogenicity. One method evaluating such alterations could be by determining the reactivity of FVIII with specific antibodies. Materials and methods: Since heat treatment is currently used to reduce the risk of viral transmission, we evaluated the immunoreactivity of plasma-derived FVIII before and after heating at different temperatures and for different periods. Freeze-dried FVIII was used for these experiments as part of the validation procedure of a novel FVIII preparation. Results: Heating FVIII for up to 72 h at 80 °C does not alter its reactivity with specific rabbit antibodies or mouse monoclonal antibodies, although some loss of FVIII activity occurred after 72 h. After heating for 2 h at 100 °C, a procedure that reduced FVIII activity by about 50%, there were still no significant effects on FVIII reactivity with monoclonal antibodies. Conclusions: Freeze-dried preparations of plasma-derived FVIII seem to be resistant to heat-induced structural denaturation.     

Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity.     

Considération critique sur l’extension de la bipolarité, psychopathologie des mouvements d’humeur et de l’euphorie morbide

Objectives

From manic-depressive psychosis to bipolar spectrum, today's psychiatry allows us to observe a widening of bipolar criteria. This article aims at studying this evolution, its consequences with a critical look and the psychopathology of mood changes and morbid euphoria.

Methods

All of our considerations refer to current data on bipolar disorders (review with Medline and Science Direct) compared with studies from classical psychiatrists (Kraepelin, Ey) and various authors inspired by psychoanalysis (Freud, Racamier) and phenomenology (Binswanger, Tellenbach, Tatossian).

Results

Many contemporary authors encourage clinicians to detect bipolar disorders from symptoms, early signs and attenuated or atypical expressions. The concept of a widened spectrum is supposed to be closer to clinical reality and it would be an opportunity to diagnose this disease and its deleterious consequences better and thus to set up an appropriate therapy at an early stage. Other authors, on the other hand, deplore a dilution of bipolar disorders together with harmful diagnostic inflation around a concept that has become too heterogeneous to be effective, that subjugates or interferes with other pathologic entities in an excessive manner and abandoning a psychopathological approach. In this view, we shall analyze the nosographic shifts of bipolar disorders throughout the history of psychiatry, from manic-depressive psychosis to bipolar disorder and spectrum. We shall then scrutinize the autonomy and limitations related to bipolar disorders as opposed to normality, confusing clinical presentations and other major mental diseases: Psychosis, depression, pathological personality, anxiety, impulse-control, attention deficit-hyperactivity, addiction and psycho-organic disorders. This work shall first introduce a discussion on the concept of bipolar disorders for children, and then through the case of some historical figures. Then we will deal with the contemporary social factors that are currently furthering the extension of this diagnosis. Last, this article sheds a light on psychopathological specificities of mania – the cornerstone in bipolar disorders – mood changes and morbid euphoria.

Conclusion

We think that classic psychiatry, phenomenology and psychoanalysis would act as a guiding light through this debate and could help the clinician in this daily practice. Mood variations require a careful clinical observation and a rigorous set of interpretation, before being specified too excessively or hastily as a symptom of a real bipolarity.