[Can myocardial damage following heart infarct be reversible?].
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Heart↗
Biomedical subjects
P Stulz
Publications and source records attributed to P Stulz.
DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.
Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity--found in 49.5% of the tumours--was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 +/- 10.2) than in p53-negative tumours (10.3 +/- 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.
Aneuploidy↗
Dyspnea after pneumonectomy: the result of an atrial septal defect.
We report the case of severe hypoxemia attributable to right-to-left shunting through an atrial septal defect after right-sided pneumonectomy that developed in a 70-year-old man. Normal right atrial and pulmonary artery pressures were measured. Right-to-left shunting through a patent foramen ovale is known as a rare complication after pneumonectomy. Our patient, however, demonstrated a true atrial septal defect (septum secundum defect) upon open operative repair of the interatrial connection.
Aged↗
Diagnostic and therapeutic thoracic surgery in leukemia and severe aplastic anemia.
BACKGROUND: Pulmonary complications often occur in patients with leukemia and severe aplastic anemia. Particularly in patients having undergone bone marrow transplantation, respiratory diseases account for a significant number of deaths. In a retrospective study, we evaluated 41 patients with leukemia and severe aplastic anemia who were operated on consecutively from 1980 to 1995. METHODS: Fourteen open lung biopsies, four video-assisted lung biopsies, and 24 lung resections were performed in 24 male and 17 female patients. Mean age was 32.2 years. RESULTS: Eleven (27%) early deaths occurred (30-day mortality): ten in patients after lung biopsy (56%) and one after lung resection (4%) (p < 0.001). Perioperative morbidity relating to pulmonary disease or operation included 10 (24.4%) cases of prolonged (> 24 hours) postoperative mechanical ventilation and two (4.8%) cases of bleeding or hematoma. In one (2.4%) patient a slowly developing, contained bronchial stump insufficiency appeared after lobectomy, which was successfully operated on 3 weeks later. CONCLUSION: We conclude that resection of localized pulmonary lesions, be it for diagnostic or therapeutic (or combined) purposes, can be carried out with low morbidity and mortality in patients with leukemia and severe aplastic anemia. However, early mortality is high after open or thoracoscopic lung biopsies in patients with acute-onset diffuse pulmonary disease, and little therapeutic benefit is realized in these cases.
Adolescent↗
Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function.
OBJECTIVES: The aim of this study was to evaluate the effects of high intensity exercise training on left ventricular function and hemodynamic responses to exercise in patients with reduced ventricular function. BACKGROUND: Results of studies on central hemodynamic adaptations to exercise training in patients with chronic heart failure have been contradictory, and some research has suggested that training causes further myocardial damage in these patients after a myocardial infarction. METHODS: Twenty-five men with left ventricular dysfunction after a myocardial infarction or coronary artery bypass graft surgery were randomized to an exercise training group (mean age +/- SD 56 +/- 5 years, mean ejection fraction [EF] 32 +/- 7%, n = 12) or a control group (mean age 55 +/- 7 years, mean EF 33 +/- 6%, n = 13). Patients in the exercise group performed 2 h of walking daily and four weekly sessions of high intensity monitored stationary cycling (40 min at 70% to 80% peak capacity) at a residential rehabilitation center for a period of 2 months. Ventilatory gas exchange and upright hemodynamic measurements (rest and peak exercise cardiac output; pulmonary artery, wedge and mean arterial pressures; and systemic vascular resistance) were performed before and after the study period. RESULTS: Maximal oxygen uptake (VO2max) increased by 23% after 1 month of training, and by an additional 6% after month 2. The increase in VO2max in the trained group paralleled an increase in maximal cardiac output (12.0 +/- 1.8 liters/min before training vs. 13.7 +/- 2.5 liters/min after training, p < 0.05), but maximal cardiac output did not change in the control group. Neither stroke volume nor hemodynamic pressures at rest or during exercise differed within or between groups. Rest left ventricular mass, volumes and EF determined by magnetic resonance imaging were unchanged in both groups. CONCLUSIONS: High intensity exercise training in patients with reduced left ventricular function results in substantial increases in VO2max by way of an increase in maximal cardiac output combined with a widening of maximal arteriovenous oxygen difference, but not changes in contractility. Training did not worsen hemodynamic status or cause further myocardial damage.
