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Biomedical subjects

M Unger

Publications and source records attributed to M Unger.

At least 19 recordsLinked to original sources

[Developing and establishing an expanded and more comprehensive HIV/AIDS nursing practice].

Developing and establishing an advanced nursing practice is an essential step toward future-oriented nursing care. An action research process was initiated to establish advanced nursing practice at the HIV clinic of the outpatient department at the University Hospital Basel with the goal to offer advanced nursing care to patients. Participatory action research allows generating knowledge about a social system while at the same time tempts to promote social change. The most important goal is to constantly analyse, improve, and evaluate nursing care for patients and family caregivers. Advanced nursing practice in HIV/AIDS is based on solid knowledge regarding the illness and current therapies. Central concepts are caring, clinical experiences, evidence based practice, and patient preferences. Through a systematic step-by-step process, the nurses at the HIV clinic are being better educated and more experienced in these concepts. An essential aspect of advanced nursing practice is the specialization of each nurse in a self selected topic within HIV/AIDS care. These nurses now offer new services such as medication management and adherence support, health maintenance and prevention, and symptom management. This ongoing process of learning while establishing advanced nursing practice in HIV/AIDS, enables the nurses to face future changes in health care in a proactive way.

Acquired Immunodeficiency Syndrome↗

Single-molecule measurements calibrate green fluorescent protein surface densities on transparent beads for use with 'knock-in' animals and other expression systems.

Quantitative aspects of synaptic transmission can be studied by inserting green fluorescent protein (GFP) moieties into the genes encoding membrane proteins. To provide calibrations for measurements on synapses expressing such proteins, we developed methods to quantify histidine-tagged GFP molecules (His6-GFP) bound to Ni-NTA moieties on transparent beads (80-120 microm diameter) over a density range comprising nearly four orders of magnitude (to 30000 GFP/microm2). The procedures employ commonly available Hg lamps, fluorescent microscopes, and CCD cameras. Two independent routes are employed: (1) single-molecule fluorescence measurements are made at the lowest GFP densities, providing an absolute calibration for macroscopic signals at higher GFP densities; (2) known numbers of His6-GFP molecules are coupled quantitatively to the beads. Each of the two independent routes provides linear data over the measured density range, and the two independent methods agree with root mean square (rms) deviation of 11-21% over this range. These satisfactory results are obtained on two separate microscope systems. The data can be corrected for bleaching rates, which are linear with light intensity and become appreciable at intensities > approximately 1 W/cm2. If a suitable GFP-tagged protein can be chosen and incorporated into a 'knock-in' animal, the density of the protein can be measured with an absolute accuracy on the order of 20%.

Animals↗

Glucosylation of isatin-3-oxime followed by 2D in situ NMR in plant cells at highest magnetic field without labelling.

The glucosylation of isatin-3-oxime (1) was monitored by in situ 2D 1H-13C inverse correlated gradient assisted NMR spectroscopy in plant cell suspension cultures of Rauvolfia serpentina without labelling. The applied high magnetic field of 800 MHz allowed measurements within 20 min at concentrations of 1 of 5.76 mM. Complete glucosylation of 1 occurs inside the cells within 72 hours. During this time isatin-3-oxime-glucoside (2) accumulates without further metabolism.

Carbon↗

Results of surgery for aortic root aneurysm in patients with the Marfan syndrome.

OBJECTIVE: To evaluate the results of two operations, aortic valve-sparing and aortic root replacement, in patients with aortic root aneurysm and the Marfan syndrome. METHODS: A retrospective review of 78 consecutive patients with aortic root aneurysm and the Marfan syndrome according to the Gent criteria indicated that 42 patients with normal aortic cusps had an aortic valve-sparing operation, and 36 patients had aortic root replacement (mechanical valve in 25 patients and biological valve in 11). The mean age was similar in both groups, but patients who had aortic root replacement had larger aneurysms, higher grade aortic insufficiency, worse left ventricular function and more cardiac co-morbidity than patients who had aortic valve-sparing operations. The mean follow-up was 41+/-35 months for patients who had aortic valve-sparing, and 65+/-50 months for those who had aortic root replacement. RESULTS: Kaplan-Meyer estimates of survival at 5 years was 100% for patients who had aortic valve-sparing, and 88+/-6% for those who had aortic root replacement (P=0.04). Five patients who had aortic root replacement required seven aortic root re-replacements: three for endocarditis and four for valve failure (biological valves). There have been no reoperations in patients who had aortic valve-sparing operations and annual Doppler echocardiography revealed mild or no aortic insufficiency in 39 patients and moderate aortic insufficiency in three. CONCLUSIONS: These data suggest that aortic valve-sparing operations are safe in patients with the Marfan syndrome and may provide better clinical outcomes than aortic root replacement. Since the size of the aneurysm often determines the feasibility of a valve-sparing procedure, we now recommend surgery when the diameter of the aortic root reaches 50 mm in patients with the Marfan syndrome who have echocardiographically normal aortic valve cusps.

Adolescent↗

Surface composition of spray-dried particles of bovine serum albumin/trehalose/surfactant.

PURPOSE: To characterize via electron spectroscopy for chemical analysis (ESCA) the surface of spray-dried particles of trehalose plus a protein (bovine serum albumin). Additionally, to show how and why the addition of a surfactant reduces protein adsorption, and by this mechanism could reduce protein instability during spray-drying. METHODS: Aqueous solutions of trehalose plus bovine serum albumin (bSA) were spray-dried with increasing concentrations of surfactant. The surface composition of the dried particles was examined using ESCA. RESULTS: The presence of bSA, trehalose, and surfactant could be detected quantitatively in the particle surface. In the absence of surfactant the bSA had a large surface excess concentration (determined via its N atoms). Increasing concentration of polysorbate 80 reduced the surface excess of bSA in a concentration-dependent manner. At high polysorbate 80 concentration (5 mg/ml) the bSA could no longer be detected in solid surface. Using sodium dodecyl sulfate it was shown that the reduction in surface concentration of the protein is accompanied by a simultaneous increase in surface concentration of the surfactant. Neither surfactant fully covers the surface at the point of complete protein exclusion. CONCLUSIONS: ESCA provides a direct, quantitative measure of the surface composition of spray-dried trehalose/protein/surfactant particles. Surfactant reduces protein adsorption at the water/air-interface. This appears to be a result of complex formation with the surfactant within the bulk spray solution.

Animals↗

Lung cancer. Diagnostic tools.

Early diagnosis of lung cancer represents the best method for improving survival rates. The diagnostic aids available have improved exponentially on old and new techniques over the past 20 years. The greatest impact has been in computed tomography and positron emission tomography scanning imaging techniques. In the future, these techniques will improve, and others such as monoclonal antibody scans and antisense imaging techniques will certainly further enhance the physician's ability to diagnose earlier, and thereby, treat earlier.

Biopsy, Needle↗

Pulmonary embolism and myocardial hypoxia during extracorporeal membrane oxygenation.

The treatment of a newborn with severe meconium aspiration by venoarterial extracorporeal membrane oxygenation (ECMO) was complicated by myocardial hypoxia with a marked decrease of myocardial contractility. The onset of the cardiac hypoxia was related to a pulmonary artery embolus. The origin of the embolus was a deep femoral vein thrombosis, caused by a central vein catheter, which was inserted 1 day before ECMO by venous cutdown. The possible pathophysiology of myocardial hypoxia in this patient is discussed, especially with regard to myocardial perfusion, supporting the hypothesis of coronary perfusion occuring with blood from the left ventricle and not from the arterial cannula in the aorta.

Catheterization, Central Venous↗

Single-molecule fluorescence observed with mercury lamp illumination.

We demonstrate that it is possible to observe single fluorescent molecules using a standard fluorescence microscope with mercury lamp excitation and an inexpensive cooled charge-coupled device (CCD) camera. With this equipment, we have been able to observe single molecules of tetramethyl-rhodamine, rhodamine 6G, fluorescein isothiocyanate and green fluorescent protein. Immobilized molecules were observed both in air and in aqueous solution.

Green Fluorescent Proteins↗

Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria.

Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.

Animals↗

Prognostic significance of DNA content and S-phase fraction in epithelial ovarian carcinomas analyzed by image cytometry.

The objective of this study was to evaluate the prognostic significance of DNA ploidy and S-phase fraction (SPF) in epithelial ovarian carcinomas analyzed by image cytometry. Frozen tissue of 103 epithelial ovarian carcinomas was analyzed for DNA ploidy and SPF with a Cell Analysis System Image Analyser (CAS 200, Becton-Dickinson) and correlations with clinical and histomorphologic factors and time to progression and overall survival were evaluated by univariate and multivariable analysis. Fifty-four percent of the ovarian carcinomas were found to be diploid, 38% aneuploid, and 8% tetraploid. The S-phase fraction was low (<5%) in 27%, intermediate (5-14.5%) in 47%, and high (>/=14.5%) in 26% of the patients. By univariate analysis overall survival and time to progression were significantly correlated with the S-phase fraction (P = 0.003 and P = 0.003), but not with DNA ploidy (P = 0. 31 and P = 0.51). A DNA index > 1.4 was correlated with poor outcome but the result did not achieve formal statistical significance (P = 0.08 and P = 0.12). A high SPF was a strong predictor of early recurrence, while a low SPF identified patients with a favorable long-term outcome. Other significant predictors of survival were FIGO stage, grade of differentiation, presence of distant metastasis, residual tumor, lymph node metastasis, and patient age. In multivariable statistical analysis only FIGO stage, histologic grade, and residual tumor after surgery were independent predictors of overall survival and time to progression.

Adult↗

Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy.

BACKGROUND: In the treatment of lung cancer, the best outcome is achieved when the lesion is discovered in the intraepithelial (preinvasive) stage. However, intraepithelial neoplastic lesions are difficult to localize by conventional white-light bronchoscopy (WLB). OBJECTIVE: To determine if autofluorescence bronchoscopy, when used as an adjunct to WLB, could improve the bronchoscopist's ability to locate and remove biopsy specimens from areas suspicious of intraepithelial neoplasia as compared with WLB alone. METHOD: A multicenter clinical trial was conducted in seven institutions in the United States and Canada. WLB followed by fluorescence examination with the light-induced fluorescence endoscopy (LIFE) device was performed in 173 subjects known or suspected to have lung cancer. Biopsy specimens were taken from all areas suspicious of moderate dysplasia or worse on WLB and/or LIFE examination. In addition, random biopsy specimens were also taken from other parts of the bronchial tree. RESULTS: The relative sensitivity of WLB + LIFE vs WLB alone was 6.3 for intraepithelial neoplastic lesions and 2.71 when invasive carcinomas were also included. The positive predictive value was 0.33 and 0.39 and the negative predictive value was 0.89 and 0.83, respectively, for WLB+LIFE and WLB alone. CONCLUSION: Autofluorescence bronchoscopy, when used as an adjunct to standard WLB, enhances the bronchoscopist's ability to localize small neoplastic lesions, especially intraepithelial lesions that may have significant implication in the management of lung cancer in the future.

Adult↗

Villous cytotrophoblast proliferating potential in complete and partial hydatidiform mole: diagnostic value of silver-stained nucleolar organizer region (AgNOR)-associated proteins.

Aside from their typical morphologic features, complete (CHM) and partial hydatidiform mole (PHM) are characterized by variable trophoblastic proliferation and/or atypia. CHM and PHM usually present little diagnostic difficulty. However, some may be extremely difficult to distinguish by morphologic features alone. Therefore, we investigated the diagnostic value of silver-stained nucleolar organizer region (AgNOR)-associated proteins in cytotrophblasts as compared to cytogenetic features of nine CHM, nine PHM and six non-molar spontaneous embryonic abortions (controls), as well as of two suspected CHM and two histologically suspected PHM. Tissue sections were submitted to autoclave pretreatment and to silver colloid solution. The proliferating potential of cytotrophoblasts was determined by the analysis of mean number and mean area of AgNORs per nucleus using a PC-based image analysis system. Mean values of AgNOR parameters were significantly different from each other (p < 0.001). Each of the four cases of tentative diagnosis could be assigned to the corresponding group of examined trophoblastic lesions. The evaluation of AgNORs in cytotrophoblasts contributes to a reliable discrimination of CHM and PHM; this fairly simple and economical method could serve as an useful addition to conventional methods of diagnosis in gestational trophoblastic disease.

