John Organtzis

Experimentation with inhaled bronchodilators and corticosteroids

BACKGROUND Inhaled bronchodilators and corticosteroids have been used for decades with different production systems. MATERIALS AND METHODS The following jet-nebulizers: (a) Invacare, (b) Sunmist, (c) Maxineb and ultrasound nebulizers: (a) GIMA, (b) OMRON and (c) EASY NEB II were used as production systems. The jet-nebulizers were used with different residual cups and volume filling, while the ultrasound nebulizers with different volume fillings and face mask versus inlet. RESULTS Inhalation and ultrasound process detect significant differences between the factors and interactions considered, but each technique follows a specific pattern of magnitude effect. Thus the inhaled mechanism ranks the factor effects in decreasing order: residual cup>drug>nebulizer>loading (2, 3, 4 ml) and also drug>residual cup>nebulizer (loading 8 ml). The ultrasound mechanism orders as follows: nebulizer>drug>loading. In fact, varying micro environmental conditions created during the performance of the devices in both processes alternate the magnitude of factor significance allowing for unique capacities. CONCLUSIONS PULMICORT, MAXINEB, design cup J and loading 6 ml are the best options for the inhaled process. Optimal combinations are provided by FLIXOTIDE and cup B and also by MAXINEB and cup J. The incorporation of large residual cups suggests one out of six drugs, the SUNMIST nebulizer and design D as the best choices. Ultrasound performance informs for other optimal conditions: ZYLOREN, MAXINEB, 4 ml load and MAXINEB×loading 4 ml.

Interleukin-7 and Interleukin-15 for Cancer

Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.

Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System.

Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled non-specific cytotoxic agents have been evaluated as a future treatment for local disease control and distant metastasis control. There are few information regarding the influence of local transporters and gene expression of the respiratory epithelium to the absorption of administered drugs. In the current work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs® in order to investigate whether gene therapy can be used as a pre-treatment to enhance the efficiency of inhaled cisplatin. We included the following groups to our work: a) control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus cisplatin administration. The results indicate that the aerosol cisplatin group had a long term survival with the intratumoral cisplatin group following. The enhancement of the ABCA family locally to the respiratory system prior to the aerosol cisplatin administration can be used safely and efficiently. Future treatment design of local therapies should include the investigation of local transporters and genes.

Tyrosine Kinase Inhibitors for the Elderly

Until few years ago non-specific cytotoxic agents were considered the tip of the arrow as first line treatment for lung cancer. However; age > 75 was considered a major drawback for this kind of therapy. Few exceptions were made by doctors based on the performance status of the patient. The side effects of these agents are still severe for several patients. In the recent years further investigation of the cancer genome has led to targeted therapies. There have been numerous publications regarding novel agents such as; erlotinib, gefitinib and afatinib. In specific populations these agents have demonstrated higher efficiency and this observation is explained by the overexpression of the EGFR pathway in these populations. We suggest that TKIs should administered in the elderly, and with the word elderly we propose the age of 75. The treating medical doctor has to evaluate the performance status of a patient and decide the best treatment in several cases indifferent of the age. TKIs in most studies presented safety and efficiency and of course dose modification should be made when necessary. Comorbidities should be considered in any case especially in this group of patients and the treating physician should act accordingly.

Could Somatostatin Enhance the Outcomes of Chemotherapeutic Treatment in SCLC

Purpose: Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Furthermore, somatostatin (SST) receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and are overexpressed in tumors. Since, human small-cell lung cancer overexpresses somatostatin receptors (STTR), they could be legitimate targets for treating SCLC.The aim of this study was the evaluation of cytotoxicity of somatostatin in combination with several anticancer drugs in HTB-175 cell line (Small Cell Lung Cancer Cell line that expresses neuron specific enolase). Methods: Docetaxel, Paclitaxel, Carboplatin, Cisplatin, Etoposide, Gemzar, Navelbine, Fluorouracil, Farmorubicin are the chemotherapeutic drugs that we used for the combination before and after adding somatostatin in SCLC cell culture. HTB-175 cell line was purchased from ATCC LGC Standards.At indicated time-point, 48h after the combination, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Results: Flow cytometry showed that Docetaxel, Paclitaxel, Gemzar and Cisplatin induced apoptosis more when they were added before somatostatin, whereas etoposide induced apoptosis more after somatostatin treatment. Navelbine alone or in combination with somatostatin showed no differences in apoptosis. Farmorubicin showed equal toxicity in all combinations. Fluorouracil and Carboplatin induced apoptosis more when added alone in HTB-175 cell line. However, increased apoptosis was also observed when Carboplatin was administered before somatostatin in higher concentrations. Conclusion: Our results indicated that depending on the drug, somatostatin treatment before or after chemotherapeutic drugs increased apoptosis in small cell lung cancer cells. We suggest that long acting somatostatin analogues could be used as additive and maintenance therapy in combination to antineoplastic agents in SCLC patients.

