Georgios Bougioukas

Lung cancer: An organized cellular and metabolic domain

Immunohistochemical evaluation of lung carcinomas for key enzymes involved in cellular metabolism (lactate dehydrogenase LDH 1 and 5, pyruvate dehydrogenase PDH, pyruvate dehydrogenase kinase PDHK-1, monocarboxylate transporters MCT 1, 2 and 4, glucose transporter GLUT1, hypoxia inducible factors HIF1α and 2α) show a complementary metabolic profile between cancer cells and tumor-associated stroma. Cancer cells share enzyme/transporter activities suggestive of an anaerobic metabolism with high affinity for glucose absorption, anaerobic glycolysis and lactate extrusion. On the other hand, the tumour-associated fibroblasts express patterns involved in aerobic pathways and lactate oxidation. These findings bring forward the hypothesis that tumor associated stroma is an accomplice in tumor growth and survival sustaining an independent cellular and metabolic tumor domain. The development of agents exploiting such cancer specific metabolic pathways may prove of importance in the treatment of lung cancer.

Organ Toxicity and Mortality in Propofol-Sedated Rabbits Under Prolonged Mechanical Ventilation

BACKGROUND: Prolonged administration of propofol at large doses has been implicated in propofol infusion syndrome in intensive care unit patients. In this study we investigated organ toxicity and mortality of propofol sedation at large doses in prolonged mechanically ventilated rabbits and determined the role of propofols lipid vehicle. METHODS: Eighteen healthy male rabbits were endotracheally intubated and sedated with propofol 2% (Group P), sevoflurane (Group S) or sevoflurane while receiving Intralipid 10% (Group SI). Sedation lasted 48 h or until death (Group P) or the maximum surviving period of Group P (Groups S and SI). The initial propofol infusion rate (20 mg · kg−1 · h−1) or sevoflurane concentration (1.5%) was adjusted, if needed, to maintain a standard level of sedation. Blood biochemical analysis was performed in serial blood samples and histologic examination in the heart, lungs, liver, gallbladder, kidneys, urinary bladder, and quadriceps femoris muscle at autopsy. RESULTS: The mortality rate was 100% (surviving period, 26–38 h) for Group P, whereas 0% for Groups S and SI. The initial propofol infusion rate had to be increased up to 65.7 ± 4.6 mg · kg−1 · h−1 and sevoflurane concentration up to 4%. Serum liver function indices, lipids and creatine kinase were significantly increased (P < 0.05) in Groups P and SI and lactate was increased only in Group P, whereas amylase was increased in all groups. In Group P, histologic examination revealed myocarditis, pulmonary edema with interstitial pneumonia, hepatitis, steatosis, and focal liver necrosis, cholangitis, gallbladder necrosis, acute tubular necrosis of the kidneys, focal loss of the urinary bladder epithelium, and rhabdomyolysis of skeletal muscles; in Group S, low-grade bronchitis and incipient inflammation of the liver and the kidneys; and in Group SI, low-grade bronchitis, liver steatosis and hepatitis, and incipient inflammation of the gallbladder, kidneys, and urinary bladder. CONCLUSIONS: Continuous infusion of 2% propofol at large doses for the sedation of rabbits undergoing prolonged mechanical ventilation induced fatal multiorgan dysfunction syndrome similar to the propofol infusion syndrome seen in humans. Our novel findings including lung, liver, gallbladder, and urinary bladder injury were also noted. The role of propofols lipid vehicle in the manifestation of the syndrome was minor. Sevoflurane proved to be a safe alternative medication for prolonged sedation.

