Pioglitazone prevents smoking carcinogen-induced lung tumor development in mice.

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is known to have anti-tumor activity by inducing tumor cell apoptosis. However, it is unknown whether it can be used to prevent smoking carcinogen-induced lung tumor development. We induced mouse lung tumors using smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given at two early stages before the tumor formation. The role and the functional mechanism of PGZ were investigated in the development of mouse pulmonary tumors. The tumor development was monitored and PPARγ activity and endogenous PPARγ ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ before alveolar hyperplasia formation (Group NPa) and at the early phase of alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor development especially in Group NPb mice (all p < 0.05). PGZ not only prevented the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but also increased 13(S)-HODE level in Group NPb mice. PPARγ transcriptional activity was increased in NNKstimulated lung tissues when PGZ was given. The in vivo results were confirmed in the human lung cancer cells, which showed that PGZ induced lung cancer cell apoptosis through up-regulating nuclear PPARγ expression, inducing PPARγ transcriptional activity and increasing the levels of PPARγ ligands in NNK-treated cells. The early application of PGZ is able to prevent NNK-induced lung tumor development through maintaining the level of endogenous PPARγ ligands 15(S)-HETE and 13(S)-HODE and activation of PPARγ.

Video-assisted thoracic surgery for mediastinal extramedullary haematopoiesis.

Extramedullary haematopoiesis is a rare cause of an intrathoracic mass. We report a case of posterior mediastinal extramedullary haematopoietic mass in a 50-year-old man who presented with non-specific symptoms and a paravertebral mass on chest X-ray. Diagnosis was achieved by using video-assisted thoracic surgery.

Hemodynamic performance of the 21-mm Sorin Bicarbon mechanical aortic prostheses using dobutamine Doppler echocardiography.

BACKGROUND: Small-sized mechanical aortic prostheses are commonly associated with generation of high transvalvular gradients, particularly in patients with large body surface area, and can result in patient-prosthesis mismatch. This study evaluates the hemodynamic performance of 21-mm Sorin Bicarbon bileaflet mechanical prostheses using dobutamine stress echocardiography. METHODS: Fourteen patients (7 women; mean age, 63+/-8 years) who had undergone aortic valve replacement with a 21-mm Sorin Bicarbon bileaflet mechanical prosthesis 32.4+/-5.1 months previously were studied. After a resting Doppler echocardiogram, a dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 30 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed- and continuous-wave Doppler echocardiographic studies were performed at rest and at the end of each increment of dobutamine. Both peak and mean velocity and pressure gradient across the prostheses were measured, and effective orifice area, discharge coefficient, and performance index were calculated. RESULTS: Dobutamine stress increased heart rate and cardiac output by 83% and 81%, respectively (both p < 0.0001), and mean transvalvular gradient increased from 15.6+/-5.5 mm Hg at rest to 35.4+/-11.9 mm Hg at maximum stress (p < 0.0001). Although the indexed effective orifice area was significantly lower in patients with a larger body surface area, this was not associated with any significant pressure gradient. The performance index of this valve was unchanged throughout the study. Regression analyses demonstrated that the mean transvalvular gradient at maximum stress was independent of all variables except resting gradient (p = 0.05). Body surface area had no association with the changes in cardiac output, transvalvular gradient at maximum stress, and effective orifice area. CONCLUSIONS: These data show that the 21-mm Sorin Bicarbon bileaflet mechanical prosthesis offers an excellent hemodynamic performance with full utilization of its available orifice when implanted in the aortic position. The lack of significant transvalvular gradient in patients with a larger body surface area suggests that patient-prosthesis mismatch is highly unlikely when this prosthesis is used.

Prevention of spinal cord ischaemia during descending thoracic and thoracoabdominal aortic surgery.

Surgery of the descending and thoracoabdominal aorta has been associated with post-operative paraparesis or paraplegia. Different strategies, which can be operative or non-operative, have been developed to minimise the incidence of neurological complications after aortic surgery. This review serves to summarise the current practice of spinal cord protection during surgery of the descending thoracoabdominal aortic surgery. The pathophysiology of spinal cord ischaemia will also be explained. The incidence of spinal cord ischaemia and subsequent neurological complications was associated with (1) the duration and severity of ischaemia, (2) failure to establish spinal cord supply and (3) reperfusion injury. The blood supply of the spinal cord has been extensively studied and the significance of the artery of Adamkiewicz (ASA) being recognised. This helps us to understand the pathophysiology of spinal cord ischaemia during descending and thoracoabdominal aortic operation. Techniques of monitoring of spinal cord function using evoked potential have been developed. Preoperative identification of ASA facilitates the identification of critical intercostal vessels for reimplantation, resulting in re-establishment of spinal cord blood flow. Different surgical techniques have been developed to reduce the duration of ischaemia and this includes the latest transluminal techniques. Severity of ischaemia can be minimised by the use of CSF drainage, hypothermia, partial bypass and the use of adjunctive pharmacological therapy. Reperfusion injury can be reduced with the use of anti-oxidant therapy. The aetiology of neurological complications after descending and thoracoabdominal aortic surgery has been well described and attempts have been made to minimise this incidence based on our knowledge of the pathophysiology of spinal cord ischaemia. However, our understanding of the development and prevention of these complications require further investigation in the clinical setting before surgery on descending and thoracoabdominal aorta to be performed with negligible occurrence of these disabling neurological problems.

