Biomedical subjects
Publications and source records attributed to E Mayer.
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BACKGROUND: The delivery of genes to the airways holds promise for the treatment of lung diseases such as cystic fibrosis and asthma. Current non-viral gene delivery systems lack sufficient transfection efficiency. Pulmonary surfactant has been reported to be a barrier to gene transfer into the airways. Here we analyze the interaction of liposomal and polycationic transfection complexes with pulmonary surfactant. METHODS: The efficiency of non-viral transfection of cultured human airway epithelial cells (16HBE14o-), COS7 cells and porcine primary airway epithelial cells was studied in the presence of various surfactant preparations in order to model the conditions prevailing in the airways during transfection. RESULTS: The natural pulmonary surfactant, Alveofact, an extract from bovine lung lavage, was found to inhibit lipofection with lipofectAMINE for all cell lines investigated. Dendrimer meditated polyfection was unaffected for pulmonary cell lines and was weakly affected for COS7 cells. PEI-mediated polyfection was unaffected for all cell lines tested. The synthetic surfactant preparation Exosurf containing L-alpha-phosphatidylcholine-dipalmitoyl (DPPC) as the sole lipid ingredient had no statistically significant effect on polymer- and lipid-mediated transfection. The transfection efficiencies are related to structural changes in the DNA complexes as demonstrated by DNase-accessibility tests and fluorescence spectroscopy. In the presence of the phospholipid POPG, which is a constituent of Alveofact, DNA condensed in lipofectAMINE lipoplexes became accessible to DNaseI, while DNA condensed with PAMAM dendrimer or PEI was less accessible to DNase I as compared to lipoplexes. Consistently, the fluorescence of a DNA-intercalating dye increased after addition of Alveofact only in the case of lipoplexes. CONCLUSIONS: In contrast to lipofection, gene transfer with cationic polymers to airway epithelial cells is not inhibited by pulmonary surfactant in vitro. Depending on the surfactant concentration even an increase in polymermediated transfection can be seen. In conclusion, cationic polymers appear to be the more stable gene delivery systems for topical application into the airways.
The exact understanding of the interaction of minor groove binding drugs with DNA is of interest due to their importance as transcription controlling drugs. In this study we performed four molecular dynamics simulations, one of the uncomplexed d(CGCGAATTCGCG)(2) dodecamer and three simulations of the DNA complexed with the minor groove binder netropsin. The charged guanidinium and amidinium ends of the small ligand were in one simulation formally uncharged, in the second one normally charged, and in the third simulation we doubled the charges of the two ends. So we are able to filter out the influence the charges exert on the DNA structure. The positive charges reduce the width of the minor groove showing that charges are able to modify the groove width by charge neutralization of the negative phosphate groups. The quality of the used force field was successfully tested by comparing the results of the uncomplexed dodecamer with already reported NMR and x-ray studies. Thus our simulations should be able to describe the minor groove width of DNA in a correct manner underlying the validity of the results.
PURPOSE: The diagnosis of the rare primary malignant tumors of the pulmonary arteries is often delayed as symptoms are nonspecific. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) of three patients with occlusion of the right pulmonary artery, two with sarcoma and one with chronic thromboembolic disease were analyzed for discriminating diagnostic criteria. RESULTS: Criteria suggesting pulmonary artery sarcoma are inhomogeneous high or low attenuation (hemorrhage, necrosis), soft-tissue density in pulmonary arteries, vascular distension, enhancement after administration of gadopentetate dimeglumine. Criteria for chronic thromboembolic disease are homogeneous soft-tissue lesions, abrupt vascular narrowings and cut-offs, as well as regional parenchymal hyperdensities. CONCLUSION: CT and MRI provide complementary findings suggesting advanced pulmonary artery sarcoma instead of chronic thromboembolism.
In 16 conscious resting dogs regional myocardial blood flow and the local coronary dilatory capacity were studied with the particle distribution technique during isovolemic hemodilution (hct = 13%). Postischemic peak coronary hyperemia following release of temporary circumflex coronary artery occlusion was used for quantification of regional coronary dilatory capacity. In hemodilution (arterial blood oxygen content less than one third of normal) left ventricular blood flow (LVBF) was 460 +/- 36 ml/100 g - min, subendocardial/subepicardial flow amounted to 1.3 +/- 0.1. During postischemic peak hyperemia LVBF increased by 33% up to 606 +/- 63 ml/100 g - min. This 33% increase in LVBF was distributed mainly to the subepicardial layer, while in the subendocardial layer there was no significant flow increase. It is concluded that the increase in heart rate and systolic coronary vascular compression in addition to the lowered arterial oxygen content lead to exhaustion of the dilatory reserve in the subendocardium during hemodilution. Therefore the remaining overall dilatory capacity is without functional significance.
The effects of short episodes (1 min) of vagally-mediated bradycardia were studied in 9 anesthetized dogs utilizing vagal stimulation and slow atrial pacing (120 and 80 beats/min) before and after graded coronary constriction of the left anterior descending (LAD) and the left circumflex (CCA). In the presence of 90% LAD stenosis, bradycardia tended to restore both the elevated total LAD coronary vascular resistance (CVR-LAD) and the reduced, total CVR-CCA towards control levels obtained at corresponding slow rates in the absence of coronary stenosis; as a result, LAD coronary flow (F-LAD) was relatively less reduced and the accessory rise of F-CCA disappeared. In the presence of combination of 90% LAD plus 70% CCA stenosis, the effects of bradycardia on total CVR-LAD and F-LAD were similar to those obtained with single 90% LAD stenosis, but the accessory flow through the CCA was abolished resulting in no significant difference of the rate-dependent alterations of total CVR-CCA and F-CCA as compared with those observed in the absence of coronary stenosis. In the presence of single or combined coronary stenosis, bradycardia restored the depressed aortic pressure and cardiac output towards control values obtained at comparable slow rates before coronary stenosis. The results support the concept that in the presence of 90% LAD stenosis vagally-mediated bradycardia 1) decreases the tension-time index (myocardial nutritional demand) shifting cardiac performance to less expensive "flow work" and 2) facilitates antegrade flow through the highly stenotic LAD thereby inhibiting accessory flow through the nonstenotic CCA.