Surgical treatment of pulmonary aspergillosis/mycosis in immunocompromised patients

Invasive pulmonary aspergillosis is a severe complication in immunosuppressed patients. Surgical resection can be curative in certain patients after antifungal treatment. Over a 7-year period, ten patients with suspected invasive pulmonary aspergillosis of two university hospitals were retrospectively reviewed. A literature review was undertaken. Patients age was 48.1 years (mean); the cause of immunosuppression was a hematological disease with consecutive therapy in seven patients and chronically corticoid therapy in three patients. After an antifungal therapy, surgical resection was performed with lobectomy/segmentectomy in 60% and with wedge-resection in 40%. Postoperative course were uneventful in seven patients, two patients died due to infectional circumstances, and one patient was reoperated because of empyema. The underlying disease marked long-term follow-up. Resection of focal pulmonary invasive aspergillosis can be curative. Clinical circumstances and dissemination must be taken into consideration to indicate surgery. To point out the best pathway randomised prospective studies are necessary.

Tolerance to propofol's sedative effect in mechanically ventilated Rabbits.

Propofol is commonly used for the sedation of critically ill patients undergoing mechanical ventilation. These patients may develop tolerance during long-term administration. Here, we describe the development of tolerance to propofol’s sedative effect in rabbits during prolonged mechanical ventilation. Six healthy male New Zealand White rabbits were endotracheally intubated and received propofol by continuous IV infusion to maintain sedation for 48 h. The propofol infusion rate (IR) was adjusted to maintain the desired level of sedation. Assessments of the sedation level were made every 30 min or earlier if there were signs of awakening. Propofol concentrations were measured in arterial plasma after every other IR adjustment, provided there was an adequate level of sedation, using high performance liquid chromatography, and calculations of systemic clearance rates were made. The mortality rate was 100% with a survival period of 30.8 ± 6.0 h (mean ± sd). The course of IR adjustments followed a 5-phase pattern: 1) steady IR (mean ± sd duration; 1.2 ± 0.6 h), 2) increasing IR (9.4 ± 5.5 h), 3) steady high-IR (2.3 ± 1.2 h), 4) decreasing IR (13.7 ± 1.9 h), and 5) steady low-IR (5.0 ± 2.7 h). The course of propofol concentrations during the experiment in relation to propofol IR followed a 3-phase pattern: 1) steady concentration with increasing IRs (6.0 ± 2.7 h), 2) increasing concentrations with increasing IR (5.8 ± 2.5 h), and 3) increasing concentrations with decreasing IR (18.8 ± 3.3 h). Propofol systemic clearance rates were progressively increased for 6.0 ± 2.7 h and then gradually decreased for 24.6 ± 4.7 h. In conclusion, all rabbits developed tolerance to propofol’s sedative effect within the first hours of administration related to changes to the drug’s metabolic clearance.

Angiogenic Growth Factors in the Treatment of Peripheral Arterial Disease

Peripheral arterial disease (PAD) remains a major cause of morbidity. Despite advances in revascularisation procedures and medical treatment, limb salvage and relief of pain are still not satisfactory in patients with severe disease. This has prompted the exploration of alternative modes of treatment including enhancement of new vessel formation (angiogenesis). Angiogenic Growth Factors (AGF), mainly Vascular Endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF) and Hepatocyte Growth Factor (HGF) have emerged as exciting therapeutic modalities. Both experimental and clinical studies have demonstrated that topical (mainly intramuscular) AGF gene therapy results in improved peripheral vasculature and alleviation of symptoms. However, most clinical work is limited to small patient series and the long-term safety and efficacy are still unclear. Clinical benefit must be balanced against potential untoward effects, such as tumour growth and atherosclerotic plaque angiogenesis leading to plaque instability. VEGF is important in the pathogenesis of diabetic microvascular disease. Further studies are required before implementation of AGF therapy in clinical practice.

A rare case of late right ventricular perforation by a passive-fixation permanent pacemaker lead.

The present paper is an interesting and rare complication of implantation of a permanent pacemaker lead. The rarity of the case is based upon that ventricular perforation is usually present during implantation, whereas in our case, it was presented late--1 month after implantation. Furthermore, in our case, the pacemaker lead had migrated through the left hemidiaphragm into the peritoneal cavity.

