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  • Pulmonary Arterial Hypertension (PAH) is characterized by an increase in mean pulmonary arterial pressure due to an increase in pulmonary vascular resistance as a result of extensive vascular remodeling and vasoconstriction. In patients with PAH, the principal lesions involve intermediate and large-sized pulmonary arteries with medial and adventitial hypertrophy/hyperplasia in addition to lumen occluding plexiform lesions. A variety of cellular abnormalities have been described in the pulmonary vasculature that may play an important role in the development and progression of PAH, such as pulmonary endothelial dysfunction with altered synthesis of nitric oxide, thromboxane A2, prostacyclin and endothelin. Our understanding of the mechanisms of the disease further include the identification of mutations in cases of PAH and of potential stimuli of endothelial dysfunction like shear stress, autoimmunity, inflammation, drugs and viruses. Today three major categories of drugs for PAH are available: prostanoids, endothelin receptor antagonists and phosphodiesterase inhibitors. Therapy also may include anticoagulation, oxygen and calcium channel blockers. Treatment of pulmonary hypertension due to left heart diseases should be focused on the underlying cause. Further research and understanding of the pathophysiologic mechanisms of PAH should lead to further improvements in the treatment of this challenging disease.
     
  • Phosphodiesterase-4 (PDE4) is a major cyclic AMP-hydrolyzing enzyme in inflammatory and immunomodulatory cells. The wide range of inflammatory mechanisms under control by PDE4 points to this isoenzyme as an attractive target for new anti-inflammatory drugs. Selective inhibitors of PDE4 have exhibited a broad spectrum of anti-inflammatory activities including the inhibition of cellular trafficking and microvascular leakage, cytokine and chemokine release from inflammatory cells, reactive oxygen species production, and cell adhesion molecule expression in a variety of in vitro and in vivo experimental models. The two main orally given PDE4 inhibitors are cilomilast and roflumilast with the latter to be considered more selective and potent with a greater therapeutic range. An additive suppressive effect on CD4 positive T-cells and dentritic cells suggests a immunomodulatory profile for these drugs. On the other hand, despite the above evidence, most of the clinical trials for both asthma and COPD do not provide strong evidence for clinical improvement with PDE4 inhibitors. Roflumilast has a better tolerability and safety profile with the main adverse events reported being nausea, diarrhea and abdominal pain. Interpretation of the up-to-date clinical results lead to a skepticism regarding the efficacy of the above drugs. This is partly supported by the fact that most of the clinical trials were presented in an abstract form and not as full paper data. Future studies and future evidence could answer whether PDE4 inhibitors represent an expensive designer theophylline or an effective anti-inflammatory drug with a strong place in guidelines. Pneumon 2006; 19(4):303-310. Key words:
     
  • K. Katsoulis
    The imbalance between oxygen free radicals and antioxidants, as defense mechanisms against free radicals, is called oxidative stress. Free radicals are reactive molecules with multiple effects on basic biomolecules such as cell membrane lipids, proteins and DNA. They are produced from extrinsic and intrinsic sources, mainly from cells involved in inflammatory procedures. Oxidative stress is involved in several respiratory diseases including bronchial asthma. Several studies regarding peripheral blood, bronchoalveolar lavage, bronchial mucosa cells, exhaled air and condensate, even urine, have shown increased free radicals production in asthma with coexistent disturbance in antioxidant mechanisms, as well as participation of free radicals in the pathogenesis and pathophysiology of asthma. There is also evidence that in some cases oxidative stress might be related to inflammation and severity of the disease. Decreased dietary antioxidant intake has been proposed as one of the factors that contribute to the increased incidence of asthma. However, research on extrinsic antioxidants administration has shown conflicting data, although administration of synthetic antioxidants in experimental animals showed more promising results. As the researchers are still interested in oxidative stress, more answers about the significance of oxidative stress and the significance of antioxidants administration in the therapy of asthma are expected. Pneumon 2006; 19(4):311-323.
     
  • Ch. Marketos
    Bone metastases and associated skeletal complications are common in patients with lung cancer. It is estimated that approximately 30- 40% of those patients will develop bone metastases, principally osteolytic lesions, with considerable skeletal morbidity including bone pain, pathologic fracture, spinal cord compression, nerve root compression, bone marrow infiltration, and hypercalcemia of malignancy. These complications result from excessive bone metabolism, particulary excessive bone resorption, and consequent derangement of bone structure. Treatment of bone metastases and their complications classically include radiotherapy and/or radionuclides administration, surgery to bone and analgesic therapy. In recent years newer nitrogen-containing bisphosphonates have proven to be an efficient and well-tolerated treatment for preventing skeletal complications associated with bone metastases in several malignant diseases including lung cancer. Bisphosphonates inhibit bone resorption by increasing apoptosis of osteoclasts by the inhibition of signaling- proteins essential for cell function and survival. In addition, they may have a direct antitumor action. Newer bisphosphonates are administered intravenοusly every 3-4 weeks with varying infusion duration. Oral medications have low bioavailability and are also associated with increased incidence of gastrointestinal side effects. Common side effects of bisphosphonate treatment include bone pain, fatigue, nausea and vomiting, headache, fever, influenza-like syndrome, anemia and renal toxicity. Although clinical benefit of bisphosphonates is less clear in lung cancer patients with bone metastases whο have poorer prognosis, often less than 6 months, several studies have shown a reduction of risk for developing a Skeletal Related Event (SRE) (with the exception of spinal cord compression), longer median time to first SRE and sustained palliation of bone pain, but no effect on survival. In summary, bisphosphonates may have an important role in the current treatment of metastatic bone disease in lung cancer patients. Further therapeutic implications, such as antitumor effect and prevention of bone metastases, are also under study. Pneumon 2006; 19(4):324-338.
     