Can CT scanning be used to select patients with unilateral primary spontaneous pneumothorax for bilateral surgery?

STUDY OBJECTIVES: Despite advances in the surgical treatment of spontaneous pneumothorax, the timing of surgical intervention continues to be a subject of controversy. We test the hypothesis that CT scanning can help to predict the probability of the occurrence of primary spontaneous pneumothorax (PSP) by detecting lung bullae. DESIGN: Prospective, longitudinal cohort study. PATIENTS AND METHODS: Between May 1994 to March 1995, 28 consecutive patients (23 men; age range, 18 to 47 years; mean, 29 years) with unilateral PSP who were to undergo video-assisted thoracic surgery (VATS) received preoperative CT of the thorax. CT scans were interpreted by one radiologist blinded to the clinical data for the presence of bullae in both lungs. All patients were followed-up in our outpatient clinic for an average of 59.0 months (range, 54 to 64 months). RESULTS: Eighty-eight percent of the blebs or bullae identified intraoperatively were demonstrated on preoperative CT scans. CT scans also showed the presence of lung blebs or bullae in the contralateral lung in 15 patients (53.6%). During the follow-up period, 4 of these 15 patients (26.7%) with contralateral blebs developed PSP in the untreated lung; none of the patients who did not have contralateral blebs (n = 13) developed PSP (p = 0.04 [chi(2) analysis]). CONCLUSIONS: The detection of lung bullae by CT scanning in the contralateral lung following unilateral PSP is associated with a higher rate of subsequent occurrence of pneumothorax in that lung. Thus, CT scanning can be used to predict the risk of occurrence of this condition, allowing preemptive surgical intervention in selected patients.

Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury.

BACKGROUND: Proinflammatory cytokines play a key role in the inflammatory cascade after cardiopulmonary bypass and may induce cardiac dysfunction. We compared the production of cytokines and the degree of postoperative myocardial injury in patients with multivessel coronary artery disease undergoing coronary artery bypass grafting through median sternotomy with or without cardiopulmonary bypass. METHODS: Forty-four consecutive patients were studied. Patients were selected for off-pump coronary artery bypass grafting whenever complete revascularization was technically feasible. There were no differences between the two groups with respect to age, sex, symptoms, or functional class. Plasma levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured before the operation, at the end of the procedure, and 2, 4, 8, 24, and 48 hours thereafter. Levels of the MB isoenzyme of creatine kinase and cardiac troponin-I were also measured after the operation. RESULTS: The number of grafts was 2+/-0.7 in the off-pump group (n = 18) and 3+/-0.8 in the cardiopulmonary bypass group (n = 26). There were no deaths or major complications in either group. Levels of tumor necrosis factor-alpha were low in both groups. No significant intergroup differences were noted regarding serial IL-6 measurements. However, IL-8 and IL-10 levels after the operation were lower in the off-pump group (IL-8, 4+/-1 versus 38+/-12 pg/mL, p < 0.01; IL-10, 5+/-2 versus 191+/-33 pg/mL, p < 0.001). Whereas postoperative creatine kinase-MB values were similar in the two groups, cardiac troponin-I levels were significantly lower in the off-pump group (8 hours, p < 0.005; 24 hours, p < 0.02, respectively). Moreover, cardiac troponin-I values 24 hours after operation correlated strongly with IL-8 levels (r = 0.61, p < 0.005), indicating that the degree of myocardial injury may be related to IL-8 production. CONCLUSIONS: Compared with conventional coronary artery bypass grafting, coronary revascularization without cardiopulmonary bypass is associated with reduced cytokine responses and less myocardial injury.

Ministernotomy for aortic valve replacement in a patient with osteogenesis imperfecta.

Open heart operations in patients with osteogenesis imperfecta are associated with increased morbidity and mortality resulting from tissue friability and bone brittleness. We used a ministernotomy approach for aortic valve replacement in a patient with osteogenesis imperfecta, with clear benefits and a satisfactory outcome.

Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion.

BACKGROUND: Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis, although the optimal route of administration remains unclear. METHODS: We designed a prospective, randomized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion. From September 1993 to November 1995, 57 patients were recruited and randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia (n = 28) or talc slurry by the bedside (n = 29). Patients with poor general condition (Karnofsky score less than 30%), poor pulmonary function (forced expiratory volume in 1 second less than 0.5 L), or trapped lungs were excluded from this study. Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry. RESULTS: There was no statistically significant difference between the two groups of patients with respect to age, sex ratio, chest drainage duration, postprocedural hospital stay, parenteral narcotics requirement, complications, or procedure failure (ie, recurrence). CONCLUSIONS: Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study. Because the former demands more resources, we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs.