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Biomedical subjects

P Braun

Publications and source records attributed to P Braun.

At least 55 records · Page 3Linked to original sources
PubMed1997

Regression of transplant coronary artery disease during chronic low-density lipoprotein-apheresis.

BACKGROUND: The pathogenesis of transplant coronary artery disease (TxCAD) is probably multifactorial. Immune mechanisms may be the primary and triggering stimuli, whereas risk factors such as hyperlipoproteinemia or lipoprotein(a) elevation may accelerate the progression of the disease. With the heparin-induced-low-density lipoprotein-precipitation (HELP), low-density lipoprotein (LDL), fibrinogen, and lipoprotein(a) can be reduced about 55%, 50%, and 60%, respectively. METHODS: We treated eight heart transplant recipients (52.6 +/- 8.1 years old; all men) with weekly LDL-apheresis (HELP-system). At the beginning of the HELP treatment, all patients had survived at least 2 years after surgery, had LDL levels higher than 150 mg/dl in spite of 10 mg pravastatin per day and diet, and had development of significant coronary artery disease as shown by annual coronary angiography. We analyzed three angiograms in each patient taken 16.2 +/- 6.5 months before, at the beginning of (-0.5 +/- 6 months), and after 21.8 +/- 7.4 months of HELP therapy. Two hundred seventy-three coronary artery segments (34 +/- 6 per patient; 6 to 65 single measurements per segment) were analyzed by quantitative coronary angiography. Statistical significances of differences between the angiograms taken at the three time points were evaluated by the paired t test. RESULTS: Measurements of all coronary artery segments showed a significant decrease of mean luminal diameter during the last 1 to 2.5 years before the HELP treatment from 3.61 +/- 1.1 mm to 3.15 +/- 1 mm (p < 0.0001). During the following 1 to 2.5 years of HELP therapy, the mean luminal diameter increased to 3.4 +/- 1.15 mm (p < 0.0001). CONCLUSIONS: In long-term heart transplantation survivors with hyperlipidemia, who have development of a rapid progressive coronary artery disease, LDL-apheresis can lead to disease regression. Further studies will be needed to determine whether immunologic factors and growth factors involved in the TxCAD pathogenesis are also eliminated by the HELP therapy and whether HELP is also effective in patients with TxCAD without severe hypercholesterolemia.

Blood Component Removal↗
PubMed1996

Genetic characterization of a mammalian protein-protein interaction domain by using a yeast reverse two-hybrid system.

Many biological processes rely upon protein-protein interactions. Hence, detailed analysis of these interactions is critical for their understanding. Due to the complexities involved, genetic approaches are often needed. In yeast and phage, genetic characterizations of protein complexes are possible. However, in multicellular organisms, such characterizations are limited by the lack of powerful selection systems. Herein we describe genetic selections that allow single amino acid changes that disrupt protein-protein interactions to be selected from large libraries of randomly generated mutant alleles. The strategy, based on a yeast reverse two-hybrid system, involves a first-step negative selection for mutations that affect interaction, followed by a second-step positive selection for a subset of these mutations that maintain expression of full-length protein (two-step selection). We have selected such mutations in the transcription factor E2F1 that affect its ability to heterodimerize with DP1. The mutations obtained identified a putative helix in the marked box, a region conserved among E2F family members, as an important determinant for interaction. This two-step selection procedure can be used to characterize any interaction domain that can be tested in the two-hybrid system.

Alleles↗
PubMed1996

Predicting the presence of plasma heparin using neural networks to analyze coagulation screening assay optical profiles.

A method for predicting the presence of heparin from coagulation screening assays is described and data are presented. This method incorporates the use of a multilayer perceptron trained through an error back-propagation algorithm in analyzing clotting optical data profiles. This method may lead to the identification of abnormalities from screening assays that might otherwise go undetected, or require additional testing to isolate.

Artificial Intelligence↗
PubMed1996

Role of the propeptide in folding and secretion of elastase of Pseudomonas aeruginosa.

