[Auditory and vestibular findings in Fabry disease: a study of 25 patients]. / Atteintes ORL de la maladie de Fabry : à propos de 25 observations.

PURPOSE: Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disorder due to deficient activity of the enzyme alpha-galactosidase A. Males and females exhibit severe organ involvement. The high incidence of otological symptoms was recently reported. PATIENTS AND METHODS: Monocentric and retrospective study of twenty-five patients with FD (13 families; seven males and 18 females). The patients underwent audiological assessment before initiation and during enzyme replacement therapy. We also analysed neurologic heart and kidney status. RESULTS: Twenty patients (80%; 13 females and seven males) complained of otologic symptoms. Audiological evaluation showed a sensorineural hearing loss in 17 patients, bilateral in 16 out of them. Vestibular examination showed a functional impairment in two patients (one female, one male). Correlations were found between hearing loss and either kidney disease (73,3%), neurological complications (100%) and cardiomyopathy (80%). Fourteen patients (56%; seven females, seven males) received enzyme replacement therapy. Improvement or stabilization of the audiological evaluation was reported in seven patients, whereas worsening was observed in three patients. CONCLUSION: This study confirms the high frequency of audiological involvements in females and males with FD. Our analysis suggests that the frequency of hearing loss is increased in the presence of renal or neurologic involvement or cardiomyopathy. There is no clinically significant efficacy of enzyme replacement therapy on hearing function. Although the pathophysiology remains unknown, a vascular mechanism responsible of the inner ear involvement seems to be privileged.

Reaction of hen egg white lysozyme with Fischer-type metallocarbene complexes. Characterization of the conjugates and determination of the metal complex binding sites.

The introduction of heavy atoms into protein crystals is sometimes rendered difficult and tedious because of the poor specificity of the available reagents for particular target residues. On the other hand, transition organometallic chemistry offers an almost untouched field for this purpose. In particular, Fischer-type metallocarbene complexes of the general formula (CO)5W=C(OR1)R2 may be attractive reagents because they contain the heavy element tungsten and specifically target amino groups to form stable, covalent aminocarbene adducts. With a small protein such as hen egg white lysozyme (HEWL) with a limited number of potential binding sites, it was possible to form protein-aminocarbene conjugates that have an average of one aminocarbene moiety per protein molecule. RP-HPLC combined with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MS analysis of the conjugates revealed that they were mixtures of the native protein, monoaminocarbenes and diaminocarbenes. Tryptic proteolysis experiments performed on the protein conjugates combined with MALDI-TOF-MS analysis of the aminocarbenic peptides allowed us to determine that lysines 13, 33, 97 and 116 were involved in the reaction of HEWL with (CO)5W=C(OMe)Me.

[Management of self poisoning at an emergency medical center]. / Régulation et prise en charge des intoxications volontaires par un service d'aide médicale d'urgence.

OBJECTIVE: We examined the response given to calls for acute self-poisonings in a French department (Vienne) in order to determine current management practices. PATIENTS AND METHODS: We reviewed retrospectively all calls to the Vienne pre-hospital emergency care center between January 1997 and December 1999 that concerned acute self-poisoning. There were 2,057 calls for 1,312 women and 708 men (mean age 35.3 +/- 13.7 years, age range 8-99 years). RESULTS: The call was made by a private person in 72.1% of the cases, by a physician in 14.4% and by a first-aid worker in 8.4%. The annual incidence was 1.83 calls per 1000 inhabitants. Self-poisoning led to death in 1% of the cases (mean age 40.8 +/- 10.8 years, age range 27-70 years). A total of 3,225 toxic agents were identified, i.e. 1.56 +/- 1 agent per poisoning (range 1-10). Psychotrops predominated and were found in 74.8% of the suicide attempts with drugs. Non-drug poisonings accounted for 2.5% of the cases. The emergency center responded to the call by dispatching an ambulance (56.4%) or a medicalized emergency care unit (22.4%), providing counsel (18.2%), or calling in a physician (1.1%). A mobile hospital unit was dispatched in 58% of the cases judged to involve a life-threatening situation. CONCLUSION: Self-poisoning is one of the most common situations managed by pre-hospital emergency care centers. The response given to emergency calls would appear to be insufficiently medicalized.