Kombiniert-heterozygote Defizienz von Komplementfaktor C7 bei einerPatientin mit rezidivierender Meningitis

Zusammenfassung: Hintergrund:: Die Assoziation zwischen Komplementdefizienzen, insbesondere von Komponenten der terminalen Kaskade (C5-C9), und dem Auftreten von Meningokokkeninfekten und bakteriellen Meningitiden ist gut beschrieben. Fallbeschreibung:: In dem vorliegenden Fallbericht wird dabei erstmals ein kombiniert-heterozygoter Defekt im C7-Gen beschrieben, der noch eine Restproduktion von C7 erlaubte. Diese Restproduktion reichte jedoch nicht aus, um vor rezidivierenden Meningitiden zu schützen. Schlussfolgerung:: Der Fallbericht zeigt erneut den Stellenwert der Komplementdiagnostik bei Patienten mit Meningokokkeninfekt und die Notwendigkeit, auch Patienten mit reduzierter, aber noch messbarer Komplementaktivität einer weiteren Abklärung auf eine Komplementdefizienz zuzuführe

Deficits of ankle muscle strength not found in children, adolescents and young adults with haemophilic ankle arthropathy

OBJECTIVES: Adequate management of haemophilia patients requires early detection of joint impairment in relatively asymptomatic patients. This study sought to quantify the impact of the ankle's structural impairment on muscle strength in children, adolescent and young adults with haemophilia (CAAwH). METHODS: Twenty-three CAAwH underwent bilateral magnetic resonance imaging (MRI) assessing the anatomical status of tibiotalar joint (TTJ) and subtalar joint (STJ) using the International Prophylaxis Study Group MRI scale. An isokinetic dynamometer enabled a detailed evaluation of muscle strength at slow and fast speed. In parallel, 10 typically developing healthy boys (TDB) participated in a 1-week interval test-retest assessment to assess the test's reliability. RESULTS: Forty-six MRI ankle scores were obtained, with 11 patients unilaterally affected and one bilaterally. Of the 13 affected feet, nine showed abnormalities at TTJ, three at the posterior STJ and the remaining one at both joints. Muscle strength was not reduced in CAAwH exhibiting TTJ and/or STJ arthropathy, as compared to healthy TDB, nor was there any difference between the CAAwH's affected or unaffected sides. CONCLUSION: Contrarily to adult patients, CAAwH with repeated ankle bleeding may be less impaired than current structural evaluations imply, with possibly a latency between the occurrence of structural and functional damage.status: publishe

Occupational exposure to cobalt is not associated with incipient signs of dilated cardiomyopathy in a Belgian refinery

BACKGROUND: Excessive absorption of cobalt has been associated with cases of dilated cardiomyopathy in the past, but it is unclear whether occupationally exposed populations are at risk. OBJECTIVE: To assess the possible relationship between occupational exposure to cobalt and incipient signs of dilated cardiomyopathy. METHODS: A cross-sectional survey was conducted in a cobalt production facility in Belgium constituting one of the largest occupational populations worldwide (n=256 male workers). Exposure to cobalt was assessed by measuring urinary cobalt concentration (µg/gcreat), reflecting recent exposure, and by computing an integrated exposure index (µg/gcreat×years), reflecting long-term exposure. The effect on the myocardium was investigated by echocardiography and electrocardiography, and dose-effect relations with cobalt exposure were traced by multiple regression analysis. RESULTS: No dose-effect relationship between exposure to cobalt and parameters reflecting dilated cardiomyopathy was found in a population of workers characterised by a median recent cobalturia of 4 µg/gcreat and a median long-term cobalturia of 100 µg/gcreat×years. A reduction in the dimensions of the left ventricular internal cavity was associated with recent exposure to cobalt. CONCLUSIONS: Occupational exposure to cobalt does not appear associated with incipient signs of dilated cardiomyopathy within the gradient of exposure recorded in this population

Paroles publiques, paroles confidentielles

Ce numéro thématique invite à une réflexion documentée sur le rapport entre les situations d’usage de la parole et leurs contextes sociaux (entendus dans un sens large). Il propose sept études fondées sur des enquêtes tout à la fois ethnographiques et historiques. Si les auteurs sont associés formellement à des disciplines différentes (anthropologie sociale et linguistique, littérature comparée, sociologie), leurs perspectives spécifiques n’en contribuent pas moins à mettre en évidence la dimension pragmatique de l’oralité des formes de discours qui sont retenues comme objet de leurs enquêtes

Mutational analysis of the zinc- and substrate-binding sites in the CphA metallo-beta-lactamase from Aeromonas hydrophila.

The subclass B2 CphA (Carbapenemase hydrolysing Aeromonas) beta-lactamase from Aeromonas hydrophila is a Zn(2+)-containing enzyme that specifically hydrolyses carbapenems. In an effort to evaluate residues potentially involved in metal binding and/or catalysis (His(118), Asp(120), His(196) and His(263)) and in substrate specificity (Val(67), Thr(157), Lys(224) and Lys(226)), site-directed mutants of CphA were generated and characterized. Our results confirm that the first zinc ion is in interaction with Asp(120) and His(263), and thus is located in the 'cysteine' zinc-binding site. His(118) and His(196) residues seem to be interacting with the second zinc ion, as their replacement by alanine residues has a negative effect on the affinity for this second metal ion. Val(67) plays a significant role in the binding of biapenem and benzylpenicillin. The properties of a mutant with a five residue (LFKHV) insertion just after Val(67) also reveals the importance of this region for substrate binding. This latter mutant has a higher affinity for the second zinc ion than wild-type CphA. The T157A mutant exhibits a significantly modified activity spectrum. Analysis of the K224Q and N116H/N220G/K224Q mutants suggests a significant role for Lys(224) in the binding of substrate. Lys(226) is not essential for the binding and hydrolysis of substrates. Thus the present paper helps to elucidate the position of the second zinc ion, which was controversial, and to identify residues important for substrate binding