Elastase of Pseudomonas aeruginosa is synthesized as a pre-proprotein. The propeptide has been shown to inhibit the enzymatic activity of elastase. In this study, we investigated a possible additional role of the propeptide in the folding and secretion of the enzyme. When elastase was expressed in Escherichia coli without its propeptide, no active elastase was produced. The enzyme was poorly released from the cytoplasmic membrane and, depending on the expression level, it was either degraded or it accumulated in an inactive form in the cell envelopes, probably as aggregates. Since proper folding is required for the release of translocated proteins from the cytoplasmic membrane and for the acquirement of a stable and active conformation, these results suggest that the propeptide is involved in the proper folding of the elastase and that it functions as an intramolecular chaperone. When mature elastase was expressed without its propeptide in P. aeruginosa, the enzyme was not secreted, and it was degraded. Therefore, proper folding of mature elastase appears to be required for secretion of the enzyme. Expression of the propeptide, as a separate polypeptide, in trans with mature elastase resulted in the formation of active elastase. This active enzyme was secreted in P. aeruginosa. Apparently, the propeptide can also function as an intermolecular chaperone.

Bacterial Proteins↗
PubMed1996

Managed care and the infectious diseases specialist.

There is growing demand to contain health care costs and to reassess the value of medical services. The traditional hospital, academic, and research roles of the infectious disease (ID) specialist are threatened, yet there is an increasing need for expertise because of growing antimicrobial resistance and emerging pathogens. Opportunities exist to develop and expand services for the care of patients infected with human immunodeficiency virus and in infection control, epidemiology, outcomes research, outpatient intravenous therapy, and resource management. It is important for ID physicians to appreciate the principles involved in managed care and the areas in which ID services can be valuable. To be effective, physicians need to know about tools such as practice guidelines, physician profiling, outcomes monitoring, computerized information management, risk sharing, networking, and marketing, as well as related legal issues. With a positive attitude toward learning, application, and leadership, ID physicians can redefine their role and expand their services through managed care.

Ambulatory Care↗
PubMed1996

Lipid disorder and transplant coronary artery disease in long-term survivors of heart transplantation.

BACKGROUND: Transplant coronary artery disease is the major cause of late mortality after heart transplantation. The underlying mechanism probably involves various factors including immunologic and nonimmunologic factors. METHODS: The influence of various risk factors concerning both the development and the progression of transplant coronary artery disease was analyzed. Fifty-two heart transplant patients, who survived at least 2 years after transplantation (24 to 60 months), were included. RESULTS: Of these patients 38.5% had angiographic evidence of transplant coronary artery disease. They had significantly higher values of total cholesterol, low-density lipoprotein cholesterol, and log triglycerides than patients without evidence of the disease (p = 0.037, p = 0.002, and p = 0.015, respectively). In addition, preoperative diagnosis of coronary artery disease was a predictor of the development of transplant coronary artery disease, whereas significant differences were not found corresponding to recipient age, donor age, ischemic time, body mass index, lipoprotein (a) value, high-density lipoprotein cholesterol value, time after transplantation, number of postoperative rejection episodes, or prednisone dosage. A 12-month angiographic follow-up indicated disease progression in 25% of the patients. With respect to the majority of factors analyzed within the study, the differences between patients with and those without progression were comparable to the differences between patients in whom transplant coronary artery disease developed and those in whom it did not. However, patients exhibiting disease progression had a higher prednisone intake dosage (p = 0.006) and had significantly higher lipoprotein (a) values (p = 0.0229) than patients without progression. CONCLUSION: This study clearly shows that in heart transplant patients surviving more than 2 years, lipid disorder is one of the main risk factors of both the development and the progression of transplant coronary artery disease.

Adult↗
PubMed1995

Regression of transplant coronary artery disease during chronic HELP therapy: a case study.

