A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.

Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease.

ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development.

The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria.

Etomidate vs. propofol to carry out suspension laryngoscopies.

Patients about to undergo a suspension laryngoscopy were randomly assigned to one of two groups (n = 10). They were given either etomidate 1 mg kg-1 followed by 1 mg kg-1 h-1, or propofol 2.5 mg kg-1 followed by 9 mg kg-1 h-1. Alfentanil 10 micrograms kg-1 was given to provide analgesia with a further half dose if necessary. Duration of apnoea, quality of anaesthesia, times between stopping hypnotic administration and the moment when the patients opened their eyes, gave their name, date of birth and the day's date were noted. Heart rate, blood pressures, respiratory frequency and blood gases were noted before induction, before suspension and when hypnotic infusion was stopped. Clinical tolerance was good, the duration of surgery, apnoea and quality of anaesthesia were the same for both groups. Blood pressure was less depressed by etomidate, but ventilatory frequency was higher. Recovery was significantly faster after propofol. Propofol is recommended for patients who require good post-operative cooperation (chronic obstructive pulmonary disease) and etomidate for those who are haemodynamically compromised.

[Comparison of the incidence of bleeding of 2 anesthetic technics midazolam-alfentanil versus propofol-alfentanil during treatment of otospongiosis]. / Comparaison de l'incidence sur le saignement de deux techniques anesthésiques midazolam-alfentanil versus propofol-alfentanil lors de la cure d'otospongiose.

This study was performed to compare the incidence of bleeding associated with two anaesthetic techniques during otolaryngological microsurgery. Twenty-eight venous interpositions for otospongiosis have been carried out at random either under local anaesthesia combined with light sedation (midazolam 0.1 mg.kg-1 and alfentanil 0 micrograms.kg-1) or using general anaesthesia (propofol 2.5 mg.kg-1, then 9 mg.kg-1.hr-1 and alfentanil 30 micrograms.kg-1, then 15 micrograms.kg-1). The patients' lungs were mechanically ventilated. Every ten minutes, heart rate, arterial blood pressure and FETCO2 were observed. Bleeding was assessed on a four-point scale and evaluated according to its duration and the annoyance that it caused. General anaesthesia was clinically better tolerated. Heart rate and arterial blood pressure were lower than with general anaesthesia. The end-expiratory CO2 was 4.7 +/- 0.2 per cent. Bleeding was less frequent, lasted less time, but when it occurred the surgical disturbance was identical in the two groups. General anaesthesia produced a less bloody operating field and local anaesthesia required the cooperation of the patient.