Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases

OBJECTIVE: To describe the response to first-line immunosuppressive therapy with or without pulmonary vasodilators in pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD). METHODS: Twenty-three consecutive patients with SLE- or MCTD-associated PAH treated with first-line immunosuppressive therapy either alone (n = 16) or in combination with pulmonary vasodilators (n = 7) were evaluated according to clinical and hemodynamic criteria before and after immunosuppressive therapy. Responders were defined as patients in New York Heart Association (NYHA) functional class I or II with hemodynamic improvement after the last pulse of cyclophosphamide. RESULTS: Among the 16 patients treated with first-line immunosuppressive therapy alone, 8 (50%) were responders. These patients had a significantly improved NYHA functional class, 6-minute walking distance, and mean pulmonary artery pressure. Patients in NYHA functional class I or II and/or a cardiac index >3.1 liters/minute/m(2) at baseline were more likely to benefit from immunosuppressive therapy. Six of the 8 nonresponders subsequently improved with pulmonary vasodilators. Among the 7 patients who were initially treated with immunosuppressive therapy and pulmonary vasodilators, 4 (57.1%) were responders. CONCLUSION: PAH associated with SLE or MCTD may respond to a treatment combining cyclophosphamide and glucocorticoids. Patients who could benefit from this immunosuppressive therapy could be those who have less severe disease at baseline. For patients with more severe disease, pulmonary vasodilators should be started, possibly in combination with immunosuppressants. In any case, clinical and hemodynamic evaluations are mandatory to monitor the response and adapt the treatment. These retrospective and uncontrolled data need to be confirmed by randomized controlled trials.     

Partial monosomy 12p13.1----13.3.

We describe a 27 month old female child with partial monosomy for the short arm of chromosome 12: 46,XX,del(12)(p13.1----p13.3). She differs from the eight cases described by others, in that she is less severely affected. Her main clinical features are developmental delay, protruding tongue, strabismus, slightly unusual facies, slight micrognathia, and speech delay.     

Migration of Additives in Polymer Coatings: Phosphonated Additives and Poly(vinylidene chloride)‐Based Matrix

Summary: The living radical terpolymerization of vinylidene chloride (VC₂), methyl acrylate (MA), and dimethyl‐2‐methacryloxyethylphosphonate (MAPHOS) was performed at 70 °C in benzene by a reversible addition fragmentation chain transfer (RAFT) process to yield a gradient terpolymer of controlled molecular weight ( = 5 800 g · mol⁻¹, I_p = 1.53) with a molar composition of 75:14:11 (VC₂/MA/MAPHOS). Such terpolymers, hydrolyzed (phosphonic acid groups) or not, were used as polymeric additives in coating formulations based on a poly(VC₂‐co‐MA) copolymer matrix ( = 63 300 g · mol⁻¹, I_p = 1.99, VC₂/MA = 80:20 molar ratio). The formulations were spun cast on stainless steel surfaces and the coatings were observed by scanning electron microscopy (SEM) coupled with X‐ray analyses (EDX). The hydrolyzed additive was shown to both segregate and migrate towards the metal interface, leading to a preferential organization of the coating. Hence, the matrix at the air surface acts as a barrier to gas while the additive ensures adhesion at the polymer/metal interface.

SEM photograph of a section of the coating with formulation 4 [poly(VC₂‐co‐MA‐co‐MAPHOS(OH)₂) (75:14:11)].     

Paradoxical sleep in mice lacking M3 and M2/M4 muscarinic receptors

Acetylcholine is crucial for the regulation of paradoxical sleep (PS) and EEG theta activity. To determine the contribution of individual muscarinic receptors to these events, we analyzed the sleep-waking cycle and EEG activities of mice lacking functional M(3) or M(2)/M(4 )receptors. Daily PS amounts were significantly decreased in M3-/- (-22%) but not in M2/M4-/- mice. Further, the theta peak frequency for PS was significantly increased in both M2/M4-/- and M3-/- mice. This study supports the potential role of M(3) rather than M(2) and M(4) muscarinic receptors in the modulation of PS in mice and strengthens the idea that multiple muscarinic receptors contribute to the regulation of the EEG theta activity during PS.