Impaired TGF-ß signaling in patients with active systemic lupus erythematosus is associated with an overexpression of IL-22.

The mechanisms leading to the disruption of self-tolerance in systemic lupus erythematosus (SLE) remain elusive. Herein, we aimed to decipher the molecular basis of the impaired response of mononuclear cells to TGF-ß1. The Smad3-pathway was explored on CD3+ lymphocytes in either active or non active SLE patients. An impaired transcription of TGF-ß1 target genes was demonstrated in the CD3+ lymphocytes of active SLE patients confirming that the defect involves T cells and pointing to its extrinsic nature. We further demonstrate that the defect did not result from an impaired TGF-ßRII expression or Smad2/3 phosphorylation suggesting that the mechanism lies downstream Smad2/3 translocation. Interestingly, the TGF-1 signaling defect did not correlate with an increased expression of soluble or membrane-bound IL-15. However, it was associated with an overexpression of IL-22. This suggests that an excessive activation of AhR pathway (through UV radiations, infections, etc.) could lead to the inhibition of immunosuppressive actions of TGF-ß thus disrupting immune homeostasis in SLE. Collectively, our data suggest that the impaired response to TGF-ß in SLE patients is associated with disease activity and provide new insights into the pathogenesis of SLE since it could establish the link between the environmental factors and the aberrancies of the immune system usually described in SLE.

[First experience with outpatient laparoscopic cholecystectomy in Tunisia]. / Cholécystectomie laparoscopique ambulatoire: première expérience en Tunisie.

INTRODUCTION: Laparoscopic cholecystectomy is the gold standard treatment for symptomatic gallstones. There is some debate as to whether it should be performed in outpatient surgery or in one-day surgery to improve patient safety. This study aimed to evaluate the impact of laparoscopic cholecystectomy performed in outpatient surgery versus one-day surgery on standards such as mortality, serious adverse events and quality of life. METHODS: We conducted a cross-sectional descriptive study in the Department of General Surgery at the Habib Thameur Hospital over the period May 2009-February 2010. We here report 67 cases of symptomatic vesical lithiasis treated with outpatient laparoscopic cholecystectomy (OLC). ASA III and IV patients, diabetic patients treated with sulfonamides or insulin, severely obese patients, patients over 65 years of age and under 18 years of age, patients with a history of major abdominal surgery, patients with suspected lithiasis of the common bile duct, acute cholecystitis or pancreatitis were excluded from the study. Patients had to reside within 50 km of the hospital and be accompanied by an adult to undergo OLC. RESULTS: Seventeen patients were included and then excluded from our study because of the perioperative detection of signs of acute cholecystitis or difficulties in dissection leading to subhepatic drainage using Redon catheter at the end of the intervention. Finally, our study included 50 patients, 7 men and 43 women; the average age was 48 years. Surgery was based on the most common procedures. After leaving the recovery room, patients were conducted in the outpatient sector where they received a liquid diet. The patients were examined before 7 o'clock in the evening and discharge was established on the basis of the possibility of establishing an oral analgesic treatment, patients tolerance to liquid diet, the lack of urinary disorder, patients acceptance for discharge and analgesic and anti-inflammatory treatment if needed. Thirty-nine patients (78%) were discharged from hospital and 11 were kept in hospital. Patients > 45 years of age, anesthesia duration > 70 minutes and post operative fatigue were identified as risk factors for unsuccessful discharge. No readmission was observed. Discharged patients were satisfied with the therapeutic protocol, resulting in excellent and good outcome in the majority of cases (94%). CONCLUSION: Outpatient laparoscopic cholecystectomy seems to be as safe as day surgery laparoscopic cholecystectomy having low rate of complications and of hospital readmissions in some selected patients and lower surgery costs.

MEFV mutations in Tunisian patients suffering from familial Mediterranean fever.

OBJECTIVES: To identify the frequency and distribution of familial Mediterranean fever (FMF) gene (MEFV) mutations in Tunisian patients. PATIENTS AND METHODS: This study was performed in the Genetic Department of Tunis University Hospital. A clinical diagnosis of FMF was made according to published criteria. Mutation screening of the MEFV gene was performed in the Human Genetic Laboratory of the "Faculté de Medecine de Tunis" for 8 mutations including the 5 most common known mutations M694V, V726A, M694l, M680l, and E148Q. The tests performed were polymerase chain reaction (PCR) restriction-digestion for M694V, V726A, M680l, R761H, E148Q; amplification refractory mutation system for A744S, M694l; and PCR-electrophoresis assay for l692del. RESULTS: Of the 139 unrelated patients investigated, 61 (44%) had 1 or 2 mutations. In 78 (56%) probands no mutation was identified: 28 patients were homozygous; 16 were compound-heterozygous; 2 had complex alleles; and 17 had only 1 identifiable mutation. Of the mutations, M680l, M694V, M694l, V726A, A744S, R761H, l692DEL, and E148Q accounted for 32, 27, 13, 5, 3, 1, 1, and 18%, respectively. CONCLUSION: The profile of the MEFV gene mutations in the Tunisian population is concordant with other Arab populations but with some differences. M680l is the most common mutation, while V726A, the commonest mutation among Arabs, is rare in our population.