Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids

Background

Limited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization.

Objectives

To evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids.

Methods

Nineteen patients were treated with thalidomide for 24 months starting with 200 mg/d for first 2 weeks, followed by 100 mg/d for 11 weeks and a maintenance dose of 100 mg on alternate days for 35 weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28).

Results

Skin score significantly decreased (P < 0.001). Lower skin scores occurred after 3 and 6 months (P < 0.05). s-ACE levels decreased over time at the third month (P < 0.001). CXR assessed by radiological stage significantly improved during the first 6 months (P < 0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment.

Conclusions

Thalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids.     

Kinetics of the free radical terpolymerization of diethyl maleate with methyl methacrylate and styrene

The kinetics of the free radical terpolymerization of diethyl maleate (DEM) (M₁) with methyl methacrylate (MMA) (M₂) and styrene (M₃) was investigated at 60°C with AIBN as initiator. The analysis of the dependence of the terpolymer composition on the feed composition was difficult due to the similar chemical and physical properties of diethyl maleate and methyl methacrylate and also by the low content of the former monomer in the terpolymers. Finally, the terpolymer composition could be determined by means of microanalyses of carbon and hydrogen content. The results of these determinations were confirmed by ¹³C NMR spectroscopy. The initiation rate constant of AIBN was studied at different feed compositions by means of the inhibition method. For the study of the over-all polymerization kinetics of this ternary system it was necessary to take into account the dependence of the termination rate on the feed composition. It was found that not only the viscosity of the solution, but also the properties of the polymer segment next to the radical site have to be considered. Containing only parameters and constants measured independently from terpolymerization, the kinetic equation obtained described satisfactorily the initial over-all rates.     

Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction

Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery. In this study, piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications, either in the absence or in the presence of a concomitant antibiotic treatment. Thirty patients were randomly assigned to three groups and treated for 3 days, before impacted lower third molar removal, as follows: (1) sublingual piroxicam-FDDF (fast dissolving dosage formulation) 20 mg/day; (2) oral azithromycin 500 mg/day; (3) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day. Oral acetaminophen (500 mg tablets) was allowed as rescue analgesic medication. Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction (day 1), and at days 2, 3, 7 after surgery. Edema and trismus were estimated at days 2 and 7. At days 1 and 2, pain intensity was significantly lower in patients treated with piroxicam-FDDF, either alone (p < 0.05) or in combination with azithromycin (p < 0.05), than in patients administered with azithromycin alone. A higher acetaminophen consumption was also recorded in the latter group (p < 0.01). Pain intensity values did not differ among treatment groups at days 3 and 7. At day 2, the facial edema was significantly less intense in patients exposed to piroxicam-FDDF alone, as compared to patients treated with azithromycin, either alone (p < 0.05) or in combination with piroxicam-FDDF (p < 0.05). No significant differences were detected when comparing groups for trismus at days 2 and 7. The present results indicate that, when given alone in the pre-operative period, piroxicam-FDDF effectively counteracts post-surgical pain and inflammatory reactions in oral tissues. Upon combined treatment with piroxicam-FDDF and azithromycin, the macrolide antibiotic may reduce the influence of piroxicam on post-operative inflammation, without affecting its beneficial effect on surgical pain.     

经食管多普勒定量估测冠状动脉血管阻力及血管储备

应用经食管多普勒超声心动图（ＴＥＥ）对３０例冠状动脉造影患者测量注射潘生丁前后左前降支平均舒张期血流率（Ｖｃｏｒ）、冠脉血管阻力（Ｒｃｏｒ）和冠脉血管储备（ＣＶＲ）。静息状态正常组与狭窄各组平均动脉压（ＭＡＰ）、Ｖｃｏｒ和Ｒｃｏｒ无显著差异。注射潘生丁后狭窄各组较对照组的Ｒｃｏｒ显著增加、Ｖｃｏｒ和ＣＶＲ显著降低而ＭＡＰ基本不变；ＰＤＳ＜７５％与≥７５％组的注药后Ｒｃｏｒ和ＣＶＲ无显著差异，血管狭窄积分（ＡＳＩ）＜１．５ｃｍ与≥１．５ｃｍ组两指标差异显著。注药后的Ｒｃｏｒ与ＡＳＩ成正相关（ｒ＝０．６３，Ｐ＜０．０１），与ＰＤＳ不相关；ＣＶＲ与ＡＳＩ和ＰＤＳ成较好的负相关（ｒ＝－０．８２，－０．５２）。本研究为冠状动脉病变功能严重度的定量估价提供了参考依据。