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  • Purpose: Lung cancer carries a dismal prognosis with conventional therapies achieving no significant improvements in survival in the last decade. In recent years, the advances achieved in understanding the molecular biology of cancer have afforded clinicians and scientists the opportunity to develop a range of novel genetic therapies for this disease. Materials and Μethods: A detailed review of the published reports dealing with gene therapy of lung cancer has been conducted. Particular emphasis has been placed on recent developments in the arena of non-viral (plasmid DNA, DNA-coated gold particles, liposomes and polymer-DNA complexes) and viral (adenovirus, retrovirus, adeno-associated virus, herpes virus and pox virus) vectors. Therapeutic strategies were categorised as corrective, cytoreductive and immunomodulatory gene therapy for the purpose of data analysis and comparison. Results: Loco-regional administration of both non-viral and viral vectors can yield impressive local gene expression and therapeutic effects but, as yet, no efficient systemically-delivered vector is available. Corrective gene therapy to restore normal patterns of tumor suppressor gene (p53, Rb, p21, p16) expression or to negate the effect of mutated tumor promoting oncogenes (ras, myc, erbB2, bcl-2) have efficacy in animal models but this approach suffers from the fact that every cancer cell must be targeted. A wide variety of cytoreductive strategies are under development, including suicide, anti-angiogenic, radioisotopic and pro-apoptotic gene therapies. Each of these approaches has strengths and weaknesses and may best be suited to use in combination. Immunomodulatory gene therapy seeks to generate an effective local immune response which translates to systemic antitumor activity. At present, most studies employ immunostimulatory cytokine genes (GM-CSF, IL-2, IL-12). Conclusions: A variety of therapeutic genes have proven activity against lung cancer in vitro and in vivo. However, the chief challenge facing clinical gene therapy strategies is the lack of efficient gene delivery by local and systemic routes and, for the foreseeable future, vector development will remain a major focus of ongoing research. Despite this caveat, it is anticipated that gene therapy approaches will make a significant contribution to the management of lung cancer in the future. Pneumon 2002, 15(1):19-37.
     
  • The incidence of fungal infections in the Intensive Care Unit (ICU) has increased with the use of advanced medical and life support systems, the prolongation of the life and the increasing number of patients with severe underlying diseases altering the immune response (cancer, chemotherapy, transplantation, AIDS). Systemic fungal infections are associated with high morbitity and mortality rates. The diagnosis remains difficult in the absence of specific techniques able to distinguish colonization from invasive and disseminated disease. Treatment of fungal infections has been classified as prophylactic, early presumptive, empiric and definitive. Several antifungal agents are or will be available, including amphotericin B with or without liposomal formulations, azoles, flucytosine, nystatin, voriconazole, echinocardins and itroconazole. Immunomodulation therapy is under investigation. Some fungal strains have intrinsic or acquired resistance against antifungal drugs. The antifungal treatment can be associated with severe complications which can prolong the ICU stay of the patients and increase the cost of hospitalization. The prognosis of the systemic fungal infections is poor. Pneumon 2002, 15(1):14-30.
     
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  • Ζoonoses are defined as infectious diseases transmitted between vertebrates and man naturally. It is estimated that there are over 180 zoonotic diseases up to date, affecting significantly both the public health and the economy sector. During the last couple of decades zoonoses are emerging or re-emerging in areas where they had disappeared for years, the phenomenon being attributed to environmental global changes and social-behavioral changes of life style in the developed and developing countries worldwide. Tuberculosis, anthrax and echinococcosis are only three of the major zoonotic diseases infecting lung. The zoonoses affecting the respiratory system are caused by various infectious agents including bacteria, fungi, parasites and viruses. For that reason WHO has issued a series of measures for prevention and control of emerging zoonoses. Pneumon 2002, 15(1):42-51.
     
  • ABSTRACT. Smoking is a recognized major risk factor for the development chronic obstructive pulmonary disease (COPD). COPD is characterized by abnormal inflammatory response of the airways to various stimuli, in which T-lymphocytes, macrophages and neutrophils are involved. The objective of this study was to assess the role of cytotoxic CD8+ lymphocytes in the inflammatory process associated with COPD. In particularly, expression of perforin and the cytotoxic activity of cytotoxic CD8+ lymphocytes were examined. The study included 36 male smokers with COPD, 25 male smokers without COPD and 10 male healthy non smokers. Cytotoxic CD8+ cell count in induced sputum was determined by immunocytochemical methods using monoclonal anti-CD3-FITC and anti-CD8-FITC antibodies. The expression of perforin was assessed by flow cytometry using anti-perforin-FITC antibody. The cytotoxic activity of CD8+ lymphocytes was assessed in their cultures with appropriate target-cells (K562). The percentage and the absolute number of cytotoxic CD8+ cells were significantly higher in smokers with COPD compared to both smokers without COPD (P = .005) and healthy non smokers (P = .0001). Smokers with COPD showed also significantly higher levels of perforin expression and cytotoxic activity of CD8+ lymphocytes in comparison to the other two study groups (P < .05). The results of this study indicate that CD8+ cells in induced sputum obtained from patients with COPD are more cytotoxic in relation to those obtained from smokers without obstruction. It is considered likely that their cytotoxic activity is a result of increased perforin release. Pneumon 2002, 15(1):63-73.
     
  • ABSTRACT. We present five cases of soldiers admitted to hospital for community acquired pneumonia; seroconversion for Ehrlichia chaffeensis (E. chaffeensis) was detected in four and permanently elevated antibody titer in one of them. Ehrlichia is a microorganism which belongs to the Rickettsiae family and frequently causes disease in dogs transmitted via tick bite. The same route of transmission, although rare, applies also in humans and results in a systemic disease associated with haematological disorders and, in few cases, affecting the respiratory system as well. Doxycyclin is considered the treatment of choice. Most of the cases have been reported in the USA, but individual cases have also been reported in Europe. Diagnosis is based mainly on the detection of specific antibodies in serum and consistent clinical manifestations. In the cases we present, all patients had negative serology testing for viruses and atypical bacteria, but showed significant and rapid clinical improvement after administration of doxycyclin. Exposure to tick bites was considered highly probable due to military activities. Based on the clinical and laboratory findings, we considered E. chaffeensis or other relative species as a potentially responsible pathogen in these patients. To our knowledge no other cases of ehrlichiosis have been reported in Greece. Pneumon 2002, 15(1):63-73.
     
  • We present a case of pulmonary actinomycosis of the right upper lobe, which was secondary to radiation pneumonitis. The patient underwent an uncomplicated left upper lobectomy en bloc with the 1st-2nd-3rd ribs and adjuvant radiotherapy, for a stage T3N0M0 (IIb) superior sulcus, adenocarcinoma, one-year ago. Radiation pneumonitis complicated his late postoperative course and he received steroids for 3 months. Four months later he suffered from thoracic pain, exhaustion and minor hemoptysis. Chest X-Ray showed two lesions, 0.5 and 1.5 cm of maximal diameter, located in the right upper obe. CT scan gave the evidence of metastatic disease and bronchoscopy was negative for intraluminal findings. The patient had exacerbation of hemoptysis and repeated Papanikolaou stained cytological examination of the sputum sample revealed “piles of actinomyces”. The patient received penicillin therapy for 6 months and he had improvement of the clinical condition and decrease by half of the diameter of right upper lobe lesions. Pneumon 2002, 15(1):31-35.
     
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