Objective. This study was undertaken to assess the characteristics and outcome of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/ DM) and to determine variables predictive of ILD deterioration in PM/DM.Methods. Among 348 consecutive patients with PM/DM, 107 patients with ILD were identified by medical records search in 4 medical centers. All patients underwent pulmonary function tests (PFTs) and pulmonary high-resolution computed tomography (HRCT) scan.Results. ILD onset preceded PM/DM clinical manifestations in 20 patients, was identified concurrently with PM/DM in 69 patients, and occurred after PM/DM onset in 18 patients. Patients with ILD could be divided into 3 groups according to their presenting lung manifestations: patients with acute lung disease (n ‫؍‬ 20), patients with progressive-course lung signs (n ‫؍‬ 55), and asymptomatic patients with abnormalities consistent with ILD evident on PFTs and HRCT scan (n ‫؍‬ 32). We observed that 32.7% of the patients had resolution of pulmonary disorders, whereas 15.9% experienced ILD deterioration. Factors that predicted a poor ILD prognosis were older age, symptomatic ILD, lower values of vital capacity and diffusing capacity for carbon monoxide, a pattern of usual interstitial pneumonia on HRCT scan and lung biopsy, and steroid-refractory ILD. The mortality rate was higher in patients with ILD deterioration than in those without ILD deterioration (47.1% versus 3.3%).Conclusion. Our findings indicate that ILD results in high morbidity in PM/DM. Our findings also suggest that more aggressive therapy may be required in PM/DM patients presenting with factors predictive of poor ILD outcome. Polymyositis (PM) and dermatomyositis (DM)are systemic inflammatory disorders that affect skeletal muscles and other organs, especially the lungs, either primarily or through complications of muscle weakness, resulting in interstitial lung disease (ILD), ventilatory insufficiency, and aspiration pneumonia (1-4). The prevalence of pulmonary involvement has been reported to be as high as 46% in PM/DM, and pulmonary disorders are still considered to be a common cause of morbidity in PM/DM (1-4). ILD may lead to lifethreatening complications, i.e., ventilatory failure, secondary pulmonary arterial hypertension, or cor pulmonale (2,(5)(6)(7)(8)(9). Previous studies of small series have shown that once pulmonary involvement was recognized in PM/DM, the 5-year mortality rate ranged from 0 to 55% (5,7,10). The early detection of ILD is, therefore, a high priority in PM/DM patients. The aims of this retrospective study were to assess the characteristics and outcome of ILD in patients with PM/DM and to determine factors that are predictive of ILD deterioration in PM/ DM. PATIENTS AND METHODSIdentification of the patients. This retrospective study began with a search of the institutional centers' medical record 1 I. Marie, MD, PhD: Centre Hospitalier Universitaire Rouen, INSERM U 905,

Occludin and claudin-1 appeared markedly affected in IBS-D patients. In addition, our results suggest that alteration of TJ proteins may be involved in the initiation of IBS and contribute to visceral hypersensitivity.

1. The locomotor stimulatory effects induced by caffeine (1,3, 7-trimethylxanthine) in rodents have been attributed to antagonism of adenosine A(1) and A(2A) receptors. Little is known about its locomotor depressant effects seen when acutely administered at high doses. The roles of adenosine A(1) and A(2A) receptors in these activities were investigated using a Digiscan actimeter in experiments carried out in mice. Besides caffeine, the A(2A) antagonist SCH 58261 (5-amino-7-(beta-phenylethyl)-2-(8-furyl)pyrazolo[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine), the A(1) antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), the A(1) agonist CPA (N(6)-cyclopentyladenosine) and A(2A) receptor knockout mice were used. 2. Caffeine had a biphasic effect on locomotion of wild-type mice not habituated to the open field, stimulating locomotion at 6.25 - 25 mg kg(-1) i.p. doses, while depressing it at 100 mg kg(-1). In sharp contrast, caffeine dose-dependently decreased locomotion in A(2A) receptor knockout mice over the whole range of tested doses. 3. The depressant effects induced by high doses of caffeine were lost in control CD1 mice habituated to the open field. 4. The A(1) agonist CPA depressed locomotion at 0.3 - 1 mg kg(-1) i.p. doses. 5. The A(1) antagonist DPCPX decreased locomotion of A(2A) receptor knockouts and CD1 mice at 5 mg kg(-1) i.p. and 25 mg kg(-1) i.p. respectively. 6. DPCPX (0.2 - 1 mg kg(-1) i.p.) left unaltered or even reduced the stimulant effect of SCH 58261 (1 - 3 mg kg(-1) i.p.) on CD1 mice. 7. These results suggest therefore that the stimulant effect of low doses of caffeine is mediated by A(2A) receptor blockade while the depressant effect seen at higher doses under some conditions is explained by A(1) receptor blockade.