This report concerns a heart transplant patient with hypercholesterolemia who showed rapid development of a severe transplant coronary artery disease. The patient received 10 mg pravastatine per day. Quantitative coronary angiography analyses of 4 serial angiograms clearly demonstrated that in the first 2.5 years following surgery, there was a rapid simultaneous progression in both the transplant coronary disease, involving the entire coronary system, and the development of segmental stenotic lesions. During one year of weekly heparin-mediated extracorporeal LDL-cholesterol precipitation (HELP) therapy in addition to diet and pravastatine therapy, the serum low density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and fibrinogen levels could be reduced from 185 +/- 45 mg/dl, 138 mg/dl and 248 mg/dl, respectively, to interval values of 136 +/- 17 mg/dl, 48 +/- 15 mg/dl, and 185 +/- 44 mg/dl, respectively [interval value = (the concentration after HELP + the concentration before the next HELP treatment):2]. This therapy halted further progression of coronary diameter throughout the whole coronary system and brought about marked regression of segmental obstructive lesions.

Arteriosclerosis↗
PubMed1995

Migration of Salmonella enteritidis from the albumen into the egg yolk.

Migration of Salmonella enteritidis from the albumen into the egg yolk was investigated in 860 eggs. After artificial contamination of the albumen with different doses of S. enteritidis phage-type 4 the migration and the effect of temperature on the migration process during a storage period of up to 4 weeks were studied. The experiments showed that the first cells can be detected in the yolk within a few days. The process will be relatively rare during chilled storage if the albumen is only slightly contaminated. The migration rate was positively correlated with the level of contamination, the storage temperatures and the age of the eggs.

Animals↗
PubMed1995

Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections.

The lung is continuously exposed to infectious and non-infectious agents causing cell activation. Activated cells in the lung such as antigen-presenting cells which harbour HIV may favour this organ as a site for virus production. To test this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV-infected patients and healthy controls were obtained and the activation of the cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA-1. The HIV-infected individuals were subdivided into 'lung symptomatic' or 'lung asymptomatic' patients, depending on the presence or absence of secondary lung diseases besides HIV. All HIV-infected individuals demonstrated a decreased number of CD4+ lymphocytes in blood; however, normal numbers of these cells were found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and BAL was higher in lymphocytes from HIV-infected patients compared with controls. The activation state was highest in the lung symptomatic group. Lung symptomatic patients and lung asymptomatic patients with extrapulmonary infections had increased levels of free virus in plasma. Four out of four individuals without or with only low amounts of cell-free HIV in plasma belonged to the symptom-free subgroup. These results suggest that microorganisms other than HIV may promote viral replication via antigen-driven accumulation and activation of CD4+ cells in the lung or other organs, and thus may be responsible for the loss of helper T cells and the progression of the disease.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia.

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.

Adult↗
PubMed1994

Passive smoking exposure in adults and chronic respiratory symptoms (SAPALDIA Study). Swiss Study on Air Pollution and Lung Diseases in Adults, SAPALDIA Team.

The association between passive exposure to tobacco smoke and respiratory symptoms was examined in a sample of 4,197 never-smoking adults. They constituted the never-smoking subsample of a random sample of 9,651 adults (age, 18 to 60 yr) in eight areas in Switzerland. Information on passive smoking exposure and standardized questions on respiratory symptoms were obtained via a questionnaire administered by trained examiners. After controlling for age, sex, body mass index (BMI), study area, atopy, and parental and sibling history, passive smoking exposure was associated with an elevated risk of wheezing apart from colds (odds ratio [OR] = 1.94, 95% CI = 1.39 to 2.70), an elevated risk of bronchitis symptoms (OR = 1.59, 95% CI = 1.17 to 2.15), an elevated risk of symptoms of chronic bronchitis (OR = 1.65, 95% CI = 1.28 to 2.16), an elevated risk of dyspnea (OR = 1.45, 95% CI = 1.20 to 1.76), and an elevated risk of physician diagnosed asthma (OR = 1.39, 95% CI = 1.04 to 1.86). It was not associated with any increased risk of allergic rhinitis including hayfever. Adding a variable for low educational level, excluding subjects whose mother ever smoked or subjects with end-expiratory CO levels > or = 7 ppm, and controlling for paternal smoking during childhood or occupational exposure had little impact on the association. The association of passive smoking exposure with dyspnea, wheeze, and asthma showed evidence of a dose-dependent increase with hours per day of exposure, whereas association with symptoms of bronchitis was stronger with years of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Low-dose enoximone therapy in pre-transplant patients: hemodynamic, echocardiographic, and neurohumoral findings.