Cardiac Output↗
Successful surgery for perforation of the thoracic aorta caused by the tip of an intra-aortic balloon pump.
We describe a case of perforation of the thoracic aorta caused by the tip of an intra-aortic balloon pump. The perforation was confirmed by computed tomography (CT) scan and immediate surgical repair was successful. Vascular injury due to the insertion of an intra-aortic balloon pump is quite common but is predominantly confined to limb ischemia or injury to the femoral or iliac artery. Iatrogenic aortic perforation leading to significant bleeding is much less common and usually fatal.
Aged↗
Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.
Vascular endothelial growth factor (VEGF) is a potent peptide growth factor specific for vascular endothelial cells, which promotes neovascularization and increases vascular permeability in vivo. Enhanced microvascular permeability and edema are common characteristics of inflammatory and neoplastic disorders. Two proinflammatory mediators, platelet-activating factor (PAF) and platelet-derived growth factor (PDGF), are known to contribute to cellular damage and tissue remodeling in a number of lung diseases. To determine whether PAF or PDGF induce VEGF gene expression in primary cultures of human pulmonary fibroblasts and pulmonary vascular smooth-muscle cells (VSMCs), we performed Northern-blot analysis and enzyme-linked immunosorbent assays (EIA). PAF and all three isoforms of PDGF (PDGF-AA, -AB, and -BB) increased VEGF mRNA in a time- and dose-dependent manner. While PAF was shown to increase VEGF mRNA at picomolar concentrations, all PDGF isoforms were effective in inducing VEGF mRNA at nanomolar concentrations. The transcriptional activation was accompanied by increased levels of VEGF protein as determined by EIA in culture medium. These results indicate that VEGF gene expression in VSMCs and fibroblasts is mediated by PAF and/or PDGF isoforms. In a paracrine mode of action, secreted VEGF may then lead to altered endothelial cell functions and vascular hyperpermeability. In the presence of the corticosteroids cortisone, hydrocortisone, dexamethasone, or prednisolone at nanomolar concentrations, this stimulus-dependent transcription of VEGF was abolished. The inhibitory effect of corticosteroids on VEGF expression could explain the clinically well-known antiedematous potency of corticosteroids on a molecular level.
Adrenal Cortex Hormones↗
Right ventricular myxoma mimicking recurrent pulmonary embolism after primary ligament reconstruction.
Recurrent pulmonary emboli may be due to numerous causes and deep vein thrombosis are not an unusual source of pulmonary emboli following surgery. In this case report, the diagnostic approach and implications of a right ventricular myxoma as a rare source in a young patient is described. A 27-year old healthy woman presented scintigraphically proven recurrent pulmonary emboli after primary ligament reconstruction. Following a long period of diagnostic work-up for thromboembolism after surgery, a transthoracic and transoesophageal echocardiography was performed to document a right ventricular myxoma. Both transthoracic and transoesophageal echocardiography are powerful diagnostic means in a cardiac work-up and were used in this patient for the documentation of a right ventricular myxoma mimicking deep vein thromboembolism after surgery. As consequence of this case report we recommend to investigate patients with recurrent pulmonary embolism and no detectable venous thrombosis by echocardiography and a need for cardiac catheterization is restricted to patients with possible coexisting coronary artery disease. Furthermore, this case report demonstrates a myxoma in the right ventricle occurring only in 3-4% of all myxomas.
Adult↗
Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma.