Cell Division↗

Qualitative analysis of fetal movement patterns in the Neu-Laxova syndrome.

The Neu-Laxova syndrome was diagnosed in a fetus at 34 weeks' gestation on the basis of ultrasonographic qualitative analysis of fetal movement patterns and malformations. The first ultrasound study was performed at 34 weeks' gestation and a dead 960 g female fetus was delivered at 36 weeks' gestation.

Adult↗

Kinetics and dose dependence of macrophage colony-stimulating factor-induced proliferation and activation of murine mononuclear phagocytes in situ: differences between lungs, liver, and spleen.

Alveolar macrophages (AM) play an important role in antimicrobial defense mechanisms of the lung. It therefore seems reasonable to use macrophage colony-stimulating factor (M-CSF) to enhance local resistance mechanisms. However, little is known about the in vivo activity of M-CSF on macrophages in various organs. We determined the effect of a single subcutaneous dose of M-CSF (10, 50, 100, and 500 ng, respectively) on the number and functional status of AM as well as of macrophages in liver and spleen of mice. Organs were investigated immunohistochemically on days 1 and 3 after injection using monoclonal antibodies specific for F4/80, Ia antigen, and MAC-1. We found a significant increase in the number of F4/80+ AM, Kupffer cells, and splenic macrophages reaching its maximum 24 h after injection of low doses (10 and 50 ng per mouse, respectively) of M-CSF and decreasing to a level seen in untreated mice at 72 h after M-CSF in liver and spleen, whereas at a dose of 50 ng per mouse the number of AM remained high. In contrast, the numbers of AM, Kupffer cells, and splenic macrophages did not increase significantly when high doses were used (500 ng). The expression of Ia antigen and MAC-1 was increased on macrophages in the spleen but not on AM or Kupffer cells. TNF-alpha was elevated in bronchoalveolar (BAL) fluid after 3 h and IL-6 at 6, 12, and 24 h after M-CSF injection in dose-dependent manner. Nitric oxide production was not increased after injection of M-CSF. Our results point to regional differences in the response of macrophages to M-CSF. These may caused by differences in the M-CSF-induced production of TNF-alpha and IL-6. These findings may be important for the therapeutic use of M-CSF in microbial infections.

Animals↗

CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule.

The expression, serological detection, and possible functional role of the CD30 antigen in Hodgkin's disease and anaplastic large cell lymphoma is well documented. In embryonal carcinoma (EC), the expression of this cytokine receptor has been demonstrated only by immunohistology. Because the CD30 monoclonal antibody Ki-1 was found to cross-react with an unrelated molecule, we examined by in situ hybridization testicular germ cell neoplasms for the presence of CD30-specific transcripts. CD30 mRNA was detectable in the tumor cells of 9 of 9 cases of EC or mixed germ cell tumors with an EC component but in no other nonlymphoid tumors. Thus, the CD30 transcript expression pattern proved to be identical to the immunostaining pattern seen with the CD30-specific monoclonal antibody Ber-H2. By Northern blot analysis, CD30 transcripts could be demonstrated in the EC cell line Tera-2. Employing a highly sensitive second generation sandwich enzyme-linked immunosorbent assay, we could detect the soluble CD30 molecule in 8 of 8 sera from patients with a diagnosis of EC but not in 8 of 10 sera from patients with other testicular germ cell tumors. In fetal tissue, no CD30-expressing germ cells or epithelial cells could be observed. Thus, the cellularly expressed CD30 marker for testicular neoplasms of EC type. Moreover, the serum levels of soluble CD30 antigen seem to be a promising parameter for monitoring patients with EC.

Adolescent↗