  • V. Tzilas
    Αsthma is a chronic inflammatory disease of the airwaysa and a lot of progress has been made in the understanding of its pathogenesis. Yet, there are many points that need further clarification and among them Holgate’s theory regarding the reactivation of the epithelial-mesenchymal trophic unit is of great interest. Epithelial cells under the influence of various stimuli secrete mediators, which affect mucous glands and myofibroblasts of the mesenchymal layer. The final result is permanent structural alterations of the airways, otherwise known as remodelling. This theory offers new target research areas in the therapy of asthma. Pneumon 2006; 19(4):339-348.
     
  • Object of the present study constitutes the history of tuberculosis during the period from 1854 till 1901, namely the second half of the 19th century. Mainly relative scientific articles existing in the medical press of the time supported the study of this subject. Through them emerges the picture that the scientific community of the time had for the disease and how it evolved through time. The big mortality of tuberculosis prompted the scientists to deal intensively with its research. From 1854 till 1901, great discoveries take place, which will reverse many theories that were in effect up to the end of the 19th century. Specifically, after its contagious nature is proven, an end to the disagreements of doctors as for the ways of infection/contamination of tuberculosis is given while the discovery of the pathogenesis of the disease places the research for the discovery of an effective treatment on a new base. As it appears through their articles, the Greek doctors watch the researches of their foreign colleagues, where they republish and comment on foreign studies while at the same time they also publish the results of their own experimentations. Pneumon 2006; 19(4):347-354.
     
  • Metalloproteinases and their tissue inhibitors act on the metabolism of collagen in the interstitial tissue matrix and are involved in the pathogenesis of tissue remodeling and fibrosis. The study objective is to investigate the MMP9 and TIMMP1 status in patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF), and their relationship to functional and ultrasonographic markers. Patient and methods: Serum levels of MMP9 and TIMMP1 in 22 sarcoidosis patients, in 10 IPF patients and 12 control subjects were determined (ELISA, Human Biotrak, Amersam). In sarcoidosis patients, disease stage (Ga167 scintigraphy) and left ventricular diastolic function (pulse and tissue Doppler) were further assessed. In IPF patients, systolic pulmonary artery pressure (SPAP) was measured; all patients underwent comprehensive lung function testing. Results: Serum MMP9 and TIMMP1 levels were similar among patients with either pathology; however, they were significantly higher in patients with sarcoidosis (p<0.001, p<0.01), as well as in patients with IPF (p<0.01, p<0.05) compared to controls. Among sarcoidosis patients, there was a significant relationship between MMP9 levels and both FEF25-75 (p<0.05) and disease activity (p<0.01), whereas among IPF patients MMP9 levels were associated with values for DLCO (p<0.05). 41% of sarcoidosis patients showed left ventricular diastolic dysfunction in terms of impaired relaxation and 40% of IPF patients had SPAP >35 mm Hg. No significant relationship between ultrasonographic findings and MMP9 and TIMMP1 levels, and the molar ratio MMP9/TIMMP1 was found. Conclusion: MMP9 levels reflect lung function impairment in sarcoidosis and IPF patients. Nevertheless, they cannot reliably indicate cardiovascular involvement. However, in sarcoidosis they may represent a useful marker of disease activity. Pneumon 2006; 19(4):357-366.
     
  • Chest wall involvement is a rare manifestation of tuberculosis. We present a case of a 66 year old male, farmer, who was admitted to our hospital due to the appearance of a 5 cm in diameter soft tissue mass on his left lower chest wall. After one month, when the patient was admitted again for surgical resection, a three-fold increase of the diameter of the mass was observed. A percutaneous biopsy and drainage were performed and the pus was microscopically examined. The results revealed the presence of mycobacterium tuberculosis (Ziehl-Nielsen stain). The patient was started on chemotherapy for tuberculosis. This unusual manifestation of tuberculosis should be a part of the differential diagnosis in patients presenting with a chest wall mass. CT and MRI examinations are the best imaging procedures to provide useful information about the extent and the nature of the disease. Pneumon 2006; 19(4):376-380.
     
  • Chylothorax occurs in 0.25 to 0.50% of the cases following open heart surgery. A case of a post- coronary artery by pass grafting surgery chylothorax is presented. Combined treatment with pleural drainage, “nothing per os” diet, total parenteral nutrition and subcutaneous administration of octreotide was effective and led to rapid cessation of chyle production. Pneumon 2006; 19(4):381-384.
     
  • A case of Swyer-James syndrome on a 78 years old female patient, diagnosed by a CT scan, is described. The syndrome remained undiagnosed due to the mild clinical manifestations. Pneumon 2006; 19(4):385-388.
     
  • A case of sclerosing lung hemangioma in a 35 years-old woman smoker complaining of non productive cough and dyspnoea is presented. On chest x-ray, a solitary mass was found with histological findings typical of sclerosing hemangioma. Surgical excision of the mass was performed and the patient one year after excision, was in excellent condition. Sclerosing hemangioma of the lung is a benign neoplasm with excellent prognosis. Pneumon 2006; 19(4):389-392.
     
  • We present a case of a 22-year old male, who was admitted to the Pneumonology Department due to an abnormal chest X-Ray, as an incidental finding on routine examination. The patient was asymptomatic, without any abnormal findings on physical examination. The CT of the chest revealed the presence of an intrathoracic rib in the right hemithorax. The intrathoracic rib is a very rare congenital anomaly. About 40 cases have been reported in the literature and only in a few of them a CT of the chest has been performed. The need fοr diagnosis of this congenital anomaly lies on the recognition of its benign nature and the exclusion of other pathologic disorders. Pneumon 2006; 19(4):393-395.
     
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