Sex differences of continuous positive airway pressure treatment on flow-mediated dilation in patients with obstructive sleep apnea syndrome.

Introduction There is growing research evidence suggesting the presence of endothelial dysfunction and systemic inflammation in patients with obstructive sleep apnea syndrome (OSAS). Continuous positive airway pressure (CPAP) is the most effective method for treating OSAS; nonetheless, the effects of CPAP on the aforementioned pathophysiologic pathways as well as on the systemic disease that result or coexist with the OSAS remain elusive. Aim To assess the effect of 3-month CPAP therapy on endothelial-dependent dilation, plasma levels of inflammatory markers, blood pressure (BP), and glucose control on male and female patients with OSAS. Methods Our study group consisted of 40 (24 males and 16 females) patients with no prior history of cardiovascular disease, with an apnea–hypopnea index ≥15, who were assigned to receive CPAP treatment. Measurements of flow-mediated dilation (FMD), 24-hour ambulatory BP, and blood analysis were performed at baseline and 3 months after CPAP therapy. Results Baseline FMD values were negatively correlated with the apnea–hypopnea index (r=−0.55, P=0.001). After 3 months of CPAP, there was an increase in the FMD values (5.40%±2.91% vs 3.13%±3.15%, P<0.05) and a significant reduction in the patients’ 24-hour systolic BP (122.82±11.88 mmHg vs 130.24±16.75 mmHg, P<0.05), diastolic BP (75.44±9.14 mmHg vs 79.68±11.09 mmHg, P<0.05), and pulse pressure (47.38±9.77 mmHg vs 52.72±11.38 mmHg, P<0.05); daytime systolic BP (125.76±12.69 mmHg vs 132.55±17.00 mmHg, P<0.05) and diastolic BP (77.88±10.39 mmHg vs 82.25±11.01 mmHg, P<0.05); nighttime systolic BP (118.17±13.16 mmHg vs 126.22±17.42 mmHg, P<0.05) and pulse pressure (46.61±10.76 mmHg vs 52.66±11.86 mmHg, P<0.05); and C-reactive protein and HbA1c levels (0.40 [0.40–0.70] mg/L vs 0.60 [0.40–0.84] mg/L and 5.45%±0.70% vs 5.95%±1.08%, respectively; P<0.05). When divided by sex, only male patients produced similar statistically significant results, while female patients failed to show such associations. Conclusion Our results suggest that CPAP therapy improves the endothelial function, the BP, and the glucose control in male patients with OSAS. Further research is warranted in order to verify these results and to further elucidate the impact of CPAP on the cardiovascular risk of male and female patients with OSAS.

Surgical anatomy of the internal thoracic arteries and their branching pattern: a cadaveric study

BACKGROUND The purpose of this study is to review the anatomic characteristics of internal thoracic artery (ITA) and its branches, in order to pursue the extension of its utilization and avoid intraoperative and postoperative complications. METHODS The study was carried out on anterior chest walls obtained during routine autopsies of 50 specimens (30 male, 20 female). Macroscopic and microscopic dissection was performed and the following were studied: origin, length and termination of ITA, size and distance from the sternum, and types of branches. RESULTS From the origin to the termination point, the length of the left internal thoracic artery (LITA) varied from 159 to 220 mm; with a mean of 182.60 mm. The length of the right internal thoracic artery (RITA) varied from 150 to 231 mm; with a mean of 185 mm. Four types of branches were distinguished. The RITA mean diameter was 2.31 mm, measured at the 2(nd) intercostal space, while the distance from the sternum was 12.77 mm, measured at the 3(rd) intercostal space. The LITA mean diameter was 1.98 mm with the distance from the sternum measured at 12.01 mm. CONCLUSIONS ITA has become the primary conduit for cardiac bypass surgery; many studies have generated fundamental anatomical knowledge for its clinical utilization, which is always useful in order to avoid intraoperative and postoperative complications.