The prognosis of operated patients with non-small cell lung cancer (NSCLC) is poor despite thorough pre-operative staging. An improved preselection is needed of patients likely to profit from surgery. This study was undertaken to evaluate the prognostic significance of nuclear p53 overexpression in a cohort of 247 surgically treated patients with NSCLC. It showed that the prevalence of immunohistochemically detectable p53 overexpression varied between different tumour types. p53 overexpression was equally frequent in large cell carcinoma (53 per cent) and in squamous cell carcinoma (54 per cent), but significantly less frequent in adenocarcinoma (34 per cent; P = 0.009). p53 overexpression was particularly rare in bronchioloalveolar carcinoma (positivity in 1 of 17 cases). These variations may reflect aetiological differences between the histological subtypes. p53 overexpression was also associated with high tumour grade (P = 0.0157) and the presence of lymph node metastasis (P = 0.0259), but not with advanced tumour stage. Survival analysis showed no difference in clinical outcome between p53-positive and p53-negative tumours within 101 node-positive tumours. In contrast, survival time was significantly better in p53-negative tumours than in p53-positive tumours within the group of 113 node-negative tumours (P = 0.032). Stepwise regression analysis showed that p53 overexpression is an independent prognostic factor in node-negative NSCLC.
Biomarkers, Tumor↗
Localization of the angiotensin II receptor subtypes in the human atrium.
Angiotensin II has two major receptor subtypes, designated AT1 and AT2. Both have been detected in the heart of several species, but most of the known functions of angiotensin II seem to be mediated through the AT1 receptor. The major objective of this study was to specify the cell type on which the AT2 receptor is located in the atrium of human heart. Right atrial biopsies from patients with coronary artery disease were tested in membrane binding assays and found to contain high levels of angiotensin II receptor (820 +/- 175 fmol/mg), 82 +/- 2% of which was of the AT2 subtype. Cryostat sections of these biopsies were incubated with 125I-[Sar1,Ile8] angiotensin II in the presence of selective concentrations of the cold ligands losartan and CGP 42112A to detect the subtypes using microscopic autoradiography. High local densities of the AT2 receptor were observed. Comparison of the labelling patterns thus obtained with adjacent sections stained for vimentin, collagen, neurofilaments or acetylcholinesterase revealed that the high densities of AT2 receptor were always associated with fibrous tissue. However, the AT1 receptor was in general evenly distributed over the tissue at low concentrations. Higher local concentrations of this receptor subtype were observed on nervous tissue. The present finding of high densities of the AT2 receptor on fibroblasts at sites of fibrosis may have important clinical implications. Further studies to elucidate the function of this receptor subtype in the heart are therefore essential and the clinical consequences of the use of AT1 antagonists on post-infarction remodelling should be investigated.
Aged↗
Protamine-induced fulminating non-cardiogenic pulmonary edema following cardiopulmonary bypass.
Although fulminating non-cardiogenic pulmonary edema following cardiopulmonary bypass is not a new phenomenon, the exact cause and pathogenesis are still unknown. The causative agent of this potentially lethal syndrome was hypothesized to be either protamine or blood products. There was no evidence that an antibody-mediated reaction plays a role and patients were reported to have negative skin tests. We report, for the first time, a patient who presented with fulminating non-cardiogenic pulmonary edema after repeated protamine administration with a subsequent positive skin test to protamine. Specific IgG antibodies to protamine were also found; however, the level was in the range of that of exposed non-reacting controls. IgE antibodies could not be detected.
Aortic Aneurysm↗
Long-term follow-up in pulmonary embolectomy: is NYHA (dyspnea) classification reliable?
In this retrospective investigation we carried out a thorough physical examination, ventilation/perfusion scintigraphy, echocardiography and lung function test in 19 of all 21 long-term survivors consecutively operated on for massive pulmonary embolism between 1968 and 1992. Two patients refused these investigations but were both asymptomatic. The mean follow-up was 8.4 years and 12 (57%) of the patients were in NYHA I and 6 (29%) in NYHA II. The three patients in NYHA III (there were none in class IV) underwent right heart catheterization and pulmonary angiography additionally. Our findings suggest that, generally, the results of scintigraphy, echocardiography, lung function tests and physical examination correspond to the subjective status expressed as NYHA (dyspnea) class, when evaluated in combination. However, in classes III and IV other causes of dyspnea apart from residual pulmonary vascular obstruction can be found. These may also occur in combination. We observed severe chronic obstructive lung disease, hemidiaphragmatic paralysis, obesity, pulmonary hypertension of unknown origin, atrial septal defect (ASD) and neurologic residual deficit with depressive state. Thus, in evaluating long-term results of pulmonary embolectomy with regard to vascular desobliteration, NYHA classification does not seem to be reliable for classes III and IV.