Keeping pre-transplant patients alive while waiting for a suitable donor to be found is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 18 transplant candidates with heart failure progression despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. Complete hemodynamic, echocardiographic, and neurohumoral studies were performed before and 24 h after intravenous enoximone infusion. Enoximone infusion increased cardiac index (1.78 +/- 0.45 l/min/qm vs. 3.04 +/- 0.83 l/min/qm; p < 0.001) and stroke volume index (22.33 +/- 9.45 ml/qm vs. 32.28 +/- 7.29 ml/qm; p < 0.05) and decreased wedge pressure (24.1 +/- 11.98 mmHg vs. 17.78 +/- 8.76 mmHg; p < 0.05) and systemic vascular resistance (1700.8 +/- 555.8 dyn x s x cm-5 vs. 952.8 +/- 384.0 dyn x s x cm-5; p < 0.001). Heart rate and mean arterial pressure were unchanged. Left ventricular ejection time (225.1 +/- 26.9 ms vs. 242.2 +/- 25.8 ms; p < 0.05) was increased, whereas other echocardiographic parameters were unchanged (left ventricular end-diastolic dimension, left ventricular end-systolic dimension, fractional shortening, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop of norepinephrine (936.7 +/- 443.2 pg/ml vs. 522.4 +/- 287.6 pg/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Atopic dermatitis: correlation of peripheral blood T cell activation, eosinophilia and serum factors with clinical severity.

In the first part of this study peripheral blood lymphocyte subpopulations, their activation state and various serum parameters were measured in extrinsic and intrinsic atopic dermatitis (AD) patients compared to normal individuals. Beside the characteristic eosinophilia, significantly increased numbers of CD4+ T cells with increased expression of IL-2 receptors (IL-2R) and HLA-DR were noted in the AD patients. In addition, extrinsic AD patients showed increased numbers of CD23+ B cells and decreased numbers of CD16+ natural killer cells. Moreover, increased serum levels of eosinophil cationic protein (ECP) and soluble IL-2R as well as soluble factors that prolong survival of eosinophils in vitro could be demonstrated. In the second section of this study we determine how these blood immunological parameters relate to the clinical severity of the skin lesions of AD, by weekly analysis of 12 AD patients attending a high altitude clinic for 3 to 6 weeks. The patients were divided into two groups on the basis of treatment with topical steroids, but during the observation period a significant improvement in clinical status was observed in all AD patients independent of topical steroid therapy. A progressive decrease in eosinophil and activated T cell numbers, soluble IL-2R levels and serum eosinophil survival prolonging activity could be demonstrated, which closely correlated with the clinical severity of the AD.

Adolescent↗
PubMed1993

Enoximone therapy as pharmacological bridging to cardiac transplantation.

Keeping pre-transplant patients alive while waiting for a suitable donor is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 35 transplant candidates with progressive heart failure despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. In 18 out of 35 patients complete hemodynamic, echocardiographic, neurohumoral, and Holter-ECG studies were performed before and 24 hours after intravenous enoximone infusion. Patients were then continued on chronic oral therapy of 100 mg twice a day. Enoximone infusion increased the cardiac index (CI) (1.78 +/- 0.45 l/min/m2 vs 3.04 +/- 0.83 l/min/m2; p < 0.001) and stroke volume index (SVI)(22.33 +/- 9.45 ml/m2 vs 32.28 +/- 7.29 ml/m2; p < 0.05) and decreased wedge pressure (PCP)(24.1 +/- 11.98 mmHg vs 17.78 +/- 8.76 mmHg; p < 0.05) while mean arterial pressure (MAP) was unchanged. Left ventricular ejection time (LVET)(225.1 +/- 26.9 ms vs 242.2 +/- 25.8 ms; p < 0.05) was increased whereas other echocardiographic parameters were unchanged (Left ventricular end-diastolic dimension LVEDD, left ventricular end-systolic dimension LVESD, fractional shortening FS, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (Aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop in norepinephrine (936.7 +/- 443.2 pg/ml vs 522.4 +/- 287.6 pg/ml; p < 0.05). Holter-ECG parameters (ventricular premature beats VPB, couplets, ventricular tachycardia VT) were not influenced by enoximone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Planimetric quantification of aortic valve stenoses using multiplanar transesophageal echocardiography].

