RATIONALE:We and others have previously demonstrated that SLIT can effectively desensitize peanut allergic children, albeit its molecular mechanism(s) is not elucidated. We hypothesized that SLIT acts, in part, by regulating transcription factors and interleukins that are critical to lymphocyte functions and allergic responses. METHODS: Peanut-allergic subjects (1.5-10 years old) were SLITtreated, with a brief escalating dose phase, and then maintained with a dose of 2 mg daily for 3 or 5 years. Subjects then were challenged with peanut, and clinically defined as non-sustained unresponsiveness (non-SU) or sustained unresponsiveness (SU). PBMC from the SLIT-treated subjects were contemporaneously obtained, cultured with the individual's own plasma; and their cryopreserved mRNA was RT-PCR analyzed. RESULTS: The abundance of mRNA for Foxp3, Blimp1, and T-bet in PBMC cultures derived from SU subjects (N55), who underwent 3 years of SLIT-treatment, was increased by ;500% (p<0.05), ;320% (p<0.05), and ;80% (p<0.05), respectively, as compared to their non-SU counterparts (N54). In PBMC from SU subjects (N54) treated for 5 years, ZNF90 mRNA abundance became moderately increased, being ;150% (p<0.05) of that in non-SU cultures (N59). However, the expression of GATA3 and Bcl-6 did not change. In contrast, IL-5 and IL-13 mRNA abundance was reduced in PBMC of SU subjects treated for 3 years, and further reduced and became statistically significant 5 years after SLIT-treatment. CONCLUSIONS: Peanut SLIT treatment up-regulates the expression of the transcription factors Foxp3, Blimp1, T-bet, and ZNF90, while downregulating IL-5 and IL-13, suggesting that these genes play an important role in SLIT-induced peanut sustained unresponsiveness.

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Tract stenoses and occlusions were the major cause of symptomatic shunt failure after TIPS creation. Substantial bile duct transections are often associated with tract abnormalities and recurrent symptoms. Although common, hepatic vein stenoses were rarely associated with recurrent symptoms in our patient population.

We evaluated the clinical outcome of malignant inferior vena cava (IVC) syndrome after intrahepatic IVC stent placement by retrospective analysis of 50 consecutive patients (25 men, 25 women, age 32-83 years) with malignant IVC syndrome who were treated with intrahepatic stent placement. Gianturco-Rosch-Z (GRZ) stents (n = 45), and Wallstents (n = 5) were inserted. Clinical outcome was assessed from patients' records using a score based on leg swelling, scrotal/vulvar edema, ascites and anasarca before and after stent placement, as well as at last follow-up visit before death. Clinical follow-up was supplemented by duplex sonography in 36 patients. Inferior venocavography was performed in 5 patients prior to re- intervention. Follow-up time ranged from 1 to 932 days (mean 62 days). Mean pressure gradient in the IVC was reduced from 14 +/- 4.1 mmHg before to 2.9 +/- 3.2 mmHg after stent placement (p < 0.001). Four patients had stent occlusion, 2 of whom were successfully re-stented. Primary and secondary patency was 59% and 100%, respectively at 540 days. Immediate clinical data were available in 44 patients: 38 improved; 6 did not respond. Last follow-up visit data were available in 36 patients: 24 showed persistent symptom relief till death. All symptom scores were significantly improved after stent placement (p < 0.001) and with the exception of ascites, remained significantly improved (p < 0.05) until the last follow-up. Increased serum bilirubin was a common characteristic of clinical failures and recurrences. Intrahepatic IVC stent placement resulted in significant symptomatic relief in patients with malignant IVC syndrome. Palliation was effective even in patients with a very short life expectancy.