Adult↗
Angiotensin II-receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction.
Angiotensin II (AII) has been implicated as an important factor in the pathophysiology of heart diseases. Following the recent identification of two subtypes of the AII receptor in cardiac tissue of animals, we investigated the possible occurrence of these, or similar, subtypes in human atrial tissue. In right-atrial tissue from patients undergoing heart surgery, we determined the AII-receptor profile in receptor binding studies, using [125I]-angiotensin as radioligand and subtypes to identify and quantify AII-receptor subpopulations. In 35 patients (23 requiring coronary bypasses, 10 valvular surgery and two combined coronary and valvular surgery), the left-ventricular ejection fraction was determined in the preoperative phase, and right- and left-atrial pressure during surgery. In membranes of human right atria, AII receptors are present in high density (median: Bmax = 294 fmol.mg-1 protein, range: 111-2073) and two different subtypes can be distinguished. Type-1 receptors (AT1) accounted for 33 +/- 10% of the population whereas type-2 receptors (AT2) made up 67 +/- 10% of the population. There was no correlation between any of the measured cardiac functions and total AII-receptor density or receptor affinity. However, the percentage of AT1 receptors was higher in the atria of patients with normal right-atrial pressure; left-ventricular ejection fraction was positively and right-atrial pressure inversely correlated with the percentage of AT1 receptors (r = 0.740 and -0.901, respectively; P < 0.001, for both). Moreover, the percentage of AT2 receptors was directly correlated with the levels of left-atrial pressure (r = 0.853; P < 0.001). It is concluded that the ratio of AT1 to AT2 receptors correlates well with right-atrial pressure and left-ventricular function. This is a first indication of a possible involvement of AII-receptor subtypes in the pathophysiology of cardiac dysfunctions.
Adult↗
Pulmonary function and exercise capacity after lung resection.
The influence of pulmonary resection on functional capacity can be assessed in different ways. The aim of this study was to compare the effect of lobectomy and pneumonectomy on pulmonary function tests (PFT), exercise capacity and perception of symptoms. Sixty eight patients underwent functional assessment with PFT and exercise testing before (Preop), and 3 and 6 months after lung resection. In 50 (36 males and 14 females; mean age 61 yrs) a lobectomy was performed and in 18 (13 males and 5 females; mean age 59 yrs) a pneumonectomy was performed. Three months after lobectomy, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and maximal oxygen uptake (V'O2,max) were significantly lower than Preop values, increasing significantly from 3 to 6 months after resection. Three months after pneumonectomy, all parameters were significantly lower than Preop values and significantly lower than postlobectomy values and did not recover from 3 to 6 months after resection. At 6 months after resection significant deficits persisted in comparison with Preop: for FVC 7% and 36%, FEV1 9% and 34%, TLC 10% and 33% for lobectomy and pneumonectomy, respectively; and V'O2,max 20% after pneumonectomy only. Exercise was limited by leg muscle fatigue in 53% of all patients at Preop. This was not altered by lobectomy, but there was a switch to dyspnoea as the limiting factor after pneumonectomy (61% of patients at 3 months and 50% at 6 months after resection). Furthermore, pneumonectomy compared to lobectomy led to a significantly smaller breathing reserve (mean +/- SD) (28 +/- 13 vs 37 +/- 16% at 3 months; and 24 +/- 11% vs 33 +/- 12% at 6 months post resection) and lower arterial oxygen tension at peak exercise 10.1 +/- 1.5 vs 11.5 +/- 1.6 kPa (76 +/- 11 vs 86 +/- 12 mmHg) at 3 months; 10.1 +/- 1.3 vs 11.3 +/- 1.6 kPa (76 +/- 10 vs 85 +/- 12 mmHg) at 6 months postresection. We conclude that measurements of conventional pulmonary function tests alone overestimate the decrease in functional capacity after lung resection. Exercise capacity after lobectomy is unchanged, whereas pneumonectomy leads to a 20% decrease, probably due to the reduced area of gas exchange.
