Infliximab in two patients with juvenile ankylosing spondylitis

Infliximab, a monoclonal chimeric anti-tumor necrosis factor alpha (anti-TNF-) antibody, was tried in two patients suffering from severe refractory juvenile ankylosing spondylarthritis with disease duration of more than 10 years. To assess the response, validated clinical activity parameters were monitored prospectively. In both patients, treatment with infliximab at a dosage of 5 mg/kg body weight already led to considerable improvement with loss of joint pain the day after it was given. Bath Ankylosing Spondylitis Functional Index scores decreased from 5.8 to 0 and 7.2 to 1.0 and the Bath Ankylosing Spondylitis Disease Activity Index from 2.6 to 1.4 and 9.0 to 1.0. In one patient, the response to a single infusion continued for more than 8 months. Because of a recurrence of symptoms in intervals of 2 months, the fourth infusion has now been given to the second patient, resulting in immediate clinical response. No side effects have been noted. Infliximab seems to be a promising agent for treatment of active and refractory juvenile ankylosing spondylitis. Controlled studies and long-term observations are warranted.     

High-resolution CT in the differential diagnosis of consolidative processes (I. Acute processes)

Consolidations are usually result of the replacement of the alveolar air by fluid, cells or tissue but these can also be seen with extensive interstitial processes. These diseases cannot be clearly categorized into the classic classification scheme of airspace and interstitial disease since there are features of both categories seen in the imaging and histologic findings. Because this definition includes wide variety of diseases with overlapping HRCT-findings it is difficult to distinguish among these entities with imaging criteria alone. However, integration of HRCT-findings and clinical findings may enable a narrower differential diagnosis. This review describes the most common types of lung diseases associated with acute appearance of consolidation and discuss the differential diagnosis.     

Safety and efficacy of exercise training in various forms of pulmonary hypertension

The objective of this prospective study was to assess safety and efficacy of exercise training in a large cohort of patients with different forms and World Health Organization (WHO) functional classes of chronic pulmonary hypertension (PH). 183 patients with PH (pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH due to respiratory or left heart diseases received exercise training in hospital for 3 weeks and continued at home. Adverse events have been monitored during the in-hospital training programme. Efficacy parameters were evaluated at baseline, and after 3 and 15 weeks. After 3 and 15 weeks, patients significantly improved the distance walked in 6 min (6MWD) compared to baseline, scores of quality of life, WHO functional class, peak oxygen consumption, oxygen pulse, heart rate and systolic pulmonary artery pressure at rest and maximal workload. The improvement in 6MWD was similar in patients with different PH forms and functional classes. Even in severely affected patients (WHO functional class IV), exercise training was highly effective. Adverse events, such as respiratory infections, syncope or presyncope, occurred in 13% of patients. Exercise training in PH is an effective but not a completely harmless add-on therapy, even in severely diseased patients, and should be closely monitored.     

Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers.

OBJECTIVES: This study sought to assess the risks associated with right heart catheter procedures in patients with pulmonary hypertension. BACKGROUND: Right heart catheterization, pulmonary vasoreactivity testing, and pulmonary angiography are established diagnostic tools in patients with pulmonary hypertension, but the risks associated with these procedures have not been systematically evaluated in a multicenter study. METHODS: We performed a multicenter 5-year retrospective and 6-month prospective evaluation of serious adverse events related to right heart catheter procedures in patients with pulmonary hypertension, as defined by a mean pulmonary artery pressure >25 mm Hg at rest, undergoing right heart catheterization with or without pulmonary vasoreactivity testing or pulmonary angiography. RESULTS: During the retrospective period, 5,727 right heart catheter procedures were reported, and 1,491 were reported from the prospective period, for a total of 7,218 right heart catheter procedures performed. The results from the retrospective and the prospective analyses were almost identical. The overall number of serious adverse events was 76 (1.1%, 95% confidence interval 0.8% to 1.3%). The most frequent complications were related to venous access (e.g., hematoma, pneumothorax), followed by arrhythmias and hypotensive episodes related to vagal reactions or pulmonary vasoreactivity testing. The vast majority of these complications were mild to moderate in intensity and resolved either spontaneously or after appropriate intervention. Four fatal events were recorded in association with any of the catheter procedures, resulting in an overall procedure-related mortality of 0.055% (95% confidence interval 0.01% to 0.099%). CONCLUSIONS: When performed in experienced centers, right heart catheter procedures in patients with pulmonary hypertension are associated with low morbidity and mortality rates.     

Primary pulmonary hypertension in children may have a different genetic background than in adults

Mutations of the bone morphogenetic protein receptor II (BMPR2) gene on chromosome 2q33 can cause familial primary pulmonary hypertension (PPH) and may occur in 26% adult patients with sporadic disease. Other disease-related genes have been localized to chromosomes 2q31 (PPH2) and 12q13 (ALK1). The genetic background in affected children remains unclear. Thirteen children (age at diagnosis, 6 mo to 13 y; mean, 5.6 +/- 3.9 y) with invasively confirmed PPH were screened for BMPR2 mutations using denaturing HPLC and sequence analysis. In addition, all children were scanned for BMPR2 deletions by Southern blot analysis. Pulmonary artery pressure was assessed using echocardiography at rest and during exercise in 57 family members of six infants. The six families were subjected to linkage analysis. None of the 13 children had a BMPR2 mutation or deletion. Linkage to chromosome 2 or 12 could not be confirmed in any of the families investigated. In all assessed families, both parents of the index patient and/or members of both branches revealed an abnormal pulmonary artery systolic pressure (PASP)-response to exercise. PPH in children may have a different genetic background than in adults. We postulate a recessive mode of inheritance in a proportion of infantile cases.