CSF beta-amyloid 1-42 and tau in Tunisian patients with Alzheimer's disease: the effect of APOE epsilon4 allele

Alzheimer's disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. An accurate, convenient and objective test to detect AD is urgently needed for efficient drug development and effective clinical use of emerging therapies. The aim of the present work is to investigate the usefulness of cerebrospinal fluid (CSF) beta-amyloid protein (Abeta1-42) and total tau protein (t-tau) analyses in the diagnosis of AD and whether apolipoprotein E (ApoE) epsilon4 allele is a factor for AD affecting Tunisian people. Abeta1-42 and t-tau levels were measured in CSF from AD patients (n=73), non-Alzheimer dementia (nAD, n=35) and healthy controls (HC, n=38) by sandwich enzyme-linked immunosorbent assay. Abeta1-42 levels were decreased and t-tau increased in AD patients. The combination of Abeta1-42 and t-tau at baseline yielded a sensitivity of 87.4% for detection of AD. The specificities were 97.3% for controls and 82.7% for other dementia. The ApoE epsilon4 allele frequency (29.5%) was significantly higher in the AD patients than in the nAD patients (17.1%) or in the control groups (9.5%). AD patients carrying ApoE epsilon4 allele had lower Abeta1-42 (p<0.001) levels than those without a epsilon4 allele. The combination of t-tau and Abeta1-42 is a robust and reliable assay that may be useful in discriminating cases at risk for AD such as ApoE epsilon4 allele carriers from nAD patients or from age-matched control subjects.     

Pulmonary aspergillosis in a child with chronic granulomatous disease

The chronic granulomatous disease is characterised by the occurence of multiple bacterial and fungal infections since the early childhood. This susceptibility to infections must be prevented by a primary prophlylaxis against the opportunistic germs like pneumocystis and aspergillus. Our case is about a twelve-year-old boy who had a prophylaxis since his fourth month of life. At 10 years he presented a pleuro-pneumonia refractory to a large spectrum antibiotherapy. The aspergillar etiology was established on clinical, radiological and serological arguments. An amphotericine B treatment allowed a good clinical and radiological outcome of this pleuro-pulmonary affection. However, a dorsal spondylodiscitis complicated the course of the disease. A secondary vertebral aspergillosis or a Pott's disease were suspected. The vertebral bipsy was'nt conclusive. The association of antituberculous and antifungal agents with adjuvant molecules (IFN, granulotic transfusions and GM-CSF) permitted a good clinical outcome and the stabilisation of the radiological lesions.     

Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: Results from a randomized,double‐blind,multinational, Phase 3 study

Type 1 Gaucher disease (GD1), resulting from glucocerebrosidase deficiency, leads to splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone involvement. Current standard treatment is enzyme replacement therapy. Velaglucerase alfa is an enzyme replacement product for GD1, with the same amino acid sequence as naturally occurring human glucocerebrosidase. This multinational, Phase 3 trial evaluated the efficacy and safety of two doses of velaglucerase alfa in 25 treatment‐naïve, anemic patients with GD1 (4–62 years of age), randomized to intravenous velaglucerase alfa 60 U/kg (n=12) or 45 U/kg body weight (n=13) every other week for 12 months. The primary endpoint was change from baseline in hemoglobin concentration in the 60 U/kg arm. At 12 months, mean hemoglobin concentrations increased from baseline [60 U/kg: +23.3%; +2.43 g/dL (P<0.001); 45 U/kg: +23.8%; +2.44 g/dL (P<0.001)], as did mean platelet counts [60 U/kg: +65.9%; +50.9 × 10⁹/L (P=0.002); 45 U/kg: +66.4%; +40.9 × 10⁹/L(P=0.01)]. Mean splenic volume decreased from baseline [60 U/kg: ?50.4%, from 14.0 to 5.8 multiples of normal (MN) (P=0.003); 45 U/kg: ?39.9%, from 14.5 to 9.5 MN (P=0.009)]. No drug‐related serious adverse events or withdrawals were observed. One patient developed antibodies. Velaglucerase alfa was generally well tolerated and effective for adults and children with GD1 in this study. All disease‐specific parameters measured demonstrated clinically meaningful improvements after 12 months. Am. J. Hematol. 88:166–171, 2013. © 2012 Wiley Periodicals, Inc.     

La maladie de Rosai – Dorfman : enjeux thérapeutiques à propos de 2 observations

Rosai-Dorfman disease (RDD) is a benign lymphoproliferative disorder characterized by cervical lymph node enlargement with a consistent risk of airway compression and esthetic damage. Extranodal localizations are also described. There is no therapeutic consensus for pediatric forms of RDD. Through 2 pediatric cases with nodal involvement in 1 patient and a sinonasal and soft tissue localization in the other, we focus on the management problems of both nodal and extranodal RDD.     

−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (−2578C/A) and (−1154G/A) polymorphisms did not differ significantly between AD and control groups (p > 0.05). In the subgroup of ApoE ?4 carriers, the −2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE ?4 status using logistic regression, the −2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the −2578A allele may be associated with the development of AD in the individuals with ApoE ?4 allele. In addition, AD patients carrying the −2578A allele had lower Aβ42 (p = 0.029) levels than those without this allele, particularly in subjects with ApoE ?4 allele.     

Diagnostic moléculaire de la maladie de Gaucher en Tunisie

Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid β-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.