Adult↗
Rapidly growing intrathoracic mass with paraneoplastic syndrome.
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Humans↗
[Lung scintigraphy and ergospirometry in prediction of postoperative course in lung resection candidates with increased risk of postoperative complications].
Patients with impaired pulmonary function are at increased risk for the development of postoperative complications. We therefore analyzed the value of preoperative lung scanning and exercise testing for the prediction of postoperative complications and of the short- as well as long-term performance in lung resection candidates at increased risk for complications. Twenty-five (mean age 63 y; 17 m) out of 84 consecutive lung resection candidates were considered at increased risk for postoperative complications due to impaired pulmonary function (FEV1 < 2L or diffusion for carbon monoxide (DLCO) < 50% predicted, or FEV1 and DLCO < or = 80% predicted combined with New York Heart Association dyspnea index > or = 2). Candidates underwent radionuclide perfusion scans and exercise testing to predict postoperative ( = ppo) values for FEV1, DLCO and maximal O2-uptake (VO2max). They all underwent thoracotomy for neoplastic lesions; 7 had pneumonectomies, 18 lobectomies. Six had postoperative complications (within 30 days), of whom three died. Three and 6 months postoperatively, pulmonary function tests and VO2max were repeated. In the 22 survivors, the observed values were then compared with the predicted values. At 3 months, there were excellent correlations (absolute/predicted values): for FEV1r = 0.78 and 0.81; for DLCOr = 0.77 and 0.74; and for VO2max r = 0.71 and 0.83. The means of FEV1 and VO2max did not differ from the predicted values, whereas the predicted DLCO was lower than the observed value (ml/min/mmHg: 15.1 vs 17.9; percent predicted: 59.6 vs 70.9) (p < 0.05). At 6 months, correlations remained very good for FEV1 (r = 0.81 and 0.84) and for DLCO (r = 0.76 and 0.74), but had decreased for VO2max to 0.56 and 0.65, respectively. All means were higher than predicted (p < 0.05) owing to recovery in the lobectomy group. Patients with postoperative complications (group B) had a lower preoperative VO2max in percent predicted (62.8 +/- 7.5% vs 84.6 +/- 19.7%) (p < 0.01) and also a lower VO2max-ppo (10.6 +/- 3.6 vs 14.8 +/- 3.5 ml/kg/min and 44.3 +/- 13.5 vs 68.0 +/- 20.7 percent predicted) (p < 0.05) than patients without complication (group A). AVO2max-ppo < 10/ml/kg/min was associated with a 100% mortality. Although FEV1-ppo and DLco-ppo were lower in group B the difference did not reach significance. We conclude that radionuclide-based calculations of postoperative VO2max are predictive of perioperative morbidity and mortality: a VO2max-ppo of < 10 ml/kg/min may indicate inoperability. Further, short-term postoperative performance is accurately predicted by FEV1-ppo and VO2max-ppo, but long-term function is underestimated after lobectomy.
Adult↗
Development of nitrate tolerance in human arteries and veins: comparison of nitroglycerin and SPM 5185.
Nitrate tolerance is a clinical problem in patients with coronary artery disease and heart failure. Human internal mammary arteries and saphenous veins obtained intraoperatively were suspended in organ chambers, and isometric tension was measured. In the artery, nitroglycerin elicited a potent relaxation, which was significantly diminished after prolonged incubation with nitroglycerin (10(-6) M, 1 h). In contrast, no tolerance occurred in saphenous vein under the same conditions. However, incubation with 10(-5) M nitroglycerin also developed tolerance. Compared to nitroglycerin, the new cysteine-containing mononitrate SPM 5185 exhibited a lower sensitivity but comparable maximal relaxation in arteries and veins. In nitroglycerin-tolerant arteries and veins, SPM 5185 caused relaxations similar to those under control conditions. Our results show that in isolated blood vessels, vascular nitrate tolerance occurs more readily in the mammary artery than in the saphenous vein. SPM 5185 seems to be less prone to the development of tolerance, which may be advantageous during chronic nitrate therapy.
Acetylcysteine↗