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Objective. To assess the long-term outcome of esophageal complications in the group of patients receiving intravenous immunoglobulins (IVIG) for the treatment of severe steroid-refractory esophageal involvement related to polymyositis/ dermatomyositis (PM/DM). Methods. We retrospectively reviewed the medical records of 73 patients (39 with PM, 34 with DM) with steroid-resistant esophageal involvement. Esophageal involvement was evaluated by clinical and manometric investigations. Results. Seventy-three patients with steroid-refractory esophageal involvement related to PM/DM received IVIG therapy (2 gm/kg monthly). The median interval between PM/DM diagnosis and the onset of esophageal complications was 6 months. The most common clinical manifestations revealing esophageal dysfunction were dysphagia (69.9%), coughing while eating (61.6%), and gastroesophageal reflux into the pharynx and/or mouth (34.2%). Twenty-five patients exhibited life-threatening esophageal complications requiring exclusive enteral feeding; 33 patients (45.2%) with esophageal impairment developed aspiration pneumonia. Sixty patients (82.2%) exhibited resolution of esophageal clinical manifestations, leading to a return to normal oral feeding and ablation of feeding enteral tubes. Four other patients (5.5%) improved, although they still experienced mild dysphagia intermittently. Because of impaired cricopharyngeal muscle relaxation, another patient successfully underwent cricopharyngeal myotomy. Eight patients died from aspiration pneumonia (n ‫؍‬ 6) and cancer (n ‫؍‬ 2). Muscle weakness, thoracic myopathy, and aspiration pneumonia were independent predictive factors of IVIG-treated esophageal complications in PM/DM patients. Conclusion. Our findings indicate that IVIG should be considered in life-threatening esophageal impairment complicating steroid-resistant PM/DM. We also suggest that combined therapy of IVIG and high-dose steroids may be the first-line therapy in PM/DM patients with life-threatening esophageal manifestations.

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Objective. To assess the outcome of interstitial lung disease (ILD) in anti-Jo-1 patients with antisynthetase syndrome, determine predictive variables of ILD deterioration in these patients, and compare features of anti-Jo-1 patients with and without ILD. Methods. Ninety-one anti-Jo-1 patients were identified by medical records search in 4 medical centers. All of these patients had undergone pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans. Results. Sixty-six patients (72.5%) had ILD. Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n ‫؍‬ 12), progressive onset of lung signs (n ‫؍‬ 35), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT scans (n ‫؍‬ 19). Sixteen patients had resolution of ILD; 39 and 11 patients experienced improvement and deterioration of ILD, respectively. ILD led to decreased functional status, since 29.8% of patients exhibited a marked reduction of activities due to ILD and 13.6% had respiratory insufficiency requiring oxygen therapy; 5 of 6 patients died due to ILD complications. Predictive parameters of ILD deterioration were HRCT scan pattern of usual interstitial pneumonia, respiratory muscle involvement, and age >55 years. Furthermore, anti-Jo-1 patients with ILD, compared with those without, more frequently exhibited mechanic's hands and lower creatine kinase levels. Conclusion. Our findings confirm that ILD is a frequent complication in anti-Jo-1 patients, resulting in high morbidity. We suggest that patients with predictive factors of ILD deterioration may require more aggressive therapy. Finally, anti-Jo-1 patients with ILD, compared with those without, may exhibit a particular clinical phenotype.

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