How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

BackgroundFabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb₃), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb₃), is increased in patients with the disease. Until now, lyso-Gb₃ was not detectable in urine, possibly because of the presence of interfering compounds.MethodsWe undertook to: 1) characterize lyso-Gb₃ in urine; 2) develop a method to quantitate urinary lyso-Gb₃ by mass spectrometry; 3) evaluate urinary lyso-Gb₃ as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb₃ is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb₃ from 83 Fabry patients and 77 healthy age-matched controls.ResultsThe intraday and interday bias and precision of the method were < 15%. Increases in lyso-Gb₃/creatinine correlated with the concentrations of Gb₃ (r² = 0.43), type of mutations (p = 0.0006), gender (p < 0.0001) and enzyme replacement therapy status (p = 0.0012). Urine from healthy controls contained no detectable lyso-Gb₃. Lyso-Gb₃ did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb₃ of Fabry patients correlated well with a number of indicators of disease severity.ConclusionLyso-Gb₃ is a reliable independent biomarker for clinically important characteristics of Fabry disease.     

Bilateral inguinal hernias repair: Analytic study of 71 patients

Summary A retrospective review of a series of 71 patients operated on between January 1986 and December 1995, for bilateral inguinal hernias was carried out. The patients were treated by insertion of a non-absorbable unslit mesh via either the inguinal route or a laparoscopic approach. A two stage operation via the inguinal route was performed in 23 patients (group A). The remainder underwent a one-stage procedure: 23 patients (group B) were offered open repair using a preperitoneal mesh via a bilateral inguinal route and 25 patients (group C) underwent bilateral laparoscopic repair through a totally preperitoneal approach (n=is) or a transperitoneal approach (n=10). The three groups were broadly similar and comparable. The length of operative procedure was identical in the 3 groups. The duration of hospital stay was respectively 11.2, 5.8 and 3.3 days in the three groups. The return to normal activities was shorter in groups B and C than in group A. At long term, with a mean follow-up of two years, the rate of recurrence was similar in the 3 groups. This study confirmed that a one stage operation does not carry great risks, and has the advantages of sparing the patient a second operation. It is economical in terms of operating time, duration of hospital stay, and delay in return to work. The laparoscopic procedure seems the most suitable approach for these hernia repairs. Further investigation of this technique in comparison with other open herniorrhaphy procedures, with randomised prospective trials, is required before its widescale application can be recommended.     

The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma

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