Standard techniques used in order to quantify the severity of aortic valve stenoses in clinical practice comprise: transthoracic echocardiography, namely, by determining maximum and mean transvalvular gradients and evaluating aortic valve areas, as well as invasive techniques which quantify aortic valve areas through hemodynamic pressure measurements and application of the Gorlin formula. Since the introduction of the multiplane TEE technique, it has become feasible to scan the aortic valve in a strictly horizontal plane and quantify the aortic valve orifice by planimetry. In this study, we investigated 23 patients with various degrees of aortic valve stenoses. We compared aortic valve areas, which had been planimetrically determined by multiplane TEE scans, and mean aortic valve gradients (standard TEE technique) with pressure gradients and valve areas derived from hemodynamic measurements obtained during cardiac catheterization, and have found that the valve areas as well as the mean pressure gradients correlate well.

Adult↗
PubMed1992

Ischemia: reperfusion injury and restenosis after coronary angioplasty.

Percutaneous transluminal coronary angioplasty (PTCA) is a very effective technology that allows, without surgery, successful mechanical revascularization of acutely or chronically obstructed coronary arteries. The success of PTCA in patients with acute myocardial infarction or unstable angina is questioned by early coronary reocclusion and by so-called reperfusion injury. In a biochemical context, reperfusion injury occurs as a very complex interaction between the different tissues that build heart muscle. Free radicals play a pivotal role and initiate a deleterious cascade of events after reperfusion. Protective mechanisms such as superoxide dismutase, glutathione peroxidase, and catalase are normally present in the cell to prevent damage by free radicals. Endothelial cells have a greater number of specific physiologic and metabolic functions and influence the microcirculatory flow. In the presence of exogenous glucose, coronary endothelial cells show a pronounced lactate production under well-oxygenated conditions. Low energy demand and high glycolytic activity may be the cause of why the coronary endothelium is less severely injured than the cardiomyocytes in the ischemic and anoxic heart. The success of PTCA in patients with chronically obstructed coronary arteries (stable angina) is questioned by vessel occlusion and restenosis. Restenosis is a very complex process involving clinical, morphological, procedural, regional flow-dependent, and biological determinants. Early platelet deposition, formation of mural thrombus, coronary vasospasm, and elastic recoil forces of stretched vessel wall may contribute to early restenosis in the first days after PTCA, but the peak incidence of restenosis occurs between two and three months after PTCA. Intimal hyperplasia or proliferation of smooth muscle cells is believed to be the fundamental process of restenosis. To solve the problem of restenosis, much effort has been expended, which includes several technical and pharmacological approaches. Pharmacological strategies, systemically or locally administered, aim at increased vasomotor tone, platelet function, smooth muscle cell proliferation/migration, and fibrocollagenous healing. Up to now none of the proposed drugs has been able to reduce the restenosis rate. There is experimental evidence for a claim that the antioxidant functions of vitamins (E, C, and beta-carotene) may prevent restenosis post-PTCA. Until recently, in most post-PTCA restenosis trials the angiographic analyses were not performed using computerized measurement methods. In order to assess the efficacy of acute or long-term interventions on the natural course or acute complications of coronary artery disease, quantitative measures have been introduced and validated that make use of digital coronary angiography and computerized image processing techniques.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