The importance of single components of ischemia including hypoxia, lactic acidosis, high potassium, and sympathetic stimulation to the spontaneous occurrence of ventricular arrhythmias was studied in chloralose-anesthetized cats using systemic and local intracoronary administration. Hypoxia and acidosis provoked no spontaneous arrhythmias regardless of systemic or regional administration. Systemic or local hyperpotassemia induced regularly ventricular ectopic activity including recurrent ventricular tachycardias that were characterized by a sudden onset and termination and by a stable rate. Stimulation of the left, right or bilateral stellate ganglia failed to provoke ventricular arrhythmias during hypoxia or acidosis and had also no influence on the initiation or rate of K+-induced ventricular tachycardias. The results indicate that high extracellular K+ may be the predominant arrhythmogenic factor of the components of ischemia we studied and that sympathetic ganglia stimulation does not affect K+-induced ventricular tachycardia.
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OBJECTIVE: Computed tomography study of bronchial artery anatomy and evaluation of dilatation and tortuousity as indicators for pulmonary hypertension and surgical risk in patients with chronic thromboembolism were performed. MATERIALS AND METHODS: We retrospectively reviewed contrast-enhanced, thin section spiral CT scans of 39 patients undergoing pulmonary thromboendarterectomy. Findings were compared with mean pulmonary artery (PA) pressure in all, postoperative mortality in 33, and postoperative CT in 5 patients. Twenty patients without pulmonary hypertension served as controls. RESULTS: In the pulmonary hypertension group, 50 bronchial arteries were observed in 30 of 39 patients. Their prevalence was significantly higher than in the control group (p < 0.0001). Their proximal diameter measured > or = 1.5 mm in 20 patients (51%); a tortuous course was found in 14 (36%). The correlation between total bronchial artery diameter and mean PA pressure was poor (r = 0.2). Patients with dilated bronchial arteries had a significantly lower risk for postoperative death than patients without (p < 0.05); positive predictive value was 100% and confidence interval 0.79-1.0. Despite normal postoperative PA pressures, bronchial arteries were still visible on follow-up studies. CONCLUSION: The CT depiction of bronchial arteries, dilatation, and tortuousity provides indicators for chronic thromboembolic pulmonary hypertension. Its degree cannot be estimated. Dilated bronchial arteries are a significant predictor for survival of pulmonary thromboendarterectomy.
This is a retrospective research with nurses graduated from the Federal University of Paraná (UFPR). A brief review of records such as meetings minutes, reports, and interviews documented the facts that built nursing from 1974 to 1994 at UFPR. The program graduated 467 nurses, to whom a questionnaire, containing open and closed questions, was sent. The sample was constituted of 62 graduates who answered the questionnaire. Qualitative and quantitative outcomes are presented in tables, providing support to curriculum changes and offering an alert to the need of conceptual clarification regarding teaching, practice and nursing research.
BACKGROUND: Homocystinuria is a rare autosomal recessive disease complicated by early and aggressive occlusive arterial disease. This may be related to the grossly increased homocysteine concentrations seen in this disease. More recently, milder hyperhomocysteinemia has been proposed as an independent risk factor for coronary artery disease. SUMMARY: Many patients with homozygous homocystinuria develop severe premature atherosclerosis and thromboembolism, probably caused by abnormally high concentrations of homocysteine. Homocysteine undergoes metabolism either by remethylation or transsulfuration, and deficiency or dysfunction of any of the substances that regulate these reactions may lead to hyperhomocysteinemia. Homocysteine may have adverse effects on platelets, clotting factors, and endothelial cells. Studies have demonstrated significantly higher plasma homocysteine levels in patients with occlusive arterial disease than in controls. The causes are not clearly understood but may include deficiency of vitamin B6, vitamin B12, and folic acid and heterozygosity for cystathionine synthase deficiency. Vitamin supplementation can lower plasma homocysteine levels. CONCLUSIONS: Whether measuring plasma homocysteine levels in patients with coronary artery disease should be routine and whether treating hyperhomocysteinemia in these patients may reduce the risk of coronary events remains to be determined.
Traditional Western biomedicine emphasizes changes in structure as explanations of disease, that are produced by single causes. It seeks to understand the proximate, molecular mechanisms of disease. The consequences of this line of thought are varied and many, and are not the purpose of this essay. Psychosomatic medicine research has always been more concerned with a broader and more integrated perspective in health, illness and disease. It has attempted to study and understand persons in terms of the behaviors of interacting systems - the physiology of the organism. In the past 20 years a language has evolved that speaks of the organism's functions in dynamic, time-related terms. Both phenomenologically and mathematically functions can be described in terms of rhythms which with disease undergo change. Each function has its own characteristic features (amplitude, frequency and form) it is frequency modulated. These rhythms are the product of oscillators, and/or positive and negative or mixed feedback systems. When perturbed they undergo changes in features. Many rhythms (e.g. circadian ones) are under environmental control, or are entrained by the environment and by social relationships.
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