Video-assisted thoracic surgery reduces early postoperative stress. A single-institutional prospective randomized study

Background Video-assisted thoracic surgery (VATS) has been shown to effectively reduce postoperative pain, enhance mobilization of the patients, shorten in-hospital length of stay, and minimize postoperative morbidity rates. The aim of this prospective study is to evaluate neuroendocrine and respiratory parameters as stress markers in cancer patients who underwent lung wedge resections, using both mini muscle-sparing thoracotomy and VATS approach. Methods The patients were randomly allocated into two groups: Group A (n=30) involved patients who were operated on using the VATS approach, while in group B (n=30), the mini muscle-sparing thoracotomy approach was used. Neuroendocrine and biological variables assessed included blood glucose levels, C-reactive protein (CRP) levels, cortisol, epinephrine, and adrenocorticotropic hormone (ACTH) levels. Arterial oxygen (PaO2) and carbon dioxide (PaCO2) partial pressure were also evaluated. All parameters were measured at the following time points: 24 hours preoperatively (T1), 4 hours (T2), 24 hours (T3), 48 hours (T4), and 72 hours (T5), after the procedure. Results PaO2 levels were significantly higher 4 and 24 hours postoperatively in group A vs group B, respectively (T2: 94.3 vs 77.9 mmHg, P=0.015, T3: 96.4 vs 88.7 mmHg, P=0.034). Blood glucose (T2: 148 vs 163 mg/dL, P=0.045, T3: 133 vs 159 mg/dL, P=0.009) and CRP values (T2: 1.6 vs 2.5 mg/dL, P=0.024, T3: 1.5 vs 2.1 mg/dL, P=0.044) were found increased in both groups 4 and 24 hours after the procedure. However, their levels were significantly lower in the VATS group of patients. ACTH and cortisol values were elevated immediately after the operation and became normal after 48 hours in both groups, without significant difference. Postoperative epinephrine levels measured in group A vs group B, respectively, (T2: 78.9 vs 115.6 ng/L, P=0.007, T3: 83.4 vs 122.5 ng/L, P=0.012, T4: 67.4 vs 102.6 ng/L, P=0.021). The levels were significantly higher in group B. Conclusion This study confirmed that minimally invasive thoracic surgery, by means of VATS, significantly reduces the acute-phase response and surgical stress, while enables better postoperative oxygenation.

Apparent Diffusion Coefficient Quantification in Determining the Histological Diagnosis of Malignant Liver Lesions.

Purpose: Diffusion Weighted Imaging is an established diagnostic tool for accurate differential diagnosis between benign and malignant liver lesions. The aim of our study was to evaluate the role of Histogram Analysis of ADC quantification in determining the histological diagnosis as well as the grade of malignant liver tumours. To our knowledge, there is no study evaluating the role of Histogram Analysis of ADC quantification in determining the histological diagnosis as well as the grade of malignant liver tumours. Methods: During five years, 115 patients with known liver lesions underwent Diffusion Weighted Imaging in 3Tesla MR scanner prior to core needle biopsy. Histogram analyses of ADC in regions of interest were drawn and were correlated with biopsy histological diagnosis and grading. Results: Histogram analysis of ADC values shows that 5th and 30th percentile parameters have statistically significant potency of discrimination between primary and secondary lesions groups (p values 0.0036 and 0.0125 respectively). Skewness of the histogram can help discriminate between good and poor differentiated (p value 0.17). Discrimination between primary malignancy site in metastases failed for the present number of patients in each subgroup. Conclusion: Statistical parameters reflecting the shape of the left side of the ADC histogram can be useful for discriminating between primary and secondary lesions and also between well differentiated versus moderate or poor. For the secondary malignancies, they failed to predict the original site of tumour.

Electric vs. harmonic scalpel in treatment of primary focal hyperhidrosis with thoracoscopic sympathectomy

BACKGROUND Hyperhidrosis is defined as excessive sweating beyond the physiologic needs of a person. Palmar hyperhidrosis in the adolescent period may have an impact on school work and may cause psychological problems. Thoracoscopic sympathectomy is now used routinely to treat patients with disabling primary hyperhidrosis or facial blushing. PATIENTS AND METHODS From January 2008 to December of 2009 bilateral thoracoscopic sympathectomy Th2-Th4 was performed to 79 patients aged from 17 to 55, who suffered from palmar, axillar or craniofacial hyperhidrosis. For the first 39 patients (group A) thoracoscopic sympathectomy was performed using electric scalpel and for the next 40 patients (group B) thoracoscopic sympathectomy was performed using harmonic scalpel. RESULTS Based on our results we did not find any significant differences between electric or harmonic scalpel usages for thoracoscopic sympathectomy. Moreover, there was no significant difference between complications and the severity of pain, with slightly higher intensity of pain with harmonic scalpel usage. Both electric and harmonic scalpel provided adequate treatment for primary hyperhidrosis, with the fact that non-disposable electric scalpel costs were less than that of the disposable harmonic scalpel. CONCLUSIONS Sympathectomy should be preferred for palmar hyperhidrosis treatment, as it is much technically shorter, simpler to implement, and also easier to learn. Thoracoscopic sympathectomy is safe and effective for the treatment of primary palmar hyperhidrosis in the adolescent period without any major side effects.