Sternoclavicular joint septic arthritis and mediastinitis. A case report and review of the literature

Septic arthritis of the sternoclavicular joint is rare. Its causes have been reported to include immuno-compromizing diseases, intravenous drug abuse, fractures of the clavicle or catheterization of the subclavian vein. We report a case of septic arthritis of the SCJ in a diabetic patient following periarticular injection of steroids in the ipsilateral shoulder, as this route of infection has not been documented, to our knowledge, in the literature to date. We review the literature regarding epidemiology and methods of surgical treatment that have been proposed, and present our own surgical experience. Bacterial infection should always be suspected in cases of SCJ arthritis. If surgery is required, it is important to remember that bony procedures leave vascular structures exposed, making their cover by myoplasty mandatory.

DYNAMIC MECHANICAL PROPERTIES OF ARTERIAL AND VENOUS GRAFTS USED IN CORONARY BYPASS SURGERY

In this work we studied the frequency dependence of the dynamic mechanical characteristic s of saphenous vein (SV) and internal mammary artery (IMA) grafts. Rectangular longitudinal strips from 14 patients were tested under cyclic uniaxial tensile loading in the frequency range of 0.1–20 Hz, at 37°C in wet conditions. The dynamic mechanical parameters (the storage modulus ES and the hysteresis ratio h (loading/loop area)) together with the collagen phase modulus EH were computed as a function of frequency. The results showed that in all graft types ES and EH varied with frequency in the range 0.5–10 Hz, presenting a maximum in the neighboring of 1 Hz. The hysteresis ratio h was increased in the frequency range 1–20 Hz. It seems from the results that the physical resonance frequency of the components of the tissue responsible for their elastic behavior may lay in the range around 1 Hz, while that for the viscous behavior in the range of 20 Hz or more. Early clinical outcomes of both grafting were studied in parallel. In a one-year postoperative period the follow-up (clinical examination, electrocardiography, echocardiography and stress test) did not reveal any sign of graft occlusion or severe stenosis except one perioperative infraction but without any correlation to the graft quality.

Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis

AimThe factors mediating the paracrine effects of perivascular adipose tissue (PVAT) in atherosclerosis are largely unknown. The adipokine leptin has been implicated in the increased cardiovascular risk in obesity and may locally promote neointima formation independently of circulating leptin levels. In patients with established coronary artery disease, we examined the expression of leptin as well as of its possible inducers in ‘cardiac’ PVAT surrounding the aortic root and coronary arteries (C-PVAT), and compared it to the PVAT surrounding the internal mammary artery (IMA-PVAT), a vessel resistant to atherosclerosis.Methods and resultsTissue specimens collected from male patients undergoing coronary artery bypass surgery were processed for real-time PCR, ELISA, in situ hybridization, and immunohistochemistry analysis. Leptin protein expression was elevated in C-PVAT compared to IMA-PVAT, independent of serum leptin levels. Compared to IMA-PVAT, C-PVAT exhibited more pronounced angiogenesis and inflammation, as indicated by significantly higher numbers of PECAM1-positive vessels and CD68-positive macrophages, and was characterized by a greater extent of fibrosis and hypoxia. Increased expression of hypoxia-inducible factor-1α and Fos-like antigen (FOSL)2, factors known to enhance leptin gene transcription, was observed in C-PVAT. As a proof of concept, exposure of human adipocytes to chemical hypoxia resulted in significantly increased FOSL2 and leptin mRNA levels.ConclusionsA higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

Adenocarcinoma in pulmonary sequestration.

A 67-year-old male smoker presented with hemoptysis and recurrent pneumonia. Chest computed tomography showed an emphysematous cyst and air-fluid level cavities in the left lower lobe. A left lower lobectomy was performed. The intraoperative finding was intralobar sequestration. Histopathology revealed adenocarcinoma within the sequestrated lobe. Only 8 cases of lung cancer and sequestration have been reported since 1963.