Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms: evidence for a family of platelet-aggregation inhibitors.

The purification, complete amino acid sequence, and biological activity are described for several homologous snake venom proteins that are platelet glycoprotein (GP) IIb-IIIa antagonists and potent inhibitors of platelet aggregation. The primary structures of kistrin (from Agkistrodon rhodostoma), bitan (from Bitis arietans), three isoforms of trigramin (from Trimeresusus gramineus), and an isoform of echistatin (from Echis carinatus) were determined by automated sequence analysis and fast atom bombardment mass spectrometry analysis. Each of the protein in this family, which range from 47 to 83 residues, contains an Arg-Gly-Asp amino acid sequence found in protein ligands that binds to GPIIb-IIIa, a high (17 +/- 1%) cysteine content conserved in the primary sequence, and a homologous N-terminal region absent only in the echistatin isoforms. Each protein directly inhibits the interaction of purified platelet GPIIb-IIIa to immobilized fibrinogen about 100 times more effectively than does the pentapeptide Gly-Arg-Gly-Asp-Ser; IC50 values range from 1.1 to 3.0 nM. The IC50 value for the inhibition of platelet aggregation, using human platelet-rich plasma stimulated with ADP, ranges from 110 to 550 nM for the various proteins, about 1000-fold more potent than Gly-Arg-Gly-Asp-Ser. Kistrin binds reversibly to both resting and ADP-activated human platelets with high affinity (Kd = 10.8 nM and 1.7 nM, respectively) and to purified GPIIb-IIIa with a lower affinity (Kd = approximately 100 nM). Finally, kistrin injected at 1.0 mg/kg into rabbits reversibly inhibits platelet aggregation ex vivo over 30 min without induction of thrombocytopenia. We propose that these proteins are members of a general class of proteins found in the venom of pit vipers that inhibit platelet aggregation by antagonism of the GPIIb-IIIa-fibrinogen interaction and as such serve as potential antithrombotic agents.     

Terminal ileitis due to Yersinia enterocolitica in infants

Yersinia enterocolitica infection presents a wide clinical spectrum; in infants and young children it usually presents as uncomplicated acute diarrhea, while in older children and adolescents it more frequently presents as terminal ileitis and/or mesenteric adenitis. We describe two infants who developed terminal ileitis complicating Y. enterocolitica infection, which is exceptionally rare. The clinical, laboratory and radiologic findings are described and ultrasound study is emphasized as a simple and reliable tool for investigation of terminal ileitis.     

Fiberoptic intubation in adult patients with predictive signs of difficult intubation: inhalational induction using sevoflurane and an endoscopic facial mask

OBJECTIVE: To evaluate the combination of inhalational induction with sevoflurane and fiberoptic intubation through a specific facial mask for anticipated difficult tracheal intubation (DI) in adults. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: Eighteen consecutive patients at risk of DI. After premedication made of hydroxyzine 2 mg x kg(-1), preoxygenation, 0.1 microg x kg(-1) sufentanil was administered (T0), then, inhalational induction was started: sevoflurane 8% in 100% O2 l x min(-1). After 1 min, sevoflurane was decreased to 5% and, if necessary, adapted to obtain an adequate depth of anaesthesia (Ramsay score > 3). Fiberoptic bronchoscopy was performed through a Fibroxy mask. BP was measured every 2.5 min, HR, SpO2, RR were recorded. The results were analyzed by Newman-Keuls test. RESULTS: Intubation was easily realized but it was necessary to assist ventilation in patients presenting prolonged apnea lasting more than 30 s (5 out of 9 patients who presented apnea during procedure). Intubation was quickly realized (T+ 4 +/- 3 min). Haemodynamics and saturation were not altered during procedure. Inhalatory induction using sevoflurane costs 6 10 versus 16 80 for intravenous target controlled propofol anesthesia (using only one preconditionned syringe). CONCLUSION: Inhalational induction with sevoflurane and fiberoptic intubation appeared easy, fast and cheap.     

Cerebral and renal toxicity of acyclovir in a patient treated for meningoencephalitis

We report the case of a 65-year-old man treated with intravenous acyclovir and amoxicilline for meningoencephalitis. Six days later, he suddenly developed acute renal failure, associated with central nervous system symptoms. The high acyclovir concentration in plasma and spinal fluid confirmed the hypothesis of acyclovir toxicity. Continuous haemofiltration resulted in a rapid amendment of neurologic and renal symptoms. Despite the high therapeutic index of acyclovir, manifestations of neurotoxicity and nephrotoxicity are not a rare event. The risk is increased in the elderly and in patients with renal insufficiency. Rapid intravenous injections are contraindicated. Continuous haemofiltration is rapidly efficient. The value of acyclovir concentration determination in plasma and spinal fluid are stressed.