Biomedical subjects
Publications and source records attributed to George Patlakas.
Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives.
BACKGROUND: The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). METHODS: We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). RESULTS: An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively). CONCLUSIONS: BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS.
INTRODUCTION: The i.v. administration of the cytoprotective agent amifostine is associated with reversible clinical hypotension, protracted emesis, and malaise in a various percentage of patients. We evaluated, prospectively, whether the s.c. route is a better tolerated alternative to the i.v. route in patients receiving chemotherapy. PATIENTS AND METHODS: Fifty-nine patients treated with "once every 2 weeks" regimens received 1000 mg of amifostine i.v. before chemotherapy. Patients who developed protracted vomiting and malaise and/or clinical hypotension for two consecutive i.v. administrations received the same dose of amifostine s.c. for the subsequent cycles (i.v./s.c. study). In an additional cohort of 12 patients (s.c. study), 1000 mg of amifostine were given s.c. since the first chemotherapy cycle. RESULTS: In the i.v./s.c. study, 8 (13.5%) patients showed protracted emesis/malaise and/or clinical hypotension during the first two cycles. An additional 4 (6.6%) patients developed similar side effects during the subsequent cycles. Switching to the s.c. route, an improved tolerance was noted. In the s.c. study, a total of 76 injections was administered. Protracted vomiting or clinical hypotension was absent, and this tolerance profile was significantly better than the i.v. one (P = 0.001). There were no other systemic side effects related to the s.c. administration. CONCLUSIONS: Amifostine, at a dose of 1000 mg, is better tolerated when administered s.c. Switching to the s.c. route in patients with poor tolerance using the i.v. administration allows the continuation of cytoprotection with minor side effects. Although preliminary, 1000 mg of amifostine effectively protected against the lower, still more frequently administered doses of chemotherapy given once every 2 weeks.
The activity of a triplet of chemotherapeutic drugs, namely docetaxel, gemcitabine and liposomal doxorubicin, was investigated in patients with advanced non-small cell lung cancer. The regimen was supported with amifostine cytoprotection (1000mg injected subcutaneously) and hemopoietic growth factors (rhuG-CSF and rhuEPO) in an attempt to minimize the substantial toxicity reported in previous studies investigating docetaxel/gemcitabine chemotherapy. Twenty chemotherapy- naïve patients with advanced non-small cell lung cancer (NSCLC) (18 with stage IV and 2 with stage IIIb) were recruited. None of the patients presented with grade 3-4 hematological or non-hematological toxicity. Palmar-plantar erythrodysesthesia grade 2 was noted in 6/20 (30%), mucositisloesophagitis grade 2 in 3/20 (15%) and mild alopecia in 6/20 (30%) patients. No case of interstitial pneumonia was noted. The overall response rate (complete and partial) in 18 evaluable patients was 33% (6/18), with 1/18 (5%) patients achieving complete response. The median survival was 11 months. The efficacy of the regimen was as high as the one reported in gemcitabine/docetaxel studies, but the toxicity was remarkably lower. Amifostine may have contributed to the better tolerance profile observed.